bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of Medicaid expansion on colorectal cancer incidence among vulnerable populations.
Authors: Qian Alexander , Nalawade Vinit , Murphy James Don 
Published: January 2022

68 Background: With the Affordable Care Act (ACA), the number of uninsured patients in states that expanded Medicaid decreased more among racial/ethnic minorities and lower income adults. Increased access to care could influence colorectal cancer (CRC) incidence through increased screening. However, we lack research on whether Medicaid expansion differentially influenced CRC incidence among vulnerable patient subgroups. This population-based study examines whether Medicaid expansion with the ACA was associated with decreased CRC incidence among racial/ethnic minorities, and adults with lower income. Methods: We queried the Surveillance, Epidemiology, and End Results Program (SEER) database to calculate the age-adjusted incidence rates of CRC among patients under 65 years of age diagnosed between 2010 and 2018. We categorized states into two groups: states that expanded Medicaid on January 1, 2014, and states that did not expand Medicaid over the study period. We determined the change in CRC incidence before Medicaid expansion (2010-2013) and after Medicaid expansion (2014-2018). We used a difference-in-difference approach to determine whether changes in CRC incidence differed by expansion status among all patients and among subgroups stratified by race/ethnicity and other socioeconomic indicators. Results: Among the entire study cohort, from 2010-2013 to 2014-2018, rates of CRC (per 100,000) increased from 26.6 to 28.3, and this increasing rate did not differ by ACA expansion status (p=0.48). We found that the impact of ACA expansion on CRC incidence varied by race/ethnicity. The increase in CRC rates was higher among non-ACA expansion states compared to ACA expansion states for Hispanics (5.4 vs. 1.6 increase per 100,000; p=0.002), and Asian or Pacific Islanders (4.3 vs. 0.4 increase per 100,000; p=0.02), but not with Black (p=0.94), or non-Hispanic white patients (p=0.91). The change in CRC incidence between 2010-2013 and 2014-2018 did not differ by county-level household income, fraction under the federal poverty level, or education level (all p>0.05). Conclusions: This study found that Medicaid expansion through the ACA might differentially benefit Hispanic and Asian patients with respect to decreases in CRC incidence. This study reports on the first 5 years after the ACA, though the true benefits of increased access to care may take longer to manifest. Additional research with longer follow-up is required to fully understand the influence of Medicaid expansion.
Second cancer after adjuvant chemotherapy in patients with colon cancer.
Authors: Teufel Andreas , Li Moying , Gerken Michael , Ebert Matthias Philip , Schlitt Hans J. , Evert Matthias , Herr Wolfgang , Klinkhammer-Schalke Monika 
Published: January 2022

86 Background: Adjuvant chemotherapeutic treatment of UICC-stage III/IV colon cancer with fluorouracil, leucovorin and oxaliplatin (FOLFOX) is widely accepted as the current standard after R0-resection. However, with continuous improvement of patients´ survival and life expectancy, long-term side effects of chemotherapy such as second cancer development are becoming increasingly important. Methods: We performed a retrospective analysis of clinical data derived from the population-based cancer registry at the Regensburg Tumor Center, Germany. Patients who were diagnosed with colon cancer UICC stage III and IV between 2002 and 2018 and underwent R0 surgical resection of primary tumor were included for the study. Second cancer was as defined new tumor occurrence at least 6 months after beginning of chemotherapy and in another localization compared to primary tumor. Second cancer rate was compared between patients with and patients without adjuvant chemotherapy. Results: Data of totally 2,856 Patients with UICC-stage III/IV colon cancer were analyzed, 1,520 (53.2%) of whom received adjuvant chemotherapy. Overall, 223 (7.8%) patients developed a subsequent second cancer. Most frequent second cancers were prostate cancer (18.4%), colon cancer (16.1%), breast cancers (8.1%), lung cancer (8.1%), rectal cancer (4.9%) and uterine cancer (4.9%). However, patients treated with adjuvant chemotherapy did not have a significantly increased risk for second cancer development compared to patients without adjuvant chemotherapy (Table). Interestingly, our data suggest a significantly decreased second cancer rate in patients treated with FOLFOX compared to FUFOL for adjuvant treatment. Conclusions: Second cancer development was not increased after adjuvant chemotherapy for UICC-stage III/IV colon cancer, which is a novel aspect in the ongoing discussions on reduction of adjuvant treatment to 3 months or treatment of lymph node negative patients. Primary tumor (N) Second tumor (N) Second tumor (%) Cumulative rate 60 months (%) Log-Rank p Chemotherapy Yes 1520 145 9.5% 8.8% No 1336 78 5.8% 9.0% 0.685 Total 2856 223 7.8% 8.9%
A phase 1b multitumor cohort study of cabozantinib plus atezolizumab in advanced solid tumors (COSMIC-021): Results of the colorectal cancer cohort.
