Long-term quality of life and sexual function of elderly people with endometrial or ovarian cancer.

BACKGROUND: With the growing number of older endometrial cancer (EC) and ovarian cancer (OC) survivors, data on long-term health-related quality of life (HRQoL) became an important issue in the management of older patients. So, the aim of this study was to describe and compare according to age long-term HRQoL, sexual function, and social deprivation of adults with either EC or OC. METHODS: A cross-sectional study was set up using data from the Côte d'Or gynecological cancer registry. A series of questionnaires assessing HRQoL (SF-12), sexual function (FSFI), anxiety/depression (HADS), social support (SSQ6) and deprivation (EPICES) were offered to women with EC or OC diagnosed between 2006 and 2013. HRQoL, sexual function, anxiety/depression, social support and deprivation scores were generated and compared according to age (< 70 years and ≥ 70 years). RESULTS: A total of 145 women with EC (N = 103) and OC (N = 42) participated in this study. Fifty-six percent and 38% of EC and OC survivors respectively were aged 70 and over. Treatment did not differ according to age either in OC or EC. The deprivation level did not differ between older and younger survivors with OC while older survivors with EC were more precarious. The physical HRQoL was more altered in older EC survivors. This deterioration concerned only physical functioning (MD = 24, p = 0.012) for OC survivors while it concerned physical functioning (MD = 30, p < 0.0001), role physical (MD = 22, p = 0.001) and bodily pain (MD = 21, p = 0.001) for EC survivors. Global health (MD = 11, p = 0.011) and role emotional (MD = 12, p = 0.018) were also deteriorated in elderly EC survivors. Sexual function was deteriorated regardless of age and cancer location with a more pronounced deterioration in elderly EC survivors for desire (p = 0.005), arousal (p = 0.015) and orgasm (p = 0.007). Social support, anxiety and depression were not affected by age regardless of location. CONCLUSION: An average 6 years after diagnosis, the impact of cancer on HRQoL is greatest in elderly survivors with either EC or OC.

Long-Term Gynecological Cancer Survivors in Côte d'Or: Health-Related Quality of Life and Living Conditions.

BACKGROUND: The likelihood that health-related quality of life (HRQoL) could depend on factors other than clinical data increases with the duration of follow-up since diagnosis. The aim of this study was to identify determinants of long-term HRQoL in women with cervical, endometrial, and ovarian cancer. Secondary objectives were to describe their living conditions (sexual function, psychological distress, social and professional reinsertion). MATERIALS AND METHODS: In a cross-sectional survey, women diagnosed with cervical, endometrial, and ovarian cancers from 2006 to 2013 were selected through the French gynecological cancers registry of Côte d'Or. Validated questionnaires exploring HRQoL (short-form health survey; SF-12), anxiety and depression (Hospital Anxiety and Depression Scale), social support (Sarason's Social Support Questionnaire), sexual function (Female Sexual Function Index), and living conditions (EPICES questionnaire) were used to assess HRQoL and its determinants. Social and professional reinsertion were also investigated using study-specific questionnaires. Determinants of HRQoL were identified using a multivariable mixed-regression model for each composite score of the SF-12. RESULTS: In total, 195 gynecological cancer survivors participated in the survey. HRQoL was deteriorated for almost all the SF-12 dimensions. The main determinants of poor HRQoL were comorbidities, deprivation, lack of availability and satisfaction with social support, and psychological outcomes. Thirty-four percent of survivors of gynecological cancer reported a negative impact of cancer on their work, and 73% reported an impaired ability to work after treatment. CONCLUSIONS: Long-term HRQoL of survivors of gynecological cancer is not impacted by stage of disease. Specific interventions should focus on issues that promote social and professional reintegration and improve HRQoL. IMPLICATIONS FOR PRACTICE: This study shows that women with gynecological cancer have problems related to work and sexual dysfunction, even 5 years after diagnosis. The results of this study will help improve clinicians' awareness of the factors affecting the lives of gynecological cancer survivors, even long after diagnosis and treatment. They will also highlight for clinicians the areas that are of importance to gynecological cancer survivors, making it possible to guide management of these patients with a view to preventing deteriorated health-related quality of life after treatment. For the health authorities, the results of this study underline that more than 5 years after gynecological cancer, the initial stage of disease no longer affects quality of life, but there is a clear need for actions targeting socio-professional reintegration of survivors.

