Management of biliary tract cancers in early-onset patients: A nested multicenter retrospective study of the ACABI GERCOR PRONOBIL cohort.

BACKGROUND & AIMS: Accumulating data has shown the rising incidence and poor prognosis of early-onset gastrointestinal cancers, but few data exist on biliary tract cancers (BTC). We aimed to analyse the clinico-pathological, molecular, therapeutic characteristics and prognosis of patients with early onset BTC (EOBTC, age ≤50 years at diagnosis), versus olders. METHODS: We analysed patients diagnosed with intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder adenocarcinoma between 1 January 2003 and 30 June 2021. Baseline characteristics and treatment were described in each group and compared. Progression-free survival, overall survival and disease-free survival were estimated in each group using the Kaplan-Meier method. RESULTS: Overall, 1256 patients were included, 188 (15%) with EOBTC. Patients with EOBTC demonstrated fewer comorbidities (63.5% vs. 84.5%, p < .0001), higher tumour stage (cT3-4: 50.0% vs. 32.3%, p = .0162), bilobar liver involvement (47.8% vs. 32.1%, p = .0002), and metastatic disease (67.6% vs. 57.5%, p = .0097) compared to older. Patients with EOBTC received second-line therapy more frequently (89.5% vs. 81.0% non-EOBTC, p = .0224). For unresectable patients with BTC, median overall survival was 17.0 vs. 16.2 months (p = .0876), and median progression-free survival was 5.8 vs. 6.0 months (p = .8293), in EOBTC vs. older. In advanced stages, fewer actionable alterations were found in EOBTC (e.g., IDH1 mutations [7.8% vs. 16.6%]; FGFR2-fusion [11.7% vs. 8.9%]; p = .029). CONCLUSIONS: Patients with EOBTC have a more advanced disease at diagnosis, are treated more heavily at an advanced stage but show similar survival. A distinctive molecular profile enriched for FGRF2 fusions was found.

Gemcitabine and Paclitaxel Versus Gemcitabine Alone After 5-Fluorouracil, Oxaliplatin, and Irinotecan in Metastatic Pancreatic Adenocarcinoma: A Randomized Phase III PRODIGE 65-UCGI 36-GEMPAX UNICANCER Study.

PURPOSE: GEMPAX was an open-label, randomized phase III clinical trial designed to assess the efficacy and tolerability of gemcitabine plus paclitaxel versus gemcitabine alone as second-line treatment for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who previously received 5-fluorouracil, oxaliplatin, and irinotecan. METHODS: Patients with histologically or cytologically confirmed mPDAC were randomly assigned (2:1) to receive GEMPAX (paclitaxel 80 mg/m2 + gemcitabine 1,000 mg/m2; IV; once at day (D) 1, D8, and D15/arm A) or gemcitabine (arm B) alone once at D1, D8, and D15 every 28 days until progression, toxicity, or patient's decision. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), quality of life, and safety. RESULTS: Overall, 211 patients (median age, 64 [30-86] years; 62% male) were included. After a median study follow-up for alive patients of 13.4 versus 13.8 months in arm A versus arm B, the median OS (95% CI) was 6.4 (5.2 to 7.4) versus 5.9 months (4.6 to 6.9; hazard ratio [HR], 0.87 [0.63 to 1.20]; P = 0.4095), the median PFS was 3.1 (2.2 to 4.3) versus 2.0 months (1.9 to 2.3; HR, 0.64 [0.47 to 0.89]; P = 0.0067), and the ORR was 17.1% (11.3 to 24.4) versus 4.2% (0.9 to 11.9; P = 0.008) in arm A versus arm B, respectively. Overall, 16.7% of patients in arm A and 2.9% in arm B discontinued their treatment because of adverse events (AEs). One grade 5 AE associated with both gemcitabine and paclitaxel was reported in arm A (acute respiratory distress), and 58.0% versus 27.1% of patients experienced grade ≥3 treatment-related AEs in arm A versus arm B, among which 15.2% versus 4.3% had anemia, 15.9% versus 15.7% had neutropenia, 19.6% versus 4.3% had thrombocytopenia, 10.1% versus 2.9% had asthenia and 12.3% versus 0.0% had neuropathy. CONCLUSION: While GEMPAX did not meet the primary end point of OS versus gemcitabine alone in patients with mPDAC in the second-line setting, both PFS and ORR were significantly improved.

