bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-line fluoropyrimidine and oxaliplatin chemotherapy in gastro-entero-pancreatic grade III well-differentiated neuroendocrine tumors (NET G3).
Authors: Lamberti Giuseppe , Pusceddu Sara , Ibrahim Toni , Bongiovanni Alberto , Prinzi Natalie , Maggio Ilaria , Campana Davide 
Published: May 2020

e16709 Background: The 2019 World Health Organization (WHO) classification of neuroendocrine neoplasia (NEN) introduced the new category of well-differentiated NEN with Ki67 proliferation index ≥20% (NET G3). Fluoropyrimidine-based regimens with oxaliplatin (FOLFOX/XELOX) were a treatment option in neuroendocrine carcinomas with low Ki67. However, FOLFOX/XELOX efficacy in this newly defined NET G3 category is unknown. Objective of this study was to describe FOLFOX/XELOX efficacy in NET G3 and identify factors associated with outcome. Methods: We retrospectively collected all metastatic gastro-entero-pancreatic NET G3 patients who received a fluoropyrimidine-based regimen with oxaliplatin (FOLFOX/XELOX) as first-line treatment at 4 NEN-dedicated Italian Centers. Concomitant somatostatin analog (SSA) treatment was allowed and recorded. Objective response rate (ORR) was defined according to RECIST criteria v1.1. Factors associated with progression-free survival (PFS), overall survival (OS), and ORR were analyzed. Results: Twenty-nine NET G3 patients (median age 57 years, range 18-79) matching inclusion criteria were identified. Twenty patients (69%) were of pancreatic origin, while 9 (31%) had gastrointestinal primary. Median Ki67 was 30% (range 21-50). Treatment was FOLFOX in 14 (48%) and XELOX in 15 patients (52%), while 12 (44%) received also concomitant SSA. After a median follow-up of 44.1 months, median PFS was 7.9 months (95%CI 6.2 -11.4) and median OS was 44.8 months (95%CI 37.1 - NA). The 12 patients whose tumor responded to treatment (44% [95%CI 26-65]) had longer PFS (26.5 vs 5.0 months; p = 0.004) and OS (194.0 vs 38.0 months; p = 0.04) compared to those who did not respond. Progressive disease was the best disease response in 7 patients (24%). Objective response was associated with a reduced risk for progression (HR: 0.22 [95%CI: 0.07-0.62]; p = 0.007) while higher Ki67 was associated with an increased risk for progression (HR: 1.11 [95%CI: 1.04-1.19]; p = 0.002) and for death (HR: 1.09 [95%CI: 1.01-1.17]; p = 0.017). After correcting for confounding factor, ORR (HR: 0.26 [95%CI: 0.08-0.83]; p = 0.023) and Ki67 (HR: 1.09 [95%CI: 1.02-1.16]; p = 0.009) retained their association with the risk for progression, but not with the risk for death. Conclusions: Fluoropyrimidine-based regimens with oxaliplatin (FOLFOX/XELOX) may be active and effective in NET G3 of gastroenteropancreatic origin.
Association of neoadjuvant chemotherapy on survival in locally advanced gallbladder cancer.
