bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell population expansion in response to allogeneic cancer vaccine alone (DPV-001) or with granulocyte-macrophage colony-stimulating factor (GM-CSF) or imiquimod (I) for definitively-treated stage III NSCLC patients (pts).
Authors: Fox Bernard A. , Boulmay Brian C. , Li Rui , Happel Kyle T , Paustian Christopher , Moudgil Tarsem Lal , Puri Sachin , Dubay Christopher , Koguchi Yoshinobu , Mehta Adi , Lund-Johansen Fridtjof , Fisher Brenda K , Redmond William L , Bifulco Carlo Bruno , Ochoa Augusto , Hu Hong-Ming , Hilton Traci , Urba Walter John , Sanborn Rachel E. 
Published: September 2018

e14639 Background: The DPV-001 DRibble is a dendritic cell-targeted microvesicle (proteasome blocked autophagosome) vaccine derived from an adenocarcinoma and a mixed histology cell line. It contains multiple TLR agonists and > 130 potential NSCLC antigens, many as prospective altered-peptide ligands. In preclinical studies, DRibble immunotherapy provided significant anti-cancer effects in a dozen models. We hypothesize that DRibble’ vaccination efficacy can be attributed to their capacity to present tumor-derived short-lived proteins (SLiPs) and defective ribosomal products (DRiPs) that are typically not processed and presented by professional antigen presenting cells and against which the host may be less tolerant. Methods: Pts received induction cyclophosphamide, 7 vaccines every 3-weeks, then every 6 weeks x 4 more doses. Pts were randomized to receive DRibble alone (A), or with I (B) or GM-CSF (C). PBMCs /serum were collected at baseline and at each vaccination to assess changes in antibodies (Ab) (ProtoArray and microsphere affinity proteomics), peripheral lymphocyte populations (flow cytometry) and T cell receptor (TCR) repertoires (Adaptive immunoSEQ). Results: 13 pts were enrolled (Arm A: 5; B: 4; C: 4). We previously reported that vaccination induced or increased IgG Ab responses against targets over-expressed by NSCLC. Patients receiving DPV-001 had a significant (p < 0.04) increase in total (CD4 + CD8) TCRs that increased 10 fold over baseline compared to normal controls (independent from trial, n = 3) and the increase in CD4 clones was similar to that seen following ipilimumab (melanoma pts, independent from trial, n = 9). Analysis of a resected metastasis (progressing on treatment), identified brisk infiltration of T cells and tumor that was strongly PD-L1+. Conclusions: Vaccination with DPV-001 expanded populations of T cells over that observed in controls and the increase in CD4 T cells was similar to that observed in patients receiving ipilimumab and may represent vaccine-reactive T cells. Clinical Trial Identifier: NCT01909752, Support: R44 CA121612 Clinical trial information: NCT01909752.
Clinicopathological features and prognosis of colorectal cancer with extranodal tumor deposits.
