bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive genomic profiling (CGP) of fibrolamellar oncocytic hepatoma (FLO) and conventional hepatocellular carcinomas (HCC): An observational study.
Authors: Shreenivas Aditya V. , George Ben , Thomas James P. , Puckett Lindsay , Chakrabarti Sakti , Awan Musaddiq , Straza Michael Wayne , Hall William A. , Loy Veronica , Rilling William S. , Hong Johnny , Kamgar Mandana , Tsai Susan , Gamblin T. Clark , Smolock Amanda , Christians Kathleen K. , Dougherty Kali , Danziger Natalie , Durazo Francisco , Ross Jeffrey S. 
Published: January 2022

474 Background: FLO is a rare variant of liver cancer that disproportionately affects young adults and is frequently progressive and fatal as it is often detected in a clinically advanced stage. It is seldom associated with cirrhosis of liver, viral hepatitis or other risk factors associated with conventional HCC. Treatment options are largely limited to surgical resection, and there is dearth of effective targeted therapies for FLO. Methods: Comprehensive genomic profiling (CGP) was performed using the Foundation Medicine Inc. (FMI) data base on 63 FLO and 1,793 HCC clinically advanced cases between 6/2013-12/2020 using a hybrid capture-based assay of up to 324 genes a to detect genomic alterations (GA), tumor mutational burden (TMB) and microsatellite instability (MSI). PD-L1 expression in tumor cells (Dako 22C3) was measured by IHC and scored using the tumor proportion score (TPS) method. Results: The FLO patients (pts) were significantly younger than HCC pts (median age 20 vs. 64, respectively) and the male preponderance was similar. The HCC group featured significantly more GA/tumor than FLO group (3.74 vs 1.31 p<.0001). In the currently untargetable GA group, CTNNB1, TERT and TP53 GA were significantly more frequent in HCC than FLO. GA in potentially targetable genes were extremely uncommon in both FLO and HCC with HCC featuring slightly more MTOR pathway targets ( PTEN, TSC2, NF1). GA in DNA damage and repair (DDR) pathway including BRCA2 were infrequent in both groups. GA in targetable kinases including EGFR, ERBB2, ALK, RET and PIK3CA were extremely uncommon in both groups. GA associated with intrahepatic cholangiocarcinoma (IDH1, FGFR2) were extremely uncommon in these tumors. Although the mean TMB was significantly higher in HCC than FLO, overall TMB was low with very few cases having TMB > 10 mutations/Mb. PD-L1 expression was relatively low in both groups. GA in genes associated with immune checkpoint inhibitors (ICPI) drug response like PBRM1, CD274, MDM2, STK11 were rarely identified in both groups. Additional details are illustrated in the table. Conclusions: Comparison of CGP of FLO with HCC illustrates the multifarious nature of these cancers. In HCC, there is a high prevalence of GA in TERT, CTNNB1 and TP53. CGP identified certain targetable GA in the MTOR and DDR pathways and TMB was higher in HCC. These findings warrant further evaluation of clinically advanced FLO and HCC pts by CGP to identify possible targetable genomic pathways. [Table: see text]
The role of serial analysis of hepatocellular carcinoma via circulating tumor DNA in identification of new actionable alterations.
