bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating tumor DNA-based genomic landscape of early-onset pancreatic cancer.
Authors: Barnett Reagan , Dada Hiba I. , Drusbosky Leylah , Clemens Keelia , Hochster Howard S. , Gulhati Pat 
Published: January 2022

588 Background: The incidence of gastrointestinal and obesity related cancers, including pancreatic cancer, is increasing in individuals <50 years old. Early-onset pancreatic cancer (EOPC; age<50 years old at diagnosis) is characterized by higher incidence in males, enrichment for KRAS wild-type tumors with targetable genomic alterations (GAs), and improved outcomes compared to average-onset pancreatic cancer (AOPC; age>50 years old at diagnosis). Little is known about the genomic correlates underlying these clinical differences. In this study, we sought to characterize the circulating tumor DNA (ctDNA) landscape in EOPC compared to AOPC. Methods: We analyzed ctDNA samples from a total of 8548 patients (EOPC n=488 [age<30yo n=13, 30-39yo n=87, 40-49yo n=388]; AOPC n=8060) collected prospectively between December 2017 to March 2021 using a 73 gene next generation sequencing panel (Guardant360). Statistical analyses were performed using Fisher’s exact test. Results: Of the 488 EOPC patients, 261 (53%) were male and 227 (47%) were female. Median age was 45yo in EOPC and 69yo in AOPC. Contrary to prior reports from tissue-based sequencing studies, EOPC patients were more likely to harbor KRAS alterations (p≤0.0001), specifically KRAS G12V (p≤0.0072) and KRAS amplifications (p≤0.0001). 1.24% of pancreatic cancer patients harbored KRAS G12C mutations; 0.05% were in EOPC patients. The most common currently-targetable GAs identified in EOPC were PIK3CA (10%), BRCA1/2 (10%), EGFR (9%), BRAF (7%), MET (7%), ATM (7%), FGFR1/2 (7%), CDK6 (5%), and ERBB2 (4%). EOPC patients had higher proportion of targetable GAs in BRCA2 (p≤0.041), MET (p≤0.005), and PIK3CA (p≤0.0023) compared to AOPC. Conversely, AOPC patients had higher proportion of GAs in TP53 (p≤0.0001) and ATM (p≤0.0001). MSI-high and TMB-high were detected in 0.07% and 0.06% of EOPC patients respectively, while 0.6% and 1.7% AOPC patients were MSI-high and TMB-high. Gene fusions were detected in 0.3% pancreatic cancer patients, predominantly in FGFR2 (0.2%) and FGFR3 (0.02%). Potential germline variants were detected in both EOPC and AOPC patients, most commonly in BRCA2 (54%). Females displayed higher proportion of TP53 (p<0.0001), EGFR (p<0.0029), CDKN2A (p<0.0001), BRCA2 (p<0.0336) and ATM (p<0.0001) mutations compared to males. Gender was predictive of the pattern of GAs in EOPC with MET (p≤0.0027) , ARID1A (p≤0.0376) , and BRAF (p≤0.0034) alterations enriched in males, and PIK3CA (p≤0.0017) alterations enriched in females. Conclusions: This study represents the first large-scale blood-based ctDNA genomic profiling of EOPC. Based on this age and gender-stratified molecular characterization of pancreatic cancer, EOPC is a distinct molecular entity compared to AOPC. Identification of multiple targetable GAs may improve patient outcomes in EOPC, especially when a tissue biopsy is not feasible or sufficient for comprehensive genomic profiling.
Extranodal extension influences prognosis in pancreatic head cancer.
