若年男性における病勢増悪リスクの増加:非転移性前立腺癌に対する高線量強度変調放射線治療後の生化学的再発と去勢抵抗性前立腺癌化への予測因子に関する解析

京都大学新制・課程博士博士(医学)甲第23081号医博第4708号新制||医||1049(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 中本 裕士, 教授 小川 誠司, 教授 武田 俊一学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Evaluation of internal margins for prostate for step and shoot intensity‐modulated radiation therapy and volumetric modulated arc therapy using different margin formulas

[Purpose] This feasibility study evaluated the intra-fractional prostate motion using an ultrasound image-guided system during step and shoot intensity-modulated radiation therapy (SS-IMRT) and volumetric modulated arc therapy (VMAT). Moreover, the internal margins (IMs) using different margin formulas were calculated. [Methods] Fourteen consecutive patients with prostate cancer who underwent SS-IMRT (n = 5) or VMAT (n = 9) between March 2019 and April 2020 were considered. The intra-fractional prostate motion was observed in the superior–inferior (SI), anterior–posterior (AP), and left–right (LR) directions. The displacement of the prostate was defined as the displacement from the initial position at the scanning start time, which was evaluated using the mean ± standard deviation (SD). IMs were calculated using the van Herk and restricted maximum likelihood (REML) formulas for SS-IMRT and VMAT. [Results] For SS-IMRT, the maximum displacements of the prostate motion were 0.17 ± 0.18, 0.56 ± 0.86, and 0.18 ± 0.59 mm in the SI, AP, and LR directions, respectively. For VMAT, the maximum displacements of the prostate motion were 0.19 ± 0.64, 0.22 ± 0.35, and 0.14 ± 0.37 mm in the SI, AP, and LR directions, respectively. The IMs obtained for SS-IMRT and VMAT were within 2.3 mm and 1.2 mm using the van Herk formula and within 1.2 mm and 0.8 mm using the REML formula. [Conclusions] This feasibility study confirmed that intra-fractional prostate motion was observed with SS-IMRT and VMAT using different margin formulas. The IMs should be determined according to each irradiation technique using the REML margin

Low incidence of late recurrence in patients with intermediate-risk prostate cancer treated by intensity-modulated radiation therapy plus short-term androgen deprivation therapy

Objectives: This study evaluated the long-term outcomes of intensity-modulated radiation therapy (IMRT) combined with short-term neoadjuvant androgen deprivation therapy (ADT) in patients with intermediate-risk (IR) prostate cancer (PCa). Materials and methods: Patients with IR PCa treated with IMRT at our institution between September 2000 and November 2010 were analyzed retrospectively. The treatment consisted of IMRT (70–78 Gy in 35–39 fractions) combined with 6 months of neoadjuvant ADT. Salvage ADT was initiated when the prostate-specific antigen level was > 4.0 ng/mL Results: In total, 106 consecutive patients with IR PCa (median age: 70 years old) were analyzed. The median follow-up period was 8.0 years. The overall survival, PCa-specific survival, biochemical failure, and clinical failure rates were 99.0%, 100.0%, 6.8%, and 1.9% at 5 years and 89.1%, 100.0%, 11.3%, and 2.9% at 10 years, respectively. Late recurrence (> 5 years) was observed in three cases (2.8%). The cumulative incidence rates of genitourinary (GU) and gastrointestinal (GI) toxicities (grade 2/3) were 10.5% and 5.8% at 5 years, and 14.7% and 5.8% at 10 years, respectively. No patient developed grade 4/5 GU toxicities or grade 3–5 GI toxicities. Conclusion: IMRT at a dose up to 78 Gy combined with short-term neoadjuvant ADT resulted in excellent long-term disease-free outcomes with acceptable morbidities among patients with IR PCa. In addition, the incidence of late recurrence was very low. Further investigation is warranted to confirm our findings

Clinical significance of IDC-P as predictive factor after intensity-modulated radiation therapy

The clinical significance of intraductal carcinoma of the prostate (IDC-P) in men with nonmetastatic prostate cancer (PCa) treated with high-dose external-beam radiation therapy remains unclear. The aim of this study was to evaluate the impact of IDC-P in men who received intensity-modulated radiation therapy (IMRT) for nonmetastatic PCa. All patients with high-risk (H-R) and very high–risk (VH-R) PCa who received IMRT between September 2000 and December 2013 at our institution were analyzed retrospectively. We re-reviewed biopsy cores for the presence of IDC-P. Treatment consisted of IMRT (median: 78 Gy at 2 Gy per fraction) plus 6-month neoadjuvant hormonal therapy (HT). In total, 154 consecutive patients with H-R and VH-R PCa were analyzed. Intraductal carcinoma of the prostate was present in 27.9% (n = 43). The median follow-up period was 8.4 years. The 10-year PCa-specific survival, biochemical failure (BF), clinical failure, and castration-resistant PCa rates were 90.0%, 47.8%, 27.5%, and 24.5% in patients with IDC-P, and 96.6%, 32.6%, 10.8%, and 7.0% in those without IDC-P, respectively (p = 0.12, 0.04, 0.0031, and 0.012, respectively). In multivariable analysis, IDC-P was not identified as an independent predictive factor for BF (p = 0.26). The presence of IDC-P was correlated with a significantly higher incidence of disease progression in men with H-R and VH-R PCa who received IMRT, although it was not identified as an independent predictive factor for BF. Further investigations are needed to determine the significance of IDC-P as an independent predictive factor for survival outcomes

