bluuebunny/crossref_metadata_2025_split huggingface dataset:
NTRK fusion positive colorectal cancer as a unique subset of CRC with high tumor mutation burden and microsatellite instability.
Authors: WANG Hui , Ou Qiuxiang , Wu Xue , Nagasaka Misako , Ou Sai-Hong Ignatius , Shao Yang 
Published: June 2021

3544 Background: Neurotrophin receptor tyrosine kinase ( NTRK) gene fusions are rare but actionable oncogenic drivers that are present in a wide variety of solid tumors. This study aims to identify the frequency and the clinicopathologic and genetic features of NTRK-driven colorectal cancers (CRC). Methods: Colonic and rectal tumor DNA specimen from colorectal cancer patients submitted for molecular profiling at a CLIA-certified genomics laboratory in China that performed NTRK1/2/3 fusion detection by hybridization-based targeted next generation sequencing (NGS) were retrospectively reviewed. Patients’ demographic, clinical characteristics, and treatment history were retrieved from the database for further evaluation. Results: A total of 2,519 unique Chinese colorectal cancer cases were profiled from April 2016 to May 2020, and 17 NTRK+ fusion events were identified (0.7%, 17/2,519) consisting of 14 cases of NTRK1+ and 3 cases of NTRK3+ fusions. Furthermore, thirteen out of 17 NTRK+ CRC tumors (76%) were microsatellite instability-high (MSI-H) tumors, a much higher rate than that of the molecularly unselected CRC population (8%) or NTRK+ non-CRC tumors ( < 1%). NTRK+ CRC patients also had increased tumor mutation burden (median TMB = 65 mut/MB) compared to that of non- NTRK+ CRC (median TMB = 7.7 mut/MB) or NTRK+ non-CRC tumors (median TMB = 4 mut/MB). POLE/POLD1 mutations were also enriched in NTRK+ CRC (8/17, 47%) relative to molecularly unstratified CRC patients (8%) with over half carrying concurrent POLE and POLD1 mutations. TPM3 was the most common fusion partner of NTRK1 (78%, N = 14), followed by LMNA and TRP. Three NTRK3+ CRC were identified (ETV6-NTRK3, RUNX1-NTRK3, CSNK1G1-NTRK3). RNF43 (71%) was the most frequently mutated gene and the aberrations of RNF43 and ARID1 were significantly enriched in MSI-positive NTRK+ tumors as compared to the MSS NTRK+ subgroup. TP53 (53%) and APC (35%) aberrations frequently co-occurred with NTRK fusions, whereas the majority of the NTRK+ cohort were RAS/BRAF wildtype, except in one case that an oncogenic KRAS Q61R variant co-occurred with RUNX1-NTRK3. Conclusions: NTRK+ colorectal cancer is rare. In addition to the absence of canonical driver mutations, NTRK+ tumors demonstrated increased tumor mutation burden, higher frequency of microsatellite instability, and an enrichment of POLE/POLD1 mutations relative to molecularly unselected CRC population.
Effect of Medicaid expansion on incidence of early-onset colorectal cancer incidence among Hispanics.
