Details of a Researcher - SOMEYA Masanori

Papers - SOMEYA Masanori

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Association between cancer immunity and treatment results in uterine cervical cancer patients treated with radiotherapy.

Masanori Someya, Takaaki Tsuchiya, Yuki Fukushima, Tomokazu Hasegawa, Yu Takada, Masakazu Hori, Katsutoshi Miura, Mio Kitagawa, Toshio Gocho, Yoshihiko Hirohashi, Toshihiko Torigoe, Masahiro Iwasaki, Motoki Matsuura, Tsuyoshi Saito, Koh-Ichi Sakata

Japanese journal of clinical oncology ( Oxford University Press (OUP) ) 50 ( 11 ) 1290 - 1297 2020.10 [Refereed] [International journal]

Authorship： Lead author , Corresponding author

OBJECTIVE: To evaluate proteins related to tumor immune response and treatment outcome from radiotherapy for uterine cervical cancer patients. METHODS: We performed a retrospective immunohistochemical staining of 81 patients with uterine cervical cancer who underwent definitive radiotherapy. We examined the expression of programmed death ligand 1, human leukocyte antigen class I, tumor-infiltrating CD8+, and forkhead box P3+ (FoxP3+) T cells in tumor tissues. RESULTS: In biopsy specimen, patients with a higher number of CD8+ T cells and FoxP3+ T cells had a better disease-specific survival than patients with a lower number of CD8+ T cells and FoxP3+ cells (P = 0.018 and P = 0.009). Multivariate analysis showed that equivalent dose in 2 Gy fractions (EQD2) of the minimum dose to 90% of the high-risk clinical target volume, FoxP3+ T cells and expression of human leukocyte antigen class I were significant prognostic factors. When the EQD2 is 70 Gy or more, a higher local control rate is obtained regardless of the number of CD8- or FoxP3-positive cells. When EQD2 is <70 Gy, the number of CD8-positive cells has a significant impact on treatment outcome: the recurrence rate (local recurrence rate + distant metastasis rate) was 46.2% in the group with a CD8 value of 230 or higher, whereas the recurrence rate was 75.7% in the group with a CD8 value of less than 230. CONCLUSION: The combination of CD8 or FoxP3 with EQD2 can be potentially useful to predict the treatment results of radiotherapy for cervical cancer, leading to individualized optimal selection of treatment for cervical cancer.

DOI PubMed

Retrospective DVH analysis of point A based intracavitary brachytherapy for uterine cervical cancer.

Masanori Someya, Tomokazu Hasegawa, Takaaki Tsuchiya, Mio Kitagawa, Toshio Gocho, Yuuki Fukushima, Masakazu Hori, Katsutoshi Miura, Yu Takada, Kensei Nakata, Koh-Ichi Sakata

Journal of radiation research 61 ( 2 ) 265 - 274 2020.03 [Refereed] [International journal]

Combining external beam radiotherapy (EBRT) with intracavitary brachytherapy (ICBT) is important for definitive treatment of cervical cancer. In cervical cancer patients receiving radiotherapy, we evaluated treatment outcomes in relation to dose-volume histogram parameters, including the computed tomography (CT)-based high-risk clinical target volume (HR-CTV) for ICBT. Between 2010 and 2015, 89 consecutive cervical cancer patients were mostly treated with 40 Gy of EBRT in 20 fractions and 18 Gy of ICBT prescribed to point A in 3 fractions. CT scans were obtained during ICBT. The HR-CTV D90 was calculated and the total doses of ICBT and EBRT were converted to the equivalent dose in 2 Gy fractions (EQD2). When the patients were divided into four groups according to EQD2 of the HR-CTV D90, the 3-year local recurrence-free survival rates were 95.2, 78.4, 52.7 and 42.9% for patients receiving >80 , 70-80 , 60-70 and <60 Gy, respectively. There was a significant negative correlation between EQD2 of the HR-CTV D90 and the HR-CTV volume at first ICBT (r = -0.713). Local recurrence was more frequent when the HR-CTV volume was ≥22 cc and EQD2 of the HR-CTV D90 was <70 Gy. Multivariate analysis showed that EQD2 of the HR-CTV D90 and concurrent chemotherapy (≥4 cycles) were significant determinants of overall survival. HR-CTV D90 was an important prognostic indicator for local recurrence. HR-CTV D90 >70 Gy is required for the better local control, especially in patients with a larger HR-CTV (≥22 cc at initial ICBT).

DOI PubMed

Prediction of acute gastrointestinal and genitourinary radiation toxicity in prostate cancer patients using lymphocyte microRNA.

Masanori Someya, Masakazu Hori, Toshio Gocho, Kensei Nakata, Takaaki Tsuchiya, Mio Kitagawa, Tomokazu Hasegawa, Yuuki Fukushima, Koh-Ichi Sakata

Japanese journal of clinical oncology 48 ( 2 ) 167 - 174 2018.02 [Refereed] [International journal]

Background: To search for novel biomarkers that can predict acute radiation toxicity, we conducted microRNA expression analysis of peripheral blood lymphocytes (PBLs). Methods: The discovery cohort was 69 patients with localized adenocarcinoma of the prostate who received intensity-modulated radiation therapy between October 2007 and October 2010. The validation cohort was 72 patients treated with low-dose-rate brachytherapy between May 2008 and March 2014. After13 microRNAs were selected by TaqMan® Array analysis in a preliminary experiment, expression of these microRNAs in all samples was analyzed by RT-PCR. Results: In the discovery cohort, the average prostate volume, the rectal volume receiving 70 Gy, and expression of miR-410 and miR-221 were significant risk factors for Grade 1-2 gastrointestinal toxicity. Receiver operating characteristic analysis showed that the area under the curve (AUC) was 0.807. The maximum dose to the urinary bladder, prostate volume, pretreatment urinary function score, and miR-99a and miR-221 expression were risk factors for Grade 2 genitourinary toxicity. The corresponding AUC was 0.796. In the validation cohort, reproducibility of these markers was confirmed for gastrointestinal toxicity, but not for genitourinary toxicity. Conclusion: Combining radiation dose parameters with microRNA expression in PBLs may be useful for predicting acute gastrointestinal toxicity of radiation therapy, thus contributing to personalized treatment of prostate cancer.

DOI PubMed

Local tumor control and DNA-PK activity of peripheral blood lymphocytes in prostate cancer patients receiving radiotherapy.

Masanori Someya, Tomokazu Hasegawa, Masakazu Hori, Yoshihisa Matsumoto, Kensei Nakata, Naoya Masumori, Koh-Ichi Sakata

Journal of radiation research 58 ( 2 ) 225 - 231 2017.03 [Refereed] [International journal]

Repair of DNA damage is critical for genomic stability, and DNA-dependent protein kinase (DNA-PK) has an important role in repairing double-strand breaks. We examined whether the DNA-PK activity of peripheral blood lymphocytes (PBLs) was related to biochemical (prostate-specific antigen: PSA) relapse and radiation toxicity in prostate cancer patients who have received radiotherapy. A total of 69 patients with localized adenocarcinoma of the prostate participated in this study. Peripheral blood was collected 2 years or later after radiotherapy and centrifuged, then DNA-PK activity was measured by a filter binding assay. The high DNA-PK activity group had a significantly higher PSA relapse-free survival rate than the low DNA-PK activity group. The 10-year PSA relapse-free survival was 87.0% in the high DNA-PK activity group, whereas it was 52.7% in the low DNA-PK activity group. Multivariate analysis showed the Gleason score and the level of DNA-PK activity were significant predictors of PSA relapse after radiotherapy. In addition, the low DNA-PK activity group tended to have a higher incidence of Grade 1-2 urinary toxicity than the high DNA-PK activity group. Prostate cancer patients with low DNA-PK activity had a higher rate of PSA relapse and a higher incidence of urinary toxicity. DNA-PK activity in PBLs might be a useful marker for predicting PSA relapse and urinary toxicity, possibly contributing to personalized treatment of prostate cancer.

DOI PubMed

Relation between Ku80 and microRNA-99a expression and late rectal bleeding after radiotherapy for prostate cancer.

Masanori Someya, Hiroyuki Yamamoto, Masanori Nojima, Masakazu Hori, Kunihiko Tateoka, Kensei Nakata, Masaru Takagi, Masato Saito, Naoki Hirokawa, Takashi Tokino, Koh-Ichi Sakata

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology ( ELSEVIER IRELAND LTD ) 115 ( 2 ) 235 - 9 2015.05 [Refereed] [International journal]

BACKGROUND AND PURPOSE: Late rectal bleeding is one of the severe adverse events after radiotherapy for prostate cancer. New biomarkers are needed to allow a personalized treatment. MATERIALS AND METHODS: Four patients each with grade 0-1 or grade 2-3 rectal bleeding were randomly selected for miRNA array to examine miRNA expression in peripheral blood lymphocytes (PBLs). Based on results of miRNA array, 1 of 348 miRNAs was selected for microRNA assays. Then, expression of DNA-dependent protein kinase mRNA and miR-99a was analyzed in the PBLs of 97 patients. PBLs were exposed to 4Gy of X-ray ex-vivo. RESULTS: In the discovery cohort, grade 2-3 rectal bleeding was significantly higher in the Ku80 <1.09 expression group compared with ⩾1.09 group (P=0.011). In radiation-induced expression of miR-99a, grade 2-3 rectal bleeding was significantly higher in the miR-99a IR(+)/IR(-) >0.93 group compared with ⩽0.93 group (P=0.013). Most patients with grade 2-3 rectal bleeding were in the group with low Ku80 and high miR-99a expression. In the validation cohort, similar results were obtained. CONCLUSION: A combination of low Ku80 expression and highly-induced miR-99a expression could be a promising marker for predicting rectal bleeding after radiotherapy.

DOI PubMed

Results and DVH analysis of late rectal bleeding in patients treated with 3D-CRT or IMRT for localized prostate cancer.

Masanori Someya, Masakazu Hori, Kunihiko Tateoka, Kensei Nakata, Masaru Takagi, Masato Saito, Naoki Hirokawa, Masato Hareyama, Koh-Ichi Sakata

Journal of radiation research 56 ( 1 ) 122 - 7 2015.01 [Refereed] [International journal]

In patients undergoing radiotherapy for localized prostate cancer, dose-volume histograms and clinical variables were examined to search for correlations between radiation treatment planning parameters and late rectal bleeding. We analyzed 129 patients with localized prostate cancer who were managed from 2002 to 2010 at our institution. They were treated with 3D conformal radiation therapy (3D-CRT, 70 Gy/35 fractions, 55 patients) or intensity-modulated radiation therapy (IMRT, 76 Gy/38 fractions, 74 patients). All radiation treatment plans were retrospectively reconstructed, dose-volume histograms of the rectum were generated, and the doses delivered to the rectum were calculated. Time to rectal bleeding ranged from 9-53 months, with a median of 18.7 months. Of the 129 patients, 33 patients had Grade 1 bleeding and were treated with steroid suppositories, while 25 patients with Grade 2 bleeding received argon plasma laser coagulation therapy (APC). Three patients with Grade 3 bleeding required both APC and blood transfusion. The 5-year incidence rate of Grade 2 or 3 rectal bleeding was 21.8% for the 3D-CRT group and 21.6% for the IMRT group. Univariate analysis showed significant differences in the average values from V65 to V10 between Grades 0-1 and Grades 2-3. Multivariate analysis demonstrated that patients with V65 ≥ 17% had a significantly increased risk (P = 0.032) of Grade 2 or 3 rectal bleeding. Of the 28 patients of Grade 2 or 3 rectal bleeding, 17 patients (60.7%) were cured by a single session of APC, while the other 11 patients required two sessions. Thus, none of the patients had any further rectal bleeding after the second APC session.

DOI PubMed

Effects of depletion of dihydropyrimidine dehydrogenase on focus formation and RPA phosphorylation.

Masanori Someya, Koh-ichi Sakata, Yoshihisa Matsumoto, Hiroshi Tauchi, Masahiro Kai, Masato Hareyama, Masakazu Fukushima

Journal of radiation research 53 ( 2 ) 250 - 6 2012 [Refereed] [International journal]

Gimeracil, an inhibitor of dihydropyrimidine dehydrogenase (DPYD), partially inhibits homologous recombination (HR) repair and has a radiosensitizing effect as well as enhanced sensitivity to Camptothecin (CPT). DPYD is the target protein for radiosensitization by Gimeracil. We investigated the mechanisms of sensitization of radiation and CPT by DPYD inhibition using DLD-1 cells treated with siRNA for DPYD. We investigated the focus formation of various kinds of proteins involved in HR and examined the phosphorylation of RPA by irradiation using Western blot analysis. DPYD depletion by siRNA significantly restrained the formation of radiation-induced foci of Rad51 and RPA, whereas it increased the number of foci of NBS1. The numbers of colocalization of NBS1 and RPA foci in DPYD-depleted cells after radiation were significantly smaller than in the control cells. These results suggest that DPYD depletion is attributable to decreased single-stranded DNA generated by the Mre11/Rad50/NBS1 complex-dependent resection of DNA double-strand break ends. The phosphorylation of RPA by irradiation was partially suppressed in DPYD-depleted cells, suggesting that DPYD depletion may partially inhibit DNA repair with HR by suppressing phosphorylation of RPA. DPYD depletion showed a radiosensitizing effect as well as enhanced sensitivity to CPT. The radiosensitizing effect of DPYD depletion plus CPT was the additive effect of DPYD depletion and CPT. DPYD depletion did not have a cell-killing effect, suggesting that DPYD depletion may not be so toxic. Considering these results, the combination of CPT and drugs that inhibit DPYD may prove useful for radiotherapy as a method of radiosensitization.

PubMed

Immunohistochemical analysis of Ku70/86 expression of breast cancer tissues.

Masanori Someya, Koh-ichi Sakata, Yoshihisa Matsumoto, Masaaki Satoh, Hideaki Narimatsu, Masato Hareyama

Oncology reports 18 ( 6 ) 1483 - 7 2007.12 [Refereed] [International journal]

DNA-dependent protein kinase (DNA-PK) has an important role in DNA double-strand break repair. We previously demonstrated the association of DNA-PK activity in peripheral blood lymphocytes (PBL) with incidence of chromosomal aberrations and risk of cancer. In this study, we examined the expression of Ku70 and Ku86 in breast cancer tissue and normal breast tissue with immunohistochemistry. We also measured the DNA-PK activity in PBL of the same patient. One hundred and ten breast cancer patients were included in this study. The expression of Ku70, and Ku86 in normal mammary epithelial cells and breast cancer cells obtained from surgical specimens was immunohistochemically examined. DNA-PK activity of PBL was measured by DNA-pull-down assay. The expression of Ku70 and that of Ku86 tended to parallel each other in normal and cancer tissues. There was also a relationship in the expression of Ku70 and Ku86 between cancer tissues and normal tissues in the same samples. Lower expression of Ku70 or Ku86 tended to be associated with higher malignant nuclear grade of cancer cells and higher frequency of axillary lymph node metastasis. The staining score of Ku70 or Ku86 of normal mammary epithelial cells or breast cancer cells had no significant relationship with DNA-PK activity of PBL. In conclusion, breast cancer cells inherited the characteristics of expression of Ku proteins from original mammary epithelial cells. The staining score of Ku70 or Ku86 of normal or cancer cells had no significant relationship with DNA-PK activity of PBL. This may be due to limitations in the assay sensitivity of immunohistochemistry.

PubMed

Association of DNA-PK activity and radiation-induced NBS1 foci formation in lymphocytes with clinical malignancy in breast cancer patients.

Masanori Someya, Koh-Ichi Sakata, Yoshihisa Matsumoto, Hiroshi Tauchi, Hideaki Narimatsu, Masato Hareyama

Oncology reports 18 ( 4 ) 873 - 8 2007.10 [Refereed] [International journal]

DNA double-strand break (DSB) is one of the most deleterious lesions induced by DNA damaging agents. DSB repair pathway is implicated in maintaining genomic integrity via suppression of genetic instability and neoplastic transformation. DNA-dependent protein kinase (DNA-PK) has a pivotal role in DNA DSB repair. The Nijmegen breakage syndrome protein (NBS1), essential for DSB repair, re-localizes into subnuclear structures upon induction of DNA damage by ionizing radiation, forming so-called ionizing radiation-induced foci (IRIF), which is visualized by immunostaining. We measured DNA-PK activity and the number of persistent NBS1 IRIF per nucleus 24 h after irradiation of peripheral blood lymphocytes (PBL) from patients with sporadic breast cancer. Chromosomal aberrations were examined by cytogenetic methods. We examined the relationship between these measurements and clinical characteristics of patients such as tumor size, lymph node metastasis and nuclear grade of cancer cells. A higher number of NBS1 IRIF or lower DNA-PK activity correlated with higher chromosome instability. Patients whose PBL had lower DNA-PK or higher NBS1 IRIF had aggressive cancer phenotypes such as a larger tumor, higher nuclear grade and positive axillary lymph node metastasis. The combination of DNA-PK activity and NBS1 IRIF were useful for predicting lymph node metastasis. The ability of DSB repair in PBL is related to aggressive breast cancer phenotypes. Axillary lymph node dissection can be avoided by examining DNA-PK activity and NBS1 IRIF of PBL, which can contribute to improving the quality of life of breast cancer patients.

