Stereotactic body radiotherapy (SBRT) re-irradiation for local failures following radical prostatectomy and post-operative radiotherapy.

PURPOSE: Local recurrences after radical prostatectomy (RP) and postoperative radiotherapy (RT) are challenging for salvage treatment. Retrospective analysis of own experiences with salvage re-irradiation was performed. METHODS: The study included all consecutive patients treated with salvage stereotactic body radiotherapy (sSBRT) for prostate bed recurrence following RP and postoperative RT at a single tertiary center between 2014 and 2021. Treatment toxicity defined as the occurrence of CTCAE grade ≥ 2 genito-urinary (GU) or gastro-intestinal (GI) adverse events (AEs) was assessed. A PSA response, biochemical control (BC) and overall survival (OS) were also evaluated. RESULTS: The study group included 32 patients with a median age of 68 years and a median follow-up of 41 months, treated with CyberKnife (53%) or Linac (47%) sSBRT. Total dose of 33.75-36.25 Gy in five fractions (72%) was applied in the majority of them. Approximately 19% patients reported grade ≥ 2 GU AEs both at baseline and at three months, and grade ≥ 2 GI toxicity increased from 0% at baseline to 6% at three months after sSBRT. There was some clinically relevant increase in late toxicity with 31% patients reporting late ≥ 2 GU, and 12.5% late ≥ 2 GI AEs. Two grade 3 AEs were recorded: recto-urinary fistulas. The majority of patients showed a PSA response (91% at one year post-sSBRT). The 3­year BC was 40% and 3­year OS was 87%. CONCLUSIONS: Manageable toxicity profile and satisfactory biochemical response suggest that SBRT in patients with local recurrence following RP and postoperative RT might be a salvage option for selected patients.

Rectum and Bladder Toxicity in Postoperative Prostate Bed Irradiation: Dose-Volume Parameters Analysis.

Although prostate cancer treatment is increasingly effective, its toxicities pose a major concern. The aim of our study was to assess the rate of adverse events (AEs) and the prognostic value of dose-volume histogram (DVH) parameters for the occurrence of treatment toxicity in patients treated with post-prostatectomy prostate bed radiotherapy (RT). The AEs were scored according to the CTCAE v.5.0. The rectum and bladder were contoured according to the RTOG Guidelines. The DVH parameters were assessed using data exported from the ECLIPSE treatment-planning system. Genitourinary (GU) and gastrointestinal (GI) toxicity were analysed using consecutive dose thresholds for the percentage of an organ at risk (OAR) receiving a given dose and the QUANTEC dose constraints. A total of 213 patients were included in the final analysis. Acute grade 2 or higher (≥G2) GU AEs occurred in 18.7% and late in 21.3% of patients. Acute ≥G2 GI toxicity occurred in 11.7% and late ≥G2 in 11.2% of the patients. Five patients experienced grade 4 AEs. The most common adverse effects were diarrhoea, proctitis, cystitis, and dysuria. The most significant predictors of acute ≥G2 GI toxicity were rectum V47 and V46 (p < 0.001 and p < 0.001) and rectum wall V46 (p = 0.001), whereas the most significant predictors of late ≥G2 GI AEs were rectum wall V47 and V48 (p = 0.019 and p = 0.021). None of the bladder or bladder wall parameters was significantly associated with the risk of acute toxicity. The minimum doses to bladder wall (p = 0.004) and bladder (p = 0.005) were the most significant predictors of late ≥G2 GU toxicity. Postoperative radiotherapy is associated with a clinically relevant risk of AEs, which is associated with DVH parameters, and remains even in patients who fulfil commonly accepted dose constraints. Considering the lack of survival benefit of postoperative adjuvant RT, our results support delaying treatment through an early salvage approach to avoid or defer toxicity.

Efficacy of CDK 4/6 Inhibitors and Radiotherapy in Breast Cancer Patients with Brain Metastases.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard of care for HR-positive/HER2-negative advanced breast cancer patients. However, their role in the treatment of brain metastases is currently unclear. We retrospectively evaluate the results of patients (pts) with advanced breast cancer treated at our institution with CDK4/6i and radiotherapy to the brain. The primary endpoint was progression-free survival (PFS). Secondary endpoints were local control (LC) and severe toxicity. Among 371 pts treated with CDK4/6i, 24 pts (6.5%) received radiotherapy to the brain before (11 pts), during (6 pts), or after (7 pts) CDK4/6i treatment. Sixteen pts received ribociclib, six received palbociclib, and two received abemaciclib. Six- and twelve-month PFS was 76.5% (95% CI: 60.3-96.9) and 49.7% (95% CI: 31.7-77.9), respectively, whereas six- and twelve-month LC was 80.2% (95% CI: 58.7-100) and 68.8% (95% CI: 44.5-100), respectively. With a median follow-up of 9.5 months, no unexpected toxicity was observed. We conclude that treatment with both CDK4/6i and brain radiotherapy is feasible and should not increase the toxicity compared to brain radiotherapy or CDK4/6i alone. However, the small number of individuals treated concurrently limits the conclusions about the combination of both modalities, and the results from ongoing prospective clinical trials are eagerly awaited to understand both the toxicity profile and the clinical response fully.