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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.

Objectives: This study aims to explore the place of the relative in these triadic consultations and how this influences communication., Methods: A mixed-methods research strategy was used. Triadic consultations for the announcement of cancer progression were recorded and following the 3 participants completed questionnaires comprising mirror-items. Recordings and answers were further investigated in a few semi-structured interviews. Comparison of quantitative responses (questionnaires) used Wilcoxon's test for matched series. Qualitative analyses (consultations, interviews) used grounded theory. Patients were over 18, followed for cancer in palliative phase, excluding brain tumors and malignant hemopathies, and presented renewed disease progression. Relatives were over 18 and authorized by the patient to participate., Results: 47 consultations (audio-recordings, answers to questionnaires) and 12 interviews conducted separately with 4 triads were collected. Half the relatives, while remaining in the background, nevertheless contributed to the discussion. For patients, the presence of a relative was considered beneficial and for oncologists it facilitated the announcement. However, symptoms perceived as intimate or private appeared difficult to express for some patients, and for relatives, prognosis was a difficult subject to broach. Although their relationship with time and their expectations may differ, patients and relatives found consultations positive. Oncologists appeared to underestimate the patient's level of understanding ( P <0.001) and perceptions of the seriousness of the disease ( P =0.009) but not those of relatives. They did not evaluate the relative's state of health and check what the dyad had retained., Significance of Results: Training via simulation sessions should be adapted to communication involving relatives.

Purpose: While perioperative chemotherapy provides a survival benefit over surgery alone in gastric and gastroesophageal junction (G/GEJ) adenocarcinomas, the results need to be improved. This study aimed to evaluate the efficacy and safety of perioperative cetuximab combined with 5-fluorouracil and cisplatin., Patients and Methods: Patients received six cycles of cetuximab, cisplatin, and simplified LV5FU2 before and after surgery. The primary objective was a combined evaluation of the tumor objective response (TOR), assessed by computed tomography, and the absence of major toxicities resulting in discontinuation of neoadjuvant chemotherapy (NCT) (45% and 90%, respectively)., Results: From 2011 to 2013, 65 patients were enrolled. From 64 patients evaluable for the primary endpoint, 19 (29.7%) had a morphological TOR and 61 (95.3%) did not stop NCT prematurely due to major toxicity. Sixty patients (92.3%) underwent resection. Sixteen patients (/56 available, 28.5%) had histological responses (Mandard tumor regression grade ≤3). After a median follow-up of 44.5 months, median disease-free and overall survival were 24.4 [95% CI: 16.4-39.4] and 40.3 months [95% CI: 27.5-NA], respectively., Conclusion: Adding cetuximab to the NCT regimen in operable G/GEJ adenocarcinomas is safe, but did not show enough efficacy in the present study to meet the primary endpoint (NCT01360086).

Purpose: Circulating tumor DNA (ctDNA) has been suggested as a major prognostic factor in resected stage-III colon cancer. We analyzed ctDNA of patients randomized in the phase III IDEA-France trial., Experimental Design: ctDNA was tested for WIF1 and NPY by droplet digital PCR with method developed and validated for colorectal cancer. Disease-free survival (DFS) and overall survival (OS) were analyzed via multivariable analysis in patients with ctDNA samples and in sub-groups according to treatment duration (3/6 months) and disease stage (high/low-risk stage III)., Results: Of 2,010 randomized patients, 1,345 had available ctDNA samples (1,017 collected both post-surgery and pre-chemotherapy). More Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 (78% versus 69%) and T4 and/or N2 (40% versus 36%) were observed in patients studied ( n = 1017) versus not analyzed ( n = 993). There were 877 ctDNA-negative (86.2%) and 140 ctDNA-positive (13.8%) patients; their baseline characteristics were similar. With a median follow-up of 6.6 years, the 3-year DFS rate was 66.39% for ctDNA-positive patients and 76.71% for ctDNA-negative patients ( P = 0.015). ctDNA was confirmed as an independent prognostic marker for DFS (adjusted HR = 1.55, 95% CI 1.13-2.12, P = 0.006) and OS (HR = 1.65, 95% CI 1.12-2.43, P = 0.011). ctDNA was prognostic in patients treated for 3 months and with T4 and/or N2 tumors, but not in those treated for 6 months and with T1-3/N1 tumors., Conclusions: In this first ctDNA assessment of a large series of patients with stage III colon cancer enrolled in phase III trial, post-surgery ctDNA was found in 13.8% of them and was confirmed as an independent prognostic marker. See related commentary by Bent and Kopetz, p. 5449 ., (©2021 American Association for Cancer Research.)

