bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of local therapy on survival among patients with metastatic anal squamous cell carcinoma.
Authors: Alese Olatunji B. , Zhang Yining , Zakka Katerina Mary , Jiang Renjian , Atallah Rami , Diab Maria , Shaib Walid Labib , Akce Mehmet , Wu Christina , El-Rayes Bassel F.
Published: January 2022

4

Background: About 10-20% of patients with anal squamous cell carcinoma (SCCa) present with metastatic disease, and are usually treated with systemic chemotherapy. The role of local therapy to control the primary tumor is controversial in this setting. We evaluated survival impact of local therapy in metastatic anal SCCa. Methods: Data were obtained from all US hospitals that contributed to the National Cancer Database (NCDB) between 2004 and 2015. We excluded patients who did not receive palliative systemic chemotherapy. Univariate (UVA) and multivariable analyses (MVA) were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the association between tumor/patient characteristics and overall survival (OS). Results: 1,160 patients were identified over 12 years. Median age was 57 years. Majority were female (64.9%), non-Hispanic Whites (79.1%) and had Charlson-Deyo Score of 0 (83.6%). Most common metastatic sites were liver (25.9%), lung (11.6%) and bone (8.5%). More than 79% of the patients received radiation to the primary site, and 10.4% underwent surgical resection for local control. Use of local therapy correlated closely with a significant improvement in OS on MVA (HR 0.66; 0.55-0.79; p < 0.001), with a 12-month and 5-year OS rates of 72.8% and 25.7% respectively, compared with 61.1% and 14.6% for patients treated with chemotherapy only. Poor prognostic factors included male gender (HR 1.44; 1.24-1.67; p < 0.001), age > 70 years (HR 1.28; 1.02-1.62; p = 0.034), lack of health insurance (HR 1.32; 1.02-1.71; p = 0.034), and cloacogenic zone location (HR 4.02; 1.43-11.30; p = 0.008). There was no benefit from abdominoperineal resection (mOS = 19.7mos; HR 1.05; 0.48-2.29; p = 0.909), but both local resection of the primary (mOS = 24.8mos, HR 0.48; 0.29-0.80; p = 0.005) and palliative radiation (mOS = 22.6 mos; HR 0.66; 0.55-0.79; p < 0.001) were associated with improved OS. Conclusions: This is the largest reported study on management of de novo stage IV SCCa. The data suggest that local control of the primary tumor through resection or radiation improved OS in patients with anal SCCa. Patients unlikely to benefit from local therapy include age over 70 years, male, lack of health insurance and cloacogenic carcinoma.
One-year duration of nivolumab plus ipilimumab in patients (pts) with microsatellite instability-high/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer (mCRC): Long-term follow-up of the GERCOR NIPICOL phase II study.
Authors: Cohen Romain , Meurisse Aurelia , Pudlarz Thomas , Bennouna Jaafar , Tournigand Christophe , De La Fouchardiere Christelle , Tougeron David , Borg Christophe , Mazard Thibault , Chibaudel Benoist , Garcia-Larnicol Marie-Line , Svrcek Magali , Menu Yves , Vernerey Dewi , Andre Thierry
Published: January 2022

