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Introduction Predictive markers of LV5FU2 maintenance benefit after first-line induction with FOLFIRINOX in patients with metastatic pancreatic cancer are necessary to select patients who will not be harmed by this strategy. Patients and Methods We focused on patients who received 12 cycles of FOLFIRINOX (arm A, N  = 88) or 8 cycles of FOLFIRINOX followed by LV5FU2 maintenance in controlled patients (arm B, N  = 91) from the PRODIGE-35 trial. Prognostic factors and predictors of efficiency were identified by using Cox regression. Median progression-free survival (PFS), overall survival (OS), and time to deterioration of quality of life (TTD-QoL) were evaluated. Results Poor independent prognostic factors were primary tumor in place, age <65 years and the presence of liver metastases for PFS, a baseline neutrophil/lymphocyte ratio (NLR) ≥5 and CA19.9 ≥500 UI/L for OS, independent of the treatment arm. Patients with one metastatic site had a longer PFS in arm A, whereas patients with ≥2 metastatic sites had a longer PFS in arm B. We also identified predictors of OS and TTD-QoL in arm B but these differences were not statistically significant. Conclusion Except for patients with one metastatic site who benefited more from 12 cycles of FOLFIRINOX, a maintenance strategy with LV5FU2 should be widely offered to mPC patients whose survival and QoL are preserved after 4 months of FOLFIRINOX. (ClinicalTrials.gov: NCT02352337). [ABSTRACT FROM AUTHOR]

About 5% of the patients with metastatic colorectal cancers (mCRC) present microsatellite instability (MSI)/deficient mismatch repair system (dMMR). While metastasectomy is known to improve overall and progression‐free survival in mCRC, specific results in selected patients with dMMR/MSI mCRC are lacking. Our study aimed to describe metastasectomy results, characterize histological response and evaluate pathological complete response (pCR) rate in patients with dMMR/MSI mCRC. We retrospectively reviewed data from all consecutive patients with dMMR/MSI mCRC who underwent surgical metastasectomy between January 2010 and June 2021 in 17 French centers. Primary outcome was to assess the pCR rate defined by tumor regression grade (TRG) 0. Secondary endpoints included relapse‐free survival (RFS) and overall survival (OS), and explored TRG as predictive factor for RFS and OS. Among the 88 patients operated, 109 metastasectomies were performed in 81 patients after neoadjuvant treatment [chemotherapy ± targeted therapy (CTT): 69, 85.2%; immunotherapy (ICI): 12, 14.8%], and pCR was achieved in 13 (16.1%) patients. Among the latter, pCR rate were 10.2% in the patients having received CTT (N = 7) and 50.0% in the patients treated with ICI (N = 6). Radiological response did not predict TRG. With a median follow‐up of 57.9 (IQR 34.2‐81.6) months, median RFS was 20.2 (15.4‐not reached) months, median OS was not reached. Major pathological responses (TRG0 + TRG1) were significantly associated with longer RFS (HR 0.12, 95% CI 0.03‐0.55; P =.006). The pCR rate of 16.1% achieved with neoadjuvant treatment in patients with dMMR/MSI mCRC is consistent with previously reported rates in pMMR/MSS mCRC. Immunotherapy showed better pCR rate than chemotherapy ± targeted therapy. Further prospective trials are needed to validate immunotherapy as neoadjuvant treatment in resectable/potentially resectable dMMR/MSI mCRC and identify predictive factors for pCR. [ABSTRACT FROM AUTHOR]

