BACKGROUND:Advanced pancreatic ductal adenocarcinoma (aPDAC) has a poor prognosis with median overall survival (OS) of about 12 months. It is therefore important to explore factors that predict the efficacy of third-line chemotherapy (L3) to identify patients who may benefit from this controversial treatment. METHODS:We conducted a multicenter retrospective cohort-based study of 202 French patients treated for aPDAC who received at least three treatment lines from January 2011 to March 2022. We used penalized Cox regressions to predict progression-free survival (PFS) and OS in patients on L3. RESULTS:Median age at the start of L3 was 64.3 years old and 63.5% had an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 0 or 1. The most frequent regimens for L3 were FOLFIRI (25.2% of patients). Median PFS was 2.2 months, while median OS was 4.2 months. In multivariate models, we identified the following predictors of both PFS and OS: age, sex, surgery for the primary tumor, FOLFIRINOX as the first-line therapy, duration of first and second-line treatments, and for L3: ECOG-PS level, peritoneum, liver and/or lung metastasis and depletion of therapeutic resources. The model incorporating these factors provided acceptable discrimination between event and event-free patients at 6 months post-L3 (area under the ROC curve of 0.83 for PFS and 0.73 for OS). CONCLUSION:The characteristics of patients and their aPDAC are readily available in clinical practice and were able to predict survival with L3. The online calculator we propose here could help physicians determine whether L3 chemotherapy would be beneficial.

In recent years, the combination of endobronchial ultrasound and endoscopic ultrasound has enabled “medical exploration” of the mediastinum for the study of mediastinal lymphadenopathies. These techniques are particularly important for the diagnosis and staging of lung cancers. Progress has been made with the availability of new-generation cutting needles for endoscopic ultrasound and new cryobiopsy needles for endobronchial ultrasound to improve the quality of samples.

Background: The impact of KRAS mutation testing on pancreatic ductal adenocarcinoma (PDAC) samples by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for reducing the need to repeat EUS-FNA has been demonstrated. Such testing however is not part of standard practice for endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). Objectives: We aim to analyse the proportion of non-contributive samples by EUS-FNB and to evaluate the impact of KRAS mutation testing on the diagnosis, theranostics and survival. Design: In this retrospective study, the impact on diagnosis and survival of KRAS testing for contributive and non-contributive samples by EUS-FNB was analysed. Methods: The EUS-FNB samples, combined with KRAS testing using the Idylla ® technique on liquid-based cytology from patients with PDAC between February 2019 and May 2023, were retrospectively reviewed. The cytology results were classified according to the guidelines of the World Health Organization System for Reporting Pancreaticobiliary Cytopathology (WHOSRPC). Results: A total of 85 EUS-FNB specimens were reviewed. In all, 25 EUS-FNB samples did not lead to a formal diagnosis of PDAC according to the WHOSRPC (30.2%). Out of these 25, 11 (44%) could have been considered positive for a PDAC diagnosis thanks to the KRAS mutation test without carrying out further diagnosis procedures. The sensitivity of KRAS mutation testing using the Idylla technique was 98.6%. According to the available data, survival rates were not statistically different depending on the type of mutation. Conclusion: KRAS mutation testing on liquid-based cytology using the Idylla or equivalent technique, combined with the PDAC EUS-FNB sample, should become a standard for diagnosis to avoid delaying treatment by doing another biopsy. Furthermore, knowledge of the KRAS status from treatment initiation could be used to isolate mutations requiring targeted treatments or inclusion in clinical research trials, especially for wild-type KRAS PDAC.

BACKGROUND:The impact of local management of pulmonary metastases on the disease course of patients with metastatic colorectal cancer is poorly assessed. METHODS:REPULCO database was a retrospective cohort on 18 years that included all patients treated for lung metastases from colorectal cancer who received local and/or systemic treatments. AIMS:Primary objective was overall survival, secondary were progression-free survival and survival without chemotherapy. RESULTS:Three hundred and fifteen patients were analyzed, 157 with only systemic treatments, 78 with only local treatments, and 80 with local and systemic treatments. Overall survival at 5 years was 26.9% (IC95%: [17.7-36.9]) for systemic treatments only, 61.0% (IC95%: [40.8-76.1]) for local treatments only, and 77.8% (IC95%: [60.1-88.3]) for local and systemic treatments. Progression-free survival at 2 years was 4.8% (IC95%: [2.1-9.2]) for systemic treatment only, 28.3% (IC95%: [17.7-39.9]) for local treatments only, and 21.8% (IC95%: [13.1-31.9]) for local and systemic treatments. Median survival without chemotherapy was 2.99 months (IC95%: [2.33-3.68]) for systemic treatments, 33.97 months (IC95%: [19.06-NA]) for local treatments, and 12.85 months (IC95%: [8.18-21.06]) for local and systemic treatments. CONCLUSION:Local treatments of lung metastasis led to prolonged survival and allowed long periods of time without chemotherapy in this cohort.