13

Background: Optimal treatment duration with immune checkpoint inhibitors (ICI) for MSI/dMMR mCRC pts remains to be determined. Different durations are used, usually a fixed duration of 2 years or treatment until progression or toxicity. The GERCOR NIPICOL phase II study evaluated 1 year of therapy with nivolumab plus ipilimumab for MSI/dMMR mCRC pts. Here, we present the efficacy data with 16 months of additional follow-up since the primary analysis. Methods: MSI/dMMR mCRC pts previously treated with fluoropyrimidine, oxaliplatin, and irinotecan ± targeted therapies received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg Q3W for 4 cycles, then nivolumab 3 mg/kg Q2W until progression or a maximum of 20 cycles. Second course of nivolumab was permitted for pts who completed the predefined year of treatment and had later progressive disease (PD). Objectives were to evaluate response rates, progression-free survival (PFS) per iRECIST, and overall survival (OS). A landmark analysis was performed for PFS in pts who remained alive and progression-free at 1 year (theoretical end of treatment). Results: Of 57 pts included between Dec 2017 and Nov 2018, 36 (63%) completed the predefined 1-year duration of treatment. Reasons of premature treatment discontinuation were PD or death (n = 13), adverse event (n = 7), and the pt wish (n = 1). Overall median follow-up was 34.5 months. One, 2, and 3-year PFS rates were respectively 75.4% (95% CI 62.0-84.6), 70.0% (95% CI 56.2-80.1), and 70.0% (95% CI 56.2-80.1). One, 2, and 3-year OS rates were 84.1 (95% CI 71.7-91.4), 78.4% (95% CI 65.1-87.1), and 73.1% (95% CI 58.4-83.4), respectively. 42/57 pts were progression-free and alive at 1 year. Among them, median follow-up was 35.0 months and the 24-month PFS rate was 92.9% (95% CI 79.5-97.6%). PD was observed in three pts whose 12-month status was stable disease (SD). These three pts received a second course of nivolumab: two achieved PR and one had PD. Conclusions: Nivolumab plus ipilimumab with a fixed duration of 1 year continued to show durable activity in pts with chemoresistant MSI/dMMR mCRC after 3 years of follow-up. Reexposure to nivolumab seems to provide additional antitumor activity for pts experiencing late resistance after discontinuation of immunotherapy. Clinical trial information: NCT033501260.
The association between preoperative CEA, the systemic inflammatory response and survival in colon cancer.
Authors: Golder Allan Matthew , Park James Hugh , Mansouri David , Horgan Paul G. , McMillan Donald C. , Roxburgh Campbell SD
Published: January 2022

27

Background: Prior to curative surgery for colon cancer, carcinoembryonic antigen (CEA) has been reported to be a poor prognostic factor recommended for routine measurement, however the majority of studies evaluating this have not adjusted for the preoperative systemic inflammatory response (SIR) –widely shown to be associated with worse outcomes. The present study aims to analyse the association between preoperative CEA and long-term outcomes when adjusted for other factors including Systemic Inflammatory Grade (SIG). Methods: The effect on overall/cancer specific survival (OS/CSS) of preoperative CEA (<5/5+) was examined in a regional cohort of patients undergoing surgery for colon cancer after adjustment for other clinicopathological factors including the SIR as measured by Systemic Inflammatory Grade (SIG). Results: 624 patients were identified undergoing curative surgery for colon cancer with a preoperative CEA available. For 3-year OS stratified by TNM Stage, CEA offered further prognostic value in patients with TNM Stage I (98% vs 75%, p=0.002), but not Stage II (p=0.444) or Stage III (p=0.351) disease. For 3-year OS stratified by SIG, CEA did not add further significant prognostic value for any SIG (all p>0.05). On multivariate analysis, age (HR 1.65, p=0.020), sex (HR 0.53, p=0.001), mode of presentation (HR 1.93, p=0.008), TNM Stage (HR 1.83, p<0.001) and SIG (HR 1.30, p<0.001) remained significant for OS, but not CEA (p=0.620). Conclusions: The present results show that there is limited prognostic value of preoperative CEA. The SIR as measured by SIG should be routinely measured prior to curative colonic surgery. A mandatory reporting dataset is required in colorectal cancer and should include SIG. [Table: see text]
A twice-daily or a three-times-daily tegafur-uracil and leucovorin calcium regimen as adjuvant therapy in patients with resected colorectal cancer: A phase III study.
Authors: Iwamoto Kazuya , Hata Taishi , Miyake Masakazu , Ohue Masayuki , Shingai Tatsushi , Tei Mitsuyoshi , Takemoto Hiroyoshi , Ikenaga Masakazu , Fujie Yujiro , Miyoshi Norikatsu , Takahashi Hidekazu , Uemura Mamoru , Matsuda Chu , Mizushima Tsunekazu , Murata Kohei , Ohno Yuko , Doki Yuichiro , Eguchi Hidetoshi
Published: January 2022

