Chemoradiotherapy versus radiotherapy alone in the management of early-stage anal squamous cell carcinoma: A comparative analysis of the French cohort FFCD-ANABASE.

INTRODUCTION: Early-stage anal squamous cell carcinomas (ASCC) are usually treated with chemoradiotherapy (CRT), with good outcomes. Radiotherapy (RT) alone might be sufficient while reducing toxicity. METHODS: Patients included in the French prospective FFCD-ANABASE and treated for T1-2N0 ASCC between 2015/01 and 2020/04 were divided into CRT and RT groups. Clinical outcomes and toxicity were reported. Propensity score matching was conducted for 105 pairs of patients. RESULTS: 440 patients were analyzed: 261 (59.3 %) in the CRT group and 179 (40.7 %) in the RT group. The median follow-up was 35.7 months. Patients receiving CRT were younger, had better Performance Status (PS) and larger tumors. No statistical difference was observed for 3-year Disease-free survival (85.3 % vs 83 %, p = 0.28), Overall survival (89.6 % vs 94.8 %, p = 0.69) and Colostomy-free survival (84.5 % vs 87.2 %, p = 0.84) between CRT and RT groups, respectively. Propensity score-matched analysis confirmed these findings. Treatment interruptions were significantly more frequent in the CRT group (36.3 % vs 21.9 %, p = 0.0013), resulting in an Overall Treatment Time (OTT) extended by 7 days. Grade 3 CTCAE v4.0 toxicities were more prevalent in the CRT group (46 % vs 19 %, p < 0.001). CONCLUSION: Adding chemotherapy to radiotherapy did not significantly improve outcomes for T1-2N0 ASCC in our study, but increased toxicity and OTT.

Neoadjuvant and adjuvant pembrolizumab in advanced high-grade serous carcinoma: the randomized phase II NeoPembrOV clinical trial.

This open-label, non-comparative, 2:1 randomized, phase II trial (NCT03275506) in women with stage IIIC/IV high-grade serous carcinoma (HGSC) for whom upfront complete resection was unachievable assessed whether adding pembrolizumab (200 mg every 3 weeks) to standard-of-care carboplatin plus paclitaxel yielded a complete resection rate (CRR) of at least 50%. Postoperatively patients continued assigned treatment for a maximum of 2 years. Postoperative bevacizumab was optional. The primary endpoint was independently assessed CRR at interval debulking surgery. Secondary endpoints were Completeness of Cytoreduction Index (CCI) and peritoneal cancer index (PCI) scores, objective and best response rates, progression-free survival, overall survival, safety, postoperative morbidity, and pathological complete response. The CRR in 61 pembrolizumab-treated patients was 74% (one-sided 95% CI = 63%), exceeding the prespecified ≥50% threshold and meeting the primary objective. The CRR without pembrolizumab was 70% (one-sided 95% CI = 54%). In the remaining patients CCI scores were ≥3 in 27% of the standard-of-care group and 18% of the investigational group and CC1 in 3% of the investigational group. PCI score decreased by a mean of 9.6 in the standard-of-care group and 10.2 in the investigational group. Objective response rates were 60% and 72%, respectively, and best overall response rates were 83% and 90%, respectively. Progression-free survival was similar with the two regimens (median 20.8 versus 19.4 months in the standard-of-care versus investigational arms, respectively) but overall survival favored pembrolizumab-containing therapy (median 35.3 versus 49.8 months, respectively). The most common grade ≥3 adverse events with pembrolizumab-containing therapy were anemia during neoadjuvant therapy and infection/fever postoperatively. Pembrolizumab was discontinued prematurely because of adverse events in 23% of pembrolizumab-treated patients. Combining pembrolizumab with neoadjuvant chemotherapy is feasible for HGSC considered not completely resectable; observed activity in some subgroups justifies further evaluation to improve understanding of the role of immunotherapy in HGSC.

Improving olaparib exposure to optimize adverse effects management.

