Standard versus fractionated high-dose cisplatin plus radiation for locally advanced head and neck cancer: Results of the CisFRad (GORTEC 2015-02) randomized phase II trial.

BACKGROUND: Chemoradiotherapy with high-dose cisplatin (HD-Cis: 100 mg/m2 q3w for three cycles) is the standard of care (SOC) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Cumulative delivered dose of cisplatin is prognostic of survival, even beyond 200 mg/m2 but high toxicity compromises its delivery. AIM: Cisplatin fractionation may allow, by decreasing the peak serum concentration, to decrease toxicity. To date, no direct comparison was done of HD-Cis versus fractionated high dose cisplatin (FHD-Cis). METHODS: This is a multi-institutional randomized phase II trial, stratified on postoperative or definitive chemoradiotherapy, comparing HD-Cis to FHD-Cis (25 mg/m2/d d1-4 q3w for 3 cycles) in patients with LA-HNSCC. The primary endpoint was the cumulative delivered cisplatin dose. RESULTS: Between December 2015 and April 2018, 124 patients were randomized. Median cisplatin cumulative delivered dose was 291 mg/m2 (IQR: 251;298) in the FHD-Cis arm and 274 mg/m2 (IQR: 198;295) in the HD-Cis arm (P = 0.054). The proportion of patients receiving a third cycle of cisplatin was higher, with a lower proportion of grade 3-4 acute AEs in the FHD-Cis arm compared to the HD-Cis arm: 81 % vs. 64 % (P = 0.04) and 10 % vs. 17 % (P = 0.002), respectively. With a median follow-up of 48 months (IQR: 41;55), locoregional failure rate, PFS and OS were similar between the two arms. CONCLUSION: Although the primary endpoint was not met, FHD-Cis allowed more cycles of cisplatin to be delivered with lower toxicity, when compared to SOC. FHD-Cis concurrently with RT is a treatment option which deserves further consideration.

Trends in incidence of invasive vaginal cancer in France from 1990 to 2018 and survival of recently diagnosed women - A population-based study.

OBJECTIVE: The aim of this study was to analyze trends in the incidence of vaginal cancer in France over a 28-year period and to present survival for recently-diagnosed women. METHODS: French cancer registries provided data on invasive vaginal cancers diagnosed from 1990 to 2015 and followed up through June 2018. Trends in incidence were analyzed using a Poisson model with a bidimensional penalized spline of age and year at diagnosis. Net survival analysis was restricted to recently-diagnosed cases (2010-2015) and used a novel approach based on a bidimensional penalized spline of age and time-since-diagnosis to model excess mortality hazard. RESULTS: With 162 new cases estimated in France in 2018, vaginal cancer represented 0.9 % of genital cancers in French women. In 2018, the world population age-standardized incidence rate was 0.2 per 100,000 person-years, median age at diagnosis was 75 years. The standardized incidence rate decreased significantly by 3 % per year (95 % CI, -3.8; -2.2) between 1990 and 2018 (0.4 cases per 100,000 person-year in 1990, vs 0.2 in 2018). Age-standardized net survival at 1 and 5 years after diagnosis was respectively 74 % and 45 %. CONCLUSIONS: This study confirms that vaginal cancer is still a rare malignancy in France with 5-year net survival that remains low. We observed a consistent decrease in the incidence rate between 1990 and 2018. It may be too early to attribute these trends to a positive impact of vaccination campaigns against hrHPV infection, since vaginal cancer mainly affects older women and HPV vaccination has only been available since the early 2000s, and only targets young girls.

Consequences of Discontinuing a 4/6 Cyclin D-Dependent Kinase Inhibitor During Endocrine Treatment in Hormone-Sensitive Metastatic Breast Cancer Patients in the Context of the COVID-19 Outbreak.