Authors: Lu Yun , Zhang Xianxiang , Hu Jilin , Wang Dongsheng , Gao Yuan , Zhang Maoshen , Liu Shisong , Liu Guangwei , Zhao Peng , Wu Jinhui , Li Zhenkai , Han Jiagang , Wang Guiying , Feng Yong , Wang Jiansheng 
Published: September 2018

e15005 Background: The study discusses clinicopathological features of colorectal cancer with extranodal tumor deposits(ENTDs) and investigates whether ENTDs is a poor prognostic factor. Methods: 1. Clinicopathological data and follow-up of colorectal cancer with ENTDs who underwent surgery between June 2007 and June 2010 in seven hospitals in North China were collected retrospectively. Kaplan-Meier method was used for survival analysis. Cox proportional hazards model was used for multivariate analysis of prognostic factors. 2. The literatures on ENTDs and postoperative survival rate in colorectal cancer published from 1990 to 2016 were retrieved in English literature databases such as MEDLINE/PubMed, Web of Science and Chinese literature databases such as CNKI. Meta-analysis was conducted by Review Manager 5.3 software. Results: 1. A total of 253 cases of colorectal cancer with ENTDs were collected. The 5-year survival with only one ENTD was 49.2% (87/177), with median survival time 60 months. The 5-year survival with more than one ENTD was 17.1% (13/76), with median survival time 44 months. Cox regression analysis revealed that age, tumor size, number of ENTDs, N, m stage, surgical approach and adjuvant treatment were independent risk factors of prognosis of colorectal cancer with ENTDs. 2. The total sample size of the studies was 4731 cases with ENTDs (+) 917 cases. Meta analysis showed that: 5-year overall survival and 5-year relapse-free survival rate were significantly lower in ENTDs (+) group than ENTDs (-) group for colorectal cancer (OR:respectively 0.25,0.30; 95% CI:respectively 0.17-0.37,0.22-0.41; both P < 0.00001); 5-year overall survival rates were both significantly lower in ENTDs (+) group than ENTDs (-) group for patients with N0 and N+ colorectal cancer (N0 group: P = 0.003; N+ group: P = 0.0008; both P < 0.05). Conclusions: 1.Age, tumor size, number of ENTDs, N, m stage, surgical approach and adjuvant treatment were independent risk factors of prognosis of colorectal cancer with ENTDs. 2. ENTDs was a poor prognostic factor in colorectal cancer. The effect of ENTDs on postoperative survival rate might resemble that of between lymph node metastasis and distant metastasis.
Hepatectomy followed by adjuvant chemotherapy with capecitabine plus oxaliplatin for three months for colorectal cancer liver metastases: A multicenter phase 2 study.
Authors: Hashida Hiroki , Satake Hironaga , Tanioka Hiroaki , Miyake Yasuhiro , Yoshioka Shinichi , Watanabe Takanori , Matsuura Masato , Kyogoku Takahisa , Inukai Michio , Kotake Takeshi , Okita Yoshihiro , Hatachi Yukimasa , Yasui Hisateru , Kotaka Masahito , Kato Takeshi , Kaihara Satoshi , Tsuji Akihito 
Published: September 2018

e15015 Background: Hepatic resection is one of the treatment strategies for resectable colorectal cancer liver metastases (CLM). The role of neoadjuvant and adjuvant chemotherapy in the management of initially resectable CLM is still unclear. Adjuvant chemotherapy consisting of capecitabine plus oxaliplatin (CapeOx) appears to be equivalent to FOLFOX in patients with stage III colon cancer. Furthermore, some studies suggest that adjuvant chemotherapy for three months after curative resection for stage II/III colorectal cancer has equivalent efficacy to adjuvant chemotherapy for 6 months. We initiated a multi-institutional, single-arm, open label, phase II trial to confirm the feasibility of adjuvant CapeOx for three months for post curative resection of CLM. Methods: Patients received one course of capecitabine followed by four courses of CapeOx for a total five courses (15 weeks) as adjuvant chemotherapy after curative resection of CLM. CapeOx consisted of a 2-hour intravenous infusion of oxaliplatin 130 mg/m2 on day 1 plus oral capecitabine 1,000 mg/m2 twice daily for 2 weeks in a 3-week cycle. The primary endpoint was completion rate of adjuvant chemotherapy. We set a threshold completion rate of protocol treatment of 45% and an expected completion rate of 70%. Given a one-sided α of 0.1 and statistical power of 80%, a minimum of 25 patients was required. Results: From May 2013 to November 2015, Twenty-eight patients were enrolled from six institutions: median age 69.5y, 54% male, 78.5% left-sided primary. Of the patients, 15 were synchronous metastases and 13 were metachronous. The locations of the metastases were unilobar in 20 patients and bilobar in 8. The mean number of lesions resected was two (range, 1 to 4). The mean size of largest tumor was 31 mm (range, 2 to 112 mm). Among the 28 patients, 20 (71.4 %: 95% CI, 53.6 to 89.3%) completed the protocol treatment. The most common grade 3 or 4 toxicities were neutropenia (29%). No treatment related death was observed. Conclusions: Adjuvant CapeOx for three months for post curative resection of CLM was feasible. Clinical trial information: UMIN000011164.
