bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of socioeconomic status (SES) on colorectal cancer patient survival: An analysis of 890,867 patients in the National Cancer Database (NCDB).
Authors: Salem Mohamed E. , Trufan Sally Jeanne , Symanowski James Thomas , Kadakia Kunal C. , Puccini Alberto , Musselwhite Laura W. , Graves Kristi D , Hartley Marion L. , Kim Edward S. , Hwang Jimmy J. , El-Rayes Bassel F. 
Published: January 2021

19 Background: SES has been associated with outcomes in cancer patients (pts). We examined associations between SES and survival of pts with colorectal cancers (CRC). Methods: The NCDB was used to examine the association of SES status with clinicopathological features and outcomes of colorectal cancer pts, categorized by the income and education level of their area of residence. Logistic regression, Cox proportional hazard model, and chi-square test were used to examine the differences between groups. Results: A retrospective analysis of 890,867 pts with CRC (right-sided 34.1%, transverse 11.9%, left-sided 46.2%, and rectal 7.8%) diagnosed between 2004 and 2016, was conducted. About half the pts were male (51.4%); 84.3% were white, 11.2% black, and 4.5% of other races. Overall, 30.8% of pts lived in the highest and 18.4% in the lowest income areas. Twenty-three percent lived in areas comprising the highest high school graduation rate areas (>93%), while 17.4% lived in the lowest (< 79%). Compared to pts living in high-income areas, pts living in the lowest income areas were more likely to be black (OR 6.2, 6.1-6.3), present at a younger age (18-30 yrs vs. >70 yrs; OR 1.28, 1.18-1.39), have T3/T4 disease at presentation (OR 1.03, 95%CI 1.02-1.04), left-sided tumors (OR 1.05, 1.04-1.06), higher Charlson-Deyo score (OR 1.34, 1.33-1.36), and have Medicaid (OR: 3.9, 3.8-4.0) or no health insurance (OR: 2.9, 2.8-3.0). Tumor location and grade, stage, age, sex, race, ethnicity, income, education, insurance status, Charlson-Deyo score, and type of treatment center were independent predictors for survival in the multivariate analysis. Pts living in the lowest income and lowest education areas had a 13% and 4% higher risk of death, respectively, compared to pts in the highest income areas and education areas. Black pts had a 7% increased risk of death. Pts with Medicaid and no insurance coverage had a 44% and 29% increased risk of death, respectively, compared to pts with private insurance. Conclusions: CRC pts living in areas of low income and low education had worse survival. Insurance status and type of treatment center also have a strong impact on survival. Sociodemographic characteristics need to be taken into account and studied further, with the aim of improving outcomes for all pts. [Table: see text]
Racial disparities negatively impact outcomes for patients with early-onset colorectal cancer independent of income or education status.
Authors: Kamath Suneel Deepak , Torrejon Nataly Valeria , Wei Wei , Tullio Katherine , Nair Kanika G. , Liska David , Krishnamurthi Smitha S. , Khorana Alok A. 
Published: January 2021

20 Background: The incidence of colorectal cancer (CRC) in patients under age 50 is rising for reasons that are incompletely understood. We examined the effects of health disparities and socioeconomic factors on outcomes for patients with early-onset CRC compared to older-onset CRC. Methods: Patients with CRC from 2004-2015 in the National Cancer Database were included and categorized by age under or over 50 years. Differences in demographic, disease and treatment characteristics and socioeconomic factors between younger and older patients were assessed by Chi-square test. The effect of age, race, ethnicity, insurance status, community median income and community educational attainment on overall survival (OS) were assessed using Cox models. Subgroup analyses were carried out by factors with significant interactions with race. Bonferonni correction was used when indicated. Results: The study population comprised 1,061,204 patients, 108,058 (10.2%) of whom were under age 50. The proportion of patients diagnosed under age 50 increased over time: 9.4% in 2004-2006, 10.1% in 2007-2009, 10.5% in 2010-2012 and 10.7% in 2013-2015. Compared to older patients, young patients were more likely to be Black (15.1% vs. 11.3%) or Hispanic (8.6% vs. 4.6%) and to be diagnosed with stage 4 disease (24.9% vs. 17.0%), p < 0.0001 for all. Age < 50 years was associated with improved median OS (157.4 vs. 64.2 months, p < 0.0001). ). Black patients had the worst median OS (58.3 months) compared to White (67.0 months), Hispanic (91.6 months) or Asian (104.9 months) patients, p < 0.0001. Within the subgroup of early-onset CRC patients with private insurance, Blacks had worse OS compared to White patients at multiple community income and education levels. Older CRC patients did not demonstrate the same disparities. Asian and Hispanic patients had equivalent or better OS compared to White patients regardless of insurance type, income or education level. These data are shown in the Table. Conclusions: Early-onset CRC continues to increase. Patients with early-onset CRC are more likely to be Black or Hispanic and to present with stage 4 cancer compared to older patients. Alarmingly, Black patients showed worse OS compared to White patients in all income subgroups, even with private insurance. Much more work is needed to address the environmental factors and health disparities that lead to these outcomes. [Table: see text]
Results of a phase II trial of ramucirumab plus irinotecan as second-line treatment for patients with advanced gastric cancer (HGCSG 1603).