BACKGROUND: The impact of some hasty medical decision made during the first wave of the Coronavirus Disease 2019 (COVID-19) remains unknown. We have evaluated the consequences of one of these precautionary measures: the withdrawal of the cyclin D-dependent kinases 4/6 inhibitor (CDK4/6i) in patients whose metastatic disease was controlled by a combination of endocrine treatment and CDK 4/6i. METHOD: This study was noninterventional, retrospective, multicentric, and included 60 patients with HR+ HER2- metastatic disease. Their disease was controlled with the combination of endocrine treatment and CDK 4/6i. The CDK 4/6i was stopped for two months during the first COVID-19 outbreak. A univariate analysis was performed to assess the risk factors associated with disease progression. RESULTS: During this therapeutic break, 22 (37 %) patients had a radiological and/or clinical disease progression. Among them, the CDK 4/6i was re-introduced to 16 patients (n = 16/22; 73 %). A new line of treatment (chemotherapy or targeted therapy) was initiated due to the rapid symptomatic tumor progression in four patients (n = 4/22; 18 %). Two patients (n = 2/22) died in visceral crisis before another anti-tumoral treatment was introduced. In univariate analysis, the presence of liver metastases increased the risk of metastatic disease progression during the withdrawal of the CDK 4/6 (OR = 6.6; 95 % CI 1.87-23.22; P= .0033). CONCLUSION: Progression was observed in 37% of patients during the two-month treatment interruption of the CDK 4/6i. A prolonged CDK 4/6i treatment interruption in patients with clinical benefit on endocrine treatment does not seem to be a reasonable option in light of these results.

Utility values and its time to deterioration in breast cancer patients after diagnosis and during treatments.

BACKGROUND: The potential effects of breast cancer (BC) on health-related quality of life (HRQoL) should be considered in clinical and policy decision-making, as the economic burden of BC management is currently assessed. In the last decades, time-to-HRQoL score deterioration (TTD) has been proposed as an approach to the analysis of longitudinal HRQoL in oncology. The main objectives of the current study were to investigate the evolution of the utility values in BC patients after diagnosis and during follow-ups and to evaluate the TTD in utility values among women in all stages of BC. METHODS: Health-state utility values (HSUV) were assessed using the EuroQol 5-Dimension 3-Level at diagnosis, at the end of the first hospitalization and 3 and 6 months after the first hospitalization. For a given baseline score, HSUV was considered to have deteriorated if this score decreased by ≥ 0.08 points of the EQ-5D utility index score and ≥ 7 points of the EQ visual analogue scale. TTD curves were calculated using the Kaplan-Meier estimation method. RESULTS: Overall 381 patients were enrolled between February 2006 and February 2008. The highest proportions of respondents at the baseline and all follow-ups reporting some and extreme problems were in pain discomfort and anxiety/depression dimensions; more than 80% of patients experienced a deterioration in EQ-5D utility index score and EQ VAS score with a median TTD of 3.15 months and 6.24 Months, respectively. CONCLUSIONS: BC patients undergoing therapy need psychological support to cope with their discomfort, pain, depression, anxiety, and fear during the process of diagnosis and treatment to improve their QoL.

Incidence and Trend of Type I and II Endometrial Cancer in Women from Two Population-Based European Cancer Registries (1998-2012).

Endometrial cancer (EC) is the most frequent female genital tract cancer in Europe. This cohort study aimed to determine age-standardised incidence rates and long-term trends of type I and II endometrial cancer in women from population-based cancer registries in the Region of Murcia (Spain) and the Bas-Rhin area (France). Data of new cases of endometrial cancer between 1998 and 2012 were obtained from the Murcia and Bas-Rhin cancer registries. In that period, 3756 cases of endometrial cancer were recorded, with 3270 corresponding to type I EC and 486 corresponding to type II EC. The Bas-Rhin area presented higher age-adjusted incidence rates than those in the Region of Murcia for both type I EC (24.2 and 19.3 cases/100,000 person-years (py), respectively) and type II EC (4.4 and 2.3 cases/100,000 py, respectively). Joinpoint regression showed no changes in trends. In both populations, there was an increasing trend for both EC types, but the trend was steeper in the Region of Murcia and larger overall for type II EC. Finally, a significant increase was observed in the annual trend of type II EC. Further studies are warranted to determine the potential risk factors, and continued efforts are needed to improve the recording and monitoring of EC types.

