bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment strategy for metastatic colorectal cancer (mCRC) treated with chemotherapy plus biological targeted agent: Is strategy with biological targeted agent based on the primary tumor lesion possible?
Authors: Sagawa Tamotsu , Hamaguchi Kyoko , Uemura Naomi , Tamura Fumito , Fujikawa Koshi , Sato Yasushi , Takahashi Yasuo 
Published: January 2019

769 Background: The data from randomized trials suggested that primary tumor location (PTL) could represent a prognostic and predictive factor in mCRC patients, particularly during treatment with anti- EGFR therapy. However, it remains unclear whether anti-EGFR is effective for right- sided primary tumors (RT). Methods: Single-institution, retrospective, case-control study was reviewed. A total of 110 patients with mCRC were enrolled between January 2011 and December 2016. We evaluated the association between PTL and survival parameters in patients with previously untreated mCRC receiving first-line chemotherapy (FOLFOX/CapeOX or FOLFIRI/IRIS) plus cetuximab(Cmab) or bevacizumab(Bmab). The impact of PTL for Cmab and Bmab groups was analyzed, respectively. Results: 76 patients presented Left-sided primary tumors (LT) and 34 patients RT. Median PFS, median OS, and ORR were numerically superior in our study patients with LT compared with patients with RT (PFS, L vs R, 13.0 vs 6.8 M, p = 0.0040; OS, 36.2 vs 19.0 M, p = 0.002; ORR, 67.1 vs 44.1 %, p = 0.022951). In the Cmab group, LT were significantly superior to RT in terms of OS (L vs R, 56.3 vs11.3 M, p = 0.0057). Likewise, in the Bmab group, OS showed differences between the LT and RT (L vs R, 27.8 vs 19.7 M, p = 0.0116). In LT, Cmab group were significantly superior to Bmab group in terms of the OS (C vs B, 56.3 vs 27.8 M p = 0.0428). Conversely, in RT, the survival times showed no differences between Cmab and Bmab group (C vs B, 11.3 vs 19.7 M, p = 0.6555). Furthermore, while early tumor shrinkage(ETS) was associated with favorable outcome in patients with RT who treated Cmab, non-ETS represented a less favorable survival (ETS vs non-ETS, NR vs 11.3 M, p = 0.0335). ETS was a predictor for survival benefit acquired from Cmab treatment for patients with RT with wild-type KRAS/RAS tumors. Conclusions: Our study suggests the conclusion that patients with LT with KRAS/RAS wild-type should be preferentially treated with Cmab. By contrast, in RT, chemotherapy plus Bmab may be effective, but optimal treatment has yet to be defined and ETS may be able to predictive of benefit acquired from Cmab.
Prevalence and correlates of critical malnutrition (CMN) among gastrointestinal (GI) and non-GI participants in phase I/II (P1/2) clinical trials.
Authors: Jain Rishi , Handorf Elizabeth , Khare Vipin , Blau Matthew , Chertock Yana , Clinton Steven K. , Hall Michael J. 
