Moderately hypofractionated salvage radiotherapy in patients with biochemical recurrence of prostate cancer after prostatectomy: long-term results and comparative analysis of two schedules.

Hypofractionation in salvage radiotherapy (HSRT) for biochemical recurrence of prostatic cancer after prostatectomy is a debated issue and at present, it should be considered purely investigational because of the lack of evidence supporting its use. In this study, we report the outcomes of patients presenting with biochemical recurrence after radical prostatectomy who received HSRT. The additional aim of this study is to compare two moderately HSRT schedules. Patients treated to prostate bed with daily Image Guided-VMAT and a total dose of 65 Gy/26 fractions (Group A) or 66 Gy/30 fractions (Group B) were included in the study. Inclusion criteria were: pN0/pNx, pre-HSRT PSA ≥0.2 ng/ml and ≤1 ng/ml, no evidence of pelvic/extrapelvic disease at restaging, no pelvic irradiation or dose boost on macroscopic local recurrence, no neoadjuvant/concomitant Androgen Deprivation Therapy (ADT), follow-up ≥36 months, and available pre/post HSRT data. Genitourinary (GU) and gastrointestinal (GI) toxicities, early and late, were assessed using CTCAE Vers. 5.0. One hundred patients were retrospectively identified to 50 in each group. Median follow-up was 59 months. All patients completed the prescribed HSRT. 5-year biochemical failure-free survival, local control, distant relapse-free survival, and ADT- free survival were 52.1%, 85.9%, 63.7%, and 73.2%, respectively. No significant differences in these outcomes were found between the two groups. On multivariate analysis, a hypofractionation schedule was not associated with any outcome, but ISUP score ≥ 4 and pre-HSRT PSA were associated with worse biochemical failure-free survival while only ISUP score ≥ 4 was associated with worse distant relapse-free survival. No Grade 3 GU/GI acute event was reported; 6 (6%) and 2 (2%) patients experienced late Grade ≥ 2 GU and GI events, respectively. No difference was found between the two groups neither in acute nor in late GU/GI toxicities. Our findings demonstrate that HSRT is feasible, effective, and safe. Our analysis did not show any significant difference between the two hypofractionated schedules. Further studies and randomized controlled trials are required in order to confirm these results and to identify the optimal hypofractionated schedule in the salvage setting.

Clinical Use of a Commercial Artificial Intelligence-Based Software for Autocontouring in Radiation Therapy: Geometric Performance and Dosimetric Impact.

PURPOSE: When autocontouring based on artificial intelligence (AI) is used in the radiotherapy (RT) workflow, the contours are reviewed and eventually adjusted by a radiation oncologist before an RT treatment plan is generated, with the purpose of improving dosimetry and reducing both interobserver variability and time for contouring. The purpose of this study was to evaluate the results of application of a commercial AI-based autocontouring for RT, assessing both geometric accuracies and the influence on optimized dose from automatically generated contours after review by human operator. MATERIALS AND METHODS: A commercial autocontouring system was applied to a retrospective database of 40 patients, of which 20 were treated with radiotherapy for prostate cancer (PCa) and 20 for head and neck cancer (HNC). Contours resulting from AI were compared against AI contours reviewed by human operator and human-only contours using Dice similarity coefficient (DSC), Hausdorff distance (HD), and relative volume difference (RVD). Dosimetric indices such as Dmean, D0.03cc, and normalized plan quality metrics were used to compare dose distributions from RT plans generated from structure sets contoured by humans assisted by AI against plans from manual contours. The reduction in contouring time obtained by using automated tools was also assessed. A Wilcoxon rank sum test was computed to assess the significance of differences. Interobserver variability of the comparison of manual vs. AI-assisted contours was also assessed among two radiation oncologists for PCa. RESULTS: For PCa, AI-assisted segmentation showed good agreement with expert radiation oncologist structures with average DSC among patients ≥ 0.7 for all structures, and minimal radiation oncology adjustment of structures (DSC of adjusted versus AI structures ≥ 0.91). For HNC, results of comparison between manual and AI contouring varied considerably e.g., 0.77 for oral cavity and 0.11-0.13 for brachial plexus, but again, adjustment was generally minimal (DSC of adjusted against AI contours 0.97 for oral cavity, 0.92-0.93 for brachial plexus). The difference in dose for the target and organs at risk were not statistically significant between human and AI-assisted, with the only exceptions of D0.03cc to the anal canal and Dmean to the brachial plexus. The observed average differences in plan quality for PCa and HNC cases were 8% and 6.7%, respectively. The dose parameter changes due to interobserver variability in PCa were small, with the exception of the anal canal, where large dose variations were observed. The reduction in time required for contouring was 72% for PCa and 84% for HNC. CONCLUSIONS: When an autocontouring system is used in combination with human review, the time of the RT workflow is significantly reduced without affecting dose distribution and plan quality.

