bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nintedanib versus placebo in patients receiving mFOLFOX6 for metastatic, chemorefractory colorectal cancer: TRICC-C trial—Final results from the randomized phase II trial of the AIO.
Authors: Ettrich Thomas Jens , Berger Andreas Wolfgang , Decker Thomas , Hofheinz Ralf , Heinemann Volker , Hoffmann Thomas , Hebart Holger Frithjof , Herrmann Thomas , Hannig Carla Verena , Buechner-Steudel Petra , Guethle Melanie , Bartholomaeus Hanna , Beutel Alica , Perkhofer Lukas , Seufferlein Thomas 
Published: January 2019

666 Background: Anti-VEGF agents plus chemotherapy improve PFS of patients with mCRC in the first- and second-line-setting. During this treatment tumour angiogenesis is driven by other factors but VEGF. Nintedanib, a triple angiokinase inhibitor of VEGFR-1-3, FGFR-1/-3 and PDGFR-α/-β, thereby additionally targets angiogenic escape mechanisms upon resistance to anti-VEGF treatment. The TRICC-C trial evaluates the combination of mFOLFOX6 plus Nintedanib. Final results of the randomized phase II trial are presented. Methods: Patients with mCRC having received one line of non-oxaliplatin containing palliative chemotherapy, with an ECOG-PS of 0/1 were randomized 1:1 in a double-blind design to receive: mFOLFOX6 plus Nintedanib (2 x 200 mg p.o./d, d1-d14) or placebo, respectively, repeated every 14 days. Primary endpoint was PFS. Secondary endpoints were ORR, OS and safety. Patients who received at least one dose of trial medication were included in the efficacy and safety analyses. Results: From 12/2012 to 5/2016 53 patients (scheduled n = 180) were randomized. The trial was terminated prematurely due to slow accrual. Compared to mFOLFOX6 plus placebo (F+P), the combination of mFOLFOX6 plus Nintedanib (F+N) improved mPFS (F+P: 4.6 vs. F+N: 8.1 mo.; HR 0.65; 95% CI 0.32-1.30; p = 0.2156), mOS (F+P: 9.9 vs. F+N: 17.1 mo.; HR 1.03, 95% CI 0.48-2.23; p = 0.9387) and DCR (F+P: 50 vs. F+N: 66,7%; p = 0.2709). ORR was comparable in both arms (F+N: 3.8 vs. F+P: 3.7%). Toxicity was low to moderate without major differences between both arms except G 3/4 neutropenia (F+N: 19%, F+P: 12%) and GI disorders (F+N: 23%, F+P: 15%). Conclusions: Final results suggest a PFS, OS and DCR benefit for mFOLFOX6 + Nintedanib in the second-line therapy of mCRC. Due to the premature termination of the trial there was no statistical significance demonstrable. Showing no clinically significant PFS-benefit in the first-line situation (mFOLFOX6 plus Nintedanib/Bevacizumab, Ann Oncol. 2015) or the last line as single agent, respectively (ESMO 2016) the TRICC-C results suggests that Nintedanib plus mFOLFOX6 could be an interesting therapeutic option for the second-line situation. Clinical trial information: NCT01362361.
Integrating geriatric assessment into routine gastrointestinal (GI) consultation: The Cancer and Aging Resilience Evaluation (CARE).