Authors: Hsieh David , Bucheit Leslie A. , Kasi Pashtoon Murtaza , Beg Muhammad Shaalan , Zhu Hao , Dada Hiba I. , Yang Dong 
Published: January 2022

478 Background: Molecular profiling using circulating tumor DNA (ctDNA) is advantageous in cancers where tissue biopsies are not routinely obtained such as in hepatocellular carcinoma (HCC). We hypothesize that due to the expected evolution of cancer clones during treatment, serial analysis of ctDNA at the time of progression may identify additional actionable alterations. This study analyzed serial testing patterns and results for patients with HCC in a large laboratory database. Methods: Analysis of genomic results from blood samples prospectively collected between January 1, 2016-March 31, 2021 for clinical Guardant360 testing and a diagnosis of HCC as documented by ordering providers on the test requisition form (TRF) was performed. Serial tests were defined as having Guardant360 analysis performed on more than one sample collected at more than one timepoint. Chi-squared analysis was completed to assess associations between maximum variant allele fraction (maxVAF) changes and identification of new genes altered on subsequent tests. Results: 106 patients were tested serially with Guardant360 with a total of 272 tests. The median age of patients tested was 65 years (range: 16-91); 75% were male. Approximately 73% of patients had 2 serial tests, 95% had 2-4 serial tests; 5% had 5 or more. 105/106 (99%) of patients had serial tests with genomic alterations detected across multiple tests, of which 68 (64.8%) had new pathogenic alterations compared to their previous test(s) (Table). Increases in maxVAF at the time of re-testing were associated with findings of new molecular alterations (p=0.03). Potentially actionable molecular alterations accounted for 19% (13/68) of new alterations and included mutations in KIT and BRAF and amplifications in MET, BRAF, RAF1, PDGFRA, KIT, and FGFR2. Conclusions: Serial ctDNA testing in patients with HCC identified numerous potentially actionable alterations in nearly 1 in 5 patients for which a clinical trial or matched treatment option may be available. Non-invasive longitudinal genomic assessment via ctDNA provides an opportunity to examine these trends in a larger cohorts and assess impact on clinical outcomes for patients with HCC who undergo serial testing.[Table: see text]
Emerging treatments for advanced cholangiocarcinoma: Addressing the knowledge gap.
Authors: Heller Elizabeth J , Smith Keira A , Wright Kristin L , Williams Sarah L 
Published: January 2022

484 Background: The identification of actionable genetic mutations for patients with cholangiocarcinoma has enabled more effective treatments for this condition, but research indicates that clinicians face challenges in maintaining a working knowledge of evolving data. This study was conducted to determine if an online, case-based continuing medical education (CME)/nursing continuing professional development (NCPD)–approved activity could identify and address gaps in clinicians’ knowledge regarding the individualized treatment of patients with cholangiocarcinoma. Methods: The activity, Emerging Treatment Strategies for Advanced Cholangiocarcinoma, chaired by Lipika Goyal, MD, was made accessible starting on May 24, 2021. Learners participated in a 1-hour activity that highlighted emerging therapeutic targets in cholangiocarcinoma, with an emphasis on novel therapies for advanced disease and strategies to monitor and manage treatment-related adverse events. Learners completed a repeated-pairs pre- and post-activity assessment consisting of case-based questions that gauged their ability to apply emerging data to clinical decision making. Knowledge gaps and learning gains were calculated based on percentages of learners obtaining correct responses on the pre- and post-activity assessments. Significance was assessed using a chi-squared test. Results: As of September 27, 2021, 224 clinicians had completed the activity for credit. Baseline assessment data revealed gaps in knowledge regarding emerging actionable targets and management of treatment related-adverse events. The activity resulted in significant gains in knowledge and competence related to these topics, with P < 0.0001 for all learning gains. Conclusions: These data indicate that a substantial knowledge gap exists regarding the latest developments in cholangiocarcinoma treatment. They also demonstrate that online, case-based CME/NCPD-approved activities can result in statistically significant improvements in clinicians’ knowledge of therapeutic advances and management of treatment-related adverse events for patients with cholangiocarcinoma.[Table: see text]
Survey of challenges in access to diagnostics and treatment for neuroendocrine tumor patients (SCAN): The diagnostic process of GEP-NETs in Australia, Canada, China, France, Germany, the United Kingdom, and the United States of America.