Authors: Rahman Shafia , Patel Riya Jayesh , Liu Jianyou , Acuna-Villaorduna Ana , Kim Mimi , Goel Sanjay 
Published: June 2021

3547 Background: Early onset colorectal cancer (EO-CRC, age < 50 years) is an emerging public health crisis; especially in Hispanics. Access to healthcare is critical for timely detection and is tied to medical insurance. In 2010, the Affordable Care Act allowed for expansion of Medicaid eligibility across the country, however, states were permitted to opt out by the US Supreme Court ruling of 2012, which created an unintended experiment in the healthcare market. We evaluated the effects of Medicaid expansion on the incidence of EO-CRC among Hispanics with the hypothesis that it would lead to an increase in incidence and early detection EO-CRC. Methods: The National Cancer Data Base was used to collect data on newly diagnosed Hispanics with EO-CRC (40-49 years), across all stages, from 2010-2017. Data for 21 expansion states (ES) that expanded Medicaid in 2014, and 16 non expansion (NES) states was analyzed. The yearly state-wise Hispanic population was collected from U.S Census Bureau for 2010-17. Incidence was computed as number of new cases of CRC divided by size of the state’s Hispanic population. Segmented Poisson generalized linear mixed effects model was used to analyze rate of change in yearly incidence of EOCRC before and after 2014, in ES and NES. Results: Average annual incidence (AI) of EO-CRC in Hispanics was 6/100,000 and 8/100,000 pre and post expansion, in ES, and 8/100,000 and 9/100,000 pre and post 2014 in the NES, respectively. Increase in AI of EO-CRC was 3.6% per year (2010-14) (95% CI: -0.1% to 7.4%), and 9.8% (2014-17) (95% CI: 5.2% to 14.7%) for ES states; and 6.4% (2010-14) (95% CI: 2.1% to 10.8%), and 1% (2014-17) (95% CI: -3.8% to 6.1%) in NES. ES showed greater change in EO-CRC incidence post expansion (2014) vs. pre-expansion, as compared to NES (p=0.078) table. There was no difference in stage at diagnosis between pre- and pos- expansion periods between ES and NES. Conclusions: Increase in incidence of EO-CRC in ES is likely due to greater access to health care due to Medicaid coverage as compared to NES. Other potential factor is migration of Medicaid eligible persons from NES to ES. However we need data past 2017 to confirm the current trend.[Table: see text]
FOLFOX plus panitumumab or FOLFOX alone as additive therapy following R0/1 resection of RAS wild-type colorectal cancer liver metastases: The PARLIM trial (AIO KRK 0314).
Authors: Modest Dominik Paul , Karthaus Meinolf , Kasper Stefan , Moosmann Nicolas , Keitel Verena , Kiani Alexander , Fischer von Weikersthal Ludwig , Uhlig Jens , Jacobasch Lutz , Fuchs Martin , Kaiser Florian , Lerchenmuller Christian A. , Junghanss Christian , Held Swantje , Heinrich Kathrin , Jung Andreas , Stahler Arndt , Stintzing Sebastian , Heinemann Volker 
Published: June 2021

3553 Background: This trial investigates the addition of panitumumab to chemotherapy with fluorouracil/ folinic acid and oxaliplatin (FOLFOX) in a 2:1 randomized, controlled, open label, phase II trial in RAS wild-type colorectal cancer patients with R0/1-resected liver metastases. Methods: The primary endpoint was progression-free survival (PFS) two years after randomisation. The experimental arm (12 wks of biweekly mFOLFOX6 plus panitumumab followed by 12 wks of panitumumab alone) was considered active if the 2-year-PFS rate was ≥65%. Based on historical data, a 2-year-PFS rate of 50% was estimated in the control arm (12 wks of biweekly FOLFOX). The trial was performed with a power of 80% and an alpha of 0.05. Secondary endpoints included overall survival (OS) and toxicity. The trial is registered with ClinicalTrials.gov, NCT01384994. Results: The full analysis set consists of 70 patients (pts) in the experimental arm and 36 pts in the control arm. The 2-year-PFS rate was 34.3% with FOLFOX plus panitumumab and failed to meet the primary endpoint. The 2-year-PFS rate in the control arm was 25%. In the experimental arm, a more favourable outcome was observed with regard to PFS (HR: 0.72, 95%CI 0.45-1.17; P = 0.18) and OS (HR: 0.76 (95% CI 0.34-1.71, P = 0.51) which did, however, not reach the level of significance. Updated data including toxicity and subgroup analyses might be presented at the meeting Conclusions: The PARLIM trial clearly failed to demonstrate a PFS rate of 65% after resection of colorectal liver metastases 2 years after randomisation, potentially indicating that the generally high frequency of recurrence and the choice of primary endpoint did not correspond in this study population. However, a trend for improved PFS and OS by the addition of panitumumab to 12 wks of FOLFOX followed by 12 wks panitumumab maintenance therapy may support future trials with ant-EGFR antibodies in this specific treatment setting. Clinical trial information: NCT01384994.