Authors: Abrams Thomas Adam , Kazmi Syed Mohammad Ali , Winer Ira Seth , Subbiah Vivek , Falchook Gerald Steven , Reilley Matthew , Kunk Paul Raymond , Goel Sanjay , Garrido-Laguna Ignacio , Kochenderfer Mark D. , Werneke Scott , Andrianova Lana , Sudhagoni Ramu , Paulson Scott 
Published: January 2022

121 Background: Cabozantinib, a multiple receptor tyrosine kinase inhibitor, promotes an immune-permissive environment which may enhance the activity of immune checkpoint inhibitors. COSMIC-021 (NCT03170960) is evaluating the combination of cabozantinib with atezolizumab, an anti-PD-L1 inhibitor, in patients with advanced solid tumors. Outcomes in patients (pts) with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine-containing therapy are presented. Methods: Pts with mCRC and an ECOG PS of 0–1 who progressed during or following systemic chemotherapy including fluoropyrimidine plus oxaliplatin or irinotecan were eligible. Up to 2 prior lines of anti-cancer therapy including EGFR-targeted therapy were allowed. Microsatellite instability high (MSI-H) and/or mismatch repair (MMR)-deficient pts were excluded. Pts received cabozantinib 40 mg PO QD plus atezolizumab 1200 mg IV Q3W. The primary endpoint was objective response rate (ORR) per RECIST 1.1 by investigator. Other endpoints included safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). CT/MRI scans were performed Q6W for the first year and Q12W thereafter. Results: 31 pts received cabozantinib plus atezolizumab (median age, 60 y [range 31, 79]; male, 58%; ECOG PS 1, 61%; 2 prior lines of therapy, 71%; prior EGFR inhibitor, 16%; ≥3 tumor sites, 52%; tumors in left colorectum, 71%). Median follow-up was 28.1 mo (range, 24.2, 31.3) as of July 21, 2021. Cabozantinib plus atezolizumab demonstrated clinical activity in pts with mCRC (Table). Patients with wild-type RAS (n = 12) had numerically longer PFS and OS and higher ORR vs those with mutations (n = 19) (Table). Treatment-related adverse events (TRAEs) of any grade occurred in 28 (90%); the most common were diarrhea (52%), fatigue (42%), and nausea (35%). Grade 3-4 TRAEs occurred in 16 (52%); the most common were hypertension (10%), fatigue (6%), and lipase increased (6%); no Grade 5 events were reported. Conclusions: Cabozantinib plus atezolizumab demonstrated encouraging clinical activity with manageable toxicity in pts with previously treated advanced non-MSI-H/MMR-proficient CRC. Clinical trial information: NCT03170960. [Table: see text]
Evaluation of baseline BRAF V600E mutation in circulating tumor DNA and efficacy response from the BEACON study.