Detailed description of the methodology performed.

Objectives: To determine whether radiomics data can predict local tumor progression (LTP) following radiof-requency ablation (RFA) of colorectal cancer (CRC) lung metastases on the first revaluation chest CT. Methods: This case-control single-center retrospec-tive study included 95 distinct lung metastases treated by RFA (in 39 patients, median age: 63.1 years) with a contrast-enhanced CT -scan performed 3 months after RFA. Forty -eight radiomics features (RFs) were extracted from the 3D-segmentation of the ablation zone. Several supervised machine-learning algorithms were trained in 10 -fold cross-validation on reproducible RFs to predict LTP, with/without denoising CT-scans. An unsupervised classification based on reproducible RFs was built with k-means algorithm.Results: There were 20/95 (26.7%) relapses within a median delay of 10 months. The best model was a stepwise logistic regression on raw CT-scans. Its cross-validated performances were: AUROC = 0.72 (0.58-0.86), area under the Precision-Recall curve (AUPRC) = 0.44. Cross -validated balanced-accuracy, sensitivity and specificity were 0.59, 0.25 and 0.93, respectively, using p = 0.5 to dichotomize the model predicted probabilities (vs 0.71, 0.70 and 0.72, respectively using p = 0.188 according to Youden index). The unsupervised approach identified two clusters, which were not associated with LTP (p = 0.8211) but with the occurrence of per- RFA intra-alveolar hemorrhage, post- RFA cavitations and fistulizations (p = 0.0150). Conclusion: Predictive models using RFs from the post- RFA ablation zone on the first revaluation CT -scan of CRC lung metastases seemed moderately informative regarding the occurrence of LTP.Advances in knowledge: Radiomics approach on inter-ventional radiology data is feasible. However, patterns of heterogeneity detected with RFs on early re-evaluation CT -scans seem biased by different healing processes following benign RFA complications.

PCs expression in T cells and effect of PC inhibition on PD-1 expression, T cell signaling, survival and cytotoxicity.

Gemcitabine (Gem) alone or with Nab-paclitaxel (Gem-Nab) is used as second-line treatment for metastatic pancreatic adenocarcinoma (mPA) after FOLFIRINOX (FFX) failure; however, no comparative data exist. This study evaluates the efficacy and safety of adding Nab-paclitaxel to Gem for mPA after FFX failure. In this retrospective real-world multicenter study, from 2011 to 2019, patients with mPA receiving Gem-Nab (Gem 1000 mg/m² + Nab 125 mg/m², 3 out of 4 weeks) or Gem alone were included after progression on FFX. A total of 427 patients were included. Patients receiving Gem-Nab had more metastatic sites, peritoneal disease and less PS 2 (24% vs. 35%). After median follow-up of 22 months, Gem-Nab was associated with better disease control rate (DCR) (56% vs. 32%; P < 0.001), progression-free survival (PFS) (3.5 vs. 2.3 months; 95% CI: 0.43–0.65) and overall survival (OS) (7.1 vs. 4.7 months; 95% CI: 0.53–0.86). After multivariate analysis, Gem-Nab and PS 0/1 were associated with better OS and PFS. Grade 3/4 toxicity was more frequent with Gem-Nab (44% vs. 29%). In this study, Gem-Nab was associated with better DCR, PFS and OS compared with Gem alone in patients with mPA after FFX failure, at the cost of higher toxicity.

BACKGROUND:The high sensitivity of PET-CT can identify hypermetabolic mediastinal adenopathies during cancer management, but specificity is low and a biopsy is sometimes required to eliminate benign adenopathies.METHODS:This prospective diagnostic accuracy study included patients with hypermetabolic mediastinal lymphadenopathies revealed on PET-CT during either the initial management of a cancer, treatment evaluation, or monitoring. All patients underwent EUS-FNA. Diagnoses of malignancy based on cytological analysis following EUS-FNA were compared with clinical and radiological follow-up information. The treatment strategy decided before the results of the EUS-FNA pathology reports (Multidisciplinary Team Meeting [MTM-1]) was recorded and compared to the treatment strategy decided once pathological data from EUS-FNA were available (MTM-2).MAIN FINDINGS:Between 2013 and 2018, 75 patients were included with 47 eligible and evaluable patients. Sensitivity, specificity, and positive and negative predictive values of EUS-FNA were 93%, 100%, 100% and 90%, respectively. The concordance value between the therapeutic strategies determined for MTM-1 and MTM-2 was 44.7%. There were no significant differences in the intensity of fixation on PET-CT between malignant and benign lesions.CONCLUSION:The diagnostic accuracy of the minimally invasive EUS-FNA procedure is sufficiently robust to avoid the need for diagnostic surgery. The combination of PET-CT and EUS-FNA may alter the therapeutic strategy that would be considered after PET-CT alone.REGISTRATION:NCT01892501.