Authors: Sung Min Kyu , Park Guisuk , Park Seo Young , Lee Woohyung , Song Ki Byung , Lee Jae Hoon , Kim Song Cheol , Hwang Dae Wook , Hong Seung Mo 
Published: January 2022

593 Background: Extranodal extension (ENE) is an established prognostic factor of several gastrointestinal cancers; furthermore, ENE is already included as one component of nodal category of oral cavity, penis, and vulvar cancers. However, the prognostic impact of ENE in pancreatic cancer remains unclear. In this study, we aimed to investigate prognostic implication of ENE in patients with surgically resected pancreatic cancer. Methods: We retrospectively reviewed electronic medical records and pathologic slides of 503 surgically resected pancreatic head cancer patients, who consecutively underwent pancreaticoduodenectomy for pathologically confirmed pancreatic ductal adenocarcinoma between January 2009 and December 2013. Patients were categorized into subgroups according to ENE status and AJCC 8th pancreatic cancer staging system. We compared the disease-free survival rates of the patients according to ENE status. Cox proportional hazard analysis was performed to evaluate prognostic factors for the disease-free survival of pancreatic head cancer. Results: ENE-positive patient group showed a larger tumor size, a higher rate of lymph node metastasis, and a tendency to be positive for lymphovascular invasion, perineural invasion, and resection margin (p < 0.001). Patients with ENE had lower overall survival (OS) and disease-free survival (DFS) rates compared with those without ENE (N0, 30 months; LN+/ENE-, 20 months; LN+/ENE+, 16 months; p < 0.001), (N0, 13 months; LN+/ENE-, 8 months; LN+/ENE+, 5 months; p < 0.001). Patients with higher N categories had lower OS and DFS rates. In addition, even in the same N stage, patients with ENE showed lower OS and DFS rates than those without ENE (p < 0.001). However, there was no significant difference in survival rates between patients in the N1/ENE+ group and the N2/ENE- group. Additionally, ENE was an independent prognostic factor for pancreatic cancer. Conclusions: ENE significantly influenced adverse prognosis among patients with pancreatic head cancer especially for those with nodal metastasis. Therefore, ENE should be considered as a prognostic factor in the future editions of the AJCC staging system.
Targeted therapy (TT) in patients with KRAS wildtype (WT) pancreatic ductal adenocarcinoma (PDAC) produces durable response.
Authors: Mehdi Maahum , Annunzio Kaitlin , Taylor Bradley W. , Szabo Aniko , Shreenivas Aditya V. , Chakrabarti Sakti , Thomas James P. , Tsai Susan , Christians Kathleen K. , Evans Douglas B. , Clarke Callisia , Hall William A. , Erickson Beth , Thapa Bicky , Ahmed Gulrayz , George Ben , Kamgar Mandana 
Published: January 2022

596 Background: Genomic alterations (GA) that drive cancer development and predict therapeutic response remain elusive in patients (pts) with KRAS WT PDAC. We interrogated our institutional database to identify actionable GAs in pts with metastatic, KRAS WT PDAC and analyzed the therapeutic impact of matched TT. Methods: We reviewed electronic medical records of KRAS WT PDAC pts (n=24) who underwent comprehensive genomic profiling (CGP) utilizing Foundation One CDx (25.0%) or Tempus (75.0%) between 2015-2021. Duration of response (DOR) was calculated from date of treatment (Tx) initiation to Tx discontinuation. Overall survival (OS) was measured from the date of the diagnosis (Dx) of advanced disease (AD) to death or last follow-up. OS was estimated using the Kaplan-Meier method, with at-risk periods left-truncated at the time of CGP. The effect of covariates on survival was evaluated using Cox proportional hazards regression. Results: Of the 24 KRAS WT pts, 14 (58%) had AD: 8 (57%) pts had metastatic disease at or shortly after Dx, 6 (43%) pts developed metachronous recurrence. Median age at Dx for pts with AD was 65, and 57% were female. Seven of 14 pts with AD (50%) had highly actionable GA (HAGA), (Table). Pts with HAGA demonstrated durable responses to TT (Table) with manageable toxicities. Pts with HAGA had a median OS of 28 mo compared to 5.9 mo for those without (Hazard Ratio = 0.47, p = 0.33). Conclusions: The sustained therapeutic benefit noted with TT matched to HAGA in pts with KRAS WT PDAC underscores the need for systematic interrogation of the somatic genome in PDAC pts. Optimal sequencing of cytotoxic therapy with TT and its impact on modulating clonal selection pressure in pts with KRAS WT PDAC merits prospective evaluation.[Table: see text]
Outcomes of patients with small intestine adenocarcinoma (SIA) in a Canadian province: A population-based cohort study.