Authors: Kazmi Syed Mohammad Ali , Goksu Suleyman Yasin , Ozer Muhammet , Sanford Nina Niu , Porembka Matthew R. , Wang Sam C. , Mansour John C. , Hsieh David , Aguilera Todd Anthony , Sanjeevaiah Aravind , Khosama Leticia , Maxwell Mary Claire , Beg Muhammad Shaalan 
Published: May 2020

e16716 Background: Gallbladder cancer (GBC) is an uncommon but highly fatal malignancy. Surgery remains the only potentially curative treatment for GBC. The role of neoadjuvant chemotherapy in patients with locally advanced GBC undergoing surgery is unknown. We studied the association of neoadjuvant chemotherapy on survival in locally advanced GBC patients who underwent resection. Methods: We identified adult patients with locally advanced (stage III-IV) GBC who underwent definitive surgery between 2004 and 2016 using the National Cancer Database. Treatment was categorized as neoadjuvant chemotherapy plus surgery (NAT), surgery plus adjuvant therapy (AT), and surgery alone (SA). Categorical variables were compared using the chi-square test with Bonferroni correction. Kaplan-Meier and Cox regression were used for survival analyses. We used 1:3 nearest neighbor propensity score matching based on NAT for each group. Results: Out of a total of 5,962 patients, 122 (2.2%) received NAT, 2934 (53.6%) AT, and 2421 (44.2%) SA. NAT was associated with private insurance and treatment at an academic/research facility (all p < .001) while SA patients were older, Hispanic, had government insurance, and higher comorbidities (all p < .001). Although all groups had similar lymph node assessment (NAT: 45%, AT: 46%, SA: 37%, p < .001), NAT was associated with lymph node negative disease (NAT 23%, AT 13.2%, SA 13.2%, p < .001). Median overall survival was higher in NAT compared to AT or SA (21 vs. 14 vs. 6 months, p < .001) which persisted after propensity score matching (21 vs. 15 vs. 9 months, p < .001) and multivariable regression analysis (Table). In node positive GBC, NAT was associated with improved median overall survival (NAT 24, AT 18, SA 8 months, p < .001). Conclusions: NAT is infrequently used in patients with locally advanced GBC. NAT is associated with improved median overall survival compared to AT and SA, and appears to be most beneficial in node positive disease. Prospective studies are needed to evaluate the role of neoadjuvant chemotherapy in locally advanced GB. [Table: see text]
Muscle impairment during follow-up as an independent prognostic factor for poor overall survival in pancreatic cancer.
Authors: Lambert Aurélien , Salleron Julia , Gavoille Céline , Viard Auréline , Ayav Ahmet , Conroy Thierry , Laurent Valérie 
Published: May 2020

e16726 Background: We aimed to assess that muscle impairment during follow-up is as an independent prognostic factor for poor overall survival in pancreatic cancer (PC) and is more accurate than a single muscle mass evaluation. Methods: Data from all patients with pancreatic adenocarcinoma at our center from 2009 to 2015 were retrieved (N = 114). A retrospective review of the total psoas area (TPA) was performed using manual segmentation on a single cross-sectional image through the third lumbar vertebrae for each available scan (N = 713, median number of scans per patient was 6 [3; 8]). For each patient, when at least two CT scans were available, the decrease in the TPA from baseline (Muscle Impairment) was expressed by a percentage. Results: In the univariate analysis, a TPA level under 420 mm2/m2 during the follow-up, with a HR = 3.419 ([2.168; 5.394]; 95% CI; p < 0.0001) and a TPA decrease of more than 20% from the baseline with a HR = 7.169 ([4.526; 11.353]; 95% CI; p < 0.0001) were prognostic factors for death. The multivariate analysis confirmed the results with a HR = 5.799 ([3.418; 9.839]; 95% CI; p < 0.0001) in the non-surgery group and a HR = 8.089 ([2.157; 30.339]; 95% CI; p = 0.0019) in the surgery group for a decrease in the TPA of more than 20% from the baseline. Conclusions: Muscle impairment during follow-up is a strong and independent prognostic factor for poor overall survival in patients with PC. It is in favor of a higher risk of death.
A single institution experience of brain metastases and pancreatic adenocarcinoma: Patients' treatments and outcomes.