Background: Current knowledge on prognostic biomarkers (especially BRAFV600E/RAS mutations) in metastatic colorectal cancer (mCRC) is mainly based on mCRC patients with proficient mismatch repair (pMMR) tumors. It is uncertain whether these biomarkers have the same prognostic value in mCRC patients with deficient mismatch repair (dMMR) tumors. Methods: This observational cohort study combined a population‐based Dutch cohort (2014–2019) and a large French multicenter cohort (2007–2017). All mCRC patients with a histologically proven dMMR tumor were included. Results: In our real‐world data cohort of 707 dMMR mCRC patients, 438 patients were treated with first‐line palliative systemic chemotherapy. Mean age of first‐line treated patients was 61.9 years, 49% were male, and 40% had Lynch syndrome. BRAFV600E mutation was present in 47% of tumors and 30% harbored a RAS mutation. Multivariable regression analysis on OS showed significant hazard rates (HR) for known prognostic factors as age and performance status, however showed no significance for Lynch syndrome (HR: 1.07, 95% CI: 0.66–1.72), BRAFV600E mutational status (HR: 1.02, 95% CI: 0.67–1.54), and RAS mutational status (HR: 1.01, 95% CI: 0.64–1.59), with similar results for PFS. Conclusion: BRAFV600E and RAS mutational status are not associated with prognosis in dMMR mCRC patients, in contrast to pMMR mCRC patients. Lynch syndrome is also not an independent prognostic factor for survival. These findings underline that prognostic factors of patients with dMMR mCRC are different of those with pMMR, which could be taken into consideration when prognosis is used for clinical decision‐making in dMMR mCRC patients and underline the complex heterogeneity of mCRC. [ABSTRACT FROM AUTHOR]

Efficacy of immune checkpoint inhibitors (ICI) as monotherapy in 2nd line treatment for gastric or gastro-oesophageal junction (GEJ) adenocarcinoma is low, with no evaluation of efficacy and safety of ICI combined with chemotherapy. The DURIGAST PRODIGE 59 study is a randomised, multicentre, phase II study designed to assess the efficacy and safety of the combination of FOLFIRI + Durvalumab +/− Tremelimumab as 2nd line treatment of patients with advanced gastric/GEJ adenocarcinoma. Here, we report data from the safety run-in phase with FOLFIRI Durvalumab (arm A) or FOLFIRI Durvalumab and Tremelimumab (arm B). Among the 11 patients included, 63.6% experienced at least one grade 3–4 adverse events (AEs) related to the treatment, most frequently neutropenia (36.4%). There was only one immune-related AE (grade 2 hyperthyroidism). Ten serious AEs were described among six patients, but only two were related to the treatment, due to the chemotherapy. One seizure epilepsy related to a brain metastasis was observed, but was not related by the investigator to the treatment. However, the Independent Data Monitoring Committee recommended brain imaging at inclusion. This safety run-in phase demonstrates an expected safety profile of FOLFIRI with Durvalumab +/− Tremelimumab combination allowing the randomised phase II. [ABSTRACT FROM AUTHOR]

Few studies have explored the association between baseline characteristics and the occurrence of early toxicities in patients treated with first-line chemotherapy for metastatic colorectal cancer (mCRC). Individual patient data of 2190 patients enrolled in 10 prospective FFCD (Fédération Francophone de Cancérologie Digestive) trials were analysed. Severe early toxicity was defined as the occurrence of grade ≥III toxicity within 3 months after initiation of chemotherapy (ET3). Patients received monotherapy based on 5-FU (n = 1068), a cytotoxic doublet (n = 395) or tritherapy with a cytotoxic doublet plus anti-VEGF agent or a cytotoxic triplet (n = 727). The patients received 5-FU (100%), Irinotecan (39.6%), Oxaliplatin (13.4%), Bevacizumab (29.6%) or Aflibercept (1.8%). ET3 occurred in 244 patients (22.8%) with monotherapy, 248 patients (62.8%) with doublet and 392 patients (53.9%) with tritherapy. The most frequent ET3s were related to biological abnormalities and/or gastrointestinal, general and vascular disorders. The prognostic factors for the occurrence of an ET3 in multivariate analysis were a performance status of 2 rather than 0–1 (OR 2.57; 95% CI [1.16, 5.73]; p = 0.02), tritherapy versus monotherapy (OR 2.31; 95% CI [0.84, 6.33]; p = 0.02), alkaline phosphatase > 300 UI/l (OR 3.07; 95% CI [1.79, 5.27]; p < 0.001) and non-resected primary tumour versus resection (OR 1.59; 95% CI [1.06, 2.39]; p = 0.02). Median overall survival in patients without ET3 was significantly longer than that in patients with ET3 (HR 0.87; 95% CI [0.80–0.96]; p = 0.004). ET3 is frequent whatever the treatment regimen and is associated with certain baseline characteristics. The clinical impact of ET3 on prognosis in mCRC warrants further investigation. • Severe drug toxicity has a negative impact on prognosis in metastatic colorectal cancer. • Early toxicity within 3 months after first-line regimen initiation may be a key factor. • Early grade III or more toxicity is a new prognostic marker. • Some baseline characteristics are associated with ET3 occurrence. • Early grade III or more toxicity correlates with poorer overall survival. [ABSTRACT FROM AUTHOR]

