bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the prognostic value of TP53 and PIK3CA mutations in metastatic colorectal cancer (mCRC): Applying Structured Query Language (SQL) algorithms to real-world data from a high-volume U.K. tertiary cancer center.
Authors: Fong Caroline , Mohamed Ali Abdulnabi , de Paula Neto Geraldo Alves , Teare Marion , Bourmpaki Elli , Peckitt Clare , Watkins David J. , Rao Sheela , Starling Naureen , Chau Ian , Cunningham David 
Published: January 2022

57 Background: Real world data is a valuable research resource but manual data collection is time consuming and labour intensive. As there is no consensus on the prognostic role of TP53 and PIK3CA mutations in mCRC, we assessed the feasibility of using SQL, a programming language, to derive data from routine electronic clinical notes to investigate the prognostic impact of TP53 and PIK3CA mutations in mCRC. Methods: A cohort of patients (pts) diagnosed with metastatic or recurrent colorectal cancer as per ICD-10 classification from January 2015 to December 2017 and managed at the Royal Marsden Hospital were identified using SQL algorithms developed in-house. Baseline demographics, histopathological and molecular characteristics and death dates were derived from the Electronic Patient Record and extracted in a structured format for statistical analysis. Mutational analysis of TP53 and PIK3CA were performed with standard of care KRAS, NRAS and BRAF testing using next generation sequencing. Overall survival (OS) according to TP53 or PIK3CA mutational status was estimated using the Kaplan-Meier method. Uni- and multivariate Cox regression included KRAS, NRAS, BRAF, sidedness and mismatch repair (MMR) status. Association between TP53 or PIK3CA and MMR status was tested by the Chi squared test. Results: A total of 367 mCRC pts were identified; 10 were excluded due to ineligibility or inadequate data availability. Based on a final dataset of 357 pts, 342 and 354 pts had TP53 and PIK3CA results available. The incidence of TP53 mutations was 75% (n = 257/342) and PIK3CA 16% (n = 55/354). Co-mutations with KRAS, NRAS and BRAF were seen (Table). The overall median follow-up was 42.3 and 42.7 months for TP53 and PIK3CA respectively. There was no difference in OS between TP53 mutant (MT) and wild type (WT) pts (22.0 vs. 22.8 months, p = 0.96) and between PIK3CA MT and WT pts (21.7 vs. 22.4 months, p = 0.49). Right sided and BRAF MT tumours were associated with poorer survival than left sided and BRAF WT tumours when all other factors were constant for TP53 (p<0.001 & p=0.033 respectively) and PIK3CA (both p<0.001) OS on multivariate analysis. MMR deficient tumours were significantly more frequent in TP53 WT compared to TP53 MT tumours (15% vs. 4%, p=0.001) while they were significantly more frequent in PIK3CA MT compared to PIK3CA WT tumours (20% vs. 5%, p < 0.001). Conclusions: Bespoke SQL algorithms enables large-scale data extraction to facilitate research. Based on this dataset, we have shown that TP53 and PIK3CA mutations have no prognostic impact in mCRC. [Table: see text]
Assessment of dietary quality in patients on surveillance for colorectal cancer (CRC) using a computerized food frequency questionnaire (FFQ).