Radiofrequency ablation (RFA) of lung metastases of colorectal origin can improve patient survival and quality of life. Our aim was to identify pre- and per-RFA features predicting local control of lung metastases following RFA. This case-control single-center retrospective study included 119 lung metastases treated with RFA in 48 patients (median age: 60 years). Clinical, technical, and radiological data before and on early CT scan (at 48 h) were retrieved. After CT scan preprocessing, 64 radiomics features were extracted from pre-RFA and early control CT scans. Log-rank tests were used to detect categorical variables correlating with post-RFA local tumor progression-free survival (LTPFS). Radiomics prognostic scores (RPS) were developed on reproducible radiomics features using Monte-Carlo cross-validated LASSO Cox regressions. Twenty-six of 119 (21.8%) nodules demonstrated local progression (median delay: 11.2 months). In univariate analysis, four non-radiomics variables correlated with post-RFA-LTPFS: nodule size (> 15 mm, p < 0.001), chosen electrode (with difference between covered array and nodule diameter < 20 mm or non-expandable electrode, p = 0.03), per-RFA intra-alveolar hemorrhage (IAH, p = 0.002), and nodule location into the ablation zone (not seen or in contact with borders, p = 0.005). The highest prognostic performance was reached with the multivariate model including a RPS built on 4 radiomics features from pre-RFA and early revaluation CT scans (cross-validated concordance index= 0.74) in which this RPS remained an independent predictor (cross-validated HR = 3.49, 95% confidence interval = [1.76 – 6.96]). Technical, radiological, and radiomics features of the lung metastases before RFA and of the ablation zone at 48 h can help discriminate nodules at risk of local progression that could benefit from complementary local procedure. • The highest prognostic performance to predict post-RFA LTPFS was reached with a parsimonious model including a radiomics score built with 4 radiomics features. • Nodule size, difference between electrode diameter, use of non-expandable electrode, per-RFA hemorrhage, and a tumor not seen or in contact with the ablation zone borders at 48-h CT were correlated with post-RFA LTPFS.

Patient de 61 ans opéré en 1995 d’une tumeur neuroendocrine grêlique. Une première récidive biologique avec ascension du taux sérique de chromogranine A conduit à l’exérèse chirurgicale d’une adénopathie mésentérique évolutive en 1996, puis à une radiofréquence d’une métastase osseuse fémorale en 2018. En février 2019, une nouvelle augmentation du taux de chromogranine A conduit à la réalisation d’une TEP-TDM 68Ga-DOTATOC sans injection de produit de contraste iodé. Cet examen met en évidence un unique nodule intensément hyperfixant dans la queue du pancréas (17 mm–SUVmax 69,4), dont l’intensité de fixation est supérieure à la fixation splénique physiologique (SUVmax 35,1). La lecture rétrospective des TDM annuels de suivi retrouve ce nodule stable depuis 2009, isodense au pancréas et de cinétique de rehaussement sensiblement identique. Devant la stabilité morphologique de ce nodule intra-pancréatique, un nodule de rate accessoire intra-pancréatique est suspecté, classiquement hyperfixant en 68GA-DOTATOC. Cependant, l’intensité de fixation de ce nodule, supérieure à la rate, est atypique pour un nodule de splénose intrapancréatique et conduit à la réalisation d’une IRM et d’une scintigraphie aux globules rouges-altérés. L’IRM pancréatique met en évidence un nodule hyperartérialisé de signal et rehaussement non strictement parallèle à ceux de la rate ne permettant pas de confirmer formellement l’hypothèse de nodule de rate accessoire. La scintigraphie aux globules rouges altérés retrouve l’absence de séquestration du traceur et conduit à la décision en RCP d’exérèse chirurgicale du nodule. L’analyse anatomopathologique de la pièce opératoire confirme une tumeur neuroendocrine bien différenciée de Ki67 < 1 % de grade II, qui correspond bien aux données d’imagerie complémentaire par scintigraphie aux globules rouges-altérés. Ce poster présente en parallèle les différents éléments d’imagerie préopératoire.