Published: January 2019

770 Background: Patients (pts) with cancer, in particular GI malignancies, are vulnerable to CMN from both tumor-related digestive symptoms and treatment-related toxicity (TRT). CMN is associated with poor cancer outcomes, including reduced quality of life, poor treatment tolerance and decreased survival. P1/2 trial participants are not routinely screened for CMN or potentially associated psychological and physical activity impairments. Methods: Baseline assessments of nutrition (PG-SGA), distress (NCCN-DT), anxiety (HADS-A), depression (HADS-D), and sedentary lifestyle (SL, Godin-LTQ) were conducted in pts beginning a P1/2 trial. CMN was defined as a PG-SGA score of ≥9. Statistical significance was determined by Fisher’s exact test. A regression model was used to identify a composite predictor of CMN. Results: 100 pts (87% P1, 13% P2) were enrolled. Results of assessments are shown in Table 1. 39% of pts had CMN and 52% had a SL. CMN was more common in non-whites (p = 0.05) and those on P1 trials (p = 0.073). No differences were noted by age, gender, or prior lines of therapy. CMN was strongly associated with depression (p < 0.001) and SL (p < 0.001). 31 pts had GI malignancies [CRC (15), pancreas (8), and other (8)]. CMN was more prevalent in GI pts than non-GI (61% vs 29%, p = 0.004). When evaluating the predictive value of commonly used clinical indicators for CMN such as BMI ( < 25), weight loss (WL) past 2 weeks, or WL past month, having 2/3 of these indicators was the optimal cut-point predictor of CMN (76% sensitivity, 85% specificity). TRT data collection is ongoing. Conclusions: CMN and SL are highly prevalent in P1/2 trial pts, particularly in those with GI cancers and minorities. CMN is strongly associated with depression and SL. A composite clinical indicator (BMI + WL) may be most useful in screening for CMN. Urgent nutritional interventions in these participants may be warranted in light of magnified mortality and toxicity risks. [Table: see text]
Neoadjuvant chemotherapy and high dose intensity modulated radiotherapy followed by rectal sparing TEM for distal rectal cancer.
Authors: Parikh Kinjal , DeNittis Albert S. , Marks Gerald J. , Zeger Erik L. , Cho David , Marks John 
Published: January 2019

771 Background: For distal rectal tumors, abdominoperineal resection (APR) may achieve a complete resection; however is associated with significant morbidity. Full thickness local excision (FTLE) via transanal endoscopic microsurgery (TEM) may provide disease control with fewer complications. Additionally, Intensity Modulated Radiation Therapy (IMRT) may minimize toxicity by limiting small bowel exposure to radiation. We report on 14 years of prospective data from Lankenau Medical Center for distal rectal cancer pts treated with neoadjuvant chemotherapy and high dose IMRT followed by FTLE via TEM. Methods: From 2002 to 2016, 44 pts were treated for cT1(n = 4), cT2 (n = 24), cT3 (n = 16), N0, M0 distal rectal cancer using IMRT at 5580 cGy along with concurrent 5FU-based chemotherapy, followed by FTLE. Local recurrence (LR), disease free survival (DFS) and overall survival (OS) was reported using Kaplan-Meier survival analysis. Results: At the time of FTLE complete pathological response was achieved in 18 pts, good response in 25 pts, and 1 pt with poor response. Median time to follow-up is 58 months. 3 of 44 pts (6.8%) had isolated local recurrence, all achieving local control with surgical salvage. Mean DFS is 10.68 years (95% CI 8.77 to 12.60). Mean OS is 11.78 years (95% CI 9.99 to 12.58). 34 pts (77%) are currently alive with NED. 6 pts developed metastatic disease, 5 of whom died, and one who was surgically salvaged. 5 pts died from causes outside of their malignancy. In adjusted analysis, DFS was strongly associated with pathologic response to chemoradiotherapy (p = 0.025). Post-operative Grade I-II complications noted in 17 pts, all managed with conservative measures; Grade III occurred in 2 pts. No pts required a diverting colostomy. Conclusions: Neoadjuvant high dose IMRT and chemotherapy followed by FTLE to treat distal rectal cancers is well tolerated and effective. Local excision surgery may provide excellent tumor control and improved quality of life in appropriately selected pts. A randomized clinical trial is needed to compare it to standard surgery. Also a dose escalation study with IMRT may allow for improvement in pathologic response without increasing toxicity.
Randomized phase II trial of CapOX plus bevacizumab versus CapIRI plus bevacizumab as first-line treatment in Japanese patients with metastatic colorectal cancer (CCOG-1201).