Authors: Kawamoto Yasuyuki , Yuki Satoshi , Sawada Kentaro , Nakamura Michio , Muto Osamu , Sogabe Susumu , Shindo Yoshiaki , Ishiguro Atsushi , Sato Atsushi , Tsuji Yasushi , Dazai Masayoshi , Okuda Hiroyuki , Sasaki Takahide , Harada Kazuaki , Nakano Shintaro , Nakatsumi Hiroshi , Sekiguchi Mari , Sakata Yuh , Sakamoto Naoya , Komatsu Yoshito ,   Hokkaido Gastrointestinal Cancer Study Group (HGCSG)
Published: January 2021

217 Background: Ramucirumab (RAM) is a fully human IgG1 monoclonal vascular endothelial growth factor receptor-2 (VEGFR-2) antibody. The RAINBOW trial showed RAM plus paclitaxel (PTX) increased overall survival (OS) compared with PTX alone for advanced gastric cancer (AGC) in second-line treatment. WJOG 4007 trial demonstrated equivalent efficacy between irinotecan (IRI) and PTX. We conducted this trial to examine the efficacy and safety of RAM plus IRI combination therapy in the second-line treatment for AGC. Methods: This non-randomized, single arm, phase 2 trial was carried out at 22 institutes in Japan. AGC patients with refractory or intolerance to primary chemotherapy were eligible. RAM 8 mg/kg and IRI 150 mg/m2 combination therapy administered every two weeks were continued until progression or emergence of adverse events requiring discontinuation. The primary endpoint was progression-free survival (PFS) rate at six-month, the target was set as 16% with an expected threshold of 39%. A total of 35 cases are planned for registration. The secondary endpoints were OS, PFS, response rate (RR) and safety. This trial was registered with Japan Registry of Clinical Trials, number jRCTs011180029. Results: Between Jan 2018 and Sept 2019, 35 patients were enrolled. Median age was 70 (range, 47-80); female/male were 10/25; ECOG PS 0/1, 22/13. PFS rate at six months was 26.5% (95%C.I., 13.2-41.8%, p = 0.1353). Median PFS and OS were 4.2 (95%C.I., 2.5-5.4 months) and 9.6 months (95%C.I., 6.5-16.6 months), respectively. RR was 26% and disease control rate was 85%. Grade 3 or higher adverse events that occurred in more than 5% of patients were neutropenia (51%), leucopenia (43%), anemia (20%), anorexia (14%), febrile neutropenia (11%), diarrhea (9%), hypertension (9%), proteinuria (9%), hypokalemia (9%), hypoalbuminemia (9%), thrombocytopenia (6%), and hyponatremia (6%). No death and new safety signals with a causal relation to study treatment were observed. Conclusions: Although the primary endpoint was not achieved statistically, the results are clinically encouraging, especially take into account that more elderly patients enrolled in this trial. The combination of RAM plus IRI has anti-cancer activity and manageable safety profile in second-line treatment for patients with AGC. Clinical trial information: jRCTs011180029.
Phase Ib trial of varlitinib plus weekly paclitaxel in EGFR/HER2 co-expressing advanced gastric cancer (AGC).
