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BackgroundColorectal cancer (CRC) patients have a better prognosis if metastases are resectable. Initially, unresectable liver-only metastases can be converted to resectable with chemotherapy plus a targeted therapy. We assessed which of chemotherapy doublet (2-CTx) or triplet (3-CTx), combined with targeted therapy by RAS status, would be better in this setting.MethodsPRODIGE 14 was an open-label, multicenter, randomised Phase 2 trial. CRC patients with initially defined unresectable liver-only metastases received either, 2-CTx (FOLFOX or FOLFIRI) or 3-CTx (FOLFIRINOX), plus bevacizumab/cetuximab by RAS status. The primary endpoint was to increase the R0/R1 liver-resection rate from 50 to 70% with the 3-CTx.ResultsPatients (n = 256) were mainly men with an ECOG PS of 0, and a median age of 60 years. In total, 109 patients (42.6%) had RAS-mutated tumours. After a median follow-up of 45.6 months, the R0/R1 liver-resection rate was 56.9% (95% CI: 48–66) with the 3-CTx versus 48.4% (95% CI: 39–57) with the 2-CTx (P = 0.17). Median overall survival was 43.4 months with 3-CTx versus 40 months with 2-CTx.ConclusionWe failed to increase from 50 to 70% the R0/R1 liver-resection rate with the use of 3-CTx combined with bevacizumab or cetuximab by RAS status in CRC patients with initially unresectable liver metastases.

Background Splenic flexure adenocarcinoma poses unique challenges in surgical management due to its location and lymphatic drainage. This study compared the efficacy and oncological safety of extended right hemicolectomy (ERC) and left colectomy (LC) for treating this condition. Methods This study followed the PRISMA and AMSTAR 2 guidelines. Key outcomes included postoperative mortality, morbidity, severe complications, operative results, pathological findings (R0 resection, lymph nodes), and oncological results (overall survival and disease-free survival at 3 and 5 years). Results Twelve non-randomised studies were included involving 1710 patients (713 ERC group, 997 LC group). The analysis showed that ERC was associated with more lymph nodes and a lower conversion rate. However, there were no significant differences between ERC and LC in terms of mortality, morbidity, severe complications, anastomotic leak, wound infection, ileus, reoperation, R0 resection, hospital stay, and overall and disease-free survival rates. Conclusions ERC and LC are comparable in terms of postoperative and long-term oncological outcomes for splenic flexure adenocarcinoma, with ERC potentially producing a higher lymph node harvest rate and a lower conversion rate. ERC could be suggested for a better stage of the disease and when the surgical team considers the laparoscopic approach.

Background: Recurrent acute pancreatitis (RAP) of alcoholic etiology is a major risk factor for chronic pancreatitis (CP). Early chronic pancreatitis (ECP) represents an intermediate stage where structural changes can be identified before advanced disease develops. The 2019 Japanese Pancreas Society (JPS) imaging criterion, defined as >3 dilated side branches on magnetic resonance imaging (MRI), provides a standardized approach for early diagnosis. Objective: To assess the prevalence of MRI-positive findings per JPS imaging criterion in patients with alcohol-related RAP and to identify clinical predictors of progression. Methods: We retrospectively analyzed 26 patients with alcohol-related RAP admitted between January 2023 and December 2024. All underwent MRI 4–8 weeks post-discharge. Patients were classified as MRI-positive or nonMRI-positive per JPS imaging criterion. Clinical, biochemical, and imaging parameters were compared using univariate and multivariate analyses. Results: Nine of twenty-six patients (34.6%) were MRI-positive per JPS imaging criterion. These patients had a significantly higher number of RAP episodes (p = 0.021). Disease duration also differed between groups (p = 0.034). No significant differences were observed in computer tomography severity scores or biochemical markers. In multivariate analysis, only the number of RAP episodes was associated with MRI-positive status (OR 4.00, 95% CI 0.79–20.3, p = 0.09). Conclusions: MRI-positive findings per JPS imaging criterion were present in one-third of alcohol-related RAP patients. Having ≥3 RAP episodes was the most consistent risk factor for structural progression. Systematic MRI during the inter-critical phase may allow early identification of high-risk patients and inform closer surveillance.

