bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective clinical study of circulating tumor cells for colorectal cancer screening.
Authors: Tsai Wen-Sy , Nimgaonkar Ashish , Segurado Oscar , Chang Ying , Hsieh Ben , Shao Hung-Jen , Wu Jen-chia , Lai Jr-Ming , Javey Mana , Watson Drew , Mei Rui 
Published: January 2019

556 Background: Colorectal cancer (CRC) is among the most preventable cancers when precancerous lesions are detected at an early stage. Current screening methods for CRC require bowel prep or stool-based testing that are inconvenient, resulting in low compliance. Stool based tests have limited sensitivity for the detection of precancerous lesions. We have conducted a prospective clinical study over a period of > 3 years to assess a novel assay to detect and enumerate circulating tumor cells (CTCs) in a blood sample for early CRC detection. Methods: A single-center, IRB-approved, prospective and blinded clinical study was conducted in 620 subjects including 438 with adenoma, polyps or stage I-IV CRC and 182 healthy controls. For each subject, 2mL peripheral whole blood collected through a routine blood draw was processed using the CellMax biomimetic platform (CMx). The CMx test is a proprietary microfluidic biochip that minimizes non-specific binding and accurately enumerates CTCs. A multivariate analysis was performed to assess the clinical performance characteristics of the CMx test. Results: Disease status was evaluated by a standard clinical protocol which included colonoscopy and biopsy results. Probability of CRC risk was assessed by an age-adjusted regression model which correlated CTCs to clinical status. The CMx test’s overall accuracy was 88% for all stages of colorectal illness, including precancerous lesions. Conclusions: The study has demonstrated high accuracy for the detection of CRC using a novel CTC assay. It is the first study to show high sensitivity in the detection of precancerous colorectal lesions. The simple blood draw required can be easily integrated into a patient’s routine physical, increasing test compliance.[Table: see text]
Reverce: Randomized phase II study of regorafenib followed by cetuximab versus the reverse sequence for metastatic colorectal cancer patients previously treated with fluoropyrimidine, oxaliplatin, and irinotecan.
Authors: Shitara Kohei , Yamanaka Takeharu , Denda Tadamichi , Tsuji Yasushi , Shinozaki Katsunori , Komatsu Yoshito , Kobayashi Yoshimitsu , Furuse Junji , Okuda Hiroyuki , Asayama Masako , Akiyoshi Kohei , Kagawa Yoshinori , Kato Takeshi , Oki Eiji , Ando Takashi , Ohashi Yasuo , Yoshino Takayuki 
Published: January 2019

557 Background: The optimal treatment sequence in current standard care for patients (pts) with anti-EGFR antibodies-naïve metastatic colorectal cancer (mCRC) is cetuximab (C) followed by regorafenib (R). The objective of this randomized phase II trial is to evaluate efficacy and safety of the therapeutic sequence of R followed by C compared with that of C followed by R for mCRC pts. Methods: Pts with KRAS exon 2 wild-type mCRC after failure of fluoropyrimidine, oxaliplatin, and irinotecan were randomized to receive sequential treatment with R followed by C ± irinotecan (R-C arm) or reverse sequence (C ± irinotecan followed by R; C-R arm). The primary endpoint was OS. Key secondary endpoints included PFS with initial treatment (PFS1), PFS with second treatment (PFS2), safety, and QOL. The exploratory endpoint was serial biomarker analyses including oncogenic alterations from ctDNA or multiple serum proteins. Results: Between November 2013 and September 2016, 101 pts (51 in the R-C arm and 50 in the C-R arm) were randomized and eligible for efficacy analysis. Baseline characteristics were well-balanced in both arms. Bevacizumab had been previously administered in 96% and 98% pts in R-C and C-R, respectively. Sequential treatment was succeeded in 86% pts in both arms. After a median follow-up of 29.0 months with 81 death events, median OS in R-C and C-R were 17.4 and 11.6 months, respectively (stratified logrank P = 0.0293), with a hazard ratio (HR) of 0.61 for OS (95% CI, 0.39–0.96). HR for PFS1 (R in R-C versus C in C-R) was 0.97 (95% CI, 0.61–1.54), whereas that for PFS2 (C in R-C versus R in C-R) was 0.29 (95% CI, 0.17–0.50). No unexpected safety signals were observed in both arms. OS results in RAS/RAF wild type populations with ctDNA analysis at study entry (n = 86) were similar to those of overall population. Conclusions: This was the first randomized study to compare the two therapeutic sequences of R and C for mCRC, suggesting R followed by C is the preferred sequence. Comparable PFS1 and remarkable PFS2 improvement may lead to a longer OS in R-C sequence. The results of detailed biomarker analysis would be also reported. Clinical trial information: UMIN000011294.
Effect of physical activity trackers and daily text messages on quality-of-life in colorectal survivors (Smart Pace): A pilot randomized controlled trial.
Authors: Chan Hilary , Van Loon Katherine , Kenfield Stacey A. , Chan June M. , Mitchell Emily , Zhang Li , Paciorek Alan , Joseph Galen , Laffan Angela , Fukuoka Yoshimi , Miaskowski Christine , Meyerhardt Jeffrey A. , Venook Alan P. , Van Blarigan Erin 
Published: January 2019