Background: Olaparib is an inhibitor of the human poly-(ADP-ribose)-polymerase enzymes (PARP1/2) needed to repair single-strand DNA breaks. It is used in breast, ovarian, prostate and pancreatic cancer. Objectives: This work aimed to describe the pharmacokinetics/pharmacodynamics (PK/PD) relationship between olaparib plasma concentrations and common adverse effects (i.e. anaemia and hypercreatininaemia), in a real-life setting, to propose a target concentration for therapeutic drug monitoring. Methods: Two PK/PD models describing the evolution of haemoglobinaemia and creatininaemia as a function of time were developed, based on data from, respectively, 38 and 37 patients receiving olaparib. The final model estimates were used to calculate the incidence of anaemia and creatinine increase according to plasma trough concentrations for 1000 virtual subjects to define target exposure. Results: The final models correctly described the temporal evolution of haemoglobinaemia and creatininaemia for all patients. The haemoglobinaemia PK/PD model is inspired by Friberg's model, and the creatininaemia PK/PD model is an indirect response model. Model parameters were in agreement with physiological values and close to literature values for similar models. The mean (population) plasma haemoglobin concentration at treatment initiation, as estimated by the model, was 11.62 g/dL, while creatinine concentration was 71.91 µmol/L. Using simulations, we have identified a target trough concentration of 3500-4000 ng/mL, above which more than 20% of patients would report grade ≥3 anaemia. Conclusion: Based on real-world data, we were able to properly describe the time course of haemoglobinaemia and plasma creatininaemia during olaparib treatment.

Can Chatbot Artificial Intelligence Replace Infectious Diseases Physicians in the Management of Bloodstream Infections? A Prospective Cohort Study.

BACKGROUND: The development of chatbot artificial intelligence (AI) has raised major questions about their use in healthcare. We assessed the quality and safety of the management suggested by Chat Generative Pre-training Transformer 4 (ChatGPT-4) in real-life practice for patients with positive blood cultures. METHODS: Over a 4-week period in a tertiary care hospital, data from consecutive infectious diseases (ID) consultations for a first positive blood culture were prospectively provided to ChatGPT-4. Data were requested to propose a comprehensive management plan (suspected/confirmed diagnosis, workup, antibiotic therapy, source control, follow-up). We compared the management plan suggested by ChatGPT-4 with the plan suggested by ID consultants based on literature and guidelines. Comparisons were performed by 2 ID physicians not involved in patient management. RESULTS: Forty-four cases with a first episode of positive blood culture were included. ChatGPT-4 provided detailed and well-written responses in all cases. AI's diagnoses were identical to those of the consultant in 26 (59%) cases. Suggested diagnostic workups were satisfactory (ie, no missing important diagnostic tests) in 35 (80%) cases; empirical antimicrobial therapies were adequate in 28 (64%) cases and harmful in 1 (2%). Source control plans were inadequate in 4 (9%) cases. Definitive antibiotic therapies were optimal in 16 (36%) patients and harmful in 2 (5%). Overall, management plans were considered optimal in only 1 patient, as satisfactory in 17 (39%), and as harmful in 7 (16%). CONCLUSIONS: The use of ChatGPT-4 without consultant input remains hazardous when seeking expert medical advice in 2023, especially for severe IDs.

Effect of Adapted Physical Activity in Patients With Advanced Pancreatic Cancer: The APACaP GERCOR Randomized Trial.