Authors: Yanko Emma , Le Duc , Mahmood Shazia , Ginther Nathan , Chalchal Haji I. , Kanthan Rani , Haider Kamal , Zaidi Adnan , Dorie-Anna Dueck , Ahmed Shahid 
Published: January 2022

641 Background: SIA is a rare cancer. Limited data is available about clinicopathological factors and interventions that correlate with its outcomes. The current study aims to determine outcomes of patients with SIA who were diagnosed in a Canadian province. Methods: In this retrospective population-based cohort study patients with biopsy proven SIA diagnosed during 2008-2017 in the province of Saskatchewan were assessed. A Cox Proportional multivariate regression analysis was performed to determine correlation between survival and exploratory factors. Results: 112 eligible patients with median age of 73 yrs and M:W 53: 59 were identified. 75% had a comorbid illness, 34% had a secondary cancer and 45% had WHO performance status (PS) < 2. Of 112 patients, 51 (46%) had early-stage disease and 61 (54%) had advanced-stage disease. Median neutrophil: lymphocyte (NLR) was 4.5. The median overall survival (mOS) in relation to stage of the disease were as follow: stage 1, 59 months, stage 2, 30 months, stage 3, 20 months and stage 4, 3 months (P < 0.001). The patients with early-stage disease had mOS of 36.0 months (95% CI: 8.0-64.0) vs. 3.0 months (1.74-4.26) with advanced disease (P < 0.0001). Of 21 patients with stage 3 disease their median disease-free survival was 26 months (23.1-28.9) with chemotherapy vs. 4 months (0.0-9.1) with no chemotherapy, p = 0.04. Patients with stage 4 disease who had surgery and or chemotherapy had mOS of 18 months (13.70-23.32) vs. 4 months (2.20-5.82) with chemotherapy alone p = 0.03. On univariate analysis age ≥70 yrs, WHO PS > 1, stage 4 disease, low albumin, elevated creatinine, high alkaline phosphatase, duodenal cancer, lack of surgery, and NLR of > 4.50 were significantly correlated with inferior survival. On multivariate analysis stage 4 disease, HR, 3.20 (95%CI:1.84-5.40), WHO PS > 1, HR, 2.22 (1.42-3.45), no surgery, HR, 2.10 (1.25-3.50), and NLR > 4.5, HR, 1.72 (1.10-2.71) were significantly correlated with inferior survival. Conclusions: Most patients with SIA were diagnosed with advanced-stage. In addition to advanced-stage disease and poor PS, lack of surgery and baseline LNR of > 4.5 were significantly correlated with inferior survival.
Integration of molecular cancer classification and NGS to identify metastatic patients eligible for IDH inhibitors.
Authors: Kasi Pashtoon Murtaza , Ma Li , Treuner Kai , Wong Jenna , Schnabel Catherine A. 
Published: January 2022

647 Background: Mutations in isocitrate dehydrogenase 1 and 2 ( IDH1 and IDH2) often occur in hematologic malignancies and solid tumors. Ivosidenib was recently approved for IDH1-mutated cholangiocarcinoma based on improved progression-free survival (PFS) and overall survival (OS). Notably, cancers of uncertain diagnoses presenting as liver metastases are often cholangiocarcinoma. While several trials are ongoing to evaluate IDH1/2 inhibitor efficacy in other advanced solid tumor types, currently eligibility for IDH inhibitor therapy requires both tumor type identification and IDH mutation confirmation. The 92-gene assay (CancerTYPE ID) is a gene expression classifier of 50 tumor types and subtypes for metastatic patients with diagnostic ambiguity. Multimodal biomarker testing, including next-generation sequencing (NGS), enables identification of actionable biomarkers to guide targeted therapy selection. Here, a database of metastatic cases that integrates tumor type with biomarker analysis was used to identify those eligible for IDH inhibitor treatment. Methods: MOSAIC (Molecular Synergy to Advance Individualized Cancer Care) is an IRB-approved, de-identified database of cases submitted for CancerTYPE ID testing with tumor type-guided multimodal biomarker testing by NGS (Neogenomics). In this study, metastatic cancers classified as pancreaticobiliary and other solid tumor types with IDH1/2 mutations were identified. Results: CancerTYPE ID determined 27 different tumor types in 2377 of 2572 cases (92.4%). The most common tumor type identified was pancreaticobiliary with 644 cases; subtypes with IDH1/2 mutation status are shown in the table. An IDH1 mutation was identified in 23 out of 78 (29.5%) cholangiocarcinoma cases which are eligible for ivosidenib treatment. IDH1/2 mutations were also detected in 11 other tumor types. For patients with IDH1 mutations, 28.2% were identified in tumor types with no FDA-approved IDH therapy, whereas 50.0% of IDH2 mutations overlapped with tumor types that have ongoing trials to determine the clinical benefit of targeting IDH2. Conclusions: These findings support the clinical utility of molecular tumor type classification combined with biomarker profiling to identify approved or investigational treatment options. The MOSAIC analysis identified metastatic patients with actionable aberrations ( IDH1) eligible for FDA-approved therapy, as well as those who may be eligible for investigational IDH inhibitor therapies based on tumor type and IDH1/2 mutation status. As new and approved IDH inhibitors are evaluated for efficacy, increased patient selection may be afforded through this approach in additional tumor types.[Table: see text]
Feasibility of acupressure intervention to improve chemotherapy-related symptoms and functioning among gastrointestinal cancer patients.
