Online Adaptive MR-Guided Ultrahypofractionated Radiotherapy of Prostate Cancer on a 1.5 T MR-Linac: Clinical Experience and Prospective Evaluation.

The use of hypofractionated radiotherapy in prostate cancer has been increasingly evaluated, whereas accumulated evidence demonstrates comparable oncologic outcomes and toxicity rates compared to normofractionated radiotherapy. In this prospective study, we evaluate all patients with intermediate-risk prostate cancer treated with ultrahypofractionated (UHF) MRI-guided radiotherapy on a 1.5 T MR-Linac within our department and report on workflow and feasibility, as well as physician-recorded and patient-reported longitudinal toxicity. A total of 23 patients with intermediate-risk prostate cancer treated on the 1.5 T MR-Linac with a dose of 42.7 Gy in seven fractions (seven MV step-and-shoot IMRT) were evaluated within the MRL-01 study (NCT04172753). The duration of each treatment step, choice of workflow (adapt to shape-ATS or adapt to position-ATP) and technical and/or patient-sided treatment failure were recorded for each fraction and patient. Acute and late toxicity were scored according to RTOG and CTC V4.0, as well as the use of patient-reported questionnaires. The median follow-up was 12.4 months. All patients completed the planned treatment. The mean duration of a treatment session was 38.2 min. In total, 165 radiotherapy fractions were delivered. ATS was performed in 150 fractions, 5 fractions were delivered using ATP, and 10 fractions were delivered using both ATS and ATP workflows. Severe acute bother (G3+) regarding IPS-score was reported in five patients (23%) at the end of radiotherapy. However, this tended to normalize and no G3+ IPS-score was observed later at any point during follow-up. Furthermore, no other severe genitourinary (GU) or gastrointestinal (GI) acute or late toxicity was observed. One-year biochemical-free recurrence survival was 100%. We report the excellent feasibility of UHF MR-guided radiotherapy for intermediate-risk prostate cancer patients and acceptable toxicity rates in our preliminary study. Randomized controlled studies with long-term follow-up are warranted to detect possible advantages over current state-of-the-art RT techniques.

Radiotherapy and hyperthermia for breast cancer patients at high risk of recurrence.

PURPOSE: To evaluate the long-term efficacy of combined radiotherapy (RT) and hyperthermia (HT) in a large mono-institutional cohort of breast cancer (BC) patients affected by recurrent, newly diagnosed non-resectable or high risk resected tumor. MATERIALS AND METHODS: Records of BC patients treated with RT + HT between 1995 and 2018 were retrospectively analyzed. RT doses of 50-70 Gy concurrent to a twice per week superficial HT were applied. For HT, a temperature between 41 and 42 °C was applied for approximately 1 h. Primary endpoint was local control (LC), secondary endpoints comprised toxicity, overall survival (OS), and progression-free survival (PFS). RESULTS: A total of 191 patients and 196 RT + HT treatments were analyzed. In 154 cases (78.6%) RT + HT was performed for patients with recurrent BC. Among these, 93 (47.4% of the entire cohort) had received RT prior to RT + HT. Median follow up was 12.7 years. LC at 2, 5, and 10 years was 76.4, 72.8, and 69.5%, respectively. OS at 2, 5, and 10 years was 73.5, 52.3, and 35.5%, respectively. PFS at 2, 5, and 10 years was 55.6, 41, and 33.6%, respectively. Predictive factors for LC were tumor stage, distant metastases, estrogen/progesterone receptor expression, resection status and number of HT fractions. At multivariate analysis tumor stage and receptor expression were significant. No acute or late toxicities higher than grade 3 were observed. CONCLUSION: Combined RT + HT offers long-term high LC rates with acceptable toxicity for patients with recurrent, newly diagnosed non-resectable or resected BC at high risk of relapse.

Regional hyperthermia and moderately dose-escalated salvage radiotherapy for recurrent prostate cancer. Protocol of a phase II trial.

BACKGROUND: Current studies on salvage radiotherapy (sRT) investigate timing, dose-escalation and anti-hormonal treatment (ADT) for recurrent prostate cancer. These approaches could either be limited by radiation-related susceptibility of the anastomosis or by suspected side-effects of long-term ADT. A phase II protocol was developed to investigate the benefit and tolerability of regional hyperthermia with moderately dose-escalated radiotherapy. METHODS: The study hypothesis is that radio-thermotherapy is a safe and feasible salvage treatment modality. The primary endpoint is safety measured by frequency of grade 3+ genitourinary (GU) and gastrointestinal (GI) adverse events (AE) according to Common Toxicity Criteria (CTC) version 4. Feasibility is defined by number of hyperthermia treatments (n ≥ 7) and feasibility of radiotherapy according to protocol. Target volume delineation is performed according to the EORTC guidelines. Radiation treatment is administered with single doses of 2 Gy 5×/week to a total dose of 70 Gy. Regional hyperthermia is given 2×/week to a total of 10 treatments. RESULTS: European centres participate in the phase II trial using intensity modulated RT (IMRT) or volumetric modulated arc technique (VMAT). The initiating centres were participants of the SAKK 09/10 study, where the same patient criteria and target volume definition (mandatory successful performed dummy run) were applied insuring a high standardisation of the study procedures. CONCLUSIONS: The introduced phase II study implements highly precise image-guided radiotherapy and regional hyperthermia. If the phase II study is found to be safe and feasible, a multicenter phase III study is planned to test whether the addition of regional hyperthermia to dose-intensified sRT improves biochemical control.

Fast PRF-based MR thermometry using double-echo EPI: in vivo comparison in a clinical hyperthermia setting.

OBJECTIVE: To develop and test in a clinical setting a double-echo segmented echo planar imaging (DEPI) pulse sequence for proton resonance frequency (PRF)-based temperature monitoring that is faster than conventional PRF thermometry pulse sequences and not affected by thermal changes in tissue conductivity. MATERIALS AND METHODS: Four tumor patients underwent between one and nine magnetic resonance (MR)-guided regional hyperthermia treatments. During treatment, the DEPI sequence and a FLASH PRF sequence were run in an interleaved manner to compare the results from both sequences in the same patients and same settings. Temperature maps were calculated based on the phase data of both sequences. Temperature measurements of both techniques were compared using Passing and Bablok regression and the Bland-Altman method. RESULTS: The temperature results from the DEPI and FLASH sequences, on average, do not differ by more than ΔT = 1 °C. DEPI images showed typically more artifacts and approximately a twofold lower signal-to-noise ratio (SNR), but a sufficient temperature precision of 0.5°, which would theoretically allow for a fivefold higher frame rate. CONCLUSION: The results indicate that DEPI can replace slower temperature measurement techniques for PRF-based temperature monitoring during thermal treatments. The higher acquisition speed can be exploited for hot spot localization during regional hyperthermia as well as for temperature monitoring during fast thermal therapies.