Authors: Jain Rishi , Panick Jessie Rachel , Handorf Elizabeth A. , Vincek Karen , Stromberg Kara , Fein Leah , Ross Nicole , Senchak Jordan , Bauman Jessica R , Hall Michael J. , Denlinger Crystal S. , Fang Carolyn Y 
Published: January 2022

66 Background: Poor dietary patterns are clearly implicated in the pathogenesis of CRC and are increasingly associated with worsened CRC outcomes, including a higher risk of cancer recurrence and mortality. We evaluated the use of a novel computerized FFQ technology to assess dietary patterns in patients with CRC who were undergoing cancer surveillance. Methods: We recruited patients with stage I-III CRC who had completed curative intent therapy at least 1 year but no more than 5 years prior to enrollment. Dietary assessment was conducted using a computerized FFQ (VioScreen) either in clinic or at home. Dietary quality was defined by the Healthy Eating Index (HEI) 2015 score which was calculated automatically by the FFQ technology. Statistical significance was determined using Pearson correlation and analysis of variance (ANOVA). Results: Twenty patients (14 colon, 6 rectal; 12 male, 8 female; median age 66 [49-80]; median 3 years from diagnosis) were recruited between 10/2020-9/2021. Fourteen patients did FFQ remotely and 6 in-person. Nineteen patients were white/non-Hispanic. All received surgery, 20% radiation (all rectal) and 75% chemotherapy. Mean HEI 2015 total and sub-scores are shown in the table. There were significant differences in dietary quality by age <65 vs ≥65 (HEI 58.3 vs. 72.6, p=0.025), body-mass-index (BMI) normal/overweight vs. obese (HEI 72.4 vs. 58.6, p=0.033), and marital status of married vs non-married (HEI 61.7 vs. 76.7, p=0.032). There were no differences in dietary quality by level of education, tumor site (colon vs. rectal) or gender. There was a significant negative correlation with increased time since diagnosis and lower dietary quality (r= -0.67, p<0.001). Conclusions: Dietary patterns can be determined using a computerized FFQ in patients with CRC on surveillance both remotely and in-person. This population has a wide range of dietary patterns with particularly low scores in whole grain, fatty acid, sodium and saturated fat. Patients who are older, non-obese, non-married, and closer to completion of cancer therapy have higher dietary quality scores. Future studies of integrating a computerized FFQ into cancer care will determine whether personalized interventions targeting specific dietary patterns can improve diet quality.[Table: see text]
Cardiac toxicities of fluoropyrimidine chemotherapy: A literature review and evaluation of current practice at a large U.K. cancer center.
Authors: Williams Christopher , Saunderson Christopher , Liu Justin , Aung Noe Noe , Cartlidge Caroline , Dewdney Alice , Cubbon Richard 
Published: January 2022

72 Background: Fluoropyrimidine chemotherapy is a mainstay of the adjuvant and palliative management of colorectal cancer. Cardiac toxicities—including angina, myocardial infarction and arrhythmias—are uncommon complications thought to be mediated by coronary vasospasm. Although potentially life-threatening, they remain poorly described and consensus guidelines regarding patient selection are lacking. To assess current understanding of this toxicity, we performed a literature review of the topic. We then evaluated fluoropyrimidine use at a large UK cancer center to investigate current practice. Methods: MEDLINE, EMBASE and the Cochrane central register of controlled trials were searched to March 1 2021 using the search terms (fluorouracil OR capecitabine) AND—separately—cardiotoxicity, heart disease, and rechallenge*. Original research articles in English were included and their findings summarised. The case notes of all patients who underwent surgery for pathological stage III colon cancer between January 1 2017 and December 31 2019 at Leeds Cancer Centre were reviewed. The proportion of patients who experienced cardiac toxicity during adjuvant chemotherapy was assessed. The proportion of patients who were not offered adjuvant chemotherapy due to cardiac risk was identified. Results: The three search strategies identified 582, 55 and 21 citations respectively, of which 28, 7 and 7 full texts were retrieved for further evaluation following review of titles and abstracts. The reported incidence of fluoropyrimidine cardiotoxicity varied widely, as did its definition. Over half of toxicity cases described were ischaemic. Reported risk factors included those for coronary artery disease, although this was not a consistent finding. 125 patients underwent surgery for stage III colon cancer in the study period of whom 81 (65%) received adjuvant chemotherapy. 2 (2.5%) patients failed to complete adjuvant treatment due to cardiac toxicity (angina; cardiac arrest). Pre-existing cardiovascular disease was cited as a reason for not offering adjuvant chemotherapy in 13 of 44 cases (30%). Conclusions: Review of the literature revealed a poor evidence base to guide treatment decisions regarding fluoropyrimidine chemotherapy and cardiac risk. Rates of cardiac toxicity at our center were within expected limits. A number of patients were denied adjuvant chemotherapy due to perceived cardiac risk. A clearer understanding of the pathophysiology and management of fluoropyrimidine cardiotoxicity is urgently required to avoid unnecessarily denying patients effective anti-cancer therapy.
Utilization of next generation sequencing (NGS) in stage IV gastrointestinal (GI) cancer patients (pts) and efficacy of electronic reminder notification (ERN) in improving utilization of NGS in the private practice community-based setting.
Authors: Foster Kapil , Cedeno Carina , Marks Stephanie , Yeung Percy , Ronnen Ellen A. 
