bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial disparity in gastrointestinal cancer: Insight from national cancer database.
Authors: Singh Maharaj , Datta Samit Kumar , Papenfuss Wesley Allan , Belini Geoffrey , Chevinsky Aaron , Weese James L. 
Published: January 2019

607 Background: The number of cases of cancers originating from the gastrointestinal (GI) tract and from other associated GI organs has increased 28% between the years 2004-2014. The incidence and overall survival for GI tract related cancers shows systematic racial disparity. Our goal was evaluate racial disparity for overall survival and mortality among patients with GI tract cancers. Methods: We used the national cancer database to evaluate data from 12 types of GI tract cancers (esophagus, stomach, gallbladder, intrahepatic bile duct, extrahepatic bile duct, liver, pancreas, small intestine, colon, rectosigmoid, rectum, and anal) between the years 2004-2014. The racial categories included non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic, and Other (All other races were combined into an ‘Other’ category). We used Kaplan-Meier estimator with log-rank test for comparing the survival probability among the four race categories. We also used Cox regression to find out the hazard ratio for mortality adjusting for the age, sex, and Charlson index. Results: The study population included a total of 2,044,565 patients diagnosed with one of the GI tract cancers. Of the total 55% were male, 72% NHW 12% NHB, 0.4% Hispanic, and the rest were classified as ‘other’ race (16%) which includes majority of white or black Hispanic and Asian (82%), The mean age at diagnosis of the patients was 66.8 ± 11.3 years. Overall survival was better for the Hispanic group, followed by the ‘Other’ group, NHW and NHB (P < 0.001). Adjusted for age, sex, and for Charlson index, the hazards ratio was 0.93 (95% CI, 0.90-096, p < 0.001) for Hispanic vs other, 1.15 (95% CI, 1.14-1.16, p < 0.001) for NHB vs other, 0.98 (95% CI, 0.97-0.98, p < 0.001) for NHW vs others. Mortality rate among Hispanic, NHW, NHB, and other was 46.4%, 59.4%, 59.6%, 56.7%. Conclusions: With a very large study population the survival for Hispanic patient population as well as the ‘Other’ (majority of patients were Asian) category had higher overall survival probability and low rate mortality compared to other race categories. Possible hypotheses include dietary preferences, underlying genetic profile and environmental factors. Further studies are needed to confirm the hypotheses.
CMS subtypes characterized by high TMB shows immunosuppressive microenvironment that implies resistance to immunotherapy.
Authors: Szeto Christopher , Garner Chad , Kazmierczak Kevin , Vaske Charles Joseph , Benz Stephen Charles , Reddy Sandeep K. 
Published: January 2019

610 Background: Tumor mutational burden (TMB) is emerging as an important biomarker for immune checkpoint therapy (ICT) response. Yet even in the context of high TMB, ICT are likely ineffective in an immuno-suppressed microenvironment. Here we demonstrate that a well-characterized subtype of CRC, CMS2, associated with Wnt pathway activation, is immunosuppressive despite high TMB. Methods: Tumor/normal-paired DNAseq (WGS or WES) and deep RNAseq (∼200x106reads per tumor) was performed on 464 GI tumors from a commercial database. Samples were classified as high TMB if they had > 200 non-synonymous exonic mutations as previously established (Rizvi et al, 2015). Each sample was assigned to one of the colorectal Consensus Molecular subtypes (CMS) based on RNA classification. A curated panel of 109 genes that discriminate between 22 immune subsets was identified. For each of these immune signatures, a database containing 1880 unselected tumors was used to define a distribution of expression. The study samples were then scored for their deviances within such distributions. Significant enrichment was analyzed between immune subsets, CMS types, TMB status, and somatic mutational status. Results: Compared to other subtypes, CMS1 & CMS2 were significantly high-TMB (adj. p < 3.8E-4 & p < 4.7E-3 respectively). Perplexingly, CMS2 had significantly lower expression of 11 well-established checkpoint and TME markers including LAG3 and PDL1 (adj. p 1.5E-2 & 2.9E-9 respectively), while CMS1 (MSI-enriched) expresses selected TME markers more than other subtypes (PDL1 adj. p < 4.0E-6 & LAG3 adj. p < 1.0E-6). As expected, CMS2 tumors were significantly enriched for likely pathogenic variants in the Wnt-associated gene APC (adj. p < 1.3E-8). Immune-deconvolution indicated substantial exclusion of Tem cells from CMS2 tumors, in line with Wnt/b-catenin blockade of TcmàTem maturation for immunoreactivity. Conclusions: The most common subtype of CRC, CMS2 (~37%), is highly immunosuppressive despite high TMB. ICT is only effective in an immunologically active microenvironment. TMB alone as a biomarker likely is insufficient to indicate the effectiveness of immunotherapy.
The impact of socioeconomic factors on outcomes of patients with locally advanced rectal cancer (LARC).
Authors: Gotfrit Joanna , Thangarasa Tharshika , Marginean Horia , Dudani Shaan , Goodwin Rachel Anne , Tang Patricia A. , Monzon Jose Gerard , Dennis Kristopher , Cheung Winson Y. , Vickers Michael M. 
Published: January 2019

