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The number of robotic-assisted procedures for rectal cancer is rising. The risk of this procedure when performed by surgeon with limited robotic experience is unknown and the precise duration of the learning curve debated. We, therefore, aimed to analyze the learning curve and its related safety in a single center before the development of mentoring programs. We prospectively recorded all robotic procedures performed for colorectal cancer between 2015 and 2020 by a single surgeon. Operative times for partial and total proctectomy were analyzed. The learning curve was defined by comparison with the standard duration of the laparoscopic procedure performed in expert centers (published in GRECCAR 5 and GRECCAR 6 trials) and calculated using a cumulative summation for learning curve test (LC-CUSUM). Among the 174 patients operated for colorectal cancer, we analyzed the outcomes of the 89 patients operated by partial and total robotic proctectomy. To reach repeatedly the same surgical duration as laparoscopic procedure for partial or complete proctectomy, the LC-CUSUM identified a learning curve of 57 patients. A severe morbidity in this population, defined by Clavien–Dindo classification ≥ 3, was observed in 15 cases (16.8%) with an anastomotic leak rate of 13.5%. The rate of completeness of mesorectal excision was 90% and the mean number of harvested lymph nodes was 15 (± 9). Using operative time as end-point, the learning curve of rectal cancer robotic surgery identified a cut-off of 57 patients. The technic remained safe with acceptable morbidity and oncological outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Currently, methods including endoscopy, radiology, and carcinoembryonic antigen levels allow for the detection of colorectal cancer (CRC) at an early stage and the ability to follow the evolution of the disease during treatment. However, these are not always sensitive and specific enough for timely intervention. This leads, amongst other consequences, to delays in treatment or even to overtreatment. Circulating tumor DNA (ctDNA) has shown promise in filling this gap, allowing treatment to be personalized at each stage of the disease and, thus, tailored to each patient's needs. This review article focuses on the current clinical use and future direction of ctDNA for CRC management. Colorectal cancer (CRC) is the third most common cancer type worldwide, with over 1.9 million new cases and 935,000 related deaths in 2020. Within the next decade, the incidence of CRC is estimated to increase by 60% and the mortality by 80%. One of the underlying causes of poor prognosis is late detection, with 60 to 70% of the diagnoses occurring at advanced stages. Circulating cell-free DNA (ccfDNA) is probably the most promising tool for screening, diagnosis, prediction of therapeutic response, and prognosis. More specifically, the analysis of the tumor fraction within the ccfDNA (circulating tumor DNA, ctDNA) has great potential to improve the management of CRC. The present review provides an up-to-date and comprehensive overview of the various aspects related to ctDNA detection in CRC. [ABSTRACT FROM AUTHOR]

Simple Summary: The main prognostic factors of localized/locally advanced anal squamous cell carcinoma (ASCC) are insufficient to predict 10–20% of metastatic relapses. Fusobacterium nucleatum is among the most studied bacteria in digestive tract cancers and has been described as a poor prognostic factor in several digestive cancers. We retrospectively analyzed surgical samples from a homogeneous multicenter cohort of 166 patients with ASCC who underwent abdominoperineal resection. This study showed that F. nucleatum was an independent predictor of favorable overall survival and disease-free survival. This allowed the identification of a patient subgroup with a good prognosis (upper tercile). Our current work strengthens the new insight into the prognostic role of intratumoral F. nucleatum in cancer patients. Validation of these findings would allow to guide therapeutic strategies in dedicated trials by proposing intensification or de-escalation of systemic treatments and follow-up according to F. nucleatum loads. Main prognostic factors of anal squamous cell carcinoma (ASCC) are tumor size, differentiation, lymph node involvement, and male gender. However, they are insufficient to predict relapses after exclusive radiotherapy (RT) or chemoradiotherapy (CRT). Fusobacterium nucleatum has been associated with poor prognosis in several digestive cancers. In this study, we assessed the association between intratumoral F. nucleatum load and clinico-pathological features, relapse, and survival in patients with ASCC who underwent abdominoperineal resection (APR) after RT/CRT. We retrospectively analyzed surgical samples from a cohort of 166 patients with ASCC who underwent APR. F. nucleatum 16S rRNA gene sequences were quantified using real-time quantitative PCR. We associated F. nucleatum load with classical clinicopathological features, overall survival (OS), disease-free survival (DFS), and metastasis-free survival (MFS) using Cox regression univariate and multivariate analyses. Tumors harboring high loads of F. nucleatum (highest tercile) showed longer OS and DFS (median: not reached vs. 50.1 months, p = 0.01, and median: not reached vs. 18.3 months, p = 0.007, respectively). High F. nucleatum load was a predictor of longer OS (HR = 0.55, p = 0.04) and DFS (HR = 0.50, p = 0.02) in multivariate analysis. High F. nucleatum load is an independent favorable prognostic factor in patients with ASCC who underwent APR. [ABSTRACT FROM AUTHOR]

