bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcomes of neoadjuvant treatment strategies in localized mismatch repair-deficient rectal cancer.
Authors: Soderberg Leah C , Wookey Vanessa , Mitchell Jessica L. , Jochum Jacob A. , Tran Nguyen H. , Halfdanarson Thorvardur Ragnar , Hubbard Joleen M. , Graham Rondell P. , Mathis Kellie Leanne , Mahipal Amit , Jin Zhaohui 
Published: January 2022

192 Background: Rectal cancer treatment paradigm has been evolving over time. Historically, for locally advanced rectal cancer, standard therapy (ST) consisted of neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy. Recently, total neoadjuvant treatment (TNT) approach that delivers both neoadjuvant chemotherapy (CAPOX or FOLFOX) and chemoradiation (or radiation only) prior to surgery is increasingly being utilized. The prognostic and predictive values of mismatch repair deficient (dMMR) in rectal cancer is not well characterized. Most dMMR patients receive the same treatment as MMR proficient (pMMR) patients although there is limited data that dMMR rectal cancer patients may not have the same level of benefits from neoadjuvant treatment. This retrospective study aims to evaluate the clinicopathological/molecular characteristics, disease response, and clinical outcomes in dMMR localized rectal cancer patients. Methods: A retrospective analysis was conducted on consecutive adult patients with a diagnosis of dMMR rectal cancer who were treated at Mayo Clinic between January 2000 to September 2021. Patients who presented with concurrent primary non-colorectal malignancies were excluded. The distributions of demographics, clinicopathological features, biomarkers, and outcome data were collected. Survival was assessed using Kaplan-Meier curves and Cox models were stratified by treatment arms to determine significance of treatment strategies. Results: Forty-one patients were identified with a median age of 45.3 years. Thirty (73.2%) pts were male. The most common MMR were loss of MSH2 and MSH6 (12/42; 29.3%) followed by loss of MLH1 and PMS2 (10/42; 24.4%) and solitary loss of MSH2 (4/42; 9.8%). The treatment, pathological response, and clinical outcomes are listed in table. With a median follow up of 101 months, only 6 patients (14.3%) died and median overall survival was not reached. Conclusions: Our findings showed dMMR localized rectal cancer responded to both ST and TNT with good clinical outcomes.[Table: see text]
Characteristics and outcomes of patients with multiple synchronous colon cancer primaries.
Authors: Diab Maria , Goyal Subir , Switchenko Jeffrey M. , Alese Olatunji B. , Shaib Walid Labib , Akce Mehmet , Wu Christina , El-Rayes Bassel F. 
Published: January 2022

194 Background: Patients (pts) with multiple synchronous colon cancer primaries (MCPs) constitute a unique subset of pts with colon cancer. However, there are limited published studies about these pts. The objective of this study is to compare the characteristics and outcomes of pts with MCPs to those with single colon cancer primaries (SCPs) using the largest study population to date. Methods: Data was obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Pts with synchronous MCPs were included and were matched 1:3 with pts with SCPs based on the Coarsened Exact Matching method for age, gender, and race. Only patients with multiple synchronous primaries were included (time since index = 0 months). We excluded pts with a lag time since diagnosis of index primary of 1 month or more. Univariate (UNA) and multivariable (MVA) analyses were performed to identify factors associated with patient outcomes. Kaplan-Meier analyses and Cox proportional hazards models were used to assess the association between tumor/patient characteristics and overall survival (OS). Results: A total of 3322 pts with MCPs and 9966 pts with SCPs were identified. Median age was 71 years. Majority were male (51.5%) and White (80.1%). 73.4% and 69.6% of pts had 12 or more lymph nodes examined for the MCPs and SCPs cohorts, respectively. The SCPs cohort included more T4 stage and more well- and moderately-differentiated histology. OS was significantly shorter in MCPs compared to SCPs (HR 1.29; 1.22-1.36; p < 0.001), with a 5- and 10-year OS rate of 47.8% and 28.2% for the MCPs and 56.4% and 41.6% for the SCPs, respectively, for all stages combined. In the MCPs cohort, the use of adjuvant chemotherapy was associated with an improved survival in AJCC stages II, III, and IV but not stage I. Conclusions: This is the largest study evaluating the impact of MCPs on outcomes. Across stages II to IV, pts with MCPs have a shorter survival than those with SCPs. Pts with stage II MCPs who receive adjuvant chemotherapy derive a survival benefit. Current guidelines do not list multiple synchronous primaries as a high-risk feature for stage II.
Effect of primary tumor location on second- or later-line treatment with anti-epidermal growth factor receptor antibodies in patients with metastatic colorectal cancer: A retrospective multicenter study.
Authors: Korphaisarn Krittiya , Archwamety Anita , Sintawichai Nattaya , Siripoon Teerada , Poungvarin Naravat , Tanasanvimon Suebpong , Sirachainan Ekaphop , Akewanlop Charuwan 
Published: January 2022