Authors: McDonnell Mark , Bouvier Catherine , Pavel Marianne E. , Singh Harjit , Howe James R. , Singh Simron , Chen Jie , Van Genechten Dirk , Gellerman Elyse , Dureja Sugandha , Leyden Simone , Rodien-Louw Christine , Kolarova Teodora , O'Toole Dermot 
Published: January 2022

502 Background: SCAN assessed the global delivery of NET diagnostics and treatment. This analysis focused on the diagnostic process in gastroenteropancreatic (GEP) neuroendocrine tumor (NET) patients in countries with more robust respondent samples (at least 100 units of analysis): Australia (AU), Canada (CA), China (CH), France (FR), Germany (DE), United Kingdom (UK), and the United States (USA). Methods: During Sept-Nov 2019, 2359 NET patients & caregivers, and 436 healthcare professionals (HCPs) completed a self-reported online survey, available in 14 languages, disseminated via INCA and its partner networks. Results: 71% (1670/2359) were GEP-NET patients, 71% of which were from 7 countries (1188/1670), namely AU (7%, 120/1670), CA (9%, 154/1670), CH (7%, 114/1670), FR (8%, 137/1670), DE (9%, 149/1670), UK (11%, 191/1670) and USA (19%, 323/1670). Primary GEP-NETs were predominantly small intestinal (SI) with similar proportions in AU, CA, DE, FR,, UK and US and smaller in CH (*p < 0.001, Chi-squared). Second most common primary was pancreatic NET (similar across countries). Misdiagnosis was very frequent and occurred at least once but most commonly multiple times (table). The most frequent misdiagnoses were irritable bowel syndrome (AU 60%, CA 34%, CH 14%, FR 27%, DE 31%, UK 55%, USA 55%) and gastritis (AU 42%, CA 37%, CH 51%, FR 51%, DE 37%, UK 30%, USA 51%). Patients presented with stage IV disease in more than half of cases in 5 countries (table). On average three HCPs were involved in the diagnostic process in all above-mentioned countries. The HCPs who most often suggested the test that led to the correct diagnosis were gastroenterologists in CH 28%, FR 43%, DE 34%, USA 28%, and GPs in AU 28%, CA 27%, and UK 24% (45/191). In the majority of cases the diagnosis was received in a hospital without a NET specialist, except for CH (AU 38%; CA 42%; CH 25%; FR 36%, DE 51%, UK 44%, USA 45%). Conclusions: SCAN demonstrates some interesting geographical variations with respect to tumor demographics and stage at presentation. Nonetheless, delayed GEP-NET diagnosis remains a significant global challenge. Enhanced knowledge about GEP-NETs in hospitals without NET specialists, especially among gastroenterologists and family doctors (GPs), will drive improvements in global NET care.[Table: see text]
Real-world outcomes in patients with neuroendocrine tumor receiving peptide receptor radionucleotide therapy.
Authors: Hentzen Stijn , Mehta Kathan , Al-Rajabi Raed Moh'd Taiseer , Saeed Anwaar , Baranda Joaquina Celebre , Williamson Stephen K. , Sun Weijing , Kasi Anup 
Published: January 2022

504 Background: (177)Lu-Dotatate, a form of Peptide Receptor Radionuclide Therapy (PRRT), was approved by FDA for treatment of somatostatin-receptor-positive NETs in 2018. Clinical trials prior to the FDA approval of (177)Lu-Dotatate showed favorable outcomes but there is limited published real world outcomes data. Methods: After obtaining IRB approval we retrospectively evaluated the efficacy of (177)Lu-Dotatate PRRT for somatostatin receptor positive gastroenteropancreatic NET patients at University of Kansas Cancer Center between June 2018 and September 2021. Results: A total of 65 patients received PRRT of which 58 completed treatment and 7 are still undergoing therapy. The 58 patients who completed treatment had a median age of 61.5 years, included 24 females and 34 males, and were 86% Caucasian and 12% black. These patients had primarily NETs of small bowel (n=24) and pancreatic (n=14) origin. Pathology showed grades 1 (21), 2 (25), and 3 (4) with a majority of well-differentiated tumors (47). All 4 treatments of PRRT were completed by 43 patients. In the entire cohort, response assessment to PRRT revealed 14 (26.9%) partial response (PR), 31 (59.6%) with stable disease (SD) and 7 (13.5%) with progressive disease (PD). In subset analysis, we found that patients with nonfunctional disease (n=29) had a higher rate of PR 42.3% vs 11.5% (p=0.0147) and higher disease control rate 96% vs 78% (p=0.042) than functional disease (n=29). Patients with nonfunctional disease had a lower PD 3.85% vs 23% (p=0.0147) and 53% vs 65% stable disease than functional disease. The table below shows clinical characteristics of these patients. Conclusions: Our real world outcomes analysis of NET treated with PRRT shows improved PR when compared to the initial clinical trials which is promising for patients. In addition, we found that there was statistically significant improved response rate in patients with non functional tumors which has not been described in literature before. If our study findings are validated in a larger cohort then it may guide patient selection for PRRT therapy in the future.[Table: see text]
Genomic predictors of benefit from checkpoint inhibition in neuroendocrine carcinoma.