Authors: Sasahara Masahiro , Nakayama Goro , Ishigure Kiyoshi , Yokoyama Hiroyuki , Uehara Keisuke , Ishiyama Akiharu , Matsui Takanori , Nakayama Hiroshi , Kobayashi Daisuke , Umeda Shinichi , Sunagawa Yuki , Murotani Kenta , Ando Yuichi , Kodera Yasuhiro 
Published: January 2019

781 Background: The aim of this randomized, multicenter, non-comparative phase II trial was to investigate the efficacy and safety of capecitabine/oxaliplatin (CapOX) plus bevacizumab (BEV) and capecitabine/irinotecan (CapIRI) plus BEV as a first-line treatment in Japanese patients with metastatic colorectal cancer (mCRC). Methods: Patients with untreated mCRC were randomly assigned to the following treatment arms; CapOX/BEV arm (bevacizumab 7.5mg/kg and oxaliplatin 130 mg/m2 on day 1, and oral capecitabine 1000 mg/m2 bid on day 1-14, every 3 weeks) and CapIRI/BEV arm (bevacizumab 7.5mg/kg and irinotecan 200 mg/m2 on day 1, and capecitabine 800 mg/m2 bid on day 1-14, every 3 weeks). The primary endpoint was overall response rate (ORR), and secondary end points included progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 107 patients were enrolled. The intent-to-treat population comprised 52 patients in CapOX/BEV arm and 51 patients in CapIRI/BEV arm. The ORR was 58% in CapOX/BEV arm and 57% in CapIRI/BEV arm ( p= 0.545). The median tumor shrinkage rate (DpR) was 36.0% (range, -24.0 to 100%) and 36.7% (range, -26.0 to 100%), respectively (p = 0.399). Median PFS was 12.4 months (95% confidence interval [CI], 10.6–14.3 months) in CapOX/BEV arm and 11.5 months (95% CI, 9.6–13.4 months) in CapIRI/BEV arm (hazard ratio [HR], 1.145; 95% CI, 0.760–1.725; p= 0.517). The median OS was 26.6 months (95% CI, 21.5–31.8 months) and 28.7 months (95% CI, 19.6–37.9), respectively (HR, 1.206; 95% CI, 0.0.733–1.907; p= 0.461). The frequency of hematological and non-hematological adverse events (≥grade3) were 10% and 27% in CapOX/BEV arm, and 16% and 27% in CapIRI/BEV arm, respectively. Conclusions: Both regimens, CapOX plus BEV and CapIRI plus BEV, could be equally feasible first-line treatment for Japanese patients with mCRC. Clinical trial information: UMIN_000007545.
Impact of age and frailty on survival in older adults with squamous cell carcinoma of the anus.
Authors: Yokom Daniel , Alibhai Shabbir M.H. , Puts Martine , Brierley James D. , Kim John , Krzyzanowska Monika K. 
Published: January 2019

786 Background: Patients with anal cancer (AC) can achieve long-term disease control with chemoradiation (CRT), however, the treatment has serious adverse effects. Most patients with AC are ≥65 but little is known about cancer outcomes in this population. Frailty measures have been proposed to determine the risk of treating older adults. The purpose of this study was to evaluate the impact of age and frailty on outcomes in patients with AC. Methods: A retrospective review was performed of patients age ≥65 with non-metastatic AC treated from 2007-2016 at Princess Margaret Cancer Centre. A 44-item Cumulative Deficit Score was constructed to quantify frailty as per the Rockwood model. The impact of age and frailty on treatment toxicity and overall survival (OS) was analyzed using multivariable logistic regression and survival models, respectively, adjusting for ECOG performance status (PS), stage and treatment modality. Results: Among 92 patients, median age was 72 and 42.4% were age ≥75. Seventy (76.1%) patients were treated with CRT and 17 with radical radiotherapy (RT). After a median follow-up of 34.9 mo (range 0.5-103.9) 34 patients died – 16 from metastatic AC, 16 from other or unknown causes, and 2 treatment-related deaths. For patients treated with CRT or RT (N = 87), 53 (60.9%) required treatment modification due to toxicity. Twenty patients (22.9%) had an emergency room visit or hospitalization. Frailty did not significantly increase the risk of toxicity in multivariable analysis (OR 1.9, 95% CI 0.35-10.8). Treatment with CRT increased the risk of toxicity compared to RT alone (OR 9.5, 95% CI 1.7-53.8). Patients ≥75 had shorter OS on univariable analysis (HR 1.9, 95% CI 1.0-3.8) but not on multivariable modeling (HR 1.5, 95% CI 0.72-3.4). Factors associated with shorter OS were increased frailty (HR 3.8 CI 1.4-10.2) and ECOG ≥2 (HR 3.9, 95% CI 1.7-9.1). There was good discrimination of the model with a C-statistic of 0.77. Conclusions: Older adults with AC experience a high rate of treatment toxicity especially with CRT relative to RT alone. OS was significantly associated with frailty as well as PS but not age. Frailty assessment may improve treatment planning and understanding survival for older patients with AC.