PubMed

Association of ionizing radiation-induced foci of NBS1 with chromosomal instability and breast cancer susceptibility.

Masanori Someya, Koh-ichi Sakata, Hiroshi Tauchi, Yoshihisa Matsumoto, Asako Nakamura, Kenshi Komatsu, Masato Hareyama

Radiation research 166 ( 4 ) 575 - 82 2006.10 [Refereed] [International journal]

NBS1, a protein essential for DNA double-strand break repair, relocalizes into subnuclear structures upon induction of DNA damage by ionizing radiation, forming ionizing radiation-induced foci. We compared radiation-induced NBS1 foci in peripheral blood lymphocytes (PBLs) from 46 sporadic breast cancer patients and 30 healthy cancer-free volunteers. The number of persistent radiation-induced NBS1 foci per nucleus at 24 h after irradiation for patients with invasive cancer was significantly higher than for normal healthy volunteers. The frequency of spontaneous chromosome aberration increased as the number of persistent radiation-induced NBS1 foci increased, indicating that the number of persistent radiation-induced NBS1 foci might be associated with chromosome instability. There was also an inverse correlation between the number of radiation-induced NBS1 foci and the activity of DNA-dependent protein kinase (DNA-PK), which plays an important role in the nonhomologous end-joining (NHEJ) pathway, another mechanism of DNA DSB repair, indicating a close interrelationship between homologous recombination (HR) and NHEJ in DNA DSB repair. In conclusion, the number of persistent radiation-induced NBS1 foci is associated with chromosomal instability and risk of sporadic breast cancer and hence might be used to select individuals for whom a detailed examination is necessary because of their increased susceptibility to breast cancer, although refinement of the techniques for technical simplicity and accuracy will be required for clinical use.

PubMed

The changes in irradiated salivary gland function of patients with head and neck tumors treated with radiotherapy.

Masanori Someya, Koh-ichi Sakata, Hisayasu Nagakura, Kensei Nakata, Atsushi Oouchi, Masato Hareyama

Japanese journal of clinical oncology 33 ( 7 ) 336 - 40 2003.07 [Refereed] [International journal]

BACKGROUND: To investigate and analyze changes in irradiated salivary gland function of patients with head and neck tumors treated with radiotherapy. METHODS: Thirty-seven patients with head and neck tumors, who received 40-70 Gy of irradiation to all major salivary glands, were analyzed. The weights of saliva secreted for 10 minutes at rest, and for 5 minutes with vitamin C stimulation, were measured. The salivary gland function was defined by the weight of saliva. RESULTS: With vitamin C stimulation, the weight of saliva in patients whose doses were < or =50 Gy, was significantly higher than that of patients whose doses were > or = 58 Gy (2.48 +/- 0.33 g vs. 0.73 +/- 0.18 g, P = 0.0003). When doses administered to salivary glands were < or =50 Gy, the stimulated saliva secretion recovered over time, after irradiation. However, when the doses of irradiation were > or = 58 Gy, there was no recovery in saliva secretion even after a few years. Multiple regression analysis showed that age and chemotherapy may not affect salivary gland function even years after radiotherapy. CONCLUSION: When salivary glands were irradiated with doses < or =50 Gy, gradual recovery of salivary gland function was observed over time, whereas there was no significant recovery when the irradiation dose was >58 Gy.

PubMed

Results of external irradiation and low-dose-rate intraluminal brachytherapy for esophageal cancer.

Masanori Someya, Koh-ichi Sakata, Akio Saito, Hisayasu Nagakura, Atsushi Oouchi, Masato Hareyama

Acta oncologica (Stockholm, Sweden) 41 ( 1 ) 63 - 8 2002 [Refereed] [International journal]

The results of definitive radiotherapy to elucidate the optimal doses of external irradiation (ERT) and low-dose-rate intraluminal brachytherapy (ILBT) were analyzed. Between 1979 and 1998, 100 patients with esophageal cancer were treated with ERT and ILBT. ERT was given at a dose of 40-65 Gy/25-32 fractions and ILBT at 10-24.3 Gy/2-3 fractions. The 5-year actuarial survival rate for all cases was 13% and that for patients with tumors of 5 cm or less in length was 22.64%, while for patients with tumors longer than 5 cm the rate was 5% (p < 0.005). In patients with tumors of 5 cm or less in length, the local control rate of those whose ILBT dose was 20 Gy or more was 83%, and for those with an ILBT dose of less than 20 Gy the control rate was 26.5% (p = 0.014). In patients with tumors of 5 cm or less in length, the results of treatment with 60 Gy ERT and 20 Gy ILBT were promising and did not cause severe late complications.

PubMed

Japanese version of the MD Anderson Symptom Inventory for Head and Neck Tumor module: Validation study.

Hiroto Sawaguchi, Masanori Someya, Kensei Nakata, Yu Takada, Keiko Danzuka, Mitsunori Miyashita, Mikiko Kawamura

Asia-Pacific journal of oncology nursing 12 100711 - 100711 2025.12 [International journal]

OBJECTIVE: This study aimed to examine the reliability and validity of the Japanese version of the MD Anderson Symptom Inventory Head and Neck Tumor module (MDASI-HN), a patient-reported outcome measure for head and neck cancer. METHODS: The MDASI-HN was translated into Japanese, and cognitive debriefing was conducted. A cross-sectional study was administered to patients with head and neck cancer who were recruited within 5 years of receiving surgery, chemotherapy, or radiotherapy at three cancer treatment centers. The reliability and validity of the Japanese version were confirmed through structural equation modeling, internal consistency, test-retest reliability, convergent validity, known-groups validity. RESULTS: The Japanese translation of the MDASI-HN was revised with developer feedback. Cognitive debriefing with five patients provided positive feedback regarding the ease of completion and understanding. A cross-sectional sample of 147 patients completed the questionnaire. Structural equation modeling showed a Confirmatory Fit Index of 0.975 and Root Mean Square Error of Approximation of 0.059. The Cronbach's alpha coefficient was 0.88 for head and neck cancer-specific items and 0.96 for all symptom items. The Intraclass Correlation Coefficients (2,1) were 0.72 for HNC-specific items and 0.74 for all items. The convergent validity with the EORTC QLQ-H&N module was r = 0.79. The known-groups validity showed small to moderate effect sizes for all subitems, based on the comparison of mean ECOG Performance Status Scale scores between the two groups. CONCLUSIONS: The results showed that the translated MSASI-HN was reliable, valid, and feasible for use in Japanese-speaking patients with head and neck cancer.

DOI PubMed

Autoantibody spark response predicts treatment outcome in patients receiving chemoradiation followed by durvalumab therapy.

Takeru Mori, Mio Kitagawa, Tomokazu Hasegawa, Masanori Someya, Takaaki Tsuchiya, Toshio Gocho, Tomoko Honjo, Mirei Date, Mariko Morii, Ai Miyamoto, Junichiro Futami

Scientific reports 15 ( 1 ) 27502 - 27502 2025.07 [International journal]

The PACIFIC regimen, comprising chemoradiotherapy (CRT) followed by maintenance with the immune checkpoint inhibitor (ICI) durvalumab, has become the standard of care for patients with unresectable non-small cell lung cancer (NSCLC). Although ICI is used to prevent recurrence by targeting residual microtumors, biomarkers capable of monitoring immune activity during this phase remain lacking. Here, we evaluated whether temporal changes in serum autoantibody levels can predict treatment efficacy. This retrospective study included 20 patients with unresectable stage II or III NSCLC who received the PACIFIC regimen. Serum autoantibodies against 130 antigens were quantified before CRT, after CRT, and two weeks after the first ICI dose. The primary outcome was progression-free survival (PFS), and its association with autoantibody dynamics was examined. We observed an immediate and strong autoantibody response (spark response [SR]) after ICI initiation in patients with favorable treatment outcomes. Patients with SR and programmed death ligand 1 (PD-L1) expression ≥ 50% showed better PFS (two-year PFS; 72.9% vs. 18.2%, p = 0.0021). These findings suggest that serial monitoring of serum autoantibodies can provide a noninvasive approach to assess immune activity and predict treatment outcomes in patients receiving CRT or ICI therapy.

DOI PubMed

Cisplatin intra-arterial chemotherapy for recurrent maxillary gingival cancer and metastatic lymph nodes without radiation or surgery: A case report

Akemi Ohtani, Masato Saito, Naoki Hirokawa, Hiroki Okuda, Hiroki Sato, Kenichiro Nitta, Shoh Mafune, Akihiro Miyazaki, Hironari Dehari, Masanori Someya

Radiology Case Reports 20 ( 1 ) 560 - 565 2025.01 [International journal]

Most patients with head and neck cancers struggle with their treatment, particularly those with recurrent cancer. However, there is no consensus on effective treatments for recurrent head and neck cancer. Recurrent cases are often challenging to treat because performing both reirradiation and surgical intervention can occasionally be difficult. This report describes the effective cisplatin intra-arterial chemotherapy with oral S-1 for a recurrent case of maxillary gingival cancer (rT4bN1M0, rStage ⅣB). The patient who had undergone chemoradiotherapy 13 years ago and achieved complete response (CR) was referred to us due to recurrence. His recurrent lesions were located on the left maxillary bone, and a metastatic cervical lymph node was detected. We approached the feeder of the locoregional recurrence site using Seldinger's technique and repeated the cisplatin intra-arterial chemotherapy 5 times. As a result, we achieved a complete response, including the regional metastatic lymph node, without radiation or surgery. Notably, although we infused the anticancer drug into the feeder of the locoregional metastatic area, we noticed its effect on the metastatic cervical lymph node. Initially, neck dissection following intra-arterial chemotherapy had been planned; however, owing to the high effectiveness of the treatment, the subsequent surgery was deemed unnecessary. No evidence of recurrence has been observed during the 2.5-year follow-up period. In the future, intra-arterial chemotherapy can be an alternative option for patients with recurrent head and neck cancers, and our result seems to be enough to indicate that possibility.

DOI PubMed

A Japanese multi-institutional phase II study of moderate hypofractionated intensity-modulated radiotherapy with image-guided technique for prostate cancer.

Katsumasa Nakamura, Keiji Nihei, Yoshihiro Saito, Naoto Shikama, Shin-Ei Noda, Ryusuke Hara, Toshiyuki Imagumbai, Takashi Mizowaki, Takeshi Akiba, Etsuo Kunieda, Masanori Someya, Saiji Ohga, Jiro Kawamori, Takuyo Kozuka, Yosuke Ota, Koji Inaba, Takeshi Kodaira, Yoshiyuki Itoh, Kouta Funakoshi, Yoshikazu Kagami

International journal of clinical oncology 29 ( 6 ) 847 - 852 2024.04 [Domestic journal]

BACKGROUND: The aim of this multi-institutional phase II study was to confirm the safety and the potential efficacy of moderately hypofractionated intensity-modulated radiotherapy (IMRT) with prostate-based image-guidance for Japanese patients. METHODS: Patients with low- or intermediate-risk localized prostate cancer were eligible. Patients with a part of high risk (having only one of the following factors, cT3a, 20 < PSA ≤ 30, or GS = 8 or 9) were also included. Hypofractionated IMRT using daily image-guided technique with prostate matching was performed with a total dose of 70 Gy in 28 fractions. Neoadjuvant hormonal therapy for 4-8 months was mandatory for patients with intermediate or high-risk prostate cancer. RESULTS: From 20 institutions, 134 patients enrolled. The median follow-up was 5.16 years (range, 1.43-6.47 years). The number of patients with low, intermediate, and high-risk prostate cancer was 20, 80, and 34, respectively. The 5-year overall, biochemical failure-free, and clinical failure-free survival was 94.5%, 96.0%, and 99.2%, respectively. The 5-year biochemical failure-free survival for patients with low-, intermediate-, and high-risk disease was 94.1%, 97.4%, and 93.9%, respectively. The incidences of grade 2 gastrointestinal (GI) and genitourinary (GU) late toxicities at 5 years were 5.3% and 5.3%, respectively. There are no acute or late toxicities ≥ grade 3. Of 124 patients who were followed for up to 5 years, the grade 2 late GU or GI toxicities were 10.5% (90% confidence intervals, 6.3-16.2%, p = 0.0958). CONCLUSION: The safety and efficacy of moderately hypofractionated IMRT with prostate-based image-guidance was confirmed among Japanese patients with prostate cancer.

DOI PubMed

Notch signaling genes and CD8+ T-cell dynamics: Their contribution to immune-checkpoint inhibitor therapy in oral squamous cell carcinoma: A retrospective study.

Kazuhiro Ogi, Takahiro Iwamoto, Takashi Sasaya, Koyo Nishiyama, Takaaki Tokura, Takanori Sasaki, Hironari Dehari, Yohei Arihara, Kazuyuki Murase, Masato Saito, Masanori Someya, Kohichi Takada, Akihiro Miyazaki

Cancer medicine 13 ( 5 ) e6985 2024.03 [International journal]

BACKGROUND: Aberrant Notch signaling pathway has been related with the tumorigenesis in head and neck region, involving oral cavity. Here, we report the correlation between mutations in the Notch signaling pathway and CD8+ T-cell infiltration via PD-L1, which lead to enhanced antitumor immunity and may target for immune-checkpoint inhibitors (ICIs) therapy. METHODS: This retrospective study analyzed the results of immunohistochemical staining for PD-L1 and CD8+ T-cell infiltration in 10 patients and whole-exome sequencing (WES) was conducted on five of these patients to identify frequently mutated genes. RESULTS: Four of 10 patients were positive for PD-L1 and CD8+ T. By analyzing WES in three of these four patients, we notably identified the mutations of NOTCH1, FBXW7, and noncoding RNA intronic mutation in NOTCH2NLR in two of these three patients. This study may enable better selection of ICI therapy with CD8+ T-cell infiltration via PD-L1 expression for oral squamous cell carcinoma patients with mutations in Notch signaling pathway.

DOI PubMed

Identification and Quantification of Radiotherapy-related Protein Expression in Cancer Tissues Using the Qupath Software and Prediction of Treatment Response.

Tomokazu Hasegawa, Masanori Someya, Takaaki Tsuchiya, Mio Kitagawa, Yuki Fukushima, Toshio Gocho, Shoh Mafune, Ryuu Okuda, Juno Kaguchi, Atsuya Ohguro, Ryo Kamiyama, Ayato Ashina, Yuka Toshima, Yoshihiko Hirohashi, Toshihiko Torigoe, Koh-Ichi Sakata

In vivo (Athens, Greece) 38 ( 3 ) 1470 - 1476 2024 [International journal]

BACKGROUND/AIM: Automated measurement of immunostained samples can enable more convenient and objective prediction of treatment outcome from radiotherapy. We aimed to validate the performance of the QuPath image analysis software in immune cell markers detection by comparing QuPath cell counting results with those of physician manual cell counting. PATIENTS AND METHODS: CD8- and FoxP3-stained cervical, CD8-stained oropharyngeal, and Ku70-stained prostate cancer tumor sections were analyzed in 104 cervical, 92 oropharyngeal, and 58 prostate cancer patients undergoing radiotherapy at our Institution. RESULTS: QuPath and manual counts were highly correlated. When divided into two groups using ROC curves, the agreement between QuPath and manual counts was 89.4% for CD8 and 88.5% for FoxP3 in cervical cancer, 87.0% for CD8 in oropharyngeal cancer and 80.7% for Ku70 in prostate cancer. In cervical cancer, the high CD8 group based on QuPath counts had a better prognosis and the low CD8 group had a significantly worse prognosis [p=0.0003; 5-year overall survival (OS), 65.9% vs. 34.7%]. QuPath counts were more predictive than manual counts. Similar results were observed for FoxP3 in cervical cancer (p=0.002; 5-year OS, 62.1% vs. 33.6%) and CD8 in oropharyngeal cancer (p=0.013; 5-year OS, 80.2% vs. 47.2%). In prostate cancer, high Ku70 group had worse and low group significantly better outcome [p=0.007; 10-year progression-free survival (PFS), 56.0% vs. 93.8%]. CONCLUSION: QuPath showed a strong correlation with manual counting, confirming its utility and accuracy and potential applicability in clinical practice.

DOI PubMed

Prediction of Treatment Response Based on Nutritional Status and Tumor Immunity in Oropharyngeal Cancer Patients Treated With Chemoradiotherapy.