Metastatic Colorectal Cancer Treated with Combined Liver Resection, Cytoreductive Surgery, and Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Predictive Factors for Early Recurrence.

BACKGROUND: Selection of colorectal cancer patients with concomitant peritoneal (PM) and liver metastases (LM) for radical treatment with cytoreductive surgery (CRS), including liver resection and hyperthermic intraperitoneal chemotherapy (HIPEC), needs improvement. This retrospective, monocentric study was designed to evaluate the predictive factors for early recurrence, disease-free survival (DFS), and overall survival (OS) in such patients treated in a referral center. METHODS: Consecutive colorectal cancer patients with concomitant LM and PM treated with curative intent with perioperative systemic chemotherapy, simultaneous complete CRS, liver resection, and HIPEC in 2011-2022 were included. Clinical, radiological (before and after preoperative chemotherapy), surgical, and pathological data were investigated, along with long-term oncologic outcomes. A multivariate analysis was performed to identify predictive factors associated with early recurrence (diagnosed <6 months after surgery), DFS, and OS. RESULTS: Of more than 61 patients included, 31 (47.1%) had pT4 and 27 (40.9%) had pN2 primary tumors. Before preoperative chemotherapy, the median number of LM was 2 (1-4). The median surgical PCI (peritoneal carcinomatosis index) was 3 (5-8.5). The median DFS and OS were 8.15 (95% confidence interval [CI] 5.5-10.1) and 34.1 months (95% CI 28.1-53.5), respectively. In multivariate analysis, pT4 (odds ratio [OR] = 4.14 [1.2-16.78], p = 0.032]) and pN2 (OR = 3.7 [1.08-13.86], p = 0.042) status were independently associated with an early recurrence, whereas retroperitoneal lymph node metastasis (hazard ratio [HR] = 39 [8.67-175.44], p < 0.001) was independently associated with poor OS. CONCLUSIONS: In colorectal cancer patients with concomitant PM and LM, an advanced primary tumor (pT4 and/or pN2) was associated with a higher risk of early recurrence following a radical multimodal treatment, whereas RLN metastases was strongly detrimental for OS.

The level of glucose in pancreatic cyst fluid is more accurate than carcinoembryonic antigen to identify mucinous tumors: A French multicenter study.

Background and Objectives: Pancreatic cyst fluid level of glucose is a promising marker to identify mucinous from nonmucinous tumors, but the glucose assay has not yet been recommended. The objective of this study is to compare the diagnostic performances of pancreatic cyst fluid level of glucose and carcinoembryonic antigen (CEA). Methods: In this French multicenter study, data of consecutive patients who underwent fine-needle aspiration of pancreatic cyst with intracyst glucose assay between 2018 and 2022 were retrospectively reviewed. The area under the receiver operating characteristic curve (AUROC) of glucose and corresponding sensitivity (Se), specificity (Sp), accuracy (Acc), positive predictive value (PPV), and negative predictive value (NPV) were calculated and compared with those of CEA. The best threshold of glucose was identified using the Youden index. Results: Of the 121 patients identified, 81 had a definitive diagnosis (46 mucinous, 35 nonmucinous tumors) and were included for analysis. An intracystic glucose level <41.8 mg/dL allowed identification of mucinous tumors with better diagnostic performances (AUROC, 93.6%; 95% confidence interval, 87.2%-100%; Se, 95.3%; Sp, 91.2%; Acc, 93.5%; PPV, 93.2%; NPV, 93.9%) compared with CEA level >192 ng/mL (AUROC, 81.2%; 95% confidence interval, 71.3%-91.1%; Se, 41.7%; Sp, 96.9%; Acc, 67.6%; PPV, 93.8%; NPV, 59.6%) (P = 0.035). Combining values of glucose and CEA did not offer additional benefit in terms of diagnosis. Conclusion: Our results confirm previously published data and support the use of pancreatic cyst fluid glucose for the identification of mucinous tumors when the definitive diagnosis remains uncertain.