Efficacy and Safety of External-beam Radiation Therapy for Unresectable Primary or Local Recurrent Cholangiocarcinoma

Background/Aim: Treatment options for unresectable cholangiocarcinoma are limited. The aim of the study was to evaluate the clinical outcomes of definitive external-beam radiation therapy (EBRT) for patients with unresectable cholangiocarcinoma. Patients and Methods: Patients with unresectable primary cholangiocarcinoma, or local recurrent cholangiocarcinoma after primary surgery, without distant metastasis who received definitive EBRT (≥45 Gy) between January 2006 and December 2020 at our Institution were analyzed retrospectively. EBRT was basically performed using conventional fractionation (1.8-2 Gy per fraction). Prophylactic nodal irradiation was not performed. Results: A total of 21 consecutive patients were analyzed: 7 primary and 14 recurrent cases. The median age was 70 (range=38–85) years at initiation of EBRT. A median dose of 54 (range=45-60) Gy comprising 1.8 (range=1.8-3) Gy per fraction was administered to the primary/recurrent local tumor site. The median follow-up period was 21.6 months. The 2-year overall survival, cause-specific survival, progression-free survival, and local recurrence-free rates were 35.7, 35.7, 16.1, and 32.7%, respectively. Long-term local control (>2 years after EBRT) was achieved in 19.0%. Grade 3 toxicities related to EBRT were observed in 4.8% (duodenum hemorrhage). No grade 4 or higher toxicities were observed. Conclusion: Definitive EBRT for unresectable cholangiocarcinoma was feasible and achieved long-term local control in a subset of patients. As the avoidance of local recurrence may lead to the benefits of prolonging biliary patency and subsequently alleviating the need for an invasive procedure for biliary drainage, EBRT could be one sustainable therapeutic option for patients with unresectable cholangiocarcinoma

Highly hypofractionated intensity-modulated radiation therapy for nonmetastatic prostate cancer with a simultaneous integrated boost to intraprostatic lesions: a planning study

PURPOSE: The purpose of this planning study was to develop an acceptable technique for highly hypofractionated intensity-modulated radiation therapy using simultaneous integrated boost technique (SIB-hHF-RT) for nonmetastatic National Comprehensive Cancer Network high-risk prostate cancer. MATERIALS AND METHODS: We created SIB-hHF-RT plans for 14 nonmetastatic prostate cancer patients with MRI-detectable intraprostatic lesions (IPLs) and without intestines locating close to the seminal vesicle and prostate. We prescribed 57 Gy for IPLs and 54 Gy for the remainder of planning target volume (PTV) in 15 fractions. The IPLs were contoured based on magnetic resonance imaging, and PTV was generated by adding 6-8-mm margins to the clinical target volume. For the dose-volume constraints of organs at risk (OARs), the same constraints as 54 Gy plans were used so as not to increase the toxicity. RESULTS: All created plans fulfilled the dose-volume constraints of all targets and OARs. The median estimated beam-on time was 108.5 s. For patient-specific quality assurance, the global gamma passing rates (3%/2 mm) with 10% dose threshold criteria were greater than 93% in all cases and greater than 95% in 11 cases. CONCLUSION: SIB-hHF-RT plans were developed that fulfill the acceptable dose-volume constraints and pass patient-specific quality assurance. We believe these plans can be applied to selected patients with nonmetastatic prostate cancer

Long-term safety of high-dose whole pelvic IMRT for high-risk localized prostate cancer through 10-year follow-up