559 Background: There are over 1.3 million colorectal cancer (CRC) survivors in the United States, and many of whom suffer from lower health-related quality-of-life (HRQoL) years after diagnosis and treatment. Physical activity may improve survival outcomes and HRQoL for CRC survivors. Feasible interventions to support physical activity after CRC diagnosis are needed. Methods: We conducted a two-arm randomized controlled trial of 41 men and women who had completed treatment for CRC. Participants in the intervention arm were given a Fitbit Flex™ and received daily text messages for 12 weeks. HRQoL was assessed in both arms at baseline and 12 weeks using the RAND Short Form Survey (SF-36) and the Functional Assessment of Cancer Therapy – Colorectal (FACT-C). Survey score changes from baseline to 12 weeks were compared between the two arms using independent t-tests, and scores at baseline and 12 weeks were compared using paired t-tests. SAS was used for analysis, and statistical significance was declared at p < 0.05. Results: We observed a statistically significant increase in the FACT-C functional well-being sub-scale in individuals in the intervention arm pre- and post- intervention (mean ∆ 1.81 ± 2.76; p: 0.02). There was no change in functional well-being in the control arm (mean ∆ -0.35 ± 4.12; p: 0.71). The between-arm comparison of change from baseline to 12 weeks was not statistically significantly ( p: 0.08). There was a statistically significant increase in the FACT-C emotional well-being sub-scale in the control arm (mean ∆ 1.20 ± 2.48; p: 0.04) and in the SF-36 role physical sub-scale in the control arm (mean ∆ 22.5 ± 38.8; p: 0.02). No other measures of HRQoL were statistically significantly different within groups, across time points, or between groups. Conclusions: A 12-week physical activity intervention using a Fitbit Flex™ and daily text messages may improve functional well-being among CRC survivors. Larger randomized studies are needed to definitively determine if a digital physical activity intervention improves functional well-being among CRC survivors, and if the improvement can be sustained over time. Clinical trial information: NCT02966054.
A phase Ib study of safety and clinical activity of atezolizumab (A) and cobimetinib (C) in patients (pts) with metastatic colorectal cancer (mCRC).
Authors: Bendell Johanna C. , Bang Yung-Jue , Chee Cheng Ean , Ryan David P. , McRee Autumn Jackson , Chow Laura Q. , Desai Jayesh , Wongchenko Matthew , Yan Yibing , Pitcher Bethany , Foster Paul , Cha Edward , Grossman William , Kim Tae Won 
Published: January 2019