BACKGROUND: The impact of adapted physical activity (APA) on health-related quality of life (HRQoL) in patients with advanced pancreatic ductal adenocarcinoma (aPDAC) is unknown. This study evaluated whether APA in addition to standard care improved HRQoL in patients who have aPDAC who are receiving first-line chemotherapy. PATIENTS AND METHODS: Patients with locally advanced/metastatic PDAC and an ECOG performance status of 0 to 2 were randomized (1:1) to receive standard care (standard arm) or standard care plus a home-based 16-week APA program (APA arm). The primary objective was the effect of the APA program on 3 dimensions of the EORTC QLQ-C30: global health status, physical function, and fatigue at week 16 (W16), with a one-sided type I error of 0.017 for each dimension. The primary HRQoL analysis was performed in patients with available baseline and W16 scores for the dimensions (ie, the modified intention-to-treat population 1 [mITT1]), and secondary longitudinal HRQoL analyses using the mixed model for repeated measures (MMRM) and time until definitive deterioration (TUDD) methods were performed in the mITT1 population and in patients with baseline and at least one follow-up questionnaire (mITT2 population). A difference of ≥5 points was considered to be clinically relevant. RESULTS: Of 326 included patients, 313 were randomized to the standard (n=157) or APA (n=156) arms. In the mITT1 population (n=172), the mean differences in global health status, physical function, and fatigue at W16 adjusted from baseline were -0.98 (SD, 23.9; P=.39), -2.08 (SD, 21.3; P=.26), and 4.16 (SD, 29.2; P=.17), respectively, showing a non-statistically significant benefit with APA. In the mITT2 population (n=259), APA was associated with statistically significant and clinically relevant improvement in 5 and 8 dimensions of the HRQoL in the longitudinal MMRM and TUDD analyses, respectively. CONCLUSIONS: APA improved several dimensions of HRQoL in patients with aPDAC receiving first-line chemotherapy and standard care.

Hepatic arterial oxaliplatin plus intravenous 5-fluorouracil and cetuximab for first-line treatment of colorectal liver metastases: A multicenter phase II trial.

BACKGROUND: The efficacy and tolerability of hepatic arterial infusion (HAI) oxaliplatin plus systemic 5-fluorouracil and cetuximab as frontline treatment in patients with colorectal liver metastases (CRLM) are unknown. METHODS: In this multicenter, single-arm phase II study, patients with CRLM not amenable to curative-intent resection or requiring complex/major liver resection, and no prior chemotherapy for metastatic disease, received HAI oxaliplatin and intravenous 5-fluorouracil, leucovorin and cetuximab, every two weeks until disease progression, limiting toxicity or at least 3 months after complete response or curative-intent resection/ablation. The primary endpoint was overall response rate (ORR). RESULTS: 35 patients, mostly with bilateral (89%), multiple CRLM (>4, 86%; >10, 46%) were enrolled in eight centers. The ORR was 88% (95% CI, 71%-96%) among evaluable patients (n = 32), and 95% (95% CI 70-100%) among the 22 wild-type RAS/BRAF evaluable patients. After a median follow-up of 8.8 years (95% CI, 8.7-not reached), median progression-free survival was 17.9 months (95% CI, 15-23) and median overall survival (OS) was 46.3 months (95% CI, 40.0-not reached). 23 of the 35 patients (66%), including 22 (79%) of the 25 patients with wild-type RAS tumor, underwent curative-intent surgical resection and/or ablation of CRLM. HAI catheter remained patent in 86% of patients, allowing for a median of eight oxaliplatin infusions (range, 1-19). Treatment toxicity was manageable, without toxic death. CONCLUSION: HAI oxaliplatin plus systemic 5-fluorouracil and cetuximab appears highly effective in the frontline treatment of patients with unresectable CRLM and should be investigated further.

Ovarian cancer in the older patient: where are we now? What to do next?

In recent years, major advances have been made toward the individualization of epithelial ovarian cancer care, leading to an overall improvement of patient outcomes. However, real-life data indicate that the oldest populations do not benefit from this, due to aspects related to cancer (more aggressive histopathological features), treatment (i.e. frequently suboptimal), and the host (increased toxicities in patients with lower physiological reserve). A specific risk-benefit perspective should therefore be taken when considering surgery, chemotherapy, and maintenance treatments: the decision for cytoreductive surgery should include geriatric vulnerability and surgical complexity, neo-adjuvant chemotherapy being an option when primary surgery appears at high risk; carboplatin paclitaxel association remains the standard even in vulnerable older patients; and bevacizumab and poly(ADP-ribose) polymerase inhibitors maintenance are interesting options provided they are prescribed according to their indications with a close monitoring of their toxicities. Future studies should aim to individualize care without limiting access of older patients to innovation. A specific focus is needed on age-specific translational analyses (focusing on tumor mutational burden and impaired biological pathways), a better patient stratification according to geriatric parameters, an adaptation of both oncological treatment and geriatric interventions, and treatment adaptations not a priori but according to formal pharmacokinetic data.