Authors: Williams Grant Richard , Kenzik Kelly , Parman Mariel , Rocque Gabrielle Betty , McDonald Andrew Michael , Paluri Ravi Kumar , Navari Rudolph M. , Nandagopal Lakshminarayanan , Smith Crystal Young , Robertson Matthew , Bhatia Smita 
Published: January 2019

667 Background: Integrating Geriatric Assessment (GA) in the management of older adults with cancer is recommended, yet rarely practiced in routine oncologic care. In this report, we describe the feasibility of integrating the routine incorporation of GA in the management of older adults with GI malignancies and characterize GA impairments. Methods: CARE was adapted from the Cancer and Aging Research Group GA with modifications to create a completely patient-reported version. The CARE assesses self-reported functional status, physical function, nutrition, social support, anxiety/depression, cognitive function, comorbidities, and social activities. Patients ≥ 60yo referred for consultation to the GI Oncology clinic were asked to complete the CARE (paper/pencil) on their first visit. The completed CARE was collected during nurse triage and submitted to the clinical team prior to the physician encounter. Feasibility was defined as completion of the CARE by ≥ 80% of eligible patients during the initial consultation. Results: Between September 2017 and August 2018, 199 eligible new patients attended the GI Oncology Clinic, 192 (96.5%) were approached, and 181 (90.4%) completed the CARE. Most patients (79.6%) felt the length of time to complete was appropriate (median time of 10 minutes [IQR 10-15 minutes]). The mean age was 70y (range 60-96), 54.3% were male, and 75.1% were non-Hispanic white. Common tumor types included colon (27.8%), pancreatic (21.2%), and rectal (10.2%) cancer; predominately advanced stage diseases (stage III: 26.9%; stage IV: 40.0%). GA impairments were prevalent: 48.6% reported dependence in Instrumental Activities of Daily Living, 18.0% reported dependence in Activities of Daily Living, 22.5% reported ≥ 1 fall, 29.4% reported a performance status ≥ 2, 51.3% were limited in walking one block, 75.7% reported polypharmacy (≥ 4 medications), and 84.3% had ≥ 1 comorbidity. Conclusions: Performing a GA in the routine care of older adults with GI malignancies is feasible, and GA impairments are common among older adults with GI malignancies. A fully patient-reported GA such as the CARE may facilitate broader incorporation of GA in the routine clinic work flow.
Activated interferon-γ (IFN-γ) pathway associated with clinical benefit to programmed cell death protein-1 (PD-1)/PD ligand 1 (PD-L1)-based therapy in esophageal squamous cell carcinoma (ESCC).
Authors: Guo Jhe-Cyuan , Hsieh Min-Shu , Lin Chia-Chi , Huang Ta-Chen , Chang Chun-Jung , Hsu Chih-Hung 
Published: January 2019

67 Background: Previous studies indicate a preexisting T cell response and the associated “adaptive immune resistance” are critical for the clinical efficacy of anti-PD-1/PD-L1 immunotherapy. The study explored the activated IFN-γ pathway and the expression of interferon regulatory factor 1 (IRF-1), as surrogates of preexisting T cell response, as potential biomarkers associated with clinical benefit (CB) for ESCC patients receiving anti-PD-1/PD-L1 therapy. Methods: Thirty-one ESCC patients treated with PD-1/PD-L1 blockade antibody, alone or in combination, were enrolled. Tumor response evaluation was made according to Response Evaluation Criteria in Solid Tumours 1.1, and CB was defined as complete response, partial response or stable disease at least 6 months. Formalin-fixed paraffin-embedded tissues from 31 patients were analyzed for the expression of PD-L1 and IRF-1 by immunohistochemistry; 13 tissues were analyzed for the expression of immune-related genes by NanoString nCounter Human PanCancer Immune Profiling. Results: Of 31 enrolled patients (M: F= 30: 1, median age of 58), 23 and 8 were of recurrent and de novo metastatic ESCC. Sixteen and 15 received PD-1/PD-L1 blockade alone and PD-1/PD-L1-based combination therapy, respectively; 13 had received at least 2 lines of systemic therapy for advanced disease. The response rate was 10%, and the CB rate was 16%. The median progression-free-survival (PFS) and overall survival are 1.8 and 5.6 months, respectively. The 25-gene IFN-γ signature was significant higher in patients with CB than in patients without CB ( P = 0.020). Neither PD-L1 expression on tumor cells (TC) nor on immune cells (IC) was associated with CB ( P = 0.489 and 0.646, respectively). However, the IRF-1 expression on TC or on IC was significantly associated with CB ( P < 0.001 and 0.005, respectively). Conclusions: Activated IFN-γ pathway determined by 25-gene IFN-γ signature and high IHC-expression of IRF-1 were associated with CB in advanced ESCC patients receiving anti-PD-1/PD-L1-based therapy. (Supported by the grant of MOST 105-2314-B-002 -186 -MY3).