798 Background: In the context of a new cancer or relapse, the high sensitivity (Se) (95-100%) of PET-CT with 18F-FDG can lead to the demonstration of hypermetabolic mediastinal adenopathies. Its lower specificity (Sp) (89%) can require histological examination. We report the results of a prospective, single-center study evaluating the diagnostic performance of EUS-FNA in this indication. Methods: Prospective single-center study featuring patients in whom PET had revealed hypermetabolic mediastinal lymphadenopathy requiring diagnostic certainty. All EUS-FNA were performed with a 19-gauge needle (EchoTip, Cook Endoscopy). Main objective: To evaluate the diagnostic performance in terms of Se and Sp of EUS-FNA in the characterization of hypermetabolic mediastinal adenopathies in PET in the context of a new cancer or relapse. Secondary objectives: To evaluate the negative predictive value (NPV) of the EUS-FNA and to evaluate the percentage of surgical diagnostic procedures avoided. The standard technique was a thoraco-abdominopelvic CT scan at 6 months and at 12 months. Results: 52 patients were eligible and evaluable for the primary endpoint. The most common primary cancers were mammary (17.3%) and bronchial (13.5%). The lymph nodes were analyzed as malignant in 44.2% of cases, benign in 50% of cases and atypical or suspicious in 3.8% of cases. The malignant lymph nodes were metastatic for breast cancer in 21.7% of cases, bronchial cancer in 17.4% of cases, colorectal cancer in 17.4% of cases and prostate cancer in 13% of cases. The Se of the EUS-FNA was 92% (95% CI 0.74-0.99) and the Sp 100%. NPV was 87% (95% CI: 0.59-0.98). A diagnostic surgical procedure was necessary in 2% of the cases. PET and EUS-FNA often allowed the modification of the therapeutic strategy. Conclusions: When a confirmed diagnosis is required, the diagnostic accuracy of the minimally invasive procedure of EUS-FNA, is sufficiently robust to avoid a surgical diagnosis technique. The combination of PET and EUS-FNA may alter the therapeutic strategy that would have been considered after PET alone. Clinical trial information: NCT01892501.

A 60-year-old woman presented to hospital with abdominal pain and massive weight loss. Imaging studies confirmed the presence of a tumor of the pancreas. Histologic analysis of the sampling performed by echoendoscopic ultrasound fine-needle aspiration found aspects evocative of adenosquamous carcinoma. This case report highlights the difficulties of clinical pathologic diagnosis for these occasionally composite tumors. The patient underwent palliative chemotherapy based on platinum and 5-fluorouracil, followed by second-line chemotherapy with FOLFIRI after progression. Adenosquamous carcinoma of the pancreas remains a rare tumor with very poor prognosis and limited therapeutic options.

Background: Pre-operative chemotherapy for colorectal liver metastasis (CRLM) is thought to be the cause of hepatotoxicity of non-tumoural parenchyma. Studies on hepatotoxicity are contradictory. We investigated the impact of a single-line pre-operative chemotherapy on non-tumoural liver analysed by an expert hepatico-pancreatico-biliary pathologist, and the consequences on surgical outcomes. Patients and methods: Patients operated for CRLM, after a pure first-line pre-operative chemotherapy, were retrospectively included. Two comparative histopathological analyses were performed for vascular toxicity and steatohepatitis. Results: Between 2003 and 2015, 147 patients were included. Chemotherapy was based on oxaliplatin (40.1%), irinotecan (55.8%), or both (4.1%). The expert pathologist described 38.8% of vascular lesions including dilation, nodular regeneration, and peliosis. In multivariate analysis, vascular lesions correlated to male sex (P = .01), pre-operative platelets <150 g/L (P = .04), and aspartate aminotransferase to platelet ratio index (APRI) score >0.36 (P = .02). Steatohepatitis was observed in 15 patients (10.2%), more frequently after irinotecan (14.8% vs 3.4%, P = .01; odds ratio [OR] = 7.3; 95% confidence interval [CI] = [1.5-34.7]), and for patients with body mass index (BMI) >25 kg/m2 (P = .004; OR = 10.0; 95% CI = [2.1-47.5]). A total of 29 patients (19.7%) developed major complications with 2 risk factors: portal vein obstruction (PVO) and septic surgery. Reproducibility assessment of steatohepatitis and dilated lesions by 2 pathologists showed moderate agreement (Kappa score 0.53 and 0.54, respectively). Conclusions: There is a probable association between non-alcoholic steatohepatitis (NASH) and irinotecan. Oxaliplatin seems to lead to higher vascular lesions. Except in the presence of pre-existent comorbidities, liver toxicities should not restrain the use of pre-operative chemotherapy prior to parenchymal-sparing surgery.