612 Background: Patients with rectal cancer may experience disparities in outcomes due to various socioeconomic (SES) factors. We assessed the impact of SES factors on outcomes in patients with LARC who received neoadjuvant chemoradiation (nCRT) and surgery (Sx) in three Canadian provinces. Methods: Associations between clinical variables, demographics, community characteristics (2015 Canadian Census data), distance and time to the nearest cancer center (mapping software), and outcomes were evaluated. Results: 1,098 patients were included (Table 1). Median follow-up time was 67.8 months. The 5-year survival rate was 0.80 (95% CI 0.77-0.82). Factors predictive of disease-free survival in univariate analysis (UVA) included age, worse performance status (PS), driving time > 1 hour, median community income, and driving distance > 100 km. Factors that remained significant in multivariate analysis (MVA) included age (HR 1.01; 95% CI 1.00-1.02; p = 0.01), worse PS (HR 1.30; 95% CI 1.01-1.68; p = 0.04) and driving time > 1 hour (HR 1.31; 95% CI 1.01-1.71; p = 0.04). Factors predictive of overall survival in UVA included age, worse PS, driving time to the cancer centre > 1 hour, median community income, and community proportion with post-secondary education. Factors that remained significant in MVA included age (HR 1.03; 95% CI 1.02-1.04; p < 0.001), worse PS (HR 1.41; 95% CI 1.03-1.94; p = 0.03), and median community income (HR 1.00; 95% CI 1.00-1.00; p = 0.05). Conclusions: Outcomes of patients with LARC undergoing nCRT are significantly associated with driving time to the nearest cancer centre and community household income. Further efforts to understand and reduce these socioeconomic disparities are warranted. [Table: see text]
A randomized phase II study comparing oral S-1 plus 24-hour infusion of irinotecan (Iri) and bevacizumab (Bev) with FOLFIRI plus bevacizumab in patients with metastatic colorectal cancer (MCRC).
Authors: Sadahiro Sotaro , Suzuki Toshiyuki , Tanaka Akira , Okada Kazutake , Saito Gota , Miyakita Hiroshi , Ogimi Takashi , Chan Lin Fung 
Published: January 2019