195 Background: Currently, there are no guideline recommendations of anti-EGFR Ab specific to tumor sidedness in subsequent-line treatment in patients with metastatic colorectal cancer (mCRC). We previously reported the effect of primary tumor location on subsequent-line treatment with anti-EGFR Ab from a single center. Here we presented the outcome from a multi-center study. Methods: Medical records of patients diagnosed with mCRC at 3 academic centers in Thailand (Siriraj, Chulalongkorn, and Ramathibodi hospital) between 2008 and 2019 were retrospectively reviewed. Patients with KRASwt mCRC who received anti-EGFR Ab in second- or later-line treatment were included. The impact of tumor sidedness on progression-free survival (PFS) was determined using Kaplan-Meier method, and those results were compared using log-rank test. Results: Among the 2,102 patients who had KRAS analysis data, 1,130 (54%) patients had KRASwt. Of those, 413 patients received anti-EGFR Ab in second- or later-line treatment. One hundred and sixty-two of 413 (39%) patients had extended RAS analysis. Seventy (17%) patients had right-sided tumors. Two hundred and thirty-eight (58%) patients received anti-EGFR Ab in the third line, and 132 (32%) patients and 43 (10%) patients were treated in the second and more than third line, respectively. Single-agent irinotecan was the most commonly used backbone chemotherapy (303/413, 73%). Patients with right-sided tumors had non-significantly inferior PFS compared to patients with left-sided tumors (median PFS: 5.7 months (mo), 95% confidence interval [CI]: 3.9-7.5 vs. 7.5 mo, 95% CI 6.5-8.5; p =0.17). Subgroup analysis showed no difference in PFS when stratified by treatment lines. Patient with right-sided tumors had significantly inferior OS compared to patients with left-sided tumors (median OS: 23.3 mo vs. 29.9 mo; p =0.005). Conclusions: To date, this is the largest real world data of the effect of primary tumor location on anti-EGFR Ab which demonstrated that tumor sidedness has no significant impact on treatment outcomes in KRASwt mCRC patients receiving second- or later-line therapy. Our findings do not support the utility of tumor sidedness for treatment selection in these settings. We confirmed that patients with right-sided tumors had significantly worse survival.
Adverse event management costs for first-line treatment with cetuximab or panitumumab of RAS wild-type metastatic colorectal cancer patients in Latin America.
Authors: Pescott Chris , Kasle Adam , Esteso Federico , Stefani Stephen , Brust Leandro , Pinto Jose , Tilli Malena , Massello Matthew 
Published: January 2022

203 Background: Anti-EGFR treatment of RAS wild-type metastatic colorectal cancer (mCRC) in Latin America includes cetuximab or panitumumab, added to chemotherapy (cet+CT and pan+CT, respectively). Adverse event (AE) profiles for each regimen may influence the treatment decision. This study aimed to estimate the associated financial impact of AE management in three countries: Argentina (AR), Brazil (BR) and Panama (PA) from a healthcare payer perspective. Methods: We revised a published Microsoft Excel-based economic model to calculate average patient- and population-level costs from a payer perspective of mCRC AE management for first-line cet+CT and pan+CT treatment, using AE frequency and severity data derived from the authorization relevant FDA prescribing information (PI), multiplied by the country-specific unit costs of managing AEs. Costs of AE management were obtained from publicly available sources in each country and converted to US dollars (USD). Country-specific market research data were applied to calculate costs at the eligible mCRC population level. The model structure and input parameters were endorsed by local practising oncologists. Results: A 17.5% (all-grade) and 31.6% (grade 3-4) lower average per patient AE frequency were estimated from the PI, for cet+CT vs pan+CT. Cost results are presented in the table. Projected AE management costs of cet+CT for the eligible mCRC population are $297,643 (AR), $124,981 (BR) and $65,895 (PA), annually, reducing current annual estimated AE costs by $42,181 (AR), $8,548 (BR) and $4,691 (PA). Conclusions: According to the average estimated AE frequencies, patients treated with cet+CT are expected to experience fewer AEs than with pan+CT. According to our analyses, the lower frequency rates could result in lower overall and severe AEs’ management costs, resulting in 12.4% (AR), 6.4% (BR) and 6.6% (PA) lower costs of AE management for cet+CT versus pan+CT.[Table: see text]
Survival of stage III colon cancer patients with adjuvant chemotherapy: Experience from a specialized cancer institute in Latinoamerica - Peru.
Authors: Veramendi Cabana Eder Christian , Cotito Izquierdo Jorge Antonio , Macetas Jackeline , Serrano Mariana , Pacheco Cristian , Castro Victor , Araujo Jhajaira M , Montenegro Paola Catherine 
Published: January 2022

