Risk factors for loco-regional recurrence after radical cystectomy of muscle-invasive bladder cancer: A systematic-review and framework for adjuvant radiotherapy.

BACKGROUND: Radical cystectomy (RC) associated with pelvic lymph node dissection (PLND) is the most common local therapy in the management of non-metastatic muscle invasive bladder cancer (MIBC). Loco-regional recurrence (LRR), however, remains a common and important therapeutic challenge associated with poor oncologic outcomes. We aimed to systematically review evidence regarding factors associated with LRR and to propose a framework for adjuvant radiotherapy (RT) in patients with MIBC. METHODS: We performed this systematic review in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. We searched the PubMed database for articles related to MIBC and associated treatments, published between January 1980 and June 2015. Articles identified by searching references from candidate articles were also included. We retrieved 1383 publications from PubMed and 34 from other sources. After an initial screening, a review of titles and abstracts, and a final comprehensive full text analysis of papers assessed for eligibility, a final consensus on 32 studies was obtained. RESULTS: LRR is associated with specific patient-, tumor-, center- or treatment-related variables. LRR varies widely, occurring in as many as 43% of the cases and is strongly related to survival outcomes. While perioperative treatment does not impact on LRR, pathological factors such as pT, pN, positive margins status, extent of PLND, number of lymph nodes removed and/or invaded are correlated with LRR. Patients with pT3-T4a and/or positive lymph-nodes and/or limited pelvic lymph-node dissection and/or positive surgical margins have been distributed in LRR risk groups with accuracy. CONCLUSIONS: LRR patterns are well-known and for selected patients, adjuvant treatments could target this event. Intrinsic tumor subtype may guide future criteria to define a personalized treatment strategy. Prospective trials evaluating safety and efficacy of adjuvant RT are ongoing in several countries.

Lung Adenocarcinoma Survival in EGFR-Mutated African-Caribbean Patients: A Multicenter Study in the French West Indies.

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. Shorter survival has been repeatedly reported for patients of African ancestry. Multivariate analysis demonstrated that this gap could be a consequence of socio-economic disparities instead of genetic specificities. However, those results were obtained in a pre-targeted therapies era and the effect of tyrosine kinase inhibitors targeting EGFR are not known in this population. OBJECTIVE: In this French West Indies study, we report overall survival (OS) in a frequently mutated population treated for lung adenocarcinoma within an equal-access healthcare system. PATIENTS AND METHODS: Clinical, demographic, survival, and treatment data have been retrospectively assessed for all patients diagnosed with lung adenocarcinoma in the islands of Martinique and Guadeloupe between 2013 and 2015. RESULTS: Two hundred and forty-one patients (82% African-Caribbean) were included. EGFR mutations were detected in 37% of all tumor specimens and were associated with non-smoker status in multivariate analysis. Median OS was 16.2 months. For patients with advanced disease, median OS was 11.5 months, depending on EGFR mutation (23 vs. 8.3 months for non-mutated patients, p = 0.0012). There was no difference in survival according to ethnicity or island. In multivariate analysis, performance status (PS) and EGFR mutation were the only independent prognostic factors. CONCLUSIONS: Despite a higher frequency of EGFR mutations in African-Caribbean patients, ethnicity was not an independent factor of OS in lung adenocarcinoma. Lower initial PS in this mainly non-smoking African-Caribbean population may explain the absence of a difference in OS.

Tolerance of Orthotopic Ileal Neobladders to Radiotherapy: A Multi-institutional Retrospective Study.