Assessment of the prognostic role of a 94-single nucleotide polymorphisms risk score in early breast cancer in the SIGNAL/PHARE prospective cohort: no correlation with clinico-pathological characteristics and outcomes.

BACKGROUND: Genome-wide association studies (GWAS) have to date identified 94 genetic variants (single nucleotide polymorphisms (SNPs)) associated with risk of developing breast cancer. A score based on the combined effect of the 94 risk alleles can be calculated to measure the global risk of breast cancer. We aimed to test the hypothesis that the 94-SNP-based risk score is associated with clinico-pathological characteristics, breast cancer subtypes and outcomes in early breast cancer. METHODS: A 94-SNP risk score was calculated in 8703 patients in the PHARE and SIGNAL prospective case cohorts. This score is the total number of inherited risk alleles based on 94 selected SNPs. Clinical data and outcomes were prospectively registered. Genotyping was obtained from a GWAS. RESULTS: The median 94-SNP risk score in 8703 patients with early breast cancer was 77.5 (range: 58.1-97.6). The risk score was not associated with usual prognostic and predictive factors (age; tumor, node, metastasis (TNM) status; Scarff-Bloom-Richardson grade; inflammatory features; estrogen receptor status; progesterone receptor status; human epidermal growth factor receptor 2 (HER2) status) and did not correlate with breast cancer subtypes. The 94-SNP risk score did not predict outcomes represented by overall survival or disease-free survival. CONCLUSIONS: In a prospective case cohort of 8703 patients, a risk score based on 94 SNPs was not associated with breast cancer characteristics, cancer subtypes, or patients' outcomes. If we hypothesize that prognosis and subtypes of breast cancer are determined by constitutional genetic factors, our results suggest that a score based on breast cancer risk-associated SNPs is not associated with prognosis. TRIAL REGISTRATION: PHARE cohort: NCT00381901 , Sept. 26, 2006 - SIGNAL cohort: INCa RECF1098, Jan. 28, 2009.

Prognostic Factors of Survival among Women with Metastatic Breast Cancer and Impact of Primary or Secondary Nature of Disease on Survival: A French Population-Based Study.

We aim to determine whether differences in survival exist between two populations of women with metastatic breast cancer (MBC) and to identify prognostic factors of survival after metastasis diagnosis. Data on women with MBC diagnosed between 2000 and 2011 were provided by the Côte d'Or Breast cancer registry. Survival rates and median overall survival (OS) after metastasis diagnosis were determined using the Kaplan-Meier method and prognostic factors were determined in a Cox proportional hazard model. Overall, 282 women with primary MBC and 340 with secondary MBC were included. A 2-year survival rate was significantly better in women with primary MBC (50.8% [95% CI: 47.8-53.8%] versus 44.5% [95% CI: 41.8-47.2%]). However, median OS did not differ between the two groups (p = 0.1). The prognostic factors associated with worst survival were a triple-negative tumor type (p < 10-4 ), multiple metastases sites (p < 10-4 ), an older age at metastasis (p < 10-4 ), and a SBR grade G3 (p = 0.007). OS between women with primary MBC and women with secondary MBC does not seem to differ significantly. This population-based study provides original epidemiological data on French women without any selection bias inherent to hospital cohorts.

Panitumumab in combination with chemoradiotherapy for the treatment of locally-advanced anal canal carcinoma: Results of the FFCD 0904 phase II trial.