Associated Factors to Efficacy and Tolerance of Immunotherapy in Older Patients with Cancer Aged 70 Years and Over: Impact of Coprescriptions.

BACKGROUND: Immunotherapy with immune checkpoint blockers (ICB) significantly improves the prognosis for an increasing number of cancers. However, data on geriatric populations taking ICB are rare. OBJECTIVE: This study aimed to identify factors associated with the efficacy and tolerance of ICB in an older population. PATIENTS AND METHODS: This retrospective monocentric study included consecutive patients aged ≥ 70 years with solid cancer who received ICB between January 2018 and December 2019. Efficacy was assessed by progression-free survival (PFS) and tolerance was defined as cessation of immunotherapy due to the occurrence of any adverse event. RESULTS: One hundred and five patients (65.7% men) were included, mainly at the metastatic stage (95.2%); 50.5% had lung cancer. Most (80%) patients were treated with anti-PD1 (nivolumab, pembrolizumab), 19.1% with anti-PD-L1 (atezolizumab, durvalumab, and avelumab) and 0.9% with anti-CTLA4 ICB (ipilimumab). Median PFS was 3.7 months [95% confidence interval (CI) (2.75-5.70)]. PFS was shorter in univariate analysis when ICB was taken concomitantly with an antiplatelet agent (AP) [hazard ratio (HR) = 1.93; 95% CI (1.22-3.04); p = 0.005]. Tolerance was lower in univariate analysis for lung cancer [odds ratio (OR) = 3.03; 95% CI (1.07-8.56), p < 0.05] and in patients taking proton pump inhibitors (PPI) [OR = 5.50; 95% CI (1.96-15.42), p < 0.001]. There was a trend toward poorer tolerance among patients living alone [OR = 2.26; 95% CI (0.76-6.72); p = 0.14]. CONCLUSIONS: In older patients taking ICB for solid cancers, concomitant AP may influence efficacy and concomitant PPI may influence tolerance. Further studies are needed to confirm these results.

Impact of therapeutic strategy on disease-free and overall survival of early-stage cervical cancer: Surgery alone versus preoperative radiation.

BACKGROUND AND OBJECTIVES: There is no international consensus for management of early-stage cervical cancer (ESCC). This study aimed to retrospectively investigate disease-free survival (DFS) and overall survival (OS) in patients with ESCC according to the therapeutic strategy used, surgery alone versus preoperative radiation following by surgery. METHODS: Data were retrospectively collected from 1998 to 2015 using the Gynecological Cancer Registry of the Côte d'Or. The inclusion criteria were FIGO 2018 ≤ IB2; squamous cell carcinoma, adenocarcinoma or adenosquamous type. Survival curves were compared using the log-rank test. RESULTS: One hundred twenty-six patients were included. Median survival was 90 months. There was no significant difference in DFS (HR = 0.91, 95%CI [0.32-2.53], p = 0.858) or in OS between surgery alone versus preoperative radiation following by surgery (HR = 0.97, 95%CI [0.31-2.99], p = 0.961). In the subgroup of patients with stage ≥IB1, there was no significant difference in DFS (HR = 3.26, p = 0.2) or in OS (HR = 3.87, p = 0.2). CONCLUSION: Our study did not identify any difference in survival according to the treatment strategy. Preoperative radiation following by surgery can be an alternative to surgery alone for ESCC.

Impact of complete surgical staging on survival of patients with early-stage (FIGO I or II) ovarian cancer: Data from the Cote d'Or Registry of Gynecological Cancers from 1998 to 2015.