Genetic counselling referral practices for patients with pancreatic adenocarcinoma: A French retrospective multicentre observational cohort study (CAPANCOGEN).

BACKGROUND/OBJECTIVES: Genetic counselling (GC) is a key step in the identification of inherited germline mutations. However, the oncogenetic practices are poorly described for pancreatic adenocarcinoma (PA) in Europe. The CAPANCOGEN study aimed to describe the GC referral practices in France and assess the implementation of international guidelines in patients with PA. METHODS: Information about GC referrals with PA was collected in 13 French centres from September 2019 to October 2021. In the 5 largest centres, personal and familial histories of cancers and diseases associated with a higher risk of germline mutations were collected in 460 patients, according to international, American, European and French GC referral guidelines. Univariate and multivariate logistic regression analysis were performed to identify the factors influencing GC referral. RESULTS: Among 833 patients, a total of 100 patients (12%) had an indication of GC according to local multidisciplinary tumour board meetings (MTBM). Among these patients, 41% did not undergo GC. The median time between MTBM and GC was 55 days (IQR: 14.5-112). Among 460 patients with collected personal and familial history, 31.5% were not referred to a GC despite an existing indication. In multivariate logistic regression analysis, suspected CDKN2A (p = 0.032) or BRCA mutation (p < 0.001), familial pancreatic cancer history (p < 0.001) and controlled disease with first-line platinum-based chemotherapy (p < 0.001) increased the referral rate. Conversely, older age (p = 0.002) and a locally advanced PA (p = 0.045) decreased the risk of GC referral. CONCLUSIONS: GC referral is inadequate despite valuable information in patients' medical files.

A Systematic Review on the Interest of Drug-tolerant Assay in the Monitoring of Inflammatory Bowel Disease.

Many patients with inflammatory bowel disease [IBD] are treated with anti-tumour necrosis factor [TNF] therapies, of which infliximab [IFX] is most commonly used. Loss of response [LOR] to anti-TNF therapy due to immunogenic failure accounts for 20% of subsequent medical intervention and is defined, using a drug-sensitive assay, as low or undetectable concentration of drug with high titres of anti-drug antibodies [ADAb]. We performed a systematic review to investigate the use of a drug-tolerant assay during both induction and maintenance, to monitor patients treated with anti-TNFs. After the search on PubMed, 90 publications were reviewed. Most ADAb detection methods are drug-sensitive, cannot detect ADAb in the presence of drug, and therefore cannot be used close to drug administration when the drug concentration is too high. To overcome this major limitation, several drug-tolerant techniques have been developed and will be discussed in this review. Using drug-tolerant assays, ADAb against IFX or adalimumab [ADM] can be detected during induction and predict primary non-response or LOR. Drug-sensitive assays do not allow detection of ADAb during the induction phase when IFX or ADM concentration is typically high.

Chemotherapy in advanced pancreatic adenosquamous carcinoma: A retrospective multicenter AGEO study.

Pancreatic adenosquamous carcinoma (PASC) account for <5% of pancreatic malignancies. The efficacy of modern chemotherapy regimens in patients with advanced PASC is unknown. Patients with advanced PASC from 2008 to 2021 were consecutively included in this retrospective multicenter study. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method. Ninety-four PASC from 16 French centers were included (median age, 67.3 years; males, 56.4%; metastatic disease, 85.1%). The first-line treatment was chemotherapy for 79 patients (84.0%) (37 FOLFIRINOX (FX), 7 Gemcitabine-nab paclitaxel (GN) and 35 for all other regimen) or best supportive care (BSC) alone for 15 patients (16.0%). No significant difference was observed between FX and GN in terms of PFS (P = .67) or OS (P = .5). Modern regimens pooled together (FX and GN) as compared to all others chemotherapy regimens showed an improvement of overall response rate (39.5% and 9.7%, P = .002), PFS (median, 7.8 vs 4.7 months, P = .02) and OS (median, 12.7 vs 9.2 months, P = .35). This large study evaluating first-line treatment regimens in advanced PASC suggests that modern regimens as FX or GN may be preferable to all other chemotherapy regimens. These results deserve confirmation in prospective studies.

