Evaluation of the relevance of the growth modulation index (GMI) from the FFCD 0307 randomized phase III trial comparing the sequence of two chemotherapeutic regimens.

BACKGROUND: Precision medicine trials disrupted the paradigm of randomized controlled trials in large populations. Patient selection may be based on molecular alterations rather than on primary tumor location. In small patient populations, the growth modulation index (GMI) has been developed to evaluate treatment efficacy by using each patient as its own control. The FFCD 0307 randomized phase III trial compared two sequences of chemotherapy in advanced gastric cancer, which represents a unique opportunity to evaluate the relevance of the GMI. PATIENTS AND METHODS: In the FFCD 0307 trial, patients with advanced gastric cancer were randomized between two chemotherapy sequences [ECX followed by FOLFIRI at disease progression (arm A) versus FOLFIRI followed by ECX (arm B)]. GMI was defined as the ratio of the progression-free survival on second treatment (PFS2) to the time to progression on first treatment (TTP1). Sequence benefit was defined as a GMI exceeding 1.3 (GMI-high). GMI was correlated with overall survival (OS). OS1 and OS2 were measured from first randomization and second-line failure to death. RESULTS: Four hundred and sixteen patients were randomized (209 in arm A, 207 in arm B). One hundred and seventy-five patients (42%) received the two sequences and were assessable for GMI (97 in arm A, 79 in arm B). The median GMI was higher in arm A than in arm B (0.62 versus 0.47, P = 0.04). Patients with a high GMI had a longer OS1 (median 14.9 versus 11.5 months, NS). Median OS2 was doubled in the GMI-high group (3.4 versus 1.6 months, NS). CONCLUSION: GMI analyses suggest that ECX followed by FOLFIRI might represent a better therapeutic strategy than FOLFIRI followed by ECX. High GMI was associated with prolonged survival.

Prognosis and molecular characteristics of IBD-associated colorectal cancer: Experience from a French tertiary-care center.

BACKGROUND: Little is known about the prognosis of colorectal cancer associated with inflammatory bowel disease (CRC-IBD) in a real-world cohort in France. METHODS: We conducted a retrospective observational study including all patients presenting CRC-IBD in a French tertiary center. RESULTS: Among 6510 patients, the rate of CRC was 0.8% with a median delay of 19.5 years after IBD diagnosis (median age 46 years, ulcerative colitis 59%, initially localized tumor 69%). There was a previous exposure to immunosuppressants (IS) in 57% and anti-TNF in 29% of the cases. A RAS mutation was observed in only 13% of metastatic patients. OS of the whole cohort was 45 months. OS and PFS of synchronous metastatic patients was 20.4 months and 8.5 months respectively. Among the patients with localized tumor those previously exposed to IS had a better PFS (39 months vs 23 months; p = 0.05) and OS (74 vs 44 months; p = 0.03). The IBD relapse rate was 4%. No unexpected chemotherapy side-effect was observed CONCLUSIONS: OS of CRC-IBD is poor in metastatic patients although IBD is not associated with under-exposure or increased toxicity to chemotherapy. Previous IS exposure may be associated with a better prognosis.

What do surgeons need to know about the digestive disorders and paraclinical abnormalities induced by COVID-19?

