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Simple Summary: Colorectal cancer remains a prevalent neoplasm affecting both genders. Despite advancements in screening techniques facilitating early detection, effective patient management remains paramount. This study investigates the impact of a multidisciplinary team (MDT) approach on patient outcomes. Results reveal a significant improvement in survival rates among MDT-followed patients compared to those lacking MDT oversight. Notably, no-MDT patients exhibited a twofold increase in mortality risk from both colon and rectal cancers. Furthermore, advanced age (>70 years) and advanced-stage disease (III and IV) emerged as pivotal risk factors. Consequently, prioritizing MDT intervention for these high-risk cohorts is imperative to optimize therapeutic strategies. Colorectal cancer emerged as the third most prevalent malignancy worldwide, affecting nearly 2 million individuals in the year 2020. This study elucidates the pivotal role of a multidisciplinary team (MDT) in influencing the prognosis, as measured by relative survival rates, depending upon the stage and age. Cases recorded in an Italian Cancer Registry between 2017 and 2018 were included. Relative survival was reported at 1 and 3 years after diagnosis comparing MDT vs. no-MDT approaches. During the study period, 605 CRCs were recorded while 361 (59.7%) were taken care of by an MDT. Compared to no-MDT, MDT patients were younger with earlier stages and received more surgery. One year after diagnosis, survival was 78.7% (90% in MDT vs. 62% in no-MDT); stratifying by stage, in the MDT group there was no survival advantage for stage I (97.2% vs. 89.9%) and II (96.8% vs. 89.4%), but an advantage was observed for stage III (86.4% vs. 56.9%) and stage IV (63.7% vs. 27.4%). Similar values were observed at 3 years where a marked advantage was observed for stages III (69.9% vs. 35.1%) and IV (29.2% vs. 5.1%). The univariable analysis confirmed an excess risk in the no-MDT group (HR 2.6; 95% CI 2.0–3.3), also confirmed in the multivariable regression analysis (HR 2.0; 95% CI 1.5–2.5). Despite the increase in the number of MDT patients in 2018 (from 50% to 69%), this does not correspond to an improvement in outcome. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the association of adipose tissue characteristics with survival in rectal cancer patients. All consecutive patients, diagnosed with stage II–IV rectal cancer between 2010–2016 using baseline unenhanced Computed Tomography (CT), were included. Baseline total, subcutaneous and visceral adipose tissue areas (TAT, SAT, VAT) and densities (TATd, SATd, VATd) at third lumbar vertebra (L3) were retrospectively measured. The association of these tissues with cancer-specific and progression-free survival (CCS, PFS) was assessed by using competitive risk models adjusted by age, sex and stage. Among the 274 included patients (median age 70 years, 41.2% females), the protective effect of increasing adipose tissue area on survival could be due to random fluctuations (e.g., sub-distribution hazard ratio—SHR for one cm2 increase in SAT = 0.997; 95%confidence interval—CI = 0.994–1.000; p = 0.057, for CSS), while increasing density was associated with poorer survival (e.g., SHR for one Hounsfield Unit—HU increase in SATd = 1.03, 95% CI = 1.01–1.05, p = 0.002, for CSS). In models considering each adipose tissue area and respective density, the association with CSS tended to disappear for areas, while it did not change for TATd and SATd. No association was found with PFS. In conclusion, adipose tissue density influenced survival in rectal cancer patients, raising awareness on a routinely measurable variable that requires more research efforts. [ABSTRACT FROM AUTHOR]

Genetic alterations in CRC have shown a negative predictive and prognostic role in specific target therapies. The onset of immunotherapy has also undergone remarkable therapeutic innovation, although limited to a small subgroup of patients, the MSI-H/dMMR, which represents only 5% of CRC. Research is moving forward to identify whether other biomarkers can predict response to ICIs, despite various limitations regarding expression and identification methods. For this purpose, TMB, LAG3, and PD-L1 expression have been retrospectively evaluated in several solid tumors establishing the rationale to design clinical trials with concurrent inhibition of LAG3 and PD-1 results in a significant advantage in PFS and OS in advanced melanoma patients. Based on these data, there are clinical trials ongoing in the CRC as well. This review aims to highlight what is already known about genetic mutations and genomic alterations in CRC, their inhibition with targeted therapies and immune checkpoints inhibitors, and new findings useful to future treatment strategies. [ABSTRACT FROM AUTHOR]

The NIVACOR trial is a phase II study assessing the efficacy and safety of nivolumab in combination with FOLFOXIRI/bevacizumab in first-line setting in patients affected by metastatic colorectal cancer (mCRC) RAS/BRAF mutated. We report safety run-in results in the first 10 patients enrolled. Patients received triplet chemotherapy with FOLFOXIRI scheme plus bevacizumab, in association with nivolumab every 2 weeks for 8 cycles (induction phase) followed by bevacizumab plus nivolumab every 2 weeks (maintenance phase), until progression of disease or unacceptable toxicities. The first ten patients were evaluated: 7 experienced at least one adverse event (AE) related to FOLFOXIRI/bevacizumab and 2 related to nivolumab. The most frequent grade 1–2 AEs related to FOLFOXIRI/bevacizumab were diarrhea and fatigue (71%), nausea and vomiting (57%); 3 (43%) had grade 3–4 neutropenia, and 2 (20%) patients developed grade 1–2 AEs nivolumab related: skin rash and salivary gland infection. Two patients delayed the dose because of serious AEs, proteinuria and salivary gland infection; one patient discontinued experimental treatment due to the ileo-urethral fistula and concurrent Clostridium infection diarrhea. No treatment- related death occurred. The safety run-in analysis of NIVACOR trial reassured using co-administration of FOLFOXIRI/bevacizumab and nivolumab was well tolerated with an acceptable toxicity profile. Clinical Trial Registration: https://clinicaltrials.gov/ , (NCT04072198). [ABSTRACT FROM AUTHOR]

