bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment sequencing for patients with localized duodenal and ampullary adenocarcinoma.
Authors: Janardan Abhishek , George Ben , Ahmed Gulrayz , Daniel Sherin , Thapa Bicky , Mehdi Maahum , Rein Lisa , Szabo Aniko , Erickson Beth , Hall William A. , Christians Kathleen K. , Tsai Susan , Evans Douglas B. , Kamgar Mandana 
Published: January 2023

783 Background: Duodenal adenocarcinomas (DA) and ampullary adenocarcinoma (AA) are rare, comprising less than 1% of all gastrointestinal cancers. Optimal treatment sequencing strategies for patients with localized DA and AA have not been prospectively validated. We analyzed the clinical outcomes of patients with localized DA and AA treated with curative intent, multimodality therapy based on treatment sequencing – upfront surgery versus neoadjuvant therapy. Methods: Our institutional database was interrogated to identify adult patients with localized DA and AA diagnosed between January 2000 to December 2019. Adjusted survival analyses were performed to compare outcomes of patients that received neoadjuvant therapy (NAT - concurrent chemo-radiation +/-induction chemotherapy) versus upfront surgery (+/- adjuvant chemotherapy). Survival time was calculated from date of diagnosis to either death (overall survival; OS) or relapse/death (relapse free survival; RFS). Log-rank test and multiple Cox proportional hazards regression were performed to compare survival between treatment groups and adjust for relevant variables. Results: We identified 79 patients – 32 (41%) with DA and 47 (59%) with AA; Median age at diagnosis was 67. Forty two patients (53%) were male. Sixty-two patients underwent surgery – 27 (43.6%) patients with DA and 35 patients (56.4%) with AA. Among patients with DA, 18 (67%) were treated with upfront surgery, while 9 (33%) were treated with NAT. Among patients with AA, 32 (91%) were treated with upfront surgery while 3 (9%) were treated with NAT. Lymph node (LN) positivity rate in DA and AA patients treated with upfront surgery was 15% and 46% respectively, compared to 50% and 0% respectively, in patients treated with NAT (p = 0.26, p > 0.99 respectively). DA patients treated with upfront surgery had a median relapse free survival (mRFS) of 3.8 years compared to 1.4 years for those treated with NAT (p = 0.370). The median overall survival m(OS) was not reached (NR) for DA patients treated with upfront surgery (4 years +) or NAT (2.6 years +) p = 0.875). AA patients treated with upfront surgery had a median RFS of 4.7 years compared to NR for patients treated with NAT (p = 0.117) while the mOS of AA patients treated with upfront surgery and NAT were 5.9 years and NR respectively (p = 0.158). Conclusions: Among DA patients, there was no difference in outcome based on sequence of treatment delivery – NAT versus upfront surgery. DA patients with more aggressive clinical phenotype were likely treated with NAT, hence similar outcomes in both groups should prompt consideration of NAT for all patients with DA. Role of NAT in AA is not clear considering the small sample size.
Risks and implications of multiple actionable pathogenic germline variants discovered by panel-based cancer predisposition testing.
Authors: Hall Michael J. , McSweeny Michelle J , Rainey Kim , Campbell Hannah , Nguyen Chau , Neumann Catherine 
Published: January 2023

792 Background: Multi-gene hereditary cancer panels have revolutionized how patients with germline mutations are identified by testing multiple genes at the same time. Despite the availability of panel testing, many patients with a known familial mutation will only undergo single site genetic testing due to limitations in guideline recommendations and insurance coverage. This approach risks a failure to detect additional pathogenic variants and an inappropriate management of cancer risk. In our clinical experience, a subset of patients pursue multigene testing despite a known familial mutation. Our group has identified patients who carry more than one mutation and mutations that would have been missed if the patients had only undergone single site testing. We investigated the patients and families from our risk assessment clinic with multiple familial mutations and determined how medical management may have been changed due to the presence of multiple mutations in family. Methods: The Fox Chase Cancer Center Risk Assessment Program (RAP) Registry was queried to identify patients who carry more than one mutation. Pedigrees of patients and families identified with multiple germline mutations were reviewed. Screening management guidelines were determined from the most recent NCCN guidelines published at the time the patient tested (Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic and Genetic/Familial High-Risk Assessment: Colorectal). The RAP Registry is an IRB approved protocol (IRB 09-831). Results: 70 patients were found to carry at least 2 mutations (excluding patients with biallelic MUTYH mutations) since introducing multi-gene panel testing in 2014. The most common second mutation was the I1307K variant in the APC gene at 20% (14/70). We also identified 20 patients who would have received incomplete genetic risk assessment if they only underwent single site testing and screening management changed in 60% (12/20) of these patients. 35% (7/20) of these patients did not meet NCCN criteria for additional germline testing beyond single site testing. Conclusions: Multi-gene hereditary cancer panels identify patients and families with multiple germline mutations. Patients undergoing single site cascade testing are at risk of receiving inaccurate risk assessment based on incomplete ascertainment of germline cancer risks. Detection of additional actionable mutations will frequently lead to changes in medical management.