Background Previous studies showed that high and low body mass index (BMI) was associated with worse prognosis in early-stage colorectal cancer (CRC), and low BMI was associated with worse prognosis in metastatic CRC (mCRC). We aimed to assess efficacy outcomes according to BMI. Patients and methods A pooled analysis of individual data from 2085 patients enrolled in eight FFCD first-line mCRC trials from 1991 to 2013 was performed. Comparisons were made according to the BMI cut-off: Obese (BMI ≥30), overweight patients (BMI ≥ 25), normal BMI patients (BMI: 18.5–24) and thin patients (BMI <18.5). Interaction tests were performed between BMI effect and sex, age and the addition of antiangiogenics to chemotherapy. Results The rate of BMI ≥25 patients was 41.5%, ranging from 37.6% (1991–1999 period) to 41.5% (2000–2006 period) and 44.8% (2007–2013 period). Comparison of overweight patients versus normal BMI range patients revealed a significant improvement of median overall survival (OS) (18.5 versus 16.3 months, HR = 0.88 [0.80–0.98] p = 0.02) and objective response rate (ORR) (42% versus 36% OR = 1.23 [1.01–1.50] p = 0.04) but a comparable median progression-free survival (PFS) (7.8 versus 7.2 months, HR = 0.96 [0.87–1.05] p = 0.35). Subgroup analyses revealed that overweight was significantly associated with better OS in men. OS and PFS were significantly shorter in thin patients. Conclusion Overweight patients had a prolonged OS compared with normal weight patients with mCRC. The association of overweight with better OS was only observed in men. The pejorative prognosis of BMI <18.5 was confirmed. [ABSTRACT FROM AUTHOR]

Background Complete cytoreductive surgery (CCRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a validated treatment in selected patients with peritoneal metastases (PM) of intestinal origin. There is an increased risk of Colorectal Cancer (CRC) and Small Bowel Adenocarcinoma (SBA) in Inflammatory Bowel Disease (IBD). The feasibility and benefit of that surgical approach in IBD patients is unknown. Methods IBD patients with operated PM complicating CRC or SBA were extracted from a French national multicenter prospective database of patients who underwent surgery for PM in HIPEC expert centers from 1995 to 2016. IBD patients who underwent CCRS plus HIPEC were compared with a cohort of 234 patients who had the same surgery for sporadic colon cancer. Results 14 patients (male 57%, median age 40 years, 12 Crohn's disease) with CRC (n = 7) and SBA (n = 7) were included. CCRS followed by HIPEC (oxaliplatin 72.7%) was performed in 11 cases (median peritoneal cancer index 7; range 1–30). The control group had the same characteristics except an older age at HIPEC (56.52 vs 45.74; p = 0.003). Overall survival (HR = 4.47; 90% CI, 1.91 to 10.49), Relapse Free Survival (HR = 2.31; 90% CI, 1.17 to 4.56) and Peritoneal Recurrence Free Survival (HR = 3.30; 90% CI, 1.59 to 6.85) were significantly lower in IBD patients. Six of the 11 patients presented major surgical morbidity with no impact on post-operative treatment. Conclusion CCRS followed by HIPEC is less effective in IBD patients with resectable PM complicating CRC or SBA. More careful selection of those patients is needed. [ABSTRACT FROM AUTHOR]

