bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in treatment and outcomes of stage II/III rectal cancer patients treated with trimodality therapy (TT) between 2006-2016: An NCDB analysis.
Authors: Kennecke Hagen F. , Bahnson Henry T. , Lin Bruce , Kaplan Jennifer , Pham Huong , Suen Andrew , Simianu Val 
Published: January 2021

32 Background: Trimodality therapy (TT) remains standard for stage 2/3 rectal cancer and emerging evidence supports better outcomes with total neoadjuvant therapy (TNT) than similar therapy given post-operatively (Post-op). Real-world practice patterns and sequence of TT have significant implications on rectal cancer quality of care, outcomes and clinical trial design, and are not well described. Methods: The National Cancer Database was used to identify patients with clinical (c) stage 2/3 rectal adenocarcinoma diagnosed between 2006-2016, while pathologic (p) stage 2/3 was used when c stage was missing. Patients were included if they received Chemo/Radiation (C/RT), single or multiagent (SA or MA) chemotherapy (CT) and surgery. TNT was defined as receipt of pre-op C/RT and MA CT and no post-op therapy. Survival analyses were performed using Kaplan-Meier (KM) estimates and Cox univariate and multivariate hazard ratios (HRs) adjusted for TNT group, sex, race, year of diagnosis, stage, facility type, and age of diagnosis. Five-year KM survival proportions were limited to years 2006-2012, while Cox HRs were estimated from 2006 to 2015. Results: Of 32,467 patients who received TT, 8883 (27%) received TNT and 23,584 were classified no-TNT. TNT and no-TNT cohorts were numerically similar in age, race and gender. A significantly higher proportion of pStages 0-2 patients were observed in the TNT vs the no-TNT cohorts (61% vs. 48%, p < .001). In analysis of annual treatment patterns of the whole cohort, a gradual reduction in Post-op C/RT was observed between 2006 (28%) and 2016 (8%, p < .001), while use of TNT and MA CT did not increase. A migration to lower pStages 0/1/2/3 was seen between 2006 (1/10/31/57%, respectively) and 2016 (3/22/29/45%) (2016) (p < .001). Five-year OS analysis showed superior OS for Pre-op vs Post-op C/RT (74 vs 69%, HR = .81, p < .001), and MA CT vs. SA CT (76 vs 71%, HR = 0.79, p < .001) but inferior 5-y OS for the TNT vs. no-TNT cohorts (74 vs 78%, HR = 1.17, p < .001). Conclusions: Between 2006-16, a minority of patients treated with TT for stage 2/3 rectal cancer received TNT which did not increase over time. Significant annual shifts from Post-op C/RT to Pre-op C/RT, and migration to lower pStages were seen during this time period. Pre-op C/RT and MA CT were associated with improved OS, while TNT patients experienced inferior OS vs. the no-TNT cohort, possibly related to confounding factors in this observational cohort; multivariate sub-group analysis to be presented. Emerging evidence in support of TNT may further change treatment patterns and outcomes. [Table: see text]
Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors.
Authors: Wong Jeffrey Sum Lung , Kwok Gin Wai , Tang Vikki , Li Bryan , Leung Roland Ching-Yu , Chiu Joanne Wing Yan , Ma Ka Wing , She Wong-Hoi , Tsang Wing Yan Josephine , Cheung Tan To , Yau Thomas 
Published: January 2021

330 Background: Programmed cell death protein 1 (PD-1) pathway blockade with immune checkpoint inhibitors (ICI) is a standard therapy in advanced hepatocellular carcinoma (HCC) nowadays. No strategies to overcome ICI resistance have been described. We aimed to evaluate the use of ipilimumab and anti-PD-1 ICIs (nivolumab or pembrolizumab) combinations in advanced HCC patients with progression on prior ICIs. Methods: Advanced HCC patients with documented tumour progression on prior ICIs and subsequently received ipilimumab with nivolumab/pembrolizumab were analysed. Objective response rate (ORR), median duration of response (DOR), time-to-progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed. Results: Twenty-five patients were included. The median age was 62 (range 51-83). 68% were of Child-Pugh (CP) grade A and 48% had primary resistance to prior ICI. At median follow-up of 37.7 months, the ORR was 16% with a median DOR of 11.5 months (range 2.76-30.3). Three patients achieved complete response. The median TTP was 2.96 months (95% C.I. 1.61-4.31). Median OS was 10.9 months (95% C.I. 3.99-17.8) and the 1-year, 2-year and 3-year survival rates were 42.4%, 32.3% and 21.6% respectively. The ORR was 16.7% in primary resistance group and 15.4% in acquired resistance group (p=1.00). All responders were of CP A and Albumin-Bilirubin (ALBI) grade 1 or 2. CP and ALBI grades were significantly associated with OS (p=0.006 and p<0.001 respectively). Overall, 52% of patients experienced TRAEs and 12% experienced grade 3 or above TRAEs. Conclusions: Ipilimumab and nivolumab/pembrolizumab can achieve durable antitumour activity and encouraging survival outcomes with acceptable toxicity in patients with advanced HCC who had prior treatment with ICIs.
In search of novel synthetic lethality anti-cancer drug targets in intrahepatic cholangiocarcinoma: MTAP genomic loss.
Authors: Ross Jeffrey S. , Schrock Alexa Betzig , Madison Russell , Danziger Natalie , Pavlick Dean , Sokol Ethan , Hemmerich Amanda , Huang Richard , Ramkissoon Shakti H. , Israel Mason A. , Gjoerup Ole , Venstrom Jeffrey Michael , McGregor Kimberly 
Published: January 2021