Use of positron emission tomography-computed tomography (PET-CT) scan in patients with gastrointestinal (GI) cancer at the University Hospital of Montreal (CHUM).
Authors: Gebai Ahmad , Melendez Pena Carlos Enrique , Aubin Francine , Ayoub Jean-Pierre M. , Charpentier Danielle , Tehfe Mustapha 
Published: January 2023

793 Background: In the province of Quebec, Canada, PET-CT scan recommendations are published by the Institut national d’excellence en santé et en services sociaux (INESSS). These recommendations are based on evidence-based literature and publications from oncology societies (ASCO, NCCN...) Judicious use of PET-CT scans is particularly important in a public health system for appropriate allocation of resources. An analysis conducted by INESSS in 2017 demonstrated a remarkable use of 507 PET-CT scans per 100,000 persons in Quebec, an incidence more than twice as high as other provinces, and equivalent to that of the United States (510 per 100,000 person). Methods: We present a retrospective quality control study in which all PET-CT scans completed for oncologic purposes for patients of 18 years or older at CHUM between September 1st and November 30th, 2019, were included. Patients who had a PET-CT scan for non-oncologic purposes or weren’t followed at the CHUM were excluded. We reviewed disease characteristics of patients, and adherence to 2017 INESSS guidelines. All cancer types were analysed and classified according to imaging reason (staging, response to treatment, follow up). We herein report the use of PET-CT in GI cancers and how it compares to INESSS recommendation . Results: A total of 2331 PET-CT scans were completed in the studied period. Among them 975 PET-CT scans fit our inclusion criteria. 155 patients (16%) underwent PET-CT scans for GI cancers. Only 35% followed INESSS recommendations, 44% did not, and 21% had GI cancer types without revised clear recommendations from INESSS. Among specialists, surgeons requested most PET-CT scans (66%), but surgeons, oncologists, and gastroenterologist were equally non-adherent to guidelines (44, 45, and 43% respectively). Strikingly, 43% of PET-CT scans for GI cancers were prescribed for cancer follow up, yet 83% did not follow guidelines. Most PET-CT scans were used for colorectal (41%) or gastroesophageal cancers (28%), and only 40 and 53% followed guidelines, respectively. 49.7% of PET-CT scans did not result in treatment modification. Conclusions: In our university hospital, more than 40% of PET-CT scans prescribed don’t follow INESSS recommendations. In the interest of proper resource allocation in a public health care system, we recommend guideline adherence and discussion in multidisciplinary Tumour Boards prior to off-label use of PET-CT scans.
Is liquid biopsy useful in patients with GI malignancies and exclusive peritoneal disease?