Aim Several predictors of metastatic colorectal cancer (mCRC) outcomes have been described. Specific geriatric characteristics could be of interest to determine prognosis. Method Elderly patients (75+) with previously untreated mCRC were randomly assigned to receive infusional 5-fluorouracil-based chemotherapy, either alone (FU) or in combination with irinotecan (IRI). Geriatric evaluations were included as an optional procedure. The predictive value of geriatric parameters was determined for the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results From June 2003 to May 2010, the FFCD 2001-02 randomised trial enrolled 282 patients. A baseline geriatric evaluation was done in 123 patients; 62 allocated to the FU arm and 61 to the IRI arm. The baseline Charlson index was ≤1 in 75%, Mini-Mental State Examination was ≤27/30 in 31%, Geriatric Depression Scale was >2 in 10% and Instrumental Activities of Daily Living (IADL) was impaired in 34% of the patients. Multivariate analyses revealed that no geriatric parameter was predictive for ORR or PFS. Normal IADL was independently associated with better OS. The benefit of doublet chemotherapy on PFS differed in subgroups of patients ≤80 years, with unresected primary tumour, leucocytes >11,000 mm 3 and carcinoembryonic antigen >2N. There was a trend towards better OS in patients with normal IADL. Conclusion The autonomy score was an independent predictor for OS. A trend toward a better efficacy of doublet chemotherapy in some subgroups of patients was reported and should be further explored. [ABSTRACT FROM AUTHOR]

Background: The clinical benefit of first-line doublet chemotherapy (including oxaliplatin or irinotecan) compared to single-drug therapy (5FU) in elderly patients (>70 or >75 years old) with metastatic colorectal cancer (MCRC) is controversial. Therefore, we undertook a meta-analysis of all published phase III studies. Material and methods: We performed a PubMed search using keywords metastatic colorectal cancer, phase III studies, oxaliplatin, irinotecan, survival. We also screened Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) proceedings. Few studies have been published corresponding to our inclusion criteria. The efficacy outcomes were overall survival (OS) and progression-free survival (PFS). Toxicity was also examined when available. Hazard ratios (HRs) with their 95 % confidence intervals (CI) were collected from the studies and pooled. By convention, HRs <1 corresponded to a better outcome for doublets. p values <0.05 were considered statistically significant. A fixed-effect model was used. We used Comprehensive Meta-Analysis Software (Biostat, Englewood, NJ, USA). Results: This meta-analysis (MA) included five original studies (Mitry and Venderbosch for CAIRO both assessing irinotecan, De Gramont and Seymour for FOCUS2 and Ducreux assessing oxaliplatin) and an already published MA (Folprecht) of four trials comparing FOLFIRI with 5FU (Saltz, Douillard, Köhne and Seymour). Our MA included 1225 patients (70 % men). For age, we chose a cut-off of 70 years for oxaliplatin and a cut-off of 75 years for irinotecan. The performance status (PS) score was 0-1 in about 90 % of patients except for the studies by Mitry and Seymour FOCUS2 which both included 30 % of PS2 patients. Overall, doublet chemotherapy, compared to 5FU alone, did not improve OS (HR = 1.00; CI: 0.89-1.13) but significantly improved PFS (HR = 0.82; CI: 0.72-0.93). When assessed separately, FOLFIRI and FOLFOX both significantly improved PFS (HR = 0.83; 0.68-1.00 and HR = 0.81; 0.68-0.97, respectively). The main grade 3-4 toxicities for FOLFIRI were diarrhoea, nausea, vomiting and neutropenia, which occurred significantly more often than with 5FU alone. Conclusion: Addition of oxaliplatin or irinotecan to 5FU in metastatic CRC significantly improved PFS in elderly patients more than 70 years old but was associated with an increased risk of toxicity as shown for irinotecan. [ABSTRACT FROM AUTHOR]