613 Background: FOLFOX or FOLFIRI plus Bev is a first-line treatment for MCRC. Recent studies have confirmed that oral S-1 combined with Iri and Bev is equivalent to FOLFIRI plus Bev. Iri is usually administered as a short-term 90-min. infusion. However, the cytocidal activity is S-phase specific, and carboxylesterases, that convert Iri into SN-38, are less likely to become saturated when Iri is given as a long-term infusion. Therefore, a low dose of Iri given as a long-term infusion is expected to enhance antitumor activity. We conducted a randomized phase II study to compare this regimen with FOLFIRI plus Bev. Methods: The subjects comprised 120 chemotherapy-naïve patients with MCRC. The study group received 24-hr infusion of Iri at a dose of 125 mg/m2 on days 1 and 15, combined with oral S-1 80 mg/m2 on days 1 to 14. The FOLFIRI group received Iri at a dose of 150 mg/m2, 5-FU given at a dose of 400 mg/m2 as a bolus injection and at a dose of 2400 mg/m2 as a 46 hr-infusion, 200 mg/m2 of leucovorin on days 1 and 15. Bev was given at a dose of 5.0 mg/kg on days 1 and 15 in both groups. Treatment was repeated every 4 weeks. The primary endpoint was the 1 y progression-free survival (PFS). Secondary endpoints were PFS, response rates (RR), overall survival (OS), and adverse events (AEs). Results: From October 2013 through December 2017, a total of 61 patients assigned to receive IRIS plus Bev (the A group) and 59 patients assigned to receive FOLFIRI plus Bev (the B group) were included in the analysis. The 1y RFS was 37.3% in the A group and 17.0% in the B group (p = 0.0281). The PFS was 10.2 mon in the A group and 10.0 mon in the B group, and the median OS was 27.0 mon and 28.6 mon, respectively (p = 0.26, p = 0.68). RR was significantly higher in the A group (87.0%) than in the B group (61.7%) (p = 0.005). The main grade 3 or 4 AEs were neutropenia (27.8%) and diarrhea (11.1%) in the A group and neutropenia (23.4%) and leukopenia (6.4%) in the B group. Conclusions: Our results showed that Iri, given biweekly as a 24-hour infusion in combination with oral S-1 and Bev, is a highly effective and well-tolerated regimen for the first-line treatment of MCRC. Clinical trial information: UMIN000014664.
The combination of TAS-102 and bevacizumab as the third-line chemotherapy for metastatic colorectal cancer (TAS-CC3 Study).
Authors: Kosugi Chihiro , Kamiyama Hirohiko , Yoshida Yoichiro , Yoshida Hiroshi , Ishibashi Keiichiro , Ihara Keisuke , Takahashi Makoto , Kuramochi Hidekazu , Sonoda Hiromichi , Yoshimatsu Kazuhiko , Fukazawa Atsuko , Matsuda Akihisa , Yamaguchi Satoru , Ishida Hideyuki , Hasegawa Suguru , Yamada Takeshi , Narushima Kazuo , Shuto Kiyohiko , Sakamoto Kazuhiro , Koda Keiji 
Published: January 2019

614 Background: TAS-102 improved overall survival of metastatic colorectal cancer (mCRC) patients with median progression free survival (PFS) of 2.0 months (RECOURSE trial). Subsequently, the combination of TAS-102 and bevacizumab has been shown to extend median PFS with 3.7 months (C-TASK FORCE). However, this study included patients with 2nd line and 3rd line chemotherapy. Our study was planned exclusively for patients receiving this combination as a 3rd line chemotherapy to investigate clinical impact of this combination beyond cytotoxic doublet. Methods: This phase II study was conducted in investigator-initiated, open-label, single-arm, multicentered manner in Japan. Eligible patients were 20-80 years old, and had to have an ECOG performance status of 0 or 1; had confirmed unresectable mCRC with histologically diagnosed adenocarcinoma; were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in the 1st and the 2nd line chemotherapy. TAS-102 (35 mg/ m²) was given orally twice daily on days 1–5 and 8–12 in a 4-weeks cycle, and bevacizumab (5 mg/ kg) was administered by intravenous infusion for 30 minutes in every 2 weeks. The primary endpoint was progression free survival (PFS), and the secondary endpoints were time to treatment failure (TTF), response rate (RR), overall survival (OS), and safety. Results: Between June 2016 and August 2017, 32 pts were enrolled. The median PFS was 4.5 months, and the median OS was 9.3 months. Partial response was observed in 2 patients. The most common adverse events above grade 3 were neutropenia (15 patients) followed by thrombocytopenia (4 patients). Treatment-related serious adverse events were reported in 1 patient. There were no non-hematologic adverse events above grade 3. No treatment-related deaths occurred. Conclusions: This is the first study which involves the combination TAS-102 and bevacizumab as the 3rd line chemotherapy in the setting beyond cytotoxic doublet for the patients with mCRC. This study met its primary endpoint PFS, which is comparable to the results of C-TASK FORCE study. This combination has a potential to be one of therapeutic options of the 3rd line chemotherapy for mCRC. Clinical trial information: 000022438.
Timing of first surveillance colonoscopy in stage I colon cancer patients and the association with colon cancer-specific survival.
Authors: Hines Robert Brooks , Jiban Md Jibanul Haque , Specogna Adrian V. , Vishnubhotla Priya , Lee Eunkyung , Troy Steven , Zhang Shunpu 
Published: January 2019