204 Background: In Peru, colon cancer is the 5th most common cause of cancer and the sixth most deadly. Currently, surgery remains as the only curative therapy, however, there is risk of recurrence. Adjuvant chemotherapy has become a useful tool to improve progression-free survival (PFS) and overall survival (OS). In this study, we determine the current survival of our stage III colon cancer patients, submitted to adjuvant chemotherapy, and if this is similar to the evidence seen in large international studies; also, we analyze if delay of adjuvant chemotherapy has impact on survival. Methods: This descriptive cross-sectional study involved 162 patients with stage III colon cancer who underwent a resection surgery and received adjuvant fluoropyrimidine-based chemotherapy. They were evaluated, according to the TNM classification (tumor, nodule), as low risk (T1-T3, N1) and high risk (T4, N2). We also classified patients, according to the weeks of delay from surgery to adjuvant chemotherapy, into subgroups of 6, 8 and 10 weeks. Results: The mean age was 63.7 years, 63 patients were women (38.9%), 99 patients (61.1%) were men. Only 38.3% of patients started adjuvant chemotherapy in the first 6 weeks after surgery, and 85.8% of patients, in the first 10 weeks; the median time from surgery to initiation of adjuvant chemotherapy was 7.0 weeks. We estimated that, at 3 years, the median PFS is 73.5% (95% CI: 65.8-82.1). The 3-year PFS in the low-risk group was 82.9% (95% CI: 72.3-95.0) and 67.3% (95% CI: 57.2-79.2) in the high-risk group. It was estimated that at 3 years, the median OS is 81.1% (95% CI: 75.2-87.5). The 3-year OS in the low-risk group was 87.9% (95% CI: 80.4-96.2) and 76.0% (95% CI: 67.8-85.3) in the high-risk group. Conclusions: The PFS and OS in Peruvian population is similar to data evidenced in international historical studies such as the IDEA trial. This study, also, suggests that starting adjuvant treatment within 10 weeks does not present an impact on OS and PFS in our population.
A glimpse into the future of esophageal carcinoma in the United States: Predicting the future incidence based on the current epidemiological data.
Authors: Tella Sri Harsha , Mara Kristin , Kommalapati Anuhya , Chakrabarti Sakti , Desai Aakash , McGarrah Patrick Walsh , Jin Zhaohui , Mahipal Amit 
Published: January 2022

248 Background: Esophageal carcinoma is the 6th most common cause of death worldwide. While squamous cell carcinoma (SCC) was the most common among the histologic subtypes in the 20th century, recent reports have demonstrated an increased incidence of adenocarcinoma in both Eastern and Western world. With this changing paradigm of esophageal carcinoma, it is important to estimate the future burden of esophageal carcinoma by histology, age, sex, and race, that could help plan prevention, control, and treatment strategies for this cancer. Methods: We used Surveillance, Epidemiology, and End Results (SEER) 14 registries to obtain incidence data from 2000 to 2016. We applied age-period-cohort models to estimate future esophageal carcinoma incidence rates and the estimated disease burden by multiplying incidence forecasts by corresponding US Census population projections. Results: Our estimate suggests that the incidence (per 100,000 persons) of esophageal adenocarcinoma is increasing in people within the age group of 40-65 years. Our prediction showed that the incidence will increase from 2.12 in 2021 to 2.82 in 2030 (3.2% per year, 95% CI –2.3% to 9.1%, p=0.26). Notably, we noticed a similar marginal increase in incidence among Asians, Black, and Whites in the 40-65 years age group (3.1%, 3.2%, and 4.2%, per year, respectively). White males aged >65 years had the highest incidence of esophageal adenocarcinoma (17.34 in 2021), and incidence decreased 1.3% per year. We noticed a marginally decreased incidence in Black male (-1.1% per year, p=0.71) and Asian male (-3.9% per year, p=0.17) population aged >65 years. Interestingly, we found a decrease in the incidence of SCC in the current age groups 40-65 (-2.7% per year, p=0.31) and >65 years (-4.6% per year, p=0.081). We observed that Asians had the greatest decrease in incidence (-4.3% per year) as compared to that of Blacks (-4.2% per year) and Whites (-2.9% per year), although there was no statistically significant difference in the annual decrease among races. Conclusions: In our study of esophageal cancer, we predict an increased incidence of adenocarcinoma histology subtype in the younger age group (40-65 years) while the SCC subtype will have a decreased trend. Strategies to prevention esophageal adenocarcinoma, including dietary changes, should preferentially target patients <65 years of age.[Table: see text]
STLA101 assay for the detection of cancerous progression in Barrett’s esophagus: A multi-institutional study.
Authors: Hartley Christopher , Hagen Catherine E. , Mittal Sumeet K. , Abdo Joe , Thyparambil Sheeno P. , Bansal Ajay 
Published: January 2022