Published: January 2022

73 Background: NGS testing allows for identification of genetic mutations/alterations that can be important in determining treatment options for advanced cancer pts. The National Comprehensive Cancer Network (NCCN) includes NGS testing as part of standard of care for many tumor types including stage IV pancreatic cancer, colon cancer, and rectal cancer and all other GI solid tumor types. Previous reports have described the utilization of NGS in clinical practice at academic centers. To our knowledge this is the first report in the private practice setting. Methods: For the historical portion, we established baseline data to quantify NGS testing frequency in stage IV GI tumor pts in our community based oncology practice by performing a retrospective chart review. In the prospective portion, the intervention of an ERN was used to alert treating physicians if NGS had not been done. Primary endpoint is the percent (%) of pts with NGS sent compared to historical control. Secondary endpoint is the % of pts with targeted therapy options made available to them. Results: In a private practice multi-office setting, 200 charts of pts with stage IV GI cancer using Flatiron’s OncoEMR software were reviewed for the retrospective cohort between July 1 to December 31, 2020. Of the 200, 44.5% (89 pts) had colon cancer, 17.5% (35 pts) had pancreatic cancer, 15% (30 pts) had rectal cancer, and 23% (46 pts) had other types of GI cancer. Of these, 87 (43.5%) pts had NGS testing; of which 41 of 89 (46.0%) are colon pts, 13 of 35 (37.1%) are pancreatic pts and 16 of 30 (53.3%) are rectal pts. For the prospective portion, between July 1 and August 15, 2021 each physician’s schedule was evaluated and an ERN was sent shortly before each Stage IV GI pt was to be seen. A total of 114 pts were reviewed, and 92 (79%) had NGS sent. Of these, 47 pts of 54 (87%) are colon pts, 12 of 15 (80%) are pancreatic pts, 16 of 21(76%) are rectal pts, and 17 of 24 (70%) are pts with other GI cancer. 2% of pts with NGS testing had a potentially actionable mutation identified. Conclusions: NGS testing is standard of care for pts with stage IV GI cancer that wish to pursue therapy. ERN was minimally helpful in increasing NGS testing. This may be in part due to the effect of the practice's emphasis on NGS testing, which increased its baseline prospective testing rate. Increased use of a team based approach in the office would be a key element to increasing compliance with the current workflow as well as use of pathways which embed the NGS testing into the treatment plan. A more robust EMR would also be vital in increasing NGS testing rates by the use of automatic reminders or order sets. Better support of the physician and use of multiple touch points is necessary until full automation is utilized for NGS testing.
Incidence, severity, and onset of oral mucositis in 5-FU based chemotherapy for gastrointestinal cancer.
Authors: Rosemann Eva , Schaefer H , Esmaty A , Stintzing Sebastian , Karthaus Meinolf 
Published: January 2022

77 Background: 5-fluorouracil has been used in treatment of gastrointestinal cancers for more than 40 years. Numerous toxicities of 5-FU are known. Little is known about the occurrence, natural course and causes of oral mucositis (OM) of 5-FU in GI tumors. There is little data on the additional toxicity of VEGF and EGFR antibodies together with 5-FU. We followed the occurrence, severity and localization of OM of 5-FU in consecutive patients as part of their cancer treatment. The primary aim of the study was to determine the severity, course and risk factors of OM up to the first six cycles of ctx. OM was evaluated by repeated inspections of the oral cavity and patient questionnaires. Methods: Pts who received 5-FU for the first time or who had not received ctx for at least 12 months. 64 consecutive pts were included in the observational study from March 2018 to March 2019. Out of 64 pts a total of 41 (28 m/13f) had complete documentations (inspections of the oral cavity and questionnaires) and were available for the evaluation. Results: Mean age 65 ys (range 42-83), 60% were treated for CRC, 22% esophageal/gastric cancer, and 18% other GI-cancers. 13 were non-smokers, 25 former smokers; 7 pts had daily alcohol consumption while 7 pts never consumed alcohol. 10/41 pts wore a dental prosthesis. The mean BMI was 26.5 (range 18.8-41.5). Initial very good/ good oral hygiene was given in 3/20 patients. 80% of the pts developed xerostomia after the first cycle, almost every patient needed support for symptoms due to oral problems during ctx. Of 41 pts, an OM could be documented in 38 pts. A total of 93% of the patients developed a mild course of the mucositis with grade 1-2. OM developed between the 2nd and 3rd cyle in the majority of pts. At the third cyle, only 8 pts had OM of grade 0, while 23 pts had grade 1 and 9 pts were grade 2. It was of note here that of these 9 pts with grade 2, 6 had grade 0 in the 2nd cycle. During cycle 5 and 6 only seven pts had a CTC score of 0, but no pat developed a CTC 3 or 4 OM. We could not document a connection between the occurrence of oral mucositis and the oral hygiene measures used, as no severe course of OM CTC Grad 3 or 4 could be detected. We could not find any relation to the type of 5-FU therapy (doublet, triplet +/- monoclonal antibodies). Conclusions: The incidence of oral mucositis with CTC score of 1 and 2 was 93%, but serious grade 3 and 4 mucositis rates were not observed. Xerostomia was observed in 80% after the first course of treatment. Symptomatic mucositis occurs early within 4 weeks after starting chemotherapy. Local measures appear suitable for symptom control of OM.
