Biological Dose Evaluation Of Radiotherapy By Equivalent Dose In 2Gy Fractions (EQD2) In Recurrent Glioblastoma.

The standard treatment for glioblastoma is surgery followed by radiation therapy (RT) and temozolomide (TMZ) chemotherapy. A total dose of 60 Gy given in 2 Gy fractions (fr) with concurrent and adjuvant TMZ has been recommended; however, local recurrences are frequent and the prognosis remains very poor. In this study, the equivalent dose in 2Gy fr (EQD2) at the recurrent site of glioblastoma was assessed to evaluate the biological effect of RT on glioblastoma considering that α/β ratios might vary from 1 to 10 Gy. Recurrences were found in gross tumor volume (GTV) areas in all 11 patients, and 8 of them also showed recurrence in clinical target volume (CTV). Differences in EQD2 according to α/β ratios were relatively small in high-dose areas around 60 Gy; however, low-dose areas often showed significant differences of EQD2 according to the α/β ratios. In patients that received 60 Gy in 2 Gy fr, EQD2 was less than the original physical dose and became smaller as the α/β ratio became smaller. The comparison of the dose distribution of EQD2 and dose volume histogram (DVH) of EQD2 between α/β ratios 1 and 10 suggested that little difference was found in relatively high-dose areas but a significant difference was found in low-dose areas. In contrast, if the fraction size was larger than 2 Gy, EQD2 was greater than the original physical dose and it became larger as the α/β ratio became smaller. In conclusion, this study showed that the standard RT 60 Gy in 2 Gy fr is insufficient for glioblastoma, and it suggested that biological effects might differ significantly according to each fraction size of radiation and α/β ratio of the linear quadratic (LQ) model

中枢神経系原発悪性リンパ腫の放射線治療個別化の妥当性と有用性：画像評価を用いた治療効果に基づく放射線治療計画

Background: To assess the feasibility and efficacy of individualized treatment selection in radiation therapy (RT) for primary central nervous system lymphoma (PCNSL) according to treatment response by radiographic assessment. Methods: The details of recurrence and change in performance status (PS) were assessed in 31 patients with histologically confirmed PCNSL treated between 2000 and 2016. During the treatment period, radiographic assessment was conducted, and RT planning (RTP) was determined individually by treatment response. Results: At a median follow-up of 28.2 months, 9 patients were alive and 7 of whom were relapse-free. Two-year overall survival (OS) and progression-free survival (PFS) rates were 69.3% and 52.7%, with median survival times (MSTs) of 36.5 months and 24.4 months, respectively. Two-year local recurrence rate was 40.5% and the median time to local recurrence from treatment initiation was 27.9 months. All patients were scheduled to receive whole-brain RT (WBRT) and subsequent partial-brain RT(PBRT), with a median total dose to the tumor bed of 46 Gy and median WBRT dose of 30 Gy. Eight patients received reduced-dose WBRT (rd-WBRT) (<30 GY), and 13 patients who could not achive a complete response (CR) during the RT period received additional boost radiation after WBRT and PBRT, with a median dose of 6 Gy. Over 70% of local recurrence occurred within areas in which only WBRT was conducted (median dose of 30.3 Gy). Two-year occurrence rate of neurotoxicity over grade 2 was 49.5%. PS at 24 months after RT was maintained in 12 patIents. Conclusions: lndividual RTP using radiographic assessment led to reasonable survival and disease control rates with mild treatment-related toxicity. For patients not receiving chemotherapy or lacking a CR after chemotherapy and WBRT, WBRT followed by PBRT and additional boost radiation for poor RT responders might be effective. However, even for patients with CR after chemotherapy, a WBRT dose of 30 Gy or higher might be necessary for local control.博士（医学）・甲第705号・平成31年3月15

頭皮皮膚血管肉腫に対する根治的な寡分割高線量放射線治療の実行可能性と有効性の検討

Cutaneous angiosarcoma is a rare but highly aggressive vascular tumor resistant to all treatment modalities available. The aim of this study was to analyze the treatment outcomes of patients who received definitive hypofractionated high-dose radiotherapy (RT) for angiosarcoma of the scalp. Between April 2008 and December 2014, 11 patients with histologically proven cutaneous angiosarcoma of the scalp visited our Department of Radiation Oncology, because dermatologists suggested that there was no indication for surgery in those cases. One patient rejected all radical treatments and the other 10 patients were treated by RT with curative intent along with chemotherapy or immunotherapy. Eight patients were treated with 6 - 12 MeV electron beams and the other 2 patients were treated with 4 MV X-ray Intensity Modulated Radiation Therapy (IMRT) and electron beams. The total irradiated dose was 63 - 75 Gy (median: 72.5 Gy) in 26 - 30 fractions, and the fraction size was 2.5 Gy in principle. The median age of the patients treated with RT was 80 years old (range: 73 - 91) and the median follow-up time was 16.5 months (range: 5.6 - 86.3). Four patients are still alive. A complete response (CR) was achieved in 10 patients (100%) and only one patient suffered local relapse 20 months after RT. Medians of overall survival (OS), progression-free survival (PFS), and local relapse-free survival (LRFS) were 38.7, 13.4, and 19.8 months, respectively. Local control rates were 100 and 75% at 1 and 2 years, respectively. Skin ulceration was CTCAE grade 2 in 5 patients (50%) and grade 3 in 5 (50%), alopecia was grade 2 in all patients (100%), but no patient developed grade 4 or more severe adverse events after RT. Hypofractionated high-dose RT was feasible and achieved excellent local control of cutaneous angiosarcoma in the elderly patients.博士（医学）・甲第646号・平成28年3月15日Copyright: © 2015 Shimoda E. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The definitive version is available at " http://clinmedjournals.org/articles/ijccr/international-journal-of-cancer-and-clinical-research-ijccr-2-032.php?jid=ijccr

再発膠芽腫における放射線治療の生物学的線量評価 : 2Gy等価線量換算値(EQD2)による検討

The standard treatment for glioblastoma is surgery followed by radiation therapy (RT) and temozolomide (TMZ) chemotherapy. A total dose of 60 Gy given in 2 Gy fractions (fr) with the concurrent and adjuvant TMZ has been recommended; however, local recurrences are frequent and the prognosis remains very poor. In this study, the equivalent dose in 2Gy fr (EQD2) in the recurrent site of glioblastoma was assessed to evaluate the biological effect of RT on glioblastoma considering that α/β ratios might vary from 1 to 10 Gy. Recurrences were found in gross tumor volume (GTV) areas in all 11 patients, and 8 of them also showed recurrence in clinical target volume (CTV). Differences in EQD2 according to α/β ratios were relatively small in high-dose areas around 60 Gy; however, low-dose areas often showed significant differences of EQD2 according to the α/β ratios. In patients that received 60 Gy in 2 Gy fr, EQD2 was less than the original physical dose and became smaller as the α/β ratio became smaller. The comparison of the dose distribution of EQD2 and dose volume histogram (DVH) of EQD2 between α/β ratios 1 and 10 suggested that little difference was found in relatively high-dose areas but a significant difference was found in lowdose areas. In contrast, if the fraction size was larger than 2 Gy, EQD2 was greater than the original physical dose and it became larger as the α/β ratio became smaller. In conclusion, this study showed that the standard RT 60 Gy in 2 Gy fr is insufficient for glioblastoma, and it suggested that biological effects might differ significantly according to each fraction size of radiation and α/β ratio of the linear quadratic (LQ) model.博士（医学）・甲第838号・令和4年3月15