Introduction Bevacizumab, an angiogenesis inhibitor, is commonly used alongside chemotherapy for metastatic colorectal cancer (mCCR). While inducing necrosis in tumours, bevacizumab may also lead to atrophy in tumour-free organs. Artificial intelligence (AI) models offer user-friendly methods for measuring organ volumes. This study explores the relationship between bevacizumab-induced atrophy using AI-assisted volume measurement in tumour-free organs and treatment efficacy. Methods This multicenter retrospective study includes patients from the PRODIGE 9 and PRODIGE 20 trials. Organ atrophy was assessed by evaluating volume changes from diagnosis to two months after treatment initiation in patients receiving bevacizumab compared to those who did not. Statistical analyses were performed using the Wilcoxon test, with correlations between volumetric changes. Overall and progression-free survival were assessed using log-rank tests and Cox regression models. Results Among the 214 patients included, 192 received bevacizumab. Both liver and spleen volumes were measured using a deep learning-based AI model and manual measurements. AI-generated volume measurements showed a strong correlation with manual measurements (Pearson coefficient > 0.8). Bevacizumab-treated patients exhibited significant atrophy of non-tumoural liver volume ( p  = 0.0378), while no significant changes were observed in tumour or spleen volumes in either group. Survival analyses revealed that patients with a smaller decrease in non-tumoural liver volume had improved overall survival ( p  = 0.016), although this association became non-significant after adjusting for age, sex, and tumour volume at diagnosis ( p  = 0.25). Conclusion Our findings support the feasibility and reliability of AI in organ volume measurement. While bevacizumab exposure was linked to non-tumoural liver atrophy, its impact on survival remains inconclusive after adjustment. These results pave the way for further research into bevacizumab-induced organ atrophy and the potential of AI in personalizing oncology treatments.

In a prospective, randomized trial involving patients with resected pancreatic cancer, adjuvant combination chemotherapy with FOLFIRINOX resulted in a median disease-free survival of 21.6 months, as compared with 12.8 months with gemcitabine therapy. Overall survival was also longer with FOLFIRINOX.

The management of patients with colorectal cancer (CRC) and potentially resectable liver metastases (LM) requires quick assessment of mutational status and of response to pre-operative systemic therapy. In a prospective phase II trial (NCT01442935), we investigated the clinical validity of circulating tumor cell (CTC) and circulating tumor DNA (ctDNA) detection. CRC patients with potentially resectable LM were treated with first-line triplet or doublet chemotherapy combined with targeted therapy. CTC (Cellsearch®) and Kirsten RAt Sarcoma (KRAS) ctDNA (droplet digital polymerase chain reaction (PCR)) levels were assessed at inclusion, after 4 weeks of therapy and before LM surgery. 153 patients were enrolled. The proportion of patients with high CTC counts (≥3 CTC/7.5mL) decreased during therapy: 19% (25/132) at baseline, 3% (3/108) at week 4 and 0/57 before surgery. ctDNA detection sensitivity at baseline was 91% (N=42/46) and also decreased during treatment. Interestingly, persistently detectable KRAS ctDNA (p = 0.01) at 4 weeks was associated with a lower R0/R1 LM resection rate. Among patients who had a R0/R1 LM resection, those with detectable ctDNA levels before liver surgery had a shorter overall survival (p < 0.001). In CRC patients with limited metastatic spread, ctDNA could be used as liquid biopsy tool. Therefore, ctDNA detection could help to select patients eligible for LM resection.

Fluropyrimidine monotherapy is an option for some patients with inoperable metastatic colorectal cancer. Unlike bevacizumab, the addition of aflibercept, an antibody acting as an anti-angiogenic agent, has never been evaluated in this context. The aim of the study was to determine whether aflibercept could increase the efficacy of fluoropyrimidine monotherapy without increasing toxicity. This multicenter phase II non-comparative trial evaluated the addition of aflibercept to infusional 5-fluorouracil/folinic acid (LV5FU2 regimen) as first-line treatment in patients unfit to receive doublet cytotoxic chemotherapy. The primary endpoint was 6-month progression-free survival (PFS). The clinical hypotheses expected a PFS rate at 6 months of over 40% (60% expected). A total of 117 patients, with a median age of 81 years, were included: 59 in arm A (LV5FU2-aflibercept) and 58 in arm B (LV5FU2 alone). Six-month PFS was 54.7% in both arms (90% CI 42.5–66.5 in both). Median overall survival was 21.8 months (arm A) and 25.1 months (arm B). Overall toxicity was more common in arm A: grade ≥ 3 toxicity in 82% versus 58.2%. Given the 6-month PFS, the study can be considered positive. However, the toxicity of aflibercept in this population was high, and continuation of the trial into phase III is not envisaged.