Objective: To assess the impact of global physician empathy and its three subdimensions (establishing rapport, emotional and cognitive processes) on the severity of postoperative complications in a sample of cancer patients. Methods: We retrospectively analyzed data on 256 patients with esogastric cancer from the French national FREGAT database. Empathy and its subdimensions were assessed using the patient-reported CARE scale and the severity of medical and surgical complications was reported with the Clavien-Dindo classification system. The usual covariates were included in multinomial logistic regression analyses. Results: Physician empathy predicted the odds of reporting major complications. When patients perceived high empathy, they were less likely to report major complications compared to no complications (OR =.95, 95% CI = [.91–.99], p =.029). Among the three dimensions, only "establishing rapport" (OR =.84, 95% CI = [.73–.98], p =.019) and the "emotional process" (OR =.85, 95% CI = [.74–.98], p =.022) predicted major complications. Conclusions: Physician empathy is essential before surgery. Further research is needed to understand the mechanisms associating empathy with health outcomes in cancer. Physicians should be trained to establish good rapport with patients, especially in the preoperative period. [ABSTRACT FROM AUTHOR]

Background: Cellular-cell free-DNA (ccfDNA) is being explored as a diagnostic and prognostic tool for various diseases including cancer. Beyond the evaluation of the ccfDNA mutational status, its fragmentation has been investigated as a potential cancer biomarker in several studies. However, probably due to a lack of standardized procedures dedicated to preanalytical and analytical processing of plasma samples, contradictory results have been published. Methods: ddPCR assays allowing the detection of KRAS wild-type and mutated sequences (KRAS p.G12V, pG12D, and pG13D) were designed to target different fragments sizes. Once validated on fragmented and non-fragmented DNA extracted from cancer cell lines, these assays were used to investigate the influence of the extraction methods on the non-mutated and mutated ccfDNA integrity reflected by the DNA integrity index (DII). The DII was then analyzed in two prospective cohorts of metastatic colorectal cancer patients (RASANC study n = 34; PLACOL study n = 12) and healthy subjects (n = 49). Results and Discussion: Our results demonstrate that ccfDNA is highly fragmented in mCRC patients compared with healthy individuals. These results strongly suggest that the characterization of ccfDNA integrity hold great promise toward the development of a universal biomarker for the follow-up of mCRC patients. Furthermore, they support the importance of standardization of sample handling and processing in such analysis. [ABSTRACT FROM AUTHOR]

Background: This report aims to describe preliminary results concerning secondary resectability after bidirectional chemotherapy for initially unresectable malignant peritoneal mesothelioma (MPM). Methods: Between January 2013 and January 2016, 20 consecutive patients treated for diffuse MPM not suitable for upfront surgery received bidirectional chemotherapy associating intraperitoneal and systemic chemotherapy. Evaluation of the response to chemotherapy was assessed clinically and by laparoscopy. Results: The median peritoneal cancer index (PCI) score at staging laparoscopy was 27 (range 15-39). Altogether, 118 intraperitoneal chemotherapy cycles were administered without any specific adverse catheter-related event. Concerning tolerance, 85% of the patients experienced no pain or mild pain during chemotherapy administration. The clinical response rate was 60% after a median of three chemotherapy cycles. At laparoscopic reevaluation, the median PCI was 18 (range 0-35), and a secondary resectability was considered for 55% of the patients. Complete cytoreduction surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) was finally achieved for 10 patients (50%), with a median intraoperative PCI score of 14 (range 6-30). After a median follow-up period of 18 months, the 2-year overall survival rate was 83.3% for the patients treated by CRS followed by HIPEC and 44% for the patients treated by bidirectional chemotherapy. Conclusion: Bidirectional chemotherapy is a promising, well-tolerated treatment capable of increasing the resection rate for selected patients with diffuse MPM initially considered as unresectable or borderline resectable. For patients with definitively unresectable disease, bidirectional chemotherapy achieves a higher clinical response rate. [ABSTRACT FROM AUTHOR]

