[Radiotherapy of oligometastases: Sequences and interactions with systemic therapies, example of kidney cancer]. / Radiothérapie des oligométastases : interactions/séquences avec thérapies systémiques, exemple du cancer du rein.

This article is a review of the literature that aims to clarify the place of systemic and locoregional treatments, with a focus on radiotherapy and surgery in the management of patients with oligometastatic kidney cancer. We have selected articles of interest published in Medline indexed journals. We have also analysed the related guidelines: National Comprehensive Cancer Network (NCCN) 2019, European Association of Urology (EAU) 2019, European Society of Medical Oncology (ESMO) 2019, Association française d'urologie (Afu) 2018 as well as some abstracts of international congresses. The main treatments evaluated were surgery and radiotherapy. We defined the different scenarios conventionally encountered in clinical practice. The evolution of systemic therapies (increased overall survival and response rate) is likely to increase the number of patients potentially accessible to locoregional treatments. The complete analysis of the literature underlines the place of locoregional treatments whatever the scenarios mentioned. Data on stereotactic radiotherapy found a local control rate consistently above 70% in all studies with a maintained response and positive impact on overall survival and progression-free survival. The improvement of overall survival by sequential use of the various therapeutic classes confirms the need for optimization of locoregional treatments in the model of oligometastatic kidney cancer. The dogma of radioresistance must definitely be set aside with current irradiation techniques.

Implementation of intensity-modulated radiotherapy for head and neck cancers in routine practice.

PURPOSE: To report on patterns of relapse following implementation of intensity-modulated radiotherapy and subsequent changes in practice in a tertiary care centre. PATIENTS AND METHODS: Between 2008 and 2011, 188 consecutive patients (mean age 59 years old) received intensity-modulated radiotherapies with curative intent for squamous cell carcinomas of the oral cavity (17.5%), oropharynx (43%), hypopharynx (21%), larynx (14%), sinonasal cavities (6%), nasopharynx (1.5%) at the university hospital of Besançon. There were stage I and II 9%, III 24.5%, IV 66.5%. One hundred and thirty-eight underwent exclusive intensity-modulated radiotherapy, 50 underwent postoperative intensity-modulated radiotherapy, 174 had concurrent chemotherapy, 57 had induction chemotherapy. Dynamic intensity-modulated radiotherapy with static fields was performed for all patients using sequential irradiation in 174 patients and simultaneous integrated boost irradiation in 14 patients. RESULTS: With a median follow-up was 27.5 months, there was 79% of locoregional failures occurred in the 95% isodose. Two-year overall survival, disease-free, local failure-free and locoregional failure-free survival rates were73%, 60%, 79% and 72%, respectively. Prognostic factors for disease-free survival were stage (IV vs. I-III) with a relative risk of 1.7 [1.1-2.8] (P=0.02) and T stage with 1.6 [1.04-2.5] (P=0.03). CONCLUSION: The current series showed similar patterns of failure as in other tertiary care centres. We did not identify intensity-modulated radiotherapy specific relapse risks.

[Neoadjuvant before surgery treatments: state of the art in prostate cancer]. / Traitements néoadjuvants préopératoires : mise au point dans le cancer de la prostate.

GOAL: To study the impact of systemic treatment in neoadjuvant strategy before surgery in prostate cancer. MATERIALS: Literature reviews with data analysis from PubMed search using the keywords "neoadjuvant", "chemotherapy", "hormonal therapy", "prostate surgery", "radical prostatectomy", but also reports from ASCO and ESMO conferences. The articles on neoadjuvant treatment before radiotherapy were excluded. RESULTS: First studies with former therapy are more than 15-years-old and with questionable methodology: lack of power to have a clear idea of the impact on survival criteria such as overall survival or relapse-free survival. However, the impact of neoadjuvant hormone therapy on the classic risk factors for relapse (positive margins, intraprostatic disease, positive lymph nodes) was demonstrated by these studies and a Cochrane meta-analysis. The association with hormone therapy seems mandatory in comparison to treatment based solely on chemotherapy and/or targeted therapy. Promising data on the use of new drugs and their combinations arise: abiraterone acetate combined with LHRH analogue showed a fast PSA decrease and higher rates of pathologic complete response. Other results are promising with hormonal blockages at various key points. CONCLUSION: Studies with 2nd generation anti-androgene agents or enzyme inhibitors seem to show very promising results. To provide answers about the effectiveness of current neoadjuvant strategy in terms of survival, other studies are needed: randomized phase III or phase II exploring predictive biomarkers. The design of such trials requires a multidisciplinary approach with urologists, oncologists, radiologists and methodologists.

Impact of everolimus blood concentration on its anti-cancer activity in patients with metastatic renal cell carcinoma.

PURPOSE: Everolimus has demonstrated its efficacy in metastatic renal cell carcinoma (mRCC). Preliminary studies have shown high variability of everolimus blood concentrations (EBC). In other settings, its activity was correlated with EBC. We therefore decided to monitor EBC in patients treated with mRCC to assess its influence on oncologic outcomes. PATIENTS AND METHODS: Our study analyzed first 3 months' trough EBC levels in 42 patients treated in 4 French oncologic centers between March 2010 and August 2013. Patients presented a histologically confirmed diagnosis of mRCC and have failed prior anti-angiogenic (AA) therapies. RESULTS: Median follow-up was 25.9 months. A total of 113 EBC were analyzed. The median trough concentration was 14.1 µg/L (range 2.6-91.5). Fourteen patients (67 %) versus 8 (38 %) patients with median EBC above or below 14.1 µg/L were free from progression at 6 months (p = 0.06). Median progression-free survival was 13.3 versus 3.9 months (HR 0.66 95 % CI 0.33-1.31; p = 0.23), and the median overall survival was 26.2 versus 9.9 months (HR 0.62 95 % CI 0.28-1.37; p = 0.24), for patients above or below the median value of trough concentrations, respectively. CONCLUSION: Impact of drug exposure for AA tyrosine kinase inhibitors activity has been demonstrated in mRCC setting. Interpatients EBC variability was confirmed in the present study, and the results suggest a relationship between initial EBC within the first 3 months and the drug activity. It underlines the need to prospectively include EBC monitoring in future clinical trials to determine the need of its implementation in routine use.