Authors: Smolenschi Cristina , Valery Marine , Boileve Alice , Cervantes Baptiste , Tarabay Anthony , Boige Valerie , Ben-Ammar Imen , Cheaib Bianca , Gelli Maximiliano , Sourouille Isabelle , Benhaim Leonor , Fuerea Alina , Perret Audrey , Ducreux Michel , Hollebecque Antoine 
Published: January 2023

809 Background: Peritoneal carcinomatosis (PC) is a common manifestation in gastro-intestinal (GI) cancers.10-20 % of patients (pts) will present isolated, unresectable peritoneal disease with poor prognosis. In the past years, circulating tumor DNA (ctDNA) has emerged as a novel and less invasive biomarker for molecular diagnosis and disease monitoring. We aimed to evaluate the ability of PC to shed ctDNA into circulation in a cohort of pts with GI cancers and isolated PC treated in our institution. Methods: We reviewed retrospectively the results of liquid biopsies obtained at progression or at diagnosis. Genomic analysis was done using Foundation One liquid CDx panel. Data on demographics, tumor type, clinical outcomes and molecular alterations (MA) have been collected. Results: Out of 400 GI pts tested, 85 with exclusively PC were included in the analysis. The main characteristics were as follows: 45(53%) female, median age of 57 years (IQR: 24-79), majority have received systemic chemotherapy (all were progressive) (n=63, 74%) with median number of previous lines 1 (range: 0-3). Most common tumor types were as follows: gastric (n=24, 28%), colorectal (n=22, 26%) and primary peritoneal (n=20, 24%) cancers. The median index of peritoneal carcinomatosis was 23(IQR: 6-39). The tumor fraction was very low or undetectable in a proportion of 81% (n=69), median Tumor Mutational Burden was 1 mutation per megabase and was not correlated to tumor volume. Gene alterations were found in a proportion of 56% of pts (n=48) but most common alteration were TP 53 (n=22 pts, 26%) and KRAS mutation (n=14 pts, 16%). Targetable MA were identified only in 11 pts (13%) as follows: ATM, ARID1A, BRAFV600E, ERBB2, krasG12C. Three of them were included in a clinical trial. Germline mutations were found in 5 pts: ATM, CDH1, BRCA2, MSH6, BAP1. For colorectal pts known KRAS and BRAF V600E mutations were confirmed in plasma in a proportion of 32% (7 pts out of 22), for pancreatic cancer the KRAS in 17% (3 out of 18) and for gastric cancer, ERBB2 amplification in 5% (1 out of 22 pts). In pts with primary peritoneal disease: pseudomyxoma and mesothelioma, one patient harbored a known germline BAP 1 and kras G12C mutation without other targetable MA. The median survival in MA group was higher compared to non-MA. Conclusions: Isolated Pc and primary peritoneal cancers have distinct clinical and biological characteristics. The clinical utility of ctDNA seems to be limited in isolated PC or primary peritoneal cancers. However, it is not very clear if this to tumor location or to the ability of peritoneum to seed ctDNA.
Perioperative changes in geriatric functions of elderly patients undergoing surgical resection for gastric cancer.
Authors: Tanaka Chie , Kanda Mitsuro , Nakanishi Koki , Umeda Shinichi , Shimizu Dai , Inokawa Yoshikuni , Takami Hideki , Hayashi Masamichi , Nakayama Goro , Fujiwara Michitaka , Kodera Yasuhiro , Hattori Norifumi 
Published: January 2023

811 Background: Little knowledge is available for postsurgical changes in cognitive and physical functions that may be useful for considering indication for surgery in elderly patients with gastric cancer. We therefore conducted a prospective study aimed to determine the influence of gastrectomy on these patients. Methods: We recruited patients older than 75 years for whom gastrectomy for gastric cancer had been planned, and assessed their cognitive and physical functions, daily activities, episodes of depression, confusion, and delirium before surgery (baseline), upon discharge, and at 6 months after surgery (POM 6). Results: Among 54 elderly patients registered between February 2017 and February 2020. There were no significant decreases in MMSE scores between baseline and at POM 6, nor were there significant differences in physical function and indicators of depression and confusion between these time points. As many as 20% of patients were found to have the functional decline on the basic activities of daily living scores (BADL) after surgery compared with the baseline. The only variable significantly associated with a functional decline in BADL was postoperative complications. Conclusions: Postoperative cognitive functions did not significantly decline when compared with the baseline scores, although postoperative BADL scores of patients who experienced postoperative complications were significantly lower than those who did not.
Epidemiology and survival analysis of non-GIST GI sarcomas: A two-decade analysis of SEER database.