560 Background: The majority of pts with mCRC have microsatellite stable (MSS) tumors with minimal response to PD-L1/PD-1 blockade. MEK inhibition upregulates tumor major histocompatibility complex-I expression, promotes intratumoral T-cell accumulation and improves anti–PD-L1 responses (Ebert, Immunity. 2016), supporting clinical evaluation of combined anti–PD-L1 (A) plus MEKi (C) in pts with mCRC. Methods: Pts with chemotherapy-refractory or locally advanced mCRC were evaluated. A was administered IV q2w at 800 mg. C was dosed PO daily at 20 to 60 mg during dose escalation and 60 mg during dose expansion (14/14 or 21/7 d on/off schedule). Primary endpoints were safety and tolerability. Investigator-assessed ORR and PFS by RECIST v1.1 and OS were secondary endpoints. Microsatellite instability (MSI) status was locally reported and centrally confirmed by NGS-based scoring. Results: As of May 10, 2017, 84 pts (57 KRASmt, 25 KRASwt, 2 unknown) were enrolled and evaluable. 66 pts had received 5+ prior therapies; 38 had known MSI status at baseline (MSS [n = 29], MSI-low [n = 8], MSI-H [n = 1]). A + C combination was tolerable. Treatment-related Gr 1-2 and Gr 3-4 AEs occurred at 60% and 37%, respectively. The most frequent related Gr 3-4 AEs were increased blood CPK, rash, diarrhea and fatigue (5% each). No treatment-related Gr 5 AEs occurred. 13% and 24% of pts experienced AEs leading to A and C withdrawal, respectively. Median follow-up was 14.3 mo (range, 0.5-29.8). Confirmed PR was observed in 7 pts (8%; locally reported MSS [n = 3], MSI-low [n = 1], MSI unknown [n = 3]). Median DOR was 14.8 mo (95% CI: 6.0, NE); DCR (PR + SD) was 31%. Median PFS was 1.9 mo (95% CI: 1.8, 2.3); median OS was 10.0 mo (95% CI: 6.2, 14.1). The 6-mo and 1-y OS rates were 65% (95% CI: 54, 76) and 46% (95% CI: 34, 58), respectively. Molecular determinants and immune biomarkers of response will be presented. Conclusions: A + C demonstrated a tolerable safety profile and improvements in OS vs those reported with SOC in heavily pretreated pts with mCRC. Objective responses observed in pts with MSS/MSI-low mCRC were durable, suggesting benefit of this novel combination in a pt population refractory to immune therapies. Clinical trial information: NCT01988896.
Second primary cancers and recurrence in patients after resection of colorectal cancer: An integrated analysis of trials by Japan Clinical Oncology Group: JCOG0205, JCOG0212, JCOG0404 (JCOG1702A).
Authors: Tanaka Kiyo , Ogawa Gakuto , Mizusawa Junki , Eba Junko , Katayama Hiroshi , Nakamura Kenichi , Shimada Yasuhiro , Hamaguchi Tetsuya , Moriya Yoshihiro , Fujita Shin , Kitano Seigo , Inomata Masafumi , Kanemitsu Yukihide , Fukuda Haruhiko 
Published: January 2019

561 Background: Improvements in early detection and treatment have resulted in an increasing number of long-term survivors of colorectal cancer (CRC). For the survivors, Second primary cancers and recurrence are important issues, but the evidence for appropriate surveillance strategy is limited. The aim of this study was to investigate the frequency and the timing of second primary cancers and recurrence in patients (pts) after surgery using 3 randomized trials (J0205, J0212 and J0404) conducted by Colorectal Cancer Study Group of JCOG. Methods: Eligibility criteria included histologically proven CRC and having received surgery. The timing, site and frequency of second primary cancer and recurrence were investigated. Risk factors associated with the events were explored. Standardized incidence ratio (SIR) about second primary cancer compared with national database of Japan Cancer Registry was estimated. Results: A total of 2,824 pts with a median follow-up time of 6 years were included. Median age was 62 years old (23-75), male/female was 58%/42%, and stage 0/I/II/III/IV was 0.2%/8.7%/25.4%/64.8%/0.9%. Pts with 5-FU based adjuvant chemotherapy were 63%. Cumulative incidence of second primary cancer increased constantly over time (Table). Among 240 pts, the most common site was lung (37), stomach (35) and colon (32). In multivariable analysis, age (over 64 years old) and sex (male) were risk factors (age HR: 1.60 (95% CI: 1.24-2.07), sex HR: 1.36 (95% CI: 1.04-1.78)). The SIR of any second primary cancers was 1.07 (95% CI: 0.94-1.21). The SIR for second primary cancers of colon was 1.09 (95% CI: 0.79-1.47). On the other hand, cumulative incidence of recurrence almost reached at 3 years. Conclusions: Common surveillance strategy can be applied even for curatively resected CRC pts after 3 years from surgery, because the risk of second primary cancer was almost same as general population over time. The necessity of intensive follow-up to detect recurrence decreases after 3 years. [Table: see text]
Tumor characteristics and treatment in early-onset colorectal cancer.
Authors: Burnett-Hartman Andrea , Powers John D. , Chubak Jessica , Corley Douglas , Ghai Nirupa R. , McMullen Carmit K. , Pawloski Pamala A. , Feiglelson Heather S. 
Published: January 2019