Simple Summary: Research suggests that lengthening the prognosis in cancer patients (which is certainly a positive thing) requires greater attention to be paid to the onset of other pathologies. The increase in cardiovascular mortality in cancer patients (due to both exposure to risk factors and the side effects of cytotoxic drugs) requires greater collaboration between oncologists and cardiologists, and the integration of shared follow-up paths. Particular attention to the follow-up of cancer patients can reduce this risk: in the present study, patients presented an excessive risk of cardiovascular mortality only in the first two years from cancer diagnosis. The present research describes 25 years of cardiovascular mortality in a cohort of patients in Northern Italy. The study included patients with malignant cancer enrolled in the period of 1996–2019, and describes cardiovascular and cancer mortality in relation to sex, age, year of diagnosis, months of survivorship, tumor site, and standardized mortality ratio (SMR). Out of 67,173 patients, 38,272 deaths (57.7%) were recorded: 4466 from cardiovascular disease (CVD) (6.6%), and 28,579 (42.6%) from cancer. The proportion of CVD death increased from 4.5% in the first two years after diagnosis, to 7.3% after more than 10 years, while the proportion of deaths from cancer decreased from 70.5% to 9.4%. The CVD SMR comparing cancer patients with the general population was 0.87 (95% CI: 0.82–0.92) in 1996–1999, rising to 0.95 (95% CI: 0.84–1.08) in 2015–2019, without differences in terms of sex or age. The risk of dying from CVD was higher compared with the general population (SMR 1.31; 95% CI: 1.24–1.39) only in the first two years after diagnosis. The trend over time underscored that CVD deaths increased in patients with breast, bladder, prostate, and colorectal cancers, and, in the more recent period, for kidney cancer and melanoma patients. Our data confirmed that cardiovascular mortality is an important issue in the modern management of cancer patients, suggesting the need for an extensive interdisciplinary approach. [ABSTRACT FROM AUTHOR]

The aim of this study is to present the 5-year relative survival by stage of breast and colorectal cancer patients in a northern Italian province. For the period 2013-2015, cases were selected from the Reggio Emilia Cancer Registry. Breast cancer patients were divided into 3 age groups: <45, 45-74 (the target screening population) and 74+. Colorectal cancers patients were classified into <50, 50-69 (the target screening population), and over 69 years. Carcinomas in situ and unknown stage were both excluded from the survival analyses. The five-year relative survival was estimated using the Pohar Perme method. During the period examined, 1,450 breast cancers and 992 colorectal cancer cases were registered. Analyzing in detail the patients with breast cancer for the entire 2013-2015 period, we noted that 50.4% were in stage I, 33.6% in stage II, 10.8% in stage III and 3.8% in stage IV. The stage was unknown in only 1.3% of patients (19 cases). The stage data of patients with colorectal cancer showed 24.5% were in stage I, 26.1% in stage II, 23.4% in stage III, and 24.6% in stage IV, and 1.4% unknown. Breast cancer 5-year survival was 100%, 89.7%, 71.4%, and 29.1% for stages I, II, III and IV, respectively and for colon cancer 96.7%, 83.4%, 70.8% and 16.2%, respectively.The presence of cancer screening, associated with effective treatments, account for the high survival rate of early-stage breast and colon cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mangone, Marinelli, Bisceglia, Braghiroli, Damato and Pinto.)

Analysis of plasma-derived cell-free DNA (cfDNA) might allow for the early identification of resistance in metastatic colorectal carcinoma (mCRC) patients receiving anti-EGFR monoclonal antibodies. We tested plasma samples from the Erbitux Metastatic Colorectal Cancer Strategy (ERMES) phase III trial of FOLFIRI+Cetuximab in first-line treatment of RAS/BRAF wild-type mCRC. Samples were collected at baseline ( n = 37), at 8 weeks of treatment ( n = 32), progressive disease (PD; n = 36) and 3 months after PD ( n = 21). cfDNA testing was performed using the Idylla™ ctKRAS and ctNRAS-BRAF tests and the Oncomine Pan-Cancer Cell-Free Assay. Analysis of basal samples revealed RAS/BRAF mutations in 6/37 cases. A transient RAS positivity not associated with PD was observed at 8 weeks in five cases that showed no mutations at baseline and PD. The frequency of mutant cases increased at PD (33.3%) and decreased again at 3 months after PD (9.5%). The median progression-free survival (mPFS) of patients RAS/BRAF mutant at PD was 7.13 months versus 7.71 months in wild-type patients ( p = 0.3892). These data confirm that the occurrence of RAS/BRAF mutations in mCRC patients receiving anti-EGFR agents is relatively frequent. However, the cfDNA dynamics of RAS mutations in patients treated with anti-EGFR agents plus polychemotherapy are complex and might not be directly associated with resistance to treatment.