The symptoms associated with COVID-19 are mainly characterized by a triad composed of fever, dry cough and dyspnea. However, digestive symptoms have also been reported. At first considered as infrequent, they in fact seem to affect more than half of patients. The symptoms mainly include anorexia, diarrhea, nausea and/or vomiting and abdominal pain. Even though prognosis is associated with lung injury, digestive symptoms seem significantly more frequent in patients presenting with severe COVID-19 infection. Digestive presentations, which may be isolated or which can precede pulmonary symptoms, have indeed been reported, with diarrhea as a leading clinical sign. The main biological abnormalities that can suggest COVID-19 infection at an early stage are lymphopenia, elevated CRP and heightened ASAT transaminases. Thoraco-abdominal scan seems useful as a means of on the one hand ruling out digestive pathology not connected with coronavirus and on the other hand searching for pulmonary images consistent with COVID-19 infection. No data exist on the value of digestive endoscopy in cases of persistent digestive symptoms. Moreover, the endoscopists may themselves be at significant risk of contamination. Fecal-oral transmission of the infection is possible, especially insofar as viral shedding in stools seems frequent and of longer duration than at the ENT level, including in patients with negative throat swab and without digestive symptoms. In some doubtful cases, virologic assessment of stool samples can yield definitive diagnosis. In the event of prolonged viral shedding in stools, a patient's persistent contagiousness is conceivable but not conclusively established. Upcoming serology should enable identification of the patients having been infected by the COVID-19 epidemic, particularly among previously undetected pauci-symptomatic members of a health care staff. Resumption of medico-surgical activity should be the object of a dedicated strategy preceding deconfinement.

[What do surgeons need to know about the digestive disorders and paraclinical abnormalities induced by COVID-19?] / Que doivent savoir les chirurgiens à propos des troubles digestifs et des anomalies paracliniques induits par le COVID 19 ?

The symptoms associated with COVID-19 are mainly characterized by a triad composed of fever, dry cough and dyspnea. However, digestive symptoms have also been reportedAt first considered as infrequent, they in fact seem to affect more than half of patients. The symptoms are mainly manifested by anorexia, diarrhea, nausea and/or vomiting and abdominal pain. Even though prognosis is associated with lung injury, digestive symptoms seem significantly more frequent in patients presenting with severe COVID-19 infection. Digestive forms, which may be isolated or which can precede pulmonary symptoms, have indeed been reported, with diarrhea as a leading clinical sign. The main biological abnormalities that can suggest COVID-19 infection at an early stage are lymphopenia, elevated CRP and heightened ASAT transaminases. Thoraco-abdominal scan seems useful as a means of on the one hand ruling out digestive pathology unrelated to coronavirus and on the other hand searching for pulmonary images suggestive of COVID-19 infection. No data exist on the interest of digestive endoscopy in cases of persistent digestive symptoms. Moreover, the endoscopists may themselves be at significant risk of contamination. Fecal-oral transmission of the infection is possible, especially insofar as viral shedding in stools seems frequent and of longer duration than at the ENT level, including in patients with negative throat swab and without digestive symptoms. In some doubtful cases, virologic assessment of stool samples can yield definitive diagnosis. In the event of prolonged viral shedding in stools, a patient's persistent contagiousness is conceivable but not conclusively established. Upcoming serology should enable identification of the patients having been infected by the COVID-19 epidemic, particularly among previously undetected pauci-symptomatic members of a health care staff. Resumption of medico-surgical activity should be guided by dedicated strategy preceding deconfinement.

Prognosis of Lymphoma in Patients With Known Inflammatory Bowel Disease: A French Multicentre Cohort Study.

BACKGROUND AND AIMS: The prognosis of lymphoma that occurs in patients with inflammatory bowel disease [IBD] is poorly known. METHODS: A multicentre retrospective cohort analysis was done in seven French tertiary centres from 1999 to 2019. Only lymphoma occurring in patients with previous established diagnosis of IBD were analysed. The primary outcome was progression-free survival at 3 years. RESULTS: A total of 52 patients [male 65%, Crohn's disease 79%, median age 48.3 years, median duration of IBD 10.1 years] were included, of whom 37 had been previously exposed to immunosuppressants and/or biologics for at least 3 months and 20 had primary intestinal lymphomas. The lymphoma histological types were: diffuse large B cell lymphomas [N = 17], Hodgkin lymphomas [N = 17], indolent B cell lymphomas [N = 12], and others including T cell lymphomas, mantle cell lymphomas, and unclassifiable B cell lymphoma [N = 6]. The median follow-up after lymphoma was 5.1 years (interquartile range [IQR] 4-7.8). Progression-free survival at 3 years was 85% in the overall population (95% confidence interval [CI] 75%-96%) with no significant difference between the exposed and unexposed group, 79% for patients exposed to immunosuppressants and/or biologics [95% CI 67%-94%], and 83% for patients diagnosed with primary intestinal lymphoma [95% CI 67%-100%]. No relapse of IBD has been observed during chemotherapy. The IBD relapse rate at the end of the last chemotherapy cycle was 23% at 3 years [95% CI 11%-39%] in the overall population. CONCLUSIONS: In this large cohort, the prognosis for lymphomas occurring in IBD appears to be good and similar to what is expected, irrespective of the exposure to biologics and/or immunosuppressants.

