Research activity information

• Assessment of prognostic value and development of predictive model for prolonged lymphopenia in patients with glioblastoma following chemoradiotherapy.
  Shuhei Takahashi; Kentaro Nishioka; Takashi Mori; Shigeru Yamaguchi; Yukitomo Ishi; Keiji Kobashi; Yoichi M Ito; Zen-Ichi Tanei; Hiromi Kanno-Okada; Shinya Tanaka; Hidefumi Aoyama
  Journal of radiation research, 66, 5, 542, 550, 23 Sep. 2025, [International Magazine]
  English, Scientific journal, Lymphopenia during chemoradiotherapy (CRT) for glioblastoma has been shown to be a poor prognostic factor. However, the relationship between prolonged lymphopenia (PL) after CRT and prognosis remains unclear. This study aimed to explore the relationship between PL and glioblastoma prognosis and develop a predictive model for PL risk. We analyzed 87 patients with primary glioblastoma who underwent postoperative CRT with 60 Gy in 30 fractions of radiotherapy and temozolomide. PL was defined as grade 2 or higher lymphopenia 1 month after the completion of CRT. We conducted survival analysis, identified risk factors for PL, and developed a predictive model for PL risk. Of the 87 patients, 41 developed PL, and progression-free survival (PFS) was significantly shorter in the PL group (median 8.0 months vs 15.4 months, P = 0.003). However, there was no significant difference in overall survival between the two groups. PL was also a significant factor for shorter PFS in multivariable analysis (P = 0.040). Brain V20Gy (percentage of brain volume receiving ≥20 Gy), gross total resection (GTR), and preoperative Karnofsky performance status (KPS) were identified as significant risk factors for PL. The predictive model showed that the risk of PL could be predicted by brain V20Gy, sex, age, GTR and preoperative KPS. PL was identified as a PFS shortening factor. Our model suggests that reducing irradiated brain volume may help prevent PL and could potentially improve glioblastoma prognosis by preserving cancer immunity.
• Evaluation of intra-fractional target displacement by patient motion during a single-isocenter multi-target stereotactic radiation therapy for brain metastases.
  Ryota Yamada; Takaaki Yoshimura; Ryo Murata; Kentaro Nishioka; Takashi Mori; Fuki Koizumi; Yoshihiro Fujita; Shuhei Takahashi; Takahiro Hattori; Takahiro Kanehira; Kohei Yokokawa; Rie Yamazaki; Kenji Horita; Hiroshi Tamura; Yamato Wakabayashi; Yuta Ichiu; Takayuki Hashimoto; Hidefumi Aoyama
  Journal of applied clinical medical physics, 26, 9, e70219, Sep. 2025, [International Magazine]
  English, Scientific journal, BACKGROUND: Single-isocenter multi-target volumetric modulated arc therapy (SIMT-VMAT) has been implemented widely in fractionated stereotactic radiosurgery (fSRS) to treat brain metastases. The impact of rotational intra-fractional patient motion (IFPM) is influenced by the distance between the geometric target's center and the isocenter (DTI). PURPOSE: We hypothesized that IFPM's impact on each target would increase with greater DTI during fSRS. Therefore, we aimed to estimate the intra-fractional target displacement (IFTD), which represents each target's displacement caused by translational and rotational components of IFPM. METHODS: In this study, we involved 35 patients with 2-13 brain metastases, all of whom had previously undergone SIMT-VMAT fSRS. All patients were immobilized using a clamshell-style device, with 28 using a biteplate. Cone beam computed tomography (CBCT) images were obtained at the same imaging center before and after treatment. The IFPM was calculated using both CBCT datasets. The IFTD was determined by comparing the planned target coordinates with the actual coordinates while factoring in IFPM. RESULTS: We evaluated 136 targets. The mean IFTD was 0.38 mm (95% confidence interval [CI]: 0.37-0.40 mm) with the biteplate and 0.65 mm (95% CI: 0.59-0.71 mm) without it. A very weak positive correlation was observed between DTI and IFTD despite the immobilization method. This correlation indicates that the distance dependence of IFTD is nearly negligible. CONCLUSION: The findings showed that the impact of IFPM on each target demonstrated minimal dependence on the DTI. Displacement was relatively consistent regardless of the target location. In addition, the use of a biteplate was suggested to potentially reduce these effects.
• Treatment outcomes of radiotherapy with concurrent weekly cisplatin in older patients with locally advanced head and neck squamous cell carcinoma.