Mio Kitagawa, Juno Kaguchi, Masanori Someya, Yuki Fukushima, Tomokazu Hasegawa, Takaaki Tsuchiya, Toshio Gocho, Shoh Mafune, Yutaro Ikeuchi, Ryu Okuda, Atsuya Ohguro, Ryo Kamiyama, Ayato Ashina, Yuka Toshima, Yoshihiko Hirohashi, Toshihiko Torigoe, Koh-Ichi Sakata

Cancer diagnosis & prognosis 4 ( 6 ) 789 - 796 2024 [International journal]

BACKGROUND/AIM: Radiotherapy (RT) for advanced oropharyngeal cancer (OPC) is effective, especially when combined with chemotherapy (CRT). However, its success can vary depending on factors, such as tumor stage, HPV infection (p16 status), and the patient's nutritional and immune status. This study examined the controlling nutritional status (CONUT) score and tumor immunity as predictive factors for treatment outcomes in OPC, aiming to develop a personalized risk score. PATIENTS AND METHODS: A retrospective analysis was conducted on 84 patients with OPC treated with definitive RT or CRT, and survival outcomes were compared based on various factors, including BMI, CONUT score, CD8 expression, and HLA class II expression. RESULTS: We observed better overall survival (OS) rates in CD8-positive patients and those with higher HLA class II expression. The univariate analysis identified stage, p16 status, BMI, CONUT score, and CD8 expression as significantly associated with OS. In multivariate analysis, stage, BMI, and CONUT score remained significant predictors of OS. A risk scoring system was developed based on stage, p16 status, BMI, CONUT score, and CD8 expression. Patients were categorized into low-risk and high-risk groups, with significantly better survival in the low-risk group. CONCLUSION: A combined risk score incorporating clinical, nutritional, and immune factors can improve the prediction of treatment outcomes for OPC patients. This risk stratification may enable personalized treatment plans and improve ΟS rates.

DOI PubMed

[RPT Doi Award: Virtual clinical trial based on outcome modeling with iteratively redistributed extrapolation data].

Kohei Oguma, Taiki Magome, Masanori Someya, Tomokazu Hasegawa, Koh-Ichi Sakata

Igaku butsuri : Nihon Igaku Butsuri Gakkai kikanshi = Japanese journal of medical physics : an official journal of Japan Society of Medical Physics 44 ( 3 ) 52 - 52 2024 [Domestic journal]

DOI PubMed

Prediction of late adverse events in pelvic cancer patients receiving definitive radiotherapy using radiation-induced gamma-H2AX foci assay.

Masanori Someya, Tomokazu Hasegawa, Asako J Nakamura, Takaaki Tsuchiya, Mio Kitagawa, Toshio Gocho, Sho Mafune, Yutaro Ikeuchi, Hiroshi Tauchi, Koh-Ichi Sakata

Journal of radiation research 64 ( 6 ) 948 - 953 2023.11 [International journal]

Radiation can induce DNA double-stranded breaks, which are typically detected by the fluorescence of phosphorylated histone H2AX. In this study, we examined the usefulness of the dynamics of radiation-induced gamma-H2AX foci of peripheral blood lymphocytes (PBLs), as a marker of DNA repair ability, in predicting late adverse events from radiotherapy. A total of 46 patients with cervical, vaginal and anal canal cancers treated with radical radiotherapy between 2014 and 2019 were included in this analysis. Concurrent chemotherapy was administered in 36 cases (78.3%). Peripheral blood was obtained before treatment, and then irradiated ex vivo with 1 Gy X-ray. The ratio of radiation-induced gamma-H2AX foci in PBLs measured at 30 min and at 4 h was defined as the foci decay ratio (FDR). With a median follow-up of 54 months, 9 patients (19.6%) were observed to have late genitourinary or gastrointestinal (GU/GI) toxicity. The FDR ranged from 0.51 to 0.74 (median 0.59), with a significantly higher incidence of Grade 1 or higher late adverse events in the FDR ≥ 0.59 group. In multivariate analysis, FDR ≥ 0.59 and hypertension also emerged as significant factors associated with the development of late toxicities. Overall, our results suggest that measurement of radiation-induced gamma-H2AX foci in PBLs may predict the risk of late GU/GI toxicities from chemoradiotherapy, which can enable tailoring the radiation dose to minimize adverse effects.

DOI PubMed

Analysis of treatment response with proteins related to tumor immunity in postoperative irradiated cervical cancer patients

Shoh Mafune, Masanori Someya, Tomokazu Hasegawa, Takaaki Tsuchiya, Mio Kitagawa, Toshio Gocho, Ryu Okuda, Masahiro Iwasaki, Motoki Matsuura, Terufumi Kubo, Yoshihiko Hirohashi, Toshihiko Torigoe, Tsuyoshi Saito, Koh-ichi Sakata

Anticancer research 44 ( 7 ) 3077 - 3086 2023.11 [International journal]

BACKGROUND/AIM: This study evaluated the association between programmed cell death-ligand 1 (PD-L1) and prognosis in patients with cervical cancer treated with postoperative radiation and the impact of neoadjuvant chemotherapy (NAC) on this association. PATIENTS AND METHODS: Immunohistochemical analysis was performed on biopsy specimens from 42 patients who did not receive NAC and from paired samples before (biopsies) and after (resected tissues) chemotherapy from 46 patients who received NAC to determine the association of PD-L1 with radiotherapy outcomes. RESULTS: In the non-NAC group, patients with ≥10% PD-L1-expressing tumor cells prior to treatment had better recurrence-free survival (RFS) than those with <10% PD-L1-expressing tumor cells (p=0.001). In the NAC group, RFS was significantly lower (p=0.005) in the group with a ≥5% reduction of PD-L1 expression in tumor cells after chemotherapy than in those with <5% reduction. In multivariate analysis, only PD-L1 expression (non-NAC group) and the change in PD-L1 expression (NAC group) were associated with RFS. CONCLUSION: Low PD-L1 expression in a cervical tumor prior to treatment was identified as a risk factor for a poor outcome after postoperative radiotherapy. Furthermore, NAC induces an immunological shift that reduces PD-L1 levels in tumor cells, thereby negatively impacting treatment outcomes.

DOI PubMed

放射線感受性の個人差に基づく次世代の放射線治療と放射線防護腫瘍および正常組織の放射線感受性予測に基づいた個別化放射線治療の実践(Personalized radiotherapy based on the prediction of radiosensitivity of tumors and normal tissues)

Someya Masanori, Hasegawa Tomokazu, Tsuchiya Takaaki, Kitagawa Mio, Gocho Toshio, Mafune Shoh, Sakata Koh-ichi

日本放射線影響学会大会講演要旨集 ( (一社)日本放射線影響学会 ) 66回 12 - 12 2023.11

Immunohistological evaluation of patients treated with intra-arterial chemoradiotherapy and surgery for oral cancer.

Yutaro Ikeuchi, Masanori Someya, Tomokazu Hasegawa, Masato Saito, Shoh Mafune, Takaaki Tsuchiya, Mio Kitagawa, Toshio Gocho, Hironari Dehari, Kazuhiro Ogi, Takanori Sasaki, Yoshihiko Hirohashi, Toshihiko Torigoe, Naoki Hirokawa, Akihiro Miyazaki, Koh-Ichi Sakata

Medical molecular morphology 56 ( 4 ) 288 - 296 2023.07 [Domestic journal]

Preoperative intra-arterial chemoradiotherapy (IACRT) can improve the outcome and reduce the extent of surgery in patients with advanced oral cancer. However, the response to this regimen varies among patients, which may be related to the immune status of the tumor. We investigated the effects of proteins involved in tumor immunity on the outcomes of combined IACRT and surgery for oral cancer. We examined CD8 + and FoxP3 + tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression on immune cells and tumor cells in pretreatment biopsy samples from 69 patients diagnosed with oral cancer treated with IACRT at our institution during 2000-2020. Patients with abundant CD8 + TILs had significantly better 5-year disease-specific survival (DSS) compared to that of patients with less infiltration of these cells (P = 0.016). Patients with higher FoxP3 + T-cells invasion had significantly better DSS compared to that of less FoxP3 (P = 0.005). Patients with high PD-L1 expression in tumor cells and immune cells had significantly better DSS than that of patients with low PD-L1 expression in these cells (P = 0.009 and P = 0.025, respectively). Collectively, these results suggest that the tumor immune microenvironment could affect outcomes of IACRT treatment in oral cancer.

DOI PubMed

【膵癌診療ガイドライン2022改訂のポイント】放射線療法

伊藤芳紀, 中村聡明, 大栗隆行, 染谷正則, 篠藤誠

膵臓 ( (一社)日本膵臓学会 ) 38 ( 2 ) 121 - 126 2023.04

『膵癌診療ガイドライン2022年版』の放射線療法分野は局所進行切除不能膵癌に対する一次治療のCQを含めて9つのCQが設定された.局所進行切除不能膵癌に対する一次治療のCQでは2019年版と同様に化学放射線療法と化学療法単独が並列で提案された.化学放射線療法前の導入化学療法のCQについては,2019年版と異なり,ゲムシタビン塩酸塩による導入化学療法を行わないことが提案された.新たなCQとして,局所進行切除不能膵癌に対する高精度放射線治療(強度変調放射線治療,体幹部定位放射線治療,粒子線治療)とハイパーサーミアの2つの項目が設定され,高精度放射線治療を用いた線量増加を行うことが提案された.膵癌の遠隔転移・再発巣に関して,2019年版と同様に局所再発・所属リンパ節と肺転移に対して放射線療法を行うことが提案された.(著者抄録)

Virtual clinical trial based on outcome modeling with iteratively redistributed extrapolation data.

Kohei Oguma, Taiki Magome, Masanori Someya, Tomokazu Hasegawa, Koh-Ichi Sakata

Radiological physics and technology 16 ( 2 ) 262 - 271 2023.03 [Domestic journal]

Virtual clinical trials (VCTs) can potentially simulate clinical trials on a computer, but their application with a limited number of past clinical cases is challenging due to the biased estimation of the statistical population. In this study, we developed ExMixup, a novel training technique based on machine learning, using iteratively redistributed extrapolated data. Information obtained from 100 patients with prostate cancer and 385 patients with oropharyngeal cancer was used to predict the recurrence after radiotherapy. Model performance was evaluated by developing outcome prediction models based on three types of training methods: training with original data (baseline), interpolation data (Mixup), and interpolation + extrapolation data (ExMixup). Two types of VCTs were conducted to predict the treatment response of patients with distinct characteristics compared to the training data obtained from patient cohorts categorized under risk classification or cancer stage. The prediction models developed with ExMixup yielded concordance indices (95% confidence intervals) of 0.751 (0.719-0.818) and 0.752 (0.734-0.785) for VCTs on the prostate and oropharyngeal cancer datasets, respectively, which significantly outperformed the baseline and Mixup models (P < 0.01). The proposed approach could enhance the ability of VCTs to predict treatment results in patients excluded from past clinical trials.

DOI PubMed

末梢血リンパ球TCRレパトア解析を用いたNSCLCの治療効果予測(Prediction of Treatment Response in NSCLC using Peripheral Blood Lymphocyte TCR Repertoire Analysis)

Someya Masanori, Hasegawa Tomokazu, Kitagawa Mio, Tsuchiya Takaaki, Fukushima Yuki, Gocho Toshio, Mafune Shou, Kanaseki Takayuki, Tokita Serina, Sakata Koh-ichi

日本医学放射線学会学術集会抄録集 ( (公社)日本医学放射線学会 ) 82回 S173 - S173 2023.03

Combined chemoradiotherapy and programmed cell death-ligand 1 blockade leads to changes in the circulating T-cell receptor repertoire of patients with non-small-cell lung cancer.

Masanori Someya, Serina Tokita, Takayuki Kanaseki, Mio Kitagawa, Tomokazu Hasegawa, Takaaki Tsuchiya, Yuki Fukushima, Toshio Gocho, Yoh Kozuka, Shoh Mafune, Yutaro Ikeuchi, Mamoru Takahashi, Keigo Moniwa, Kazuhiko Matsuo, Tadashi Hasegawa, Toshihiko Torigoe, Koh-Ichi Sakata

Cancer science 113 ( 12 ) 4394 - 4400 2022.12 [International journal]

Combined chemoradiotherapy (CRT) and programmed cell death-ligand 1 (PD-L1) blockade is a new care standard for unresectable stage III non-small-cell lung cancer (NSCLC). Although this consolidation therapy has improved the overall survival of patients with NSCLC, the synergistic action mechanisms of CRT and immunotherapy on T cells remain unclear. In addition, there is a paucity of reliable biomarkers to predict clinical responses to therapy. In this study, we analyzed T-cell receptor (TCR) sequences in the peripheral blood of five patients with NSCLC. T-cell receptor analysis was undertaken before treatment, after CRT, and after PD-L1 blockade. Notably, we observed the expansion and alteration of the dominant T-cell clonotypes in all cases with a complete response. In contrast, neither expansion nor alteration of the TCR repertoire was observed in cases with progressive disease. T cell expansion was initiated after CRT and was further enhanced after PD-L1 blockade. Our findings suggest the systemic effect of CRT on circulating T cells in addition to the curative effect on limited tumor sites. Dynamic changes in circulating T-cell clonotypes could have a prognostic significance for combined CRT and PD-L1 blockade.

DOI PubMed

Predictive value of an exosomal microRNA-based signature for tumor immunity in cervical cancer patients treated with chemoradiotherapy.

Masanori Someya, Tomokazu Hasegawa, Takaaki Tsuchiya, Mio Kitagawa, Yuki Fukushima, Toshio Gocho, Shoh Mafune, Yutaro Ikeuchi, Yoh Kozuka, Masashi Idogawa, Yoshihiko Hirohashi, Toshihiko Torigoe, Masahiro Iwasaki, Motoki Matsuura, Tsuyoshi Saito, Koh-Ichi Sakata

Medical molecular morphology 56 ( 1 ) 38 - 45 2022.11 [Domestic journal]

Resistance of cervical cancer to radiotherapy with concurrent chemotherapy (CCRT) results in a poor prognosis. To identify new biomarkers for predicting the treatment response and prognosis, we explored exosomal microRNA (miRNA) expression signatures associated with the outcome of cervical cancer patients treated with CCRT. Exosomes were isolated from the plasma of 45 patients prior to CCRT during 2014-2020, and miRNA analysis was performed by next-generation sequencing. At a median follow-up of 38 months, 26 patients were recurrence free, 15 patients had died of the disease, and 4 patients received salvage chemotherapy due to distant metastasis. Of the 2522 miRNAs detected, 9 (miR-148a-5p, 1915-3p, 3960, 183-5p, 196b-5p, 200c-3p, 182-5p, 374a-5p, and 431-5p) showed differential expression between the recurrence-free and recurrence groups. Patients were divided into high- and low-risk groups according to the cutoff of the miRNAs-based risk score calculated from respective expression levels. The high-risk group had significantly worse disease-specific survival than the low-risk group (p < 0.001). In addition, miR-374a-5p and miR-431-5p expression showed a weak inverse correlation with tumor-infiltrating CD8+ and FOXP3+ T cells, suggesting a potential inhibitory effect on CCRT by suppressing tumor immunity. This miRNA signature could improve non-invasive monitoring and personalized treatment for cervical cancer.

DOI PubMed

Clinical and histopathologic effects of neoadjuvant intra-arterial chemoradiotherapy with cisplatin in combination with oral S-1 on stage III and IV oral cancer.

Kazushige Koike, Nobuhide Ohashi, Koyo Nishiyama, Junya Okamoto, Takanori Sasaki, Kazuhiro Ogi, Hironari Dehari, Naoki Hirokawa, Masanori Someya, Masato Saito, Hiroki Okuda, Akemi Otani, Tomoko Sonoda, Taro Sugawara, Tadashi Hasegawa, Hiroyoshi Hiratsuka, Koh-Ichi Sakata, Akihiro Miyazaki

Oral surgery, oral medicine, oral pathology and oral radiology 134 ( 3 ) 347 - 353 2022.09 [International journal]

OBJECTIVE: The aim of this study was to examine the clinical and histopathologic effects of neoadjuvant intra-arterial chemoradiotherapy (IACRT) using cisplatin in combination with oral S-1 (tegafur/gimeracil/oteracil potassium) on stage III and IV oral squamous cell carcinoma. STUDY DESIGN: Thirty patients received infusions of superselective intra-arterial cisplatin 60 mg/m2 by the Seldinger method and conventional external beam radiotherapy (total 40 Gy) combined with oral S-1 on the day of irradiation. Curative surgery and neck dissection were performed 4 to 6 weeks after IACRT. The clinical response of the primary lesion was evaluated approximately 4 weeks after IACRT. The surgically resected specimens were examined for histologic features according to the grading system for histologic evaluation and for residual tumor grade (RGrades). RESULTS: Histopathologic evaluation of the therapeutic effect was grade 2 in 10 patients and grade 3 in 16 patients. According to the distribution of RGrades, the remaining tumor cells were mostly in the central area of the primary lesion, as seen in 24 patients. CONCLUSIONS: These findings indicate that neoadjuvant IACRT with cisplatin and oral S-1 was an effective treatment, suggesting the possibility of reducing the extent of curative surgery based on RGrades.

DOI PubMed

Delayed-onset abscopal effect after palliative radiotherapy for acral melanoma treated with anti-PD-1 therapy.