Potential drug cost impact of nivolumab (N) in Canada in patients with DNA mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC).
Authors: Virik Kiran , Biagi James Joseph , Wilson Robert B 
Published: January 2019

797 Background: The overall 5 year survival for mCRC remains poor (14%) despite the sequential use of chemotherapy and biologic agents. Immunotherapy is a promising treatment option in tumors with a high mutational burden. This includes mCRC DNA mismatch repair deficient tumors (dMMR). These have upregulation of immune checkpoints and a poorer prognosis. The CheckMate 142 phase II trial in pretreated dMMR mCRC patients showed durable responses and disease control across a number of subgroups including BRAF mutant tumors. The use of immunotherapy has an anticipated budgetary impact on health care systems within the context of this potentially funded utilization of N. Methods: An estimation of the N drug cost alone for new cases diagnosed in 2017 and treated upon relapse in Canada was undertaken. A cost estimate for N treatment in the first line of dMMR mCRC in relapses and de novo was undertaken should this be a future option. N cost per patient was calculated based on treatment indication, median number of cycles, standard dose/schedule. The analysis was performed in Canadian dollars ($) and assumed complete drug delivery and uncomplicated cycles. The cost of N was obtained from the pan Canadian Oncology Drug Review (pCODR) cost for N in lung cancer. The number of target patients and N utilization was derived from constructed schema to give a budget impact estimate. Results: Estimated N cost per treated patient is $91,667. The N drug cost for prior second line and third line relapsed chemotherapy treated patients respectively ranges from $23.6 Million (M) – $36.4M and $12.7M – $17.7M. For 1st line N: the cost of treating early stage dMMR CRC which subsequently recurs would be $49.1M and the cost for treatment of dMMR de novo mCRC would be $24.6M. A sensitivity analysis was performed. Conclusions: Immunotherapy drug costs in dMMR mCRC potentially add a substantial cost burden to the publicly funded Canadian healthcare system. As data evolves, longer duration of therapy and potential first line use will add further to the estimated budgetary impact.
Cardio-respiratory fitness and functional performance in patients with a recent diagnosis of colorectal cancer.