Transarterial Embolization for Active Gastrointestinal Bleeding: Predictors of Early Mortality and Early Rebleeding.

Background: The aim of this study was to determine predictive factors of early mortality and early rebleeding (≤30 days) following transarterial embolization (TAE) for treatment of acute gastrointestinal bleeding. Methods: All consecutive patients admitted for acute gastrointestinal bleeding to the interventional radiology department in a tertiary center between January 2012 and January 2022 were included. Exclusion criteria were patients: (1) aged < 18-year-old, (2) referred to the operation room without TAE, (3) treated for hemobilia, (4) with mesenteric hematoma, (5) lost to follow-up within 30 days after the procedure. We evaluated pre and per-procedure clinical data, biological data, outcomes, and complications. Results: Sixty-eight patients were included: 55 (80.9%) experienced upper gastrointestinal bleeding and 13 (19.1%) lower gastrointestinal bleeding. Median age was 69 (61−74) years. There were 49 (72%) males. Median hemoglobin was 7.25 (6.1−8.3) g/dL. There were 30 (50%) ulcers. Coils were used in 46 (67.6%) procedures. Early mortality was 15 (22.1%) and early rebleeding was 17 (25%). In multivariate analysis, hyperlactatemia (≥2 mmol/L) were predictive of early mortality (≤30 days). A high number of red blood cells units was associated with early rebleeding. Conclusion: This study identified some predictive factors of 30-day mortality and early rebleeding following TAE. This will assist in patient selection and may help improve the management of gastrointestinal bleeding.

Structural and Socio-Spatial Determinants Influencing Care and Survival of Patients with a Pancreatic Adenocarcinoma: Results of the PANDAURA Cohort.

Background and aims: Pancreatic cancer is highly lethal and often diagnosed at an advanced stage. This cohort study analyzes the impact of care pathways, delays, and socio-spatial determinants on pancreatic cancer patients' diagnosis, treatment, and prognosis. Method: Patients with pancreatic adenocarcinoma newly diagnosed at all stages between January and June 2016 in the AuRA French region were included. The influence on survival of delays of care, healthcare centers' expertise, and socio-spatial determinants was evaluated. Results: Here, 538 patients were included in 76 centers including 116 patients (21.8%) with resectable, 64 (12.0%) borderline-resectable, 147 (27.6%) locally-advanced tumors, and 205 (38.5%) with metastatic disease. A delay between first symptoms and CT scans did not statistically influence overall survival (OS). In resected patients, OS was significantly higher in centers with more than 20 surgeries (HR<5 surgeries/year = 2.236 and HR5-20 surgeries/year = 1.215 versus centers with > 20 surgeries/year p = 0.0081). Regarding socio-spatial determinants, patients living in municipalities with greater access to a general practitioner (HR = 1.673, p = 0.0153) or with a population density below 795.1 people/km2 (HR = 1.881, p = 0.0057) were significantly more often resectable. Conclusion: This cohort study supports the pivotal role of general practitioner in cancer care and the importance of the centralization of pancreatic surgery to optimize pancreatic cancer patients' care and outcomes. However, delays of care did not impact patient survival.

Time impact on the antidiabetic effects of key bariatric surgeries: a network meta-analysis of randomized controlled trials with meta-regression.

BACKGROUND: Few studies compare the efficacy of the key bariatric procedures in type 2 diabetes management over the long term. None offer a reliable comparison of their respective efficacy loss over time. OBJECTIVES: To analyze and compare the time evolution of the antidiabetic effects of the key bariatric procedures. SETTING: Obesity surgery departments in America, Europe, and Asia. METHODS: All the randomized clinical trials assessing the efficacy of bariatric surgery in type 2 diabetes management with 1-5 years of follow-up were reviewed. A network meta-analysis with meta-regression was performed to compare the effectiveness of each technique and its respective efficacy loss temporal dynamics. RESULTS: Thirty-one trials involving 1906 patients were included. In comparison to Roux-en-Y gastric bypass, the 5-year complete or partial diabetes remission rates were inferior with medical treatment (odds ratio [OR] = .05; 95% credible interval [CrI]: .02-.13) and gastric banding (OR = .38; 95% CrI: .16-.87), equivalent with sleeve gastrectomy (OR = 1.08; 95% CrI: .59-1.97), and superior with 1 anastomosis gastric bypass (OR = 3.00; 95% CrI: 1.12-8.33) and biliopancreatic diversion and its affiliated techniques (OR = 3.71; 95% CrI: 1.16-12.55). However, remission rates and glycemic control progressively decreased whatever the treatment option evaluated. Moreover, this loss of efficacy followed a statistically comparable temporal dynamic to those of Roux-en-Y gastric bypass regardless of the therapeutic strategy implemented. CONCLUSIONS: No therapeutic modality offered stable antidiabetic effects. The gap observed between the techniques after a 5-year follow up concerning remission rates and glycemic control could depend essentially on the magnitude of the effects initially obtained. However, these results need to be confirmed over longer follow-up periods.