Anxiety during Radiation Therapy: A Prospective Randomized Controlled Trial Evaluating a Specific One-on-One Procedure Announcement Provided by a Radiation Therapist.

BACKGROUND: Anxiety impacts patient outcomes and quality of life in response to cancer diagnosis. A prospective phase 3 trial randomizing 126 patients was conducted to determine whether a specific one-on-one procedure announcement provided by a radiation therapist before CT scan simulation decreases anxiety for patients with breast cancer requiring radiotherapy. MATERIAL AND METHODS: Anxiety was measured using the STAI form, and the QLQ-C30 and BR-23 questionnaires were used to evaluate quality of life. RESULTS: Mean trait or state anxiety scores before CT scan simulation, before the first and second sessions, and at the end of radiation treatment were not significantly different. We observed a decrease in the level of anxiety with time; however, no significant difference in mean state anxiety scores at any of the time intervals was detected. Factors, such as anxiety trait score, professional and marital status, age, and use of alternative therapy, did not significantly influence the evolution of anxiety status over time or the mean value. Anxiety was significantly influenced by the level of fatigue. Patients who benefited from the radiation therapists' advice felt significantly better informed. CONCLUSIONS: The one-on-one program announcement occurring before CT scan simulation led to patients being more informed and greater satisfaction but did not decrease anxiety.

What is the most appropriate period to define synchronous cancers?

BACKGROUND: Studies about second primary cancers (SPC) incidence exclude a period following the first cancer diagnosis given the high probability of diagnosing another primary cancer during this phase (synchronous cancers). However, definition of synchronicity period varies widely, from one to six months, without clear epidemiological justification. The objective of this study was to determine the most appropriate synchronicity period. METHODS: Data from 13 French population-based cancer registries were used to establish a cohort of all patients diagnosed with a first cancer between 1989 and 2010. The incidence rate of subsequent cancer was computed by day within 1 year of follow-up after the first diagnosis. Incidence was modelized by joinpoint regression models with an initial quadratic trend and a second constant part (plateau). The joinpoint was the point from which the plateau began and defining the synchronicity period. RESULTS: Our cohort included 696,775 patients with a first cancer, of which 12,623 presented a SPC. The median joinpoint for all sites combined was estimated at 120.5 days [112.0-129.0]. Analysis by gender reported a higher difference in 32 days for males (127.8 vs 96.1 days). Noteworthy differences were found depending on patient age and the site of first cancer, with joinpoint ranging from 84.7 (oesophagus cancer) to 250.1 days (bladder cancer). CONCLUSION: Although some heterogeneity was observed based on the characteristic of the patients, the appropriate synchronicity period appears to be 4 months after the diagnosis of first cancer.

Cancer Among Adolescents and Young Adults Between 2000 and 2016 in France: Incidence and Improved Survival.