Background FOLFOX second-line treatment seems to be a validated option for patients with pancreatic cancer (PC) progressing after gemcitabine chemotherapy. However, other therapeutics strategy has developed in first-line therapy, as the FIRGEM phase II study that evaluated gemcitabine alone versus FOLFIRI.3 alternating with gemcitabine every two months. The present study assessed the efficacy and safety of FOLFOX after failure of the first-line therapy used in the FIRGEM study. Methods In this prospective observational cohort study, we analysed all consecutive patients who received second-line chemotherapy with FOLFOX among 98 patients with metastatic PC included in the FIRGEM study. Progression-free survival (PFS) and overall survival (OS) were estimated from the start of second-line chemotherapy using the Kaplan-Meier method. Results Among 46 patients who received second-line chemotherapy, 27 patients (male, 55%; median age, 61 years; performance status (PS) 0-1, 44%) were treated with FOLFOX after progression to first-line gemcitabine alone (n = 20) or FOLFIRI.3 alternating with gemcitabine (n = 7). Grade 3 toxicity was observed in 33% of patients (no grade 4 toxicity). At the end of follow-up, all patients had progressed and 25 had died. No objective response was observed, and disease control rate was 36%. Median PFS and OS were 1.8 and 4.3 months, respectively. In multivariate analysis, PS was the only independent prognostic factor. For patients PS 0-1 versus 2-3, median PFS was 3.0 versus 1.2 months (log rank, p = 0.002), and median OS was 5.9 versus 2.6 months (log rank, p = 0.001). Conclusions This study suggests that FOLFOX second-line therapy offered interesting efficacy results with an acceptable toxicity profile in metastatic PC patients with a good PS. [ABSTRACT FROM AUTHOR]

Abstract: Background: Several database studies report a lack of care in elderly patients with colorectal cancer. Purpose: To describe the management of elderly patients admitted for colorectal cancer; to identify factors associated with standard management according to recommendations and to study factors influencing the survival. Patients and methods: All consecutive patients over 75 years managed for a colorectal adenocarcinoma in our hospital from 1995 to 2000 and followed until 2006 were retrospectively included. The appropriateness of the management of their disease according to the recommendations available at that time was assessed. Several risk factors in receiving the standard cancer treatment were tested using univariate and then multivariate logistic regression. Risk factors of survival were studied using univariate and then multivariate survival analysis. Results: One hundred and ten patients were included. Median age was 82 years (range: 75–96). A surgical treatment was performed in 96 patients. The median overall survival was 32 (1–108) months. A standard cancer treatment according to recommendations was performed in 53 (48%) patients: adjuvant chemotherapy in 6/23 patients with stage III tumour, palliative chemotherapy in 3/18 patients with stage IV tumour and adjuvant radiotherapy in 4/14 patients who had a rectal tumour resection. Multivariate analysis retains tumour stage I or II (OR=7.6, 95% C.I.=[2.9–19.9], p <0.0001) as the only factor associated with standard treatment and presence of metastasis (HR=3.9, 95% C.I. [1.4–10.8], p =0.005), and Charlson''s score >3 (HR=28.9, 95% C.I. [2.5–335.6], p =0.001) as independent risk factors of poor survival. Conclusions: Fifty two percent of elderly patients have had a sub-standard cancer treatment. The majority had a surgical treatment, but only a few received chemotherapy or radiotherapy. Metastasis, older age and Charlson''s comorbidity score are the main prognosis factors of poor survival. [Copyright &y& Elsevier]