Hiroshi Sasaki, Junji Kato, Kohei Horimoto, Sayuri Sato, Yuna Hosokawa, Toshiya Handa, Eri Kobayashi, Kazuki Furudate, Haruka Sigyo, Takaaki Tsuchiya, Masanori Someya, Hisashi Uhara

The Journal of dermatology 49 ( 8 ) e255-e256 2022.03 [International journal]

DOI PubMed

Radiotherapy for HPV-related cancers: prediction of therapeutic effects based on the mechanism of tumor immunity and the application of immunoradiotherapy.

Masanori Someya, Yuki Fukushima, Tomokazu Hasegawa, Takaaki Tsuchiya, Mio Kitagawa, Toshio Gocho, Shoh Mafune, Yutaro Ikeuchi, Yoh Kozuka, Yoshihiko Hirohashi, Toshihiko Torigoe, Masahiro Iwasaki, Motoki Matsuura, Tsuyoshi Saito, Koh-Ichi Sakata

Japanese journal of radiology 40 ( 5 ) 458 - 465 2022.01 [Domestic journal]

Human papillomavirus (HPV)-related cancer is one of the diseases entities for which the applications of radiotherapy have been increasing. Recently, the process of carcinogenesis from HPV infection and the mechanism of tumor immunity that develops during disease progression have been elucidated. In this review, we will describe the mechanism of tumor immunity and how chemoradiotherapy may overcome and improve the efficacy of tumor immunity. We will also discuss the usefulness of proteins involved with tumor immunity as a predictive marker of radiotherapy response, and present an overview of ongoing clinical trials of combinations of immune checkpoint inhibitors and radiotherapy to demonstrate the promising combination therapy that has been currently emerging.

DOI PubMed

Stiff coils enhance shape retention and pressure resistance in an aneurysm model even at low volume.

Hiroki Okuda, Naoki Hirokawa, Masato Saitoh, Akemi Otani, Masanori Someya, Yoko Usami, Koh-Ichi Sakata

Minimally invasive therapy & allied technologies : MITAT : official journal of the Society for Minimally Invasive Therapy 31 ( 5 ) 1 - 10 2021.09 [International journal]

PURPOSE: To elucidate the characteristics of 3 D frame coils and identify the optimal coil for visceral aneurysms. MATERIAL AND METHODS: Using a vascular model, we compared the postembolization coil distribution and repulsive force of three coils: Guglielmi detachable coil (GDC; stock wire diameter, 0.004 in; primary diameter, 0.015 in), Target XL (0.003, 0.014), and Target XXL (0.003, 0.017). Additionally, the coil area, roundness, and center of gravity were quantitatively compared. The coil repulsive force was measured by compressing the postembolization vessel model with a digital force gauge. RESULTS: There were no significant differences in the coil area and roundness among the three coil types. Compared with the Target coils, the GDC deployed evenly along the vessel wall, its center of gravity was less displaced, and although it had the lowest embolic density, its repulsive force was greater regardless of the number of coils used. CONCLUSIONS: GDC coils with a larger stock wire diameter and a smaller primary diameter unfolded evenly along the wall and had a greater repulsive force. Coil stiffness contributes to coil stability and shape retention, indicating the possibility of preventing recurrence by selecting a frame coil with a focus on coil stiffness.

DOI PubMed

Prediction of treatment response from the microenvironment of tumor immunity in cervical cancer patients treated with chemoradiotherapy.

Masanori Someya, Takaaki Tsuchiya, Yuki Fukushima, Tomokazu Hasegawa, Masakazu Hori, Mio Kitagawa, Toshio Gocho, Shoh Mafune, Yutaro Ikeuchi, Yoshihiko Hirohashi, Toshihiko Torigoe, Masahiro Iwasaki, Motoki Matsuura, Tsuyoshi Saito, Yoshihisa Matsumoto, Koh-Ichi Sakata

Medical molecular morphology 54 ( 3 ) 245 - 252 2021.09 [Domestic journal]

To supplement clinical decision-making in the management of cervical cancer, various prognostic factors, including tumor immune microenvironments, were examined in patients with cervical cancer treated with definitive chemoradiotherapy. We retrospectively analyzed the expression of CD8, FoxP3, HLA-1, PD-L1, and XRCC4 in 100 cases of cervical cancer. The observed tumor immune microenvironments were also classified into three types: inflamed, excluded, and cold type. Less FoxP3+ T cells and cold-type tumor were found to be poor prognostic factors in addition to non-SCC, large pre-treatment tumor volume, and three or less cycles of concurrent chemotherapy based on multivariate analysis. Cold-type tumors had significantly worse prognoses than the other two types, whereas inflamed- and excluded-type tumors showed similar 5-year disease-specific survival (P < 0.001; 0% vs. 60.3% vs. 72.3%). Radiotherapy could overcome the inhibitory immune microenvironment that occurs in excluded type. Individualized combination therapy adapted to pre-treatment tumor immunity may be necessary to improve radiotherapy outcomes in cervical cancer.

DOI PubMed

肛門管癌に対するS-1+MMCを用いた化学放射線療法

池内佑太郎, 福島悠希, 眞船翔, 小塚陽介, 土屋高旭, 長谷川智一, 堀正和, 染谷正則, 坂田耕一

北海道放射線医学雑誌 ( (NPO)メディカルイメージラボ ) 1 22 - 26 2021.03

本邦では、肛門管の原発性扁平上皮癌(SCC)は稀な疾患であり、治療方法及び治療成績に関する報告は少ない。現在、肛門管癌に対する化学放射線療法の標準治療は、5-FU+MMC+RTとされており、救済治療として手術が考えられている。5-FUは持続静注投与であり、入院加療が必要となり、そのため、経口剤であるS-1を用いたS-1+MMC+RTの方が、利便性が高いと考える。さらに、S-1は、5-FUのプロドラックであるテガフールと、ギメラシルが含まれている。ギメラシルは、5-FUの肝臓での分解を強力に抑え、結果としてフルオトウラシルを生体内で高濃度かつ長時間維持させる目的でS-1に含有されているが、他施設及び当科の基礎研究でギメラシルの放射線増感があることが示唆されており、それに期待してS-1を使用することとした。今回、当院で肛門管癌(StageI-IIIC(UICC8th))に対してS-1+MMC+RTを施行した9症例に対して検討した。(著者抄録)

Association between radiotherapy-induced alteration of programmed death ligand 1 and survival in patients with uterine cervical cancer undergoing preoperative radiotherapy.

Takaaki Tsuchiya, Masanori Someya, Yu Takada, Tomokazu Hasegawa, Mio Kitagawa, Yuki Fukushima, Toshio Gocho, Masakazu Hori, Kensei Nakata, Yoshihiko Hirohashi, Toshihiko Torigoe, Tsuyoshi Saito, Koh-Ichi Sakata

Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 196 ( 8 ) 725 - 735 2020.08 [Refereed] [International journal]

PURPOSE: To evaluate radiotherapy-induced changes in the expression of programmed death ligand 1 (PD-L1), programmed death 1 (PD-1), and human leukocyte antigen class I (HLA-1) in patients with uterine cervical cancer, as well as infiltration of CD8+ and Forkhead box P3+ (FoxP3+) T lymphocytes into tumor tissue and the prognostic value of these parameters. MATERIALS AND METHODS: We performed immunohistochemical analysis of pre-radiotherapy biopsies and corresponding post-radiotherapy resected tissues in 104 uterine cervical cancer patients undergoing preoperative chemoradiotherapy or radiotherapy alone. We scored the expression of various proteins to distinguish positive from negative samples. RESULTS: PD-L1-expressing tumor cells (PD-L1 TC) increased significantly after chemoradiotherapy (p = 0.043). CD8+ T cell infiltration (p = 0.002) and FoxP3+ T cell infiltration (p = 0.003) decreased significantly after chemoradiotherapy. Expression of PD‑1, PD-L1-expressing immune cells (PD-L1 IC), and HLA‑1 did not change after chemoradiotherapy. In biopsy specimens obtained before chemoradiotherapy or radiotherapy, greater infiltration of CD8+ T cells (p = 0.001) and FoxP3+ T cells (p = 0.003) were significant predictors of better overall survival (OS). In surgical specimens obtained after chemoradiotherapy or radiotherapy, greater infiltration of PD-L1 TC was the only significant predictor of better OS (p < 0.001) and was related to a significantly lower probability of out-of-field recurrence (p = 0.005). CONCLUSION: Chemoradiotherapy induced an immunologic shift that increased PD-L1 TC. Chemoradiotherapy has immunological effects that can influence the results of treatment for uterine cervical cancer.

DOI PubMed

Prediction of Results of Radiotherapy With Ku70 Expression and an Artificial Neural Network

TOMOKAZU HASEGAWA, MASANORI SOMEYA, MASAKAZU HORI, TAKAAKI TSUCHIYA, YUUKI FUKUSHIMA, YOSHIHISA MATSUMOTO, KOH-ICHI SAKATA

In Vivo ( Anticancer Research USA Inc. ) 34 ( 5 ) 2865 - 2872 2020.05 [Refereed] [International journal]

Background/Aim: Accurate prediction of radiotherapy results is indispensable for the individualized selection of treatment modalities of cancer. We examined the application of the artificial neural network (ANN) model in predicting radiotherapy results using clinical factors and immunohistochemical staining of Ku70 as inputs. Patients and Methods: We analyzed 79 prostate cancer patients with localized adenocarcinoma treated with radiotherapy between August 2001 and October 2010. We also analyzed 46 hypopharyngeal cancer patients with squamous cell carcinoma treated with radiotherapy between March 2002 and December 2009. The properly trained ANN analysis using a standard feedforward, back-propagation neural network was used to predict the radiotherapy treatment results. Results: The areas under the receiver-operating characteristic curve (AUC) were 0.939 for patients treated with intensity modulated radiotherapy (IMRT)+androgen deprivation therapy (ADT), 0.803 for IMRT alone, and 0.960 for 3D-conformal radiotherapy (CRT) alone in prostate cancer. Sensitivity and specificity were 85.7% and 90.4% for IMRT+ADT, 75.0% and 88.5% for IMRT alone, and 92.3% and 100% for 3D-CRT alone. The AUC was 0.901 for hypopharyngeal cancer. Sensitivity and specificity were 66.7% and 88.2%, respectively. Conclusion: We demonstrated a possibility to predict the radiotherapy treatment results in prostate and hypopharyngeal cancer using ANN in combination with Ku70 expression and clinical factors as inputs.

DOI PubMed

Evaluation of the urethral alpha/beta ratio and tissue repair half-time for iodine-125 prostate brachytherapy with or without supplemental external beam radiotherapy

Toshio Gocho, Masakazu Hori, Yuuki Fukushima, Masanori Someya, Mio Kitagawa, Tomokazu Hasegawa, Takaaki Tsuchiya, Masato Hareyama, Masaru Takagi, Kohei Hashimoto, Naoya Masumori, Koh-ichi Sakata

BRACHYTHERAPY ( ELSEVIER SCIENCE INC ) 19 ( 3 ) 290 - 297 2020.05 [International journal]

PURPOSE: To assess the correlation between postimplant dosimetric quantifiers and the genitourinary (GU) toxicity of low-dose rate brachytherapy for prostate cancer.METHODS AND MATERIALS: The minimum urethral dose (UD10, 30, and 90) and the percent volume of the urethra receiving the prescription dose (V100, V150) were calculated from the post-implant dose-volume histograms of 182 patients. We then calculated various urethral biologically equivalent doses (uBEDs) using different values of the alpha/beta ratio and tissue repair half-time (t1/2) and examined the correlations with GU toxicity.RESULTS: Common dosimetric quantifiers, such as UD90 (brachytherapy) + UD50 (external beam radiotherapy), showed no correlation with Grade >= 2 GU toxicity. There was a significant correlation between Grade GU toxicity and uBED when the alpha/beta value was 0.5 or 1 Gy and t1/2 was 0.5-2.5 h. An uBED (alpha/beta = 1.0, t1/2 = 0.5) had the largest hazard ratio for GU toxicity, and it was also significantly correlated with Grade >= 2 GU toxicity according to multivariate analysis.CONCLUSIONS: We observed a significant correlation of uBED with GU toxicity when alpha/beta was 0.5 or 1.0 Gy and t1/2 was 0.5-2.5 h. As the simple formula we used has not been verified in basic experiments, more data are needed to validate our results. (C) 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

DOI PubMed

Chemotherapy after progression on nivolumab is essential for responders with genetic alterations of driver gene: Review of two recurrent/metastatic oral squamous cell carcinoma patients.

Kazuhiro Ogi, Junichi Kobayashi, Takafumi Nakagaki, Junya Okamoto, Kazushige Koike, Naoki Hirokawa, Masanori Someya, Hiroki Sakamoto, Kohichi Takada, Takashi Tokino, Yasushi Sasaki, Hiroyoshi Hiratsuka, Akihiro Miyazaki

Oral oncology ( Elsevier {BV} ) 102 104509 - 104509 2020.03 [Refereed] [International journal]

DOI PubMed

放射線治療を施行した進行子宮頸癌患者における腫瘍免疫と生存の関連性(Association between tumor Immunity and survival in patients with advanced uterine cervical cancer treated with raiotherapy)

Someya Masanori, Hasegawa Tomokazu, Tsuchiya Takaaki, Fukushima Yuuki, Kitagawa Mio, Hori Masakazu, Sakata Koh-ichi, Takada Yu, Nakata Kensei, Miura Katsutoshi

日本医学放射線学会学術集会抄録集 ( (公社)日本医学放射線学会 ) 79回 S176 - S176 2020.02

Phase 2 Study of Neoadjuvant Treatment of Sequential S-1-Based Concurrent Chemoradiation Therapy Followed by Systemic Chemotherapy with Gemcitabine for Borderline Resectable Pancreatic Adenocarcinoma (HOPS-BR 01).

Tsuyoshi Hayashi, Toru Nakamura, Yasutoshi Kimura, Makoto Yoshida, Masanori Someya, Hiroshi Kawakami, Yusuke Sakuhara, Norio Katoh, Kuniyuki Takahashi, Yoshiyasu Ambo, Katsutoshi Miura, Masayo Motoya, Eiichi Tanaka, Katsuhiko Murakawa, Takumi Yamabuki, Hajime Yamazaki, Akio Katanuma, Satoshi Hirano

International journal of radiation oncology, biology, physics ( Elsevier {BV} ) 105 ( 3 ) 606 - 617 2019.11 [Refereed] [International journal]

PURPOSE: Preoperative treatment is recommended for borderline resectable pancreatic ductal adenocarcinoma. However, the standard treatment has not yet been determined. We conducted a multicenter phase 2 study to investigate the efficacy of neoadjuvant treatment of sequential chemoradiation followed by chemotherapy. METHODS AND MATERIALS: All enrolled patients were treated by preoperative chemoradiation (a total dose of 50.4 Gy in 28 fractions and orally administered S-1 at 80 mg/m2 on the day of irradiation) followed by chemotherapy (administration of gemcitabine at 1000 mg/m2/dose on days 1, 8, and 15 in 3 cycles of 4 weeks) and attempted curative resection. The primary outcome was an R0 resection rate among patients who completed preoperative treatment and pancreatectomy. The threshold of the R0 resection rate was defined as 74% based on a previous study of up-front surgery. RESULTS: Forty-five patients were included. Twenty-one patients could not undergo pancreatectomy because of progressive diseases (n = 14), adverse events (n = 5), or consent withdrawal (n = 2), and 4 patients underwent additional resection after dropping out. The resection rates were 53.3% and 62.2% in the per-protocol set (PPS) and full analysis set (FAS) populations, respectively. The R0 resection rates were 95.8% (95% confidence interval, 78.9%-99.9%) and 96.4% (81.7%-99.9%) in the PPS and FAS populations, respectively. The median overall survival and progression-free survival of all the included patients were 17.3 and 10.5 months, respectively. The median survival time of the patients with pancreatectomy was significantly longer than that of the patients without pancreatectomy in the PPS (27.9 vs 12.3 months; P = .001) and FAS populations (32.2 vs 11.8 months; P < .001). CONCLUSIONS: This study revealed that a long duration of preoperative treatment of sequential chemoradiation followed by systemic chemotherapy provides a high rate of R0 resection and sufficient survival time in patients undergoing pancreatectomy.

DOI PubMed

Influence of XRCC4 expression by breast cancer cells on ipsilateral recurrence after breast-conserving therapy.