Predicting Local Failure after Partial Prostate Re-Irradiation Using a Dosiomic-Based Machine Learning Model.

The aim of this study is to predict local failure after partial prostate re-irradiation for the treatment of isolated locally recurrent prostate cancer by using a machine learning classifier based on radiomic features from pre-treatment computed tomography (CT), positron-emission tomography (PET) and biological effective dose distribution (BED) of the radiotherapy plan. The analysis was conducted on a monocentric dataset of 43 patients with evidence of isolated intraprostatic recurrence of prostate cancer after primary external beam radiotherapy. All patients received partial prostate re-irradiation delivered by volumetric modulated arc therapy. The gross tumor volume (GTV) of each patient was manually contoured from planning CT, choline-PET and dose maps. An ensemble machine learning pipeline including unbalanced data correction and feature selection was trained using the radiomic and dosiomic features as input for predicting occurrence of local failure. The model performance was assessed using sensitivity, specificity, accuracy and area under receiver operating characteristic curves of the score function in 10-fold cross validation repeated 100 times. Local failure was observed in 13 patients (30%), with a median time to recurrence of 36.7 months (range = 6.1-102.4 months). A four variables ensemble machine learning model resulted in accuracy of 0.62 and AUC 0.65. According to our results, a dosiomic machine learning classifier can predict local failure after partial prostate re-irradiation.

RR Myelo POINT: A Retrospective Single-Center Study Assessing the Role of Radiotherapy in the Management of Multiple Myeloma and Possible Interactions with Concurrent Systemic Treatment.

Background and purpose: Although chemotherapy, biological agents, and radiotherapy (RT) are cornerstones of the treatment of multiple myeloma (MM), the literature regarding the possible interactions of concurrent systemic treatment (CST) and RT is limited, and the optimal RT dose is still unclear. Materials and methods: We retrospectively analyzed the records of patients who underwent RT for MM at our institution from 1 January 2005 to 30 June 2020. The data of 312 patients and 577 lesions (treated in 411 accesses) were retrieved. Results: Most of the treated lesions involved the vertebrae (60%) or extremities (18.9%). Radiotherapy was completed in 96.6% of the accesses and, although biologically effective doses assuming an α/ß ratio of 10 (BED 10) > 38 Gy and CST were significantly associated with higher rates of toxicity, the safety profile was excellent, with side effects grade ≥2 reported only for 4.1% of the accesses; CST and BED 10 had no impact on the toxicity at one and three months. Radiotherapy resulted in significant improvements in performance status and in a pain control rate of 87.4% at the end of treatment, which further increased to 96.9% at three months and remained at 94% at six months. The radiological response rate at six months (data available for 181 lesions) was 79%, with only 4.4% of lesions in progression. Progression was significantly more frequent in the lesions treated without CST or BED 10 < 15 Gy, while concurrent biological therapy resulted in significantly lower rates of progression. Conclusion: Radiotherapy resulted in optimal pain control rates and fair toxicity, regardless of BED 10 and CST; the treatments with higher BED 10 and CST (remarkably biological agents) improved the already excellent radiological disease control.