337 Background: The association of BRCA tumor suppressor gene (TSG) inactivation and PARP inhibitor efficacy through a mechanism of synthetic lethality (SL) is now well-established. Recently, the PRMT5 arginine methyltransferase dependence in cells with MTAP (S-methyl-5'-thioadenosine phosphorylase) genomic alterations (GA) has been proposed as a new SL based anti-tumor strategy and under consideration for development for intrahepatic cholangiocarcinoma (IC). Methods: 2,170 cases of clinically advanced IC were submitted for comprehensive genomic profiling (CGP) to detect genomic alterations (GA), tumor mutational burden (TMB) and microsatellite instability (MSI) using a hybrid capture based assay (F1CDx). PD-L1 expression in tumor cells (Dako 22C3) was measured by IHC and scored using the tumor proportion score (TPS) method. Results: 328 (15%) ICs featured MTAP inactivation (MTAP-IC). 48% of MTAP-IC cases were female and 52% were male with a median age of 66 years (range 26-93 years). MTAP-IC featured 6.3 GA per sample. The median TMB was 2.5 mut/Mb with only 2% of cases with TMB ≥10 mut/Mb. No (0%) MTAP-IC cases were MSI-high. Of 112 MTAP-IC IHC stained for PD-L1, 4% were PD-L1 high (> 50%), 14% were PD-L1 low (1-49%) and 82% were PD-L1 negative. 99% of MTAP inactivation was by copy number (CN) loss and 1% was due to non-CN mutation. In MTAP-IC, 99% featured CDKN2A loss and 95% featured CDKN2B loss (9p21 co-deletion). TP53 was mutated in 31% and KRAS in 24% (3% G12C). Other currently non-targetable GA included ARID1A (19%), BAP1 (16%) and SMAD4 (13%). Among potentially targetable GA, the MTAP-IC featured 12% FGFR2 GA (8% rearrangements), 10% BRAF (8% V600E), 7% IDH1, 7% PIK3CA, 4% BRCA2, 4% ERBB2 (2% amplification) and 3% MET. Conclusions: Comprehensive genomic profiling elucidated that MTAP GA are frequent in IC and features relatively high GA/tumor, including 9p21 co-deletion, but relatively low TMB and PD-L1 expression. Isolated MTAP deletion without CDKN2A/B co-deletion was extremely rare. In addition to the potential targeting of PRMT5 in MTAP-IC tumors, co-altered genes known to be targets in IC such as FGFR2, IDH1 and BRAF are still prevalent in MTAP-IC, indicating potential for combining targeted therapies in some MTAP-IC patients.
Health-related quality of life and time from diagnosis among young adult colorectal cancer survivors.
Authors: Miller Kimberly Ann , Stal Julia , Gallagher Phuong , Kaslander Jonathan N , Freyer David R. , Marin Priscilla , Lenz Heinz-Josef , Milam Joel , Barzi Afsaneh 
Published: January 2021