Authors: Armstrong Samantha Ann , Wang Judy Huei-yu , Liu Geng-Hao , Arieta Carla , Thomas Maya , Geng Stephanie , Fritz Zach , He Aiwu Ruth , Noel Marcus Smith , Weinberg Benjamin Adam , Marshall John 
Published: January 2022

657 Background: Chemotherapy-related symptoms, including fatigue, pain, insomnia, nausea, and vomiting, affect cancer patients’ (pt) physical and mental functioning. Acupressure (AP), which uses fingers to stimulate acupoints in the body per traditional Chinese medicine, has shown beneficial effects in improving chemotherapy-related symptoms. Yet, AP has been understudied in gastrointestinal cancer (GI) pts’ symptom management. Methods: This single-arm pilot trial enrolled 24 patients with stage I-IV GI cancers undergoing chemotherapy. They were trained to self-administer AP to 4 acupoints (Li4, PC6, ST36, SP6) on each side of the body, then practice one minute per acupoint for 8 minutes every day and fill daily logs through an 8-week intervention period. The primary endpoint examined the feasibility (interest, retention, and adherence rates) of delivering self-administered AP. Chemotherapy-related symptoms and functional status at baseline and 8-week post-intervention follow-up were assessed using NIH patient-reported outcome assessments (PRO-CTCAE and PROMIS short forms). Paired t-tests were run to examine change scores in symptom outcomes before and after intervention. Results: Pt demographics were 50% male, 21% African American, 67% Caucasian and 12% other (mean age = 56). They included 38% colorectal cancer, 25% pancreatic cancer, 17% cholangiocarcinoma, and 20% upper GI cancers. Feasibility outcomes showed that 83% of approached pts were interested in participation; 24 of 31 eligible pts (77%) were enrolled; retention rate was 71% (N = 17). Seven pts did not complete the trial due to two with infections, three concerning time to fill daily logs, and two with unspecified reasons. Approximately 65% of pts adhered to performing AP for over 80% of the time and filling daily logs every week. No adverse events were attributed to AP. Data from PRO-CTCAE showed that over 93% of pts reported no or mild nausea and vomiting through the intervention period except one reporting a moderate level of vomiting. Data from PROMIS surveys showed that after the 8-week intervention, patient-reported pain interference with daily activities and physical functioning remained similar to the baseline level. Yet, pts had reduced fatigue (-4.4 points), sleep disturbance (-3.1), depression (-3.3), anxiety (-2.7), and increased cognitive function (2.6) after AP intervention. These improvements were not statistically significant due to the small sample size, but a 3-point change in the PROMIS symptom scores is clinically meaningful. Conclusions: This trial shows that self-administered AP proves to be a feasible, safe, and low-cost approach and may be beneficial for GI cancer pts to relieve treatment-related symptoms. Future randomized trials are needed to determine efficacy.
Medications to manage cancer-associated anorexia/cachexia syndrome (CACS) in patients with advanced gastrointestinal (GI) cancer.