Trajectories of body weight change and survival among mCRC patients treated with systemic therapy: Pooled analysis from the ARCAD database.
Authors: Franko Jan , Yin Jun , Adams Richard , Zalcberg John Raymond , Fiskum Jack , VanCutsem Eric , Goldberg Richard M. , Hurwitz Herbert I. , Bokemeyer Carsten , Kabbinavar Fairooz F. , Curtis Alexandra , Chibaudel Benoist , Yoshino Takayuki , De Gramont Aimery , Shi Qian 
Published: January 2022

80 Background: Higher baseline body mass index is associated with improved survival in metastatic CRC (mCRC). Whether weight gain or loss after mCRC diagnosis is associated with survival remains largely unknown. Methods: We analyzed individual patient data from 3504 patients with previously untreated mCRC enrolled in five phase III randomized trials (AVF2017g, AVF2192g, CRYSTAL, N9741, OPUS) conducted between 2000 and 2006. Weight measurements were prospectively collected at 3 months after diagnosis and then up to 5 years. Patients were categorized into three groups based on the percent weight change at 3 months: stable weight or gain, weight loss up to 5% of baseline weight, and ≥5% weight loss of baseline weight. Cox models were used to assess the prognostic associations of weight change at 3 months with overall survival (OS) and progression-free survival (PFS), adjusting for baseline BMI, age, sex, performance score, chemotherapy backbone (oxaliplatin vs. irinotecan), and biologics type (cetuximab vs. bevacizumab). Sub-analyses included Cox models adjusted for additional clinical-pathological factors (primary tumor sidedness [right colon vs. left colon-rectum], and BRAF status; N=1,511). Results: Median percent weight change at 3 months was -0.5% (IQR -4.0 to+1.6%). OS was better in patients with weight stability or gain than in those with weight loss (up to 5% or ≥5%; (Table). Results were consistent for PFS for patients with ≥5% weight loss of baseline weight, as well as for sub-analyses. Conclusions: Patients losing weight during the first 3 months of systemic therapy for metastatic colorectal cancer have significantly shorter overall survival than those with stable or increasing weight. Degree of weight loss is proportional to the observed increased risk of death and remains evident among underweight, normal weight and obese individuals. Further studies examining possible usefulness of on-treatment early weight loss as a novel intermediary end-point are needed.[Table: see text]
Exploratory analysis of baseline tumor burden in the TRUSTY study: A randomized phase 2/3 study of trifluridine/tipiracil plus bevacizumab versus irinotecan and fluoropyrimidine plus bevacizumab as second-line treatment in patients with metastatic colorectal cancer.