INTRODUCTION: Early-stage ovarian cancer represents 20 to 33% of all ovarian cancers and is thus quite rare in France, with around 1200 new cases per year. No study to date has convincingly demonstrated the utility of lymphadenectomy in early-stage ovarian cancer. We sought to evaluate the impact on overall survival of complete surgical staging in patients management for FIGO stage I and II ovarian cancer. METHODS: We performed a retrospective observational study using data from the Cote d'Or Registry of Gynecological Cancers. We included patients with invasive early stage epithelial ovarian cancer (FIGO stages I and II), diagnosed between 1 January 1998 and 31 December 2015. RESULTS: A total of 179 patients were included in the study. Patients who had lymphadenectomy were younger on average (P<0.001) and had fewer comorbidities (P=0.03). Lymphadenectomy was performed during the first surgery in 59.2% of cases (58 patients) and during a second, re-staging surgery in 40.8% (n=40). When complete surgical staging was performed, the rate of up-staging (to at least FIGO stage III) was 11.2% (11/98). The median follow-up was 8.4 years. At the study, 31.6% patients with complete surgical staging had died and 48.4% patients also died in the group without lymphadenectomy, HR 0.59 CI [0.36-0.97] P<0.04. CONCLUSION: In patients with early-stage ovarian cancer, complete surgical staging appears to yield a benefit in terms of overall survival. In 10 to 15% of cases, it leads to upstaging, with the resultant indication for maintenance therapy, which has also shown a survival benefit.

Quality of life and perceived burden of the primary caregiver of patients aged 70 and over with cancer 5 years after initial treatment.

PURPOSE: Long-term effects of being the primary caregiver of an older patient with cancer are not known. This study aimed to assess health-related quality of life (HRQoL) in primary caregivers of patients aged 70 and older with cancer, 5 years after initial treatment. Secondly, to compare the HRQoL between former primary caregivers whose caregiving relationship had ceased (primary caregiver no longer directly assisting the patient because of patient death or removal to another city or admission to an institution) and current caregivers, and to determine the perceived burden of the primary caregivers. METHODS: Prospective observational study including primary caregivers of patients aged 70 and older with cancer. HRQoL and perceived burden were assessed using the SF-12 and Zarit Burden Interview (ZBI) at baseline and 5 years after initial treatment. RESULTS: Ninety-six caregivers were initially included; at 5 years, 46 caregivers completed the SF-12 and ZBI between June 15 and October 26, 2020. Primary caregiver's HRQoL scores had significantly decreased over time for physical functioning (mean difference = -10, p=0.04), vitality (MD= -10.5, p=0.02), and role emotional (MD= -8.1, p=0.01) dimensions. The comparison at 5 years according to caregiving status showed no difference for all HRQoL dimensions. There was no decrease in perceived burden at 5 years. CONCLUSION: Some dimensions of HRQoL decreased at 5 years with a stable low perceived burden. TRIAL REGISTRATION: NCT04478903.

Real-World Data on Olaparib in Relapsed BRCA-mutated Ovarian Cancer: A Multicenter GINECO RETROLA Cohort Study.

BACKGROUND/AIM: Olaparib was approved in 2014 by the European Medicines Agency (EMA) as maintenance treatment for patients with breast cancer gene (BRCA)-mutated platinum-sensitive relapsed high-grade epithelial ovarian cancer (EOC) following the results of the Study 19. We present the results of a national real-world study on the effectiveness of olaparib in relapsed BRCA-mutated EOC patients. PATIENTS AND METHODS: Patients with EOC, peritoneal, and/or fallopian-tube cancer treated with olaparib in a French Center between May 2014 and March 2017 were included. The primary end-point of the study was progression-free survival. RESULTS: Of the 128 patients analyzed, 89 were treated according to the EMA label. The median progression-free survival was 17.0 months. The most common treatment-related toxicity was fatigue. Treatment-related myelodysplastic syndrome (n=5) and a second cancer (n=1) were diagnosed. CONCLUSION: In this real-life setting, olaparib confirmed its efficacy and safety profile, as previously shown in clinical trials.

Adherence to oral anti-cancer therapies in older patients is similar to that of younger patients.