Authors: Alvarez-Bustos Alejandro , Gutierrez Sanz Lourdes Gutierrez , Nuñez García Beatriz , Soriano Maria , Fiuza-Luces Carmen , Ramos Javier , Sen Jorge D. , Sánchez-Ruiz Antonio Carlos , Gomez-Bravo Raquel , De La Puente Blanca , Lucia Alejandro , Ruiz-Casado Ana 
Published: January 2019

804 Background: Physical capability describes the ability to do the physical tasks of everyday living. Oncologists usually evaluate physical capability through anamnesis generating a performance status (PS) score. Some authors have proposed the use of cardiorespiratory reserve, muscular strength and objective evaluation of physical activity to avoid the subjective, unreliable and non-reproducible condition of PS. Methods: Patients with a recent diagnosis of colorectal cancer who accepted to participate were evaluated at the hospital setting. Walking speed was evaluated through both one-mile walk test and six-minute walk test. VO2max was calculated through the Kilne formula. Muscular strength was measured through dynamometry (hand-grip) and “sit to stand” test. Physical activity was objectively evaluated with accelerometers. Fatigue was evaluated through the PERFORM questionnaire (12-60). ECOG was evaluated by the medical oncologist. Results: 100 pats were recruited between March 15 and Jul 17. ECOG O/1/2 (80/14/2). 40 (40 %) were metastatic. Mean age 66 (25-81), Sex M/F; 68/32. Conclusions: Objective evaluation of physical condition is feasible at the hospital setting. There were no differences in BMI, heart rate, fatigue, muscular strength and objective functional performance (weekly PA) between localized and metastatic CRC. In metastatic pts with an excellent ECOG-PS the time to walk one mile and the estimated VO2max could be more sensitive than ECOG to evaluate the functional capacity impairment. In pts with cancer the One- mile walk test could be superior to the Six-minute walk to estimate the cardiorespiratory fitness. The objective evaluation of physical condition is a useful additional tool to select pts for aggressive therapies. [Table: see text]
Metastatic colorectal cancer (mCRC) treatment patterns in the Medicare population.
Authors: Snider Jeremy , Wang Ed , Anderson Sibyl , Steelquist Jordan , Warnick Greg S , Fedorenko Catherine R. , Shankaran Veena , Ramsey Scott David 
Published: January 2019

823 Background: Few studies have examined how patterns of care relate to clinical consensus guidelines for metastatic colorectal cancer (mCRC) in real-world settings. This study investigated treatment patterns around systemic therapies for older mCRC patients using SEER-Medicare data. Methods: We utilized data from a linkage of national Medicare claims data with records from the 12 Surveillance, Epidemiology, and End Results (SEER) regions for patients diagnosed with stage IV CRC between 2011 and 2014. Other inclusion criteria included adenocarcinoma histology, being > 65 years of age, and continuous Part A/B enrollment 12 months prior to diagnosis. We conducted bivariate analysis and multivariate modeling to evaluate the association between age, race, gender, SEER region, and comorbidity score with receipt of systemic therapy. We examined first and subsequent lines of therapy, and classified them as adherent or non-adherent to NCCN guidelines. Results: Of 102,461 CRC patients, 6,360 (6.2%) patients had evidence of metastatic disease and met all inclusion criteria. 3,155 (49.6%) received no systemic therapy. Of the 2,976 (46.8%) who received systemic therapy with identifiable regimens, FOLFOX/CAPOX was the most common 1L regimen (32.9%), followed by 5-FU or capecitabine alone (26.4%) – both identified as guideline-adherent therapies. Non-guideline adherent regimens (such as use of single-agent oxaliplatin or bevacizumab) were uncommon as 1L therapies (1.4%). 1,553 patients (52.2%) progressed to a 2L therapy, 715 (24.0%) progressed to a 3L therapy, and 320 (10.8%) to a 4L therapy. A large proportion of 2L (26.9%) and 3L (24.2%) treatments contained bevacizumab. 96 patients (3.2%) received regorafenib, representing 6.7% of 3L and 10.6% of 4L therapies. Patients who did not receive systemic therapy were older (mean age of 80.8 vs 74.9) and had multiple comorbidities (63.1% vs 48.4% with Klabunde score > 1). Conclusions: In a Medicare-insured mCRC cohort, patients generally received systemic therapy adhering to consensus guidelines. However, many patients did not receive systemic therapy – suggesting there may be delays in diagnosis and barriers to treatment which lower systemic therapy utilization.
Nivolumab versus nivolumab with ipilimumab versus trifluridine/tipiracil for metastatic microsatellite instability-high colorectal cancer: A modeling decision analysis.