Purpose: This study was undertaken to determine cancer survival and describe the spectrum of cancers diagnosed among French adolescent and young adult (AYA) population. Methods: All cases of cancer diagnosed in 15-24 years, recorded by all French population-based registries (18% of the French population), over the 2000-2016 period, were included. Age-standardized incidence rates, conventional annual percentage change (cAPC) of incidence over time, and 5-year overall survival (5yOS) were calculated. Results: We analyzed 2734 cancer diagnoses in adolescents and 4199 in young adults. Overall incidence rates were 231.9/106 in 15-19 year olds and 354.0/106 in 20-24 year olds. The most frequently diagnosed cancers in male AYA were malignant gonadal germ-cell tumors (GCT), Hodgkin lymphoma (HL), and malignant melanoma and were HL, thyroid carcinoma, and malignant melanoma in females. Cancer incidence was stable over time with a cAPC of 0.8% (p = 0.72). For all cancers combined, 5yOS was 86.6% (95% CI: 85.8-87.4), >85% for HL, non-Hodgkin lymphomas (NHL), GCT, thyroid carcinomas, and malignant melanomas, and around 60% and lower for osteosarcomas, Ewing tumors, hepatic carcinomas, and rhabdomyosarcomas. The 5yOS has significantly improved from 2000-2007 to 2008-2015 for all cancers pooled, with a substantial gain of 4% for 15-19 year olds and 3% for 20-24 year olds. Conclusion: Notwithstanding the encouraging results for some cancers, and overall, persistent poorer survivals in AYA were shown compared to children for acute lymphoblastic leukemia, osteosarcoma, Ewing tumor, rhabdomyosarcoma, and malignant hepatic tumors. These disparities require further investigation to identify and address the causes of these inferior outcomes.

Evaluation of long-term living conditions in patients treated for localised prostate cancer.

PURPOSE: To evaluate the evolution of living conditions (LC) in long-term survivors of localised prostate cancer 10 years after treatment compared with those of a same-age control group from the general population. METHODS: Two hundred and eighty-seven patients diagnosed with prostate cancer in 2001 were selected in 11 French cancer registries. They were matched with controls randomly selected for age and residency. Both patients and controls completed a self-administered LC questionnaire concerning their familial, social and professional life, and general and specific quality of life (QoL) and anxiety and depression questionnaires. RESULTS: Compared with controls, patients reported more sexual modifications (p < .0001), but without any difference in marital status. Patients' circle of friends was more stable than that of the controls (91% vs. 63%; p < .0001) and patients reported fewer friendship modifications than controls (p < .0006). Their professional and physical activities were also preserved. They reported more anxiolytic intake (p = .002) but did not consult their general practitioner more often. Type of specialist consulted differed in the two groups. CONCLUSION: Patients treated for localised prostate cancer had the same living conditions as men of the same age. Their social life was satisfying on the whole, albeit they reported more sexual difficulties than their counterparts.

Persistent taxane-induced neuropathy in elderly patients treated for localized breast cancer.

Breast cancer is the most common cancer among women. Localized breast cancer treatments involve taxanes which are often responsible for acute peripheral neuropathy. The persistence of taxane-induced peripheral neuropathy (TIPN) is scarcely described among elderly women. A monocenter historical cohort study including all women over 65 years of age treated between 2001 and 2016 with a taxane-based chemotherapy for localized breast cancer was carried out at the Paul Strauss Regional Comprehensive Cancer Center. All cases included were followed up for at least 2 years, deaths from causes unrelated to TIPN were excluded. We report on the frequency and risk factors and establish a prognostic score of persistent Common Terminology Criteria for Adverse Events (CTCAE) grade 2 and 3 TIPN. Among the 302 included patients, 21% and 9% developed persistent TIPN of grade 2 and 3, respectively. Two patients died from complications of grade 3 TIPN. Risk factors of persistent grade 2 and higher neuropathy included age (P < .0001), body mass index (P < .0001), and diabetes (P = .0093). Persistent TIPN was more frequent with paclitaxel than docetaxel (OR = 5.43; P < .0001). Patients presenting all four major risk factors had a 97.2% probability of developing long-term symptoms against 1.2% for patients showing no risk factor. We therefore identified 3 prognostic groups. TIPN is a frequent and sometimes severe persistent side effect of breast cancer treatment among elderly women with a major impact on health-related quality of life. Chemotherapy regimens without taxane could therefore be a valid option in elderly patients with neurotoxicity risk factors.

SFCE-RAPIRI Phase I Study of Rapamycin Plus Irinotecan: A New Way to Target Intra-Tumor Hypoxia in Pediatric Refractory Cancers.