Authors: McGarrah Patrick Walsh , Gile Jennifer , Liu Alex John , Mansfield Aaron Scott , Leventakos Konstantinos , Desai Aakash , Tella Sri Harsha , Sonbol Bassam Bassam , Starr Jason S. , Hobday Timothy J. , Halfdanarson Thorvardur Ragnar 
Published: January 2022

512 Background: The role of immune checkpoint inhibitors (ICIs) in the treatment of extrapulmonary neuroendocrine carcinoma (EP-NEC) has yet to be established. While objective responses have been observed, it is still unknown which patients are likely to derive benefit. We investigated the genomic profiles of patients who did and did not benefit from ICIs. Methods: Previously we reported the objective responses to ICI in a retrospective series of patients with EP-NEC. RECIST 1.1 criteria were used to categorize patients as achieving disease control (DC = CR, PR, or SD) vs progressive disease (PD). The EMR was reviewed to identify patients who had genomic panels performed, and results were extracted for analysis. Results: Of 31 patients eligible for RECIST assessment, 19 had genomic panels available (9 with DC: 4 SD, 5 PR vs 10 with PD). Of those with NEC histology specified, 9 were small cell, 1 combined large and small cell, 3 were large cell. All tumors were microsatellite-stable. All but one (with TMB = 25) of 16 tumors with TMB status available were < 10 m/MB. Of those with disease control, 67% had both TP53 and RB1 alterations, compared with only 10% in those with progressive disease; this was statistically significant ( p = 0.0198, Fisher exact). Of 7 tumors with TP53 + RB1 alterations, 4 were specified as small cell carcinoma. Half of those with PD showed alterations in β-catenin pathway genes CTNNB1 or APC, compared to only one of the DC group, but this did not reach significance ( p = 0.1409, Fisher exact). In an analysis of all Mayo patients (not just those treated with ICI) with NGS data available (Tempus and FoundationOne), concurrent TP53 + RB1 alteration was significantly more common in SCLC than in EP-NEC (Table). Conclusions: In this small series of patients with EP-NEC treated with ICIs, the SCLC-like genomic signature of concurrent TP53 + RB1 alterations was significantly more common in those with disease control than in those with progressive disease. An analysis of all patients with NGS data (not just on ICI) showed that the dual alteration was more common in SCLC, and SCLC also had more TMB-high tumors. This may explain why ICIs are more effective in SCLC than in EP-NEC. Further study is warranted to determine whether TP53 + RB1 mutations predict response to ICI in NEC.[Table: see text]
A multi-institutional study of the impact of the COVID-19 pandemic on pancreatic cancer diagnosis and management.
Authors: Rosso Claudia , Valerin Jennifer B. , Oviedo Parisa , Radgoudarzi Niloofar , Chen Wen-Pin , McLaren Christine E. , White Rebekah Ruth , Zell Jason 
Published: January 2022

526 Background: The impact of COVID-19 on cancer patients may be attributed not only to its direct effects on the immune system but also to delays in diagnosis and treatment. Data on the effects of COVID-19 on pancreatic ductal adenocarcinoma (PDAC) patients are scarce. Therefore, we set out to determine the impact of the pandemic on diagnosis and treatment initiation. We hypothesized that time from diagnosis to treatment would be increased in the COVID era compared to the pre-COVID era. Methods: We conducted an IRB-approved retrospective chart review of 488 patients diagnosed with PDAC from March 2019 to September 2020 at two academic medical centers. Patients were divided into two groups, based on the date of initial pathologic diagnosis. We defined the pre-COVID era as March 2019 to March 2020, the 12-month time period before California’s statewide lockdown. The COVID era was defined as the 6 months following the lockdown, March 2020 to September 2020. Demographics, clinical stage, and treatment type were recorded. In addition, initial clinical encounter date, pathologic diagnosis date, and initial treatment date were also collected. All data were gathered at two large-scale academic institutions. Descriptive statistics were used in the analysis. Results: There were 333 patients diagnosed during the pre-COVID era and 155 patients during the COVID era. While race/ethnicity and age at diagnosis were statistically similar for both groups, females made up a significantly larger proportion of COVID era patients than pre-COVID era patients ( p= 0.02). There was no significant difference in clinical stage at diagnosis between the two groups ( p= 0.84). In the pre-COVID era, 19.5% of cases were resectable, 11.1% borderline resectable, 20.1% locally advanced, and 31.8% metastatic. In the COVID era, 17.4% of patients were resectable, 11% borderline resectable, 23.9% locally advanced, and 32.9% metastatic. Median time from pathologic diagnosis to initiation of treatment was 32 days for the pre-COVID era patients and 28 days for the COVID era patients ( p= 0.38). Initial treatment type was also similar between the two groups ( p= 0.29). Conclusions: Fortunately, our data indicate that the COVID-19 pandemic has not significantly prevented PDAC patients from seeking care. Additionally, it does not appear that COVID-19 has delayed treatment initiation or changed initial treatment type. We believe that the successful adoption of telemedicine and other safety protocols have allowed patients with PDAC to continue receiving appropriate care during the pandemic.[Table: see text]
Cancer Commons’ virtual tumor board program: A patient-centric advisory panel and real-world data registry.