Authors: Sang Yunbeom , Jung Minkyu , Kim Hyo Song , Kang Beodeul , Lee Choong-kun , Chung Hyun Cheol , Rha Sun Young 
Published: January 2021

227 Background: EGFR and HER2 are over-expressed in gastric cancer, and activation of EGFR signaling in HER2-overexpressing gastric cancer can confer resistance to HER2-directed treatment like trastuzumab. Varlitinib (also known as ASLAN001) is a small-molecule, adenosine triphosphate competitive inhibitor of the tyrosine kinases - EGFR, HER2, and HER4. We present phase 1b results of the phase1b/2 study to evaluate the safety and efficacy of varlitinib in combination with weekly paclitaxel in EGFR/HER2 co-expressing AGC patients as a second-line treatment. (KCT0003583). Methods: An open-label phase Ib trial was conducted using a 3+3 design. AGC patients who had failed first-line fluoropyrimidine-containing chemotherapy, with evidence of both EGFR and HER2 overexpression by IHC (≥1+), were enrolled. The primary objective was to assess the dose limiting toxicity (DLT) and recommended phase 2 dose (RP2D) of varlitinib [Dose 1: 300 mg BID, Dose -1: 300mg intermittent dose] and weekly paclitaxel (80 mg/m2 D1,8,15) every 4 weeks along with evaluation of anti-tumor activity. Results: From July 2019 to May 2020, 9 patients were enrolled at Dose 1 level of varlitinib 300mg bid and 6 patients were evaluable for safety per protocol. Two patients did not finish DLT period: one patient withdrew after 1 week and one patient received palliative surgery for panperitonitis caused by gastric cancer metastasis. One patient had major violation in IP administration as the patient took varlitinib intermittently. Among the 6 evaluable patients, there was 1 DLT of G4 AST/ALT elevation and G3 hyperbilirubinemia, which resolved after 3 weeks. The most common treatment related adverse events (TRAEs) were neutropenia (n=5), all of which were grade ≥ 3, but no lasting more than 7 days. Grade 2 TRAEs included rash (n=2), mucositis (n=2) and peripheral sensory neuropathy (n=2). After a median follow-up of 3.0 (range, 1.9~ 6.2) months, the best responses were stable disease in 4 patients. Currently, 4 patients are ongoing. Conclusions: The combination of varlitinib 300mg bid and weekly paclitaxel 80mg showed manageable safety profiles and determined as RP2D. Currently, multi-site phase 2 part is now underway. Clinical trial information: KCT0003583.
Clinical and molecular characteristics of early-onset versus average-onset esophagogastric cancer.
Authors: Lumish Melissa Amy , Sabwa Shalom , Maron Steven Brad , Ku Geoffrey Yuyat , Ilson David H. , Won Elizabeth , Li Jia , Joshi Smita Suhas , Gu Ping , Strong Vivian E. , Molena Daniela , Jones David Randolph , Sihag Smita , Coit Daniel G. , Yoon Sam S. , Tang Laura H. , Hechtman Jaclyn Frances , Janjigian Yelena Y. , Cercek Andrea 
Published: January 2021

250 Background: While the rate of esophagogastric (EG) cancer is declining, early onset (EO) gastric cancer prior to age 50 is rising. It is unknown whether EO-EG cancer represents a distinct entity. This study investigates the clinical and molecular characteristics of EO compared with average onset (AO)-EG cancers. Methods: We reviewed clinical and molecular features of gastric (G), esophageal (E) and gastroesophageal junction (GEJ) cancer in patients treated at MSKCC between 2005 and 2018. We defined early onset as age < 49, based on the age cutoff for urgent endoscopy referral. Clinical symptoms at diagnosis, primary tumor location, histology, HER2 and MSI status and molecular alterations were compared using Fisher’s exact test. Benjamini-Hochberg method was used to decrease the false discovery rate. Results: We analyzed 738 pts with EG cancer (age < 49 n=151; age >50 n=587). Race and sex were different with more Asian (19% vs. 9%), fewer Caucasian (62% vs. 81%) ( P<0.001) and more female patients (40% vs. 29%, P=0.014) in the EO group. Time from symptom onset to diagnosis was longer in the EO group (median (IQR) 144 d (66-276) vs. 75 d (34-136), P=0.009), though stage did not differ ( P=0.49). Patients with EO-EG cancer had less weight loss ( P<0.001), but no other distinct presenting symptoms. Primary disease site was different with more gastric in the EO group (66% vs. 55%, P=0.04). Signet-ring histology was more common in the EO group (11% vs. 3%; P=0.0009). ERBB2 amp and MSI-H were similar, with a trend toward more MSI-H in the AO group (ERBB2 amp P=0.88, Q=0.830; MSI-H P=0.0157, Q=0.056). The most frequent somatic alterations were similar in EO vs. AO pts, including TP53 (68% vs. 70%, P=0.370, Q=0.825), CDH1 (15% vs. 11%, P=0.139, Q=0.825), RHOA (6% vs. 5%, P=0.395, Q=0.825). There was a trend toward more ARID1A (19% vs. 7%, P<0.01, Q=0.250) and FBWX7 (5% vs. 2%, P=139, Q=0.825) mutations in the AO group. Conclusions: Presenting symptoms, stage, histology, HER2 and MSI status are similar in patients with EO vs. AO-EG cancer. There is a trend in EO toward longer time to diagnosis, gastric primary site of disease, signet-ring histology and fewer ARID1A and FBWX7 mutations. Expanded clinical and molecular data will be presented. [Table: see text]
Cross-sectional adherence with the multitarget stool DNA test for colorectal cancer screening in a large, national study of insured patients.