Concurrent BRAFV600E and BRCA mutations in microsatellite stable (MSS) metastatic colorectal cancer (mCRC): Prevalence and case series of mCRC (pts) with prolonged overall survival (OS).
Authors: Cannon Timothy Lewis , Randall Jamie , Sokol Ethan , Alexander Sonja , Wadlow Raymond Couric , Barnett Daniel , Rayes Danny , Deeken John F. , Nimeiri Halla , McGregor Kimberly 
Published: June 2021

3561 Background: BRAF V600E+, MSS mCRC patients comprise up to 10% of advanced CRC. They have a poor prognosis with median survivals typically <1 year. Despite use of multi-agent first-line chemotherapy regimens and combination targeted therapies, outcomes are still poor. In our Institutional Molecular Tumor Board database, we identified 3 consecutive mCRC pts with MSS/ BRAF V600E who also had a BRCA1 or BRCA2 co-mutation and had prolonged overall survival. Prior studies suggested that BRCA mutations are uncommon in CRC and we queried the Foundation Medicine (FM) genomic database to evaluate the prevalence of these cases as well as those with co-mutations in other homologous recombination genes. Methods: 36,966 CRC pts were sequenced by FMI using hybrid capture comprehensive genomic profiling (CGP) to evaluate all classes of genomic alterations (GA) for pathogenic BRAF mutations and/or a mutation in BRCA1/2 or a co-mutation in other homologous recombination (HR) genes ( BARD1, CDK12, FANCL, PALB2, ATM, RAD54L, CHEK2, BRAF, BRIP1, RAD51D, RAD51C, RAD51B, CHEK1). Selected cohort analysis were BRAF V600E co-mutated with BRCA1 and BRCA2, separated into MSI-H and MSS cohorts. The clinicopathological features and genomic loss of heterozygosity (gLOH) of those with a BRAF V600E and a BRCA1/BRCA2 mutation are described along with 3 consecutive cases of CRC patients, identified through the Inova Schar Cancer Institute (ISCI) molecular tumor board (MTB) registry, whom had prolonged OS. Results: Of 36,966 colorectal cancer pts, 6.6% were BRAF V600E+ and 1.5% had any co-occurring HR gene mutation(s) with 0.6% having co-mutations of BRAF V600E and BRCA1/2. BRCA co-mutations were higher in MSI-High BRAF V600E, however 24.1% of these occurred in MSS BRAF V600E. BRCA1 co-mutated was more commonly associated with MSS BRAF V600E and was associated with a higher gLOH than MSI-H BRAF V600E (18.7% vs 2.8%; p <0.001 ). In our institutional MTB database, (3/241;1.2%) CRC patients were MSS, BRAF V600E+ with BRCA1 or BRCA2 co-mutations, one confirmed germline and 2 somatic in origin, and had average gLOH of 21.4% with overall survivals of 72+(alive), 17+(alive), and 30 months, respectively. Conclusions: Co-existence of BRAF V600E/ BRCA1/2 may represent a unique subset of advanced MSS CRC that may have a better prognosis and represent an opportunity to test novel targeted therapies. Larger prospective clinical validation trials in this subset is warranted.[Table: see text]
Neoadjuvant chemotherapy to improve colon cancer survival in resectable metastatic colon cancer: A real world NCDB data analysis.
