bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved overall survival for patients with early-onset pancreatic ductal adenocarcinoma.
Authors: Nair Kanika G. , Kamath Suneel Deepak , Wei Wei , Tullio Katherine , Estfan Bassam N. , Khorana Alok A. 
Published: January 2021

379 Background: The median age of diagnosis of pancreatic ductal adenocarcinomas (PDAC) is 70 years. Only about 20% of patients are diagnosed prior to the age of 60. We sought to identify clinical characteristics and outcomes of patients with early-onset PDAC as compared to later-onset PDAC. Methods: We identified histologically confirmed cases of pancreatic adenocarcinoma with information about age and overall survival (OS) diagnosed between 2004 and 2016 from the National Cancer Database (NCDB). Differences in demographic, disease and treatment characteristics and socioeconomic factors between younger and older patients were assessed by Chi-square test. The effect of age, race, insurance status, community median income and community educational attainment on overall survival (OS) were assessed using log rank test. Results: Of 321,896 patients who met inclusion criteria, 71,263 (22%) were younger than 60 years and 250,633 were 60 years of age or older at diagnosis. Median OS for younger patients was 9.5 months, compared to 5.6 months for older patients ( p< 0.0001). Younger patients were more likely to be diagnosed with stage IV disease (47.8% vs 43.4%), to be Black (16.1% vs 10.7%) or Hispanic (6.4% vs 4.5%), have a Charlson-Deyo comorbidity index of 0 (73.5% vs 63.3%), have private insurance (65.1% vs 20.5%), and receive treatment at academic centers (45.9% vs 40.9) (all p< 0.0001). Younger patients were also more likely to receive surgery (26.2% vs 19.5%), radiation (23.0% vs 15.9%), and chemotherapy (65.9% vs 46.7%) (all p< 0.0001). Conclusions: Survival for patients with early-onset PDAC is significantly better than older patients despite more patients being diagnosed with stage IV disease. This may be attributable to younger patients having less comorbidities and receiving more treatment. Concerningly, Black and Hispanic patients make up a larger proportion of younger patients with PDAC, and further work is needed to investigate these differences and underlying causes.
Adjuvant therapy in patients with resected pancreatic adenocarcinoma: Analysis of treatment allocation patterns in a Canadian provincial institution.
Authors: Chahal Manik , Loree Jonathan M. , Lim Howard John , Davies Janine Marie , Renouf Daniel John , Gill Sharlene 
Published: January 2021

383 Background: In recent years adjuvant therapy (AT) for pancreatic cancer has evolved. Improved overall survival (OS) was demonstrated first in 2017 with gemcitabine and capecitabine (GemCap), and then further improved in 2018 with FOLFIRINOX compared to gemcitabine (gem) alone. Given these options, we retrospectively reviewed the patterns of AT allocation in the province of British Columbia (BC) during these periods of adoption of newer AT regimens. Methods: Patients (pts) treated at BC Cancer centers between January 2017 to June 2018 (the GemCap era), and July 2018 to July 2019 (the FOLFIRINOX era), who had undergone curative intent resection and received at least one cycle of AT were included for chart review. Patient and disease characteristics, treatment details, and stated rationale for choice of AT regimen were collected. Analyses were performed with one-way ANOVA for comparison of means between regimens, and Chi-squared or Fisher Exact tests to determine correlation between clinicopathologic factors and likelihood of undergoing a given AT regimen. Results: 122 pts were identified: 67 treated in the GemCap era (gem: 25, 37%, and GemCap: 42, 63%) and 55 treated in the FOLFIRINOX era (gem: 18, 33%, GemCap: 18, 33%, FOLFIRINOX: 19, 34%). Examined variables included age, gender, ECOG, T and N stage, margins, lymphovascular invasion and post-operative CA19-9. In the GemCap era, use of GemCap vs Gem was associated with younger average age (p = 0.001) and positive lymph node status (91% vs. 60%, p = 0.005). In the FOLFIRINOX era, use of gem AT was associated with a delayed time from surgery to consultation. (p = 0.036) AT assignment was not influenced by high volume vs low volume centre in the GemCap era; however, pts were more likely to receive GemCap in low-volume centres during the mFOLFIRINOX era (p = 0.045). The most common stated reasons for choice of a less intense AT regimen were pt comorbidities or functional status (GemCap era: 24% and FOLFIRINOX era: 31%). Conclusions: Despite improvements in survival with newer AT regimens, the majority of pts in our real-world setting were assigned a less intense AT regimen. Within the limits of a small sample size, significant pt or disease factors predictive of AT assignment were not identified aside from age and lymph node positivity in the GemCap era, and time from surgery to consultation in the FOLFIRINOX era. Efforts to improve adoption of newer AT regimens and optimize pt eligibility for FOLFIRINOX are warranted.