Hypoxic environment is a prognostic factor linked in pediatric cancers to a worse outcome, favoring tumor progression and resistance to treatments. The activation of mechanistic Target Of Rapamycin (mTor)/hypoxia inducible factor (HIF)-1 pathway can be targeted by rapamycin and irinotecan, respectively. Therefore, we designed a phase I trial associating both drugs in pediatric refractory/relapsing solid tumors. Patients were enrolled according to a 3 + 3 escalation design with ten levels, aiming to determine the MTD (maximum tolerated dose) of rapamycin plus irinotecan. Rapamycin was administered orally once daily in a 28-day cycle (1 to 2.5 mg/m2/day), associating biweekly intravenous irinotecan (125 to 240 mg/m2/dose). Toxicities, pharmacokinetics, efficacy analyses, and pharmacodynamics were evaluated. Forty-two patients, aged from 2 to 18 years, were included. No MTD was reached. Adverse events were mild to moderate. Only rapamycin doses of 1.5 mg/m2/day reached over time clinically active plasma concentrations. Tumor responses and prolonged stable disease were associated with a mean irinotecan area under the curve of more than 400 min.mg/L. Fourteen out of 31 (45.1%) patients had a non-progressive disease at 8 weeks. Most of them were sarcomas and brain tumors. For the phase II trial, we can then propose biweekly 125 mg/m2 irinotecan dose with a pharmacokinetic (PK) follow-up and a rapamycin dose of 1.5 mg/m2/day, reaching a blood concentration above 10 g/L.

[Long-term occupational situation after cancer: A French registry-based study]. / Situation professionnelle à long terme après un cancer : étude réalisée à partir de registres de population.

INTRODUCTION: Few studies have explored the long-term occupational situation after cancer. The aim of our study were to study the employment status among long-term cancer survivors and to compare it to cancer-free controls from the general population at 5, 10 or 15 years after cancer diagnosis. METHODS: From data of a registry-based study, long-term survivors from breast,cervical and colorectal cancer, randomly selected from three tumor registries in France, were compared to cancer-free controls randomly selected from electoral lists. We selected active cancer survivors and cancer-free controls aged less than 60 at the time of the survey. We have studied the employment status of cases vs. controls and the factors associated with employment status. RESULTS: At 5, 10 or 15 years after diagnosis, we did not observe any significant difference in employment status between cases and controls. Among cases, 17% had lost their jobs. Older age, lower incomes, lower education, a short-term employment contract, the presence of co-morbidities, fatigue and a worse quality of life were associated with job loss. DISCUSSION: Although the employment status of the cases was comparable to that of the controls, efforts should be intensified to make it easier for patients diagnosed with cancer to return to work.

Impact of Lymphadenectomy on Survival of Patients with Serous Advanced Ovarian Cancer After Neoadjuvant Chemotherapy: A French National Multicenter Study (FRANCOGYN).

BACKGROUND: The population of interest to this study comprised individuals with advanced-stage ovarian carcinoma who were exposed to neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS). Those who had not received systematic lymphadenectomy (SL; Group 1) were compared to those who had received SL (Group 2). Outcome measures included progression-free survival (PFS), overall survival (OS), and surgical complications. METHODS: This was a retrospective, multicenter cohort study in nine referral centers of France between January 2000 and June 2017. OS analysis using the multivariate Cox regression model was performed. PFS and surgery-related morbidity were analyzed. RESULTS: Of the 255 patients included, 100 were in Group 1 and 155 in Group 2. Patient majority was, on average, younger and less comorbid, with predominant R0 surgery in Group 2. Dindo-Clavien score was similar between the two groups (p = 0.15). Median OS was 26.8 months in Group 2 and 27.6 months in Group 1. SL was not statistically significant on OS (p = 0.7). Median PFS was 18.3 months in Group 2 and 16.6 months in Group 1. SL had positive impact on PFS (p = 0.005). CONCLUSIONS: patients who had received SL (Group 2) had significantly higher PFS regardless of node-positivity status when compared to those who had not received SL (Group 1).