Authors: Parasramka Saurabh , Jacob Aasems , Chen Quan , Huang Bin , Hao Zhonglin 
Published: June 2021

3567 Background: According to the SEER database, approximately 21% of colon cancer patients have synchronous metastatic disease at presentation with a five-year survival of only 14%. Liver is by far the most common site of metastasis. For resectable and borderline resectable metastatic lesions after conversion to surgical resection, five-year survival ranges between 40-70% in different series. Survival advantage of neoadjuvant chemotherapy is not clear. We present here an updated analysis of effect of different variables on survival of 3,247 patients from the National Cancer Database (NCDB) treated from 2010-2015. Methods: Adults 20 years or older with primary colon cancer and single organ metastatic disease either in the liver and/or lung at diagnosis were identified. All patients had received surgery to the primary site, resection of the distant site and chemotherapy within 1 year of diagnosis. Patients were categorized into 2 cohorts based on whether they received chemotherapy in the pre-operative/peri-operative setting (neoadjuvant chemotherapy –NAC) or post-operative setting (adjuvant chemotherapy AC). Descriptive analysis, Kaplan-Meier plots, Log-Rank tests and Cox regression models for multivariate survival analyses were performed. To assess uncertainty of estimates, a sensitive analysis was also performed based on the intention to treat principle by including additional surgery only and chemotherapy only cases. Results: A total of 3,247 patients with colon cancer with liver or lung metastases were identified. A large majority 2,527 patients (77.8%) received AC. 54.5% were males and 45.5% females. On multivariate analysis, patients who received NAC had overall survival (OS) advantage with hazard ratio (HR) 0.86 (0.75-0.98). Clinical factors associated with worse survival included age > 75 HR 1.31; positive margin status with R1 HR 1.49 or R2 HR 2.33; Comorbidity index ≥ 2 HR 1.68; positive KRAS status HR 1.20; N2 disease HR1.95; ; having liver metastasis compared to lung HR 1.65 ;. Factors associated with improved survival were CEA less than 30 ng/ml at diagnosis and left sided tumor with HR of 0.64 (0.56-0.72) and 0.75(0.67-0.84) respectively. Conclusions: Metastatic colon cancer with single organ liver or lung lesions benefit from neoadjuvant chemotherapy based on our analysis of the real-world data. The survival advantage in this setting has not been shown before.
Mucinous colorectal cancer: Disease characteristics, treatment outcomes and the impact of metastasectomy.
Authors: Cowzer Darren , Harrold Emily , Sui Jane Sze Yin , Lucas Mairi , Fenlon Helen M , Redmond Karen C , Eaton Donna , Conneely John B , McEntee Gerry P , Brannigan Ann E , Shields Conor J , Mulsow Jurgen , Kelly Catherine Margaret , Greally Megan , McCaffrey John 
Published: June 2021

3586 Background: Mucinous colorectal cancer (CRC) differs from adenocarcinoma with regard to clinical and histological features and is reported to have inferior outcomes when compared to non-mucinous CRC. This study aims to evaluate the clinical features and outcomes of patients with mucinous CRC at our institution. Methods: Medical records of patients with CRC that were referred to medical oncology between September 1999 and September 2018 were retrospectively reviewed. Mucinous histology was defined as those containing > 50% mucin identified on histology specimens. Statistical analysis was performed using Prism V9.0. Results: We identified 1,115 patients with CRC that were referred to medical oncology during this period. The tumours of 81 (7.3%) patients were classified as mucinous. Median age was 65 (28-94 years) and 45 (55.5%) were male. Forty-one patients (51%) had right sided tumours, 27 (33%) had left sided tumours and 13 (16%) had rectal tumours. Twenty-three (28.4%) had de novo metastatic disease. Eleven of 24 patients (46%) with stage II disease relapsed and 18 of 33 (55%) of those with stage III disease relapsed. Radiological surveillance identified 20/29 (69%) of relapsed disease, 5 (17%) were symptomatic and 4 (14%) had a rise in CEA. Median follow up for patients with stage II disease was 53 months and 3 year and 5-year disease free survival (DFS) was equal in both groups at 60.9%. For stage III disease 3- and 5-year DFS was 58.1% and 48.4% respectively with a median follow up of 43 months. In the metastatic setting, we observed no significant difference in overall survival (OS) between left and right sided tumours ( p = 0.550). Median OS for pts with stage IV mucinous CRC who received any treatment was 25 months. Metastasectomy was performed in 25/52 (48%) patients and was associated with a significant improvement in OS, 23 vs 51 months ( p < 0.005, HR 0.4). Conclusions: Mucinous CRC has been associated with inferior responses to treatment and worse overall outcomes compared to non-mucinous histologies. Survival in advanced-stage disease in our cohort is higher than what has been reported in the literature. With an effective multi-disciplinary approach and the increasing use of metastasectomy as a treatment option, survival in the advanced disease setting may be comparable to non-mucinous CRC.