Authors: Gouton Etienne , Chanez Brice , Launay Simon , Loir Elika , Moureau-Zabotto Laurence , Turrini Olivier , Gilabert Marine 
Published: May 2020

e16737 Background: Brain metastases (BM) occur extremely rare in pancreatic adenocarcinoma (PDAC) and few data are available regarding those patients‘ care and outcomes. Methods: We performed a retrospective monocentric analysis of our database to identify patients (pts) diagnosed with PDAC and BM from July 1997 to December 2019. Results: 16 pts were eligible among 4900 pts diagnosed with PDAC in our institution (0.3%). Median age was 64 years (38.2-74.6) with 50% female. At diagnosis, 68.8% were metastatic including 27.3% with synchronous BM. About 1/3 pts had ≥ 2 lines of chemotherapy before BM. BM were discovered from neurological symptoms in 62% of cases and either with systematic brain CT/MRI or unknown in 19% for both. BM treatment was: surgery (25%), whole brain radiation therapy (RT) (43.8%), stereotactic RT (6.3%), radiosurgery (6.3%), best supportive care (BSC) or unknown (6.3%). At follow-up cutoff date (01/01/2020), most of pts were dead (75%), 2 were alive and 2 lost of follow-up. Mean interval between initial diagnosis and BM was 9.9 months (mths) (0-73). Median time to develop BM was different between pts with non-metastatic or metastatic disease at diagnosis: 16.3 mths (6.5-44) and 4.2 mths (0-36.1), respectively (HR = 0.43 (CI95: 0.14-1.09; p = 0.09)). Median overall survival (mOS) was 14.5 mths (1.6-80.2). Definitely, the non-metastatic group at diagnosis had better survival with mOS of 40.2 mths (24.7-80.2) compared to 6.5 mths (1.7-49.8) for the metastatic group (HR = 0.24 (CI95: 0,06-0,63; p = 0.012)). The median survival period after diagnosis of BM was only 3.4 mths (0.5-13.7). Pts who underwent BM surgery had better survival with a median survival from surgery of 5.5 months (4-13.7) compared to RT (0.8 mths (0.4-2)) or BSC (0.6 mths (0.5-5.9)). HR for surgery versus RT was 0.12 (CI95: 0.02-0.31; p = 0.003). After BM diagnosis, 43.8% of patients had a systemic chemotherapy, without objective response on BM. One interesting metastatic pt with BRCA1 mutation achieved a complete response (CR) after FOLFIRINOX. One BM occurred 2 years after diagnosis, was treated with surgery + RT but relapsed 4.5 mths later with new BM. Extra-cranial CR was persistent. This pt, still alive, had the longest survival period after diagnosis of BM (13.7 mths) and OS (49.8 months). Conclusions: To our knowledge, this is one of the largest cohort reported of BM in PDAC. Very few cases exist to guide therapy. Surgery appears to be the best treatment for BM, when feasible. Further investigations are still needed to understand the pathogenicity of BM in pancreatic cancer.
Germline mutations in Brazilian pancreatic carcinoma patients.
Authors: Rodrigues Livia Munhoz , Maistro Simone , Katayama Maria Lucia Hirata , Leite Luiz A.Senna , Glasberg Joao , Ribeiro Ulysses , Guindalini Rodrigo Santa Cruz , Koike Folgueira Maria A. A. 
Published: May 2020

e16749 Background: Pancreatic cancer has the prospect of becoming the second leading cause of cancer death by 2030. The NCCN Guidelines recommend genetic testing for all patients with pancreatic cancer, however, the spectrum of germline mutations has not been extensively evaluated because recent studies with genetic testing have explored only a limited number of genes and have focused predominantly on Caucasian populations. Therefore, our objective is to evaluate the frequency and spectrum of germline mutations in unselected patients with pancreatic cancer in a multiethnic population. Methods: Patients from Instituto do Câncer do Estado de São Paulo (Brazil) with histopathological diagnosis of non-endocrine pancreatic carcinoma were included, regardless of the family history of cancer. These patients answered a life habits and family history of cancer questionnaire and supplied blood for the Next Generation Sequencing (MiSeq platform) with the TruSight Hereditary Cancer panel (Illumina), which includes 115 cancer predisposing genes. Variant analysis was performed with the VarStation, a Brazilian tool that offers post-sequencing computational support and aid for clinical interpretation. Results: To the present moment, 77 patients were evaluated. The mean age of the patients was 62 years (27-83), among whom, 13% with young age (≤50 years) and 47 women (61%). Thirty-eight patients (49%) reported cases of cancer in first-degree relatives. Regarding risk factors, 41 patients (53%) reported smoking, 19 (25%) alcohol ingestion and 20 (26%) had obesity. Seven out of 77 patients presented pathogenic variants in ATM (n = 2) , CHEK2, FANCM (n = 2) or PALB2 (n = 2) genes. Two of these patients ( CHEK2 and FANCM) had early onset pancreatic cancer (≤45 years), both denied smoking habit and family history of cancer in 1st degree relatives. Two patients, who were ATM mutation carriers, reported 1st or 2nd degree relatives with cancer and are alive after 4 and 8 years of diagnosis. Conclusions: In this unselected group of pancreatic cancer patients, 15% were young, almost half reported first-degree relatives with cancer and 9% were carriers of pathogenic variants in genes related with the homologous recombination DNA repair.