Impact of the COVID-19 pandemic on disease stage and treatment for patients with pancreatic adenocarcinoma: A French comprehensive multicentre ambispective observational cohort study (CAPANCOVID).

BACKGROUND: The COVID-19 pandemic caused major oncology care pathway disruption. The CAPANCOVID study aimed to evaluate the impact on pancreatic adenocarcinoma (PA) - from diagnosis to treatment - of the reorganisation of the health care system during the first lockdown. METHODS: This multicentre ambispective observational study included 833 patients diagnosed with PA between September 1, 2019 and October 31, 2020 from 13 French centres. Data were compared over three periods defined as before the outbreak of COVID-19, during the first lockdown (March 1 to May 11, 2020) and after lockdown. RESULTS: During the lockdown, mean weekly number of new cases decreased compared with that of pre-pandemic levels (13.2 vs. 10.8, -18.2%; p = 0.63) without rebound in the post-lockdown period (13.2 vs. 12.9, -1.7%; p = 0.97). The number of borderline tumours increased (13.6%-21.7%), whereas the rate of metastatic diseases rate dropped (47.1%-40.3%) (p = 0.046). Time-to-diagnosis and -treatment were not different over periods. Waiting neoadjuvant chemotherapy in resectable tumours was significantly favoured (24.7%-32.6%) compared with upfront surgery (13%-7.8%) (p = 0.013). The use of mFOLFIRINOX preoperative chemotherapy regimen decreased (84.9%-69%; p = 0.044). After lockdown, the number of borderline tumours decreased (21.7%-9.6%) and advanced diseases increased (59.7%-69.8%) (p = 0.046). SARS-CoV-2 infected 39 patients (4.7%) causing 5 deaths (12.8%). CONCLUSION: This cohort study suggests the existence of missing diagnoses and of a shift in disease stage at diagnosis from resectable to advanced diseases with related therapeutic modifications whose prognostic consequences will be known after the planned follow-up. TRIAL REGISTRATION: Clinicaltrials.gov NCT04406571.

Gastric Pneumatosis with Portal Venous Gas can be Treated Non-operatively: A Retrospective Multi-institutional Study.

BACKGROUND: Gastric pneumatosis (GP) is a rare radiologic finding with an unpredictable prognosis. The aim of this study was to identify mortality risk factors from patients presenting with GP on computed tomography (CT), and to develop a model which would allow us to predict which patients would benefit most from operative management. METHODS: Between 2010 and 2020, all CT-scan reports in four tertiary centers were searched for the following terms: "gastric pneumatosis," "intramural gastric air" or "emphysematous gastritis." The retrieved CT scans were reviewed by a senior surgeon and a senior radiologist. Relevant clinical and laboratory data for these patients were extracted from the institutions' medical records. RESULTS: Among 58 patients with GP, portal venous gas and bowel ischemia were present on CT scan in 52 (90%) and 17 patients (29%), respectively. The 30-day mortality rate was 31%. Univariate analysis identified the following variables as predictive of mortality at the time of the diagnosis of GP: abdominal guarding, hemodynamic instability, arterial lactate level >2 mmol/l, and the absence of gastric dilatation. Multivariable analysis identified the following variables as independent predictors of mortality: arterial lactate level (OR: 1.39, 95% CI: 1.07-1.79) and the absence of gastric dilatation (OR: 0.07, 95% CI: 0.01-0.79). None of the patients presenting with a baseline lactate rate<2 mmol/l died within 30 days following diagnosis, and no more than 17 patients out of 58 had bowel ischemia (29%). CONCLUSIONS: GP could be managed non-operatively, even in the presence of portal venous gas. However, patients with arterial lactate level>2 mmol/l, or the absence of gastric dilation should be surgically explored due to a non-negligible risk of mortality.