AGIG chemo-immunotherapy in patients with advanced pancreatic cancer: A single-arm, single-center, phase II study.
Authors: Dai Wangshu , Qiu Xin , Lu Changchang , Zou Zhengyun , Sha Huizi , Kong Weiwei , Liu Baorui , Du Juan 
Published: January 2021

384 Background: To date, chemotherapy remains the only effective treatment of unresectable pancreatic adenocarcinoma. In the last few years, the interest in the use of immunological anticancer strategies is greatly increased. AGIG is a novel chemo-immunotherapy regimen that combines nab-paclitaxel + gemcitabine chemotherapy with sequential recombinant interleukin-2 and granulocyte-macrophage colony stimulating factor (GM-CSF) therapy. We conducted a single-arm prospective phase II study to determine the efficacy and safety of the first-line treatment of advanced pancreatic cancer with AGIG regimen. Methods: Nab-paclitaxel (120 mg/m2) and gemcitabine (1000 mg/m2) were administered intravenously to all patients on days 1 and 8 triweekly, interleukin-2 and GM-CSF (100 µg) were administered subcutaneously on days 3-5 after chemotherapy. The primary end point was ORR by the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included safety profile, progression-free survival (PFS), overall survival (OS). Patients’ conditions and the efficacy and safety were assessed every 4 cycles. Results: Between 11/2018 and 01/2020, 64 patients were enrolled. In the 64 evaluable patients, the ORR and DCR were 43.75% and 76.6%, respectively. The median follow-up time was 12.1 (range 7.1–22.4) months, the median PFS was 5.7 (range 1.63–15.8) months, and the median OS was 14.2 (range 2.9–22.0) months. The most common adverse event was fever (75%). The incidence of grade 3/4 neutropenia was 4.69%. In subgroup analyses, we found that eosinophil count in the blood elevated three times higher than baseline level predicted a longer survival. Conclusions: The AGIG Chemo-immunotherapy regimen has presented encouraging ORR, OS, and manageable toxicities as first-line therapy for advanced pancreatic cancer. This regimen may be a novel reliable therapeutic option for patients with preserved performance status. The improvement of treatment efficiency may be related to the activation of non-specific immune response. Clinical trial information: NCT0376867. Research Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School. [Table: see text]
Real-world genomic and treatment landscape in advanced colorectal cancer identifies treatment differences pre- and post-ctDNA genomic profiling.