Authors: Nutalapati Snigdha , Patel Reema Anil , Chen Quan , Huang Bin 
Published: January 2023

812 Background: Primary adult non-GIST (gastrointestinal stromal tumors) gastrointestinal sarcomas are rare, accounting for 1-2% of all GI malignancies. Given the paucity of literature, we aimed to study the epidemiology and clinical outcomes of these sarcomas. Methods: National SEER-18 registry database was analyzed from 2001 to 2019 to identify non-GIST-GI sarcomas among adults aged 20 years and older. Demographics and clinical factors, including age at diagnosis, gender, race, primary cancer site, histology group, tumor grade and treatment, were examined in descriptive analysis. Log-rank tests, KM plots and Cox regression were utilized for observed survival analysis. P-value of <0.01 was considered statistically significant. Retroperitoneal sarcomas were excluded. Results: A total of 1277 non-GIST-GI sarcomas were identified, 53.6% were male. Common primary sites include small intestine (32.4%), stomach (27.0%), colon (23.0%), esophagus (8.4%), rectum (8.3%) and anus (0.9%). Most common histological subtype was leiomyosarcoma (52.8%) followed by sarcomatoid carcinoma (10.6%), spindle cell sarcoma (6.2%), carcinosarcoma (5.9%), liposarcoma (5.2%) and angiosarcoma (4.7%). Surgery only was the most common treatment received (61.4%). Stratified by primary tumor site, five-year survival rate was highest for colon (46%; 95% CI 40-52) followed by anus (HR 44%; 95% CI 15-70), stomach (HR 42%; 95% CI 36-47), rectum (HR 36%; 95% CI 27-46), small intestine (HR 36%; 95% CI 31-41) and esophagus (HR 30%; 95% CI 21-38).Similarly, for common histological subtypes 5-year survival was highest for liposarcoma (HR 56%; 95% CI 43-68) followed by leiomyosarcoma (HR 46%; 95% CI 42-50) and spindle cell sarcoma (HR 36%; 95% CI 25-47) and lowest for carcinosarcoma (HR 15%; 95% CI 8-25) followed by sarcomatoid carcinoma (HR 17%; 95% CI 11-24), and angiosarcoma (HR 17%; 95% CI 9-28).On multivariate cox regression analysis, factors associated with unfavorable prognosis were male gender (HR 1.21; 95% CI 1.06-1.39), small intestine (HR 1.38; 95% CI 1.15-1.65) sarcomatoid sarcoma (HR 1.42; 95% CI 1.06-1.92), poorly differentiated tumors(HR 2.90; 95% CI 1.99-2.43). Esophageal primary (HR 0.66; 95% CI 0.49-0.87) and leiomyosarcoma (HR 0.81; 95% CI 0.70-0.94) had a favorable prognosis. Conclusions: Non-GIST-GI sarcomas are very rare with slight male predominance and more than three quarters of cases diagnosed among 55 years and older. Leiomyosarcoma was the most common subtype and small intestine was most common primary site. Overall liposarcoma had the highest five year survival rate and carcinosarcoma had the lowest.On multivariate analysis male gender, small intestinal primary, sarcomatoid carcinoma had unfavorable prognosis.
BAYONET trial: A multicenter phase II trial of staged combination with encorafenib + binimetinib + cetuximab following encorafenib + cetuximab in patients with BRAF V600E-mutant metastatic colorectal cancer.
Authors: Matsubara Yuki , Bando Hideaki , Kotani Daisuke , Kagawa Yoshinori , Harada Kazuaki , Osumi Hiroki , Izawa Naoki , Kawakami Takeshi , Boku Shogen , Matsumoto Toshihiko , Wakabayashi Masashi , Yoshino Takayuki 
Published: January 2023

TPS271 Background: While the triplet combination of encorafenib (ENCO) + binimetinib (BINI) + cetuximab (CET) indicated higher response rate compared to the doublet combination of ENCO + CET, no significant survival benefits of the triplet combination were observed in patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC) according to BEACON CRC study. Although ENCO + CET is the standard 2nd-line therapy in the United States and European Union, poor prognoses are expected after disease progression. As resistant mechanisms of BRAF + EGFR blockage, several MAPK pathway alternations, including RAS and RAF mutations were reported, which suggests the additional blockade of MAPK signaling may be an effective strategy for ENCO + CET refractory mCRC. In addition, the preclinical study suggested BRAF inhibitor + anti-EGFR antibody resistant BRAF V600E-mutant colorectal cancer cell-lines were sensitive to the combination of BRAF inhibitor + MEK inhibitor + anti-EGFR antibody (Oddo D, et al. Cancer Res. 2016). Methods: BAYONET is a single-arm multicenter phase II trial to evaluate the efficacy and safety of the staged combination with ENCO + BINI + CET for patients with BRAF V600E-mutant mCRC who were refractory to ENCO + CET. The main eligibility criteria are as follows; RAS wild-type/ BRAF V600E-mutant mCRC; age ≥ 20; ECOG PS 0 or 1; within 4 weeks from the last administration of previous ENCO or CET; no administration of other systemic therapy after refractoriness to ENCO + CET; complete response, partial response, or ≥4 months of stable disease were observed in the previous ENCO + CET. Included patients receive the combination treatment of ENCO (300mg once a day) + BINI (45mg twice a day) + CET (400mg/m2 initial dose and then 250mg/m2 once a week) in a 28 day-cycle as a study treatment. The primary endpoint of this trial is 12-week progression-free survival (PFS) rate. The secondary endpoints include PFS, overall survival, objective response rate, disease control rate, time to treatment failure, and the incidence of adverse events. The targeted sample size was calculated to be 30 on the basis of a power of 80%, a significant level of 10% (one-sided), the threshold 12-week PFS rate of 20%, and the expected 12-week PFS rate of 40%. As a translational analysis, circulating tumor DNA for next-generation sequencing using Guardant360 is collected at twice time points (before and after study treatment) to investigate the resistance mechanisms. Enrollment started from Jan 2022 and is ongoing at 25 facilities in Japan. As of Sep 20, 2022, 9 patients were enrolled. Clinical trial information: jRCTs031210510 .
Trial in progress: A phase 2 study of CTX-009 in adult patients with metastatic colorectal cancer who have received two or three prior systemic chemotherapy regimens.
Authors: Fontaine Marilyn , Pilgrim Sarah , Schuetz Thomas 
Published: January 2023

TPS281 Background: CTX-009 is a recombinant bispecific antibody that binds both delta-like ligand-4 (DLL4) and vascular endothelial growth factor A (VEGF-A). The antibody simultaneously inhibits the DLL4-Notch 1 and VEGF A-VEGF receptor signaling pathways. Patients with unresectable locally advanced and unresectable metastatic colorectal cancer (CRC) are sequentially treated with various combinations or single agent courses of cytotoxic chemotherapy agents including 5-fluorouracil and its orally administered family members (capecitabine, TAS-102) oxaliplatin, and irinotecan, as well with targeted therapies such as bevacizumab or aflibercept (anti-VEGF), cetuximab or panitumumab (anti-EGFR), or multitargeted tyrosine kinase inhibitors (regorafenib). In subsets of patients who have had multigene panel testing done and whose tumors have been identified as having mutations that drive their disease such as defective mismatch repair, HER-2 overexpression, or NTRK fusions specific treatments with respectively PD-1 or PD-L1 inhibitors, traztuzumab or larotrectinib or entrectinib can also be used effectively. Despite the approval of multiple new agents in the past two decades, the goals of therapy are generally palliative although some patients will have long disease-free intervals when they respond to therapy. In the cases of patients whose disease has progressed, or who have not tolerated 2 or 3 prior lines of therapy, the expectation for tumor response with the available treatments are less than 5% and the median overall survival is approximately 6 months (for 3rd line therapy) or less (for 4th line therapy). In a Phase 1 study with CTX-009, responses have been seen in patients with colorectal cancers who were treated in the 4th line setting. Since CTX-009 targets tumor induced neoangiogenesis, and monoclonal antibodies that target vascular endothelial growth factor (VEGF) has been shown to extend the lives of patients with advanced colorectal cancer, testing of CTX-009 in the setting of advanced treatment refractory colorectal cancer is justified. Methods: CTX-009 is being evaluated in an open label study in patients with previously treated metastatic CRC. This study is designed as an adaptive Simon Two Stage study, with approximately 37 patients to be enrolled into Stage 1. If criteria are met to move to Stage 2, an additional 47 patients will be enrolled, for a total of approximately 84 patients. To move to stage 2 of the study, 3 or more Complete or Partial Responses must be confirmed via RECIST 1.1. Patients will be treated in 28-day cycles, with CTX-009 administration on Day 1 and 15. The primary objective of the study is to assess the efficacy of CTX-009, as measured by Overall Response Rate (ORR). The study is currently activating sites with first patient in expected in 2022. Clinical trial information: NCT05513742 .