We assessed a schedule alternating 4 FOLFOX and 4 FOLFIRI cycles in 39 patients with 5-FU resistant metastatic colorectal cancer. Patients alternatively received 4 FOLFOX-6 cycles (oxaliplatin 100 mg/m 2 , leucovorin 200 mg/m 2 d1 followed by bolus 400 mg/m 2 5-FU and by a 46-hour 2,400 mg/m 2 5-FU infusion, every 2 weeks), and 4 FOLFIRI cycles (oxaliplatin replaced by irinotecan 180 mg/m 2 d1) until progression or limiting toxicity. Eigteen patients achieved an objective response (46.1 percent). Median progression-free and overall survivals were 8.8 and 18.7 months, respectively. Only 2 patients (5.1 percent) had Grade 3 oxaliplatin-related sensory-neuropathy. This schedule had so promising efficacy and safety. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) and hepatocyte growth factor (HGF)/mesenchymal–epithelial transition (MET) pathways, which promote tumour growth and proliferation, are often deregulated in advanced gastroesophageal adenocarcinomas. We assessed whether adding panitumumab (an EGFR inhibitor) or rilotumumab (a HGF inhibitor) to first-line fluoropyrimidine-based and platinum-based chemotherapy (modified oxaliplatin, leucovorin and fluorouracil [mFOLFOX6]) benefits to patients with advanced gastroesophageal adenocarcinoma. This phase II, open-label, randomised, three-arm study enrolled patients ≥18 years, with advanced gastroesophageal adenocarcinoma, Eastern Cooperative Oncology Group performance status 0–1 and no known HER2 overexpression. Patients were randomly assigned (1:1:1) mFOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2 bolus then 2400 mg/m2 over 46 h) alone or combined with panitumumab (6 mg/kg) or rilotumumab (10 mg/kg) every 2 weeks until limiting toxicity, patient's refusal or disease progression. The primary end-point was the 4-month progression-free survival (PFS) rate. Secondary end-points included overall survival (OS) and tolerance. The study enrolled 162 patients in 29 French centres. The median follow-up was 23.6 months (interquartile range = 16.4–29.0). The 4-month PFS rate was 71% (95% confidence interval [CI] = 57–82) with chemotherapy alone, 57% (95% CI = 42–71) combined with panitumumab and 61% (95% CI = 47–74) combined with rilotumumab. Median OS was 13.1 months (95% CI = 8.7–16.9) with chemotherapy alone, 8.3 months (95% CI = 6.2–13.2) combined with panitumumab and 11.5 months (95% CI = 7.9–17.1) combined with rilotumumab. Adverse events grade ≥III occurred less frequently with chemotherapy alone (62%) than with panitumumab (83%) and rilotumumab (89%). We found no benefit in adding panitumumab or rilotumumab to mFOLFOX6 first-line chemotherapy to treat advanced gastroesophageal adenocarcinoma patients. European Clinical Trials Database, number 2009-012797-12. • Fluoropyrimidine-platinum doublets are the standard for advanced gastric cancer. • EGFR and HGF/MET pathways are often deregulated in advanced gastric cancer. • Panitumumab and rilotumumab are directed against EGFR and HGF, respectively. • Adding panitumumab to chemotherapy is ineffective in advanced gastric cancer. • Adding rilotumumab to chemotherapy is ineffective in advanced gastric cancer. [ABSTRACT FROM AUTHOR]

Baseline circulating tumour DNA (ctDNA) is a potential prognostic marker in metastatic colorectal cancer (mCRC) patients. However, few studies have compared ctDNA with the usual prognostic factors, and no ctDNA cut-off has been proposed for daily use in clinical practice. Chemotherapy-naive patients with mCRC were prospectively included. Plasma samples were collected at diagnosis and analysed centrally by both NGS and methylation digital PCR. Baseline patient and disease characteristics, treatment regimens, and secondary surgeries were collected. The restricted cubic spline method was used to define the optimal cut-off of ctDNA mutated allelic frequency (MAF). Prognostic values were assessed on overall survival (OS) using Cox models. From July 2015 to December 2016, 412 patients were included. ctDNA was undetectable in 83 patients (20%). ctDNA was an independent prognostic marker for OS considering the whole study population. The optimal cut-off for ctDNA MAF was 20% with median OS of 16.0 and 35.8 months for patients with MAF ≥20% and<20%, respectively (hazard ratio = 0.40; 95% confidence intervals: 0.31–0.51; P < 0.0001). The independent prognostic value of ctDNA MAF at 20% was confirmed in subgroups defined by RAS/BRAF status or resectability of metastases. Combining ctDNA MAF and carcinoembryonic antigen levels allowed us to define three different prognostic groups with median OS of 14.2, 21.1, and 46.4 months (P < 0.0001). ctDNA with a MAF cut-off of 20% improves prognostication of chemotherapy-naïve mCRC patients and may be useful in the future for individualised therapeutic decisions and as a stratification factor in clinical trials. Trial registration: Clinicaltrials.gov, NCT02502656 • ctDNA at baseline was a strong prognostic biomarker. • An optimal mutated allelic frequency (MAF) cut-off of 20% was defined. • Prognostic value of ctDNA was found in all subgroups. • CEA and ctDNA MAF had an independent prognostic value and are not correlated. • CEA and MAF combination classified patients in three prognostic subgroups. [ABSTRACT FROM AUTHOR]