Safety and efficacy of emergency transarterial embolization for mesenteric bleeding.

BACKGROUND: Patients with spontaneous or traumatic active mesenteric bleeding cannot be treated endoscopically. Transarterial embolization can serve as a potential alternative to emergency surgery. Literature on transarterial embolization for mesenteric bleeding remains very scarce. The objective of this study was to evaluate the safety and efficacy of transarterial embolization for mesenteric bleeding. We reviewed all consecutive patients admitted for mesenteric bleeding to the interventional radiology department, in a tertiary center, between January 2010 and March 2021. Mesenteric bleeding was defined as mesenteric hematoma and contrast extravasation and/or pseudoaneurysm visible on pre-operative CT scan. We evaluated technical success, clinical success, and complications. RESULTS: Among the 17 patients admitted to the interventional department for mesenteric bleeding, 15 presented with active mesenteric bleeding requiring transarterial embolization with five patients with hemodynamic instability. Mean age was 67 ± 14 years, including 12 (70.6%) males. Technical success was achieved in 14/15 (93.3%) patients. One patient with technical failure was treated by percutaneous embolization with NBCA-Lipiodol mixture. Three patients (20%) had early rebleeding: two were treated by successful repeat embolization and one by surgery. One patient (6.7%) had early death within 30 days and two patients (13.3%) had late death after 30 days. Mean length of hospitalization was 12.8 ± 7 days. There were no transarterial embolization-related ischemic complications. CONCLUSION: Transarterial embolization is a safe and effective technique for treating mesenteric bleeding even in patients with hemodynamic instability. Transarterial embolization doesn't close the door to surgery and could be proposed as first intention in case of mesenteric bleeding.

Swapping Versus Dose Optimization in Patients Losing Response to Adalimumab With Adequate Drug Levels.

BACKGROUND: In cases of loss of response due to mechanistic failure under antitumor necrosis factor agents, it is recommended to switch to another class of biologics. Two different strategies were compared in patients with inflammatory bowel disease (IBD) who were treated with nonoptimized adalimumab (ADA) and experienced a loss of response despite therapeutic trough levels of adalimuma-either ADA dose optimization or switching to vedolizumab or ustekinumab. METHODS: Patients under maintenance therapy with ADA monotherapy (40 mg every 14 days) and who experienced a secondary loss of response with trough levels > 4.9 µg/mL were included prospectively in this nonrandomized study. The primary end point was the survival rate without therapeutic discontinuation after ADA dose optimization or switching to another class of biologics. RESULTS: Adalimumab was optimized (n = 61 patients, 42 Crohn's disease, 19 ulcerative colitis) or swapped for vedolizumab (n = 40, 20 ulcerative colitis) or ustekinumab (n = 30, 30 Crohn's disease). At 24 months, 11 out of 70 patients (14.8%) in the swap group discontinued treatment compared with 36 out of 61 (59.6%) patients in the optimization group (P < 0.001). The median time without therapeutic discontinuation was significantly longer in the swap group (>24 months) than in the optimization group (13.3 months, P < 0.001). In the optimization group, treatment discontinuation was positively associated with baseline fecal calprotectin >500 µg/g (HR, 3.53; 95% CI, 1.16-10.72; P = 0.026) and inversely associated with variation of trough levels of adalimumab (>2 µg/mL from baseline to week 8 after optimization; HR, 0.51; 95% CI, 0.13-0.82; P = 0.03). In the swap group, no factor was associated with treatment discontinuation. CONCLUSION: In IBD patients under ADA maintenance therapy who experience a secondary loss of response and in whom trough levels are >4.9µg/mL, swapping to another class is better than optimizing ADA, which is, however, appropriate in a subgroup of patients.