Background: Folfirinox (FFX) and gemcitabine/nab-paclitaxel (GN) are both standard first-line treatments in patients with metastatic pancreatic cancer (mPC). However, data comparing these two chemotherapeutic regimens and their sequential use remain scarce. Methods: Data from two independent cohorts enrolling patients treated with FFX ( n = 107) or GN ( n = 109) were retrospectively pooled. Primary endpoint was overall survival (OS). Progression-free survival (PFS) was the secondary endpoint. A propensity score based on age, gender, performance status (PS), and presence of liver metastases was used to make groups comparable. Results: In the whole study population, OS was significantly higher in FFX (14 months; 95% CI: 10–21) than in GN groups (9 months; 95% CI: 8–12) before ( p = 0.008) and after ( p = 0.021) adjusting for age, number of metastatic sites, liver metastases, peritoneal carcinomatosis and CA19.9 level at baseline. PFS tends to be higher in FFX (6 months) than GN groups (5 months; p = 0.053). After matching ( n = 49/group), patients were comparable for all baseline characteristics including PS. In the matched population, there was a trend toward greater OS in patients treated with FFX (HR = 0.67; p = 0.097). However, survival in each group was not solely a result of the first-line regimen. The proportion of patients who were fit for GN after FFX failure (FFX–GN sequence) was higher (46.9%) than the reverse sequence (20.4%; p = 0.01), which suggests a higher feasibility for the FFX–GN sequence. Corresponding median OS were 19 months versus 9.5 months, respectively ( p = 0.094). Conclusion: This study shows greater OS with FFX than with GN in patients with mPC. GN after FFX failure appears more feasible than the reverse sequence.

We report the first case of sarcoidosis-like reaction in a patient treated by anti-PD-L1 for a breast cancer. A 69-year-old woman presented with a histologically confirmed lung metastasis of a triple negative breast cancer. She was treated by nab-paclitaxel plus anti-PD-L1 in first line. After 2 months, a dramatic lung response was noticed but an involvement of mediastinal lymph nodes appeared. Endoscopic ultrasound-guided fine-needle aspiration of these lymph nodes revealed multiple epitheloid granulomas without caseating necrosis in favour of a sarcoidosis-like reaction. The patient remained free of symptom and in complete lung response on anti-PD-L1 treatment as a maintenance therapy.

Background: A combination of nab-paclitaxel plus gemcitabine (N + G) has recently become a standard first-line treatment in patients with metastatic pancreatic adenocarcinoma (MPA), but there are currently no published data concerning second-line treatment after N + G. The aim of this study was to evaluate the survival outcomes and tolerability of three usual fluoropyrimidine-based regimens FOLFOX, FOLFIRI and FOLFIRINOX after N + G failure in MPA patients. Methods: Patients receiving N + G as first-line regimen were prospectively identified in 11 French centers between January 2014 and January 2017. After disease progression or unac-ceptable toxicity, patients eligible for second-line therapy were enrolled in the study. The primary endpoint was overall survival following the second-line regimen. Secondary endpoints were objective response, progression-free survival and safety. Results: Out of 137 patients treated with N + G as first-line regimen, 61 (44.5%) received second-line chemotherapy, including FOLFOX (39.4%), FOLFIRI (34.4%) or FOLFIRINOX (26.2%). Baseline characteristics were not different between the 3 groups. In particular, median age was 71.7 years, sex ratio was 1/1, and performance status (PS) was 0 in 11.5% of case. Main grade 3 toxici-ties were neutropenia (4.9%) and nausea (3.3%), without major differences between the groups. No toxic death was observed. Median second-line progression-free survival (PFS) and overall sur-vival (OS) were 2.95 (95% CI: 2.3-5.4) and 5.97 months (95% CI: 4.0-8.0), respectively, with no difference between the 3 groups. Median OS from the start of first-line chemotherapy was 12.7 months (10.4-15.1) and was significantly better in patients receiving FOLFIRI after N + G failure, 18.4 months (95% CI: 11.7-24.1, P < 0.05), as compared with FOLFOX or FOLFIRINOX (10.4 and 12.3 months, respectively). Conclusion: This study suggests that second-line fluoropyrimidine-based regimens after N + G failure are feasible, have a manageable toxicity profile in selected patients with MPA, and are associated with promising clinical outcomes, in particular when combined with irinotecan. Randomized phase 3 trials are needed to confirm this trend. (C) 2019 Published by Elsevier Masson SAS.