Radiotherapy or chemotherapy for clinical stage IIA and IIB seminoma: a systematic review and meta-analysis of patient outcomes.

BACKGROUND: Outcomes of radiotherapy (RT) compared with chemotherapy (CT) remain poorly defined for clinical stage (CS) IIA and IIB seminoma. We aimed to evaluate the current role of the two treatment modalities in this setting of testicular seminoma. PATIENTS AND METHODS: A systematic review and meta-analysis (MA) was carried out to identify all evaluable studies. Search was limited to studies published after 1990 and included the Medline, Embase databases, and abstracts from ASCO (GU), ESMO, AUA, and ASTRO meetings up to April 2014. Sensitivity analyses were applied including the following: CSIIA and CSIIB, paraortic + iliac RT only in both stages, RT dose (≥30 versus <30 Gy), and PEB/EP regimens only. RESULTS: Thirteen studies have been selected for MA on relapse outcome. No randomized trials compared RT and CT. There were 4 prospective and 9 retrospective studies, with a total of 607 patients receiving RT and 283 patients CT. The pooled relapse rate (RR) was similar between the RT [0.11, 95% confidence interval (CI) 0.08-0.14, P for heterogeneity = 0.096, I(2) = 38%] and CT groups (0.08, 95% CI 0.01-0.15, P for heterogeneity <0.001, I(2) = 82.5%). However, in the sensitivity analysis, the pooled RR for RT in CSIIB was 0.12 (95% CI 0.06-0.17) while it was 0.05 (95% CI 0-0.11) for CT. Long-term side-effects and incidence of second cancers were more frequently reported following RT. The overall incidence of nontesticular second malignancies was 0.04 (95% CI 0.01-0.02) in the RT group and 0.02 (95% CI 0.003-0.04) in the CT group. CONCLUSIONS: Although RT and CT appeared to be equal options in CSIIA and IIB seminoma, a trend in favor of CT for a lower incidence of side-effects and RR in CSIIB was found. This evidence is limited by the retrospective quality of studies and their small sample size.

Modelling late stool frequency and rectal pain after radical radiotherapy in prostate cancer patients: Results from a large pooled population.

AIM: To investigate late gastrointestinal toxicity in a large pooled population of prostate cancer patients treated with radical radiotherapy. Normal tissue complication probability models were developed for late stool frequency and late rectal pain. METHODS AND MATERIALS: Population included 1336 patients, 3-year minimum follow-up, treated with 66-80Gy. Toxicity was scored with LENT-SOMA-scale. Two toxicity endpoints were considered: grade ⩾2 rectal pain and mean grade (average score during follow-up) in stool frequency >1. DVHs of anorectum were reduced to equivalent uniform dose (EUD). The best-value of the volume parameter n was determined through numerical optimization. Association between EUD/clinical factors and the endpoints was investigated by logistic analyses. Likelihood, Brier-score and calibration were used to evaluate models. External calibration was also carried out. RESULTS: 4% of patients (45/1122) reported mean stool frequency grade >1; grade ⩾2 rectal pain was present in the TROG 03.04 RADAR population only (21/677, 3.1%): for this endpoint, the analysis was limited to this population. Analysis of DVHs highlighted the importance of mid-range doses (30-50Gy) for both endpoints. EUDs calculated with n=1 (OR=1.04) and n=0.35 (OR=1.06) were the most suitable dosimetric descriptors for stool frequency and rectal pain respectively. The final models included EUD and cardiovascular diseases (OR=1.78) for stool frequency and EUD and presence of acute gastrointestinal toxicity (OR=4.2) for rectal pain. CONCLUSION: Best predictors of stool frequency and rectal pain are consistent with findings previously reported for late faecal incontinence, indicating an important role in optimization of mid-range dose region to minimize these symptoms highly impacting the quality-of-life of long surviving patients.

Bladder spatial-dose descriptors correlate with acute urinary toxicity after radiation therapy for prostate cancer.

PURPOSE: To assess bladder spatial-dose parameters predicting acute urinary toxicity after radiotherapy for prostate cancer (PCa) through a pixel-wise method for analysis of bladder dose-surface maps (DSMs). MATERIALS & METHODS: The final cohort of a multi-institutional study, consisting of 539 patients with PCa treated with conventionally (CONV:1.8-2Gy/fr) or moderately hypo-fractionated radiotherapy (HYPO:2.2-2.7Gy/fr) was considered. Urinary toxicity was evaluated through the International Prostate Symptoms Score (IPSS) administered before and after radiotherapy. IPSS increases ⩾10 and 15 points at the end of radiotherapy (ΔIPSS⩾10 and ΔIPSS⩾15) were chosen as endpoints. Average DSMs (corrected into 2Gy-equivalent doses) of patients with/without toxicity were compared through a pixel-wise method. This allowed the extraction of selected spatial descriptors discriminating between patients with/without toxicity. Previously logistic models based on dose-surface histograms (DSH) were considered and replaced with DSM descriptors. Discrimination power, calibration and log-likelihood were considered to evaluate the impact of the inclusion of spatial descriptors. RESULTS: Data of 375/539 patients were available. ΔIPSS⩾10 was recorded in 76/375 (20%) patients, while 30/375 (8%) experienced ΔIPSS⩾15. The posterior dose at 12mm from the bladder base (roughly corresponding to the trigone region) resulted significantly associated to toxicity in the whole/HYPO populations. The cranial extension of the 75Gy isodose along the bladder central axis was the best DSM-based predictor in CONV patients. Multi-variable models including DSM descriptors showed better discrimination (AUC=0.66-0.77) when compared to DSH-based models (AUC=0.58-0.71) and higher log-likelihoods. CONCLUSION: DSMs are correlated with the risk of acute GU toxicity. The incorporation of spatial descriptors improves discrimination and log-likelihood of multi-variable models including dosimetric and clinical parameters.

High quality surface reconstruction in radiotherapy: Cross-sectional contours to 3D mesh using wavelets.

A novel approach for three-dimensional (3D) surface reconstruction of anatomical structures in radiotherapy (RT) is presented. This is obtained from manual cross-sectional contours by combining both image voxel segmentation processing and implicit surface streaming methods using wavelets. 3D meshes reconstructed with the proposed approach are compared to those obtained from traditional triangulation algorithm. Qualitative and quantitative evaluations are performed in terms of mesh quality metrics. Differences in smoothness, detail and accuracy are observed in the comparison, considering three different anatomical districts and several organs at risk in radiotherapy. Overall best performances were recorded for the proposed approach, regardless the complexity of the anatomical structure. This demonstrates the efficacy of the proposed approach for the 3D surface reconstruction in radiotherapy and allows for further specific image analyses using real biomedical data.