Clinicopathological and molecular characteristics of early-onset stage III colon adenocarcinoma: An analysis of 25 studies with 35,713 patients in the Adjuvant Colon Cancer End Points (ACCENT) database.
Authors: Jin Zhaohui , Dixon Jesse G. , Parekh Hiral , Sinicrope Frank A. , Yothers Greg , Haller Daniel G. , Schmoll Hans , De Gramont Aimery , Kerr Rachel , Taieb Julien , Van Cutsem Eric , Twelves Chris , Saltz Leonard B. , Tomita Naohiro , Yoshino Takayuki , Andre Thierry , Mahipal Amit , Goldberg Richard M. , George Thomas J. , Shi Qian 
Published: June 2021

3597 Background: Colon cancer (CC) incidence and mortality have decreased since the 1970s, but the incidence in young adults (20-49 years) is increasing. There are limited data suggesting that, as a group, patients with early onset CRC (eoCC) may have different phenotypic characteristics compared to those with late onset CRC (loCC, age ≥ 50 years). Methods: Individual patient data on 35,713 subjects with stage III CC from 25 randomized studies (recruiting between 1987 and 2009) in the ACCENT database were pooled. The distributions of demographics, clinicopathological features, biomarkers, and outcome data were summarized by age group. Overall survival (OS), disease-free survival (DFS), recurrence free rate (RFR), and survival after recurrence (SAR) were assessed by Kaplan-Meier curves and Cox models stratified by treatment arms within studies, adjusting for gender, race, body mass index, performance status, disease stage, grade, risk group, number of lymph nodes examined, disease sidedness and molecular markers. Results: Using a 5% difference between age groups as the clinically meaningful cutoff, patients with stage III eoCC (n = 6246) had similar distributions according to gender, race, PS, risk group, tumor sidedness and T/N stage compared to those with loCC (n = 29467). Patients with eoCC were significantly less likely to be overweight (30.2% vs 36.2%) but more commonly had ≥ 12 lymph nodes resected (69.5% vs 58.7%). The eoCC tumors were more frequently mismatch repair deficient (16.4% vs 11.5%), and less likely to have BRAFV600E (5.6% vs 14.0%), suggesting a higher frequency of Lynch syndrome in eoCC. In univariate analysis, patients with stage III eoCC had significantly better OS, DFS, and SAR; the difference between 3-year DFS and RFR strongly suggests the OS/DFS difference between these the eoCC and loCC may be due to increased competing risks and comorbidities in patients with loCC. In multivariate analysis, age at onset lost its prognostic value when outcome was adjusted for molecular markers. The clear relation between age of onset and KRAS/BRAF status was confirmed in the interaction analysis. Conclusions: Tumor biology was an important determinant of prognosis regardless of patient age. In multivariate analysis age of onset was not a statistically significant determinant of outcome.[Table: see text]
Impact of radiotherapy for local control in T3 N0 rectal cancer managed with total mesorectal excision: A systematic review and meta-analysis.