Mio Kitagawa, Masanori Someya, Tomokazu Hasegawa, Toshihiko Mikami, Kazuaki Asaishi, Tadashi Hasegawa, Yoshihisa Matsumoto, Goro Kutomi, Ichiro Takemasa, Koh-Ichi Sakata

Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 195 ( 7 ) 648 - 658 2019.07 [Refereed] [International journal]

BACKGROUND: We examined the expression of nonhomologous end-joining (NHEJ) proteins by breast cancer cells in patients with or without ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy. We also investigated whether there was a difference of NHEJ-related protein expression by tumor cells between two types of IBTR, i.e., true recurrence (TR) with regrowth from the tumor bed or development of a new primary tumor (NP). PATIENTS AND METHODS: The original cohort comprised 560 breast cancer patients who received breast-conserving therapy between February 1995 and March 2006, including 520 patients without IBTR and 40 patients with IBTR. Propensity score matching was employed to select 40 trios (120 patients) consisting of 1 patient with IBTR and 2 patients without IBTR. Immunohistochemical examination of proteins related to NHEJ was performed in surgical specimens. RESULTS: The 40 patients with IBTR included 22 patients who developed TR and 18 who had NP. The 15-year overall survival rate was 85.9% for patients with NP and 95.5% for those with TR, while it was 96.5% for patients without IBTR. Patients with high XRCC4 expression in tumor cells had significantly higher IBTR rates than those with low XRCC4 expression (P < 0.001). The frequency of TR was significantly higher in patients with high expression of XRCC4 than in those with low XRCC4 expression (p < 0.001). XRCC4 expression by tumor cells was not significantly related to development of NP. CONCLUSION: IBTR due to TR may be related to low radiosensitivity of tumor cells, possibly related to high XRCC4 expression.

DOI PubMed

Histopathological differences of experimental aneurysms treated with bare platinum, fibered, and bioactive coils.

Yoko Usami, Naoki Hirokawa, Masato Saitoh, Hiroki Okuda, Masanori Someya, Tadashi Hasegawa, Yasunari Takakuwa, Koh-Ichi Sakata

Minimally invasive therapy & allied technologies : MITAT : official journal of the Society for Minimally Invasive Therapy 28 ( 3 ) 172 - 177 2019.06 [Refereed] [International journal]

PURPOSE: To evaluate the histopathological features of experimental aneurysms embolized with bare platinum, fibered, and bioactive coils. MATERIAL AND METHODS: Twelve experimental aneurysms were constructed in three swine. The aneurysms were divided into four groups and were embolized using a bare platinum coil alone (P group, n = 2), a bioactive coil alone (B group, n = 2), a combination of fibered and bare platinum coils (F/P group, n = 4) and a combination of fibered and bioactive coils (F/B group, n = 4). Histopathological data for all aneurysms recorded at 63 days were analyzed in terms of neointima formation, fibrosis, foreign-body giant-cell infiltration, and organization. RESULTS: Fibrosis was significantly greater in group B compared with that in group F/P (p = .02). Inflammation with foreign-body giant-cell infiltration was significantly greater in groups F/P and F/B compared with that in groups P and B (p = .007). CONCLUSION: The present study revealed that the embolic effect of fibered coils was not a thrombus but instead was a foreign-body response in the chronic phase.

DOI PubMed

Efficacy of combined radiotherapy and anti-programmed death 1 therapy in acral and mucosal melanoma.

Junji Kato, Tokimasa Hida, Masanori Someya, Sayuri Sato, Masahide Sawada, Kohei Horimoto, Mao Fujioka, Tomoyuki Minowa, Yoshiyuki Matsui, Takaaki Tsuchiya, Mio Kitagawa, Kensei Nakata, Koh-Ichi Sakata, Toshihiko Torigoe, Hisashi Uhara

The Journal of dermatology 46 ( 4 ) 328 - 333 2019.04 [Refereed] [International journal]

Some studies showed that clinical response to immune check point inhibitors is lower in acral and mucosal melanoma than in cutaneous melanoma. Although the synergistic effect of radiotherapy (RT) and ipilimumab has been reported in patients with brain metastasis, the efficacy of combined RT and anti-programmed death 1 (PD-1) therapy for acral and mucosal melanoma is unclear. The present study aimed to evaluate the efficacy of combined RT and anti-PD-1 therapy for acral and mucosal melanoma. We retrospectively analyzed patients with acral or mucosal melanoma who were treated with anti-PD-1 and RT at Sapporo Medical University Hospital. In 10 patients (acral, 3; mucosal, 7), the response rate (RR) and the disease control rate (DCR) were 40% and 60%, respectively. As regards mucosal melanoma, four of the seven patients had achieved complete response + partial response, and three had progressive disease (RR = 57.1%). Meanwhile, two of the three patients with acral melanoma had stable disease and one had progressive disease (RR and DCR were 0% and 66.6%, respectively). Except for the patients treated with palliative RT for bone metastasis in the present study, the RR was 50% (4/8 patients), and the DCR was 75% (6/8 patients). Vitiligo developed after RT in five (50%) patients at a median duration of 2 months after RT. The clinical response and the high occurrence of vitiligo suggest that the combination of RT and anti-PD-1 therapy could be effective in some patients with mucosal melanoma.

DOI PubMed

Successful rechallenge with nivolumab therapy after radiotherapy in mucosal melanoma.

Junji Kato, Tokimasa Hida, Kohei Horimoto, Sayuri Sato, Keiju Kobayashi, Masahide Sawada, Mao Fujioka, Takaaki Tsuchiya, Masanori Someya, Hisashi Uhara

The Journal of dermatology 46 ( 2 ) e72-e73 - e73 2019.02 [Refereed] [International journal]

DOI PubMed

当院で腔内照射を施行した子宮頸癌の線量解析(DVH Analysis of Intracavitary Brachytherapy for Uterine Cervical Cancer)

Someya Masanori, Hasegawa Tomokazu, Tsuchiya Takaaki, Kitagawa Mio, Gocho Toshio, Fukushima Yuuki, Takada Yu, Miura Katsutoshi, Hori Masakazu, Sakata Koh-ichi

日本医学放射線学会学術集会抄録集 ( (公社)日本医学放射線学会 ) 78回 S264 - S264 2019.02

Influence of PD-L1 expression in immune cells on the response to radiation therapy in patients with oropharyngeal squamous cell carcinoma.

Yuki Fukushima, Masanori Someya, Kensei Nakata, Masakazu Hori, Mio Kitagawa, Tomokazu Hasegawa, Takaaki Tsuchiya, Toshio Gocho, Hikaru Ikeda, Yoshihiko Hirohashi, Toshihiko Torigoe, Shintaro Sugita, Tadashi Hasegawa, Tetsuo Himi, Koh-Ichi Sakata

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 129 ( 2 ) 409 - 414 2018.11 [Refereed] [International journal]

BACKGROUND AND PURPOSE: To investigate influences of proteins involved with tumor immunity on outcomes of radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC). MATERIAL AND METHODS: We performed immunohistochemical staining to examine expressions of p16 and proteins involved with tumor immunity in 92 OPSCC patients treated with radiotherapy. RESULTS: Patients with abundant infiltrating CD8-positive cells had the significantly better overall survival (OS) rate than patients with fewer CD8-positive cells (p = 0.026). Patients with higher PD-L1 expression in tumor cells (TC 1-3) had a better outcome than those with low PD-L1 expression in tumor cells (TC 0) for both OS (p = 0.019) and progression-free survival (PFS) rate (p = 0.032). Patients with high PD-L1 expression in infiltrating immune cells (IC 3) showed significantly better OS (p = 0.009) and PFS (p = 0.011) than those with low PD-L1 expression (IC 0-2). Patients with p16-negative and IC 3 showed similar OS to patients with p16-positive and IC 0-2. P16-positive tumors had a significantly higher CD8-positive cell infiltration and PD-L1 expression in tumor cells than p16-negative tumors. CONCLUSIONS: In addition to tumor p16 expression, PD-L1 expression in TC and IC can be useful for predicting the response of OPSCC to radiotherapy.

DOI PubMed

Differential diagnosis between intraductal papillary mucinous neoplasm with an associated invasive carcinoma and pancreatic ductal adenocarcinoma on ultrasonography: the utility of echo intensity and contrast enhancement.

Masato Saito, Naoki Hirokawa, Yoko Usami, Masanori Someya, Koh-Ichi Sakata

Ultrasonography (Seoul, Korea) ( Korean Society of Ultrasound in Medicine ) 36 ( 3 ) 260 - 269 2017.07 [Refereed] [International journal]

PURPOSE: The aim of this study was to investigate the utility of echo intensity and contrast enhancement in the differential diagnosis between intraductal papillary mucinous neoplasm with an associated invasive carcinoma (IPMN-IC) and pancreatic ductal adenocarcinoma (PDAC) on ultrasonography. METHODS: This study included eight and 37 patients who had pathologically confirmed IPMN-IC and PDAC, respectively, and were enrolled for a comparative analysis of the sonographic features of the tumors. In the quantitative echo intensity evaluation, the two groups were compared with respect to the difference between the tumor intensity and the pancreatic intensity (TI-PI) and between the tumor intensity and the vascular intensity (TI-VI). In the quantitative contrast enhancement evaluation, the increase in echo intensity (ΔTI) and increase in echo intensity per unit of time (slope) were compared between the groups. The echo intensity and contrast enhancement were also compared between the two groups in patients with T3-T4 disease. In addition, the correlations of the histological type, tumor size, stromal type, and T factor with echogenicity and contrast enhancement were analyzed. RESULTS: IPMN-IC had significantly greater echo intensity and contrast enhancement than PDAC (TI-PI, P=0.004; TI-VI, P=0.001; ΔTI, P=0.012; slope, P=0.002). In T3-T4 disease, IPMN-IC also showed greater echo intensity and faster enhancement than PDAC. Echo intensity and contrast enhancement were correlated with histological type (TI-PI, P=0.003; TI-VI, P<0.001; ΔTI, P=0.007; slope, P<0.001). CONCLUSION: IPMN-IC and PDAC can be differentiated by the quantitative evaluation of echo intensity and contrast enhancement.

DOI PubMed

Influence of XRCC4 expression in esophageal cancer cells on the response to radiotherapy.

Masakazu Hori, Masanori Someya, Yoshihisa Matsumoto, Kensei Nakata, Mio Kitagawa, Tomokazu Hasegawa, Takaaki Tsuchiya, Yuki Fukushima, Toshio Gocho, Yasushi Sato, Hiroyuki Ohnuma, Junji Kato, Shintaro Sugita, Tadashi Hasegawa, Koh-Ichi Sakata

Medical molecular morphology 50 ( 1 ) 25 - 33 2017.03 [Refereed] [Domestic journal]

DNA double-strand break (DSB) is one of the most serious forms of damage induced by ionizing irradiation and is mainly repaired by the non-homologous end joining (NHEJ) repair. Immunohistochemical analysis of proteins involved in NHEJ, such as XRCC4 (X-ray repair cross-complementing protein 4), Ku86 and DNA-PKcs (DNA-dependent protein kinase, catalytic subunits), may be useful for predicting tumor radiosensitivity. We examined 92 patients with esophageal squamous cell carcinoma (ECSS) who were treated by radiotherapy between 1999 and 2008. Immunohistochemical examination of tumor tissue for Ki-67 and DSB-related proteins, including XRCC4, Ku86, and DNA-PKcs, was performed using pretreatment biopsy specimens. Low expression of XRCC4 was detected in 31 of 92 examined samples (33.7 %). The 5-year overall survival (OS) rate was 67.7 % in the low expression group and 31.0 % in the high expression group (P = 0.00). Multivariate analysis confirmed that advanced T-stage (HR 3.24, P = 0.01), radiation dose less than 66 Gy (HR 2.23, P = 0.02), absence of systemic chemotherapy (HR 2.59, P = 0.05), and high expression of XRCC4 (HR 12.0, P = 0.02) were independent prognostic factors for predicting poor OS. Other DSB-related proteins and Ki-67 were not predictive factors. XRCC4 expression might have an influence on results of radiotherapy for patients with ESCC.

DOI PubMed

Expression of Ku70 predicts results of radiotherapy in prostate cancer.

Tomokazu Hasegawa, Masanori Someya, Masakazu Hori, Yoshihisa Matsumoto, Kensei Nakata, Masanori Nojima, Mio Kitagawa, Takaaki Tsuchiya, Naoya Masumori, Tadashi Hasegawa, Koh-Ichi Sakata

Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 193 ( 1 ) 29 - 37 2017.01 [Refereed] [International journal]

BACKGROUND AND PURPOSE: Therapeutic strategy for prostate cancer is decided according to T stage, Gleason score, and prostate-specific antigen (PSA) level. These clinical factors are not accurate enough to predict individual risk of local failure of prostate cancer after radiotherapy. Parameters involved with radiosensitivity are required to improve the predictive capability for local relapse. PATIENTS AND METHODS: We analyzed 58 patients with localized adenocarcinoma of the prostate between August 2007 and October 2010 treated with 76 Gy of intensity-modulated radiotherapy (IMRT) as a discovery cohort and 42 patients between March 2001 and May 2007 treated with three-dimensional conformal radiotherapy (3D-CRT) as a validation cohort. Immunohistochemical examination for proteins involved in nonhomologous end-joining was performed using biopsy specimens. RESULTS: Ku70 expression was not correlated with various clinical parameters, such as the Gleason score and D'amico risk classification, indicating that Ku70 expression was an independent prognostic factor. The predictive value for PSA relapse was markedly improved after the combination of Gleason score and Ku70 expression, as compared with Gleason score alone. In patients treated with radiotherapy and androgen deprivation therapy (ADT), no relapses were observed in patients with Gleason score ≤7 or low Ku70 expression. In contrast, patients with Gleason score ≥8 and high Ku70 expression had high PSA relapse rates. In the validation cohort, similar results were obtained. CONCLUSION: Treatment with 76 Gy and ADT can be effective for patients with Gleason score ≤7 or low Ku70 expression, but is not enough for patients with Gleason score ≥8 and high Ku70 expression and, thus, require other treatment approaches.

DOI PubMed

Influence of Ku86 and XRCC4 expression in uterine cervical cancer on the response to preoperative radiotherapy.

Yu Takada, Masanori Someya, Yoshihisa Matsumoto, Masaaki Satoh, Kensei Nakata, Masakazu Hori, Masato Saito, Naoki Hirokawa, Kunihiko Tateoka, Mizue Teramoto, Tsuyoshi Saito, Tadashi Hasegawa, Koh-Ichi Sakata

Medical molecular morphology ( SPRINGER JAPAN KK ) 49 ( 4 ) 210 - 216 2016.12 [Refereed] [Domestic journal]

DNA double-strand breaks (DSB) are severe damages induced by ionizing radiation. Non-homologous end joining (NHEJ) is a major mechanism for repairing DSB. Immunohistochemical analysis of proteins involved in NHEJ, such as Ku86 and XRCC4 (X-ray repair cross-complementing protein 4) may be useful for predicting tumor radiosensitivity. We examined the relationship between expression of DSB-related proteins in biopsy specimens of uterine cervical cancer and the pathological effect of 40 Gy of preoperative radiotherapy. 119 patients with uterine cervical cancer were treated between 2000 and 2011. Pathological effects of preoperative radiotherapy were classified by examining hysterectomy specimens. Patients with complete response (pCR) had a significantly better overall 5-year survival rate than those without pCR (96.3 vs. 76.9 %, P = 0.02). The pCR rate was significantly higher in patients with low Ku86 and XRCC4 expression than in other patients (47.4 vs. 21.3 %, P = 0.04). Logistic regression analysis also demonstrated that low Ku86 and XRCC4 expression was a significant predictor of pCR (P = 0.03). Patients with high Ku86 and XRCC4 expression had a significantly lower 5-year metastasis-free rate than others (79.3 vs. 93.5 %, P = 0.02). Proteins involved with NHEJ might have an influence on results of radiotherapy for uterine cervical cancer.

DOI PubMed

A Phase 1/2 Study of Definitive Chemoradiation Therapy Using Docetaxel, Nedaplatin, and 5-Fluorouracil (DNF-R) for Esophageal Cancer.

Hiroyuki Ohnuma, Yasushi Sato, Masahiro Hirakawa, Yutaka Okagawa, Takahiro Osuga, Tsuyoshi Hayashi, Tsutomu Sato, Koji Miyanishi, Masayoshi Kobune, Rishu Takimoto, Tamotsu Sagawa, Masakazu Hori, Masanori Someya, Kensei Nakata, Koh-Ichi Sakata, Tetsuji Takayama, Junji Kato

International journal of radiation oncology, biology, physics 93 ( 2 ) 382 - 90 2015.10 [Refereed] [International journal]

PURPOSE: Patient survival in esophageal cancer (EC) remains poor. The purpose of this study was to investigate a regimen of definitive chemoradiation therapy (CRT) that exerts good local control of EC. We performed a phase 1/2 study to assess the safety and efficacy of CRT with docetaxel, nedaplatin, and 5-fluorouracil (DNF-R). METHODS AND MATERIALS: Eligible patients presented with stage IB to IV EC. Patients received 2 cycles of docetaxel (20, 30, or 40 mg/m(2)) and nedaplatin (50 mg/m(2)) on days 1 and 8 and a continuous infusion of 5-fluorouracil (400 mg/m(2)/day) on days 1 to 5 and 8 to 12, every 5 weeks, with concurrent radiation therapy (59.4 Gy/33 fractions). The recommended dose (RD) was determined using a 3 + 3 design. RESULTS: In the phase 1 study, the dose-limiting toxicities were neutropenia and thrombocytopenia. The RD of docetaxel was determined to be 20 mg/m(2). In the phase 2 study, grade 3 to 4 acute toxicities included neutropenia (42.8%), febrile neutropenia (7.14%), thrombocytopenia (17.9%), and esophagitis (21.4%). Grade 3 to 4 late radiation toxicity included esophagostenosis (10.7%). The complete response rate was 82.1% (95% confidence interval: 67.9-96.3%). Both the median progression-free survival and overall survival were 41.2 months. CONCLUSIONS: DNF-R showed good tolerability and strong antitumor activity, suggesting that it is a potentially effective therapeutic regimen for EC.