Background: Identifying patients with metastatic colorectal cancer who will have an early disease progression during induction chemotherapy (IC) and identifying patients who may have a chemotherapy-free interval (CFI) after IC are two major challenges., Methods: A logistic model was used to identify factors associated with early progression during IC and with short duration of the first CFI in 488 patients enrolled in the PRODIGE 9 trial. Independent factors were defined with a threshold 0.10., Results: In multivariate analysis, baseline leukocytes >10 × 10 9 /L (OR = 1.98 [1.02-3.8], p = 0.04), and stable or increasing CEA at 2 months (OR = 3.61 [1.68-7.75], p = 0.01) were independent factors associated with progression during IC. Male gender (OR = 1.725 [0.92-3.325], p = 0.09) and no tumour response at first evaluation (OR = 1.90 [0.96-3.76], p = 0.07) were significantly associated with a short CFI. The presence of BRAF V600E mutation was also associated with short CFI (OR = 4.59 [0.95; 22.3], p = 0.058)., Conclusion: High baseline leukocyte count and the lack of CEA decrease level at first evaluation were associated with early progression, and could be in favour of early chemotherapy intensification. Male gender, no tumour response at first evaluation and BRAF mutation are associated with a short CFI, and may be considered for maintenance chemotherapy after IC., Clinical Trial Number: NCT00952029.

Purpose Reduction of adjuvant treatment duration may decrease toxicities without loss of efficacy in stage III colon cancer. This could offer clear advantages to patients and health care providers. Methods In International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France, as part of the IDEA international collaboration, patient with colon cancer patients were randomly assigned to 3 and 6 months of modified FOLFOX6 (mFOLFOX6: infusional fluorouracil, leucovorin, and oxaliplatin) or capecitabine plus oxaliplatin (CAPOX) by physician choice. The primary end point was disease-free survival (DFS), and analyses were descriptive. Results A total of 2,010 eligible patients received either 3 or 6 months of chemotherapy (modified intention-to-treat population); 2,000 (99%) had stage III colon cancer (N1: 75%, N2: 25%); 1,809 (90%) received mFOLFOX6, and 201 (10%) received CAPOX. The median age was 64 years, and the median follow-up time was 4.3 years. Overall, 94% (3 months) and 78% (6 months) of patients completed treatment (fluoropyrimidines ± oxaliplatin). Maximal grade 2 and 3 neuropathy rates were 28% and 8% in the 3-month arm and 41% and 25% in the 6-month arm ( P < .001). Final rates of residual neuropathy greater than grade 1 were 3% in the 3-month arm and 7% in the 6-month arm ( P < .001). There were 578 DFS events: 314 and 264 in the 3- and 6-month arms, respectively. The 3-year DFS rates were 72% and 76% in the 3- and 6-month arms, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05 to 1.46; P = .0112). In the 3 and 6-month arms, respectively, for patients who received mFOLFOX6, the 3-year DFS rates were 72% and 76% (HR, 1.27; 95% CI, 1.07 to 1.51); for the T4 and/or N2 population, they were 58% and 66% (HR, 1.44; 95% CI, 1.14 to 1.82); and for the T1-3N1 population, they were 81% and 83% (HR, 1.15; 95% CI, 0.89 to 1.49). Conclusion IDEA France, in which 90% of patients received mFOLFOX6, shows superiority of 6 months of adjuvant chemotherapy compared with 3 months, especially in the T4 and/or N2 subgroups. These results should be considered alongside the international IDEA collaboration data.

Background: In 2008, a study of the characteristics of hospitalised patients led to the development of a prognostic tool that distinguished three populations with significantly different 2-month survival rates. The goal of our study aimed at validating prospectively this prognostic tool in outpatients treated for cancer in terminal stage, based on four factors: performance status (ECOG) (PS), number of metastatic sites, serum albumin and lactate dehydrogenase., Patients and Methods: PRONOPALL is a multicentre study of current care. About 302 adult patients who met one or more of the following criteria: life expectancy under 6 months, performance status ≥ 2 and disease progression during the previous chemotherapy regimen were included across 16 institutions between October 2009 and October 2010. Afterwards, in order to validate the prognostic tool, the score was ciphered and correlated to patient survival., Results: Totally 262 patients (87%) were evaluable (27 patients excluded and 13 unknown score). Median age was 66 years [37-88], and women accounted for 59%. ECOG PS 0-1 (46%), PS 2 (37%) and PS 3-4 (17%). The primary tumours were: breast (29%), colorectal (28%), lung (13%), pancreas (12%), ovary (11%) and other (8%). About 32% of patients presented one metastatic site, 35% had two and 31% had more than two. The median lactate dehydrogenase level was 398 IU/l [118-4314]; median serum albumin was 35 g/l [13-54]. According to the PRONOPALL prognostic tool, the 2-month survival rate was 92% and the median survival rate was 301 days [209-348] for the 130 patients in population C, 66% and 79 days [71-114] for the 111 patients in population B, and 24% and 35 days for [14-56] the 21 patients in population A. These three populations survival were statistically different (P <0.0001)., Conclusion: PRONOPALL study confirms the three prognostic profiles defined by the combination of four factors. This PRONOPALL score is a useful decision-making tool in daily practice., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: In 2006, bevacizumab, a targeted therapy agent was combined with FOLFIRI for the firstline treatment of patients with unresectable metastatic colorectal cancer., Methods/results: A study on a homogenous series of 111 patients from the Brittany and Pays de la Loire areas who received bevacizumab-FOLFIRI as first-line treatment in 2006 showed the following results: 51 responses, 29 stabilisations, 21 progressions and 10 cases of toxicity prior to assessment. Median overall survival (OS) was 25.1 months and median progression-free survival was 10.2 months. Surgery secondary to treatment tripled median OS which reached 59.2 months in resected patients versus 18.8 months in unresected patients. Comparison of patients aged more or less than 70 years showed no differences in terms of benefits or risks., Conclusion: Bevacizumab-FOLFIRI could be administered as part of a routine care protocol to elderly patients previously evaluated by a geriatric assessment and validated by a multidisciplinary staff.