Authors: Fabregas Jesus C. , Bang Andrew , Tjong Michael , Kucharczyk Michael 
Published: June 2021

3604 Background: Total mesorectal excision (TME) significantly improved rectal cancer outcomes. Radiotherapy (RT) is recommended for T3N0 rectal cancers, though benefit has not been demonstrated in combination with TME for this specific population. This meta-analysis could provide evidence to ameliorate toxicities from treatment. Methods: Randomized clinical trials and observational studies published until October 18, 2020 were identified via PubMed and Embase. Objective: To determine whether RT decreased the risk of local recurrence (LR) in T3N0 rectal cancer managed with TME. Study Selection and Extraction: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were observed for literature search, extraction, and screening. Studies with LR data specific to T3N0M0 rectal cancer, treated with and without RT, were included. Reviews, non-English articles, and non-TME studies were excluded. Newcastle Ottawa Scale (NOS) evaluated quality. Meta-analysis was done with a random-effects model. Main outcome: Meta-analysis of the relative risk of LR was conducted. Results: 7,246 studies were screened, 134 full-text studies assessed for eligibility, 5 studies were included in the final analysis. No randomized data reported results specific to our study population. Five retrospective cohort studies involving 932 participants reported LR outcomes. The median follow-up ranged from 38.4 months up to 71 months. Four studies took place in Asia (797 participants) and one in North America (135 participants) (Table). Quality according to NOS ranged from 7–9. The estimated average relative risk for LR at 5 years was 0.63 (95% CI 0.31–1.29; I2=41.8%) when RT was used. Conclusions: This meta-analysis’ supports that there is no clear benefit to LR with the addition of RT in T3N0 patients with rectal adenocarcinoma undergoing TME. As meta-analysis was limited to retrospective cohort studies, there is concern for bias. Registration Prospero number CRD42020216058 .[Table: see text]
The prognostic value of tumor markers in patients (pts) with resectable gastric cancer (GC) receiving perioperative therapy in the CRITICS trial.
Authors: Slagter Astrid E. , Vollebergh Marieke A. , Caspers Irene A , van Sandick Johanna W. , Sikorska Karolina , Lind Pehr A. , Nordsmark Marianne , Putter Hein , Braak Jeffrey P.B.M. , Meershoek – Klein Kranenbarg Elma , Van De Velde Cornelis J.H. , Jansen Edwin PM , Cats Annemieke , Van Laarhoven Hanneke W.M. , van Grieken Nicole C.T. , Verheij Marcel 
Published: June 2021

4024 Background: Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 are well-known tumor markers. Most studies on CEA and CA 19-9 in pts with GC were performed in Asia, and/or in the metastatic setting. The aim of this study was to investigate the prognostic value of blood derived laboratory parameters in a cohort of European pts with resectable non-metastatic GC. Methods: In the CRITICS trial, 788 pts with resectable GC underwent perioperative therapy (preoperative chemotherapy plus either postoperative chemotherapy or postoperative chemoradiotherapy). Blood levels of CEA, CA 19-9, alkaline phosphatase (AP), creatinine, neutrophils, hemoglobin (Hb) and lactate dehydrogenase (LDH) were determined prior to treatment. Data for these variables were available for at least 89% of the pts. Factors significant on univariable cox regression analysis were further explored in multivariable analysis. Probabilities to undergo potentially curative surgery was investigated for factors significant on multivariable analysis. The relationship between tumor markers and the presence of circulating tumor DNA (ctDNA) was explored in 50 pts with available ctDNA data. Results: CEA and CA 19-9 were identified as independent prognostic factors for survival (Table). Probabilities to undergo potentially curative surgery were 86%, 77% and 60% for pts with no elevated tumor makers versus those with elevated CEA or elevated CA 19-9 versus those with both tumor markers elevated, respectively (p<0.001). No relationship was found between elevated tumor marker(s) and the presence of ctDNA neither pretreatment nor preoperatively. Conclusions: Pretreatment blood levels of CEA and CA 19-9 were identified as prognostic factors for overall survival in a large cohort of European GC pts with potentially curable disease. These factors may guide treatment choices at an early phase and should be included in future trials to determine their role in clinical decision making.[Table: see text]