Authors: Arora Nivedita , Ramesh Vidhyalakshmi , Virnig Beth A. , Blaes Anne Hudson , Gupta Arjun 
Published: January 2022

658 Background: Patients with advanced GI cancer have a high prevalence of CACS. Medications used for CACS have limited efficacy, unwanted side effects, and high costs. We sought to describe the prescribing patterns of medications for CACS in patients with advanced GI cancer. Methods: We identified patients with advanced GI cancer (primary pancreatic, gastric, colorectal, and hepatobiliary) treated at the UM Fairview Medical Center, Minneapolis, MN from 2011-2019. We extracted sociodemographics, clinicopathological data (e.g. body mass index [BMI]), other treatments (e.g. nutrition referral), and prescriber specialty (e.g. oncology). The primary outcome was medication use for CACS: outpatient oral prescription of ≥7 days of megestrol, dronabinol, mirtazapine, olanzapine, or cyproheptadine as any formulation (e.g., tablet, solution) on a scheduled basis. Since medications can have overlapping indications, we clarified prescription indication through chart review if needed. We excluded dexamethasone given extremely non-specific use. Results: We identified 974 patients with advanced GI cancer (45.9 % women, 84.2% White, 4.7% Black, median age 65 years, 36.8% pancreatic cancer, median overall survival 212 days). Of these, 265 (27.2%) patients received at least 1 prescription for CACS (Table). There were 736 unique prescriptions (41.8% dronabinol, 26.9% mirtazapine, 22.4% olanzapine, 8.4% megestrol and 0.4% cyproheptadine). Brand-name formulations comprised 2.7% prescriptions. Most prescriptions were provided by oncologists (67.1%), followed by primary care practitioners (20.3%), and palliative care (6.0%). The median times from advanced cancer diagnosis to first prescription, and from last prescription to death were 73 and 50 days respectively. The median BMI (kg/m2) and serum albumin (g/dL) at time of first prescription were 24.3 (range 11.8-51.1) and 2.5 (range 0.7-4.5) respectively. Conclusions: Almost 1/3rd of patients with advanced GI cancers received medications for CACS. Prescribing was primarily driven by oncologists, and was common in the last weeks of life. Our findings can guide interventions to optimize CACS care by reducing reflexive medication prescribing for CACS, while underscoring the need to develop better pharmacologic and non-pharmacologic CACS treatments.[Table: see text]
Core homologous recombination mutations and improved survival in nonpancreatic GI cancers.
Authors: Tan Elaine , Whiting Junmin , Walko Christine Marie , Knepper Todd C , Xie Hao , Imanirad Iman , Carballido Estrella M. , Felder Seth , Frakes Jessica M. , Mo Qianxing , Permuth Jennifer , Kim Richard D. , Anaya Daniel A. , Fleming Jason B. , Sahin Ibrahim Halil Halil 
Published: January 2022

663 Background: GI malignancies continue to be a major cause of cancer related deaths, despite advances in therapy options. In pancreatic cancer, the presence of homologous recombination mutations (HRM) has been shown to confer increased sensitivity to platinum chemotherapy. However, the role of HRM mutations in other GI cancers remains to be determined. The focus of this study is to evaluate the prognostic nature of core and noncore HRM in nonpancreatic GI cancers. Additionally, we aim to understand the predictive nature of these mutations related to platinum exposure. Methods: This was a retrospective review of patients at Moffitt Cancer Center with a primary stage IV nonpancreatic GI cancer treated with platinum therapy. All patients had next generation sequencing and were in the Clinical Genomics Action Committee database between 1/1/2013 and 11/1/2020. All patients had either a core HRM (BRCA1, BRCA2, PALB2) or noncore HRM (such as ATM, ATR, BARD1, BRIP1, FANCA, NBN, and RAD51). Patients were grouped into core HRM vs. noncore HRM. Response was stratified between responders (complete response and partial response) vs. non responders (stable disease and progressive disease), based on RECIST criteria. Progression free survival and overall survival were estimated using Kaplan-Meier method, and the log-rank test was used to assess the difference in progression free survival (PFS) and overall survival (OS) by HRM status and type of platinum therapy used. Results: There were 72 patients included in the study: the majority of patients were male (65.3%) and Caucasian (87.5%). Twenty-one (29.2%) patients had a core HRM and 51 (70.8%) had a noncore HRM. There was no significant difference in response rate between patients with core HRM and patients with noncore HRM for evaluable patients (n = 66): 20.0% of patients with core HRM vs. 21.7% of patients with noncore HRM demonstrated a response to platinum therapy (p = 0.41). An improved OS was noted for patients with core HRM vs. those with noncore HRM at 68.9 vs. 24.3 months (p = 0.019). An improved PFS was also seen in patients with core HRM at 10.4 months vs. 6.3 months with noncore HRM (p = 0.027). There was no difference in PFS based on type of platinum therapy used (oxaliplatin vs. carboplatin vs. cisplatin), while an improved OS was noted for patients treated with oxaliplatin vs. carboplatin vs. cisplatin at 43.1 vs. 28.2 vs. 16.0 months (p = 0.011). Conclusions: Our study demonstrated that in stage IV nonpancreatic GI malignancies treated with platinum therapy, patients with core HRM had a greater OS and PFS compared to those with noncore HRM, suggesting a potential prognostic and predictive role of these mutations. Further studies are needed to confirm our findings.