Authors: Miller-Wilson Lesley-Ann , Finney Rutten Lila J , Van Thomme Jack , Ozbay Burak , Limburg Paul J. 
Published: January 2021

27 Background: Colorectal cancer (CRC) is the second most deadly and fourth most frequently diagnosed cancer in the United States. Early detection can improve CRC outcomes, but overall screening rates (62%) remain below the 80% goal set by the National Colorectal Cancer Roundtable. Multiple options are endorsed for average-risk CRC screening, including the multi-target stool DNA (mt-sDNA) test, which includes patient and provider navigation support. Cross-sectional adherence with the mt-sDNA test was previously reported in a large Medicare population (71%). In the current study we investigated cross-sectional adherence with the mt-sDNA test in a broader, national sample of insured patients. Methods: Aggregate data from Exact Sciences Laboratories LLC (ESL; Madison, WI) were retrospectively analyzed in compliance with HIPAA requirements. Study participants included individuals ages 50 years and older who were covered by commercial insurance or Medicare, had a valid mt-sDNA test order placed between January 1–December 31, 2018, and received a test kit shipped from ESL. Cross-sectional adherence, defined as successful completion and return of the test kit within 365 days of the shipment date, was assessed overall and by patient- and provider-level factors. Results: In total, 1,420,460 participants met the study criteria (61.2% women; mean age 65.7 years). Overall cross-sectional adherence was 66.8%. Adherence was 72.1% in participants with Traditional Medicare, 69.1% in participants with Medicare Advantage, and 61.9% in participants with commercial insurance (p<0.001). Adherence increased by participant age (p<0.001): 60.8% for ages 50-64, 71.3% for ages 65-75, and 74.7% for ages 76+ years. For Traditional Medicare patients, ages 65-75, adherence was 73.6%. Participants with mt-sDNA tests ordered placed by gastroenterologists had a higher adherence rate (78.3%) than those with orders placed by primary care clinicians (67.2%) (p<0.001). Adherence rates were highest among patients with ordering providers in the Pacific region (71.4%) and West North Central region (70.1%), and lowest in the Mid-Atlantic region (65.7%), New England (65.2%), West South Central region (64.6%), and Puerto Rico and US territories (60.7%). Conclusions: Novel data from this large, national sample of insured patients demonstrate high cross-sectional adherence with the mt-sDNA test (66.8%), supporting the substantial contribution this guideline-endorsed option plays in average-risk CRC screening. At the patient-level, adherence increased with patient age, and was highest in those covered by Traditional Medicare. Provider-level stratification showed the highest adherence for mt-sDNA tests ordered by gastroenterologists. This study adds to data regarding the impact of accompanying navigation support and at-home convenience of mt-sDNA on screening completion rates.
Longitudinal evaluation of quality of life (QoL) in patients (Pts) with FGFR2-driven cholangiocarcinoma (CCA) treated with pemigatinib.
Authors: Valle Juan W. , Bibeau Kristen , Cho Yohan , Ren Haobo , Féliz Luis , Lihou Christine Francis , Abou-Alfa Ghassan K. 