Authors: Yu Junhua , Raghav Kanwal Pratap Singh , Parikh Aparna Raj , Hanna David , Marino Enrique , Raymond Victoria M. , Nagy Rebecca , Zhang Nicole , Corcoran Ryan Bruce , Kopetz Scott , Strickler John H. , Lang Kathryn 
Published: January 2021

39 Background: Clinical insights gained from real-world data have led to numerous advances in oncology including new and expanded drug approvals and an understanding of real-world clinical utilization. In this precision oncology age, integrating real-world clinical data with genomic data can lead to further advancements. We aimed to understand the genomic and treatment landscape in advanced colorectal cancer (aCRC) by leveraging a uniquely large and detailed clinical-genomic database. Methods: The GuardantINFORM (Guardant Health) database comprises aggregated commercial payer health claims and de-identified records from over 100,000 individuals with comprehensive ctDNA results (Guardant360). GuardantINFORM was queried for patients (pts) with a diagnosis of CRC. Pts with fewer than two pharmacy claims prior to or after the first ctDNA test were excluded from the regimen analysis. Latest claims data was truncated as of 8/31/2020. Results: 10,845 pts had a total of 13,510 ctDNA tests (1 – 19 tests/pt). The first ctDNA test date was from 06/2014 - 06/2020. The majority of pts had one ctDNA test (86.7%) while 5% had three or more tests. 87.9% of ctDNA tests had at least one genomic alteration identified, with the distribution of alterations consistent with prior reports (Table). 78% of pts had at least two pharmacy claims before and/or after the first ctDNA test. Of those pts with at least one CRC treatment, the most commonly prescribed CRC regimens up to one year prior to the first ctDNA test were FOLFOX +/- bevacizumab (16%, 18%), FOLFIRI +/- bevacizumab (17%, 11%), capecitabine (15%), 5-FU (12%), and regorafenib (5.2%). Anti-EGFR mono and combination therapy was reported in 6% and 16% of pts pre ctDNA testing. Immune checkpoint inhibitor (ICPi) mono and combination therapy was reported in 2% and 0.5% of pts. The most commonly prescribed CRC regimens post first ctDNA test were capecitabine (16%), FOLIRI +/- bevacizumab (15%, 13%), tipiracil and trifluridine (15%), FOLFOX +/- bevacizumab (12%, 14%), 5-FU (11%), and regorafenib (10%). Anti-EGFR mono and combination therapy was reported in 8% and 18% of pts post ctDNA testing. ICPi mono and combination therapy was reported in 5% and 1% of pts. Conclusions: Using a large and uniquely detailed clinical-genomic dataset, we produced results that replicate the observed distribution of ctDNA identified mutations present in aCRC. This genomic information combined with real-world clinical data provides valuable insights into the variety of longitudinal treatments, including before and after comprehensive ctDNA genomic profiling, allowing for detailed outcomes research, especially focused on precision oncology. [Table: see text]
Real-world study of treatment patterns and outcomes among patients with metastatic pancreatic ductal adenocarcinoma (PDAC) in Europe.
Authors: Taieb Julien , Hammel Pascal , Reni Michele , Palmer Daniel H. , Bridgewater John A. , Cubillo Antonio , Prager Gerald W. , Vermeire Alice , D'Esquermes Nathalie , Biville-Hedouin Fabienne , Teng Zhaoyang , Seufferlein Thomas , Macarulla Teresa 
Published: January 2021

391 Background: Few data are available regarding real-world treatment patterns and outcomes for metastatic PDAC (mPDAC) in Europe. Methods: This retrospective, observational, chart-review study involved medical oncologists and gastroenterologists from France, Germany, Italy, Spain, and the UK. Physicians completed online patient (pt) reports for 20 consecutive pts diagnosed with PDAC between 01 and 10/2016. Here, the analysis is focused on treated pts diagnosed with mPDAC. Reports provided information on general disease and pt characteristics, diagnosis, and treatment of metastatic disease. Outcomes included median PFS and OS according to each line of metastatic therapy. In addition, how baseline performance status (PS) and treatment sequence affected OS and PFS were assessed. Results: 304 physicians (France [n=62], Germany [n=60], Italy [n=63], Spain [n=66], UK [n=53]) participated and enrolled 6,000 pts with PAC, of whom 3827 had mPDAC. Of the 3827, 3432 were treated for their metastatic disease. The most common first-line therapies were modified FOLFIRINOX (28.4%), gemcitabine + nab-paclitaxel (28.0%), and gemcitabine monotherapy (23.0%), while the most common second-line therapies were gemcitabine monotherapy (25.0%), 5-FU + oxaliplatin (21.8%), and gemcitabine + nab-paclitaxel (16.7%). The longest median PFS and OS were obtained when using mFOLFIRINOX as first-line therapy, with gemcitabine-based combinations as second-line therapy. However, pt characteristics were more favorable with FOLFIRINOX compared with the other regimens used in first line. The most common treatment in first line for patients with a worse baseline PS (PS >1) was gemcitabine monotherapy (571 patients [46%]); in addition, having a worse baseline PS was predictive of shorter survival in second line. The most common reason for discontinuation of either line was disease progression. The study showed that the choice of first- and second-line treatment among European physicians is in accordance with current ESMO guidelines; in contrast, the choice of subsequent line was more heterogeneous, according to local practices. Additional data concerning first and second line OS and PFS per treatment regimen will be presented at the meeting. Conclusions: This large real-life study highlights a clear picture of treatment patterns in European real-world clinical practice and outcomes for metastatic PDAC, which may help in more effectively managing such patients in the future. Further univariate and multivariate analysis will complete this first description.