38

Background: Tegafur-uracil (UFT)/leucovorin calcium (LV) is an adjuvant chemotherapy treatment for colorectal cancer. We conducted a multicenter randomized trial to assess the noninferiority of a twice-daily compared with a three-times-daily UFT/LV regimen for stage II/III colorectal cancer in an adjuvant setting. Methods: Patients were randomly assigned to group A (three doses of UFT [300 mg/m2 per day]/LV [75 mg per day]) or B (two doses of UFT [300 mg/m2 per day]/LV [50 mg per day]). The schedule of 28-day oral administration followed by a 7-day rest period was repeated. Five 35-day cycles were repeated. The primary endpoint was 3-year disease-free survival. The secondary endpoints included 5-year overall survival and toxicity. Results: In total, 386 patients were enrolled between July 28, 2011, and September 27, 2013. The 3-year disease-free survival rates of group A (n = 194) and B (n = 192) were 79.4% and 81.4% (95% confidence interval, 72.6-84.4-74.5-85.9), respectively. The 5-year overall survival rates of group A and B were 89.7% and 91.0% (95% confidence interval, 83.3-92.8-84.8-93.8), respectively. The most common grade 3/4 adverse events in group A and B were diarrhea (3.9% vs. 7.3%), neutropenia (2.9% vs. 1.6%), increase in aspartate aminotransferase (4.0% vs. 3.9%), increase in alanine aminotransferase (6.2% vs. 6.8%), nausea (1.7% vs. 3.4%), and fatigue (1.1% vs. 2.3%). Conclusions: Group B outcomes were not inferior to group A outcomes, and adverse events did not increase. Clinical trial information: UMIN000005594.
Real-world data analysis of antiangiogenic targeted treatments in second-line following anti-EGFR antibodies and FOLFOX in first-line for patients with metastatic colorectal cancer.
Authors: Kagawa Yoshinori , Satake Hironaga , Shinozaki Eiji , Tanizawa Yoshinori , Cai Zhihong , Jin Long , Makiyama Akitaka
Published: January 2022

43

Background: Three antiangiogenic (AA) drugs, bevacizumab (BEV), ramucirumab (RAM) and aflibercept (AFL) are recommended as the second-line (2L) treatment for metastatic colorectal cancer (mCRC) in the CRC treatment guidelines of multiple countries and regions including the US, EU and Japan. However, little evidence of 2L RAM and AFL after anti-EGFR antibodies (EGFRab) in first- line (1L) has been reported. This study assessed treatment sequence for mCRC patients who received 2L irinotecan-based chemotherapy with AA drug after FOLFOX + EGFRab in 1L, treatment duration from the start of 2L to the end of last treatment line (treatment duration from 2L) and factors associated with the treatment duration from 2L. Methods: This is a real-world observational study using a hospital-based claims database of 393 hospitals in Japan. The mCRC patients who started 1L treatment with FOLFOX + EGFRab between May 2016 and Sep 2019 (identification period) and further treated with irinotecan-based chemotherapy + AA drug were enrolled. The key outcomes were the treatment sequence, treatment duration from 2L by AA drug, and factors associated with the treatment duration from 2L. Survival curves were estimated using the Kaplan–Meier method. Associated factors were investigated using Cox regression analysis. Results: Among 2,453 patients with 1L FOLFOX + EGFRab during the identification period, 506 patients who received the intended 2L therapies were enrolled in this study (mean age 63.5 years, male 66.6%). Number (%) of patients who used BEV, RAM and AFL in 2L was 345 (68.2), 120 (23.7) and 41 (8.1), respectively. Patient characteristics involving tumor location, metastatic site and prior anti-tumor therapy before starting 2L were similar among BEV, RAM and AFL. The treatment duration from 2L (median month and its 95%CI) was 11.1 (10.2-12.5) in the overall population and was similar among the patients who received BEV (10.8 [9.9-13.1]), RAM (11.2 [10.0-14.2]) and AFL (12.8 [6.9-NA]) in 2L. The treatment duration from 2L (median month and its 95%CI) for the patients who took or didn’t take proteinuria tests during 2L was 12.5 (11.1-15.2) and 8.5 (6.5-11.2), respectively. Factors positively associated with treatment duration from 2L were left-sided CRC (HR [95%CI] = 0.71 [0.53-0.96]) and ≥6 months of 1L duration (0.72 [0.56-0.93]); having renal disease (1.92 [1.28-2.88]) or received NSAIDs (1.63 [1.25-2.13]) within 60 days before starting 2L were associated negatively. Conclusions: The real-world data revealed that treatment duration were similar among BEV, RAM and AFL in 2L after EGFRab. Tumor location and 1L duration were associated with the treatment duration from 2L positively, while negative association was observed with renal disease and received NSAIDs. Treatment management was important for treatment continuation.
General and mental health status following colorectal cancer treatment and its association with mortality among a racially diverse population-based cohort.
Authors: Yoon Paul , Navarro Stephanie , Ochoa Carol , Garrett Elleyse , Arizpe Angel , Farias Albert
Published: January 2022