DOI PubMed

Analysis of Prostate Deformation during a Course of Radiation Therapy for Prostate Cancer.

Takuya Nakazawa, Kunihiko Tateoka, Yuichi Saito, Tadanori Abe, Masaki Yano, Yuji Yaegashi, Hirokazu Narimatsu, Kazunori Fujimoto, Akihiro Nakata, Kensei Nakata, Masanori Someya, Masakazu Hori, Masato Hareyama, Koichi Sakata

PloS one 10 ( 6 ) e0131822 2015 [Refereed] [International journal]

PURPOSE: Accurate analysis of the correlation between deformation of the prostate and displacement of its center of gravity (CoG) is important for efficient radiation therapy for prostate cancer. In this study, we addressed this problem by introducing a new analysis approach. METHOD: A planning computed tomography (CT) scan and 7 repeat cone-beam CT scans during the course of treatment were obtained for 19 prostate cancer patients who underwent three-dimensional conformal radiation therapy. A single observer contoured the prostate gland only. To evaluate the local deformation of the prostate, it was divided into 12 manually defined segments. Prostate deformation was calculated using in-house developed software. The correlation between the displacement of the CoG and the local deformation of the prostate was evaluated using multiple regression analysis. RESULTS: The mean value and standard deviation (SD) of the prostate deformation were 0.6 mm and 1.7 mm, respectively. For the majority of the patients, the local SD of the deformation was slightly lager in the superior and inferior segments. Multiple regression analysis revealed that the anterior-posterior displacement of the CoG of the prostate had a highly significant correlation with the deformations in the middle-anterior (p < 0.01) and middle-posterior (p < 0.01) segments of the prostate surface (R2 = 0.84). However, there was no significant correlation between the displacement of the CoG and the deformation of the prostate surface in other segments. CONCLUSION: Anterior-posterior displacement of the CoG of the prostate is highly correlated with deformation in its middle-anterior and posterior segments. In the radiation therapy for prostate cancer, it is necessary to optimize the internal margin for every position of the prostate measured using image-guided radiation therapy.

DOI PubMed

Phase I study of oral S-1 and concurrent radiotherapy in patients with head and neck cancer.

Kensei Nakata, Koh-Ichi Sakata, Masanori Someya, Katsutoshi Miura, Junichi Hayashi, Masakazu Hori, Masaru Takagi, Tetsuo Himi, Atsushi Kondo, Masato Hareyama

Journal of radiation research 54 ( 4 ) 679 - 83 2013.07 [Refereed] [International journal]

This study investigated the maximum tolerated dose (MTD) of S-1 with concurrent radiotherapy in patients with head and neck cancer, based on the frequency of dose-limiting toxicities (DLT). S-1 was administered orally at escalating doses from 40 mg/m(2) b.i.d. on the days of delivering radiotherapy, which was given at a total dose of 64-70 Gy in 32-35 fractions over 6-7 weeks. A total of 12 patients (3 patients at 40 mg/m(2), 6 patients at 60 mg/m(2), and 3 patients at 80 mg/m(2)) were enrolled in this trial. At the dose of 80 mg/m(2), two of the three patients developed DLT (Grade 3 anorexia and rhabdomyolysis) due to S-1, so the MTD was determined to be 80 mg/m(2). Among the 12 enrolled patients, 9 (75%) showed a complete response and 3 (25%) showed a partial response. The overall response rate was 100%. The recommended dose of S-1 with concurrent radiotherapy is 60 mg/m(2).

DOI PubMed

Analysis and results of Ku and XRCC4 expression in hypopharyngeal cancer tissues treated with chemoradiotherapy.

Jyunichi Hayashi, Koh-Ichi Sakata, Masanori Someya, Yoshihisa Matsumoto, Masaaki Satoh, Kensei Nakata, Masakazu Hori, Masaru Takagi, Atsushi Kondoh, Tetsuo Himi, Masato Hareyama

Oncology letters 4 ( 1 ) 151 - 155 2012.07 [Refereed] [International journal]

DNA double-strand break (DSB) is one of the most serious forms of damage induced by ionizing irradiation. Non-homologous end-joining (NHEJ) is a key mechanism of DNA DSB repair. The immunohistochemical analysis of proteins involved in NHEJ may have potential as a predictive assay for tumor radiosensitivity. We examined the correlation between the expression of proteins involved in DNA DSB in biopsy specimens and the results of chemoradiotherapy in hypopharyngeal cancers. Fifty-seven patients with previously untreated squamous cell carcinoma of the hypopharynx were treated between March 2002 and December 2009. Most patients (75%) had stage III or IV disease. The chemotherapy consisted of cisplatin plus 5FU or S-1. A tumor dose of 50 Gy was usually administered to the primary tumor and regional lymph nodes. Doses of 10-20 Gy were usually added to the primary tumor with reduced fields after 50 Gy. The 5-year disease-free survival rate was 100% for patients in stage I, 90% in stage II, 64% in stage III and 50% in stage IV. In stages I-III, patients with a lower expression of Ku70 or XRCC4 tended to have better locoregional control. These results indicated that a lower expression of Ku70 or XRCC4 may be correlated with higher radiosensitivity. Two patients had distant metastasis alone, of which one had 0% expression of Ku70 and the other had 0% expression of Ku86. The absence of Ku70 or Ku86 expression indicates low DNA-PK activity. Low DNA-PK activity due to a low expression of Ku may result in the genetic alteration of cancer cells, leading to a higher tendency of distant metastasis. This finding suggests that proteins involved in NHEJ may have an impact on the treatment results of chemoradiotherapy in hypopharyngeal cancer.

PubMed

The combination of olaparib and camptothecin for effective radiosensitization.

Katsutoshi Miura, Koh-ichi Sakata, Masanori Someya, Yoshihisa Matsumoto, Hideki Matsumoto, Akihisa Takahashi, Masato Hareyama

Radiation oncology (London, England) 7 62 - 62 2012.04 [Refereed] [International journal]

BACKGROUND: Poly (ADP-ribose) polymerase-1 (PARP-1) is a key enzyme involved in the repair of radiation-induced single-strand DNA breaks. PARP inhibitors such as olaparib (KU-0059436, AZD-2281) enhance tumor sensitivity to radiation and to topoisomerase I inhibitors like camptothecin (CPT). Olaparib is an orally bioavailable inhibitor of PARP-1 and PARP-2 that has been tested in multiple clinical trials. The purpose of this study was to investigate the characteristics of the sensitizing effect of olaparib for radiation and CPT in order to support clinical application of this agent. METHODS: DLD-1 cells (a human colorectal cancer cell line) and H1299 cells (a non-small cell lung cancer cell line) with differences of p53 gene status were used. The survival of these cells was determined by clonogenic assay after treatment with drugs and X-ray irradiation. The γH2AX focus formation assay was performed to examine the influence of olaparib on induction and repair of double-stranded DNA breaks after exposure to radiation or CPT. RESULTS: A radiosensitizing effect of olaparib was seen even at 0.01 μM. Its radiosensitizing effect after exposure for 2 h was similar to that after 24 h. H1299 cells with depletion or mutation of p53 were more radioresistant than H1299 cells with wild-type p53. However, similar enhancement of radiosensitization by olaparib was observed with all of the tested cell lines regardless of the p53 status. Olaparib also sensitized cells to CPT. This sensitizing effect was seen at low concentrations of olaparib such as 0.01 μM, and its sensitizing effect was the same at both 0.01 μM and 1 μM. The combination of olaparib and CPT had a stronger radiosensitizing effect. The results of the γH2AX focus assay corresponded with the clonogenic assay findings. CONCLUSION: Olaparib enhanced sensitivity to radiation and CPT at low concentrations and after relatively short exposure times such as 2 h. The radiosensitizing effect of olaprib was not dependent on the p53 status of tumor cells. These characteristics could be advantageous for clinical radiotherapy since tumor cells may be exposed to low concentrations of olaparib and/or may have different levels of p53 mutation. The combination of olaparib and CPT had a stronger radiosensitizing effect, indicating that combining a PARP inihibitor with a topoiomerase I inhibitor could be promising for clinical radiosensitization.

DOI PubMed

The combination of hyperthermia or chemotherapy with gimeracil for effective radiosensitization

M. Takagi, K. Sakata, M. Someya, Y. Matsumoto, H. Tauchi, M. Hareyama, M. Fukushima

STRAHLENTHERAPIE UND ONKOLOGIE ( URBAN & VOGEL ) 188 ( 3 ) 255 - 261 2012.03 [Refereed]

Purpose. 5-chloro-2,4-dihydroxypyridine (gimeracil) is a component of the oral fluoropyrimidine derivative S-1. Gimeracil was originally added to S-1 to yield prolonged 5-fluorouracil (5-FU) concentrations in serum and tumor tissues by inhibiting dihydropyrimidine dehydrogenase, which degrades 5-FU. We previously demonstrated that gimeracil enhances the efficacy of radiotherapy through the suppression of homologous recombination (HR) in DNA double strand repair. The goal of this paper was to examine the effects of gimeracil on the sensitivity of anticancer drugs and hyperthermia in order to obtain effective radiosensitization. Materials and methods. Various cell lines, including DLD 1 (human colon carcinoma cells) and cells deficient in HR or nonhomologous end-joining (NHEJ), were used in clonogenic assays. The survival of these cells after various treatments (e.g., drug treatment, heat treatment, and radiation) was determined based on their colony-forming ability. Results. Gimeracil enhanced cell-killing effects of camptothecin (CPT), 5-FU, and hydroxyurea. Gimeracil sensitized effects of CPT or 5-FU to cells deficient in HR or NHEJ to a similar extent as in other cells (DLD1 and a parent cell), indicating that its sensitizing mechanisms may be different from inhibition of HR or NHEJ. Combination of gimeracil and CPT or 5-FU sensitized radiation more effectively than each modality alone. Gimeracil also enhanced heat sensitivity at 42 degrees C or more. The degree of heat sensitization with gimeracil increased as the temperature increased, and the combination of gimeracil and heat-sensitized radiation was more effective than each modality alone. Conclusion. Gimeracil enhanced sensitivity of CPT, 5-FU, and hyperthermia. Combination of these modalities sensitized radiation more efficiently than each modality alone.

DOI PubMed

A clinical survey of hospitalization with radical radiotherapy for early stage glottic laryngeal cancer:

Kensei Nakata, Koichi Sakata, Masaru Takagi, Masanori Someya, Atsushi Kondo, Tetsuo Himi, Masato Hareyama

Japanese Journal of Head and Neck Cancer 38 ( 3 ) 315 - 317 2012

We retrospectively investigated the relationship between the duration of hospitalization and the regimen of definitive radiotherapy for patients with early stage glottic laryngeal cancer in our institution during the period from 2006 to 2011. The total number of hospitalized patients who underwent radiation therapy in this period was 45 (43 men, 2 women). Twenty-one patients had been treated by accelerated hyperfractionation (AHF), 19 patients by conventional fractionation (CF, and 5 patients by accelerated fractionation (AF). Average duration of radiation therapy was 23.4, 48.5, 38.4 days respectively and average duration of hospitalization was 37.3, 57.4, and 49 days respectively. Our data suggest that the AHF method can shorten the period of hospitalization by 20 days on average compared to the CF method.

DOI

Gimeracil, an inhibitor of dihydropyrimidine dehydrogenase, inhibits the early step in homologous recombination.

Koh-Ichi Sakata, Masanori Someya, Yoshihisa Matsumoto, Hiroshi Tauchi, Masahiro Kai, Minoru Toyota, Masaru Takagi, Masato Hareyama, Masakazu Fukushima

Cancer science 102 ( 9 ) 1712 - 6 2011.09 [Refereed] [International journal]

Gimeracil (5-chloro-2, 4-dihydroxypyridine) is an inhibitor of dihydropyrimidine dehydrogenase (DPYD), which degrades pyrimidine including 5-fluorouracil in the blood. Gimeracil was originally added to an oral fluoropyrimidine derivative S-1 to yield prolonged 5-fluorouracil concentrations in serum and tumor tissues. We have already reported that gimeracil had radiosensitizing effects by partially inhibiting homologous recombination (HR) in the repair of DNA double strand breaks. We investigated the mechanisms of gimeracil radiosensitization. Comet assay and radiation-induced focus formation of various kinds of proteins involved in HR was carried out. siRNA for DPYD were transfected to HeLa cells to investigate the target protein for radiosensitization with gimeracil. SCneo assay was carried out to examine whether DPYD depletion by siRNA inhibited HR repair of DNA double strand breaks. Tail moments in neutral comet assay increased in gimeracil-treated cells. Gimeracil restrained the formation of foci of Rad51 and replication protein A (RPA), whereas it increased the number of foci of Nbs1, Mre11, Rad50, and FancD2. When HeLa cells were transfected with the DPYD siRNA before irradiation, the cells became more radiosensitive. The degree of radiosensitization by transfection of DPYD siRNA was similar to that of gimeracil. Gimeracil did not sensitize DPYD-depleted cells. Depletion of DPYD by siRNA significantly reduced the frequency of neopositive clones in SCneo assay. Gimeracil partially inhibits the early step in HR. It was found that DPYD is the target protein for radiosensitization by gimeracil. The inhibitors of DPYD, such as gimeracil, could enhance the efficacy of radiotherapy through partial suppression of HR-mediated DNA repair.

DOI PubMed

Gene expression associated with DNA-dependent protein kinase activity under normoxia, hypoxia, and reoxygenation.

Tadashi Tsuchimoto, Koh-ichi Sakata, Masanori Someya, Hiroyuki Yamamoto, Ryoichi Hirayama, Yoshihisa Matsumoto, Yoshiya Furusawa, Masato Hareyama

Journal of radiation research 52 ( 4 ) 464 - 71 2011 [Refereed] [International journal]

DOI PubMed

The association of DNA-dependent protein kinase activity of peripheral blood lymphocytes with prognosis of cancer

Someya, M., Sakata, K-I, Matsumoto, Y., Kamdar, R. P., Kai, M., Toyota, M., Hareyama, M.

British Journal of Cancer ( NATURE PUBLISHING GROUP ) 104 ( 11 ) 1724 - 1729 2011 [Refereed]

BACKGROUND: Repair of various types of DNA damages is critical for genomic stability. DNA-dependent protein kinase (DNA-PK) has an important role in DNA double-strand break repair. We examined whether there may be a correlation between DNA-PK activity in peripheral blood lymphocytes (PBLs) and survival percentages in various cancer patients. We also investigated the changes of DNA-PK activity in PBLs after radiotherapy. METHODS: A total of 167 of untreated cancer patients participated in this study. Peripheral blood was collected, separated, and centrifuged. DNA-PK activity was measured by DNA-pull-down assay. Chromosomal aberrations were examined by cytogenetic methods. RESULTS: DNA-PK activity of PBLs in advanced cancer patients was significantly lower than that in early stage. The patients with lower DNA-PK activity in PBLs tended to have the lower disease-specific survivals and distant metastasis-free survivals than those with higher DNA-PK activity in advanced stages. There was also a tendency of inverse correlation between DNA-PK activity and excess fragments. The DNA-PK activity of PBLs in most patients decreased in response to radiation as the equivalent whole-body dose increased. CONCLUSION: Cancer patients in advanced stage, with lower DNA-PK activity of PBLs might have higher distant metastasis and exhibit poorer prognosis. Therefore, DNA-PK activity in PBLs could be used as a marker to predict the chromosomal instability and poorer prognosis. British Journal of Cancer (2011) 104, 1724-1729. doi:10.1038/bjc.2011.158 www.bjcancer.com Published online 10 May 2011 (C) 2011 Cancer Research UK

DOI PubMed

Gimeracil sensitizes cells to radiation via inhibition of homologous recombination.

Masaru Takagi, Koh-ichi Sakata, Masanori Someya, Hiroshi Tauchi, Kenta Iijima, Yoshihisa Matsumoto, Toshihiko Torigoe, Akari Takahashi, Masato Hareyama, Masakazu Fukushima

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 96 ( 2 ) 259 - 66 2010.08 [Refereed] [International journal]

BACKGROUND AND PURPOSE: 5-Chloro-2,4-dihydroxypyridine (Gimeracil) is a component of an oral fluoropyrimidine derivative S-1. Gimeracil is originally added to S-1 to yield prolonged 5-FU concentrations in tumor tissues by inhibiting dihydropyrimidine dehydrogenase, which degrades 5-FU. We found that Gimeracil by itself had the radiosensitizing effect. METHODS AND MATERIALS: We used various cell lines deficient in non-homologous end-joining (NHEJ) or homologous recombination (HR) as well as DLD-1 and HeLa in clonogenic assay. gamma-H2AX focus formation and SCneo assay was performed to examine the effects of Gimeracil on DNA double strand break (DSB) repair mechanisms. RESULTS: Results of gamma-H2AX focus assay indicated that Gimeracil inhibited DNA DSB repair. It did not sensitize cells deficient in HR but sensitized those deficient in NHEJ. In SCneo assay, Gimeracil reduced the frequency of neo-positive clones. Additionally, it sensitized the cells in S-phase more than in G0/G1. CONCLUSIONS: Gimeracil inhibits HR. Because HR plays key roles in the repair of DSBH caused by radiotherapy, Gimeracil may enhance the efficacy of radiotherapy through the suppression of HR-mediated DNA repair pathways.