The impact of multidisciplinary team (MDT) management on outcome of hepatic resection in liver-limited colorectal metastases.
Authors: Corallo Salvatore , Calegari Maria Alessandra , Zurlo Ina Valeria , Marchesani Silvio , Orlandi Armando , Dadduzio Vincenzo , Di Stefano Brunella , Camarda Floriana , Di Dio Carmela , Garufi Giovanna , Barbaro Brunella , Vellone Maria , Ardito Francesco , Giuliante Felice , Pozzo Carmelo , Cassano Alessandra , Barone Carlo Antonio , Bria Emilio , Basso Michele 
Published: January 2019

671 Background: Hepatic resection is the gold standard treatment for pts with liver-limited mCRC with 5- and 10-yrs survival rates reaching up to 60% and 20%. Although multidisciplinary team (MDT) management might ensure a more accurate assessment of pts and a faster referral to surgeons, reports discussing the impact of MDTs on survival are controversial and to date there are no strong evidences supporting routinely MDT discussion. The aim of this study was to evaluate the benefit of MDT management in pts with liver-limited mCRC in our single institution experience. Methods: Clinical records of pts with liver-limited mCRC who underwent radical surgery at Fondazione Policlinico “A. Gemelli” - IRCCS from Jan-2006 to Dec-2016 were retrospectively analyzed. The objective of the analysis was to compare survivals of pts managed within our MDT (MDT cohort) to those of pts referred to surgery from other hospitals without MDT discussion (non-MDT cohort). Primary endpoints were DFS and OS. Differences in baseline characteristics and in post-operative morbidity were evaluated. Results: Of the 619 pts analyzed, 230 were included in the MDT cohort and 389 in the non-MDT cohort. No significant difference between the two groups was found in terms of DFS (12vs11 m; p 0.09) and OS (55vs51 m; p 0.68). Concerning baseline characteristics, in the MDT cohort compared to non-MDT cohort there was a statistically higher number of median metastases (4.5vs2.6; p < 0.0001) and a higher rate of synchronous metastases (61.7vs39.3%; p < 0.001). Despite pre-operative CT rate was higher in the MDT group (75.8vs70.7%), the median duration of CT before surgery was significantly lower in MDT pts (7 vs 8 cycle; p < 0.001). Moreover, post-operative morbidity was significantly lower in the MDT cohort (6.2vs19.2%; p < 0.00001). Conclusions: Our study does not demonstrate a survival benefit from MDT management of pts with liver limited mCRC. However, the analysis shows that MDT assessment allows to consider eligible for surgery pts with a more advanced disease. Moreover, MDT discussion seems to reduce the median duration of pre-operative CT with a consequent lower rate of post-operative morbidities. Our data warrant prospective validation.
Predictors of survival in rectal squamous cell carcinoma: An analysis from the National Cancer Database (NCDB).
Authors: Tella Sri Harsha , Kommalapati Anuhya , Goyal Gaurav , Mahipal Amit 
Published: January 2019

672 Background: Rectal squamous cell carcinoma (RSCC) is a rare form of gastrointestinal malignancy. Using the NCDB, we determined the prognostic factors and survival outcomes of RSCC in the United States. Methods: We identified histologically confirmed cases of RSCC from the National Cancer Data Base (2004-2015). Univariate and multivariable methods were used to assess factors associated with survival. Kaplan-Meier method and log-rank test were used to perform overall survival (OS) analysis. Results: Of the 5,527 cases included in our analysis, 67% were female. Median age at diagnosis was 61 years and did not differ by sex. The proportion of patients with stage 1, 2, 3 and 4 diseases were 22%, 16%, 20%, and 11%, respectively (30% unknown stage). Among the ones who received surgical resection of primary tumor, 41%, 30%, 20% and 8% are of stages 1, 2, 3 and 4 respectively. The rate of R0 resection was 54%, 63%, 55% and 38% in stage 1, 2, 3 and 4, respectively. The R0 resection rate was much higher in patients who received neoadjuvant chemo or radiation therapy or both (87%, 78%, 74%, and 57% in stages I, 2, 3 and 4, respectively) as compared to that of their counterparts. On stage wise sub-group OS analysis, stage 1-3 patients had OS benefit from surgery (as compared to no-surgery) (145 vs 90 months, p<0.001) as opposed to 4 disease (16 vs 11 months, p=0.06). Adjuvant radiation therapy improved the median OS in stage 1-3 patients (as compared to no-adjuvant radiation) in patients with positive surgical margins (not reached vs 40 months, p<0.0001). Patients with stage 4 disease treated with radiation therapy had a better median OS than those without (16 vs 6 months, p<0.0001). On therapy wise sub-group analysis, the patients who received surgery only had a median OS of 145 months; surgery + chemoradiation (adjuvant and neoadjuvant) = not reached; whereas patients with chemoradiation only had median OS of 80 months. Conclusions: This is the largest registry-based study on RSCC to date. RSCC had a diverse OS varied significantly according to stage of the disease at presentation and therapy received. Surgical resection of primary tumor was associated with improved OS as compared to that of patients who received chemoradiation.