Loss of SMARCB1 expression in colon carcinoma.

SMARCB1 is a tumor suppressor gene, which is part of SWI/SNF complex involved in transcriptional regulation. Recently, loss of SMARCB1 expression has been reported in gastrointestinal carcinomas. Our purpose was to evaluate the incidence and prognostic value of SMARCB1 loss in colon carcinoma (CC). Patients with stage III CC (n= 1695), and a second cohort of 23 patients with poorly differentiated CC were analyzed. Immunohistochemistry for SMARCB1 was performed on tissue microarrays, and cases with loss of expression were controlled on whole sections. Loss of SMARCB1 was compared with the clinico-pathological and molecular characteristics, and the prognostic value was evaluated. Loss of SMARCB1 was identified in 12 of 1695 (0.7%) patients with stage III CC. Whole section controls showed a complete loss in only one of these cases, corresponding to a medullary carcinoma. SMARCB1 loss was not associated with histological grade, tumor size nor survival. In the cohort of poorly differentiated CC, we detected 2/23 (8.7%) cases with loss of SMARCB1; one was rhabdoid while the other had medullary and mucinous histology. These 2 cases were deficient for MisMatched Repair (dMMR) and mutated for BRAF. SMARCB1 loss is rare in stage III CC, but appears more frequent in poorly differentiated CC.

Management of colorectal peritoneal metastases: Expert opinion.

When peritoneal metastases are diagnosed (strong agreement of experts): (i) seek advice from a multidisciplinary coordination meeting (MCM) with large experience in peritoneal disease (e.g. BIG RENAPE network); (ii) transfer (or not) the patient to a referral center with experience in hyperthermic intraperitoneal chemotherapy (HIPEC), according to the advice of the MCM. With regard to systemic chemotherapy (strong agreement of experts): (i) it should be performed both before and after surgery, (ii) for no longer than 6 months; (iii) without postoperative anti-angiogenetic drugs. With regard to cytoreductive surgery (strong agreement of experts): (i) Radical surgery requires a xiphopubic midline incision; (ii) no cytoreductive surgery via laparoscopy. With regard to HIPEC: HIPEC can be proposed for trials outside an HIPEC referral center (weak agreement between experts): (i) if surgery is radical; (ii) if the expected morbidity is "reasonable"; (iii) if the indication for HIPEC was suggested by a MCM, and; (iv) mitomycin is preferred to oxaliplatin (which cannot be recommended) for this indication.

Prognostic factors in patients treated with second-line chemotherapy for advanced gastric cancer: results from the randomized prospective phase III FFCD-0307 trial.