Background and Aims: Treatment of metastatic colorectal cancer with new drugs (NDs) as oxaliplatin and irinotecan had improved response and survival. In order to check whether the promising achievements of the trials are obtained in routine clinical practice, we have reviewed retrospectively our results for two periods, before (period A: 1993-1995, n=63) and after (period B:1998-2000 n=103) the introduction of these NDs. Patients characteristics, treatment modalities, survival, and prognostic factors were compared., Patients: There were 74 women and 92 men, aged 60.8+/-11.6 yr, 7 patients received best supportive care only, 91 had synchronous metastasis., Results: Period B patients were older, with WHO score>1 more often, more adjuvant treatment, more metachronous metastasis, and NDs used more frequently (24% vs 59%). Median survival was similar (16 vs 15 mo). But when looking at the population aged<75 years with WHO score<2, median survival was 13 mo (period A) vs 21 mo (period B); survival at 1, 2, and 3 yr were respectively 59.5+/-8%, 16.2+/-6 %, 13.5+/-6 % vs 69.8+/-6%, 49.6+/-7%, 29.8+/-7%, p<0.01). In multiparametric analysis, factors correlated with survival were the absence of elevated serum alkaline phosphatase, a unique metastatic organ, and administration of NDs., Conclusion: In our routine clinical experience the use of NDs for metastatic CRC has allowed a significant improvement in survival among patients with unresectable tumors.

We report a series of 7 glucagonoma patients seen between 1994 and 2001, 5 males and 2 females, aged 32-69 years, with: necrolytic migratory erythema (NME) (n = 2), liver metastases (n = 3), jaundice (n = 1) and 1 case of familial history of multiple endocrine neoplasia. The diagnosis combined histology and hyperglucagonemia; 6 patients developed metastasis (5 initially); during the follow-up 3 developed a necrolytic erythema migraticum (NEM) worsening the general status. Somatostatin receptor scanning was highly positive in all. Four patients were operated, 5 received chemotherapy (2 OR and 2 SD), 3 had chemoembolization (1 transient improvement). Somatostatin was efficient on general status or skin lesions in all patients. Two died and 5 are alive with a follow up ranging from 12 to 60 months. We want to emphasize on the higher frequency than expected of this disease, the frequency of NEM, the efficacy of SMS on NEM and general status and on the fairly good prognosis. The high uptake of SMS by tumors on scanning could rise hopes about radioconjugate therapy., (Copyright John Libbey Eurotext 2003.)

Introduction: Although rare, the malignant degeneration of epidermoid cysts is well documented. Its occurrence with leptomeningeal dissemination and malignant cells in CSF is scarce. To the best of our knowledge only four cases have been reported., Case Report: The authors report the case of malignant transformation of an epidermoid cyst with leptomeningeal carcinomatosis (which simulates aseptic meningitis) in a 54 year-old woman. Changes in CSF and radiological features are not correlated with the clinical course. Despite improvement of both the lesions on the scan images and the malignant cells in the CSF under chemotherapy the patient died., Conclusion: The differential diagnosis of malignant degeneration of epidermoid cyst, and leptomeningeal carcinomatosis are discussed. The diagnosis of malignant transformation should be retained when MRI (or CT scan) shows contrast enhancement at the epidermoid site, and malignant cells are detected in CSF The prognosis is generally poor.

The authors report two cases of severe bilateral interstitial pneumopathies occurring after a medical treatment for esophageal carcinoma. In both cases a broncho-alveolar lavage revealed the presence of herpes virus and a specific treatment rapidly cured the patients.

Primary small-cell carcinoma (SCC) of the esophagus is rare, with about 200 cases reported up till now in the literature. Like pulmonary SCC, it is an aggressive tumor associated with a poor prognosis. Between 1994 and 1997, three patients with SCC of the esophagus were treated at Besançon University Hospital and this represented 1.85% of all esophageal malignancies diagnosed during this period: one patient had a limited tumor and underwent initial surgical resection, then chemotherapy with cisplatine and etoposide, and radiotherapy for recurrences. The other patients had extensive disease at diagnosis and were treated by the same chemotherapy. This retrospective study reports our experience of patients with this particular tumor and outlines the management strategy based on the available literature.