Authors: Kopetz Scott , Murphy Danielle A. , Pu Jie , Yaeger Rona , Ciardiello Fortunato , Desai Jayesh , Van Cutsem Eric , Wasan Harpreet Singh , Yoshino Takayuki , Elez Elena , Golden Adele , Zhu Zhou , Zhang Xiaosong , Tabernero Josep 
Published: January 2022

162 Background: In the randomized phase 3 BEACON study, encorafenib + binimetinib + cetuximab (triplet) and encorafenib + cetuximab (doublet) regimens improved overall survival (OS) and objective response rate (ORR) versus standard of care (control) in patients (pts) with previously treated BRAF V600E-mutant metastatic colorectal cancer. To identify whether detection of a BRAF V600E mutation in baseline circulating tumor DNA (ctDNA) correlated with response, we evaluated the status and allele frequency of BRAF V600E compared with clinical outcomes. Methods: Plasma samples were collected at Cycle 1 Day 1 and end of treatment for ctDNA analysis and analyzed using GuardantOMNI. Variant allele frequency (VAF) of BRAF V600E was grouped into high (> median) and low (≤median) categories. Low VAF samples included those where BRAF V600E mutation was not detected or no ctDNA was detected. ORR, based on blinded independent central review, and OS were compared between treatment arms according to VAF levels. ORR comparisons used Chi-square test and logistic regression. OS was summarized using the Kaplan-Meier method. HRs and 95% CIs were estimated using a Cox model. Additional correlation analyses between BRAF V600E status in baseline tumor tissue, as well as clonality, will be presented. Results: Baseline plasma samples were analyzed from 544 of 631 pts in the ctDNA analysis: 88.3% (196/222) in the triplet arm, 86.6% (187/216) in the doublet arm, and 83.4% (161/193) in the control arm. BRAF V600E mutations were detected in 90.4% (492/544) of pts (90.3% [177/196] triplet, 90.4% [169/187] doublet, and 90.7% [146/161] control). Pts with BRAF V600E mutations with high VAF had significantly ( P≤0.0001) increased ORR (95% CI) in the triplet and doublet arms (27.3% [19.5–36.8] and 15.9% [9.7–25.0], respectively) compared with control (0% [0.0–4.3]). Similar response trends were observed in pts with BRAF V600E mutations with low VAF (triplet: 28.9% [20.8–38.9]; doublet: 25.3% [17.7–34.6]; control: 5.3% [2.1–12.8]). OS decreased in BRAF V600E pts with high VAF (median OS [95% CI]: triplet 7.2 [6.0–8.0] months, n = 99; doublet 5.4 [4.4–6.1] months, n = 88; control 4.2 [3.4–4.8] months, n = 85) compared with pts with low VAF (triplet 14.8 [10.2–19.8] months, n = 97; doublet 14.8 [11.7–23.0] months, n = 99; control 9.3 [7.5–11.3] months, n = 76). Conclusions: ctDNA analyses showed the majority of pts in BEACON analyzed at baseline had a detectable BRAF V600E mutation. Increased response rates were observed in pts treated with triplet or doublet therapy compared with control, independent of VAF. Pts with a higher VAF for BRAF V600E may have a worse prognosis. Clinical trial information: NCT04607421.
Clinicopathological characteristics and outcomes of patients with deficient mismatch repair colorectal cancer.
Authors: Viñal David , Martinez-Perez Daniel , Martínez-Recio Sergio , Ruiz Iciar , Jiménez Bou Diego , Peña Jesus , Martin-Montalvo Gema , Rueda-Lara Antonio , Alameda Maria , Gutiérrez Sainz Laura , Custodio Ana B. , Palacios Maria Elena , Ghanem Ismael , Rodriguez Salas Nuria , Feliu Jaime 
Published: January 2022

181 Background: Patients with microsatellite-instability–high (MSI-H) or deficient mismatch repair (dMMR) colorectal cancer (CRC) represent a unique subgroup of patients with evolving treatment opportunities. Methods: We included all of the patients with pathologically confirmed diagnosis of CRC at Hospital Universitario La Paz from October 2016 to September 2020. Results: A total of 1,152 patients were diagnosed with CRC. IHC for MMR was available in 1,014 patients. Of those, 100 (9,8%) patients were deficient for MLH1 and PSM2 (n = 78), MSH2 and MSH6 (n = 12), PMS2 (n =5), MSH6 (n = 4), or MSH2 (n = 1). Baseline characteristics are depicted in the table. Female sex (55% vs. 38%; p = 0,001), right primary tumor location (75% vs. 29%; p = 0,001), histological grade 3 (20% vs. 8%; p <0,001), and mucinous component (39% vs. 10%; p < 0,001), and localized disease at diagnosis (97% vs. 79% p < 