45

Background: Patient-reported outcomes (PROs) are recognized as strong predictors of cancer prognosis, outcomes, and care. However, racial/ethnic minorities with colorectal cancer (CRC) tend to report poorer general health status (GHS) and mental health status (MHS) compared to non-Hispanic whites. The objectives of this study were to determine: (1) if there are racial/ethnic differences in GHS and MHS within 36 months of CRC diagnosis and (2) if poorer GHS and MHS in recently diagnosed CRC patients are associated with mortality. Methods: We used the population-based Surveillance, Epidemiology, and End Results (SEER)-Consumer Assessment of Healthcare Providers and Systems (CAHPS) dataset to analyze Medicare beneficiaries aged ≥65 years who were diagnosed with CRC between 1998 and 2011, received surgical resection for their tumor, and completed a CAHPS survey within 6-36 months post-diagnosis. CAHPS surveys captured patient-reported GHS and MHS on a five-point Likert scale ranging from “poor” to “excellent.” We used stepwise multivariable logistic regression to examine associations between patient race/ethnicity and fair or poor health status, adjusting for clinical and sociodemographic factors. Additionally, a multivariable Cox proportional hazards regression was used to determine the risks of mortality associated with fair or poor GHS and MHS. Results: Of 1,867 patients with CRC, 79.5% were non-Hispanic white (NHW), 6.4% were non-Hispanic black (NHB), 7.5% were Hispanic, and 6.6% were non-Hispanic Asian (NHA). In Model 1 of our stepwise logistic regression, NHB patients had higher unadjusted odds for fair or poor GHS (OR 1.56, 95% CI 1.06-2.28) compared to NHW patients while Hispanic patients had higher unadjusted odds for both fair or poor GHS (1.48, 1.04-2.11) and MHS (1.92, 1.23-3.01). In Model 2, this relationship persisted after adjusting for clinical factors, with NHB patients being more likely to report fair or poor GHS (1.62, 1.10-2.40) and Hispanic patients being more likely to report fair or poor GHS (1.49, 1.04-2.13) and MHS (1.92, 1.22-3.00). In Model 3, after adjusting for both clinical and sociodemographic factors, the association between race/ethnicity and fair or poor GHS ( p = 0.53) and MHS ( p = 0.23) no longer remained. Reporting fair or poor GHS and MHS was associated with a greater risk of mortality among all CRC patients (HR 1.52, 95% CI 1.31-1.76 and 1.62, 1.34-1.99, respectively). Conclusions: Our study illustrates that racial/ethnic differences in PROs are largely driven by sociodemographic factors as opposed to clinical factors. As fair or poor GHS and MHS shortly after diagnosis reflect a higher risk of mortality in CRC patients, efforts to understand unmet biopsychosocial concerns may help further elucidate racial differences in CRC survival that may be otherwise overlooked in standard clinical practice.
Metastasectomy in colorectal cancer patients with concurrent lung and liver metastasis: Trends in utilization and impact on survival.
Authors: Khatib Jude , Goksu Suleyman Yasin , Reddy Sarah , Chowattukunnel Nivan , Sanford Nina Niu , Sanjeevaiah Aravind , Beg Muhammad Shaalan , Kazmi Syed Mohammad Ali
Published: January 2022

