Linac-based stereotactic salvage reirradiation for intraprostatic prostate cancer recurrence: toxicity and outcomes.

BACKGROUND: The rates of local failure after curative radiotherapy for prostate cancer (PC) remain high despite more accurate locoregional treatments available, with one third of patients experiencing biochemical failure and clinical relapse occurring in 30-47% of cases. Today, androgen deprivation therapy (ADT) is the treatment of choice in this setting, but with not negligible toxicity and low effects on local disease. Therefore, the treatment of intraprostatic PC recurrence represents a challenge for radiation oncologists. Prostate reirradiation (Re-I) might be a therapeutic possibility. We present our series of patients treated with salvage stereotactic Re­I for intraprostatic recurrence of PC after radical radiotherapy, with the aim of evaluating feasibility and safety of linac-based prostate Re­I. MATERIALS AND METHODS: We retrospectively evaluated toxicities and outcomes of patients who underwent salvage reirradiation using volumetric modulated arc therapy (VMAT) for intraprostatic PC recurrence. Inclusion criteria were age ≥ 18 years, histologically proven diagnosis of PC, salvage Re­I for intraprostatic recurrence after primary radiotherapy for PC with curative intent, concurrent/adjuvant ADT with stereotactic body radiation therapy (SBRT) allowed, performance status ECOG 0-2, restaging choline/PSMA-PET/TC and prostate MRI after biochemical recurrence, and signed informed consent. RESULTS: From January 2019 to April 2022, 20 patients were recruited. Median follow-up was 26.7 months (range 7-50). After SBRT, no patients were lost at follow-up and all are still alive. One- and 2­year progression free survival (PFS) was 100% and 81.5%, respectively, while 2­year biochemical progression-free survival (bFFS) was 88.9%. Four patients (20%) experienced locoregional lymph node progression and were treated with a further course of SBRT. Prostate reirradiation allowed the ADT start to be postponed for 12-39 months. Re­I was well tolerated by all patients and none discontinued the treatment. No cases of ≥ G3 genitourinary (GU) or gastrointestinal (GI) toxicity were reported. Seven (35%) and 2 (10%) patients experienced acute G1 and G2 GU toxicity, respectively. Late GU toxicity was recorded in 10 (50%) patients, including 8 (40%) G1 and 2 (10%) G2. ADT-related side effects were found in 7 patients (hot flashes and asthenia). CONCLUSION: Linac-based SBRT is a safe technique for performing Re­I for intraprostatic recurrence after primary curative radiotherapy for PC. Future prospective, randomized studies are desirable to better understand the effectiveness of reirradiation and the still open questions in this field.

How smart is artificial intelligence in organs delineation? Testing a CE and FDA-approved Deep-Learning tool using multiple expert contours delineated on planning CT images.

Background: A CE- and FDA-approved cloud-based Deep learning (DL)-tool for automatic organs at risk (OARs) and clinical target volumes segmentation on computer tomography images is available. Before its implementation in the clinical practice, an independent external validation was conducted. Methods: At least a senior and two in training Radiation Oncologists (ROs) manually contoured the volumes of interest (VOIs) for 6 tumoral sites. The auto-segmented contours were retrieved from the DL-tool and, if needed, manually corrected by ROs. The level of ROs satisfaction and the duration of contouring were registered. Relative volume differences, similarity indices, satisfactory grades, and time saved were analyzed using a semi-automatic tool. Results: Seven thousand seven hundred sixty-five VOIs were delineated on the CT images of 111 representative patients. The median (range) time for manual VOIs delineation, DL-based segmentation, and subsequent manual corrections were 25.0 (8.0-115.0), 2.3 (1.2-8) and 10.0 minutes (0.3-46.3), respectively. The overall time for VOIs retrieving and modification was statistically significantly lower than for manual contouring (p<0.001). The DL-tool was generally appreciated by ROs, with 44% of vote 4 (well done) and 43% of vote 5 (very well done), correlated with the saved time (p<0.001). The relative volume differences and similarity indexes suggested a better inter-agreement of manually adjusted DL-based VOIs than manually segmented ones. Conclusions: The application of the DL-tool resulted satisfactory, especially in complex delineation cases, improving the ROs inter-agreement of delineated VOIs and saving time.

Dose-Volume Constraints fOr oRganS At risk In Radiotherapy (CORSAIR): An "All-in-One" Multicenter-Multidisciplinary Practical Summary.

BACKGROUND: The safe use of radiotherapy (RT) requires compliance with dose/volume constraints (DVCs) for organs at risk (OaRs). However, the available recommendations are sometimes conflicting and scattered across a number of different documents. Therefore, the aim of this work is to provide, in a single document, practical indications on DVCs for OaRs in external beam RT available in the literature. MATERIAL AND METHODS: A multidisciplinary team collected bibliographic information on the anatomical definition of OaRs, on the imaging methods needed for their definition, and on DVCs in general and in specific settings (curative RT of Hodgkin's lymphomas, postoperative RT of breast tumors, curative RT of pediatric cancers, stereotactic ablative RT of ventricular arrythmia). The information provided in terms of DVCs was graded based on levels of evidence. RESULTS: Over 650 papers/documents/websites were examined. The search results, together with the levels of evidence, are presented in tabular form. CONCLUSIONS: A working tool, based on collected guidelines on DVCs in different settings, is provided to help in daily clinical practice of RT departments. This could be a first step for further optimizations.

Importance of the correct assessment of bone fractures in the clinical management of metastatic castration-resistant prostate cancer treated with radium-223: A case report.

Patients who undergo radium-223 treatment for metastatic castration-resistant prostate cancer (mCRPC) generally have a long history of androgen deprivation therapy and/or steroid therapy, which leads to bone loss and causes osteoporosis. Notably, Osteoporosis in combination with metastatic bone disease increases the risk of bone fracture. An 84-year-old man with multi-metastatic bone CRPC underwent six administrations of intravenous radium-223, which induced a good biochemical and clinical response. However, two months following the treatment, the patient reported acute pain localized to the lumbar spine mimicking bone progression disease and presented with stable prostate-specific antigen levels. A prostate-specific membrane antigen-positron emission tomography scan showed no tracer uptake in that site, whereas a magnetic resonance imaging scan and subsequent vertebral biopsy confirmed the absence of cancer progression and showed the presence of vertebral crushing of L4-L5, which was probably due to an osteoporotic process. The patient had never received bisphosphonate therapy and refused it during α-emitting therapy with radium-223. The osteoporotic process, in association with metastatic bone disease, more easily leads to bone fractures that have an important impact on performance status, quality of life and prognosis quoad vitam in patients with advanced prostate cancer. Use of bisphosphonates or anti-RANKL antibody appears to be effective in improving bone mineral density. Notably, patients with multi-metastatic bone disease who undergo radium-223 therapy should be treated in conjunction with anti-osteoporotic therapy (bisphosphonates or anti-RANKL antibody) and adequate calcium and vitamin D supplementation. Early recognition and differentiation of osteoporotic processes when determining the progression of cancer-associated bone disease is crucial in evaluating the response to radium-223 therapy and, consequently, for further therapeutic decision making.