0,001), were more frequent in dMMR group. Among patients with dMMR CRC, 53% were ≥75 years old. The prevalence of BRAF V600E mutation was 56%. More female sex (67% vs. 40%; p = 0,006) and BRAFV600E mutation (66% vs. 48%; p = 0,06) were found in older vs. younger dMMR patients. Six patients were diagnosed with Lynch syndrome. After a median follow-up of 24 months, 279 patients have died. Median overall survival (OS) was not reached in either group (p = 0,327). Three-year OS was 75% (95% CI: 70-80) and 69 (95% CI: 67-71) in the dMMR and pMMR, respectively. In patients with localized disease that underwent antineoplastic treatment (n = 856), median disease-free survival (DFS) and OS were not reached in either group (p =0,403 and p = 0,232). Three-year DFS in patients with stage I (n = 216) was 64% (95% CI: 46-82) and 85% (95%CI: 80-90), p = 0,055; in patients with stage II (n = 274) was 84% (95% CI: 77-91) and 70% (95% CI: 66-74), p = 0,588; and in patients with stage III (n = 366) was 79 (95% CI: 71-87) and 66% (95% CI: 62-70%), p = 0,322; in dMMR and pMMR, respectively. No baseline characteristics were associated with recurrence in patients with localized dMMR CRC. Conclusions: Patients with MSI-High/dMMR CRC display distinctive clinical and pathological features. Overall prognosis does not differ in our series, but older age of dMMR patients may have influenced the outcomes.[Table: see text]
Circulating tumor DNA dynamics on front-line chemotherapy with bevacizumab or cetuximab in metastatic colorectal cancer: A biomarker analysis for acquired genomic alterations in CALGB/SWOG 80405 (Alliance) randomized trial.
Authors: Raghav Kanwal Pratap Singh , Ou Fang-Shu , Venook Alan P. , Innocenti Federico , Sun Ryan , Lenz Heinz-Josef , Kopetz Scott 
Published: January 2022

193 Background: Enhanced understanding of the evolving clonal architecture under treatment stress is crucial to optimizing care and developing effective therapies in metastatic colorectal cancer (mCRC). Emergence of genomic alterations (GAs) [mutations (muts) and amplifications (amps)] in RAS, BRAF, EGFR, ERBB2, and MET have been recognized as key resistance mechanisms to anti-EGFR therapy in later lines in mCRC. Data regarding occurrence of these GAs under selective pressure in the first line setting is lacking. Methods: CALGB/SWOG 80405 was a randomized trial of bevacizumab (bev) vs cetuximab (cet) in first line mCRC. Patients (pts) with paired plasma samples (pre-treatment and post-progression) available for circulating tumor DNA (ctDNA) testing were included in this substudy. Sequencing of ctDNA was performed by Guardant360 assay in a CLIA-certified environment to detect GAs in 73 genes. RAS/BRAF status [mut vs. wild type (wt)] was based on clonal muts [pre-defined cutoff of relative MAF (rMAF) ≥ 25%] in ctDNA. Only samples with ≥1 GA were analyzed to minimize false negatives. The primary objective was to determine and compare prevalence of acquired GAs between study arms: bev (anti-VEGF) and cet (anti-EGFR). Descriptive statistics and Fisher’s exact test were used. Results: Baseline characteristics of ctDNA cohort were similar to the 80405 population. Among 133 randomized RAS/BRAF wt pts, 11 (15.3%) and 5 (8.2%) developed acquired GAs (OR 2.0, P = 0.29), in bev and cet arm, respectively. Key comparative data for pts with regard to acquired pathogenic GAs are shown in the table. Conclusions: In this randomized mCRC cohort, the ctDNA profile of acquired GAs with front line anti-EGFR chemotherapy appears to be strikingly distinct from that seen with later lines of therapy. Acquisition of GAs, classically associated with EGFR resistance in later line, was not only rare with upfront cet-chemotherapy but also comparable to bev-containing (anti-VEGF) regimen. The mechanisms of acquired resistance appear to differ when anti-EGFR therapy is administered in combination with highly active first line chemotherapy. Our findings have critical translational relevance to the timing and value of ctDNA-guided anti-EGFR rechallenge in mCRC pts, especially in those treated with anti-EGFR therapy upfront.[Table: see text]
Safety and efficacy of encorafenib, binimetinib, plus cetuximab for BRAF V600E-mutant metastatic colorectal cancer: Results of a prospective study as an expanded access program.