53

Background: Colorectal cancer (CRC) frequently presents with concurrent metastasis to the lung and liver. Metastasectomy may offer extended disease control in a select group of patients but its utilization is unknown. We aimed to investigate the trends in utilization of metastasectomy in CRC patients with concurrent lung and liver metastasis and explore its impact on survival. Methods: We queried the National Cancer Database and identified stage 4 CRC patients with concurrent lung and liver metastasis between 2010 – 2016 and categorized them into those that underwent metastasectomy vs. those that did not. Categorical variables were compared using the chi-square test, and statistically significant factors were included in multivariable logistic regression analysis. In addition, 1:2 propensity score matching was performed, and a multivariable Cox regression model was used to define survival predictors among matched cohorts. The Kaplan-Meier method was used to estimate the median survival. Results: Out of total 77,719 stage 4 CRC patients, 10,106 (13.0%) patients had concurrent lung and liver metastasis. Six percent (n = 630) of these patients underwent metastasectomy of both sites. Patients that underwent metastasectomy were more likely to be younger (< 50 years; p = 0.009), female ( p < 0.001), and White ( p = 0.01). These patients were also more likely to have right-sided CRC ( p = 0.001) and had resection of the primary site (p < 0.001). Additionally, they were more likely to have private health insurance ( p < 0.001) and receive treatment at an academic center ( p = 0.03). On adjusted multivariable analysis, female gender, care at an academic center, primary tumor resection and receiving chemotherapy were associated with the metastasectomy group. We did not find a statistically significant difference between comorbidity score, KRAS status and microsatellite status between the 2 groups. In the matched analysis, overall survival (OS) was significantly improved for patients who underwent metastasectomy (23.2 months) vs. those who did not (11.6 months, p < 0.001). On multivariable analysis, this difference remained, and metastasectomy was an independent predictor of better OS (HR 0.74 [0.65-0.85], p < 0.001). Conclusions: The utilization of metastasectomy in concurrent lung and liver metastasis is low. It is more frequently used in younger, female and White patients, as well as in patients treated at an academic center. Metastasectomy is independently associated with improved overall survival in patients eligible for such an approach.
Real-world experience of pembrolizumab in microsatellite instability-high CRC: A Scottish multicenter analysis.
Authors: Ghaus Aisha , Pheely Ashley , Murdock Victoria , Shareef Hala , Samuel Leslie M. , Clive Sally , Tough Fay , Rodgers Lisa Jane
Published: January 2022

54

Background: KEYNOTE-177 established pembrolizumab as a new standard of care in untreated microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). Patients within clinical trials are not always representative of the general population. This underpins the importance of real-world data to offer insights into the outcomes achieved with anti-cancer therapies in routine practice. We report the initial efficacy and safety outcomes of patients treated with pembrolizumab for MSI-H CRC in Scotland. Methods: A retrospective analysis of all patients with advanced MSI-H CRC treated with pembrolizumab in the Scottish National Health Service was undertaken. Patient demographic and clinico-pathological data were collated via a standardised collection tool. Statistical analysis was performed using SPSS version 28. Results: 39 patients were identified (37 metastatic, 2 with locally advanced unresectable disease). All but 2 patients were treated in the first line setting. The median age was 68 years (range 48-82). 23 (59%) were age ≥65 years. 12 (30.7%) of patients were of Eastern Cooperative Oncology Group performance status (PS) 0, 23 (58.9%) of PS 1 and 4 (10.2%) of PS 2. 21 (53.8%) had BRAF V600E mutations. The median duration of pembrolizumab therapy was 24 weeks (range 2-104). After a median follow-up of 36 weeks (range 3-193), 5 deaths had occurred. The median progression free survival had not been reached. The overall response rate was 51% (20/39 patients), with 1 complete response observed. Radiological disease progression occurred in 7 patients (18%), 6 (86%) of which were BRAF V600E mutant. Treatment failure (radiologically confirmed disease progression or clinical suspicion of progression without radiological confirmation) occurred in 15 patients (38%). 3 out of 4 patients with PS 2 achieved a partial response. There were no grade ≥3 immune related adverse events. There was 1 treatment suspension due to grade 2 immune toxicity but no permanent discontinuations. Conclusions: Our real-world Scottish population was of poorer performance status than those recruited to KEYNOTE-177 (31% PS 0 vs. 49% in KEYNOTE-177). They were also older (59% age ≥65 years vs. 48% in the trial). Patients of PS 2 were excluded from the study, however 3 of our 4 PS 2 patients demonstrated a partial response to treatment, suggesting that PS 2 should not be an absolute contraindication to treatment. Our observed overall response rate was greater than that observed in KEYNOTE-177 (43.8%). Pembrolizumab was safe and well tolerated in this setting. These preliminary findings support the results of KEYNOTE-177. Long term survival data in our population is awaited. Further follow-up and patient numbers will allow for determination of possible clinico-pathological predictors (BRAF and KRAS status, Glasgow Prognostic Score, metastatic burden) of response to immunotherapy in this population.
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