  Yusuke Uchinami; Koichi Yasuda; Satoshi Kano; Manami Otsuka; Seijiro Hamada; Takayoshi Suzuki; Nayuta Tsushima; Shuhei Takahashi; Yoshihiro Fujita; Tomohiko Miyazaki; Hajime Higaki; Jun Taguchi; Yasushi Shimizu; Tomohiro Sakashita; Akihiro Homma; Hidefumi Aoyama
  Discover oncology, 14, 1, 226, 226, 08 Dec. 2023, [International Magazine]
  English, Scientific journal, BACKGROUND: Tri-weekly cisplatin and radiotherapy (CDDP + RT) is a standard of care for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) but is sometimes challenging to complete in older patients. Weekly CDDP + RT has shown mild toxicity compared to tri-weekly CDDP + RT for LA-HNSCC and is a promising option for older adults. We aimed to report the treatment outcomes and prognostic factors in patients with LA-HNSCC treated with weekly CDDP + RT. METHODS: We analyzed patients aged ≥ 70 years who started weekly CDDP + RT for LA-HNSCC between July 2006 and October 2022. LA-HNSCC includes cancer in the oropharynx, hypopharynx, or larynx with a clinical stage of 3 or 4 without distant metastases based on the Union for International Cancer Control staging system 8th edition. The radiation dose of 70 Gy was delivered in 35 fractions by 3-dimensional conformal radiotherapy, intensity-modulated radiotherapy, or proton beam therapy. The primary endpoint was the 3-year overall survival (OS), and the secondary endpoints were the 3-year progression-free survival (PFS) and 3-year cause-specific survival (CSS). The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was used to evaluate statistical significance. A Cox proportional hazards model was used for the multivariate analysis of prognostic factors. RESULTS: The median age of the 49 patients was 72 (range: 70-78) years. The median CDDP dose was 200 (40-280) mg/ m2, and 47 patients completed scheduled radiotherapy. Forty-eight patients (98.0%) had a performance status of ≥ 1 at the initial visit. The 3-year OS, PFS, and CSS were 80.9% (95% confidence interval [CI]: 64.8-90.7), 68.3% (95% CI 51.8-81.2), and 85.0% (95% CI 68.7-93.4), respectively. In the multivariate analysis, the cumulative CDDP dose (< 200 or ≥ 200 mg/m2) was a significant factor for OS (hazard ratio: 0.29 [95% CI 0.08-0.97], p = 0.044). There was one case of early mortality. Grade 3 or higher late adverse events were observed in four patients (8.2%). CONCLUSIONS: Weekly CDDP + RT in older patients led to good survival outcomes with an acceptable rate of adverse events. CDDP should be administered at a dose of at least 200 mg/m2 in older patients. Trial registration Retrospectively registered.
• The need of radiotherapy optimization for glioblastomas considering immune responses.
  Kentaro Nishioka; Shuhei Takahashi; Takashi Mori; Yusuke Uchinami; Shigeru Yamaguchi; Manabu Kinoshita; Masaaki Yamashina; Hajime Higaki; Katsuya Maebayashi; Hidefumi Aoyama
  Japanese journal of radiology, 41, 10, 1062, 1071, Oct. 2023, [Domestic magazines]
  English, Scientific journal, Glioblastoma is the most common of malignant primary brain tumors and one of the tumors with the poorest prognosis for which the overall survival rate has not significantly improved despite recent advances in treatment techniques and therapeutic drugs. Since the emergence of immune checkpoint inhibitors, the immune response to tumors has attracted increasing attention. Treatments affecting the immune system have been attempted for various tumors, including glioblastomas, but little has been shown to be effective. It has been found that the reason for this is that glioblastomas have a high ability to evade attacks from the immune system, and that the lymphocyte depletion associated with treatment can reduce its immune function. Currently, research to elucidate the resistance of glioblastomas to the immune system and development of new immunotherapies are being vigorously carried out. Targeting of radiation therapy for glioblastomas varies among guidelines and clinical trials. Based on early reports, target definitions with wide margins are common, but there are also reports that narrowing the margins does not make a significant difference in treatment outcome. It has also been suggested that a large number of lymphocytes in the blood are irradiated by the irradiation treatment to a wide area in a large number of fractionations, which may reduce the immune function, and the blood is being recognized as an organ at risk. Recently, a randomized phase II trial comparing two types of target definition in radiotherapy for glioblastomas was conducted, and it was reported that the overall survival and progression-free survival were significantly better in a small irradiation field group. We review recent findings on the immune response and the immunotherapy to glioblastomas and the novel role of radiotherapy and propose the need to develop an optimal radiotherapy that takes radiation effects on the immune function into account.