566 Background: While overall incidence and mortality of colorectal cancer (CRC) has declined, incidence and mortality are increasing in those < 50 years old (early-onset CRC). Our objective was to better understand early-onset CRC by comparing tumor characteristics and initial treatment type between early-onset and normal/late-onset CRC. Methods: We used health system and national tumor registries to identify patients diagnosed with adenocarcinoma of the colon or rectum from 2010-2014 at 6 US integrated health systems in the Patient Outcomes To Advance Learning (PORTAL) network. Tumor registry data included: age at diagnosis, stage, grade, anatomic site, histology, number of lymph nodes examined, and receipt of initial systemic therapy (chemotherapy or immunotherapy). Demographics and other patient characteristics were obtained from the EHR. We used logistic regression to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing the distribution of tumor characteristics and treatment patterns in early-onset ( < 50 years old) vs. normal/late-onset CRC. Results: There were 1,424 early-onset and 10,810 normal/late onset CRC cases in our analyses. Compared to normal/late onset cases, patients with early-onset CRC were more likely to be Hispanic, obese, never smokers, and to have Charlson comorbidity scores < 3. After adjustment for patient characteristics, compared to normal/late onset CRC, early-onset CRC was associated with more advanced stage disease (OR for stage 4 vs. stage 1 = 2.8, CI: 2.4-3.4), high grade histology (OR for poorly differentiated/undifferentiated vs. well/moderately differentiated = 1.2, CI: 1.1-1.5), signet ring histology (OR for signet ring vs. non-mucinous adenocarcinoma = 1.7, CI: 1.1, 2.6), and rectal (OR for rectum vs. cecum = 2.4, CI: 1.9-2.9) or left colon location (OR for left colon vs. cecum = 2.2, CI: 1.8-2.8). After adjustment for patient and tumor characteristics, early-onset patients were more likely than normal/late onset patients to have > 12 lymph nodes examined (OR = 1.6, CI: 1.4-1.8) and to receive systemic therapy (OR = 2.8, CI: 2.4, 3.4). Conclusions: Early-onset CRC is associated with aggressive tumor characteristics, distal location, and systemic therapy use.
Colorectal tumor patterns among adolescents, emerging adults, and young adults.
Authors: Holowatyj Andreana Natalie , Lewis Mark Andrew , Schmit Stephanie , Kirchhoff Anne C. , Figueiredo Jane , Ulrich Cornelia M 
Published: January 2019

567 Background: Despite overall reductions in colorectal cancer (CRC) incidence, this trend has shifted among young individuals. Incidence rates continue to rise in this population, yet causes remain unknown. We examined CRC tumor patterns within the adolescent, emerging adult, and young adult (AYA) population in the United States. Methods: Using Surveillance, Epidemiology, and End Results program data, we identified individuals aged 15 to 39 years diagnosed with CRC from 2010-2014. Unadjusted and adjusted multinomial logistic regression models were used to quantify the associations between age of onset [adolescents (15-18 years), emerging adults (19-25 years) and young adults (26-29, 30-34, 35-39 years)] and CRC tumor site and sidedness. Results: We identified 4,417 AYA patients (33 adolescents; 298 emerging adults; 4,086 young adults) with CRC over the 5-year study period. The percentage of cases diagnosed with colon cancer decreased across all AYA groups compared to rectal cancer cases ( P-trend=0.03). Age group was associated with sidedness ( P-trend=0.01). Individuals aged 26 to 29 years remained more likely to be diagnosed with right-sided (Odds ratio, OR=1.35, 95% CI 1.08-1.69, P=0.009) and high-grade (OR=1.29, 95% CI 1.02-1.64, P=0.03) colorectal tumors compared to counterparts aged 35 to 39 years, after adjusting for sex, race/ethnicity, stage, grade, and county-level poverty. Conclusions: CRC site and sidedness were associated with age at diagnosis within the AYA population. These data are the first to define clinical patterns of CRC among AYAs. Elucidating etiologies underlying these patterns in young-onset CRCs are needed for tailoring CRC screening/surveillance and treatment.
Diagnostic colonoscopy following abnormal FIT results: A quality improvement analysis.
Authors: Heavener Trace , Jaeger Victoria , Stephenson Kristen , McStay Frank , Sing Tommy 
Published: January 2019