618 Background: Surveillance colonoscopy following curative surgery in stage I colon cancer patients is controversial. This study was conducted to assess the relationship between timing of first surveillance colonoscopy and 5-year colon cancer-specific survival. Methods: This was a retrospective cohort study of the Surveillance, Epidemiology, and End Results database combined with Medicare claims. Stage I colon cancer patients (66-84 years of age) were categorized according to receipt of first colonoscopy following cancer-directed surgery as: Year 1, Year 2, Year 3, and No Colonoscopy within 3 years of surgery. Propensity score weighting was used to balance covariates. Cox regression was used to obtain hazard ratios for the relative risk of 5-year colon cancer-specific death, adjusted survival estimates, and the number needed to treat (NNT) with colonoscopy in Year 1 to prevent a colon cancer-specific death in the other groups. Results: There were 8,494 stage I colon cancer patients available for analysis. Regarding 5-year colon cancer-specific mortality, compared to Year 1 patients, the No Colonoscopy group experienced 2.2 times the risk of colon cancer-specific death (HR, 2.23; 95% CI, 1.38 to 3.61). Those who received ≥ 1 additional colonoscopies in the two years following their initial assessment experienced a significant 73% decreased risk of death (HR, 0.27; 95% CI, 0.16 to 0.45). Delaying colonoscopy (Years 2 & 3) did not result in a statistically significant increased risk of death. Although the absolute difference in 5-year adjusted survival was small, if all patients in the No Colonoscopy group received a colonoscopy in Year 1, 46.2% (n = 49.9) of the 108 colon cancer deaths that occurred in this group could have been prevented. Conclusions: Although stage I colon cancer patients have a good prognosis, patients who received colonoscopy within one year of cancer-directed surgery experienced significantly better survival than patients who did not receive colonoscopy within 3 years of surgery. The results of this study justify efforts to ensure that stage I colon cancer patients receive colonoscopic surveillance testing approximately 1 year following cancer-directed surgery.
Trends in radiation dose and technique for anal canal squamous cell carcinoma.
Authors: Abel Stephen , White Richard , Hasan Shaakir , Finley Gene Grant , Monga Dulabh K. , Raj Moses S. , Kirichenko Alexander V. , McCormick James , Wegner Rodney E 
Published: January 2019

621 Background: Anal canal squamous cell carcinoma (SCC) is managed definitively with chemo and XRT, reserving surgery for salvage. Many different radiation dose schemes have been used, varying from 30 Gy to doses exceeding 60 Gy. RTOG 0529 established IMRT as a standard of care for anal canal SCC, using doses of 50.4-54 Gy. We used the National Cancer Database(NCDB) to examine trends in dose selection and radiation technique over time, as well as any potential effect on outcome. Methods: We queried the NCDB from 2004-2015 for cases of anal canal SCC stage 1-3, treated with definitive doses of XRT to the pelvis with chemo. Dose escalation was defined as > 54 Gy. Univariable and multivariable analyses were performed to identify factors predictive of increased dose and overall survival (OS). Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias. Results: We identified 7,792 patients meeting the eligibility criteria, with 4,269 treated to conventional doses and 3,163 treated to > 54 Gy. Patients that were older, had government or private insurance, were treated with IMRT, or at an academic center in a more recent year were less likely to get dose escalation. Increasing T and N stage were predictive of escalated dose. The use of dose escalation decreased over time, from 50% in 2005 to 30% in 2015. In contrast, IMRT use increased over that time from 2% to 63%. On multivariable analysis increasing age, higher comorbidity score, treatment at an academic center, and increasing stage corresponded to worse OS. Increased income, private insurance, IMRT use, increased distance to facility, and female gender all predicted improved OS. Multivariable analysis with propensity score included confirmed increased age, higher comorbidity score, income, distance, and gender as predictive of OS. In addition, escalated dose was found to have inferior outcome (OR: 1.10 95%CI: 1.01-1.20, p = 0.03). Conclusions: The results of this NCDB analysis show a steady increase in the use of IMRT over time, with a corresponding decrease in dose escalation. In this study, dose escalation was shown to have inferior outcomes, although that result is likely influenced by the increasing age, stage, and comorbidity scores in that group of patients.
Squamous cell carcinoma of the rectum: Practice trends and patient survival.
Authors: Dutta Sunil W , Alonso Clayton E , Waddle Mark Raymond , Khandelwal Shiv R. , Janowski Einsley-Marie , Trifiletti Daniel Michael 
Published: January 2019

