Preventative and Personalized Approach to the Treatment of Malignant Melanoma: A Case Report.

This case report is focused on malignant melanoma, a common potentially lethal skin cancer, and its unique management. In our pa­tient’s case, the primary cutaneous melanoma occurred 28 years prior to presenting with axillary lymphadenopathy, which was later determined to be a metastatic focus of melanoma; subsequent nodules were found in his spleen. After completion of his treatment and routine screening, additional nodules were discovered in his chest. Primary and secondary prevention were important in the man­agement of this patient, as well as personalization of his treatment. Cette étude de cas porte sur le mélanome malin, un cancer de la peau potentiellement mortel avec une gestion unique. Dans le cas de notre patient, le mélanome s’est présenté 28 ans avant la présentation d’une lymphadénopathie axillaire, ce qui a été démontré par la suite comme une zone étant métastatique du mélanome. Des nodules ont été découverts dans sa rate. Suite à la fin des traitements et des suivis de routine, des nodules additionnels ont été découverts dans sa poitrine. Des préventions primaires et secondaires sont importantes pour la gestion de ce patient ainsi qu’un traitement personnalisé

Enumerating pelvic recurrence following radical cystectomy for bladder cancer: A canadian multi-institutional study

Introduction: We aimed to enumerate the rate of pelvic recurrence following radical cystectomy at university-affiliated hospitals in Canada. Methods: Canadian, university-affiliated hospitals were invited to participate. They were asked to identify the first 10 consecutive patients undergoing radical cystectomy starting January 1, 2005, who had urothelial carcinoma stages pT3/T4 N0-2 M0. The first 10 consecutive cases starting January 1, 2005 who met these criteria were the patients submitted by that institution with information regarding tumour stage, age, number of nodes removed, and last known clinical status in regard to recurrence and patterns of failure. Results: Of the 111 patients, 80% had pT3 and 20% pT4 disease, with 62% being node-negative, 14% pN1, and 27% pN2; 57% had 10 or more nodes removed. Cumulative incidence of pelvic relapse was 40% among the entire group Conclusions: This review demonstrates a high rate of pelvic tumour recurrence following radical cystectomy for pT3/T4 urothelial cancer

Adjuvant radiotherapy for pathological high-risk muscle invasive bladder cancer: time to reconsider?

Radical cystectomy with extended pelvic lymph-node dissection, associated with neo-adjuvant chemotherapy, remains the standard of care for advanced, non-metastatic muscle-invasive bladder cancer (MIBC). Loco-regional control is a key factor in the outcome of patients since it is related to overall survival (OS), disease-free survival (DFS) and cause-specific survival. The risk of loco-regional recurrence (LRR) is correlated to pathological factors as well as the extent of the lymphadenectomy. In addition, neither pre- nor post-operative chemotherapy have shown a clear impact on LRR-free survival. Several recent publications have led to the development of a nomogram predicting the risk of LRR, in order to identify patients most likely to benefit from adjuvant radiotherapy. Given the high risk of LRR for selected patients and improvements in radiation techniques that can reduce toxicity, there is a growing interest in adjuvant radiotherapy; international cooperative groups have come together to provide the rationale in favor of adjuvant radiotherapy. Clinical trials in order to reduce the risk of pelvic relapse are opened based on this optimizing patient selection. The aim of this critical literature review is to provide an overview of the rationale supporting the studies of adjuvant radiation for patients with pathologic high-risk MIBC

The Rationale for Post-Operative Radiation in Localized Bladder Cancer

Local-regional recurrence for patients with ≥pT3 disease after radical cystectomy is a significant problem. Chemotherapy has not been shown to reduce the risk of local-regional recurrences in randomized prospective trials, and salvage therapies for local-regional failure are rarely successful. There is promising evidence, particularly from a recent Egyptian NCI trial, that radiation therapy plus chemotherapy can significantly reduce local recurrences compared to chemotherapy alone, and that this improvement in local-regional control may translate to meaningful improvements in disease-free and overall survival with acceptable toxicity. In light of the high rates of local failure following cystectomy for locally advanced disease and the progress that has been made in identifying patients at high risk of failure and the patterns of failure in the pelvis, the NCCN guidelines were revised in 2016 to include post-operative radiotherapy as an option to consider for patients with ≥pT3 disease. Despite advances in our understanding of the problem of local-regional failure after cystectomy and the potential role of adjuvant radiotherapy, the question of whether adjuvant radiotherapy should have a defined role for patients with locally advanced urothelial carcinoma has not yet been determined. The results of the NRG, European, Indian, and Egyptian trials on adjuvant radiotherapy are eagerly awaited. While none of these trials on their own may provide definitive conclusions, their aggregate outcomes will help clarify whether this treatment should have a role in the management of patients with locally advanced bladder cancer