AIM: The aim of this study was to determine prognostic factors in patients treated with second-line therapy (L2) for locally advanced or metastatic gastric and gastro-esophageal junction (GEJ) adenocarcinoma in a randomized phase III study with predefined L2. METHODS: In the FFCD-0307 study, patients were randomly assigned to receive in L1 either epirubicin, cisplatin, and capecitabine (ECX arm) or fluorouracil, leucovorin, and irinotecan (FOLFIRI arm). L2 treatment was predefined (FOLFIRI for the ECX arm and ECX for the FOLFIRI arm). Chi square tests were used to compare the characteristics of patients treated in L2 with those of patients who did not receive L2. Prognostic factors in L2 for progression-free survival (PFS) and overall survival (OS) were analyzed using a Cox model. RESULTS: Among 416 patients included, 101/209 (48.3%) patients in the ECX arm received FOLFIRI in L2, and 81/207 (39.1%) patients in the FOLFIRI arm received ECX in L2. Patients treated in L2, compared with those who only received L1 had : a better ECOG score (0-1: 90.4% versus 79.7%; p = 0.0002), more frequent GEJ localization (40.8% versus 27.6%; p = 0.005), and lower platelet count (median: 298000 versus 335000/mm3; p = 0.02). In multivariate analyses, age < 60 years at diagnosis (HR 1.49, 95% CI 1.09-2.03, p = 0.013) and ECOG score 2 before L2 (HR 2.62, 95% CI 1.41-4.84, p = 0.005) were the only significant poor prognostic factors for OS. CONCLUSION: Age ≥ 60 years at diagnosis and ECOG score 0/1 before L2 were the only favorable prognostic factors for OS.

RAS mutation analysis in circulating tumor DNA from patients with metastatic colorectal cancer: the AGEO RASANC prospective multicenter study.

Background: RAS mutations are currently sought for in tumor samples, which takes a median of almost 3 weeks in western European countries. This creates problems in clinical situations that require urgent treatment and for inclusion in therapeutic trials that need RAS status for randomization. Analysis of circulating tumor DNA might help to shorten the time required to determine RAS mutational status before anti-epidermal growth factor receptor antibody therapy for metastatic colorectal cancer. Here we compared plasma with tissue RAS analysis in a large prospective multicenter cohort. Patients and methods: Plasma samples were collected prospectively from chemotherapy-naive patients and analyzed centrally by next-generation sequencing (NGS) with the colon lung cancer V2 Ampliseq panel and by methylation digital PCR (WIF1 and NPY genes). Tumoral RAS status was determined locally, in parallel, according to routine practice. For a minimal κ coefficient of 0.7, reflecting acceptable concordance (precision ± 0.07), with an estimated 5% of non-exploitable data, 425 subjects were necessary. Results: From July 2015 to December 2016, 425 patients were enrolled. For the 412 patients with available paired plasma and tumor samples, the κ coefficient was 0.71 [95% confidence interval (CI), 0.64-0.77] and accuracy was 85.2% (95% CI, 81.4% to 88.5%). In the 329 patients with detectable ctDNA (at least one mutation or one methylated biomarker), the κ coefficient was 0.89 (95% CI, 0.84-0.94) and accuracy was 94.8% (95% CI, 91.9% to 97.0%). The absence of liver metastases was the main clinical factor associated with inconclusive circulating tumor DNA results [odds ratio = 0.11 (95% CI, 0.06-0.21)]. In patients with liver metastases, accuracy was 93.5% with NGS alone and 97% with NGS plus the methylated biomarkers. Conclusion: This prospective trial demonstrates excellent concordance between RAS status in plasma and tumor tissue from patients with colorectal cancer and liver metastases, thus validating plasma testing for routine RAS mutation analysis in these patients. Clinical Trial registration: Clinicaltrials.gov, NCT02502656.

Colorectal cancer (CRC) monitoring by 6-monthly 18FDG-PET/CT: an open-label multicentre randomised trial.