INTRODUCTION: The use of oral anti-cancer therapies is becoming increasingly common in the management of cancers, raising the question of adherence. The objective of this study was to assess adherence to oral anti-cancer therapies, as well as the impact of various factors that may influence it. METHODS: Patients starting oral chemotherapy (tyrosine kinase inhibitor or cytotoxic) were followed up for 3 months using a medication diary, which was given to the patient by the pharmacist during a multidisciplinary consultation. Adherence was assessed using the diary, as well as by counting the tablets they brought back. RESULTS: One hundred and fifty patients were included in the study. The main oral chemotherapy agents prescribed were palbociclib (23.3%), everolimus (18.7%), and capecitabine (13.3%). The adherence at the end of the 3 months, by means of dose intensity (i.e. percent of the dose prescribed that has been taken), was 95.5%. No significant difference in adherence was found based on age, sex, family circumstances, health status, co-medication, type of oral therapy, tumor location, number of previous treatment lines, or presence of toxicity. The main reasons for non-adherence were forgetting (50%) and toxicity (21%). Fifty-seven patients prematurely discontinued the study: 40.3% for toxicity and 36.8% for disease progression. CONCLUSION: Adherence in this study is high in comparison to literature, which can be explained by close multidisciplinary follow-up. Moreover, no significant difference was observed between younger and older patients.

Preliminary tolerance analysis of adjuvant chemotherapy in older patients after resection of stage III colon cancer from the PRODIGE 34-FFCD randomized trial.

BACKGROUND: Colon adenocarcinoma mainly occurs in older patients. Oxaliplatin-based adjuvant chemotherapy improved disease-free survival after stage III colon cancer resection, but this improvement was not demonstrated in older patients. METHODS: The purpose of ADAGE-PRODIGE 34, randomized open phase III trial is to compare in patients over 70 years oxaliplatin plus fluoropyrimidine with fluoropyrimidine alone in fit patients (Group 1) and fluoropyrimidine with observation in frail patients (Group 2) after resection of stage III colon adenocarcinoma. We report a preliminary tolerance analysis on 50% of the first patients enrolled. RESULTS: The analysis was conducted on 491 patients (378 in Group 1 and 113 in Group 2). Patients in Group 2 were older and showed more frailty criteria than those in Group 1. Cumulative grade 3-5 toxicities were more frequent in patients treated with oxaliplatin in Group 1 or with fluoropyrimidine in Group 2 than in patients treated with fluoropyrimidine in Group 1. At least one course was deferred in more than half of the patients in all groups. Early treatment cessation was more frequent in Group 2. CONCLUSION: No safety concerns were raised for the continuation of accrual. The frailty criteria distribution suggests that the investigator's evaluation for group allocation was accurate.

Paclitaxel with or without pazopanib for ovarian cancer relapsing during bevacizumab maintenance therapy: The GINECO randomized phase II TAPAZ study.

BACKGROUND: Anti-angiogenic rechallenge with bevacizumab plus chemotherapy is effective in recurrent ovarian cancer (rOC); however, data are limited on tyrosine kinase inhibitors after progression on maintenance bevacizumab. METHODS: In the randomized phase II TAPAZ trial, patients with rOC during the first year of bevacizumab maintenance therapy were assigned 2:1 to either weekly paclitaxel 65 mg/m2 plus pazopanib 600-800 mg daily or standard weekly paclitaxel 80 mg/m2. The primary endpoint was 4-month progression-free survival (PFS) rate. RESULTS: Overall, 116 patients were randomized and treated: 79 with combination therapy and 37 with single-agent paclitaxel. Median follow-up was 13.1 months. There was no difference between treatment arms in 4-month PFS rate (61% [95% CI, 51-73%] with the combination versus 68% [95% CI, 54-85%] with paclitaxel alone), median PFS (4.9 [95% CI, 4.1-6.1] versus 5.8 [95% CI, 4.8-7.4] months, respectively) or median overall survival (13.6 versus 12.9 months, respectively). The combination was associated with more grade 3/4 toxicities (87% versus 70%, respectively) and toxicity-related paclitaxel discontinuations (22% versus 11%). Pazopanib was discontinued for toxicity in 44% of patients, most commonly for gastrointestinal and vascular events. There were two treatment-related deaths, both in the combination arm (pulmonary embolism and gastrointestinal perforation). At month 4, patient-reported outcomes deteriorated from baseline in the combination arm, particularly for abdominal/gastrointestinal symptoms, which showed a clinically important difference versus paclitaxel alone. CONCLUSIONS: In rOC progressing during maintenance bevacizumab, adding pazopanib to paclitaxel did not improve efficacy, increased toxicity, and compromised chemotherapy delivery. CLINICALTRIALS: govregistration:NCT02383251.