Abstract Background Second-line FOLFOX-bevacizumab treatment is effective in metastatic colorectal cancer (mCRC) treatment after irinotecan-based chemotherapy failure. First- or second-line raltitrexed-oxaliplatin (TOMOX) treatment has an acceptable toxicity profile in mCRC. The aim of this study was to evaluate TOMOX-bevacizumab combination as a second-line treatment. Methods The BEVATOMOX study was a non-comparative, prospective, randomized, open-label, multicentric phase II trial. Patients with histologically proven unresectable mCRC and progressive metastatic disease after irinotecan-based chemotherapy were randomized (1:2) to receive mFOLFOX6-bevacizumab (control arm, bevacizumab 5 mg/kg, mFOLFOX6 D1 = D15, 12 cycles) or TOMOX-bevacizumab (experimental arm, bevacizumab 7.5 mg/kg, raltitrexed 3 mg/m2 based on creatinine clearance, oxaliplatin 130 mg/m2, D1 = D21, 8 cycles). The primary endpoint was 6-month progression-free survival (6PFS). Target enrollment was 30 and 62 patients in the control and experimental arms, respectively. Results Eighty-three patients (median age 66 [48-82] years, 63.9% male, 54.2% KRAS mt) were included: 33 in the control and 50 in the experimental arms. The 6PFS rate and median overall survival were 51.5 (95% CI, 36-67) and 11.1 months (9.5-16.4) in the control arm vs 38 (95% CI, 26-51) and 9.3 (5.7-11.6) months in the experimental arm. In the experimental arm, left-sided tumors had a longer overall survival vs right-sided (11.6 vs 4.6 months, P < .001). Grade 3-4 toxicities (mucositis, neutropenia, febrile neutropenia, paresthesia, hand-foot syndrome) were similar between arms. Conclusion The TOMOX-Bev combination is a feasible second-line mCRC treatment with an acceptable toxicity profile. Recruitment failure prevents efficacy conclusions, but TOMOX-Bev may be an alternative if fluropyrimidines are contraindicated. Trial registration number ClinicalTrials.gov, NCT01532804.

In this study, a four-drug combination chemotherapy regimen was associated with objective responses in more than 30% of patients and increased survival by more than 4 months, as compared with standard gemcitabine. Pancreatic adenocarcinoma was the fourth leading cause of death from cancer in the United States in 2010, 1 and it carries a grim prognosis: the 5-year survival rate is 6% in Europe and the United States. 1 , 2 Gemcitabine became the reference regimen for advanced pancreatic cancer after a randomized trial showed significant improvement in the median overall survival as compared with fluorouracil administered as an intravenous bolus (5.6 vs. 4.4 months, P=0.002). 3 In the subsequent phase 3 trials of single-agent gemcitabine, 4 the median overall survival ranged from 5.0 to 7.2 months. The combination of gemcitabine with a variety of cytotoxic and . . .

The COVID-19 pandemic has been associated with substantial reduction in screening, case identification, and hospital referrals among patients with cancer. However, no study has quantitatively examined the implications of this correlation for cancer patient management. To evaluate the association of the COVID-19 pandemic lockdown with the tumor burden of patients who were diagnosed with metastatic colorectal cancer (mCRC) before vs after lockdown. This cohort study analyzed participants in the screening procedure of the PANIRINOX (Phase II Randomized Study Comparing FOLFIRINOX + Panitumumab vs FOLFOX + Panitumumab in Metastatic Colorectal Cancer Patients Stratified by RAS Status from Circulating DNA Analysis) phase 2 randomized clinical trial. These newly diagnosed patients received care at 1 of 18 different clinical centers in France and were recruited before or after the lockdown was enacted in France in the spring of 2020. Patients underwent a blood-sampling screening procedure to identify their RAS and BRAF tumor status. mCRC. Circulating tumor DNA (ctDNA) analysis was used to identify RAS and BRAF status. Tumor burden was evaluated by the total plasma ctDNA concentration. The median ctDNA concentration was compared in patients who underwent screening before (November 11, 2019, to March 9, 2020) vs after (May 14 to September 3, 2020) lockdown and in patients who were included from the start of the PANIRINOX study. A total of 80 patients were included, of whom 40 underwent screening before and 40 others underwent screening after the first COVID-19 lockdown in France. These patients included 48 men (60.0%) and 32 women (40.0%) and had a median (range) age of 62 (37-77) years. The median ctDNA concentration was statistically higher in patients who were newly diagnosed after lockdown compared with those who were diagnosed before lockdown (119.2 ng/mL vs 17.3 ng/mL; P < .001). Patients with mCRC and high ctDNA concentration had lower median survival compared with those with lower concentration (14.7 [95% CI, 8.8-18.0] months vs 20.0 [95% CI, 14.1-32.0] months). This finding points to the potential adverse consequences of the COVID-19 pandemic and related lockdown. This cohort study found that tumor burden differed between patients who received an mCRC diagnosis before vs after the first COVID-19 lockdown in France. The findings of this study suggest that CRC is a major area for intervention to minimize pandemic-associated delays in screening, diagnosis, and treatment.