Background: [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18FDG-PET/CT) has high sensitivity for detecting recurrences of colorectal cancer (CRC). Our objective was to determine whether adding routine 6-monthly 18FDG-PET/CT to our usual monitoring strategy improved patient outcomes and to assess the effect on costs. Patients and methods: In this open-label multicentre trial, patients in remission of CRC (stage II perforated, stage III, or stage IV) after curative surgery were randomly assigned (1 : 1) to usual monitoring alone (3-monthly physical and tumour marker assays, 6-monthly liver ultrasound and chest radiograph, and 6-monthly whole-body computed tomography) or with 6-monthly 18FDG-PET/CT, for 3 years. A multidisciplinary committee reviewed each patient's data every 3 months and classified the recurrence status as yes/no/doubtful. Recurrences were treated with curative surgery alone if feasible and with chemotherapy otherwise. The primary end point was treatment failure defined as unresectable recurrence or death. Relative risks were estimated, and survival was analysed using the Kaplan-Meier method, log-rank test, and Cox models. Direct costs were compared. Results: Of the 239 enrolled patients, 120 were in the intervention arm and 119 in the control arm. The failure rate was 29.2% (31 unresectable recurrences and 4 deaths) in the intervention group and 23.7% (27 unresectable recurrences and 1 death) in the control group (relative risk = 1.23; 95% confidence interval, 0.80-1.88; P = 0.34). The multivariate analysis also showed no significant difference (hazards ratio, 1.33; 95% confidence interval, 0.8-2.19; P = 0.27). Median time to diagnosis of unresectable recurrence (months) was significantly shorter in the intervention group [7 (3-20) versus 14.3 (7.3-27), P = 0.016]. Mean cost/patient was higher in the intervention group (18 192 ± 27 679 € versus 11 131 ± 13 €, P < 0.033). Conclusion: 18FDG-PET/CT, when added every 6 months, increased costs without decreasing treatment failure rates in patients in remission of CRC. The control group had very close follow-up, and any additional improvement (if present) would be small and hard to detect. ClinicalTrials.gov identifier: NCT00624260.

Clinical and molecular characterisation of hereditary and sporadic metastatic colorectal cancers harbouring microsatellite instability/DNA mismatch repair deficiency.

BACKGROUND: Patients treated with chemotherapy for microsatellite unstable (MSI) and/or mismatch repair deficient (dMMR) cancer metastatic colorectal cancer (mCRC) exhibit poor prognosis. We aimed to evaluate the relevance of distinguishing sporadic from Lynch syndrome (LS)-like mCRCs. PATIENTS AND METHODS: MSI/dMMR mCRC patients were retrospectively identified in six French hospitals. Tumour samples were screened for MSI, dMMR, RAS/RAF mutations and MLH1 methylation. Sporadic cases were molecularly defined as those displaying MLH1/PMS2 loss of expression with BRAFV600E and/or MLH1 hypermethylation and no MMR germline mutation. RESULTS: Among 129 MSI/dMMR mCRC patients, 81 (63%) were LS-like and 48 (37%) had sporadic tumours; 22% of MLH1/PMS2-negative mCRCs would have been misclassified using an algorithm based on local medical records (age, Amsterdam II criteria, BRAF and MMR statuses when locally tested), compared to a systematical assessment of MMR, BRAF and MLH1 methylation statuses. In univariate analysis, parameters associated with better overall survival were age (P < 0.0001), metastatic resection (P = 0.001) and LS-like mCRC (P = 0.01), but not BRAFV600E. In multivariate analysis, age (hazard ratio (HR) = 3.19, P = 0.01) and metastatic resection (HR = 4.2, P = 0.001) were associated with overall survival, but not LS. LS-like patients were associated with more frequent liver involvement, metastatic resection and better disease-free survival after metastasectomy (HR = 0.28, P = 0.01). Median progression-free survival of first-line chemotherapy was similar between the two groups (4.2 and 4.2 months; P = 0.44). CONCLUSIONS: LS-like and sporadic MSI/dMMR mCRCs display distinct natural histories. MMR, BRAF mutation and MLH1 methylation testing should be mandatory to differentiate LS-like and sporadic MSI/dMMR mCRC, to determine in particular whether immune checkpoint inhibitors efficacy differs in these two populations.

