Stereotactic radiotherapy for managing ovarian cancer oligoprogression under poly (ADP-ribose) polymerase inhibitors (PARPi).

OBJECTIVE: Poly (ADP-ribose) polymerase inhibitors (PARPi) have become a new standard of care for the maintenance treatment of advanced epithelial ovarian cancer. This study aims to evaluate the efficacy and safety of combining stereotactic body radiotherapy with PARPi continuation as a strategy to treat ovarian cancer oligoprogression on PARPi. METHODS: This is a multicenter retrospective study including ovarian cancer patients treated with stereotactic body radiotherapy and PARPi continuation for oligoprogression under PARPi maintenance therapy between June 2012 and May 2023 in three Italian centers. PARPi treatment was continued until further disease progression or unacceptable toxicity. The primary endpoint was the next-line systemic therapy-free interval. The Kaplan-Meier method was used to assess local control, progression-free survival, and overall survival. Univariate and multivariate Cox regression analyses were performed to evaluate potential clinical outcomes predictors. RESULTS: 46 patients were included, with a total of 89 lesions treated over 63 radiotherapy treatments. Lymph nodes were the most frequently treated lesions (80, 89.9%), followed by visceral lesions (8, 9%) and one case with a bone lesion (1.1%). Median follow-up was 25.9 months (range 2.8-122). The median next-line systemic therapy-free interval was 12.4 months (95% CI 8.3 to 19.5). A number of prior chemotherapy lines greater than five was significantly associated with a reduced next-line systemic therapy-free interval (HR 3.21, 95% CI 1.11 to 9.32, p=0.032). At the time of analysis, 32 (69.6%) patients started a new systemic therapy regimen, while 14 (30.4%) remained on the PARPi regimen. The 2-year progression-free survival, local failure-free survival, and overall survival rates were 10.7%, 78.1%, and 76.5%, respectively. Four patients (8.7%) experienced acute toxicity with G1 gastrointestinal events. CONCLUSION: Stereotactic body radiotherapy combined with PARPi continuation may be an effective and safe strategy for managing ovarian cancer patients with oligoprogression on PARPi maintenance therapy. Prospective research is warranted to shed more light on this approach.

Moderate hypofractionation and simultaneous integrated boost by helical tomotherapy in prostate cancer: monoinstitutional report of acute tolerability assessment with different toxicity scales.

INTRODUCTION: Based on radiobiology evidence, hypofractionated radiotherapy has the potential of improving treatment outcome in prostate cancer patients. In this study, we evaluated the safety, in terms of acutetoxicity, of using moderate hypofractionated radiotherapy delivered with Helical Tomotherapy (HT) to treat prostate cancer patients. MATERIALS AND METHODS: Between December 2012 and April 2014, 42 consecutive patients were treated with hypofractionated radiotherapy using HT. All patients received 70 Gy in 28 fractions to PTV1, which included the prostate. In the intermediate risk group, 61.6 Gy were delivered to PTV2, which included the seminal vesicles. In high risk patients, the pelvic nodes were added (PTV3) and received 50.4 Gy. Acute toxicity was recorded prospectively with RTOG and Common Terminology Criteria for Adverse Events 3.0, retrospectively with CTCAE 4.0. Expanded Prostate Cancer Index Composite (EPIC) was measured at baseline and 3 months after end of treatment, to investigate health related quality of life with regards to bladder and gastrointestinal function. RESULTS: Acute toxicity was acceptable, independently from the system used to score side effects. Moderate genitourinary toxicity was more frequent than gastrointestinal toxicity. No correlation between acute side effects and patients' characteristics or physical dose parameters was registered. EPIC evaluation showed a negligible difference in urinary and bowel function post-treatment, that did not reach statistical significance. CONCLUSIONS: Our experience confirms the safety of moderate hypofractionation delivered with HT in prostate cancer patients with low, intermediate and high risk.

Moderate hypofractionated helical tomotherapy for localized prostate cancer: preliminary report of an observational prospective study.

OBJECTIVE: To report preliminary findings of a phase II study exploring the clinical outcomes of moderate hypofractionated radiotherapy performed with helical tomotherapy (HT) using computed tomography-magnetic resonance imaging-based planning for localized prostate cancer. METHODS: The phase II prospective study received ethics approval from our institutional ethics committee. A dose of 60 Gy/20 fractions for low-intermediate risk prostate cancer by means of HT was explored. Primary endpoints of the study were acute and late gastrointestinal (GI) and genitourinary (GU) toxicities. Secondary endpoints were quality of life and biochemical-free survival. RESULTS: A total of 35 patients were included in this interim report. At the time of the analysis, median follow-up was 36 months (range, 13-62). Acute GI toxicity was recorded as follows: grade 1 in 34% and grade 2 in 14%; acute GU toxicity was grade 1 in 71% and grade 2 in 11%. For the entire population of the study, no acute toxicities ⩾ grade 3 occurred. A single case of late grade 3 GU toxicity was registered, whereas no late GI toxicity ⩾grade 3 was recorded. At the time of the final assessment, no biochemical failure was detected. CONCLUSIONS: The preliminary results of the present phase II trial, using HT for moderate hypofractionation in localized prostate cancer, are optimal. In fact, HT guaranteed an acceptable tolerability profile with low rates of GU and GI side effects and, more specifically, no acute severe adverse events were recorded. Long-term findings are warranted.

Optimal local control and tolerability of three-dimensional conformal radiation therapy in prostate cancer: a single institutional experience of dose escalation in 125 patients.

AIMS: To evaluate long-term late side effects, clinical and biochemical relapse in non-metastatic prostate cancer patients treated with dose escalation, from 74 to 78 Gy, by means of three dimensional conformal radiation therapy. MATERIALS AND METHODS: Clinical data of 125 patients with prostate cancer who underwent three-dimensional conformal radiation therapy were retrospectively evaluated. All patients were stratified, according to the NCCN classification, in low, intermediate and high risk, and all of them showed histologically proven adenocarcinoma stage T1-T3 with at least 2 years of follow-up. Late toxicity was analyzed using a modified Radiation Therapy Oncology Group toxicity scale. RESULTS: With a median of follow-up of 48 months, grade ≥2 late genitourinary toxicity was reported in 18% and grade ≥2 gastrointestinal toxicity was detected in 12%. The PSA relapse rate was 20% in the high-risk group, 7% in the intermediate-risk group, and 3% in the low-risk group. CONCLUSIONS: Late side effects and tumor control in patients with non-metastatic prostate cancer in dose escalation from 74 to 78 Gy was acceptable. Three-dimensional conformal radiation therapy still represents a valid therapeutic option for departments where intensity-modulated radiation therapy or image-guided radiation therapy is still not available.