Trends in real-world clinical outcomes among patients (pts) with metastatic pancreatic adenocarcinoma (mPDAC) treated with liposomal irinotecan based regimens in the United States (US).
Authors: Koeller Jim M. , Cockrum Paul , Belanger Bruce , Corvino Frank A. , Surinach Andy , Kim George P. 
Published: May 2020

e16751 Background: The NAPOLI-1 study, a randomized phase 3 study in pts with mPDAC previously treated with gemcitabine-based therapy, demonstrated an improvement in overall survival (OS) with liposomal irinotecan + 5-fluorouracil/ leucovorin (5-FU/LV) vs. 5-FU/LV. In this analysis we describe the trends in pt characteristics, real-world OS (rwOS), and real-world time to-treatment failure (rwTTF) among pts with mPDAC treated with liposomal Irinotecan based regimens overall and stratified by tx initiation prior to 2018 (pre-2018) or after 2018 (post-2018). Methods: This retrospective observational study used de-identified data from Flatiron Health EHR database from over 280 cancer clinics in the US. Pt characteristics, rwOS, and rwTTF were assessed in adult pts diagnosed with mPDAC who received liposomal irinotecan treatment (tx) between January 1, 2016 and October 31, 2019. Results: Of the 590 pts treated with liposomal irinotecan based regimens, 53% were male, 56% were initially diagnosed with Stage IV disease, 92% were treated in the community setting, and median age at tx initiation was 69 (IQR: 62 – 75) years. Among pts with available ECOG scores (N = 435), 77% had a score of 0 or 1. 43% (n = 254) initiated tx pre-2018 and 57% (n = 336) post-2018. Pre-2018, 106 (42%) pts initiated liposomal irinotecan in the third line metastatic setting or later (3rd line+), 125 (49%) had ECOG score of 0-1, and median age was 68 (62–74) years. Post-2018, 36% of pts initiated tx in 3rd line+, 211 (63%) had ECOG score of 0-1, and median age was 70 (63 – 75) years. Median rwOS was 4.4 months [95% CI: 4.3–6.2] pre-2018 and 5.2 mos [4.3–6.2] post-2018. rwTTF was 1.6 mos [1.4–1.9] pre-2018 and 2.1 mos [1.6–2.5] among pts post-2018. Among pts treated in first- or second-line, pre-2018 rwOS was 5.3 mos [3.9–6.4] and post-2018 rwOS was 6.3 mos [5.0– 7.6]. Conclusions: In this descriptive real-world study of pts with mPDAC receiving liposomal irinotecan based regimens, pts initiating treatment post-2018 appear to be less pre-treated, older, and have better performance status than pts pre-2018. Pts treated post-2018 experienced numerically longer rwTTF and rwOS than pts treated pre-2018.
Real-world survival outcomes of using neoadjuvant chemotherapy in pancreatic cancer patients: Findings from the PURPLE clinical registry.
Authors: Lee Belinda , Witmond Vincent , Pereira-Salgado Amanda , Degeling Koen , Shapiro Julia , Thomson Benjamin N , Ananda Sumitra S , McLachlan Sue-Anne , Knowles Brett , Fox Adrian , Wong Rachel , Burge Matthew E. , Clarke Kate , Pattison Sharon Tracy , Nikfarjam Mehrdad , Nagrial Adnan , Zielinski Rob , Chee Cheng Ean , Gibbs Peter , IJzerman Maarten J. 