Endoscopic Detection of Small Bowel Dysplasia and Adenocarcinoma in Crohn's Disease: A Prospective Cohort-Study in High-Risk Patients.

BACKGROUND AND AIMS: Crohn's disease [CD] is associated with an increased risk of small bowel adenocarcinoma [SBA]. There are no recommendations on endoscopic screening of SBA in CD patients. The aim of this study was to evaluate the feasibility and value of endoscopic screening for SBA in CD patients at high-risk of SBA. METHODS: We performed an exploratory multi-centre study in a prospective cohort of CD patients at high-risk of SBA defined as long-term small bowel disease without bowel resection for the past 10 years. Depending on the location of the disease, baseline upper and/or lower enteroscopies were performed. Random and targeted biopsies using chromoendoscopy were taken. Patients were followed-up for at least 1 year after inclusion. RESULTS: In total, 101 patients [62 men; median age: 48 years; median duration of disease: 19 years] were recruited in ten centres. The endoscopic procedure was incomplete in 47 cases because of impassable strictures and dilation was performed in four patients. Indeterminate small bowel dysplasia was identified in two patients at endoscopic screening; SBA was confirmed in one after surgical resection. With an at least 1-year follow-up duration, two additional cases of SBA were identified in patients who underwent surgery for obstruction, resulting in a 33% sensitivity rate for SBA endoscopic screening. CONCLUSION: In a cohort of high-risk patients, the prevalence of dysplasia and SBA on CD was 4%. Because of its low sensitivity, endoscopic screening cannot be recommended for surveillance in CD patients at high-risk of SBA.

Small bowel adenocarcinoma phenotyping, a clinicobiological prognostic study.

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare tumour with a poor prognosis. Molecular biology data on SBA carcinogenesis are lacking. METHODS: Expression of HER2, ß-catenin, p53 and mismatch repair (MMR) protein was assessed by immunohistochemistry. KRAS, V600E BRAF mutations and microsatellite instability were investigated. RESULTS: We obtained samples from 63 SBA patients (tumour stages: I-II: 30%; III: 35%; IV: 32%; locally advanced: 3%). HER2 overexpression (3+) was observed in 2 out of 62 patients, overexpression of p53 in 26 out of 62, abnormal expression of ß-catenin in 12 out of 61, KRAS mutation in 21 out of 49, BRAF V600E mutation in 1 out of 40 patients, MMR deficiency (dMMR) in 14 out of 61 and was consistent with Lynch syndrome in 9 out of 14 patients. All of the dMMR tumours were in the duodenum or jejunum and only one was stage IV. Median overall survival (OS) was 36.6 months (95% CI, 26.9-72.2). For all patients, in univariate analysis, stages I-II (P<0.001), WHO PS 0-1 (P=0.01) and dMMR phenotype (P=0.02) were significantly associated with longer OS. In multivariate analysis, disease stage (P=0.01) and WHO PS 0-1 (P=0.001) independently predicted longer OS. For stage IV patients, median OS was 20.5 months (95% CI: 14.6; 36.6 months). In multivariate analysis, WHO PS 0-1 (P=0.0001) and mutated KRAS status (P=0.02) independently predicted longer OS. CONCLUSION: This large study suggests that molecular alterations in SBA are closer to those in colorectal cancer (CRC) than those in gastric cancer, with low levels of HER 2 overexpression and high frequencies of KRAS mutations. The seemingly higher frequency of dMMR than in CRC may be explained by the higher frequency of Lynch syndrome in SBA patients. A dMMR phenotype was significantly associated with a non-metastatic tumour (P=0.02). A trend for a good prognosis and a duodenum or jejunum primary site was associated with dMMR.

Management of cutaneous adverse events induced by anti-EGFR (epidermal growth factor receptor): a French interdisciplinary therapeutic algorithm.