BACKGROUND AND PURPOSE: Standard treatment of squamous cell carcinoma of the anus (SCCA)is 5-fluorouracil (5FU) and mitomycin C (MMC) based chemoradiotherapy (CRT). This phase II study (EudraCT: 2011-005436-26) assessed the tolerance and complete response (CR) rate at 8 weeks of panitumumab (Pmab) combined with MMC-5FU-based CRT. METHODS: Patients with locally advanced tumors without metastases (T2 > 3 cm, T3-T4, or N + whatever T stage) were treated with IMRT up to 65 Gy and concomitant CT according to the doses defined by a previous phase I study (MMC: 10 mg/m2; 5FU: 400 mg/m2; Pmab: 3 mg/kg). The expected CR rate was 80%. RESULTS: Forty-five patients (male: 9, female: 36; median age: 60.1 [41.5-81]) were enrolled in 15 French centers. The most common related grade 3-4 toxicities observed were digestive (51.1%), hematologic (lymphopenia: 73.4%; neutropenia: 11.1%), radiation dermatitis (13.3%), and asthenia (11.1%) with RT interruption in 14 patients. One patient died because of mesenteric ischemia during the CRT, possibly related to treatment. In ITT analysis, the CR rate at 8 weeks after CRT was 66.7% [90%CI: 53.4-78.2]. Median follow-up was 43.6 months [IC 95%: 38.61-47.01]. Overall survival, recurrence-free and colostomy-free survival at 3 years were 80% [95%CI: 65.1-89], 62.2% [IC95%: 46.5-74.6] and 68.8 % [IC95%: 53.1-80.2] respectively. CONCLUSION: Panitumumab in combination with CRT for locally advanced SCCA failed to meet the expected CR rate and exhibited a poor tolerance. Furthermore, late RFS, CFS, and OS did not suggest any outcome improvement to justify further clinical trials. CLINICALTRIALS: gov identifier: NCT01581840.

Population-based study of breast cancer in older women: prognostic factors of relative survival and predictors of treatment.

BACKGROUND: A large proportion of women with breast cancer (BC) are elderly. However, there is a lack of information regarding BC prognostic factors and care in this population. The aims of this study were to assess the prognostic factors of relative survival (RS) among women with BC aged ≥ 75 years old and to identify the predictive factors of treatments administered to this population. METHODS: A population-based study was performed using data from the Cote d'Or breast and gynaecological cancer registry. Women aged 75 years and older with primary invasive BC and resident in Cote d'Or at the time of diagnosis made between January 1998 and December 2008 were retrospectively selected. Prognostic factors of RS were estimated in a generalized linear model with a Poisson error structure. RS rate for the whole population was given at 5 years. Logistic regression models were used to identify the predictors of the treatments administered. RESULTS: Six hundred and eighty-one women were included. Median age at diagnosis was 80. Comorbidities (p = 0.02), pT stage (p = 0.04), metastases (p =< 0.001), having a family doctor (p = 0.03) and hormone-receptor status (p = 0.006) were independent prognostic factors of RS. The RS rate at 5 years for the whole population was 78.2%, 95%CI = [72.2-83.0]. Age, pT stage, metastases, histoprognostic SBR grade, hormone receptor status and comorbidities were frequently found to be predictors of treatment with surgery alone, hormone therapy alone, breast conserving surgery plus adjuvant therapy and mastectomy plus adjuvant therapy. CONCLUSIONS: Comorbid conditions adversely affect survival in older women with breast cancer. Moreover the results of this study showed that there are numerous predictors of the type of treatment administered, and that the most important were age and comorbidities.

MRI-Based Radiomics Input for Prediction of 2-Year Disease Recurrence in Anal Squamous Cell Carcinoma.

PURPOSE: Chemo-radiotherapy (CRT) is the standard treatment for non-metastatic anal squamous cell carcinomas (ASCC). Despite excellent results for T1-2 stages, relapses still occur in around 35% of locally advanced tumors. Recent strategies focus on treatment intensification, but could benefit from a better patient selection. Our goal was to assess the prognostic value of pre-therapeutic MRI radiomics on 2-year disease control (DC). METHODS: We retrospectively selected patients with non-metastatic ASCC treated at the CHU Bordeaux and in the French FFCD0904 multicentric trial. Radiomic features were extracted from T2-weighted pre-therapeutic MRI delineated sequences. After random division between training and testing sets on a 2:1 ratio, univariate and multivariate analysis were performed on the training cohort to select optimal features. The correlation with 2-year DC was assessed using logistic regression models, with AUC and accuracy as performance gauges, and the prediction of disease-free survival using Cox regression and Kaplan-Meier analysis. RESULTS: A total of 82 patients were randomized in the training (n = 54) and testing sets (n = 28). At 2 years, 24 patients (29%) presented relapse. In the training set, two clinical (tumor size and CRT length) and two radiomic features (FirstOrder_Entropy and GLCM_JointEnergy) were associated with disease control in univariate analysis and included in the model. The clinical model was outperformed by the mixed (clinical and radiomic) model in both the training (AUC 0.758 versus 0.825, accuracy of 75.9% versus 87%) and testing (AUC 0.714 versus 0.898, accuracy of 78.6% versus 85.7%) sets, which led to distinctive high and low risk of disease relapse groups (HR 8.60, p = 0.005). CONCLUSION: A mixed model with two clinical and two radiomic features was predictive of 2-year disease control after CRT and could contribute to identify high risk patients amenable to treatment intensification with view of personalized medicine.