QoL from TASCO1: Health-related quality of life of trifluridine/tipiracil-bevacizumab and capecitabine-bevacizumab as first-line treatments in metastatic colorectal cancer patients not eligible for intensive chemotherapy—Results from the TASCO1 phase II study.
Authors: Moiseyenko Vladimir , Saunders Mark P. , Wasan Harpreet Singh , Argiles Guillem , Borg Christophe , Creemers Geert-Jan , Fedyanin Mikhail , Glynne-Jones Robert , Pfeiffer Per , Punt Cornelis J. A. , Stroyakovskiy Daniil , Ten Tije Albert J. , Van de Wouw Agnes W , Kanehisa Akira , Fougeray Ronan , Sabater Javier , Amellal Nadia , Van Cutsem Eric 
Published: January 2019

676 Background: TASCO1 is a phase II study which evaluated the safety and efficacy of trifluridine/tipiracil + bevacizumab (TT-B) and capecitabine + bevacizumab (C-B) in first-line unresectable mCRC patients non-eligible for intensive therapy. Promising activity was shown on progression-free survival with TT-B (9.2 months) and C-B (7.8 months). Here we present the Quality of Life (QoL) analysis of the two treatment arms. Methods: In TASCO1, patients were randomized 1:1 to receive TT-B (n = 76) on a four-week cycle or C-B (n = 77) on a three-week cycle. QoL was assessed in TASCO1 at baseline and at each 12 weeks thereafter, until discontinuation of study treatment, using the QLQ-C30 and QLQ-CR29 questionnaires. Responses were described separately in each arm using descriptive statistics. Results: For QLQ-C30, 121 patients completed baseline questionnaire. No clinically relevant difference was observed on treatment in mean change of score from baseline for the global health status, functioning scales, and for most of the symptom scales, except for nausea/vomiting and diarrhoea (worsening in the TT-B group and stable in the C-B group for both symptoms), fatigue (stable in the TT-B group and worsening in the C-B), loss appetite (worsening in the two groups) and insomnia (improvement in the two groups). For QLQ-CR29, 117 patients completed baseline questionnaire. No clinically relevant difference on treatment was observed in mean change of score from baseline for most of items except for the following: hair loss, trouble with taste (worsening for both symptoms in the TT-B group while stable for hair loss and improvement for trouble with taste in the C-B group), sore skin, dry mouth (stable in the TT-B group and worsening in the C-B group for both symptoms), and anxiety (stable in the TT-B group and improvement in the C-B group). Conclusions: The Global Health Scale was maintained in Trifluridine/tipiracil+bevacizumab arm as well as in the capecitabine+bevacizumab arm. No clinically relevant difference from baseline was observed over time in both groups except for few sub-scales. Clinical trial information: NCT02743221.
Feasibility of using a fitness tracker to assess activity level and toxicity in colorectal cancer patients.