Authors: Takashima Atsuo , Kotani Daisuke , Kato Takeshi , Satoh Taroh , Masuishi Toshiki , Komatsu Yoshito , Shiozawa Manabu , Esaki Taito , Izawa Naoki , Takeuchi Shinji , Bando Hideaki , Iwasa Satoru , Hasegawa Hiroko , Yamaguchi Toshifumi , Taniguchi Hiroya , Yoshino Takayuki 
Published: January 2022

199 Background: The encorafenib, binimetinib, and cetuximab (triplet) regimen showed survival benefit and a higher response rate over standard chemotherapy among pretreated patients (pts) with BRAF V600E-mutant metastatic colorectal cancer (mCRC) in the phase III BEACON trial. Herein, we report the safety and efficacy of the triplet regimen in a prospective study (JapicCTI-205146) as a Japanese expanded access program (EAP). Methods: The key eligibility criteria were age ≥18 years and a diagnosis of BRAF V600E-mutant mCRC with progression observed after one or two prior systemic chemotherapy. Encorafenib (300 mg QD), binimetinib (45 mg BID), and weekly cetuximab (400 mg/m2, followed by 250 mg/m2) were administered. Patients who had received at least one dose of any study drug were included in this analysis. Adverse events were evaluated using CTCAE v4.0. The objective response rate (ORR) was evaluated using RECIST Guideline Version 1.1. Results: A total of 86 pts were enrolled from 10 Japanese institutions from February to December 2020. Safety and efficacy were evaluated in 81 pts. The median age was 60 years. Fifty-four pts (67%) had ECOG PS 0 and 50 pts (62%) received one prior chemotherapy. Treatment-related serious adverse events and grade 3 or higher treatment-related adverse events were observed in 14 (17%) and 24 (30%) pts, respectively. Treatment-related death occurred in one pts. Among the 76 pts with target lesions, 21 pts were responders, and the confirmed ORR was 27.6%. Stable disease was observed in 42 pts, resulting in a disease control rate of 82.9%. The ORR was consistent regardless of ECOG PS status, the number of prior chemotherapy lines, and the number of metastatic organs. Conclusions: The safety and efficacy of the triplet regimen in the Japanese EAP were comparable to those in the BEACON trial. These results support the triplet regimen as a new standard-of-care treatment option in the second- or third-line treatment of pts with BRAF V600E-mutant mCRC in the Japanese population, as there was a promising response without any new safety signals. Clinical trial information: JapicCTI-205146.
Correlation of combined positive score of PD-L1 expression and clinical efficacy for advanced esophageal squamous cell carcinoma treated with nivolumab monotherapy.