Cumulative intracranial tumour volume prognostic assessment: a new predicting score index for patients with brain metastases treated by stereotactic radiosurgery.

Brain metastases (BM) represent the most common intracranial malignancy in adults. Limitations of existing prognostic models reduce their predictivity and clinical applicability. The aim of this study is to validate the cumulative intracranial tumour volume prognostic assessment (CITVPA) as a new prognostic score system for patients with BM treated by Stereotactic Radiosurgery (SRS). Between January 2001 and December 2015, 1894 patients underwent Gamma Knife SRS treatment. The CITVPA model was implemented and validated as follows: the CITV cut-offs were identified thanks to a receiver-operating characteristic (ROC) curve analysis; the survival predictive factors were selected through a Cox proportional hazard model; its prognostic power was compared to RPA, SIR and GPA through the Harrel concordance index (HCI). According to the ROC curve analysis, the CITV cut-off values were set at 1.5 and 4.0 cc. Based on the multivariate analysis, the CITVPA model included: age (OR 1.010, 95% CI 1.005-1.015, p < 0.001), KPS (OR 0.960, 95% CI 0.956-0.965, p < 0.001), extracranial metastases (OR 1.287, 95% CI 1.154-1.437, p < 0.001), BM number (OR 1.193, 95% CI 1.047-1.360, p = 0.008), and CITV (OR 1.028, 95% CI 1.020-1.036, p < 0.001). A score between 0 and 1 was attributed to each prognosticator; a global CITVPA score ranging from 0 to 5 was assigned with higher results corresponding to worse outcomes. The CITVPA (HCI = 0.64) exhibited a significantly (p < 0.001) higher prognostic power compared to RPA (HCI = 0.55), SIR (HCI = 0.55) and GPA (HCI = 0.61). The CITVPA represents a reliable prognostic system for patients with BM treated by SRS. However, further prospective and multicentric studies are necessary before its applicability in clinical practice.

Prognostic value of two geriatric screening tools in a cohort of older patients with early stage Non-Small Cell Lung Cancer treated with hypofractionated stereotactic radiotherapy.

OBJECTIVES: To investigate whether assessment with two geriatric screening tools shows a correlation with clinical outcomes of patients aged 65 years or more, with early-stage Non-Small Cell Lung Cancer (es-NSCLC) treated with hypofractionated stereotactic radiotherapy. METHODS: From March 2014 to June 2018 we retrospectively evaluated 42 patients with stage I and II lung tumors. Patients were assessed with Charlson Comorbidity Index (CCI) and G8 screening tool. Median age was 74 years (range, 65-91). Stereotactic radiotherapy was performed with Helical Tomotherapy delivering 50-70 Gray (Gy) in 8-10 fractions. Toxicity was evaluated using Common Terminology Criteria for Adverse Events v4.0 criteria. RESULTS: Median CCI and G8 scores were 6 (4-11) and 14 (12-17), respectively. With a median follow-up of 14 months (3-37), we observed: 3 cases of acute Grade 2 (G2) radiation pneumonitis, 1 late G2 non-cardiac chest pain, 1 late G2 dysphagia and 1 case of late G2 radiation pneumonitis. At statistical analysis, G8 scores ≤14 were significantly associated with late toxicity rates (p = .0073). Local failure was predictive of disease free survival and Overall Survival (p < .001 and p = .001). Death occurred in 12 patients, 6 for non-cancer related causes, with 1- and 2-yrs cancer specific survival rates of 94.8% and 90%, 1- and 2-yrs OS rates of 93% and 80%, respectively. CONCLUSIONS: Our experience shows a correlation between G8 scores and late toxicity in older patients treated with stereotactic radiotherapy for lung cancer, suggesting the need for prospective studies evaluating its use for the identification of patients at higher risk of adverse events.