Single-arm phase II trial to evaluate efficacy and tolerance of regorafenib monotherapy in patients over 70 with previously treated metastatic colorectal adenocarcinoma FFCD 1404 - REGOLD.

BACKGROUND: Regorafenib significantly increases overall survival (OS) in patients with metastatic colorectal cancer previously treated but gives toxicities. OBJECTIVES: to assess the efficacy and safety of regorafenib at it's approved dose in the older population. PATIENTS AND METHODS: This multicenter single-arm phase II enrolled patients ≥70 years old after the failure of fluoropyrimidine-based chemotherapy, anti-VEGF, and anti-EGFR treatment. The primary endpoint was disease control rate (DCR) 2 months after initiation of regorafenib (160 mg/day, 3 weeks on/1 week off). RESULTS: Forty-three patients were enrolled, with a median age of 77 years. The 2 months DCR was 31.4% in the 35 evaluable patients. For the 42 patients that received at least one dose of regorafenib, median progression-free survival and OS were 2.2 and 7.5 months. The median time to autonomy degradation and quality of life degradation was 3.1 and 3.2 months, respectively. A grade 3-4 treatment-related adverse events was observed in 35/42 patients, notably: fatigue (45.2%), hand-foot skin reaction (19.0%), hypertension (21.4%), and diarrhea (7.1%). There is a trend to achieve DCR in patients ≤80 years and a trend to discontinue the study due to toxicity in patients with ECOG ≥1, over 80 years and with impaired baseline autonomy. CONCLUSION: Treatment with regorafenib in pretreated patients ≥70 years is feasible and demonstrate similar efficacy that was observed in previous studies in young patients. Fatigue is the most frequent severe adverse event. However, caution should be taken for older patients with ECOG ≥1, over 80 years, and with impaired baseline autonomy.

Breast cancer subtype of French women is not influenced by socioeconomic status: A population-based-study.

CONTEXT: The molecular subtype of breast tumours plays a major role in cancer prognosis and treatment options. Triple negative tumours (TN) carry the worst prognosis and affects most frequently women of low socioeconomic status (SES). Studies have shown that non-biologic factors, such as the socioeconomic status could have an influence on tumour biology. To this date no study has been done investigating this association in French women. The objective is to study the association between the SES and the molecular tumour subtype of breast cancer patients in the French county of Côte d'Or. This study benefits from the population data from the Côte d'Or breast cancer registry known for its strict quality control policy. METHODS: Invasive breast cancer cases between 2003 and 2013 were extracted from the Breast cancer registry database in Côte d'Or. A multivariate analysis was conducted using a hierarchical polytomous regression for the multinomial outcomes for the cancer subtype with HR+/HER2 as reference category. RESULTS: A total of 4553 cases were included in our study. There was no significant association found between SES and tumour subtype in French women at diagnosis. Women older than 75 years were less likely to have a TN and HR+/HER2+ breast cancer (OR = 0.66; CI95% = [0.46-0.94] and OR = 0.51; CI95% = [0.37-0.70] respectively). Women with TN tumour subtype had significantly less lymph node invasion when compared to HR+/HER2- subtype (OR = 0.71; CI95% = [0.54-0.92]). CONCLUSION: No significant association was found between socioeconomic status and molecular subtype. Further studies are needed to clarify the mechanisms associated with developing each tumour subtype.

Constitutional variants are not associated with HER2-positive breast cancer: results from the SIGNAL/PHARE clinical cohort.