Genomic characterization of ATM alterations in advanced pancreatic ductal adenocarcinoma (PDAC).
Authors: Perera Sheron , Denroche Robert Edward , Holter Spring , Kelly Deirdre , Zhang Amy , Wang Yifan , Dodd Anna , Ramotar Stephanie , Hutchinson Shawn , Tehfe Mustapha , Ramjeesingh Ravi , Biagi James Joseph , Wilson Julie , Notta Faiyaz , Fischer Sandra , Zogopoulos George , Grant Robert C , Gallinger Steven , Knox Jennifer J. , O'Kane Grainne M. 
Published: January 2021

396 Background: BRCA1/2 and PALB2 are genes critical to the faithful repair of double strand breaks through the homologous recombination repair (HRR) pathway. Alterations in these genes serve as predictive biomarkers to both platinum and PARP inhibitors. Ataxia-telangiectasia mutated ( ATM) is also indirectly involved in HRR; however, its role as a predictive biomarker to DNA damage response agents is debated. Herein we evaluated the genomic characteristics and clinical outcomes of patients with ATM alterations on the Comprehensive Molecular Characterization of Advanced Ductal Pancreas Adenocarcinoma for Better Treatment Selection (COMPASS) trial. Methods: Patients on this study undergo a biopsy for whole genome sequencing (WGS) and RNA sequencing prior to chemotherapy; those with germline variants in ATM were reviewed by a genetics counsellor and defined as pathogenic, likely pathogenic, variant of unknown significance (VUS) or benign/likely benign. Genomic characteristics were reviewed and published classifiers of homologous recombination deficiency (HRD) were applied to all cases and included the percentage of substitution base signature (SBS) 3, the HRDetect score, the computed algorithm of large scale transitions, telomeric allelic imbalances and loss of heterozygosity (LOH), otherwise known as the genomic instability score (GIS). Results: As of January 2020, 304 patients were enrolled and 245 patients had both WGS and clinical data available. 86 germline variants in ATM were present in 70 patients. The majority of these (80%) were classified as benign or likely benign. 10 VUS were detected and 4 patients (2%) had pathogenic/likely pathogenic variants (PV). Of these 4 patients, LOH or a second somatic hit was evident in 1 case. Upon review of the PVs and VUS, SBS were consistent with typical PDAC and tumour mutational burden was low. HRDetect scores were low ( < 0.1) for 13/14 cases with either a VUS or PV; one VUS without biallelic loss, had a high HRDetect score, with presence of SBS 3 and a high GIS. This particular case was also found to have a tandem duplicator phenotype. None of the 4 cases with PV had evidence of HRD. Furthermore all four were treated with platinum based regimens without evidence of response. Conclusions: In a large series of sequenced pancreatic cancers, the presence of pathogenic germline variants in ATM was rare, with none of the cases demonstrating evidence of HRD. This suggests that this population is unlikely to benefit from PARP inhibition.
Opportunity costs of undergoing surgical resection and perioperative chemotherapy for pancreatic adenocarcinoma.