249 Background: Since 1975, Esophageal adenocarcinoma (EAC) incidence has increased more than any other cancer (̃700%). Pre-malignant metaplastic tissue, or Barrett's Esophagus (BE), is the only known precursor for EAC. Periodic histological assessment of endoscopic biopsy along dysplasia-carcinoma sequence is used to assess progression risk. Current surveillance protocols have clinical limitations as 80% of patients still present with stage II-IV EAC. The aim of this study is to compare novel proteomic expression patterns to distinguish stable BE patients from those who developed EAC using the STLA101 assay. Methods: After Institutional Review Board approval patients with BE/GERD were identified. Two cohorts were selected: progressors (progressed to EAC at subsequent interval of 0.5-3 years) and non–progressors (̃10 yrs of f/u surveillance without progression along dysplasia/carcinoma path). 24 normal esophageal mucosa samples with no h/o of BE were also retrieved for baseline expression levels. Tissue sections were microdissected to isolate pure BE cells from surrounding stromal cells. BE cells underwent a multi-step process where tissue was heated and digested to produce a liquid biopsy for mass spec. Isotopically labeled control peptides representing the STLA101 panel were spiked in with digested tissue samples to quantify all of the markers simultaneously using a Triple-quad mass spectrometer. Results: A total of 95 tissues were analyzed. 29 BE biopsies progressed to EAC within a mean of 380 days while the remaining 28 BE and 14 GERD specimens did not progress over a 10-yr period. All 8 biomarkers were expressed at a higher level in BE tissue that progressed to cancer when compared to BE/GERD tissue that remained stable over 10 years. The assay had a 100% technical success rate as no samples yielded “non-detectable” data points. Conclusions: The differential overexpression of the STLA101 panel on progressive and non-progressive BE tissues demonstrates the clinical utility of STLA101 as a predictive biomarker panel for early detection of esophageal carcinogenesis. Non-progressive BE tissues were similar to normal mucosa, therefore, patients whose BE tissue samples resemble this profile may receive a reduced screening cadence. On the other hand, patients with overexpression of the STLA101 panel may be eligible to receive more frequent screening or therapeutic intervention.
Geriatric-8 (G8) screening tool stratified the efficacy of S-1 plus ramucirumab in elderly patients with advanced/recurrent gastric cancer: A post-hoc analysis of the KSCC1701 trial.
Authors: Hu Qingjiang , Suyama Koichi , Kobayashi Kazuma , Katsuya Hiroo , Izawa Naoki , Uenosono Yoshikazu , Kusumoto Tetsuya , Otsu Hajime , Orita Hiroyuki , Kawanaka Hirofumi , Shibao Kazunori , Koga Satoshi , Shimokawa Mototsugu , Makiyama Akitaka , Saeki Hiroshi , Oki Eiji , Baba Hideo , Mori Masaki 
Published: January 2022

