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

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<SOMEYA Masanori>

Papers - SOMEYA Masanori