568 Background: Published rates of colorectal cancer (CRC) screening with diagnostic colonoscopy after abnormal fecal immunochemical test (FIT) findings have varied substantially from 42% to 83% and median days to follow up colonoscopy have ranged from 41 to 184 days. Although data for lack of follow up exists for urban safety-net hospital systems, Veteran’s Affairs systems, and healthcare systems not located in the southern US to our knowledge no data exists for the Baylor Scott & White Health System (BSWH) which is the largest not-for-profit healthcare system in Texas. Methods: The initial retrospective chart review searched BSWH’s Central Texas division for whom a FIT was ordered during the following dates: June 1, 2014 to June 1, 2016. Eligible patients were between and including 50 and 75 years of age. The search results were manually screened by two resident Internal Medicine physicians. Results: The initial screen produced 232 patients with a positive FIT test. After excluding for testing reasons other than CRC screening, 94 patients were included in the final analysis. Most of those (70/94, 74.47%) received a gastroenterology clinic visit within one year, and most (62/94, 65.96%) received or were offered a colonoscopy. The most common reasons for not completing colonoscopy were patient no-show (14/32, 43.75%) and no documented reason (12/32, 37.5%). Of those receiving a colonoscopy at our institution, median time from positive FIT to colonoscopy was 64 days, a quarter (11/43, 25.58%) waited longer than 6 months, and 22/43 (51.16%) had an abnormal finding. The abnormal findings on colonoscopy included: 3/22 (13.64%) were dysplastic polyps, 13/22 (59.10%) were adenomatous polyps and 6/19 (31.58%) were hyperplastic polyps. Conclusions: Colonoscopy following an abnormal FIT is an important part of preventing and diagnosing CRC. Although fecal based screening tests are more convenient and affordable, it appears that poor follow up is not limited to government and indigent health systems. As one of the largest not-for-profit health systems in the nation, a 65.96% follow up colonoscopy rate after abnormal FIT testing leaves much room for improvement.
Comprehensive genomic profiling of ctDNA in patients with colon cancer and its fidelity to the genomics of the tumor biopsy.
Authors: Gregg Jeffrey P. , Li Gerald , Pavlick Dean , Chung Jon , Cooke Matthew , He Jie , Schrock Alexa Betzig , Lipson Doron , Forcier Brady , Clark Travis A , Nahas Michelle , Ali Siraj Mahamed , Stephens Phil , Miller Vincent A. 
Published: January 2019

569 Background: The liquid biopsy offers the ability to non-invasively analyze the genome of a tumor through circulating tumor (ct) DNA to identify targetable and prognostic genomic alterations. Few studies have rigorously analyzed ctDNA results and determined the fidelity with which they recapitulate the genomics of the tumor. The clinical utility study (CUS) for FoundationACT (Foundation Medicine, Cambridge, MA; NCT02620527) is a large multi-center prospective clinical study to validate this ctDNA assay for multiple solid tumor types. In this subset of the CUS study, paired specimens from 98 patients with colon cancer were analyzed with comprehensive genomic profiling of the tumor (FoundationOne) and a blood sample (FoundationACT). Methods: Maximum somatic allele fraction (MSAF) was used to estimate the fraction of ctDNA in the sample. The set of genes and targeted regions common to both FoundationOne and FoundationACT were compared for each subject. Results: 60% were male; 73 had stage IV, 17 had stage III, and 8 had stage II disease. 16% of cases had an MSAF value of 0, indicating that no ctDNA were in these samples. For the cases with MSAF > 0, 153 insertion/deletions (indels)/substitutions were identified in the tumor, and 73% of these identical alterations were also identified in the ctDNA samples. As robust analytical performance for FoundationACT has been demonstrated at MSAF > 0.5% for indel/subs, further analysis was conducted using this threshold. 83% of the alterations identified with FoundationOne were identified with FoundationACT. Further, 90% of NRAS/KRAS and 75% BRAF alterations (NCCN guideline genes) were concordant between the two assays. Lastly, there were 11 patients with tumor biopsy and blood draw taken within 30 days of each other, and in these there was 100% concordant. Association of the genomics results with other clinical variables will be presented for the available subset of patients. Conclusions: In cases where tumor profiling is not possible, these results provide compelling evidence that comprehensive molecular profiling of ctDNA in colon cancer can be used to identify most clinically relevant alterations and has fidelity to the genomics of the tumor. Clinical trial information: NCT02620527.