Development and Validation of Consensus Contouring Guidelines for Adjuvant Radiation Therapy for Bladder Cancer After Radical Cystectomy

PURPOSE: Several organizations are developing clinical trials to evaluate adjuvant radiotherapy (RT) for bladder cancer patients at elevated risk of locoregional failure after radical cystectomy. Clinical target volumes (CTVs) and organs at risk (OARs) for this treatment have not been defined in detail. Our purpose was to develop multi-institutional consensus CTVs and OARs for male and female bladder cancer patients undergoing adjuvant RT in clinical trials. METHODS AND MATERIALS: We convened a multi-disciplinary group of bladder cancer specialists from fifteen centers and five countries. Six radiation oncologists and seven urologists participated in the development of the initial contours. The group proposed initial language for the CTVs and OARs, and each radiation oncologist contoured them on CT scans of a male and female cystectomy patient with input from ≥1 urologist. Based on the initial contouring, the group updated its CTV and OAR descriptions. The cystectomy bed, the area of greatest controversy, was contoured by another six radiation oncologists, and the cystectomy bed contouring language was again updated. To determine if the revised language produced consistent contours, CTVs and OARs were redrawn by six additional radiation oncologists. We evaluated their contours for level of agreement using the Landis-Koch interpretation of the κ-statistic. RESULTS: The group proposed that patients at elevated risk for local-regional failure with negative margins should be treated to the pelvic nodes alone (internal/external iliac, distal common iliac, obturator, and presacral) whereas patients with positive margins should be treated to the pelvic nodes and cystectomy bed. Proposed OARs included the rectum, bowel space, bone marrow, and urinary diversion. Consensus language describing the CTVs and OARs was developed and externally validated. The revised instructions were found to produce consistent contours. CONCLUSIONS: Consensus descriptions of CTVs and OARs were successfully developed and can be employed in clinical trials of adjuvant RT for bladder cancer

Prostate Radiotherapy With Adjuvant Androgen Deprivation Therapy (ADT) Improves Metastasis-Free Survival Compared to Neoadjuvant ADT: An Individual Patient Meta-Analysis.

PurposeThere remains a lack of clarity regarding the influence of sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) on outcomes in prostate cancer (PCa). Herein, we evaluate the optimal sequencing of ADT with prostate-directed RT in localized PCa.MethodsMEDLINE (1966-2018), Embase (1982-2018), ClinicalTrials.gov, and conference proceedings (1990-2018) were searched to identify randomized trials evaluating the sequencing, but not duration, of ADT with RT. Two randomized phase III trials were identified, and individual patient data were obtained: Ottawa 0101 and NRG Oncology's Radiation Therapy Oncology Group 9413. Ottawa 0101 randomly assigned patients to neoadjuvant or concurrent versus concurrent or adjuvant short-term ADT. Radiation Therapy Oncology Group 9413, a 2 × 2 factorial trial, included a random assignment of neoadjuvant or concurrent versus adjuvant short-term ADT. The neoadjuvant or concurrent ADT arms of both trials were combined into the neoadjuvant group, and the arms receiving adjuvant ADT were combined into the adjuvant group. The primary end point of this meta-analysis was progression-free survival (PFS).ResultsThe median follow-up was 14.9 years. Overall, 1,065 patients were included (531 neoadjuvant and 534 adjuvant). PFS was significantly improved in the adjuvant group (15-year PFS, 29% v 36%, hazard ratio [HR], 1.25 [95% CI, 1.07 to 1.47], P = .01). Biochemical failure (subdistribution HR [sHR], 1.37 [95% CI, 1.12 to 1.68], P = .002), distant metastasis (sHR, 1.40 [95% CI, 1.00 to 1.95], P = .04), and metastasis-free survival (HR, 1.17 [95% CI, 1.00 to 1.37], P = .050) were all significantly improved in the adjuvant group. There were no differences in late grade ≥ 3 gastrointestinal (2% v 3%, P = .33) or genitourinary toxicity (5% v 5%, P = .76) between groups.ConclusionThe sequencing of ADT with prostate-directed RT has significant association with long-term PFS and MFS in localized PCa. Our findings favor use of an adjuvant over a neoadjuvant approach, without any increase in long-term toxicity