Abstract: Background: For resectable gastric cancer, both postoperative chemoradiotherapy and perioperative chemotherapy demonstrate high-level evidence for improved survival in Western populations. To evaluate the feasibility of pre- or postoperative chemoradiotherapy, we proposed two multicentre phase II studies. Patients and methods: Patients with localised, histologically confirmed gastric cancer and Eastern Cooperative Oncology Group (ECOG) performance status <2 judged suitable for curative resection were eligible. Eligible patients were assigned to either preoperative chemoradiotherapy followed by surgical resection or surgical resection followed by chemoradiotherapy depending on each centre. Chemoradiotherapy regimen included four courses of FOLFIRI (5 Fluorouracil, Leucovorin, Irinotecan) regimen then Concurrent fluorouracil at 200mg/m2/d by continuous infusion 5days each week. A dose of 50Gy in 25 fractions in the preoperative study, or 45Gy in 25 fractions in the postoperative study, was delivered. The primary end-point for both studies was the proportion of patients, who completed the therapeutic sequence. Results: Between September 2007 and January 2010, 63 patients were included in both studies. The postoperative study was stopped for futility at the first step. In the preoperative study, 31 patients (73.8%, confidence interval (CI) 95%: 65.8–90.1%) received complete therapeutic sequence. Serum albumin and dietary restriction evaluated by QLQ-STO22 (Quality of Life-Stomach module) score were significantly linked with chemoradiotherapy feasibility in univariate analysis with respectively Odds-ratio (OR) 1.16 [CI 95%: 1.01–1.33] and 0.17 [0.03–0.89], p =0.04. Median overall survival time was 26.4months in the preoperative study. Conclusion: Feasibility of chemoradiotherapy was not achieved for these studies: 73.8% (CI 95%: 65.8–90.1) and 42.9% (CI 95%: 21.8–66%) in preoperative and postoperative settings respectively. [Copyright &y& Elsevier]

Purpose: To analyze the efficacy, toxicity, and pattern of relapse after adjuvant cisplatin-based chemotherapy followed by three-dimensional irradiation and concomitant LV5FU2 chemotherapy (high-dose leucovorin and 5-fluorouracil bolus plus continuous infusion) in the treatment of completely resected high-risk gastric cancer. Methods and Materials: This was a retrospective analysis of 52 patients with high-risk gastric cancer initially treated by total/partial gastrectomy and lymphadenectomy between January 2002 and June 2007. Median age was 54 years (range, 36–75 years). Postoperative treatment consisted of 5-fluorouracil and cisplatin chemotherapy. Adjuvant chemotherapy was followed by three-dimensional conformal radiotherapy in the tumor bed and regional lymph nodes at 4500 cGy/25 fractions in association with concomitant chemotherapy. Concomitant chemotherapy consisted of a 2-h infusion of leucovorin (200 mg/m²) followed by a bolus of 5-fluorouracil (400 mg/m²) and then a 44-h continuous infusion of 5-fluorouracil (2400–3600 mg/m²) given every 14 days, for three cycles (LV5FU2 protocol). Results: Five-year overall and disease-free survival were 50% and 48%, respectively. Distant metastases and peritoneal spread were the most frequent sites of relapse (37% each). After multivariate analysis, only pathologic nodal status was significantly associated with disease-free and overall survival. Acute toxicities were essentially gastrointestinal and hematologic. One myocardial infarction and one pulmonary embolism were also reported. Eighteen patients had a radiotherapy program interruption because of acute toxicity. All patients but 2 have completed radiotherapy. Conclusion: Postoperative cisplatin-based chemotherapy followed by conformal radiotherapy in association with concurrent 5-fluorouracil seemed to be feasible and resulted in successful locoregional control. [ABSTRACT FROM AUTHOR]