PURPOSE: Cutaneous adverse events induced by epidermal growth factor receptor (EGFR) inhibitors can hamper the patients' quality of life. The aim of our work was to draft an algorithm for the optimised management of this skin toxicity. METHODS: This algorithm was built in three steps under the responsibility of a steering committee. Step I: a systematic literature analysis (SLA) has been performed. Step II: the collection of information about practices was performed through a questionnaire.These questions were asked during regional meetings to which oncologists, gastro-enterologists, radiotherapists, and dermatologists were invited. Step III: a final meeting was organised involving the bibliography group and the steering committee and regional scientific committees for proposing a final algorithm. RESULTS: Step I: 14 publications were selected to evaluate the use of cyclines as curative or prophylactic treatment of the folliculitis induced by EGFR inhibitors. Nineteen publications were retained for the topical treatment of the folliculitis. Forty-six articles were selected for the management of the cutaneous lesions in link with appendages and 12 for xerosis and pruritus. Step II: 96 delegates attended the seven regional meetings and 67 questionnaires were analysed. Step III: a final algorithm was proposed on the basis of the conclusions of the first two steps and expert opinions present at this final meeting. The different propositions were unanimously approved by the 14 experts who voted. CONCLUSIONS: This multidisciplinary study summarising published data and current practices produced a therapeutic algorithm, which should facilitate the standardised, optimised management of skin toxicity associated with EGFR inhibitors in France.

Efficacy of venlafaxine for the prevention and relief of oxaliplatin-induced acute neurotoxicity: results of EFFOX, a randomized, double-blind, placebo-controlled phase III trial.

BACKGROUND: Oxaliplatin neurosensory toxicity is dose limiting and may present as acute symptoms and/or cumulative peripheral neuropathy. PATIENTS AND METHODS: From October 2005 to May 2008, patients with oxaliplatin-induced acute neurotoxicity were randomized into a double-blind study, to receive either venlafaxine 50 mg 1 h prior oxaliplatin infusion and venlafaxine extended release 37.5 mg b.i.d. from day 2 to day 11 or placebo. Neurotoxicity was evaluated using numeric rating scale (NRS) for pain intensity and experienced relief under treatment, the Neuropathic Pain Symptom Inventory and the oxaliplatin-specific neurotoxicity scale. The primary end point was the percentage of patients with a 100% relief under treatment. RESULTS: Forty-eight patients were included (27 males, median age: 67.6 years). Most patients had colorectal cancer (72.9%). Median number of cycles administered at inclusion was 4.5 (mean cumulative oxaliplatin dose: 684.6 mg). Twenty out of 24 patients in arm A (venlafaxine) and 22 out of 24 patients in arm B (placebo) were assessable for neurotoxicity. Based on the NRS, full relief was more frequent in the venlafaxine arm: 31.3% versus 5.3% (P=0.03). Venlafaxine side-effects included grade 1-2 nausea (43.1%) and asthenia (39.2%) without grade 3-4 events. CONCLUSION: Venlafaxine has clinical activity against oxaliplatin-induced acute neurosensory toxicity.

[Prospective study of quality of life after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy using oxaliplatin for peritoneal carcinomatosis]. / Étude prospective de la qualité de vie après une CHIP par oxaliplatine pour carcinose péritonéale.