Published: January 2021

276 Background: CCA is associated with poor prognosis and reduced QoL. In the phase 2 FIGHT-202 study (NCT02924376) of the selective oral FGFR1–3 inhibitor pemigatinib, 35.5% and 46.7% of pts with previously treated advanced CCA and FGFR2 fusions/rearrangements (RE) had a complete or partial response (CR/PR) and stable disease (SD), respectively; 14.9% had progressive disease (PD) [Abou-Alfa et al., Lancet Oncology 2020;21:671-684]. QoL was an exploratory endpoint. Methods: Pts received pemigatinib 13.5 mg once daily (21-day cycle; 2 weeks on, 1 week off). QoL was assessed longitudinally by best overall response (BOR) per RECIST with the EORTC-QLQ-C30 and the biliary tract cancer-specific EORTC-QLQ-BIL21 questionnaires. QoL scores and longitudinal changes from baseline (BL) were analyzed using descriptive statistics. Treatment-related changes in QoL were a priori expected to be evident by cycle 6 day 1 (week 16). Results: Of 107 pts with FGFR2 RE, 100 (93%) were evaluable for QoL, including36, 48, and 15 with CR/PR, SD, and PD, respectively. From BL to week 16, QLQ-C30 overall health status was maintained in pts with CR/PR and SD and worsened in pts with PD (Table). Emotional functioning remained stable and similar in pts with CR/PR and SD but worsened in pts with PD. All subgroups showed decline in role and social functioning. Pts with CR/PR and SD experienced decreases in QLQ-BIL21 pain and anxiety; all subgroups showed increases in QLQ-BIL21 treatment side effects. Conclusions: In these pts with advanced CCA, those with an SD as BOR had a similar pattern of changes in QoL as those with CR/PR to pemigatinib. Changes in QoL were directionally more favorable in pts with CR/PR or SD than pts with PD. Clinical trial information: NCT02924376. [Table: see text]
The dose-optimisation of lenvatinb for patients with unresectable hepatocellular carcinoma in clinical practice: A retrospective analysis of real-world evidence in China.
Authors: Zhang Lan , Wang Yanhong , Ge Ningling , Gan Yu-Hong , Ren ZhengGang , Chen Yi ,   Liver Cancer Institute, Zhongshan Hospital, Fudan University
Published: January 2021

280 Background: Lenvatinib has become available as first-line therapy in patients with unresectable hepatocellular carcinoma (u-HCC). Although 8mg or 12mg/day is the standard starting dose according to weight, the high rate of adverse events (AEs) leading to dose reduction often limits its application. Various dosing schedules are used clinically to alleviate toxicities in practice. This study evaluated the safety and antitumor activity of two dosing strategies for lenvatinib administrations. Methods: Patients administered lenvatinib for u-HCC between April 2018 and July 2019 were enrolled. The dose-escalation strategy was conducted as follow, starting dose 4mg/day orally with biweekly escalation (As common AE always occurred within 2 weeks after administered), per 4 mg increment, to 8 or 12mg finally per body weight if no significant drug-related (no more than G2) adverse events occurred. Patients with a standard-dose strategy (8/12mg/day orally per body weight) were also included for comparison.Objective response rate(ORR) and progression-free survival (PFS) were assessed according to RECIST1.1 criteria. Dose-reduction rate was recorded and treatment-related adverse events (TRAE) was evaluated according to the CTCAE 5.0. Results: Totally 56 patients were included (37 in dose-escalation group and 19 in standard-dose group). The mean weight was 64.79±1.66 kg in dose-escalation group and 58.76±2.45 kg in standard-dose group, BCLC stage C proportion was 51.4% and 63.2%, Child-pugh B proportion was 16.2% and 5.3% respectively. Baseline demographic parameters were comparable between two groups (P>0.05). There was no significant difference in response rate (32.43% vs 42.1%, P=0.335), disease control rate (86.4% vs 84.2%, P=0.686) and PFS (P=0.631). The proportion of patients who reached the full dose (per weight) was also similar (48.6% vs 63.2%, p=0.399). Dose reduction rate was significantly higher in standard-dose group than dose-escalation group (36.8%vs 13.5%,p=0.044). Although, no difference in grade 3/4 adverse events was found between two groups (P=0.083), patients in standard-dose group(36.8%,7/19) have a higher incidence trend of G3/4 AEs than those of dose-escalation group(16.2%,6/37). Conclusions: The dose-escalation strategy may be an alternative approach to prolong lenvatinib treatment period, with comparable efficacy and more tolerance. More data are needed to confirm the long-term efficacy and safety of the dose-escalation strategy.