Machine learning application for incident prostate adenocarcinomas automatic registration in a French regional cancer registry.

Cancer registries are collections of curated data about malignant tumor diseases. The amount of data processed by cancer registries increases every year, making manual registration more and more tedious. OBJECTIVE: We sought to develop an automatic analysis pipeline that would be able to identify and preprocess registry input for incident prostate adenocarcinomas in a French regional cancer registry. METHODS: Notifications from different sources submitted to the Bas-Rhin cancer registry were used here: pathology data and, ICD 10 diagnosis codes from hospital discharge data and healthcare insurance data. We trained a Support Vector Machine model (machine learning) to predict whether patient's data must be considered or not as a prostate adenocarcinoma incident case that should therefore be registered. The final registration of all identified cases was manually confirmed by a specialized technician. Text mining tools (regular expressions) were used to extract clinical and biological data from non-structured pathology reports. RESULTS: We performed two successive analyses. First, we used 982 cases manually labeled by registrars from the 2014 dataset to predict the registration of 785 cases submitted in 2015. Then, we repeated the procedure using the 2089 cases labeled by registrars from the 2014 and 2015 datasets to predict the registration of 926 cases submitted in the 2016 data. The algorithm identified 663 cases of prostate adenocarcinoma in 2015, and 610 in 2016. From these findings, 663 and 531 cases were respectively added to the registry; and 641 and 512 cases were confirmed by the specialized technician. This registration process has achieved a precision level above 96 %. The algorithm obtained an overall precision of 99 % (99.5 % in 2015 and 98.5 % in 2016) and a recall of 97 % (97.8 % in 2015 and 96.9 % in 2016). When the information was found in pathology report, text mining was more than 90 % accuracy for major indicators: PSA test, Gleason score, and incidence date). For both PSA and tumor side, information was not detected in the majority of cases." CONCLUSION: Machine learning was able to identify new cases of prostate cancer, and text mining was able to prefill the data about incident cases. Machine-learning-based automation of the registration process could reduce delays in data production and allow investigators to devote more time to complex tasks and analysis.

Cancer-related fatigue among long-term survivors of breast, cervical, and colorectal cancer: a French registry-based controlled study.

BACKGROUND: While several studies have documented fatigue during and after cancer treatment, long-term cancer survivor fatigue is underreported. In this study, we compare fatigue, quality of life (QoL), and anxiety between relapse-free cancer survivors 15 years after diagnosis and healthy controls. METHODS: Cancer survivors (CS) were randomly selected from three large population-based cancer registries (Bas-Rhin, Calvados, and Doubs, France). Cancer-free controls were randomly selected from electoral lists with stratification on age group, residence area, and gender. All participants completed self-reported fatigue (MFI), QoL (EORTC QLQ-C30), and anxiety (STAI) questionnaires. Univariable and multivariable logistic regression were used to study the association between fatigue and cancer status, in three cancer subgroups: breast cancer (BC), cervical cancer (CC), and colorectal cancer (CRC). RESULTS: Two hundred sixty-three CS and 688 controls (125/275, 45/153, 93/260 CS/controls for BC, CC, and CRC respectively) were included. The mean age was 66 years. In multivariable analyses, CS had higher general and mental fatigue than controls p = 0.04 and p = 0.02, respectively. No difference in QoL was observed between CS and controls. CS were more anxious than controls (p < 0.01). Anxiety was associated with general fatigue (p < 0.0001) and mental fatigue (p < 0.0001). CONCLUSION: Fifteen years after diagnosis, cancer survivors reported more general and mental fatigue compared with controls. Our results reinforce guidelines, identifying fatigue as a persistent symptom.

Impact of neoadjuvant chemotherapy cycles on survival of patients with advanced ovarian cancer: A French national multicenter study (FRANCOGYN).