Authors: Chu Jacqueline N. , Choi Jin G. , Ostvar Sassan , Torchia James A. , Reynolds Kerry Lynn , Gainor Justin F. , Chung Daniel C. , Clark Jeffrey W. , Hur Chin 
Published: January 2019

829 Background: Microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) patients who have failed chemotherapy have shown response to checkpoint blockade. We investigate optimal third-line treatment in MSI-H mCRC with regard to overall survival, quality of life years gained (QALYs), and cost-effectiveness. Methods: A Markov Model was created for a base case of a 57 year old man with MSI-H mCRC refractory to two lines of chemotherapy. Treatments compared were nivolumab, nivolumab with ipilimumab, and trifluridine/tipiracil. Patients could remain stable, progress to fourth-line chemotherapy or palliative care, experience drug toxicity, die from age/sex mortality, or die from cancer over their simulated lifetimes. Transitions between health states were based on the CheckMate 142 and RECOURSE trials. Outcomes were survival or unadjusted life years, QALYs, and incremental cost-effectiveness ratios (ICERs). The willingness to pay threshold was $100,000/QALY. Results: Nivolumab with ipilimumab was the most effective strategy as it yielded more unadjusted life-years (4.24) and QALYs (2.53) compared to nivolumab (3.95 LY, 2.33 QALYs) and trifluridine/tipiracil (0.74 LY, 0.07 QALYs). However, nivolumab with ipilimumab was not cost-effective compared to nivolumab and neither treatment strategy was cost-effective compared to trifluridine/tipiracil. Sensitivity analysis found nivolumab monotherapy could be cost-effective with decrease in drug cost to $2000/dose. Conclusions: Our modeling analysis finds that both single and dual checkpoint blockade yield significantly increased overall survival and QALYs for MSI-H mCRC compared to third-line chemotherapy, but were not cost-effective because of nivolumab cost. Decreases in drug pricing and/or duration of maintenance nivolumab could make nivolumab monotherapy cost-effective. [Table: see text]
Patterns of care and outcomes with the addition of radiotherapy to surgery for stage I rectal adenocarcinoma.
Authors: Zhao Nan , Lin Chi 
Published: January 2019

831 Background: The standard of care for stage I (T1/2N0M0) rectal adenocarcinoma is surgery alone. We investigated practice patterns and outcomes associated with administration of radiotherapy (RT) to surgery for stage I rectal adenocarcinoma. Methods: Using National Cancer Database from 2004 to 2014, 12494 patients with clinical stage T1-2N0M0 rectal adenocarcinoma who had definitive surgery were analyzed. 8265 received definitive surgery alone and 4229 received definitive surgery with preoperative or postoperative RT. Between groups, demographic, tumor and treatment characteristics were compared. Multivariate logistics regression was used to examine factors associated with the receipt of RT. Overall survival (OS) were estimated by Kaplan-Meier method; the log-rank test was used to compare survival curves. Cox proportional hazards modeling determined variables associated with death. Results: Of 12494 patients, 34% received RT; among them, 94% received chemotherapy (CT). Patients who received RT tended to be younger, male, diagnosed in early years, covered by Medicaid/Medicare/Not Insured, treated at community cancer program, a lower Charlson/Deyo score, a T2 clinical stage, a poorly differentiated or a larger tumor. Survival analysis revealed no difference in patients with or without RT (Median survival of 142 months vs. 137 months and 5 year OS of 79% vs. 82%, p = 0.50). Multivariate Cox models showed that variables significantly associated with increased hazard of death (p < 0.05) were older age (HR = 1.06), male gender (HR = 1.24) , Charlson/Deyo score 1 (HR = 1.54)/ Charlson/Deyo score 2 (HR = 2.29) (vs. Charlson/Deyo score 0), clinical T2 stage (HR = 1.15), pathological III/IV stage (HR = 4.16), poorly differentiated grade (HR = 1.38), Medicaid (HR = 1.70) /Medicare (HR = 1.24) /Not Insured (HR = 2.28) (vs. private insurance), community cancer program (HR = 1.17) and lower income (HR = 1.25). After adjusting for all above variables, RT or CT was not associated with improved OS. Conclusions: Addition of RT (with or without chemotherapy) to definitive surgery was not associated with survival advantage in stage I rectal adenocarcinoma.