34 Background: Incidence of colorectal cancer (CRC) in patients under 50 years of age is rising. Quality of life in survivorship is not well-described in this population. We compared health-related quality of life (HRQoL) in CRC survivors ≤ 50 years old who were 6-18 months or 19-36 months from initial diagnosis or relapse. Methods: A cross-sectional online survey was administered in collaboration with a national organization for young CRC survivors. The Functional Assessment of Cancer Therapy (FACT-C) was used to measure HRQoL, which assesses HRQoL globally, including a CRC specific scale, and emotional, physical, social, and functional well-being domains. T-tests were conducted to compare HRQoL between survivors who were 6-18 months versus 19-36 months from diagnosis/relapse. Results: This sample (n=308) had a mean age of 33.76 SD±6.68; 201 (65.3%) were male; tumor location was colon or rectal in 41.7% and 58.3%, respectively. The majority (55.23%) were diagnosed with stage 2 disease; 98.0% were non-metastatic. 42.2% experienced relapse; 25% had an ostomy. Most survivors were 6-18 months (N=189; 61.4%) from diagnosis/relapse, and key demographics and disease characteristics did not significantly differ between those who were shorter versus longer time from diagnosis/relapse. The mean global HRQoL score was 67.3 out of a possible score of 136. Across domains, scores were low, with social well-being the highest (15.15/28) and emotional well-being the lowest (11.44/24). Social well-being was significantly higher among survivors who were 6-18 months from diagnosis/relapse compared to those 19-36 months (15.98 for 6-18 months vs. 13.83 for 19-36; p<0.01), as was functional well-being (13.20 for 6-18 months vs. 11.12 for 19-36; p<0.01). Emotional well-being and physical well-being did not significantly differ between groups. Conclusions: Overall HRQoL scores were low among younger CRC survivors, and social and functional well-being were significantly worse for those longer from diagnosis. Appropriate counseling and other targeted interventions are necessary to maintain HRQoL over time in this at-risk population. [Table: see text]
Clinical correlation of cadherin-17 (CA17 aka CDH17) marker with advanced tumor stages and poor prognosis of cholangiocarcinoma in a retrospective cohort of 180 patients.
Authors: Zheng Bohao , Shen Sheng , Wong Tony K , Gong Zi-Jun , Sun Wentao , Ni Xiaojian , Wang Jiwen , Hu Mei-yu , Liu Han , Ni Xiaoling , Liu Houbao , Luk Moon Ching , Suo Tao 
Published: January 2021

344 Background: Aberrant expression of cadherin-17 (CA17, aka CDH17) cancer marker is often observed in major gastrointestinal (GI) cancers. In this retrospective study, we examined the CA17 tissue expression and analyzed its clinical significance in cholangiocarcinoma (CCA). Methods: A total of 180 patients with detailed demographic and clinical data were enrolled in this study and randomly divided into a training cohort (N = 120) and a validation cohort (N = 60). Biopsy samples (tumor and adjacent normal tissue) collected for tissue microarray were examined by immunohistochemistry using a mouse anti-CA17 monoclonal antibody (Clone 7C5). Image pro plus was applied to score the staining intensity and expression level of CA17 marker. Kaplan-Meier analysis, Cox's proportional hazards regression, and nomogram were applied to evaluate the prognostic significance of CA17. Results: CA17 cancer biomarker over-expression was significantly observed in CCA compared to their non-tumor counterparts (P < 0.001), and positively correlated with aggressive tumor phenotypes, like larger tumor size (P = 0.004), lymph node metastasis (P < 0.001), and advanced TNM stage (P < 0.001). Meanwhile, patients with high expression of CA17 correlated with worse postoperative overall survival (OS)(P = 0.002) and recurrence-free survival (P = 0.03). Besides, multivariate analysis identified that CA17 expression was an independent prognostic factor for cholangiocarcinoma patients (Training cohort: HR:1.716, 95% CI:1.116-2.638; P = 0.014; Validation cohort: HR: 1.811, 95%CI:1.028-3.892; P = 0.035), which indicated that the CA17 is much more efficient than serum CA19-9 (Training cohort: HR: 1.000, 95%CI: 1.000-1.001; P = 0.006; Validation cohort: HR: 1.000,95%CI:1.000-1.001; P = 0.013) in predicting the OS of CCA patients. Notably, the nomogram integrating CA17 expression had a better prognostic performance as compared with current TNM staging systems. Conclusions: CA17 cancer biomarker was aberrantly expressed in CCA tumor tissues, and its high expression level positively correlated with aggressive tumor phenotypes. Furthermore, CA17 was an independent adverse prognostic factor for CCA patients’ survival, which may serve as a potential drug target for CCA patients.
Targeted therapies in cholangiocarcinoma: Assessment of US oncologist practice patterns.
Authors: Parikh Kinjal , Cameron Davecia Ragoonath , Abair Tristin , Kugel Patrick , Vogel Arndt 
Published: January 2021