OBJECTIVE: The purpose of this study was to compare two groups of patients presenting advanced ovarian carcinoma benefiting from neoadjuvant chemotherapy (NAC) followed by cytoreductive surgery: after 3-4 cycles (group 1) or ≥ 5 cycles (group 2), regarding overall survival (OS) and progression-free survival (PFS), complications related to surgery as well as the extent of cytoreduction were assessed. STUDY DESIGN: We conducted a retrospective, multicenter cohort study in nine referral centers of France, reviewing the charts of all patients who underwent NAC between January 2000 and June 2017. We performed an OS analysis using multivariate Cox regression models adjusted for potential confounders. We also analyzed PFS and surgery-related morbidity. RESULTS: Of 501 patients included, 236 (47.1 %) benefited from ≤ 4 NAC cycles and 265 (52.9 %) from ≥ 5 NAC cycles. Characteristics data were similar in both groups. The rate of achievement of complete surgery was similar in both groups (p = 0.28). Surgical morbidity and postoperative complications showed no significant differences between both groups. The median OS was 54.2 months, 64 months for group 1 and 49.2 months for group 2. The 5-year survival rate was 45.6 % and 27.6 %. This difference was not statistically significant [HR 1.81 (0.89-3.71), p = 0.09]. Five-year PFS was 19.7 % and 11.7 % respectively (p = 0.31). CONCLUSION: In a large series of advanced ovarian cancer, patients receiving late IDS (≥ 5 NAC cycles) seem to show a poorer prognosis than patients operated on earlier. The survival appears to be mainly determined by optimal resection and response to chemotherapy.

Fulvestrant and palbociclib combination in heavily pretreated hormone receptor-positive, HER2-negative metastatic breast cancer patients.

PURPOSE: We report the results of a retrospective analysis of the fulvestrant and palbociclib combination within a temporary authorization of use (TAU) program in 77 heavily pretreated patients with hormone receptor-positive (HR+), HER2-negative metastatic breast cancer. METHODS: All patients who received the fulvestrant and palbociclib combination within this TAU program were included. Toxicities were graded using the CTCAE v5 scale. RESULTS: The majority of patients (62.3%) were previously treated with the mTOR inhibitor everolimus. The median number of previous treatments for their metastatic disease was 4. With a median follow-up of 14 months, the median progression-free survival (PFS) was 7.6 months. The median PFS significantly (p < 0.0001) decreased with the number of previous treatment lines in the metastatic setting. The median PFS was 5.5 months in patients who had previously progressed on everolimus compared to 9.3 months in the everolimus non-pretreated subgroup. No significant difference in median PFS was detected in patients according to age. The median overall survival rate was not reached. The clinical benefit rate was 64%, including 4% of complete responses, 26% partial responses, and 34% stable diseases for the entire cohort. CONCLUSIONS: The fulvestrant and palbociclib combination exerts an appreciable effect on metastatic heavily pretreated patients with a tolerable toxicity profile.

Factors of the evolution of fatigue dimensions in patients with breast cancer during the 2 years after surgery.

Women with breast cancer are increasingly being cured of the disease but fatigue remains the most frequently reported symptom. The aims of our study were to identify distinct trajectories in four fatigue dimensions during 2 years after breast cancer surgery and to explore the demographic, clinical and personality characteristics associated with these profiles. We included women from the prospective longitudinal multicenter FATSEIN cohort in France. They completed the Multidimensional Fatigue Inventory for nine follow-ups over 24 months after surgery. A group-based trajectory model identified distinct trajectories in each fatigue dimension. Multinomial logistic regression determined the factors associated with each profile. From the 459 women followed, 3-5 fatigue trajectories were revealed in each fatigue dimension, from its absence to its severest degree. In our multivariate analysis, the risk of severe fatigue was decreased in all dimensions by a high quality of life before surgery (measured by the European Organization for Research and Treatment of Cancer 30-item QoL questionnaire; e.g., for general and physical fatigue: OR = 0.93, 95% CI 0.91, 0.96), especially a high physical and emotional functions for general and physical fatigue, and a high cognitive function for mental fatigue. Both severe mental fatigue and severely reduced motivation worsened with low optimism before surgery (e.g., for mental fatigue: OR = 0.93, 95% CI 0.89, 0.97). Severely reduced activities increased by having chemotherapy (OR = 9.41, 95% CI 2.28, 38.79). Targeting women at risk for severe fatigue can provide early preventive and curative treatment and appropriate psychological support.