Outcome of use of regorafenib in metastatic colorectal cancer in routine clinic practice in Saudi Arabia.
Authors: Aljubran Ali Husain , Zahir Muhammad , Gad Ahmed , Al-Dalee Abdelmuniem , Bazarbashi Shouki , Elshenawy Mahmoud Abdelsatar , Al Zahrani Ahmad 
Published: September 2018

e15021 Background: Regorafenib is a multi-kinase inhibitor that was FDA approved for the treatment of refractory advanced colorectal cancer. It has been found in the clinical trials to have modest benefit and relatively high toxicity, but the outcome of its routine use in the clinic practice is lacking. Our aim is to assess the outcome in our local clinic practice. Methods: Records of all colorectal cases who were treated with regorafenib were reviewed. Structured CRF was developed. Clinical, pathological and molecular data were collected. Efficacy and toxicity details were analyzed. Results: Thirty-two cases of metastatic colorectal cancer were treated with regorafenib from February 2014 to February 2016. All patients received prior oxaliplatin, irinotecan and bevacizumab based regimens, and cetuximab if wild type. Median age: 53.5 years. Male: 15 (46.9%). Primary tumor was right sided in 10 patients (31.3%), and left sided (including rectum) in 22 (68.7%). Pan RAS mutant: 21 (65.6%). Fifteen patients (46.9 %) had ECOG Performance Status of one, whereas 16 patients (50%) have ECOG 2. Starting dose was reduced to 120mg in 11 (34.4%). Only 5 (15.6%) continued beyond 3 cycles. 18 patients (56.3%) required dose reduction. Overall response: PR/CR: zero; Stable disease: 4 (12.5%); Progressive disease: 25 (78.1%); Clinical progression in 1 (3.1%), and 2 cases were not evaluated. After median follow up of 7 months, 22 patients (68.8%) have died, 5 (15.6%) are still alive and 5 (15.6%) are lost to follow up. Median survival: 9.3 months, and median PFS: 2.5 months. Conclusions: Regorafenib has poor tumor response in the routine clinic practice when given to patients with ECOG PS > 1. The median survival in this series is probably overestimated because of the relatively high rate of loss to follow up. Selection of patients is required in the routine clinic practice. Predictive markers are more important for such treatment with modest benefit, and significant toxicity and cost.
A phase II trial of total neoadjuvant treatment (TNT) (Capox plus radiotherapy) for local advanced rectal cancer patients with high risk factors.
Authors: Wang Xin , Yu Yongyang , Deng Xiangbing , Meng Wenjian , Zhu Hong , Jiang Dan , Zhuang Hua , Wu Bing , Li Zhiping , Qiu Meng , Gou Hongfeng , Bi Feng , Xu Feng , Wang Ziqiang , Zhou Zonggung 
Published: September 2018

e15025 Background: Standard neoadjuvant concurrent chemoradiotherapy didn't achieve improved overall survival in stage II-III rectal cancer. Total neoadjuvant treatment (TNT) might be a proper treatment option for patients with high risk factors. Therefore, this phase II trial was conducted to evaluate the safety and efficacy of TNT (Capox and IMRT/VMAT) in rectal cancer patients with high risk factors. Methods:Patients who were diagnosed stage II-III rectal cancer with at least one of the following high risk factors were recruited: cT4b, cN2, EMVI +, MRF+, lateral LN +. Three cycles of induction Capox were followed by pelvic IMRT/VMAT and two cycles of concurrent Capox. Three cycles of consolidation Capox were delivered after radiotherapy. Primary endpoints were pathological complete response (pCR) and R0 resection rate. Secondary endpoints were DFS, OS, toxicities and QOL. Here we present the initial results of this study. Results: From Jun 2015 to Jan 2017, 42 patients were evaluable. One patient (2.4%) who had acute intestinal obstruction after the first cycle of chemotheraoy underwent emergency TME. A total of 27 patients (64.3%) completed 8 cycles of chemotherapy. Forty-one patients (97.6%) completed the planned radiotherapy. 15 of 42 patients (35.7%) achieved a pCR or cCR, in which 12 patients (80%) completed 8 cycles of chemotherapy. Five patients refused the operation and selected Watch & Wait. R0 resection rate of patients who underwent TME were 100%. The mean time of operation was 207 minutes (120-370 minutes). And the mean estimated blood loss was 89ml (10-500ml). The most common grade 3 or higher adverse events associated with the neoadjuvant administration were leucopenia (9.5%), diarrhea (4.8%), radiation dermatitis (4.8%) and thrombocytopenia (2.4%). The most common grade 3 or worse surgery-related complications were pelvic abscesses, anastomotic leaks and hemorrhage which were observed in one patient, respectively. Conclusions: Total neoadjuvant treatment (TNT) is effective and safe for local advanced rectal cancer patients with high risk factors. Long-term efficacies of TNT need to be evaluated.