347 Background: Chemotherapy is a mainstay treatment modality for patients with advanced cholangiocarcinoma (CCA). Recent developments and new approvals have led to changing paradigms, incorporating the use of targeted therapies for patients with progressive disease. Given the need for a greater understanding of the molecular alterations, varying targets, and available and emerging therapies, education is needed to assess knowledge regarding these recent advances in unresectable CCA. The goal of this activity was to increase the knowledge of self-assess the learning needs of oncologists in treating patients with unresectable CCA. Methods: The education included 25 multiple choice questions in a continuing medical education (CME)-certified clinical practice assessment to assess practice gaps. The questions were designed to measure knowledge, competence, confidence, and attitudes of oncologists regarding clinical evidence, role of molecular testing, and place in the treatment paradigm for targeted therapies in unresectable CCA. The self-assessment was made available online to physicians as a learning tool to gain foundational knowledge, as well as receive feedback about their performance as compared to other test-takers, to improve self-awareness of their own personal educational gaps. The activity launched 6/24/20, and data are reported through 8/31/20. Results: A total of 1,009 learners, including 758 physicians, participated in the activity. Of the 104 oncologists that participated, a majority practiced in the community setting, saw patients with a range of cancers, and were not confident about using targeted therapies or recognizing targets for biomarker testing. Oncologists demonstrated the following gaps related to: NGS sequencing and biomarkers: 21% do not use; 32% use upon progressive disease; 35% did not realize that not all panels detect FGFR2 fusions; 20% do not test for biomarkers; 29% and 56% test for IDH or FGFR, respectively; 60% recognize the incidence of IDH1 mutations; Clinical trial (FIGHT202 and ClarIDHy): 45% were able to identify biomarker eligibility for pemigatinib; 9% were able to identify pemigatinib OS outcomes; 30% were able to recognize most common grade 3 AE of pemigatinib; 51% recognized the PFS endpoint with ivosidenib; 34% were able to identify eligibility for ivosidenib; 55% recognized most common AEs of ivosidenib. Conclusions: This CME-certified clinical practice assessment identified gaps in knowledge, competence, and confidence regarding testing and use of targeted therapies and emerging data in patients with unresectable CCA. As new data emerges and the number of targets and targeted therapies expand, continued education remains important to continue to optimize patient care.
Tumor burden in serotonin secreting pancreatic neuroendocrine tumors after initiating telotristat ethyl.
Authors: Giacalone Susan , Di Gialleonardo Valentina , Murali Kris , Joish Vijay N. 
Published: January 2021

367 Background: Pancreatic neuroendocrine tumors (pNETs) characterized by high serotonin levels and carcinoid syndrome (CS) are rare. We evaluated tumor burden in a subgroup of patients with pNETS from the real-world TELEACE study before and after initiating telotristat ethyl (TE) in US clinical practice. Methods: Detailed methods of the TELEACE study have been reported previously. This was a retrospective, single arm, pre-post physician panel-based chart review of patients who received TE for at least 6 months. Descriptive statistics analyzed demographic, clinical, laboratory and radiological data extracted from medical charts of TELEACE patients with pNETS. Results: Fifty-two patients with pNETS initiating TE were eligible for this analysis. The average age at the time of TE initiation was 60+10.4 years; 64% were males. The majority of patients had well-differentiated (60%) tumors and low-grade (54%) tumor status. Patients received TE for an average of 11.5+7.84 months, and 21% were still receiving TE at the time of data extraction. Diarrhea and flushing were the most common CS symptoms recorded at the time of TE initiation. Urinary 5-HIAA levels were reported for 9 patients before and for 2 patients after TE initiation. Mean (median) 5-HIAA levels before and after TE initiation were 693 (211) and 22 (22) µmol/24h, respectively. Significant mean reduction in tumor size of 0.67 cm after TE initiation (P = 0.017) was observed. Conclusions: This subgroup analysis of the TELEACE study population showed that the addition of TE to somatostatin analog treatment may positively impact tumor burden for patients with functional pNETs.
Copy number alterations in plasma cell-free DNA from metastatic gastroenteropancreatic neuroendocrine neoplasms.
Authors: Boons Gitta , Vandamme Timon , Lybaert Willem , Roeyen Geert , Rondou Tim , Papadimitriou Konstantinos , Janssens Katrien , Demey Wim , Dero Isabel , Van Camp Guy , Peeters Marc , Op de Beeck Ken 
Published: January 2021