Assessment of the efficacy of successive endocrine therapies in hormone receptor-positive and HER2-negative metastatic breast cancer: a real-life multicentre national study.

BACKGROUND: For luminal metastatic breast cancer (MBC), endocrine therapy (ET) is the recommended initial treatment before chemotherapy. Our objective was to evaluate the efficacy of multiple ET lines in a real-life study. METHODS: The Breast Cancer Epidemiological Strategy and Medical Economics (ESME) project analysed data from all patients with systemic treatment for MBC initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres. The primary end-point was the successive progression-free survival (PFS) evaluation. RESULTS: The ESME research programme included 9921 patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2) negative (HER2-) MBC. Before any chemotherapy, 4195 (43.4%), 1252 (29.8%) and 279 (6.6%) patients received one, two or three ET ± targeted therapy, respectively. The median PFS for first-, second- and third-line ET ± targeted therapy was 11.5 (95% confidence interval [CI], 10.8-12.1), 5.8 (95% CI, 5.3-6.1) and 5.5 (95% CI, 4.6-6.3) months, respectively. In a multivariate analysis, time from diagnosis to metastatic recurrence (P < 0.0001), presence of symptoms at metastatic relapse (P = 0.01), number of metastatic sites (P = 0.0003) and their localisation (P < 0.0001) were prognostic factors for PFS1. Duration of previous PFS was the only prognostic factor for subsequent PFS (10% threshold). Ten percent of the patients showed long-term response to ET, with a total treatment duration before chemotherapy ≥43.6 months. CONCLUSIONS: Median PFS in our HR+/HER2- real-life cohort is similar to median first-line PFS reported in clinical trials, regardless of ET used as second- and third-line treatment. Despite the international consensus on early initiation of ET, the latter is not prescribed in most of the cases. Patients with a low tumour burden may achieve prolonged response on ET.

Gastric MALT lymphoma in a population-based study in France: clinical features, treatments and survival.

BACKGROUND: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a rare disease, and most available data on gastric MALT lymphoma (GML) come from clinical studies of selected patients treated in centres of excellence. AIMS: To analyse the clinical features, management and survival of GML patients in a population-based study in France METHODS: All new cases of GML diagnosed between 2002 and 2010 in 11 French areas covered by cancer registries were included. Pathology reports were verified and, if necessary, reviewed by an expert pathologist. All clinical data were retrospectively collected from medical files and analysed using stata V. 14 software. RESULTS: Four hundred and sixteen patients with confirmed GML (50% male, median age 67 years) were identified. Among them, 44 showed an early transformation into diffuse large B cell lymphoma and were considered to have had an initially missed high-grade lymphoma. At diagnosis, 76% of patients were at stage IE/II, and 24% at stage III/IV of the disease. Helicobacter pylori infection was found in 57% of the patients. Eradication treatment was administered to 76% of patients and complete remission (CR) was obtained in 39%. One hundred and ninety patients received at least one other treatment, including 10 already in CR after eradication. Altogether, CR was obtained in 70% of patients and the 5-year overall survival was 79% (95% CI [75-83]). CONCLUSIONS: In comparison to clinical series, in the general population, GMLs are more frequently diagnosed at an advanced stage, their clinical management is heterogeneous, and there is a risk of misdiagnosis and overtreatment. These results highlight the necessity of following currently available guidelines in this field.