CENP-A Subnuclear Localization Pattern as Marker Predicting Curability by Chemoradiation Therapy for Locally Advanced Head and Neck Cancer Patients.

Effective biomarkers predictive of the response to treatments are key for precision medicine. This study identifies the staining pattern of the centromeric histone 3 variant, CENP-A, as a predictive biomarker of locoregional disease curability by chemoradiation therapy. We compared by imaging the subnuclear distribution of CENP-A in normal and tumoral tissues, and in a retrospective study in biopsies of 62 locally advanced head and neck squamous cell carcinoma (HNSCC) patients treated by chemoradiation therapy. We looked for predictive factors of locoregional disease control and patient's survival, including CENP-A patterns, Ki67, HPV status and anisokaryosis. In different normal tissues, we reproducibly found a CENP-A subnuclear pattern characterized by CENP-A clusters both localized at the nuclear periphery and regularly spaced. In corresponding tumors, both features are lost. In locally advanced HNSCC, a specific CENP-A pattern identified in pretreatment biopsies predicts definitive locoregional disease control after chemoradiation treatment in 96% (24/25) of patients (OR = 17.6 CI 95% [2.6; 362.8], p = 0.002), independently of anisokaryosis, Ki67 labeling or HPV status. The characteristics of the subnuclear pattern of CENP-A in cell nuclei revealed by immunohistochemistry could provide an easy to use a reliable marker of disease curability by chemoradiation therapy in locally advanced HNSCC patients.

Stereotactic ablative radiotherapy for early stage non-small cell lung cancer: A critical literature review of predictive factors of relapse.

Stereotactic ablative radiation therapy (SABR) has become the standard treatment for peripheral medically non-operable patients with early stage non-small cell lung cancer (NSCLC). Previous attempts of trials to compare SABR and surgery have failed and new randomized studies (SABRtooth, STABLEMATES, and VALOR) are ongoing. While predictive factors of relapse have been extensively studied in patients receiving surgery, there is scarce data on such putative factors in SABR patients. The purpose of this review is to analyze such predictive factors through a critical review of the literature.

[Single center experience with bevacizumab in a cohort of patients treated for a relapsing glioblastoma]. / Expérience monocentrique d'un traitement par bévacizumab dans la prise en charge des glioblastomes récidivant.

PURPOSE: Although there is no standard treatment for recurrent glioblastoma, prospective data in selected patients have suggested the usefulness of bevacizumab. We report our single center experience with bevacizumab in a cohort of patients treated for a relapsing glioblastoma. METHODS: We performed a retrospective analysis of consecutive patients treated with bevacizumab for a relapsed glioblastoma, between 2008 and 2013. Tumor responses, toxicities, time to progression and overall survival rates were analyzed. RESULTS: Thirty-five consecutive patients were identified. They were treated with bevacizumab 10mg/kg biweekly, associated with irinotecan (n=29; 84%), temozolomide (n=3; 9%) or as single agent (n=3; 9%) for a glioblastoma relapsing after chemoradiation (n=29) or after first line temozolomide only because of a poor general health status or because of multifocal tumor. Two (6%), 28 (80%) and five (14%) patients presented with Recursive Partitioning Analysis (RPA) III, IV and V-VI, respectively. After 2-3 months of treatment, median dose of prednisolone per patient was decreased three times. Clinical improvements or stability were reported in eight (23%) and 17 patients (49%). The best tumor response was partial response in 14 patients (40%), stable disease in nine patients (26%) and tumor progression in 11 patients (31%). Toxicities requiring treatment disruption were reported in five patients (14%). Median survival was 18.4 months (5-41 months). Median time interval between bevacizumab initiation and its disruption because of clinical/radiological progression and/or toxicity was 5.0 months (0.6-21.4 months). Median survival from bevacizumab initiation was 8.1 months (1.4-34 months). CONCLUSION: This single center retrospective experience suggests that bevacizumab is active for recurrent glioblastoma, in a series of poorly selected patients. Median survival times were in the range of those reported in therapeutic trials. This study questions the validity of usual predictive factors in the era of bevacizumab.

[Impact of radiotherapy on female fertility]. / Impact de la radiothérapie sur la fertilité féminine.

Radiation therapy may have deleterious effects on female fertility. It can cause ovarian dysfunction, uterine damages or disrupt the hypothalamic-pituitary axis. These effects occur at varying dose levels usually relatively low compared to the prescribed doses. Other co-factors influence the effects of radiation therapy on fertility, such as age or therapy with alkylating agents. This review aims to make an update on the current state of knowledge about the impact of radiotherapy on female fertility.

Safety of spinal radiotherapy in metastatic cancer patients receiving bevacizumab therapy: a bi-institutional case series.

We retrospectively assessed the outcome of patients receiving emergency spinal radiation therapy (RT) concurrently with bevacizumab. Clinical records of 18 consecutive patients receiving emergency spinal RT for symptomatic vertebral metastases during the course of bevacizumab-based therapy were examined. Patients were receiving biweekly bevacizumab combined with paclitaxel (n=17) or with docetaxel/carboplatin (n=1) or as a single agent (n=1) for advanced metastatic carcinoma. RT was delivered at doses of 30 Gy in 10 fractions (n=8), 20 Gy in five fractions (n=9) or 18 Gy in nine fractions (n=1). In 10 patients (56%), irradiation field encompassed the thoracic vertebrae. The median time interval between the bevacizumab infusion and the RT course was 1.5 days (0-8 days). The median follow-up was 8.3 months (2 days-42 months). A clinical benefit of RT was reported in 13 patients (72%), including four patients with complete pain relief. Two of the three patients with neurological impairment at the time of RT experienced a partial improvement in their symptoms. No pain recrudescence was reported within the irradiated field after RT completion. All toxicities were mild to moderate, with no acute toxicity reported in 13 patients (72%). No RT disruption was necessary because of acute toxicity. No delayed toxicity was reported within RT fields among 11 patients with at least 6 months of follow-up. Spinal RT during the course of bevacizumab-based therapy was not associated with the occurrence of unexpected adverse effects. This suggests that emergency RT should not be contraindicated in these patients, provided that doses and treatment volumes are defined carefully.