Authors: Rahib Lola , Chang David Kuang-Fu , Sohal Davendra , Kinsey Conan Grant , Christensen Deborah , Shapiro Mark , Zelada-Arenas Fatima , Paulson Andrew Scott , Beg Muhammad Shaalan 
Published: January 2022

527 Background: We initiated a nationwide Virtual Tumor Board (VTB) program for pancreatic cancer (PC) patients (pts). The VTB consists of oncology experts and serves as an advisory panel by providing information on treatment (Tx) options based on a comprehensive review of patients’ oncologic history. Personalized Tx options and their rationales are provided and outcomes tracked in a prospective registry (XCELSIOR). Methods: PC pts who participated in XCELSIOR shared access to their full medical records, which were collected, processed, and abstracted. The panel reviewed cases asynchronously through an interactive platform followed by a VTB which was held weekly through videoconferencing. Tx options were summarized into a written report and provided to patients and their physicians. Outcomes and quality of life are tracked longitudinally through an IRB-approved 21CFR11 compliant observational registry (XCELSIOR). Results: From 9/2020 to 8/2021, the VTB reviewed 79 unique cases; 56% were male; median age at diagnosis was 66 (50-87). At the time of VTB, 68 (87%) had metastatic disease and 8 (10%) had locally advanced disease. Median prior therapy lines was 2 (0-9), with 26 (35%), 24 (32%), 6 (8%), and 19 (25%) pts having received 1, 2, 3 and 4+ lines of therapy, respectively. Median time from diagnosis for pts presenting after 1, 2, and 3+ lines of prior Tx was 9.5, 11, and 17.5 months, respectively. First-line Tx was FOLFIRINOX in 40 (53%) pts and gemcitabine/nab-paclitaxel in 22 (29%) pts. At the time of VTB, 32 (37%) of patients had stable disease, 23 (26%) had disease progression, 18 (21%) had recently started a new Tx, 7 (8%) were responding to Tx, 3 (3%) had stable disease on imaging but rising CA 19-9, and 4 (4%) were others. Prior to VTB, 69 (87%) pts had molecular profiling results available. Collectively the VTB provided 375 Tx and diagnostic (NGS, imaging, etc.) options with a median of 4 (1-12) options per patient. As of 9/8/2021, 87 VTB reports were provided. Of 25 instances of ‘no Tx decision’, 10 (40%) are deceased, 10 (40%) are stable, and 5 (10%) had other reasons. Of the 25 people who started a subsequent Tx, 14 (56%) were identified by the VTB. These included 9 (64%) FDA-approved, 3 (21%) off-label, and 2 (14%) on-trial Tx. Tx not identified by the VTB included 3 (33%) FDA-approved, 2 (22%) off-label, 2 (22%) on-trial, and 2 (22%) local Tx. Conclusions: We present our experience of utilizing a platform for patients to receive a virtual tumor board review and utilize an IRB-approved registry as a learning system. Early data indicate successes in identifying treatment and clinical trial opportunities. Future steps include streamlining communication with primary oncologists and enhancing access to treatments. NCT03793088.