Published: May 2020

e16755 Background: Only a minority of pancreatic cancer patients (pts) are surgical candidates at presentation. Neoadjuvant chemotherapy (NAT) is proposed to increase the proportion of surgical candidates. This study investigates the impact of NAT in routine care of pancreatic cancer. Three cohorts were analysed, patients with early-stage resectable (ER), borderline resectable (BR) and locally advanced (LA) pancreatic cancer. Within these groups, survival outcomes of those undergoing immediate resection (IR) was compared to those receiving NAT with nab-paclitaxel and Gemcitabine (nabPGem) and NAT with FOLFIRINOX. Methods: The PURPLE registry consists of 1492 pancreatic cancer pts from 27 hospitals in Australia, New-Zealand and Singapore, collated between 2016-2019. After exclusion of LA unresectable and metastatic pts (n = 809), 683 pts were included. Kaplan-Meir curves estimated survival between groups with 95% confidence intervals. Multivariable cox proportional hazards models adjusted for age, gender and ECOG performance status. Results: Of 683 pts, 107 received NAT and 576 underwent IR. Those in the NAT group had favourable characteristics, including younger age (mean 63 vs. 66 yrs, p < 0.01) and higher proportion of ECOG 0 vs. ≥1 (64% vs 46%) than those undergoing IR. Of those that received NAT, 64 received FOLFIRINOX and 35 nabPGem. Those receiving FOLFIRINOX were younger (mean: 60 vs. 67 yrs, p < 0.01) and were more likely ECOG 0 compared to those receiving nabPGem (72% vs. 46%, p = 0.02). Resection rates for pts undergoing IR vs. NAT were 88% vs. 50% in ER and 16% vs. 43% in BR. Rates of R0 resection margins in pts undergoing IR vs. NAT were 54% vs. 25% in ER and 6% vs. 21% in BT. Comparing ER to BR, mOS was 29.9 vs. 20.3 mths (HR: 0.54, p < 0.01). Within BR, mOS was 20.3 vs. 17.2 mths for NAT vs. IR (HR: 1.11, p = 0.74). Comparing those receiving FOLFIRINOX vs. nabPGem over all groups, mOS was 22 mths vs. 12 mths (HR: 0.31, p < 0.01). Conclusions: Real-world data confirms the use of NAT remains infrequent in this Asia-Pacific population. The use of FOLFIRINOX was associated with better survival than nabPGem based on this observational study. Improved methods for treatment selection are required. Potential biomarkers including circulating tumor DNA are being explored in the DYNAMIC-Pancreas clinical trial.
The role of response as predictor of improved outcome in advanced pancreatic cancer (APC) patients (pts) treated with first-line Gemcitabine plus Nab-paclitaxel (GemNab).
Authors: Bensi Maria , Di Stefano Brunella , Bagalà Cinzia , Spring Alexia , Chiaravalli Marta , Ribelli Marta , Camarda Floriana , Maratta Maria Grazia , Tortora Giampaolo , Salvatore Lisa 
Published: May 2020

e16758 Background: GemNab is one of the first-line standard treatment (tx) of APC. To date, no predictive factors, both clinical and molecular, of benefit from this regimen exist. Two retrospective studies showed that early tumor shrinkage (ETS) can predict an improved outcome in APC pts receiving a first-line tx with FOLFIRINOX or GemNab. However, data regarding GemNab, limited to a small population of only 57 pts, seem to not confirm the association of ETS with a better outcome. Hence, we retrospectively analysed an homogeneous population of APC treated with first-line GemNab at our Institution, investigating the impact of several clinical factors, including response and ETS. Methods: APC pts receiving a first-line tx with GemNab were included in the analysis. The association of RECIST response and ETS with PFS and OS was evaluated. The following variables were collected: gender; age ( > vs ≤ 55 years and ≥ vs < 70 years ); baseline ECOG PS; Ca 19.9 baseline level (≥ vs < 200); anamnesis of diabetes; site of primary tumor (head/uncinate process vs body/tail); locally A vs metastatic (m) PC; synchronous vs metachronous; number of m sites (1 vs > 1); m sites (liver, peritoneum, lung, nodes); number of tx lines (1 vs > 1). Univariate and multivariate analyses for PFS and OS were performed. Results: A total of 184 APC pts receiving first-line GemNab at our Institution from February 2014 to May 2019 were included in the analysis. RR and ETS were assessed in 174 and 168 pts, respectively. RR was 30%, disease control rate (DCR) 63% and ETS was 24%. Responders had a significant better PFS (12.5 vs 5.7 months, p < 0.0001) and OS (25.1 vs 12.1 months, p < 0.0001). ETS was significantly associated with improved PFS (12.3 vs 6.2 months, p < 0.0001) and OS (24.0 vs 12.8 months, p < 0.0001). At the multivariate analysis a significant association with survival parameters was confirmed for RECIST response, but not for ETS. At the multivariate analysis, also metachronous disease and number of tx lines > 1 were independently associated with better OS. Conclusions: Despite its retrospective nature, this is one of the largest series of APC pts treated with first-line GemNab investigating the role of RECIST response and ETS in predicting outcome. On the basis of our results, RECIST response may be considered a positive prognostic factor, whereas ETS does not. In conclusion, achieving tumor shrinkage, not necessarily early, significantly delays PC progression and prolongs survival in pts treated with first-line GemNab.