625 Background: Leverage the National Cancer Database (NCDB) to evaluate trends in management of squamous cell cancer (SCC) of the rectum and their effect on survival for this uncommon tumor. Methods: Data was obtained from the NCDB for patients diagnosed with SCC of the rectum between 2004 and 2014, including cT1-4, cN0-2, cM0 (cohort A, n = 2,296) tumors. A subgroup analysis was performed on locally advanced tumors (cT1-T2, N+ or cT3, N any, subcohort B, n = 883), treated with chemoradiation (n = 706) or trimodality therapy (n = 177) including chemotherapy, radiation, and surgery. Pathological complete response rate following neoadjuvant therapy was obtained. Univariate and multivariate logistic regression analyses were performed to generate hazard ratios (HR) investigating factors associated with overall survival. Kaplan-Meier (K-M) method was used to estimate overall surviving proportion at 5 and 10 years. Results: The median age was 60 years with a strong female predilection (71% female). Among patients treated with neoadjuvant therapy, 36% achieved a complete pathological response at a median interval of 67 days from completion of radiation therapy to surgery. The K-M estimated 5 and 10 year overall survival for stage I disease was 71.3% and 57.8%, respectively; stage II disease was 57.0% and 38.9%, respectively; stage III disease was 57.8% and 41.5%, respectively. On multivariate analysis, increased age, male gender, more co-morbidities, and higher cT category ( P < 0.001 for each) resulted in worse survival. For locally advanced tumors (subcohort B), there was no difference in survival between chemoradiation alone compared to trimodality therapy ( P = 0.909 on multivariate analysis). Conclusions: Most providers manage locally advanced SCC of the rectum similar to anal cancer, which results in equivalent overall survival and spares patients from the additional morbidity associated with surgical resection. [Table: see text]
Benefit of adjuvant chemotherapy in patients with high-risk UICC II colon cancer T4N0M0: A ten-year population-based analysis of 3544 cases.
Authors: Teufel Andreas , Fürst Alois , Gerken Michael , Hohenthanner Ina , Klinkhammer-Schalke Monika 
Published: January 2019

628 Background: The benefit of adjuvant chemotherapy in UICC stage III colon carcinoma has been demonstrated in numerous studies. For UICC stage II such an advantage was not shown. However, it remains controversial whether adjuvant chemotherapy might be considered in certain high-risk UICC stage II situations. High-risk factors include T4 tumors, associated with an increased risk of recurrence and poorer prognosis due to their more aggressive biological behavior. Methods: The present population-based, multicenter cohort study investigated the influence of adjuvant chemotherapy on survival and recurrence rates in UICC stage II in the high-risk situation T4N0M0. It is based on an anonymized nationwide ADT dataset and includes 208,030 patients diagnosed with colorectal cancer from 2002 to 2011. A total of 3544 patients with a T4 tumor were identified, of whom 34.3% (1215 patients) received adjuvant chemotherapy and 65.7% (2329 patients) none. Results: Median overall survival was markedly prolonged in subjects who received adjuvant chemotherapy from 4.5 years (SD 0.163, 95% CI 4.1-4.8) to 8.1 years (SD 0.474, 95% CI 7.2 -9.0; p < .001). After 5 years, 69.5% of chemotherapy patients were still alive compared to 45.1% of non-chemotherapy patients. After adjusting for factors in a multivariable Cox regression analysis, the significant benefit of adjuvant chemotherapy for overall survival was maintained (HR = 0.642, 95% CI 0.555-0.743, p < .001). The relative cumulative risk of recurrence in the multivariable analysis was HR = 0.696 (95% CI 0.580-0.843, p < .001) for chemotherapy patients. Furthermore, a highly significant improvement in relapse-free survival through chemotherapy was demonstrated (HR = 0.634, 95% CI 0.555-0.725, p < .001). Conclusions: In this representative study, a significant advantage of adjuvant chemotherapy for UICC stage II colon carcinoma patients with a T4 tumor was demonstrated in terms of overall survival, recurrence rate and relapse-free survival. On the basis of these results, adjuvant chemotherapy is recommended for the high-risk situation T4.