The presence of limited and resectable extrahepatic metastases (EHM) in addition to colorectal liver metastases (LM) is no longer a contraindication to surgery. Long-term survival (between 25 and 30 % at 5 years) is possible for highly selected patients. The site of occurrence is a key prognostic factor. Results are best for lung EHM and limited peritoneal metastases (PM), lower when EHM invade the proximal hepatic lymph nodes, and worse for other EHM. Treatment decision making is difficult when faced with an infinite number of possible combinations between the different sites of metastases, their number, and the overall tumor load. General performance status, technical contingency, and chemosensitivity are also important factors to be reckoned with. In the future, a considerable amount of data concerning these patients and new statistical tools will be required to create clear decision trees. [ABSTRACT FROM AUTHOR]

Purpose: The potential impact of different SNPs of VEGF/VEGFR pathway on the clinical outcome of mCRC patients receiving bev-containing regimens has been investigated in retrospective experiences with contrasting results. We previously reported the association of VEGFA rs833061 C/T variants with PFS in metastatic colorectal cancer patients treated with first-line FOLFIRI plus bevacizumab. The primary objective of this work was to prospectively validate that retrospective finding. A confirmatory analysis of other SNPs of VEGF/VEGFR pathway genes was included. Experimental design: To detect a HR for PFS of 1.7 for VEGFA rs833061 T/T compared to C- variants in metastatic colorectal cancer patients treated with first-line FOLFIRI plus bevacizumab, setting two-sided α = 0.05 and β = 0.20, 199 events were required. VEGFA rs699946 A/G, rs699947 A/C, VEGFR1 rs9582036 A/C and rs7993418 A/G, VEGFR2 rs11133360 C/T, rs12505758 C/T and rs2305948 C/T and EPAS1 rs4145836 A/G were also tested. Germ-line DNA was extracted from peripheral blood. SNPs were analyzed by PCR and sequencing. Results: Four-hundred-twenty-four pts were included. At the univariate analysis, no differences according to VEGFA rs833061 C/T variants were observed in PFS (p = 0.38) or OS (p = 0.95). Among analyzed SNPs, only VEGFR2 rs12505758 C- variants, compared to T/T, were associated to shorter PFS (HR: 1.36 [1.05–1.75], p = 0.015, dominant genetic model) and OS, with a trend toward significance (HR: 1.34 [0.95–1.88], p = 0.088). In the multivariate model, this association retained significance (HR: 1.405 [1.082–1.825], p = 0.012) in PFS, that was lost by applying multiple testing correction (p = 0.14). Conclusion: This prospective experience failed to validate the hypothesized predictive impact of VEGFA rs833061 variants. Retrospective findings on different candidate SNPs were not confirmed. Only VEGFR2 rs12505758 variants, whose prognostic and not predictive impact was previously reported, correlated with PFS. Given the complexity of angiogenesis, it is rather unlike that a single germ-line SNP might be a good predictor of benefit from bevacizumab. [ABSTRACT FROM AUTHOR]

The pharmacogenomics field is crucial for optimizing the selection of which chemotherapy regimen to use according to the patient's genomic profile. Indeed, the individual's inherited genome accounts for a large proportion of the variation in his or her response to chemotherapeutic agents both in terms of efficiency and toxicity. Patients with metastatic disease are more likely to receive different lines of chemotherapy with variable efficacy and experience some related complications. It is therefore critical to tailor the best therapeutic arsenal to improve the efficacy and avoid as much as possible related complications that are susceptible to interrupt the treatment. The pharmacogenomics approach investigates for each drug the implicated metabolic pathway and the potential personal variations in gene function. The aim of this review is to present a clear overview of the most accurate polymorphisms that have been identified as related to drug response in patients with mCRC. [ABSTRACT FROM AUTHOR]