The impact of 2nd-line treatment (tx) after 1st-line Gemcitabine plus Nab-paclitaxel (GemNab) in advanced pancreatic cancer (APC) patients (pts).
Authors: Di Stefano Brunella , Bensi Maria , Bagalà Cinzia , Spring Alexia , Chiaravalli Marta , Ribelli Marta , Maratta Maria Grazia , Camarda Floriana , Tortora Giampaolo , Salvatore Lisa 
Published: May 2020

e16759 Background: Three main phase III randomized studies investigated the role of 2nd-line tx in APC pts. The PANCREOX study failed to demonstrate a survival advantage of mFOLFOX vs 5FU/LV. Conversely, the CONKO-003 and NAPOLI-1 trials, demonstrated a significant survival improvement from the combination regimen OFF and 5FU+Nal-IRI, respectively, in comparison to 5FU/LV alone. Recently, final OS analysis from NAPOLI-1 demonstrated an association of specific characteristics (ECOG PS, age, Ca 19.9 baseline level, neutrophil-to-lymphocyte ratio and no liver metastases (m)) with OS > 1 year. The main limit of all these studies was due to the period they were carried out: no pts received 1st-line GemNab. Hence, we retrospectively analysed an homogeneous population of APC treated with 1st-line GemNab at our Institution, investigating the impact of 2nd-line tx. Methods: APC pts receiving a 2nd-line tx after 1st-line GemNab were included in the analysis. The following variables were collected: gender; age ( > vs ≤ 55 years and ≥ vs < 70 years ); baseline ECOG PS (0-1 vs 2-3); Ca 19.9 baseline level (≥ vs < 200); anamnesis of diabetes; site of primary tumor (head/uncinate process vs body/tail); number of m sites (1 vs > 1); m sites (liver, peritoneum, lung, nodes); RECIST response and ETS during 1-line GemNab. Univariate and multivariate analyses for PFS and OS were performed. Results: Out of 167 APC pts progressed to 1st-line GemNab, 93 (56%) pts received a 2nd-line tx, specifically 58 pts received an oxa-based regimen, 11 FOLFIRINOX, 8 FOLFIRI and 16 pts received other tx. Median 2nd-line PFS and OS were 3.3 and 5.6 months, respectively. Out of 87 pts evaluable for response, 7 pts achieved a partial response and 27 a stable disease, with a RR and a disease control rate (DCR) of 8% and 39%, respectively. Pts with baseline ECOG PS 0-1 had a significant better outcome in comparison to pts with PS 3-4 (PFS 4.2 vs 1.2 months, p < 0.0001; OS 7.2 vs 2.6 months, p = 0.0001). This significant association with survival parameters and ECOG PS was confirmed at the multivariate analysis. Conclusions: Despite the limited number of pts evaluated and the restrospective nature of our analysis, our results are in line with previous evidences, confirming the importance of a 2nd-line combination tx, when feasible, as well in an homogeneous population of APC pts treated with 1st-line GemNab. On the basis of our results, ECOG PS may be considered a prognostic factor and the choice of 2nd-line tx should be guided in primis by the baseline general conditions of APC pts.