Management and Outcomes of Pancreatic Cancer in French Real-World Clinical Practice.

Background: Our objective was to describe real-world patterns of care and outcomes in pancreatic cancer. Methods: 912 patients diagnosed with pancreatic cancer from 2014 to 2017 were registered by the population-based cancer registry of Burgundy (France). Progression-free and net survival were estimated. Results: at diagnosis, 52% of tumors were associated with metastases. Among the 20% of patients fulfilling resectability criteria, half of those aged 75−84 years and none of those ≥85 years actually underwent resection. Age was not associated with 3-year observed survival in patients who underwent resection. Overall, 77% of patients aged <75 years, 55% of those aged 75−84 years and 8% of those ≥85 years received chemotherapy. Among patients who were offered chemotherapy, 73% of those aged ≥85 years refused. Chemotherapy toxicity was higher with Gemcitabine_Oxaliplatin/Gemcitabine_Abraxane and FOLFIRINOX than with Gemcitabine alone. Patients resected after induction FOLFIRINOX and those treated with adjuvant Gemcitabine presented the lowest risk of progression. Three-year net survival was 35% in patients with non-metastatic resectable tumors and under 10% for other patients. Conclusions: Only half of patients aged 75−84 years with a resectable tumor actually underwent resection. Two thirds of patients aged ≥85 years refused chemotherapy, thus underlining the need to expand geriatric assessments.

Cervical cancer in older women: Does age matter?

OBJECTIVES: Cervical cancer is frequently diagnosed in older women, but few studies have focused on cervical cancer in this specific population. The objectives of this study were to provide an overview of the demographic profile and therapeutic care of women with cervical cancer, and to identify whether age is a prognostic factor. STUDY DESIGN: Retrospective population-based study from a gynecological cancer registry in a French Regional University Hospital and Comprehensive Cancer Center. 292 women diagnosed with cervical cancer between January 1, 2005, and December 31, 2015, were included. They were classified into younger women (YW), that is, under 70 years of age (N = 228), and older women (OW), that is, aged 70 years or more (N = 64). MAIN OUTCOME MEASURES: The primary outcome was overall survival (OS). Cox proportional hazards models were developed to assess the impact of age on OS. RESULTS: Compared with YW, larger proportions of OW had comorbidities (14% vs 7% with a score ≥ 2 on the Charlson Comorbidity Index, P <0.001) and more advanced tumors (37.3% vs 19.7% with FIGO IV, P <0.001); the OW group had a lower treatment rate (81.3% vs 95.6%, P <0.001), and a smaller proportion had undergone surgery (37.5% vs 81.7%, P<.001) but a larger proportion had radiotherapy (67.2% vs 49.6%, P = .01). One-year, 5-year and 10-year OS rates were: 91.6%, 74.1% and 63.9% for YW, and 69.9%, 36.4% and 12.3% for OW, respectively (P <0.001). The hazard ratio for death was twice as high in OW compared with YW with cervical cancer (HR = 2.19 [1.41 - 3.40], P <0.001), independently of FIGO stage, histology, and comorbidities. CONCLUSIONS: The prognosis for cervical cancer depends on age. Screening with the G8 tool followed by a comprehensive geriatric assessment could lead to more suitable treatment being offered to older patients.

Association of Anti-EGFR Antibody and MEK Inhibitor in Gynecological Cancer Harboring RAS Mutation: A Case Series.