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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

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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

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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.
Changes in prescribing patterns in stage III colon cancer (CC) since the IDEA collaboration.
Authors: Walden Daniel , Ou Fang-Shu , Larson Joseph J. , Wu Christina , Kang Sandra , Liu Alex John , Griswold Cassia R , Ueberroth Benjamin Edward , Patel Bhamini , Draper Amber , Rone Kelley , Raman Puneet , Bekaii-Saab Tanios S. , Ahn Daniel H.
Published: January 2022

92

Background: Since the publication of the MOSAIC trial, stage III CC has been treated with a six-month (mo) regimen of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin). Recently, the IDEA collaboration challenged this practice by demonstrating that the 3-year rate of disease-free survival (DFS) was non-inferior to 6mo of treatment (Rx) when given for low risk CC (83.1 vs. 83.3%) and resulted in significantly lower rates of grade 2 and higher neuropathy. In high risk (T4, N2) patients (pts) the DFS of 3mo of CAPOX was equivocal to 6mo (64.1 vs. 64.0%), while 3mo of FOLFOX was inferior to 6mo (61.5 vs. 64.7%). We hypothesized that trends in prescribing would favor shorter courses of Rx with a preference towards CAPOX given its efficacy across both high and low risk CC. Methods: We performed a retrospective analysis of stage III CC pts from 4 institutions. We evaluated prescribing patterns of 3mo or 6mo of Rx and CAPOX vs. FOLFOX over a period of 5 years from Jan 2016 to Jan 2021, a time period that traverses before and after the release of IDEA. Logistic and multinomial logistic regression models, with a linear time trend, were used to estimate the percentage of pts receiving CAPOX vs. FOLFOX and the combination of Rx and duration, respectively, while adjusting for baseline characteristics. The prescribing patterns in important subgroups were examined by incorporating the interaction term in the models. Results: A total of 366 pts met inclusion criteria. From 2016-2021, there was a significant increase per quarter in patients treated with CAPOX when compared to FOLFOX (OR 1.16 95% CI 1.11 – 1.21, p <.001). Prior to IDEA, 78.3% of pts received 6mo FOLFOX and 7.4% received 3mo CAPOX. Two years after IDEA, only 17.3% of pts were on 6mo FOLFOX compared to 67.5% of pts on 3mo CAPOX (Table). At present, high risk pts are more likely to receive 6mo FOLFOX (47.8%) than 3mo of FOLFOX (3.9%), 3mo CAPOX (25.8%), or 6mo CAPOX (22.4%). Low risk pts are more likely to receive 3mo of CAPOX (67.9%) than other Rx. Conclusions: Our findings suggest that since IDEA, physician practice has significantly changed in favor of CAPOX and shorter courses of Rx. The use of CAPOX has significantly increased overall, presumably due to its efficacy across all risk groups and relatively reduced toxicity.[Table: see text]