DOI PubMed

Phase I Study of Oral S-1 and Concurrent Radiotherapy in Patients with Head and Neck Cancer

K. Nakata, M. Someya, M. Takagi, J. Hayashi, K. Miura, K. Sakata, M. Hareyama

INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS ( ELSEVIER SCIENCE INC ) 78 ( 3 ) S450 - S451 2010 [Refereed]

The treatment outcome of patients undergoing breast-conserving therapy: the clinical role of postoperative radiotherapy.

Atsushi Oouchi, Koh-Ichi Sakata, Hideji Masuoka, Mitsuharu Tamakawa, Hisayasu Nagakura, Masanori Someya, Kensei Nakata, Kazuaki Asaishi, Minoru Okazaki, Yutaka Okazaki, Tousei Ohmura, Masato Hareyama, Masakazu Hori, Izuru Shimokawara, Akira Okazaki, Yoshiki Watanabe, Tsuyoshi Yamada, Tomokazu Yuyama, Taishi Satoh, Koichi Hirata

Breast cancer (Tokyo, Japan) 16 ( 1 ) 49 - 57 2009 [Refereed] [Domestic journal]

BACKGROUND: Treatment outcome was evaluated in patients who underwent breast-conserving therapy and tangential irradiation. After verifying background factors including systemic therapy, the clinical efficacy of postoperative irradiation was investigated. METHOD: There were 708 study subjects, all of whom had early breast cancer treated between 1992 and 2002. The median follow-up period was 83 months. After breast-conserving surgery, in patients with negative surgical margins, only tangential irradiation at 48 Gy/24 fr was performed. In contrast, in those with positive surgical margins, 10 Gy of radiation boost to the tumor bed with electrons was administered after tangential irradiation with 50 Gy/25 fr. Treatment outcome was analyzed using the Kaplan-Meier method and Cox's proportional hazards regression model. RESULTS: The disease-free survival and no-recurrence rates within the ipsilateral breast after 5 years were 93.4 and 97.2%, respectively. Risk factors for recurrence within the ipsilateral breast included younger age of patient, the number of positive lymph nodes, and no endocrine therapy. However, the surgical margin was not a risk factor. Risk factors for relapse outwith the ipsilateral breast included younger age, the number of positive lymph nodes, and recurrence within the ipsilateral breast. CONCLUSIONS: From our analysis of 708 Japanese women who received breast-conserving therapy, which can be regarded as a standard method in Japan, the treatment outcome was compatible with previous reports from other countries.

DOI PubMed

[Clinical application of altered fractionation theory].

Koh-ichi Sakata, Masanori Someya, Kensei Nakata, Masaru Takagi, Masato Hareyama

Gan to kagaku ryoho. Cancer & chemotherapy 35 ( 11 ) 1823 - 6 2008.11 [Refereed] [Domestic journal]

Altered fractionation schedules are based on two different concepts of radiobiology. One concept is that the radiation repair capability of cells in late responding tissues is higher than that of cells in acute responding tissues which include tumor tissues. Hyperfractionation utilizes this concept. The other concept is that accelerated repopulation of tumor cells occurs in a later period of radiation therapy. In order to overcome repopulation of tumor cells, accelerated hyperfractionation is proposed. These two concepts are independent and some fractionation methods include both concepts. Clinical results of altered fractionation schedules of radiation therapy could be predicted with a biological model (the linear quadratic model theory)for fractionated radiation. When this biological model is applied to tumors in which the tumor cell repopulation during radiotherapy period is negligible, the correction for tumor proliferation is required. Since the calculation of the biological effect dose with this model uses several assumptions, we should consider the biological effect dose as a crude approximation. Especially, in case of concomitant chemotherapy and altered fractionation, it is difficult to predict its results with a simple radiobiology model. The randomized trial is required to examine the significance of chemoradiotherapy using altered fractionation.

PubMed

Hyperfractionated accelerated radiotherapy for T1,2 glottic carcinoma. Consideration of time-dose factors.

Koh-ichi Sakata, Masanori Someya, Masakazu Hori, Kensei Nakata, Masaru Takagi, Masato Hareyama

Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 184 ( 7 ) 364 - 9 2008.07 [Refereed] [International journal]

BACKGROUND AND PURPOSE: Hyperfractionated accelerated radiotherapy without a split (AF) has been performed to improve the local control probability of early glottic carcinomas since 1990 in the authors' institution. Here, they report their experience treating early glottic cancer patients with AF in a single institution who have a long follow-up period. PATIENTS AND METHODS: 131 T1 N0 M0 glottic cancers and 65 T2 N0 M0 glottic cancers were treated with conventional fractionation (CF) from 1984 to 1989 and with AF since 1990. CF consisted of five daily fractions of 2 Gy per week, to a total dose of 64 Gy. AF consisted of 1.72 Gy per fraction, two fractions per day, 5 days a week, to a total dose of 55 or 58.5 Gy. RESULTS: The 5-year local control probability for T1 tumors was 94% with 58.5 Gy and 87% with 55 Gy of AF, whereas it amounted to 80% with CF. For T2 tumors, it was 56% with 58.5 Gy and 68% with 55 Gy of AF, whereas it amounted to 64% with CF. The data of T2 should be evaluated with caution due to the small number of patients. Patients with AF had more severe mucosal reactions but no severe late reactions. CONCLUSION: AF significantly improved the local control rates for T1 glottic cancer.

DOI PubMed

Brachytherapy for oral tongue cancer: an analysis of treatment results with various biological markers.

Koh-ichi Sakata, Masanori Someya, Hisayasu Nagakura, Kensei Nakata, Atushi Oouchi, Masaru Takagi, Masato Hareyama

Japanese journal of clinical oncology 38 ( 6 ) 402 - 7 2008.06 [Refereed] [International journal]

OBJECTIVE: Low-dose-rate (LDR) brachytherapy is an effective treatment for tongue cancer. However, little is known about the biological mechanism underlying this therapy, characterized by delivery of continuous exposures of LDR irradiation. It is reported that lower microvessel density (MVD), lower Ki-67 index or higher expression of endogenous hypoxic markers such as carbonic CA IX and Glut-1 are related to the poor control of tumors treated with external irradiation. To elucidate the biological characteristics of LDR brachytherapy, we analyzed our results in cases of tongue cancer treated with LDR brachytherapy by using immunohistochemical stainings with antibodies against Ki-67 and MVD, Glut-1 and CA IX. METHODS: The prognostic value of Ki-67 index, MVD and the expression of CA IX and Glut-1 was assessed in 68 tongue cancers treated with LDR brachytherapy. The specimens were taken from tongue cancers before radiation therapy and immunohistochemical staining was performed. RESULTS: The local recurrence-free survival rates were significantly different between T1+T2 and T3 (P = 0.00067), but not between low and high Ki-67 indexes (P = 0.54), between low and high MVD (P = 0.071), low and high CA IX indexes (P = 0.062) or low and high Glut-1 indexes (P = 0.107). T stage, the size of the tumor was the only significant factor for local control in multivariate analyses (P = 0.0377). CONCLUSION: LDR could overcome the radioresistence of non-cycling and hypoxic cells; however, we cannot draw firm conclusions due to the limited number of patients.

DOI PubMed

Tissue oxygenation in a murine SCC VII tumor after X-ray irradiation as determined by EPR spectroscopy.

Hirotada Fujii, Koh-Ichi Sakata, Yoshihiro Katsumata, Rikiya Sato, Makoto Kinouchi, Masanori Someya, Shin-Ichiro Masunaga, Masato Hareyama, Harold M Swartz, Hiroshi Hirata

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 86 ( 3 ) 354 - 60 2008.03 [Refereed] [International journal]

PURPOSE: The goal of this study was to clarify the dynamics of oxygenation (partial pressure of oxygen, pO(2)) in SCC VII murine tumors in mice after X-ray irradiation. MATERIALS AND METHODS: Changes in pO(2) in tumors were measured by 1.2-GHz electron paramagnetic resonance (EPR) spectroscopy after they were exposed to various doses of irradiation. The pO(2) in tumors was followed for up to six days after irradiation at doses of 0, 5, 10, 15, and 20 Gy. Paramagnetic crystals were used as an oximetry probe and implanted into normal or tumor tissues in mice for prolonged periods. RESULTS: The pattern of tumor oxygen after a single dose of radiation with the 5-Gy dose was different from those with other doses (10, 15, and 20 Gy). After 5 Gy, pO(2) increased rapidly (P<0.01, Student's t test) and then returned to the level observed before irradiation by 12h (P<0.01). In contrast, after 10, 15, or 20 Gy, pO(2) increased rapidly by 6h after irradiation, continued to increase until at least 24h (P<0.01), and then gradually decreased. CONCLUSIONS: In tumors that received 5 Gy, post-irradiation increases in pO(2) at 4h after irradiation were detected by EPR oximetry (P<0.01) noninvasively.

PubMed

The enhanced expression of the matrix metalloproteinase 9 in nasal NK/T-cell lymphoma.

Koh-ichi Sakata, Masanori Someya, Mutsuko Omatsu, Hiroko Asanuma, Tadashi Hasegawa, Shingo Ichimiya, Masato Hareyama, Tetsuo Himi

BMC cancer 7 229 - 229 2007.12 [Refereed] [International journal]

BACKGROUND: Nasal NK/T cell lymphoma is an aggressive disease and has a poor prognosis. Nasal NK/T cell lymphoma is refractory to conventional chemotherapy and has strong tendency of widespread relapse or dissemination into distant sites. METHODS: We immunohistochemically studied nasal NK/T-cell lymphoma to elucidate the unique characteristics of nasal NK/T-cell lymphoma, such as its higher metastatic tendency and its vast necrosis which leads to destruction of the involved tissues. The expression of P-glycoprotein and MMP-9 was evaluated in the 20 patients with nasal NK/T-cell lymphoma and 25 with nasal non-NK/T-cell lymphoma and the relationship between expression of these proteins and clinical results were analyzed in this report. RESULTS: Overall 5-year survival rates for patients with nasal NK/T cell lymphoma, and nasal non-NK/T cell lymphoma were 51%, and 84%. Distant involvement free 5-year survival rates for patients with nasal NK/T cell lymphoma, and nasal non-NK/T cell lymphoma were 53%, and 79%. Overall positivity for P-glycoprotein was observed in 10 of 19 patients with NTL and in 13 of 23 patients with non-NTL. When the overall survival rate was compared between patients with P-glycoprotein positive and negative, there was no difference between them. Sixteen of the 19 patients with nasal NK/T cell lymphoma expressed MMP-9. In contrast, only 8 of the 22 patients with nasal non-NK/T cell lymphoma expressed MMP-9. Distant involvement free 5-year survival rates for patients with MMP-9 negative, and MMP-9 positive were 92%, and 61%, respectively. The difference was statistically significant (p = 0.027). CONCLUSION: Positive immunoreactivity for P-glycoprotein was not an independent prognostic factor in nasal NK/T-cell lymphomas, which stresses the importance of exploring other mechanisms of drug resistance. The strong expression of MMP-9 is uniquely characteristic of nasal NK/T cell lymphoma and may contribute to its strong tendency to disseminatate and the extensive necrosis which is always seen. However, our results are based on univariate comparisons, and as such, should be viewed with some caution.

PubMed

Ability to repair DNA double-strand breaks related to cancer susceptibility and radiosensitivity.

Koh-Ichi Sakata, Masanori Someya, Yoshihisa Matsumoto, Masato Hareyama

Radiation medicine 25 ( 9 ) 433 - 8 2007.11 [Refereed] [Domestic journal]

Traditional radiobiology has aimed at elucidating the mechanism of radiosensitivity of cancer cells and normal cells. Because the mechanism of DNA double-strand break (DSB) repair, which is inherently important to radiosensitivity, was unknown, it has been difficult to obtain results applicable to clinical radiotherapy from traditional radiobiology research. Today, however, the molecular mechanism of DNA DSB repair has been elucidated because of the rapid advances in molecular biology. In DNA DSB repair, at least two major repair mechanisms, homologous recombination and nonhomologous end joining (NHEJ) have been reported. In the NHEJ pathway, DSBs are directly, or after processing of the DNA ends, rejoined at an appropriate chromosomal end. DNA-dependent protein kinase (DNA-PK) plays an important role in DNA DSB repair by NHEJ. We have investigated how the ability of repair of DNA DSB influences cancer susceptibility and the radiosensitivity of tumors and normal tissues by focusing on the activity of DNA-PK. In the near future, research on DNA DSB repair mechanism will be able to be applied to research on carcinogenesis, prediction of radiosensitivity of tumors and normal cells, and sensitization of tumor cells.

PubMed

The efficacy and usefulness of problem based learning in undergraduate medical school education of radiation oncology

Minako Uchino, Tomoko Itazawa, Masanori Someya, Satoaki Nakamura

Journal of JASTRO 19 ( 3 ) 139 - 145 2007.09

The Japanese Association for Therapeutic Radiation Oncology (JASTRO) holds a seminar for medical students every summer, which has developed into a joint program with a session addressing radiation treatment planning. To clarify this topic for medical students, we have incorporated Problem Based Learning skills into the session. Not only has the students' comprehension improved but the instructors have also found this teaching experience valuable and productive in advancing their own clinical skills. Our experience suggests that the application of this Problem Based Learning session for radiation treatment planning in undergraduate medical school education has proven to be effective.

cDNA analysis of gene expression associated with DNA-dependent protein kinase activity.

Koh-ichi Sakata, Hiroyuki Yamamoto, Yoshihisa Matsumoto, Masanori Someya, Masato Hareyama

International journal of oncology 30 ( 2 ) 413 - 20 2007.02 [Refereed] [International journal]

DNA-dependent protein kinase (DNA-PK) is thought to play a pivotal role in DNA double-strand break repair. We recently demonstrated the association of DNA-PK activity in peripheral blood lymphocytes (PBL) with the incidence of chromosomal aberrations and the risk of cancer. In this study, we applied cDNA array technology to find the expression of genes which are associated with DNA-PK activity in PBLs with various levels of DNA-PK activity. Most genes correlated with DNA-PK activity involved cell cycle regulation. Moreover, the transcription factor E2F1, which plays an important role in cell cycle progression, exhibited strong correlation with the DNA-PK activity and Rbp130, which is considered a negative regulator of E2F, showed inverse correlation with DNA-PK activity. In silico promoter analyses showed the presence of at least one E2F binding site in the promoter regions of Ku70, Ku86, DNA-PKcs and genes associated with DNA-PK activity. In order to examine the relationship among the E2F1 expression, the expression of genes related with DNA-PK activity, and DNA-PK activity, we activated PMLs by PHA to progress the cell cycle. After PHA activation of PML, the expression of E2F1 and DNA-PK activity increased. The expression of most genes in PHA-stimulated PBLs had a similar relationship with DNA-PK activity to that without PHA stimulation. These results indicate that the E2F transcription factor may regulate the concerted expression of genes related with DNA-PK activity.

PubMed

The application of theory of altered fractionation on clinics

Koh-ichi Sakata, Masanori Someya, Kensei Nakata, Masaru Takagi, Kazuo Kojima, Masato Hareyama

Toukeibu Gan 33 ( 3 ) 280 - 282 2007

Altered fractionation schedules are based on two different concepts of radiobiology. One concept is that the radiation repair capability of cells in late responding tissues is higher than that of cells in acute responding tissues which include tumor tissues. Hyperfractionation utilizes this concept. The other concept is that accelerated repopulation of tumor cells occurs in a later period of radiation therapy. In order to overcome repopulation of tumor cells, the technique of accelerated hyperfractionation has been developed. Clinical results of altered fractionation schedules of radiation therapy could be predicted with the linear quadratic model thery for fractionated radiation. However, in the case of concomitant chemotheraoy and altered fractionation, it is difficult to predict its results with a simple radiobiology model. Randomized trias are required to examine the significance of chemoradiotherapy using altered fractionation. © 2007, Japan Society for Head and Neck Cancer. All rights reserved.

DOI

A clinical study of hypoxia using endogenous hypoxic markers and polarographic oxygen electrodes.