Authors: Lim Szu-Aun , Hao Scarlett , Boyd Breana , Mitsakos Anastasios , Irish William , Parikh Alexander A. , Snyder Rebecca A 
Published: January 2021

398 Background: Treatment of early stage pancreatic ductal adenocarcinoma (PDAC) includes surgical resection and either neoadjuvant or adjuvant chemotherapy. Due to the intensity of treatment and perioperative morbidity rates of pancreatic resection, patients may spend a significant portion of their survival time in receipt of clinical care. However, time spent in receipt of care has not been previously described in patients with early stage PDAC. The primary aim of this study was to determine the total time spent in receipt of surgical and perioperative chemotherapy in patients with resectable PDAC. Methods: A retrospective cohort study was performed of patients diagnosed with PDAC who underwent curative-intent resection at a single institution tertiary care center between January 2015 and October 2019. Patients who died within 30 days of surgery were excluded. Total care time, including all relevant clinician visits, laboratory, radiologic and procedural studies, and treatment visits, was abstracted from the primary medical record. Care time included estimated travel time based on patient address. Care time was divided into preoperative, surgical, and systemic therapy phases of care. Time spent in surgical care included the hospital length of stay, postoperative follow-up visits, and admissions for postoperative complications. Results: A total of 86 patients were identified. Median total preoperative care time was 29 hours (IQR 11-135; 0.4% of survival time, range 0% - 72.7%). Median total time spent in surgical care was 216 hours (IQR 164-371; 2% of survival time, range 0.3% - 68.4%). Among the patients who received systemic chemotherapy care within the same institutional health system (N = 41), median total time spent in receipt of systemic therapy was 447 hours (IQR 194-647; 3% of survival time, range 0.1% - 55.4%). 10.5% of patients (N = 9) spent more than 10% of total survival time in surgical care and 5.8% (N = 5) patients spent more than 10% of survival time in receipt of systemic care. Median cumulative travel time for patients was 19 hours (IQR 10.2-37.6). Conclusions: For the majority of patients undergoing resection for PDAC, time spent in receipt of surgical care does not appear to represent a substantial time burden relative to survival time. However, for a subset of patients, the time burden is considerable. Further research to determine predictors of increased time spent in receipt of multimodality cancer care is warranted to better inform patient and surgeon communication and decision-making.
POLO: Radiologic assessment of the impact of maintenance olaparib in patients (pts) with metastatic pancreatic cancer (mPaC).
Authors: Schwartz Lawrence Howard , Kindler Hedy L. , Hammel Pascal , Reni Michele , Van Cutsem Eric , Macarulla Teresa , Hall Michael J. , Park Joon Oh , Hochhauser Daniel , Arnold Dirk , Oh Do-Youn , Reinacher-Schick Anke C. , Tortora Giampaolo , Algül Hana , O'Reilly Eileen Mary , Fromageau Jeremie , Ghiorghiu Dana C. , McGuinness David , Locker Gershon Y. , Golan Talia 
Published: January 2021

412 Background: The phase III POLO study (NCT02184195) demonstrated a benefit of maintenance olaparib over placebo in the radiologically assessed primary endpoint of progression-free survival (PFS) in pts with mPaC (median 7.4 vs 3.8 months [mo]; 12-mo rate 34% vs 15%). The impact of radiologic assessment of pancreatic lesions, which is considered challenging, was explored. Methods: Tumors were assessed using Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review (BICR) in pts with mPaC treated with maintenance olaparib or placebo. PFS was analyzed in subsets of pts based on various event criteria. Results: All 154 randomized pts had mPaC prior to chemotherapy, of whom 122 had disease in the pancreas at POLO baseline (BL); 34% (53/154) had pancreas-only target lesions (TL), 26% (40/154) also had ≥1 TL outside of the pancreas, and in 19% (29/154) pancreatic disease was recorded as non-TL. Sensitivity analyses were consistent with the primary PFS analysis (Table), including when all pancreas lesion assessments were discounted (median PFS 7.4 vs 4.7 mo; 12-mo rate 38% vs 22%). Of 53 pts with pancreas-only TLs at BL, 34 had disease progression (PD); in 20 pts this was not solely based on TL measurements (16 had new lesions; 4 had multiple-cause PD). Confirmed objective responses occurred during study maintenance treatment in 20% of olaparib pts (18/92) and 10% of placebo pts (6/62). In pts with pancreas-only TLs at BL there were 7 responses in the olaparib arm (1 complete response [CR], 6 partial responses [PR]) and 2 (2 PR) in the placebo arm. In pts who had ≥1 TL outside of the pancreas at BL there were 11 (1 CR, 10 PR) and 4 (4 PR) responses, respectively. Responses were generally durable irrespective of TL location. Conclusions: The significant PFS benefit with maintenance olaparib over placebo shown in the primary analysis was consistent across all sensitivity analyses and was not impacted by radiologic assessment of pancreatic TLs. Taken together, these findings suggest that contrary to historically held belief, primary pancreas TLs may be appropriate for inclusion as sites of RECIST-evaluable disease and for assessment of treatment outcome. Clinical trial information: NCT02184195. [Table: see text]