Authors: Mikuni Hayato , Yamamoto Shun , Sawada Ryoichi , Honma Yoshitaka , Sekine Shigeki , Oguma Junya , Saruta Masayuki , Daiko Hiroyuki , Kato Ken , Ishiyama Koshiro 
Published: January 2022

289 Background: Based on the results of the ATTRACTION-3 trial, nivolumab has shown superiority compared to taxane monotherapy as second-line treatment for advanced esophageal squamous cell carcinoma (ESCC) patients (pts). However, the PD-L1 expression by tumor proportion score (TPS) did not obviously correlate to the efficacy. In contrast, PD-L1 expression by combined positive score (CPS) was used as a companion diagnosis for pembrolizumab in ESCC. There are little data on CPS with nivolumab in ESCC. Methods: We retrospectively reviewed the medical records of the pts with ESCC who received nivolumab monotherapy in our hospital. The CPS before nivolumab was evaluated by 22C3 antibody. We evaluated the correlation of CPS and clinical efficacy of progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR) by using Cox proportional regression model and Fisher’s exact test. Results: Eighty-seven pts were selected for this analysis with a median follow-up time of 7.9 (1.2-84.1) months. Thirty pts (34.5%) had CPS < 10, and 57 patients (65.5%) had CPS≥10. Between two groups, the characteristics were as follows; median age (range): 62 (35-85) and 66 (46-85) years, PS 0: 20.0/36.8%, prior taxane: 50.0/40.4%, prior radiotherapy: 86.7/77.2%, respectively. The median PFS (95%CI) were 1.8 (1.2-2.8)/2.6 (1.8-33.8) months (HR: 0.85 [0.52-1.38], p = 0.50). The ORR/DCR were 21.1/31.6% in CPS < 10 group, and 22.2/57.8% in CPS≥10 group, and there was no statistical significance, respectively (p = 1.0/0.10). In multivariate analysis, only higher age was the favorite factor for PFS. From the result with another cut-off level of CPS, the proportion of CPS≥1/CPS≥20 was 90.8/36.8%. The HR of multivariate analysis with CPS≥1/CPS≥20 was 1.24/0.73, respectively. Conclusions: There was a trend toward better PFS with a higher cut-off point of CPS. CPS had the potential to be a biomarker even for nivolumab for advanced ESCC pts.
Perioperative sintilimab combination with SOX for resectable locally advanced gastric/gastroesophageal junction cancer(GC/GEJC): Initial findings of a single-arm phase II trial.
Authors: Ding Xuewei , Li Bin , Xue Qiang , Cai Mingzhi , Cui Jingli , Wang Baogui , Ke Bin , Zhang Rupeng , Liang Han 
Published: January 2022

294 Background: Perioperative treatment is very important to improve long-term survival for gastric/gastroesophageal junction cancer(GC/GEJC), The RESOLVE study showed that perioperative-SOX have a clinically meaningful improvement in patients with locally advanced GC/GEJC who had D2 gastrectomy. Adding PD-1 inhibitor to the chemotherapy have shown significant clinical benefits in first-line treatment of GC/GEJC. This trial was designed to assess the feasibility and efficacy of this combination in perioperative treatment of resectable locally advanced GC/GEJC. Methods: This is a prospective, single-arm, single-center phase II study. Patients of histopathology confirmed locally advanced GC/GEJC, with clinical stage II-IV A per AJCC8th, ECOG PS 0-1, were enrolled and treated with 3 cycles of preoperative sintilimab (200mg, iv, d1) and SOX (oxaliplatin 130mg/m2, iv, d1 and S-1 40-60mg, po, bid, d1-14) every 3 weeks, and 12 months of postoperative sintilimab (200mg, iv, d1) and S-1 (40-60mg, po, bid, d1-14) every 3 weeks. The primary endpoint was 2-year DFS rate. The second endpoints were pCR, MPR, R0 resection rate, safety and 3-year OS. Results: As of June 2021, 21 patients were enrolled, with median age 56 years (range 31-72 years), males 10 (47.6%), cT2/3/4a/4b 2(9.5%)/0/16(76.2%)/3(14.3%), cN1/N2 7(33.3%)/14(66.7%) and GC/GEJC 14(66.7%)/7(33.3%). All 21 patients had completed gastrectomy. 7 patients (33.3%) achieved pathological complete response (pCR), 8 patients (38.1%) had major response (TRG 0-1) and 21 patients (100%) achieved R0 resection. Common TRAEs were anemia (38.1%), lymphopenia (28.6%), neutropenia (19.0%), leukopenia (14.3%), ALT increase (9.5%), AST increase (4.8%), thrombocytopenia (4.8%). Grade 3 or more TRAEs included anemia (9.5%). There were no severe complications and death related to the operation. The median postoperative hospital stay was 10 days (range 7-41 days). Conclusions: Adding sintilimab to the chemotherapy resulted in an encouraging pCR and MPR as perioperative treatment for resectable locally advanced GC/GEJC, and safety was manageable. A Phase II randomized study is ongoing. Clinical trial information: ChiCTR2100043572.