256 Background: KSCC1701 trial showed the efficacy and safety of S-1 plus ramucirumab as a first-line treatment for elderly patients with advanced/recurrent gastric cancer. However, some frail patients may not benefit from S-1 plus ramucirumab. We aimed to clarify the usefulness of G8 screening tool for stratifying the efficacy and safety of S-1 plus ramucirumab therapy to elderly patients with advanced/recurrent gastric cancer. Methods: Patients aged 70 and older with previously untreated unresectable or recurrent gastric cancer were included from 23 institutes in Japan. They received S-1 (40-60 mg twice daily for 28 days, every 6 weeks) plus ramucirumab (8 mg/kg, every 2 weeks) until disease progression. The primary endpoint was the one-year survival rate. The secondary endpoints included progression-free survival (PFS), overall survival (OS), response rate (RR), and safety. The exploratory endpoint was detection of differences in treatment response by G8 screening tool. Results: Between September 2017 and November 2019, 48 patients were enrolled in this study. The cut-off value of G8 was determined as 11 by time-dependent ROC curve analysis for OS. Patients of G8 high (> = 11) and low (< 11) were 31 and 15, respectively. The characteristics of patients with G8 high/low were male: 21 (65.6%)/13 (81.3%), median age: 77/78 years, and PS (0): 16 (50.0%)/4 (25.0%). The one-year survival rate (total/G8-high/G8-low) was 65.2%/82.6%/26.7%. The median OS and PFS (total/G8-high/G8-low) were 16.4/20.7/6.9 months and 5.8/7.2/3.9 months, respectively. On Cox proportional hazards regression analysis for OS and PFS, the hazard ratio of G8-high was 0.156 [95%CI:0.066-0.367 (p < 0.0001)] and 0.391 [95%CI:0.202-0.755 (p = 0.0038)], respectively. The best RR (total/G8-high/G8-low) was 41.9%/55.6%/23.1%. The frequent grade 3 adverse events (total/G8-high/G8-low) was 78.7%/77.4%/81.3%. The frequent grade 4 adverse events (total/G8-high/G8-low) was 14.9%/16.1%/12.5%. Conclusions: Based on the results, G8 screening tool is useful for selecting elderly patients with advanced/recurrent gastric cancer in whom S-1 plus ramucirumab treatment shows a longer survival and a higher RR. Further examination including adverse events is therefore warranted. Clinical trial information: UMIN000028309.
Health-related quality of life (HRQoL) in patients (pts) with advanced esophageal squamous cell carcinoma (ESCC) treated with nivolumab (N) plus chemotherapy (CT) or nivo plus ipilimumab (I) versus chemo: Results from CheckMate 648.
Authors: Bridgewater John A. , Chau Ian , Gricar Joseph , Blum Steven I. , Taylor Fiona , Lawrance Rachael , Padilla Brad , Yip Christine , Wyrwicz Lucjan 
Published: January 2022

262 Background: This analysis evaluated HRQoL as exploratory endpoints in CheckMate 648, a randomized, open-label, global Phase 3 study, evaluating treatment with N+I, N+CT and CT alone in inoperable advanced, recurrent, or metastatic ESCC. Methods: The effects of N+I vs N+CT vs CT on HRQoL were assessed using the Functional Assessment of Cancer Therapy-Esophageal (FACT-E) (including the GP5 item to assess impact of side effects) and EQ-5D-3L. A mixed model for repeated measures was used to evaluate longitudinal changes from baseline (BL) and differences between treatment groups. Comparison of the risk of being bothered by the side effects of treatment was estimated for the GP5 using generalized estimating equation (GEE). Time to confirmed deterioration (TTCD) was assessed using Kaplan-Meier plots along with Cox proportional hazard models. Analyses were conducted on both the all-randomized population and the subset of patients with PD-L1 expression ≥1%. Results: 970 pts were randomized 1:1:1 to N+I (n=325), N+CT (n=321), or CT (n=324). 90% of pts completed both a BL and at least one on-treatment assessment and were included in the PRO analysis population. FACT-E (all randomized pts). Study showed similar BL scores across all 3 treatment groups. Changes from BL showed a trend towards better HRQoL for pts treated with N+I and N+CT compared to CT alone, however these results were not statistically significant. Patients treated with N+I had significantly decreased risk of experiencing bother associated with the side effects of treatment than patients treated with either N+CT or CT. TTCD analysis demonstrated delayed deterioration for pts treated with N+CT vs CT. Findings for PD-L1 ≥1% subpopulation were similar to all randomized pts. Conclusions: In pts with inoperable advanced, recurrent, or metastatic ESCC, HRQoL is maintained throughout treatment with N+I and N+CT. Trends towards better HRQoL and decreased risk of deterioration were observed with N+I and N+CT compared to CT alone. Clinical trial information: NCT03143153. [Table: see text]