Gemcitabine/Nab-Paclitaxel versus FOLFIRINOX in Locally Advanced Pancreatic Cancer: A European Multicenter Study.

BACKGROUND: Gemcitabine/nab-paclitaxel (GN) and FOLFIRINOX (FFX) are two standard first-line therapies for metastatic pancreatic cancer (PC) but have rarely been compared, especially in patients with locally advanced PC (LAPC). METHODS: This is a retrospective European multicenter study including patients with LAPC treated with either GN or FFX as the first-line therapy between 2010 and 2019. Coprimary objectives were progression-free survival (PFS) and overall survival (OS), both estimated using the Kaplan-Meier method. RESULTS: A total of 147 patients (GN: n = 60; FFX: n = 87) were included. Tumor resection rates were similar between the two groups (16.7% vs. 16.1%; p = 1), with similar R0 resection rates (88.9%). Median PFS rates were not statistically different: 9 months (95% CI: 8-13.5) vs. 12.1 months (95% CI: 10.1-14.6; p = 0.8), respectively. Median OS rates were 15.7 months (95% CI: 12.6-20.2) and 16.7 months (95% CI: 14.8-20.4; p = 0.7), respectively. Abdominal pain at the baseline (HR = 2.03, p = 0.03), tumors located in the tail of the pancreas (HR = 4.35, p = 0.01), CA19-9 > 200 UI/L (HR = 2.03, p = 0.004) and tumor resection (HR = 0.37, p = 0.007) were independent prognostic factors for PFS, similarly to OS. CA19-9 ≤ 200 UI/L (OR = 2.6, p = 0.047) was predictive of the tumor response. Consolidation chemoradiotherapy, more often used in the FFX group (11.7% vs. 50.6%; p < 0.001), was not predictive. CONCLUSION: This retrospective study did not show any difference between GN and FFX as the first-line treatment in patients with LAPC.

Randomized Phase II Trial Evaluating Two Sequential Treatments in First Line of Metastatic Pancreatic Cancer: Results of the PANOPTIMOX-PRODIGE 35 Trial.

PURPOSE: Metastatic pancreatic cancer (mPC) still harbors a dismal prognosis. Our previous trial (PRODIGE 4-ACCORD 11) demonstrated the superiority of 6-month chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) over gemcitabine for overall survival. The high limiting oxaliplatin-related neurotoxicity supports the evaluation of an oxaliplatin stop-and-go strategy and a sequential strategy in mPC. METHODS: In this phase II study, patients were randomly assigned to receive either 6 months of FOLFIRINOX (arm A), 4 months of FOLFIRINOX followed by leucovorin plus fluorouracil maintenance treatment for controlled patients (arm B), or a sequential treatment alternating gemcitabine and fluorouracil, leucovorin, and irinotecan every 2 months (arm C). The primary end point was progression-free survival at 6 months. RESULTS: Between January 2015 and November 2016, 276 patients (mean age: 63 years; range: 40-76 years) were enrolled (A: 91, B: 92, and C: 90). Grade 3 or 4 neurotoxicity occurred in 10.2% of patients in arm A and 19.8% in arm B. The median ratio of received dose/targeted dose of oxaliplatin was 83% in arm A and 92% in arm B. The 6-month progression-free survival was 47.1% in A, 42.9% in B, and 34.1% in C. The median overall survival was 10.1 months in arm A, 11.2 in arm B, and 7.3 in arm C. Median survival without deterioration in quality-of-life scores was higher in the maintenance arm (11.4 months) than in arms A and C (7.2 and 7.5 months, respectively). CONCLUSION: Maintenance with leucovorin plus fluorouracil appears to be feasible and effective in patients with mPC controlled after 4 months of induction chemotherapy with FOLFIRINOX. Severe neurotoxicity was higher in the maintenance therapy arm, probably because of the higher cumulative dose of oxaliplatin.

Management of Patients with Pancreatic Ductal Adenocarcinoma in the Real-Life Setting: Lessons from the French National Hospital Database.