Authors: Ward William Harrell , Meeker Caitlin R. , Hill Maureen , Handorf Elizabeth A. , Hall Michael J. , Sigurdson Elin R. , Astsaturov Igor A. , Denlinger Crystal S. , Reddy Sanjay S. , Meyer Joshua E. , Zibelman Matthew R. , Madnick David , Moccia Matthew , Dotan Efrat , Farma Jeffrey M. , Vijayvergia Namrata 
Published: January 2019

684 Background: Performance status (PS) is traditionally used to predict tolerance and morbidity associated with colorectal cancer (CRC) treatment. Monitoring activity level at the start of therapy using a wearable fitness tracker (Fitbit) may provide a more accurate estimate of overall patient (pt) PS and help predict treatment-related toxicity. Methods: With IRB approval, we prospectively enrolled CRC pts undergoing therapy into two cohorts: medical (M) and surgical (S). Our primary aim was to assess the feasibility of using Fitbit to assess activity level and toxicity. After documenting baseline ECOG PS, M and S pts wore Fitbit for four days while receiving chemotherapy or prior to surgery, respectively. Pts’ mean steps per day (SPD) were calculated, excluding days Fitbit was worn < 12 hours. To stratify the prediction of toxicity risk, a cutoff of 5,000 SPD was selected and any post-operative complication (S pts) or ≥ grade 3 toxicity (M pts) was counted as toxicity. The study is ongoing to accrue 80 pts. Results: On interim analysis, 43 pts were evaluated for the primary aim. Seventy nine percent (34/43) of pts had at least 3 days with ≥ 12 hours of Fitbit usage, meeting the 75% feasibility endpoint. Forty pts (25 M, 15 S) had at least 1 day with ≥ 12 hours of Fitbit usage and had data available for analysis. Mean SPD for PS 0 and PS 1 pts was 7,183 and 3,214, respectively (p=0.01), and overall was 6,290 (SD 4,416). Eight M pts and 2 S pts experienced toxicity (Table). The rate of toxicity was 23% (7/30) in pts with PS 0 and 33% (3/10) in pts with PS 1. With SPD as cutoff, the toxicity rate was 11% (2/19) in pts with > 5000, compared to 38% (8/21) in pts with < 5000. Conclusions: We observed high rates of compliance with a fitness tracker in CRC pts. SPD serves as a useful identifier for toxicity and may be a better predictor than traditional PS. These findings provide rationale to study SPD in lieu of PS for risk stratification of patients undergoing therapy and possibly incorporate pre-habilitation programs in high-risk groups, though validation in larger studies is needed. [Table: see text]
Evaluating the prognostic significance of lymphovascular invasion in stage II and III colon cancer.
Authors: Mutabdzic Dorotea , O'Brien Shalana BL , Handorf Elizabeth A. , Devarajan Karthik , Reddy Sanjay S. , Sigurdson Elin R. , Denlinger Crystal S. , Meyer Joshua E. , Farma Jeffrey M. 
Published: January 2019

685 Background: Presence of lymphovascular invasion (LVI) is known to be a predictor of lymph node involvement in colon adenocarcinoma (CA). Lymph node involvement is associated with poorer prognosis necessitating adjuvant therapy. While some studies have suggested that LVI is a predictor of worse overall survival in early stage colon cancer, the significance of LVI on prognosis has not been tested in a comprehensive North American data set. Methods: Patients with stage II and III CA with LVI data available and those who received predefined standard of care treatment were identified from the National Cancer Data Base (NCDB) from 2011 to 2015. The relationship between LVI and overall survival was tested using Kaplan-Meier survival curves and Cox proportional hazards regression analysis after adjusting for relevant clinical and demographic variables. Hazard ratios and 95% confidence intervals are reported along with median overall survival (OS) where available. Results: The dataset included 93,070 patients with stage II and 66,701 patients with stage III CA. The proportion of patients with LVI was 13% in stage II and 47% in stage III CA. After adjusting for age, sex, gender, race, comorbidities, socioeconomic status, T, and N stage, LVI was associated with worse OS in stage II, HR 1.2 (1.15-1.25, p < 0.001), and in stage III, HR 1.25 (1.21-1.30, p < 0.001), CA. Median OS was 6.51 years with LVI versus. 6.85 years without LVI in stage II compared with 6.57 years with LVI versus not reached without LVI in stage III CA. Of the stage II patients with LVI, 20% received adjuvant chemotherapy (CT) and median OS was 6.91 years for those who did versus 6.07 years for those who did not receive CT. Conclusions: Our data suggest that LVI is an important predictor of OS in stage II and III CA. There is evidence that adjuvant chemotherapy improves OS in advanced CA but there remains uncertainty as to the benefit in stage II. Despite this uncertainty, guidelines suggest consideration of adjuvant CT in patients with high-risk stage II disease. Our data support the recommendation that LVI be considered a high-risk feature in stage II disease. Further studies are necessary to examine whether the type or duration of CT should differ for patients with CA and LVI.
