Spohn Simon K B, Zamboglou Constantinos, Bürkle Sophia L, Freitag Martin T, Brumberg Joachim, Engel Hannes, Gainey Mark, Kamps Marius, Toncheva Paolina, Sprave Tanja, Kirste Simon, Sigle August, Jilg Cordula, Gratzke Christian, Adebahr Sonja, Mix Michael, Bamberg Fabian, Zschaeck Sebastian, Ghadjar Pirus, Baltas Dimos, Grosu Anca L
Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine. University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site, Freiburg, Germany.
Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine. University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site, Freiburg, Germany; National Center for Tumour Diseases (NCT), Berlin, Germany; German Oncology Center, European University of Cyprus, Limassol, Cyprus.
Radiother Oncol. 2025 Jul;208:110883. doi: 10.1016/j.radonc.2025.110883. Epub 2025 Apr 15.
To present the primary endpoint results, toxicities and quality of life (QoL) after two-year follow-up (FU) of the HypoFocal Phase II trial.
Intermediate- and high-risk prostate cancer (PCa) patients were treated with moderately hypofractionated radiotherapy (MHRT) of 60 Gy in 20 fractions and a focal-boost of up to 75 Gy in Arm A, or high-dose-rate-brachytherapy (HDR-BT) of 15 Gy to the whole-gland with a boost of up to 19 Gy, followed by external beam RT (EBRT) of 44 Gy in 20 fractions in Arm B. Boost was based on combined information by multiparametric-magentic-resonance-tomography (mpMRI) and positron-emission-tomography targeting prostate-specific-membrane-antigen (PSMA-PET). Genitourinary (GU) and gastrointestinal (GI) toxicities were assessed according to CTCAEv5.0. QoL was assessed with validated questionnaires (IPSS, QLQ-PR25 and QLQ-PR30).
Twenty-five patients were treated with MHRT and 30 patients with HDR-BT + EBRT. At two-year-FU, the rate of grade 2 + GU and GI toxicity was 24 % and 8 % in Arm A and 10 % and 0 % in Arm B, respectively. Two grade 3 GI toxicities were reported in Arm A, which can be attributed to multifactorial genesis and interventions. QoL was good with significant and minimally-important-differences only in bowel symptoms in Arm A and sexual functioning in Arm B. One patient in each arm relapsed. Limitations are the relatively small sample size.
This is the first trial do demonstrate safety and feasibility of focal dose-escalation based on mpMRI and PSMA-PET in MHRT and HDR-BT + EBRT in intermediate- and high-risk PCa. Particularly, HDR-BT offers good toxicity and QoL profiles. Radiation proctitis demands careful management.
呈现低分割II期试验两年随访后的主要终点结果、毒性及生活质量（QoL）。
中高危前列腺癌（PCa）患者在A组接受20次分割、总剂量60 Gy的适度低分割放疗（MHRT）及最高75 Gy的局部加量放疗，或在B组接受全腺15 Gy的高剂量率近距离放疗（HDR-BT）及最高19 Gy的加量放疗，随后接受20次分割、总剂量44 Gy的外照射放疗（EBRT）。加量放疗基于多参数磁共振断层扫描（mpMRI）和靶向前列腺特异性膜抗原（PSMA）的正电子发射断层扫描的综合信息。根据CTCAEv5.0评估泌尿生殖系统（GU）和胃肠道（GI）毒性。使用经过验证的问卷（IPSS、QLQ-PR25和QLQ-PR30）评估生活质量。
25例患者接受了MHRT治疗，30例患者接受了HDR-BT + EBRT治疗。在两年随访时，A组2级及以上GU和GI毒性发生率分别为24%和8%，B组分别为10%和0%。A组报告了2例3级GI毒性，这可归因于多因素成因和干预措施。生活质量良好，仅在A组的肠道症状和B组的性功能方面存在显著且具有最小重要意义的差异。每组各有1例患者复发。局限性在于样本量相对较小。
这是第一项证明在中高危PCa的MHRT和HDR-BT + EBRT中基于mpMRI和PSMA-PET进行局部剂量递增的安全性和可行性的试验。特别是，HDR-BT具有良好的毒性和生活质量特征。放射性直肠炎需要谨慎处理。