Human epidermal growth factor receptor 2-positive breast cancer is a subtype of interest regarding its outcome and the impressive impact of human epidermal growth factor receptor 2 targeted therapy. Constitutional variants may be involved in the aetiology of human epidermal growth factor receptor 2-positive breast cancer, and we propose a case-case study to test the hypothesis that single nucleotide polymorphisms may be associated with human epidermal growth factor receptor 2 status. A Genome-Wide Association Study was used in a cohort of 9836 patients from the SIGNAL/PHARE study (NCT00381901-RECF1098). The main goal was to identify variants specifically related to human epidermal growth factor receptor 2-positive breast cancer. A two-staged genotyping strategy was carried out to cover as large a proportion of the genome as possible. All subjects were genotyped using the Illumina HumanCore Exome chip set. Principal Components Analysis and k-means were then used to characterize the ancestry of the participants. A random sample of subjects from the main "European" cluster was genotyped with the Omni5 chip set. These data were then used to impute missing genotypes from the remaining subjects genotyped only using the HumanCore Exome array. From the 9836 patients, a total of 8703 cases including 3230 patients with human epidermal growth factor receptor 2-positive breast cancer were analyzed. Despite having 80% power to detect an odds ratio of 1.23 in this population, no variant achieved genome-wide significance for association with the occurrence of human epidermal growth factor receptor 2-positive breast cancer vs. any other subtype of breast tumour. Our study was unable to identify constitutional polymorphisms that are strongly associated with human epidermal growth factor receptor 2-positive status among breast cancer patients.

GWAS in the SIGNAL/PHARE clinical cohort restricts the association between the FGFR2 locus and estrogen receptor status to HER2-negative breast cancer patients.

Genetic polymorphisms are associated with breast cancer risk. Clinical and epidemiological observations suggest that clinical characteristics of breast cancer, such as estrogen receptor or HER2 status, are also influenced by hereditary factors. To identify genetic variants associated with pathological characteristics of breast cancer patients, a Genome Wide Association Study was performed in a cohort of 9365 women from the French nationwide SIGNAL/PHARE studies (NCT00381901/RECF1098). Strong association between the FGFR2 locus and ER status of breast cancer patients was observed (ER-positive n=6211, ER-negative n=2516; rs3135718 OR=1.34 p=5.46×10-12). This association was limited to patients with HER2-negative tumors (ER-positive n=4267, ER-negative n=1185; rs3135724 OR=1.85 p=1.16×10-11). The FGFR2 locus is known to be associated with breast cancer risk. This study provides sound evidence for an association between variants in the FGFR2 locus and ER status among breast cancer patients, particularly among patients with HER2-negative disease. This refinement of the association between FGFR2 variants and ER-status to HER2-negative disease provides novel insight to potential biological and clinical influence of genetic polymorphisms on breast tumors.

In breast cancer, are treatments and survival the same whatever a patient's age? A population-based study over the period 1998-2009.

AIM: The present study aimed to describe treatments, relative survival and prognostic factors in breast cancer patients according to age. METHODS: All women with primary invasive breast cancer, diagnosed from 1998 to 2009 in the department of Côte d'Or, were retrospectively selected. Variations in treatments administered according to age (<50 years, 50-74 years, >74 years) and period were assessed using Cochran-Armitage trend tests and χ(2) -tests, respectively. Prognostic factors according to age were estimated using a generalized linear model with a Poisson error structure. RESULTS: Overall, 4305 women were included. The oldest women (aged >74 years) were more likely than the youngest women to have comorbidities, advanced stage tumors, hormone receptor-positive tumors and be human epidermal growth factor receptor 2-negative. The use of breast conserving surgery plus adjuvant therapy decreased in older women (>74 years), whereas the proportions of women without treatments and with adjuvant hormone therapy increased with age. Multivariate relative survival analyses according to age showed an increased risk of death in women aged 50-74 years and >74 years with comorbidities compared with those without comorbidities; relative excess risks were 1.85 (1.13-3.02) and 3.23 (1.26-8.31), respectively. In contrast, a decreased risk of death was observed in women aged 50-74 years diagnosed by medical imaging compared with those diagnosed by clinical signs; relative excess risks 0.44 (0.22-0.89). CONCLUSION: Elderly women compared with the youngest women were diagnosed with more favorable tumor biology (hormone receptor-positive tumors, human epidermal growth factor receptor 2-negative). However, survival was poor in elderly women who had comorbid conditions, did not attend screening mammography examinations and were undertreated.