Impact of molecular testing on the surgical management of advanced epithelial ovarian cancer.

Ovarian carcinoma remains the most lethal gynaecologic malignancy. Half of all high-grade serous ovarian cancers (HGSOCs) have a homologous recombination deficiency (HRD) with regard to the repair of double-strand DNA breaks and are candidate to receive maintenance treatment with PARP inhibitors. While a wealth of literature exists regarding the therapeutic guidance of patients from a medical standpoint, the influence of the HRD status on the surgical outlook has been comparatively limited. In this review, the clinical and biological features of advanced ovarian cancers with BRCA1/2 mutation and/or HRD status are considered with particular reference to their impact on the surgical management and on the medico-surgical sequence. The modification of the surgical indications according to the results of molecular testing in first-line and recurrent settings are discussed.

Metabolomic prediction of breast cancer treatment induced neurological and metabolic toxicities.

BACKGROUND: Long-term treatment-related toxicities, such as neurological and metabolic toxicities, are major issues in breast cancer. We investigated the interest of metabolomic profiling to predict toxicities. METHODS: Untargeted high-resolution metabolomic profiles of 992 patients with ER+/HER2- breast cancer from the prospective CANTO cohort were acquired (n=1935 metabolites). A residual-based modeling strategy with a discovery and validation cohort was used to benchmark machine learning algorithms, taking into account confounding variables. RESULTS: Adaptive LASSO has a good predictive performance, has limited optimism bias, and allows the selection of metabolites of interest for future translational research. The addition of low-frequency metabolites and non-annotated metabolites increases the predictive power. Metabolomics adds extra performance to clinical variables to predict various neurological and metabolic toxicity profiles. CONCLUSIONS: Untargeted high-resolution metabolomics allows better toxicity prediction by considering environmental exposure, metabolites linked to microbiota, and low-frequency metabolites.

Magnitude and Temporal Variations of Socioeconomic Inequalities in the Quality of Life After Early Breast Cancer: Results From the Multicentric French CANTO Cohort.

PURPOSE: Socioeconomic status (SES) influences the survival outcomes of patients with early breast cancer (EBC). However, limited research investigates social inequalities in their quality of life (QoL). This study examines the socioeconomic inequalities in QoL after an EBC diagnosis and their time trends. PATIENTS AND METHODS: We used data from the French prospective multicentric CANTO cohort (ClinicalTrials.gov identifier: NCT01993498), including women with EBC enrolled between 2012 and 2018. QoL was assessed using the European Organisation for Research and Treatment of Cancer QoL Core 30 questionnaire (QLQ-C30). summary score at diagnosis and 1 and 2 years postdiagnosis. We considered three indicators of SES separately: self-reported financial difficulties, household income, and educational level. We first analyzed the trajectories of the QLQ-C30 summary score by SES group. Then, social inequalities in QLQ-C30 summary score and their time trends were quantified using the regression-based slope index of inequality (SII), representing the absolute change in the outcome along socioeconomic gradient extremes. The analyses were adjusted for age at diagnosis, Charlson Comorbidity Index, disease stage, and type of local and systemic treatment. RESULTS: Among the 5,915 included patients with data on QoL at diagnosis and at the 2-year follow-up, social inequalities in QLQ-C30 summary score at baseline were statistically significant for all SES indicators (SIIfinancial difficulties = -7.6 [-8.9; -6.2], SIIincome = -4.0 [-5.2; -2.8]), SIIeducation = -1.9 [-3.1; -0.7]). These inequalities significantly increased (interaction P < .05) in year 1 and year 2 postdiagnosis, irrespective of prediagnosis health, tumor characteristics, and treatment. Similar results were observed in subgroups defined by menopausal status and type of adjuvant systemic treatment. CONCLUSION: The magnitude of preexisting inequalities in QoL increased over time after EBC diagnosis, emphasizing the importance of considering social determinants of health during comprehensive cancer care planning.

SafeHeal Colovac Colorectal Anastomosis Protection Device evaluation (SAFE-2) pivotal study: an international randomized controlled study to evaluate the safety and effectiveness of the Colovac Colorectal Anastomosis Protection Device.

AIM: Although proximal faecal diversion is standard of care to protect patients with high-risk colorectal anastomoses against septic complications of anastomotic leakage, it is associated with significant morbidity. The Colovac device (CD) is an intraluminal bypass device intended to avoid stoma creation in patients undergoing low anterior resection. A preliminary study (SAFE-1) completed in three European centres demonstrated 100% protection of colorectal anastomoses in 15 patients, as evidenced by the absence of faeces below the CD. This phase III trial (SAFE-2) aims to evaluate the safety and effectiveness of the CD in a larger cohort of patients undergoing curative rectal cancer resection. METHODS: SAFE-2 is a pivotal, multicentre, prospective, open-label, randomized, controlled trial. Patients will be randomized in a 1:1 ratio to either the CD arm or the diverting loop ileostomy arm, with a recruitment target of 342 patients. The co-primary endpoints are the occurrence of major postoperative complications within 12 months of index surgery and the effectiveness of the CD in reducing stoma creation rates. Data regarding quality of life and patient's acceptance and tolerance of the device will be collected. DISCUSSION: SAFE-2 is a multicentre randomized, control trial assessing the efficacy and the safety of the CD in protecting low colorectal anastomoses created during oncological resection relative to standard diverting loop ileostomy. TRIAL REGISTRATION: NCT05010850.

Robotic beyond total mesorectal excision for locally advanced rectal cancers: Perioperative and oncological outcomes from a multicentre case series.

BACKGROUND: Around 20% of rectal tumors are locally advanced with invasion into adjacent structures at presentation. These may require surgical resections beyond boundaries of total mesorectal excision (bTME) for radicality. Robotic bTME is under investigation. This study reports perioperative and oncological outcomes of robotic bTME for locally advanced rectal cancers. MATERIALS AND METHODS: A multicentre, retrospective analysis of prospectively collected robotic bTME resections (July 2015-November 2020). Demographics, clinicopathological features, short-term outcomes, recurrences, and survival were investigated. RESULTS: One-hundred-sixty-eight patients (eight centres) were included. Median age and BMI were 60.0 (50.0-68.7) years and 24.0 (24.4-27.7) kg/m2. Female sex was prevalent (n = 95, 56.8%). Fifty patients (29.6%) were ASA III-IV. Neoadjuvant chemoradiotherapy was given to 125 (74.4%) patients. Median operative time was 314.0 (260.0-450.0) minutes. Median estimated blood loss was 150.0 (27.5-500.0) ml. Conversion to laparotomy was seen in 4.8%. Postoperative complications occurred in 77 (45.8%) patients; 27.3% and 3.9% were Clavien-Dindo III and IV, respectively. Thirty-day mortality was 1.2% (n = 2). R0 rate was 92.9%. Adjuvant chemotherapy was offered to 72 (42.9%) patients. Median follow-up was 34.0 (10.0-65.7) months. Distant and local recurrences were seen in 35 (20.8%) and 15 patients (8.9%), respectively. Overall survival (OS) at 1, 3, and 5-years was 91.7, 82.1, and 76.8%. Disease-free survival (DFS) at 1, 3, and 5-years was 84.0, 74.5, and 69.2%. CONCLUSION: Robotic bTME is technically safe with relatively low conversion rate, good OS, and acceptable DFS in the hands of experienced surgeons in high volume centres. In selected cases robotic approach allows for high R0 rates during bTME.