BACKGROUND: Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is now the reference technique for limited peritoneal carcinomatosis (PC). Operative mortality is actually at 3 or 4%, and decrease as morbidity. Together, they did not limit acceptation of HIPEC. However, one of the major limitation of this aggressive treatment is that patient can be afraid to impair overall quality of life (QoL). The aim of this article was to assess QoL in patients at least 12 months after HIPEC using Oxaliplatin. METHOD: Patients completed a questionnaire before and after surgery at 1, 3, 6 and 12 months. QoL was assessed with the EORTC QLQ-C30 questionnaire. RESULTATS: Between September 2006 and October 2008, 32 of 35 patients who had undergone HIPEC were interviewed. PC originated in primary lesions of the colon/rectum (N = 17), ovary (N = 3), stomach (N = 3), appendix (N = 2), mesothelium (N = 2), pseudomyxoma peritonei (N = 3) and primary carcinoma of peritoneum (N = 2). The percentage of patients completing the questionnaire at each time point was: baseline = 87% (N = 28); 1 and 3 months = 46% (N = 15); 6 months = 62% (N = 20); and 12 months = 59% (N = 19). Morbidity and mortality were respectively 35 and 5%. Median hospital stay was 19 days. QoL score had decreased considerably in 60% of patients in the early postoperative assessment period after HIPEC (1 month), as compared with baseline score. Forty five per cent had reported significant pain and limitations on physical functioning. QoL score had returned to baseline at 3 months in 53,3% of patients: 20% reported lack of energy and fatigue. Fifty-five and 73% of patients had recovered their overall QoL at 6 and 12 months, respectively. Also, psychosocial problems, diarrhea and constipation, and peripheral neuropathy of oxaliplatin were reported in 20% of survivors over the course of the first year after HIPEC. CONCLUSION: Short-term QoL with physical and functional well-being are impaired in the first few months after surgery plus HIPEC using oxaliplatin. Long-term QoL returns to baseline at 3 months; however 20% of patients still report psychosocial problems, gastrointestinal symptoms and oxaliplatin-induced neuropathy. It is useful and important for patients to see this HIPEC QoL data at the time of consultation before treatment.

Chemotherapy of advanced small-bowel adenocarcinoma: a multicenter AGEO study.

BACKGROUND: Small-bowel adenocarcinoma (SBA) is a rare tumor of poor prognosis. Data on the efficacy of chemotherapy for advanced SBA are scarce. PATIENTS AND METHODS: All patients with advanced SBA who received frontline chemotherapy from 1996 to 2008 were eligible for this retrospective multicenter study. RESULTS: Ninety-three consecutive patients were included. In the entire population, the median progression-free survival (PFS) and overall survival (OS) times were 6.6 and 15.1 months, respectively. Median PFS times among patients treated with LV5FU2 (n = 10), FOLFOX (n = 48), FOLFIRI (n = 19) and LV5FU2-cisplatin (n = 16) were 7.7, 6.9, 6.0 and 4.8 months, respectively, while median OS times were 13.5, 17.8, 10.6 and 9.3 months, respectively. In multivariate analysis, World Health Organization performance status (PS) (P < 0.0001) and elevated serum levels of carcinoembryonic antigen (CEA) (P = 0.02) and carbohydrate antigen 19-9 (CA 19-9) (P = 0.03) were the only variables significantly associated with poor OS. In the subgroup of patients treated with platinum-based chemotherapy, multivariate analysis showed that LV5FU2-cisplatin was associated with poorer PFS (P < 0.0001) and OS (P = 0.02) compared with FOLFOX. CONCLUSIONS: This is the largest study of chemotherapy in advanced SBA. Baseline PS and CEA and CA 19-9 levels were the main prognostic factors. FOLFOX seems to be the most effective platinum-based chemotherapy regimen.

[From retroperitoneal fibrosis to gastric linitis]. / De la fibrose rétropéritonéale à la linite gastrique.

Retroperitoneal fibrosis may reveal many diseases, including neoplasias. An 83-year-old man presented with an acute renal failure due to compressive retroperitoneal fibrosis. Clinically the only abnormal feature was a cutaneous subclavicular infiltrated lesion and laboratory features included hypereosinophilia, anemia and elevated acute phase reactants. A thoracic CT-scan showed pleuritis and para-esophageal lymph node and the 18FDG-PET-scan an hypermetabolism lesion of the oesophagus. Gastroscopy and colonoscopy found a gastric linitis, already multi-metastatic at diagnosis. The gastric linitis can present with many decepting clinical forms, increasing the risk of delayed diagnosis.