Koh-ichi Sakata, Masanori Someya, Hisayasu Nagakura, Kensei Nakata, Atushi Oouchi, Masato Hareyama, Masaaki Satoh

Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 182 ( 9 ) 511 - 7 2006.09 [Refereed] [International journal]

PURPOSE: To examine various kinds of endogenous hypoxia markers' expression in the tissues of uterine cervix cancer and to elucidate the characteristics and pitfalls when they are used as a hypoxia marker, by comparing these expressions with tumor oxygen partial pressure (pO2) values. PATIENTS AND METHODS: Assessment of pO2 using polarographic oxygen electrodes was performed in 69 patients with cervix carcinomas. Biopsies were taken from the region of electrode measurements. Expression of endogenous hypoxic markers in biopsy specimens such as vascular endothelial growth factor, glucose transporter-1 (GLUT-1), involucrin, and osteopontin was detected by immunohistochemistry. A double immunolabeling technique with GLUT-1 and MIB-1 as a marker of proliferation was also performed. RESULTS: There was no significant correlation between expression of endogenous hypoxic markers and pO2. The only significant association seen was between the fraction of necrosis and pO2. A significant but weak correlation was found among expression of endogenous hypoxic markers. The levels of necrosis were related negatively with levels of expression of endogenous hypoxic markers. The double immunolabeling technique with GLUT-1 and MIB-1 indicated that there were about 20% MIB-1-positive tumor cells without GLUT-1 expression in tissues adjacent to areas of necrosis. CONCLUSION: The existence of necrosis affected the expression of endogenous hypoxic markers. Some hypoxic tumor cells without expressions of hypoxia markers can maintain clonogenicity and influence the treatment results. The combined use of hypoxic markers is recommended because their expression is influenced by factors other than hypoxia.

PubMed

The association of DNA-dependent protein kinase activity with chromosomal instability and risk of cancer.

Masanori Someya, Koh-ichi Sakata, Yoshihisa Matsumoto, Hiroyuki Yamamoto, Manami Monobe, Hideyuki Ikeda, Koichi Ando, Yoshio Hosoi, Norio Suzuki, Masato Hareyama

Carcinogenesis 27 ( 1 ) 117 - 22 2006.01 [Refereed] [International journal]

The DNA double-strand breaks (DSBs) repair pathway has been implicated in maintaining genomic integrity via suppression of chromosomal rearrangements. DNA-dependent protein kinase (DNA-PK) has an important role with DNA DSBs repair. In this study, 93 of untreated cancer patients and 41 of cancer-free healthy volunteers were enrolled. Peripheral blood was collected, separated and centrifuged; DNA-PK activity was measured by DNA-pull-down assay. The expressions of DNA-PKcs, Ku70 and Ku86 were examined by RT-PCR assay and western blotting. Chromosomal aberrations were examined by cytogenetic methods. DNA-PK activities of peripheral blood lymphocytes (PBL) in patients with uterine cervix or breast cancer were significantly lower than those in normal volunteers. Age and smoking had no association with DNA-PK activity, whereas DNA-PK activity and the expression of Ku70, Ku86 and DNA-PKcs in RT-PCR were interrelated. A similar tendency was seen in western blot assay but less clear than in RT-PCR. Therefore, the association between DNA-PK activity and expression of DNA-PK in protein level could not be concluded. The frequency of chromosome aberration, such as dicentric chromosomes and excess fragment increased as the DNA-PK activity decreased. In conclusion, DNA-PK activity is associated with chromosomal instability. DNA-PK activity in PBL is associated with risk of breast and uterine cervix cancer. DNA-PK activity in PBL can be used to select individuals for whom an examination should be performed because of their increased susceptibility to breast and uterine cervix cancer.

PubMed

Analysis of local control in patients with non-Hodgkin's lymphoma according to the WHO classification.

Koh-Ichi Sakata, Masaaki Satoh, Masanori Someya, Hisayasu Nagakura, Atushi Oouchi, Kensei Nakata, Katsuhisa Kogawa, Kazumitsu Koito, Masato Hareyama, Tetsuo Himi

Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 181 ( 6 ) 385 - 91 2005.06 [Refereed] [International journal]

PURPOSE: To analyze the influence of radiotherapy doses, chemotherapy doses, and clinical parameters on in-field disease control to assess the optimal radiation doses for treatment of non-Hodgkin's lymphoma according to the newly proposed WHO classification. PATIENTS AND METHODS: Subjects consisted of 35 extranodal marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type, 75 diffuse large B-cell lymphomas (DLBCL), 14 follicular lymphomas, 17 extranodal natural killer (NK)/T-cell lymphomas, nasal type, eight unclassified peripheral T-cell lymphomas, four anaplastic large-cell lymphomas, T/null cell type, and five others. 59 patients received radiotherapy alone. 98 patients received CHOP, modified CHOP, or more intensive chemotherapy, and six patients were treated with other combination. RESULTS: No patients with MALT lymphoma had in-field local recurrence. There were no recurrences in DLBCL patients who received chemotherapy in which the doses of adriamycin were > 200 mg/m(2), nor in DLBCL patients who were treated with > 45 Gy. Only nine of 15 patients with T-cell lymphoma treated with < or = 50 Gy and three of five patients treated with > 50 Gy had local control. The dose of adriamycin had no influence on local control of T-cell lymphoma. CONCLUSION: T/NK-cell lymphomas were more radioresistant than B-cell lymphomas. The prognosis for peripheral T/NK-cell lymphomas is poor even when treated by irradiation combined with chemotherapy.

PubMed

Three cases of diffuse large B-cell lymphoma of the mandible treated with radiotherapy and chemotherapy.

Masanori Someya, Koh-Ichi Sakata, Hisayasu Nagakura, Katsuya Itou, Kensei Nakata, Atsushi Oouchi, Masaaki Satoh, Masato Hareyama

Radiation medicine 23 ( 4 ) 296 - 302 2005.06 [Refereed] [Domestic journal]

CASE REPORT: We report three cases of diffuse large B-cell lymphoma of the mandible and a review of the literature. All 3 of our patients had stage I AE disease and had complete remission for more than 2 years after 42-46 Gy of irradiation to the primary tumor with regional lymph nodes and 3 courses of chemotherapy consisting of cyclophosphamide, adriamycin, vincristine, and predonisolone (CHOP). Literature analysis, although biased toward published data, indicated that the 3-year disease-specific survival rates for non-Hodgkin's lymphoma (NHL) of the mandible were 90.5% and 47.6% for stages I and II, respectively. The treatment results for NHL of the mandible may be similar to general primary bone NHL and to other extranodal NHL's. CONCLUSION: Radiotherapy alone is not sufficient for tumor control for stage I+II, disease, and combination chemotherapy may be needed.

PubMed

Preliminary clinical results of conformal radiation therapy for prostate cancer

Atsushi Oouchi, T. Nakata, K. Aratani, M. Hori, T. Tsuchimoto, M. Someya, H. Nagakura, K. Sakata, M. Hareyama, N. Masumori, Y. Tsukamoto

Japanese Journal of Clinical Radiology 50 ( 5 ) 633 - 637 2005

We evaluated clinical results of delivered conformal radiation therapy (70 to 72Gy) in our hospital to 52 patients with T1-T3 prostate cancer. The median follow-up period is 23 months. The 5-year PSA relapse free survival rates (b-NED) were calculated according to T-stage. Gleason score, serum PSA and prognostic risk group. GU and GI morbidities were also examined. By the affection of adjuvant hormonal therapy, we were not able to find any statistical significant factor of local control. However, it is suspected that the conformal radiation therapy is useful for favorable risk group and that the radiation dose escalation or the combination of endocrine therapy will be required for improving b-NED of the other risk groups.

Expression of matrix metalloproteinase 9 is a prognostic factor in patients with non-Hodgkin lymphoma.

Koh-ichi Sakata, Masaaki Satoh, Masanori Someya, Hiroko Asanuma, Hisayasu Nagakura, Atushi Oouchi, Kensei Nakata, Katsuhisa Kogawa, Kazumitsu Koito, Masato Hareyama, Tetsuo Himi

Cancer 100 ( 2 ) 356 - 65 2004.01 [Refereed] [International journal]

BACKGROUND: Non-Hodgkin lymphoma (NHL) represents a heterogeneous group of tumors that vary with regard to their biologic aggressiveness and clinical course. In in vitro studies, matrix metalloproteinase 9 (MMP9) was reportedly expressed by human NHL cells and elevated levels of MMP9 have been observed in a subset of patients with high-grade NHL. METHODS: The expression of MMP2 and MMP9 was evaluated in 158 patients with NHL and the relation between the expression of these proteins and clinicopathologic factors was analyzed. All but 1 patient had received radiation therapy and 92 patients also were treated with intensive combination chemotherapy. RESULTS: Nearly all the patients with extranodal natural killer NK/T-cell lymphoma nasal type and anaplastic large cell lymphoma, T-cell/null cell type expressed MMP9. In contrast, only a small fraction of the patients with mucosa-associated lymphoid tissue (MALT) lymphomas and follicular lymphomas expressed MMP9. Approximately 50% of the diffuse large B-cell lymphoma (DLBCL) cases expressed MMP9. The expression of MMP2 was noted in some of the patients with DLBCL and nasal NK/T-cell lymphoma. The overall survival rates of patients who expressed MMP9 were significantly lower than that of those who did not. Such a correlation was not demonstrated in MMP2 expression. When MMP9 expression was analyzed in DLBLC patients, the overall survival rates of patients who expressed MMP9 were significantly lower than those who did not express MMP9. Chemotherapy was associated with better overall survival in DLBCL patients who expressed MMP9. Overall survival rates of T-cell/NK-cell lymphoma patients who expressed MMP9 appeared to be lower than that in those who did not express MMP9. However, chemotherapy was not found to improve overall survival in patients who expressed MMP9. CONCLUSIONS: MMP9 expression was observed in patients with aggressive NHL and was characterized by poor overall survival.

PubMed

THE CAREER PATHS OF THE PARTICIPANTS IN A RADIATION ONCOLOGY SEMINAR FOR MEDICAL DOCTOR CANDIDATES IN 1997

IMAGUMBAI Toshiyuki, UCHINO Minako, ITAZAWA Tomoko, SOMEYA Masanori, BITO Seiji

J Jpn Soc Ther Radiol Oncol ( Japanese Society for Therapeutic Radiology and Oncology ) 16 ( 4 ) 225 - 229 2004

Since 1995, the Japanese Society for Therapeutic Radiology and Oncology (JASTRO) has held a teaching seminar for medical doctor candidates. In 1997, thirty-three students participated in the seminar. After graduation, eighteen (18/33) of the participants became radiologists and twelve of them (12/18) majored in radiation oncology. These results imply that the seminar might have an impact on their career paths. Hence, we propose that the seminar can have an influence upon the career decision of medical students, and it could yield a breakthrough to overcome in the shortage of radiation oncologists in Japan.

DOI CiNii J-GLOBAL

Treatment strategy for oropharyngeal carcinoma (from the standpoint of radiotherapy)

Koh-ichi Sakata, Masato Hareyama, Masanori Someya, Hisayasu Nagakura, Atsushi Oouchi, Katsushi Asano, Shinji Ooguro

Toukeibu Gan 30 ( 3 ) 419 - 422 2004

In the treatment of oropharyngeal carcinoma, concomitant chemoradiotherapy using platium-based treatment schedules has yielded better results than radiotherapy alone and has been recently used by an increasing number of institutions. In the treatment of head and neck cancer including oropharyngeal cancer, salvage operation can be performed when radiotherapy fails to obtain locoregional control in some cases treated with radiotherapy alone. Such feasibility of salvage operation has influenced the decision on treatment modality and radiotherapy tends to be selected as a first-line treatment. However, salvage operation may be difficult to perform after concomitant chemoradiotherapy using platium-based treatments because the increased damage of the normal tissues by chemoradiotherapy may cause complications for the operation. Therefore, closer communication and more careful discussion between head and neck surgeons and radiation oncologists has become more important when the first-line treatment is decided. © 2004, Japan Society for Head and Neck Cancer. All rights reserved.

DOI

High-dose-rate intracavitary brachytherapy: results of analyses of late rectal complications.

Koh-ichi Sakata, Hisayasu Nagakura, Atushi Oouchi, Masanori Someya, Kensei Nakata, Mitsuo Shido, Kazumitsu Koito, Satoru Sagae, Ryuichi Kudo, Masato Hareyama

International journal of radiation oncology, biology, physics 54 ( 5 ) 1369 - 76 2002.12 [Refereed] [International journal]

PURPOSE: To examine the incidence of radiation-induced late rectal complications by analyzing the data of measured rectal doses in patients with cancer of the uterine cervix treated with high-dose-rate intracavitary brachytherapy. METHODS AND MATERIALS: We measured doses to the rectum in 105 patients with cancer of the cervix during high-dose-rate intracavitary brachytherapy with a semiconductor dosimeter that can measure five points in the rectum simultaneously. On the basis of these measurements, equivalent doses, to which the biologically equivalent doses were converted as if given as fractionated irradiation at 2 Gy/fraction, were calculated as components of the cumulative dose at five rectal points in intracavitary brachytherapy combined with the external whole pelvic dose. RESULTS: The calculated values of equivalent doses for late effects at the rectum ranged from 15 to 100 Gy (median 60 Gy for patients who did not develop complications and 76 Gy for patients who subsequently developed Grade II or III complications). When converted to a graph of absolute rectal complication probability, the data could be fitted to a sigmoid curve. The data showed a very definite dose-response relationship, with a threshold for complications at approximately 50 Gy and the curve starting to rise more steeply at approximately 60 Gy. The steepest part of the curve had a slope equivalent to approximately 4% incidence/1 Gy increase in equivalent doses. CONCLUSION: The radiation tolerance dose, 5% and 50% complication probability, was about 64 and 79 Gy, respectively. Our data almost agree with the prescribed dose for the rectum for the radiation tolerance doses on the basis of the recorded human and animal data. The probability of rectal complications increased drastically after the maximal rectal dose was >60 Gy.

PubMed

High-dose-rate versus low-dose-rate intracavitary therapy for carcinoma of the uterine cervix: a randomized trial.

Masato Hareyama, Koh-ichi Sakata, Atushi Oouchi, Hisayasu Nagakura, Mitsuo Shido, Masanori Someya, Kazumitsu Koito

Cancer 94 ( 1 ) 117 - 24 2002.01 [Refereed] [International journal]

BACKGROUND: This was a prospective randomized clinical trial undertaken at our institution to compare low-dose-rate (LDR) intracavitary radiation therapy versus high-dose-rate (HDR) intracavitary radiation therapy for the treatment of cervical carcinoma. METHODS: From January 1984 to December 1997, a total of 132 patients with Stage II or IIIB of invasive carcinoma of the uterine cervix were entered into this randomized study. Treatment arm by HDR or LDR was allocated according to the month of each patient's birth. External irradiation consisted of whole pelvis irradiation and pelvic irradiation. Doses of external irradiation for both groups were identical. The authors used 0.588 as the conversion factor of total intracavitary dose from LDR to HDR. RESULTS: The 5-year disease specific survival rates of Stage II and III patients treated with HDR were 69% and 51% whereas those with LDR were 87% and 60%, respectively. The 5-year pelvic recurrence free survival rates of Stage II and III patients treated with HDR were 89% and 73% whereas those with LDR were 100% and 70%, respectively. There was no significant difference in disease specific survival or pelvic recurrence free survival rates between HDR and LDR. The actuarial complication rate (Radiation Therapy Oncology Group Grade 3, 4, or 5) at 5 years was 10% in the HDR group and 13% in the LDR group, and the difference between the HDR and LDR groups was not statistically significant. CONCLUSIONS: The pelvic control or actuarial complication rates were comparable between HDR and LDR treatment. The difference between the disease specific survival rates for HDR and LDR was not statistically significant for Stage II or III, although in Stage II, patients treated with LDR appeared to have a better survival rate than those treated with HDR.

PubMed

A case of hepatocellular carcinoma: The feasibility of intravenous contrast enhanced ultrasonography in evaluating percutaneous microwave coagulation therapy

Naoki Hirokawa, Kazumitsu Koito, Sjsum, Kensei Nakata, Takeshi Ichimura, Masanori Someya, Takaharu Shounai, Naoya Yama, Hideki Hyoudou

Journal of Medical Ultrasonics 29 ( 1 ) J17 - J21 2002

Precise evaluation of the effect of treatment after ablation of liver tumors is essential. We encountered a case of hepatocellular carcinoma (HCC) in which tumoral necrosis was fairly well detected by intravenous contrast-enhanced ultrasonography (EU). An eighty-year-old woman with chronic hepatitis C underwent ultrasonographic examination (US), in which B mode US detected an HCC nodule 11 mm in diameter. This nodule was well enhanced by EU using the dynamic flow method and an ultrasound system (Toshiba PowerVision 8000) on both vascular and perfusion images. After percutaneous microwave coagulation therapy, the nodule was not enhanced by this method or enhanced CT. We think that EU should be the first choice of examination after nonsurgical treatment of liver tumors, because EU is more convenient than CT or MR and may have the same diagnostic ability to evaluate tumor viability as CT or MR.

Four Cases of Meningeal Hemangiopericytoma Treated with Surgery and Radiotherapy

M. Someya

Japanese Journal of Clinical Oncology ( Oxford University Press (OUP) ) 31 ( 11 ) 548 - 552 2001.11 [Refereed]

DOI

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