Low-grade serous carcinoma represents a minority of serous carcinoma. Although they have better prognosis than high-grade serous carcinoma, they respond poorly to chemotherapy. Thus, it appears necessary to find other treatments such as targeted therapies. Since RAS or RAF mutations occur frequently in low-grade serous carcinoma and lead to constitutively activated MAPK cascade, MEK inhibition should be effective in the treatment of low-grade serous carcinoma. So, we wanted to evaluate the clinical benefit of MEK inhibitors in the management of advanced-stage low-grade serous carcinoma harboring KRAS or NRAS mutation. We report a case series of three women with advanced-stage low-grade serous carcinoma harboring RAS mutation who had stabilization of their disease during several months under targeted therapy combining anti-EGFR antibody and MEK inhibitor. We performed in vitro experiments, confirming the effectiveness of MEK inhibitor on the KRAS-mutated OVCAR-5 cell line, and the constitutively activation of MAPK cascade in RAS-mutated carcinoma. However, it seems that the anti-EGFR antibody does not provide any additional benefit. After whole exome analysis is carried out on the patient with the shortest response, we observed the appearance of RB1 loss-of-function mutation that could be a mechanism of resistance to MEK inhibitors in RAS- of RAF-mutated cancers. The MEK inhibitor is effective in the advanced stages of low-grade serous carcinoma harboring RAS mutation with acceptable tolerance. RB1 loss could be a mechanism of resistance to MEK inhibitors in RAS-mutated low-grade serous carcinoma.

Parallel evolution and differences in seroprevalence of SARS-CoV-2 antibody between patients with cancer and health care workers in a tertiary cancer centre during the first and second wave of COVID-19 pandemic: canSEROcov-II cross-sectional study.

BACKGROUND: Patients with cancer are a population at high risk of severe infection from SARS-CoV-2. Patients with cancer regularly attend specialised healthcare centres for management and treatment, where they are in contact with healthcare workers (HCWs). Numerous recommendations target both patients with cancer and HCWs to minimise the spread of SARS-CoV-2 during these interactions. OBJECTIVE: To investigate the parallel evolution of the COVID-19 epidemic in these 2 populations over time, we studied the seroprevalence of anti-SARS-CoV-2 antibodies after both the first and second waves of the pandemic, and in both cancer patients and HCWs from a single specialised anti-cancer centre. Factors associated with seropositivity were identified in both populations. METHODS: We conducted a cross-sectional study after the second wave of the COVID pandemic in France. All participants were invited to undergo serological testing for SARS-CoV-2 and complete a questionnaire collecting data about their working conditions (for HCWs) or medical management (for patients) during this period. Results after the second wave were compared to those of a previous study among 1011 patients with cancer and 663 HCWs performed in the same centre after the first wave, using the same evaluations. FINDINGS: We included 502 HCWs and 507 patients with cancer. Seroprevalence of anti-SARS-CoV-2 antibodies was higher after the second wave than after the first wave in both HCWs (15.1% versus 1.8%; p < 0.001), and patients (4.1% versus 1.7%; p = 0.038). By multivariate analysis, the factors found to be associated with seropositivity after the second wave for HCWs were: working in direct patient care (p = 0.050); having worked in a dedicated COVID-19 unit (p = 0.0036); contact with a person with COVID-19-positive in the workplace (p = 0.0118) or outside of the workplace (p = 0.0297). Among patients with cancer, only a contact with someone who tested positive for COVID-19 was found to be significantly associated with positive serology. The proportion of reported contacts with individuals with COVID-19-positive was significantly lower among patients with cancer than among HCWs (7.6% versus 40.7%, respectively; p < 0.0001) INTERPRETATION: Between the first and second waves of the epidemic in France, the seroprevalence of anti-SARS-CoV-2 antibodies increased to a lesser extent among patients with cancer than among their HCWs, possibly due to better self-protection, notably social distancing. The risk factors for infection identified among HCWs plead in favour of numerous intra-hospital contaminations, especially for HCWs in contact with high-risk patients. This underlines the compelling need to pursue efforts to implement strict hygiene and personal protection measures (including vaccination) to protect HCWs and patients with cancer.