• Distribution of human papilloma virus genotypes and treatment outcomes in definitive radiotherapy for cervical cancer.
  Rumiko Kinoshita; Takashi Mitamura; Fumi Kato; Takahiro Hattori; Hajime Higaki; Shuhei Takahashi; Yoshihiro Fujita; Manami Otsuka; Fuki Koizumi; Yusuke Uchinami; Takashi Mori; Kentaro Nishioka; Takayuki Hashimoto; Yoichi M Ito; Hidemichi Watari; Hidefumi Aoyama
  Journal of radiation research, 64, 2, 463, 470, 23 Mar. 2023, [International Magazine]
  English, Scientific journal, Most oncogenic human papilloma virus (HPV) genotypes stratify into two species, α-7 HPV and α-9 HPV. There are several studies that evaluate the relationship between HPV species and treatment outcomes and reports that HPV species is prognostic. The HPV genotyping was conducted using biopsy specimens which had been stored in these studies. We conducted the study using the HPV test performed by cytology specimens which is less invasive and more useful in clinical settings. This study enrolled 46 patients who received HPV genotyping before the definitive radiotherapy. The results of the HPV genotyping were classified into HPVα-7, HPVα-9 and negatives. Of the 46 patients, 10 were positive for HPVα-7, 21 positive for HPVα-9 and 15 were negative. The median follow-up period was 38 months (range 4-142). The HPVα-7, HPVα-9 and negative groups showed the 3-year overall survival (OS; 59.3%, 80.4% and 72.2% [P = 0.25]); local control (LC; 67.5%, 81% and 80% [P = 0.78]); pelvic control (PC) (50%, 81% and 72.7% [P = 0.032]); pelvic lymph node (PLN) control (78.7%, 95% and 92.3% [P = 0.012]); distant metastasis free (DMF) survival (50%, 75.4% and 42.8% [P = 0.098]); and progression free survival (PFS) rate of patients (30%, 66.7% and 38.9% [P = 0.085]), respectively. Patients with HPVα-7 showed statistically significant poorer PC than the HPVα-9 group, in multivariate analysis. This result is consistent with previous studies for HPV positive patients. The HPV negativity rate was higher in this study than in other studies and further work on this may be needed for clinical use.
• Evaluation of short-term gastrointestinal motion and its impact on dosimetric parameters in stereotactic body radiation therapy for pancreatic cancer.
  Yusuke Uchinami; Takahiro Kanehira; Yoshihiro Fujita; Naoki Miyamoto; Kohei Yokokawa; Fuki Koizumi; Motoyasu Shido; Shuhei Takahashi; Manami Otsuka; Koichi Yasuda; Hiroshi Taguchi; Keiji Nakazato; Keiji Kobashi; Norio Katoh; Hidefumi Aoyama
  Clinical and translational radiation oncology, 39, 100576, 100576, Mar. 2023, [International Magazine]
  English, Scientific journal, BACKGROUND: The aim of this study is to quantify the short-term motion of the gastrointestinal tract (GI-tract) and its impact on dosimetric parameters in stereotactic body radiation therapy (SBRT) for pancreatic cancer. METHODS: The analyzed patients were eleven pancreatic cancer patients treated with SBRT or proton beam therapy. To ensure a fair analysis, the simulation SBRT plan was generated on the planning CT in all patients with the dose prescription of 40 Gy in 5 fractions. The GI-tract motion (stomach, duodenum, small and large intestine) was evaluated using three CT images scanned at spontaneous expiration. After fiducial-based rigid image registration, the contours in each CT image were generated and transferred to the planning CT, then the organ motion was evaluated. Planning at risk volumes (PRV) of each GI-tract were generated by adding 5 mm margins, and the volume receiving at least 33 Gy (V33) < 0.5 cm3 was evaluated as the dose constraint. RESULTS: The median interval between the first and last CT scans was 736 s (interquartile range, IQR:624-986). To compensate for the GI-tract motion based on the planning CT, the necessary median margin was 8.0 mm (IQR: 8.0-10.0) for the duodenum and 14.0 mm (12.0-16.0) for the small intestine. Compared to the planned V33 with the worst case, the median V33 in the PRV of the duodenum significantly increased from 0.20 cm3 (IQR: 0.02-0.26) to 0.33 cm3 (0.10-0.59) at Wilcoxon signed-rank test (p = 0.031). CONCLUSION: The short-term motions of the GI-tract lead to high dose differences.