372 Background: Recent studies, including our proof-of-concept study, demonstrated the possibility to detect tumor-derived molecular alterations in cell-free DNA (cfDNA) from plasma of patients with a gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN). More in-depth evaluation of the biomarker potential of cfDNA in GEP-NENs is warranted, since highly sensitive and specific blood-based biomarkers are an important unmet need for this tumor type. The aim of our study was to detect tumor-associated copy number alterations (CNAs) in cfDNA from GEP-NEN patients to molecularly characterize the tumor and to estimate tumor fraction, as a measure of tumor burden, and to evaluate changes in these parameters over time. Methods: Metastatic GEP-NEN patients were included within NETwerk, a multi-institutional network of nine hospitals in Belgium. Clinicopathological data were collected to correlate experimental and clinical findings. Plasma samples were collected from all patients and cfDNA was extracted and subjected to shallow whole-genome sequencing (WGS). Detection of CNAs and estimation of tumor fraction, based on the sequencing data, were performed using the R-based tool ichorCNA. Results: In total, 80 samples of 29 metastatic GEP-NEN patients were analyzed using shallow WGS. All patients had a well-differentiated GEP-NEN of Grade 1/2 and primary sites were pancreas (N = 15), small intestine (N = 9), colon (N = 1), caecum (N = 1), ileocaecal valve (N = 1), pylorus (N = 1) and unknown (N = 1). Median number of samples per patient was two, with a median time between first and last sampling of six months. In 25 cfDNA samples from nine patients (31%), CNAs with tumor fractions higher than 3% could be detected. The primary tumor site of all CNA-positive patients was pancreas, corresponding to 60% of included pancreatic NEN (PNEN) patients. Six of the CNA-positive patients were included at initiation of everolimus treatment. The detected CNA patterns were similar to the copy number profiles of PNENs described in literature, e.g. whole-chromosome gains of chromosomes 5, 7, 9, 12, 13, 14, 19 and 20. CNA profiles were relatively stable over time, although in two patients new alterations did arise. Tumor fractions changed over time, which could be linked to changes in tumor burden, tumor progression and treatment response according to RECIST1.1 criteria and will be further examined, including in additional samples that are being collected. Conclusions: Cell-free DNA of metastatic GEP-NEN patients contains CNAs that correspond to CNA profiles seen in tumor tissue samples. CNAs can be used to quantify the tumor fraction in cfDNA over time, which will be linked to tumor progression in our ongoing study, particularly in the promising subgroup of PNEN patients.
Characterization of undiagnosed pancreatic ductal adenocarcinoma on CT scans.
Authors: Chang John , Bartels Madelyn , Beyer Kelsey , Maitland Ashley , Peterson Richard Taft , Goldinger Stephen , Papesh Megan , Kundranda Maddapa , Koo Phillip , Dragovich Tomislav , Choti Michael A. 
Published: January 2021

380 Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths. At present, the best 5-year survival is 25% for resectable PDAC. For small (1 cm) stage 1 PDAC, resection has resulted in much better survival. The goal of this study was to evaluate the appearance and location of early undiagnosed PDAC on computed tomography scans (CT) prior to diagnosis with the goal of minimizing missing early PDAC. We also categorize the errors as either perceptive or cognitive. Methods: PDAC cases were retrospectively reviewed from 1/1/2012 through 12/31/2018 from our tumor registry, identifying 81 cases with paired CT scans both at the time of and prior to diagnosis. Among these, 31 contained imaging features considered diagnostic or suspicious for early PDAC(38%). These “errors” were classified by radiologic features and as well as by location. In addition, errors were classified into “perceptive errors" when the first study was read as normal, and as “cognitive errors” when the report noted an abnormality but failed to note suspicion for malignancy. Results: Among the 31 undiagnosed PDAC, 18 had features of an identifiable mass (58%), 9 had pancreatic ductal dilatation (29%), and 4 had evidence of perivascular soft tissue (13%). 44% of undiagnosed tumors were located in the head-neck, 39% in the body, and 17% in the tail. Perceptive errors were found in 58% and 42% were cognitive. No significant differences were seen between perceptive and cognitive errors based on suspicious features. Conclusions: Radiologic findings of early PDAC was retrospectively evident in more than one third of cases in which prior imaging was performed. These findings are most often masses or ductal dilatation. Location of these undiagnosed tumors were distributed throughout the gland. This study identifies the radiologic features of undiagnosed PDAC which may provide an opportunity for future prospective studies and improved technology which may improve early detection of pancreatic cancer.