Dose-finding and single-arm confirmatory study of definitive chemoradiotherapy (dCRT) with S-1/mitomycin-C (MMC) in patients (pts) with clinical (c) stage II/III squamous cell carcinoma of the anal canal (SCCA): JCOG0903.
Authors: Takashima Atsuo , Ito Yoshinori , Hamaguchi Tetsuya , Mizusawa Junki , Shimada Yasuhiro , Shiozawa Manabu , Kodaira Takeshi , Ohue Masayuki , Kinouchi Makoto , Murata Kohei , Fujita Fumihiko , Watanabe Masahiko , Moriya Yoshihiro , Iinuma Gen , Ishida Fumio , Saida Yoshihisa , Matsuda Takahisa , Katayama Hiroshi , Fukuda Haruhiko , Kanemitsu Yukihide ,   Colorectal Cancer Study Group of Japan Clinical Oncology Group
Published: January 2019

686 Background: dCRT with 5-FU/MMC is a standard treatment for cStage II/III SCCA. S-1 is an oral fluoropyrimidine and has a greater effect on radiosensitivity. We conducted this trial of dCRT with S-1/MMC to determine the recommended dose (RD) of S-1 in phase I part (P I) and to evaluate the efficacy and safety in phase II part (P II) for cStage II/III SCCA. When the primary endpoint in P II part is proven to be satisfactory, we can regard this combined treatment as the new standard treatment. Methods: Eligibility criteria included histologically proven SCCA, cStage II/III (UICC 6th), PS 0-1, and age 20-80 years. dCRT consisted of MMC (10 mg/m2 on days 1, 29) and S-1 (60 mg/m2/d in level 0 and 80 mg/m2/d in level 1 on days 1-14, 29-42) with concurrent 3-dimensional RT of 59.4 Gy/33fr. The P I adopted the 3+3 cohort design. The primary endpoint of P II was proportion of 3-year event-free survival (% 3-year-EFS). The sample size was 65 in the P II, with one-sided alpha of 5% and power of 80%, threshold and expected % 3-year EFS as 60% and 75%. Results: From Feb/2010 to Mar/2015, 69 pts (3 in level 0 and 66 [7 in P I and 59 in P II] in level 1) were enrolled. Pts’s backgrounds for level 1 were as follows: M/F, 12/54; Age, median 64 (range 33-80); cStage II/IIIA/IIIB, 29/9/28. Three in level 1 were ineligible and 63 eligible assigned to level 1 were included in efficacy analysis. In the P I, considering the details of DLTs, RD of S-1 was determined as 80 mg/m2/d. In the 63 eligible of level 1, %3-year EFS was 65.0% (90% CI 54.1-73.9%). % 3-year OS, PFS, and colostomy-free survival were 87.3% (95% CI 76.2-93.4%), 85.7% (74.3-92.3%), and 76.2% (63.7-84.9%), respectively. The complete response rate was 81% on central review. Among 65 pts receiving level 1 dCRT, common grade 3 or 4 acute toxicities were leukopenia (63.1%), neutropenia (40%), diarrhea (20%), radiation dermatitis (15.4%), and febrile neutropenia (3.1%). Only 6 (9.2%) showed grade 3 late toxicities. No treatment-related deaths were observed. Conclusions: Although dCRT with S-1/MMC showed acceptable toxicities and favorable 3-year survival, this study did not meet its primary endpoint. Clinical trial information: UMIN000003237.