[Background] The aim of this study was to evaluate the long-term efficacy and safety of whole pelvic intensity-modulated radiation therapy with a simultaneous-integrated boost (WP-SIB-IMRT) for locally advanced prostate cancer (LAPCa). [Methods] All patients with cT3–4N0M0 prostate cancer treated with WP-SIB-IMRT between February 2006 and September 2009 at our institution were analyzed retrospectively. The prescribed dose was 78 Gy to the prostate and 58.5 Gy to the prophylactic pelvic lymph nodal area in 39 fractions delivered using the simultaneous-integrated boost technique. All patients received short-term neoadjuvant androgen-deprivation therapy alone (median 8.3 months). Propensity-score matching (PSM) analysis was performed to evaluate the additional benefit of prophylactic whole pelvic radiation therapy (WPRT), using the cohort of 203 LAPCa patients treated with prostate-only IMRT (PO-IMRT). [Results] In total, 47 consecutive patients were analyzed. The median estimated risk of pelvic lymph node involvement was 57.5%. The median follow-up period was 10.5 years. The 10 year prostate cancer-specific survival and biochemical failure (BF) rates were 92.2 and 54.8%, respectively. The 10 year cumulative incidence rates of ≥ grade 2 late genitourinary and gastrointestinal toxicities were 21.6 and 17.2%, respectively. From a total of 250 patients, PSM analysis identified 76 patients with similar characteristics, and no significant difference in BF rates was observed between WP-SIB-IMRT and PO-IMRT cohorts (p = 0.261). [Conclusions] WP-SIB-IMRT for LAPCa was safe over long-term observation, although no clear benefit of WPRT was observed among our small and highly selected cohort. Regarding the additional efficacy of WPRT, further investigations are needed

Long‐term clinical outcomes of external beam radiation therapy for oligometastatic prostate cancer: A combination of prostate‐targeted treatment and metastasis‐directed therapy

OBJECTIVE: To assess the efficacy of combination of prostate-targeted treatment and metastasis-directed therapy for oligometastatic prostate cancer. METHODS: We retrospectively evaluated the clinical outcomes of synchronously diagnosed oligometastatic prostate cancer patients treated with external beam radiation therapy for the prostate and all metastatic lesions (≤3 lesions) at Kyoto University Hospital between January 2004 and April 2019. The prescribed dose was basically ≥70 Gy for the prostate with or without whole pelvic irradiation, and ≥45 Gy for the metastatic lesions. Clinical outcomes were compared with a contemporary cohort of 55 synchronous oligometastatic prostate cancer patients treated with the standard of care. RESULTS: In total, 16 consecutive patients with synchronous oligometastatic prostate cancer were analyzed. The median follow-up period was 7.4 years. The 8-year overall survival, prostate cancer-specific survival, biochemical failure-free, clinical failure-free and castration-resistant prostate cancer-free rates were 64.8%, 71.3%, 38.5%, 47.3% and 67.3%, respectively. No grade 3 or higher radiation-induced late toxicities occurred. Patients with prostate-targeted treatment plus metastasis-directed therapy had a significantly higher castration-resistant prostate cancer-free rate than those without prostate-targeted treatment plus metastasis-directed therapy (P = 0.00741). CONCLUSIONS: Prostate-targeted treatment plus metastasis-directed therapy through external beam radiation therapy can result in favorable long-term disease-free and survival outcomes with acceptable morbidities among synchronous oligometastatic prostate cancer patients. Therefore, this approach may represent a promising treatment strategy for this population. Further investigation is required

Long-term outcomes of an esophagus-preserving chemoradiotherapy strategy for patients with endoscopically unresectable stage I thoracic esophageal squamous cell carcinoma

[Background and purpose] To assess the long-term outcomes of a multimodal approach for maximum esophagus preservation in operable patients with endoscopically unresectable stage I thoracic esophageal squamous cell carcinoma (ESCC). [Materials and methods] The medical records of patients with stage I thoracic ESCC treated with our protocol between 1992 and 2005 were retrospectively reviewed. Our protocol consisted of neoadjuvant concurrent chemoradiotherapy, followed by either additional definitive chemoradiotherapy for good responders (CRT group) or surgery for moderate or poor responders (CRT-S group) after an interim appraisal. [Results] A total of 51 patients were analysed. The median age of the patients was 67 years. The median follow-up period was 124.8 months. After the interim assessment, 49 and 2 cases were assigned to the CRT and CRT-S groups, respectively. In the intent-to-treat analyses, overall survival (OS), disease-free survival (DFS), cumulative incidence for death from esophageal cancer, and that for loss of esophageal function were 78.9%, 53.5%, 10.5%, and 20.4% at 5 years, and 55.2%, 27.8%, 18.2%, and 22.9% at 10 years, respectively. Grade 3 late toxicities occurred with the following incidences: esophageal stenosis in 1 case, esophageal ulcer in 1 case, and pericardial effusion in 2 cases. No grade 4 or higher toxicities were observed. [Conclusion] Long-term survival and esophagus preservation outcomes were favorable, with acceptable toxicities. Our results suggest that CCRT is an alternative treatment for majority of operable patients with endoscopically unresectable stage I thoracic ESCC in combination with salvage therapy