BACKGROUND: The present retrospective study analyzed the tolerance of orthotopic ileal neobladders to radiotherapy by reviewing the acute and late toxicity in patients who underwent postoperative radiotherapy after radical cystectomy/cystoprostatectomy. MATERIALS AND METHODS: A multi-institutional database was created for patients who had undergone radical cystectomy/cystoprostatectomy and neobladder reconstruction, followed by adjuvant radiotherapy (RT). The patient and tumor characteristics were recorded. The RT data were reviewed to determine the treatment technique used, the radiation dose received by the neobladder, and acute and late toxicity evaluated using the Common Terminology Criteria for Adverse Events, version 4.0, scale. RESULTS: A total of 25 patients were included, with a median age of 64 years. Of the 25 patients, 18 received a dose of 45 to 50.4 Gy. The most common reasons for postoperative radiotherapy were close or positive surgical margins and pT3-pT4 or N+ disease. Ten patients underwent intensity modulated RT. All but 1 patient completed the RT course. Of the patients who completed their RT schedule, none had grade ≥ 3 acute gastrointestinal toxicity. One patient who received concurrent chemotherapy developed grade 3 acute genitourinary toxicity. Three patients reported late grade 1 genitourinary toxicity (frequency of urination, mild leakage at night), with no reports of chronic gastrointestinal toxicity. None of the patients experienced neobladder perforation, leak, or fistula. CONCLUSION: The use of moderate doses of pelvic RT (range, 45-50.4 Gy) was well tolerated among the 25 patients who underwent RT after cystoprostatectomy with orthotopic neobladder creation. This finding supports the use of postoperative RT to moderate doses in this patient population when clinically indicated.

Adjuvant radiotherapy after radical cystectomy for muscle-invasive bladder cancer: A retrospective multicenter study.

OBJECTIVES: Radical cystectomy (RC) and pelvic lymph-node dissection (LND) is standard treatment for non-metastatic muscle-invasive urothelial bladder cancer (MIBC). However, loco-regional recurrence (LRR) is a common early event associated with poor prognosis. We evaluate 3-year LRR-free (LRRFS), metastasis-free (MFS) and overall survivals (OS) after adjuvant radiotherapy (RT) for pathological high-risk MIBC. MATERIAL AND METHODS: We retrospectively reviewed data from patients in 3 institutions. Inclusion criteria were MIBC, histologically-proven urothelial carcinoma treated by RC and adjuvant RT. Patients with conservative surgery were excluded. Outcomes were evaluated by Kaplan-Meier method. Acute toxicities were recorded according to CTCAE V4.0 scale. RESULTS: Between 2000 and 2013, 57 patients [median age 66.3 years (45-84)] were included. Post-operative pathological staging was ≤pT2, pT3 and pT4 in 16%, 44%, and 39%, respectively. PLND revealed 28% pN0, 26% pN1 and 42% pN2. Median number of lymph-nodes retrieved was 10 (2-33). Forty-eight patients (84%) received platin-based chemotherapy. For RT, clinical target volume 1 (CTV 1) encompassed pelvic lymph nodes for all patients. CTV 1 also included cystectomy bed for 37 patients (65%). CTV 1 median dose was 45 Gy (4-50). A boost of 16 Gy (5-22), corresponding to CTV 2, was administered for 30 patients, depending on pathological features. One third of patients received intensity-modulated RT. With median follow-up of 40.4 months, 8 patients (14%) had LRR. Three-year LRRFS, MFS and OS were 45% (95%CI 30-60), 37% (95%CI 24-51) and 49% (95%CI 33-63), respectively. Five (9%) patients had acute grade ≥3 toxicities (gastro-intestinal, genito-urinary and biological parameters). One patient died with intestinal fistula in a septic context. CONCLUSIONS: Because of poor prognosis, an effective post-operative standard of care is needed for pathological high-risk MIBC. Adjuvant RT is feasible and may have oncological benefits. Prospective trials evaluating this approach with current RT techniques should be undertaken.

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.

18F-DOPA PET/CT in Orbital Metastasis From Medullary Thyroid Carcinoma.

A 53-year-old-woman is being followed up for a sporadic medullary thyroid carcinoma that was initially treated surgically. Nine years later, a progressive increase in calcitonin levels along with headaches was observed. An orbital metastasis from medullary thyroid carcinoma was diagnosed by performing an F-DOPA PET/CT. The orbital lesion was treated by an external beam radiation. Four months later, an MRI revealed a global morphological stability and a reduction in calcitonin levels.