Pancreatic ductal adenocarcinoma (PDAC) remains a major public health challenge, and faces disparities and delays in the diagnosis and access to care. Our purposes were to describe the medical path of PDAC patients in the real-life setting and evaluate the overall survival at 1 year. We used the national hospital discharge summaries database system to analyze the management of patients with newly diagnosed PDAC over the year 2016 in Auvergne-Rhône-Alpes region (AuRA) (France). A total of 1872 patients met inclusion criteria corresponding to an incidence of 22.6 per 100,000 person-year. Within the follow-up period, 353 (18.9%) were operated with a curative intent, 743 (39.7%) underwent chemo- and/or radiotherapy, and 776 (41.4%) did not receive any of these treatments. Less than half of patients were operated in a high-volume center, defined by more than 20 PDAC resections performed annually, mainly university hospitals. The 1-year survival rate was 47% in the overall population. This study highlights that a significant number of patients with PDAC are still operated in low-volume centers or do not receive any specific oncological treatment. A detailed analysis of the medical pathways is necessary in order to identify the medical and territorial determinants and their impact on the patient's outcome.

A Low Total Psoas Muscle Area Index Is a Strong Prognostic Factor in Metastatic Pancreatic Cancer.

OBJECTIVES: The total psoas area index (TPI) is an emerging alternative to the total skeletal muscle area index as a prognostic factor but has never been evaluated in metastatic pancreatic cancer (mPC). METHODS: Areas were manually recorded, as previously described. Sex-specific cutoffs were identified by optimum stratification of TPI using log-rank χ2 statistic associated with mortality to define sarcopenic psoas. Progression-free survival (PFS) and overall survival (OS) were the primary objectives. Two period groups were used as internal validation. RESULTS: During the period study, 79 patients were treated for mPC. The TPI was correlated with PFS (hazards ratio, 0.81; P = 0.02) and OS (hazards ratio, 0.7; P < 0.001). Optimum thresholds defining sarcopenic psoas were less than 5.73 cm2/m2 in men and less than 4.37 cm2/m2 in women. Patients with sarcopenic psoas (62.0%) had shorter median PFS (2.9 months) compared with the others (6.6 months, adjusted P log-rank = 0.01), independently to the intensity of chemotherapy, weight loss, and performance status greater than 1. Similarly, OS was independently shorter in patients with sarcopenic psoas (7.6 months) versus the others (22.2 months, adjusted P < 0.001). These results were confirmed in the 2 period groups. CONCLUSIONS: A low TPI is a stronger independent prognostic factor in mPC.

Early detection of anti-drug antibodies during initiation of anti-tumour necrosis factor therapy predicts treatment discontinuation in inflammatory bowel disease.

BACKGROUND: Anti-drug antibodies develop mostly during the induction therapy with anti-tumour necrosis factor (TNF) drugs and can be revealed by means of a drug-tolerant assay. AIM: To investigate whether the early detection of anti-drug antibodies during the induction therapy was predictive of treatment discontinuation. METHODS: In a prospective study, consecutive patients with inflammatory bowel disease (IBD), who should start an anti-TNF, were enrolled and followed regularly during 24 months or less in case of non- or loss of response (LOR) or adverse events requiring treatment discontinuation. Anti-TNF levels and anti-drug antibodies were measured at week 2 for adalimumab (ADA) and weeks 2 and 6 for infliximab (IFX) using a drug-tolerant assay. RESULTS: One hundred and eight patients were enrolled (54 under ADA). At week 2, antibodies to ADA and to IFX were detected in 76% and 67% of patients. Time to treatment discontinuation was significantly shorter (P < 0.001) in patients with antibodies to ADA ≥2.0 µg/mL-eq (6.0 vs 24 months, HR = 18.51, 95% CI [4.35-78.71]) or with antibodies to IFX ≥4.0 µg/mL-eq (5.5 vs >24 months, HR = 13.89, 95% CI [4.08-47.31]) at week 2 compared to patients without positive antibodies. Antibodies to ADA and to IFX were predictive of treatment failure within 24 months with a sensitivity of 79% and 62%, and specificities and positive predictive values of 100%. In multivariate analysis, antibodies to ADA or to IFX at week 2 were the only factors associated with treatment discontinuation. CONCLUSIONS: The prevalence of antibodies to anti-TNF is high when detected early using a drug-tolerant assay, and their appearance predicts further treatment discontinuation.