Treatment algorithm and prognostic factors for patients with stage I-III carcinoma of the anal canal: a 20-year multicenter study.

Despite a growing incidence in developed countries and a recent improved understanding of its pathogenesis, anal cancer management has not evolved over the past decades and drug combination used as first-line regimen still largely depends on clinician preferences. Aiming at paving the way for precision medicine, a large cohort of 372 HIV-negative patients diagnosed over a 20-year time period with locally advanced anal carcinoma was collected and carefully characterized at the clinical, demographic, histopathologic, immunologic, and virologic levels. Both the prognostic relevance of each clinicopathological parameter and the efficacy of different concurrent chemoradiation strategies were determined. Overall, the incidence of anal cancer peaked during the sixth decade (mean: 63.4) and females outnumbered males (ratio: 2.51). After completion of treatment, 95 (25.5%) patients experienced progression of persistent disease or local/distant recurrence and 102 (27.4%) died during the follow-up period (median: 53.8 months). Importantly, uni-multivariate analyses indicated that both negative HPV/p16ink4a status and aberrant p53 expression were far better predictors for reduced progression-free survival than traditional risk factors such as tumor size and nodal status. As for overall survival, the significant influences of age at diagnosis, p16ink4a status, cTNM classification as well as both CD3+ and CD4+ T-cell infiltrations within tumor microenvironment were highlighted. Cisplatin-based chemoradiotherapy was superior to both radiotherapy alone and other concurrent chemoradiation therapies in the treatment of HPV-positive tumors. Regarding their HPV-uninfected counterparts, frequent relapses were observed, whatever the treatment regimen administered. Taken together, our findings reveal that current anal cancer management and treatment have reached their limits. A dualistic classification according to HPV/p53 status should be considered with implications for therapy personalization and optimization.

The transfer of multigene panel testing for hereditary breast and ovarian cancer to healthcare: What are the implications for the management of patients and families?

Until recently, the molecular diagnosis of hereditary breast and ovarian cancer (HBOC) was mostly based on BRCA1/2 testing. Next generation sequencing and the recent discovery of new genes involved in HBOC now permit the transfer of genomic capture targeting multiple candidate genes from research to clinical use. However, the implications for the management of patients and their families have not been extensively studied, in particular since some of these genes are not well-established cancer predisposing genes. We studied 583 consecutive patients from Burgundy (France) fulfilling the criteria for BRCA testing using a next generation sequencing 25-genes panel including 20 well-established high-risk cancer genes as well as more recently identified predisposing HBOC cancer. A pathogenic BRCA1/2 mutation was found in 51 patients (9%). Besides, we found 37 pathogenic or likely pathogenic mutations in 10 different high to low-risk genes in 34 patients (6%). The most frequently mutated genes were CHEK2 (n = 12; 2%), ATM (n = 9; 1.5%), and PALB2 (n = 4; 0.6%). Three patients had a mutation in two different predisposing genes. The analysis of clinical actionability conducted in mutation-positive individuals revealed that additional disease-specific screening and/or prevention measures beyond those based on personal and family history alone had been recommended in 69% of cases. In conclusion, multigene panel testing is a powerful tool to identifying high to low-risk HBOC susceptibility genes. The penetrance and spectrum of cancers with these other genes are sometimes undefined, and further collaborative work is crucial to address this question.

Determinants of quality of life among long-term breast cancer survivors.

PURPOSE: To identify the impact of clinical and socio-economic determinants on quality of life (QoL) among breast cancer (BC) survivors 5 years after diagnosis. METHODS: A cross-sectional survey was conducted in women diagnosed in 2007 for primary invasive non-metastatic BC and identified through the Côte d'Or BC registry. QoL was assessed with the Medical Outcomes Study 12-item Short Form Health Survey (SF-12), the European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-C30) and the breast cancer (EORTC-QLQ-BR23) questionnaires. Social support was assessed with Sarason's social support questionnaire, and deprivation was assessed by the EPICES questionnaire. Clinical variables were collected through the registry database. Determinants of QoL were identified using multivariable mixed model analysis for each SF-12 dimension. A sensitivity analysis was conducted with multiple imputations on missing data. RESULTS: Overall, 188 patients on 319 patients (59 %) invited to participate to the survey completed the questionnaires. Five years after breast cancer diagnosis, the disease stages at diagnosis, as well as the treatment received, were not determinants of QoL. Only the age at diagnosis and comorbidities were found to be determinants of QoL. CONCLUSIONS: Five years after BC diagnosis, disease severity and the treatment received did not affect QoL.

About invasive cervical cancer: a French population based study between 1998 and 2010.

OBJECTIVES: The new French cancer plan provides the implementation of organized screening. To make an assessment of the situation, we aim to describe clinical, tumor and survival characteristics of patients with invasive cervical cancer. STUDY DESIGN: Data on women suffering from invasive cervical cancer and diagnosed from 1998 to 2010 were provided by the Cote d'Or breast cancer registry. Survival was described using the Kaplan-Meier method and prognostic factors of survival were estimated in a Cox proportional hazard model. RESULTS: On the whole, 1019 cancers have been collected including 311 (30.5%) invasive ones. The peak incidence was between 40 and 49 years, with an average age of 52 years (SD=16.4). Cancers were mostly squamous cell carcinoma (80.1%) and diagnosed at a localized stage (53.7%). Only 49% (71/145) of our population were up to date on their Pap smear follow up with lower rates in deprived women. The 5-year survival rate was 62% (15% for women with FIGO stage IV and 91% for women with FIGO stage I) with a median survival of 12.3 years [95% CI: 6.6-NR]. Multivariate analysis showed that risk of death was the highest for group age 50-59 (OR=4.93; 95% CI: [1.55-15.70]) compared to women aged less than 40, advanced stage (OR=3.12; 95% CI [1.82-5.35]), and non accurate follow up (OR=2.81; 95% CI [1.32-5.97]). After cancer diagnosis, no impact of the deprivation index on survival was found. CONCLUSION: This study confirms the poor outcome of advanced invasive cervical cancer and the importance of early detection of cervical cancer. Preventive communication should be even more developed and the implementation of a screening program may go through the provision of improved screening tools.

Impact of age-related socio-economic and clinical determinants of quality of life among long-term breast cancer survivors.

OBJECTIVES: The main purpose of this study was to identify age-related socioeconomic and clinical determinants of quality of life among breast cancer survivors five years after the diagnosis. The secondary objective was to describe quality of life in the studied population according to age. STUDY DESIGN: A cross-sectional survey in five-year breast cancer survivors was conducted in women diagnosed with breast cancer in 2007 and 2008 in Côte d'Or. MAIN OUTCOME MEASURES: Quality of life was assessed with the SF-12, the EORTC-QLQ-C30 and the EORTC-QLQ-BR23 questionnaires. Socio-economic deprivation was assessed by the EPICES questionnaire. Social support was assessed by the Sarason questionnaire and clinical features were collected through the Côte d'Or breast cancer registry. Age-related determinants of quality of life were identified using multivariate mixed model analysis for each SF-12 dimension. RESULTS: Overall 396 women completed the questionnaires. Women aged <65 years had a better quality of life and a greater availability of social support than did women aged ≥65 years. Body mass index, relapse and EPICES were found to be determinants of quality of life in younger women (p<0.006). For older women, comorbidities and EPICES deprivation scores were predictors of low quality of life scores (p<0.006). CONCLUSIONS: Five years after breast cancer diagnosis, disease severity did not affect quality of life. The major determinants of quality of life in younger women were disease relapse and EPICES deprivation scores while those in older women were comorbidities and EPICES deprivation scores.