Authors: Masuishi Toshiki , Kuboki Yasutoshi , Terazawa Tetsuji , Nakamura Masato , Watanabe Jun , Ojima Hitoshi , Makiyama Akitaka , Kotaka Masahito , Hara Hiroki , Ohta Takashi , Oki Eiji , Sunakawa Yu , Ishihara Soichiro , Taniguchi Hiroya , Nakajima Takako Eguchi , Morita Satoshi , Shirao Kuniaki , Yoshino Takayuki ,   TRUSTY study group
Published: January 2022

87 Background: In primary analysis from the TRUSTY study, trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) failed to show non-inferiority to irinotecan and fluoropyrimidine plus BEV in overall survival (OS) as second-line treatment in patients (pts) with metastatic colorectal cancer (mCRC) (median OS, 14.8 vs. 18.1 months: HR, 1.38: 95% CI; 0.99-1.93: p = 0.59 for non-inferiority; Kuboki Y, et al. ASCO 2021). Here we report a post hoc efficacy analysis by baseline tumor burden. Methods: Pts with histologically confirmed mCRC who failed first-line chemotherapy with fluoropyrimidine and oxaliplatin plus either BEV or an anti-EGFR antibody were eligible. Pts were randomized to receive either FTD/TPI plus BEV (FTD/TPI plus BEV group, FTD/TPI 35 mg/m2 twice daily on days 1–5 and 8–12 every 28-day cycle, and BEV 5 mg/kg on days 1 and 15) or either FOLFIRI or S-1 and irinotecan combined with BEV (control group). Efficacy measured by OS, progression-free survival (PFS), and disease control rate (DCR) were compared between pts grouped by baseline sum of diameter of target lesions (STL). Survival curves were drawn by direct survival estimation adjusted for stratification factors. Results: In the ITT population (N = 396), 60 mm was selected as the optimal cutoff for STL because it produced the most significant difference in OS; 151 pts had high tumor burden with STL ≥ 60 mm (FTD/TPI plus BEV, n = 76: control, n = 75), 216 had low tumor burden with STL < 60 mm (n = 107, n = 109), and 29 were excluded due to no measurable lesions. Baseline characteristics in pts with both high and low tumor burden were balanced between treatment groups. In pts with STL ≥ 60 mm, FTD/TPI plus BEV was less effective than the control: adjusted median OS was 10.9 versus 16.2 months (HR: 2.32; 95% CI: 1.42-3.79), median PFS was 3.5 versus 6.1 months (HR: 2.32; 95% CI: 1.52-3.53): and DCR was 53.9% versus 72.0% (p = 0.03). In pts with STL < 60 mm, FTD/TPI plus BEV was comparably effective to the control: median OS was 21.4 versus 20.7 months (HR: 0.92; 95% CI: 0.55-1.55), median PFS was 5.6 versus 6.0 months (HR: 1.23; 95% CI: 0.87-1.72), and DCR was 66.4% versus 71.6% (p = 0.46). Conclusions: FTD/TPI + BEV might be a second-line treatment option for mCRC pts with low tumor burden (STL < 60 mm). Clinical trial information: jRCTs031180122.
Survival in total preoperative verus perioperative chemotherapy for patients with metastatic high-grade appendiceal adenocarcinoma undergoing CRS/HIPEC.
Authors: Morgan Ryan B. , Yan Allie , Dhiman Ankit , Sood Divya , Ong Cecilia T. , Wu Xiaoyang , Shergill Ardaman , Polite Blase N. , Turaga Kiran , Eng Oliver 
Published: January 2022

90 Background: Due to the relative infrequency of high grade appendiceal adenocarcinoma with peritoneal metastases, there is limited data to guide treatment strategies. Current practices for this disease are largely extrapolated from colon cancer patients with peritoneal metastases, who typically undergo six months of systemic chemotherapy in conjunction with cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). The optimal timing of chemotherapy in relation to CRS/HIPEC remains unknown. In this study, we compare the efficacy of peri-operative chemotherapy to pre-operative chemotherapy alone. Methods: This is a retrospective review of patients who underwent CRS/HIPEC for high grade appendiceal cancers from a tertiary referral center from 2014-2020. Outcomes were compared between patients who underwent planned 6 months of chemotherapy followed by CRS/HIPEC (pre-operative group) versus planned 3 months of chemotherapy both pre- and post-operatively (peri-operative group). Results: 85 patients were treated for metastatic high-grade appendiceal cancers during the study period, of whom24 were eligible for inclusion. Of those included, 16 were in the peri-operative group and 8 in the pre-operative group. Most patients were white (75%), non-Hispanic (96%) and female (54%). Patients in the pre-operative group tended to be older (65 vs. 56 years, p = 0.02). For patients with specified histologic grading, poorly differentiated tumors were common (50%). Signet ring cell histology (42%) and mucinous features (67%) were frequent as well. Median overall survival was similar between the pre-operative and peri-operative groups (32.3 vs. 31.6 months, p = 0.97), although patients undergoing peri-operative treatment received fewer total cycles of chemotherapy on average (14.1 vs. 9.5 cycles, p < 0.01). Half of the patients in the peri-operative group (8/16) did not complete their chemotherapy regimen, with 75% discontinuing therapy due to chemotherapy-related toxicities. Within the peri-operative group, a non-significant decrease in median survival was observed for those who did not complete chemotherapy (27.8 vs > 53.6 months, p = 0.22). Conclusions: Peri-operative and total pre-operative chemotherapy strategies are associated with similar survival in patients with high grade appendiceal cancers undergoing CRS/HIPEC. Peri-operative administration may be limited by chemotherapy-related toxicities.