EGFR-targeted treatments in patients with metastatic colorectal cancer: Experience of panitumumab.
Authors: Gumus Mahmut , Geredeli Caglayan , Ucar Mahmut , Kaya Serap , Demir Hacer , Unal Olcun Umit , Degirmenci Mustafa , Gokoz Dogu Gamze , Turan Nedim , Yildirim Nilgun , Basal Fatma Bugdaycı , Arpaci Erkan , Karaagac Mustafa , Harputluoglu Hakan , Turk Haci Mehmet , Dane Faysal , Ozkan Metin 
Published: September 2018

e15028 Background: Overall survival times have been exceeded three years by the targeted treatments in metastatic colorectal cancer (MCC) . The sequence of these agents and the possible side effects constitute our discussions. We aimed to investigate the efficacy and tolerability of panitumumab use in this study. Methods: In this study 168 MCC patients from 15 different centers that were treated with panitumumab in first or second line settings were evaluated respectively. Progression free survival (PFS) and overall survival(OS) time were calculated in case of the patients treated with targeted treatments in first line setting. Results: The median follow-up time was 12(3-82) months. The median age was 60 (24-86) years and 36 % of the patients were female. Panitumumab as a component of first line treatment was used in 66 % of the patients. Median 6 (1-18) cycles treatment were given to the patients as first line chemotherapy. The median PFS was 11 (SE:2; 95% CI: 7-15) months in patients treated with panitumumab while 12 (SE:1; 95% CI: 10-14) months in patients treated with bevacizumab containing regimens as first line treatment (p:0.836). The median OS was 32 (SE:12; 95% CI: 7-56) months in patients treated with panitumumab containing regimen and the median OS has not been reached in bevacizumab group (p: NS). In univariate analysis, female gender and left-sided colon tumors have favorable PFS (p:0.030 and p:0.023 respectively). No difference between bevacizumab or panitumumab containing regimen in right- sided tumors have observed (p:0.812). But in left-sided tumors, the panitumumab containing regimens have favorable PFS (8 vs 13 months. p:0.023). Grade 2 or higher skin rash was observed in 49% . Diarrhea in 38%, neuropathy in 30%, different hematologic toxicity in 14% and infusion reaction in 2.2% of the patients were detected. The skin rash was associated to panitumumab containing regimen (p:0.000). Other toxicity frequencies were not statistically significant in both groups. Conclusions: Compilation of current life data in MCC treatment will reveal the efficacy and tolerability in our daily practice beyond as data in clinical trials. These data together with more experience will guide the optimization of the treatments.
Impact of the addition of bevacizumab, oxaliplatin or irinotecan to fluoropyrimidin in the first-line treatment of metastatic colorectal cancer in elderly patients.
Authors: Landre Thierry , Aparicio Thomas , Ghebriou Djamel , Nicolas Patrick , Taleb Cherifa , Chouahnia Kader , Zelek Laurent H. , Des Guetz Gaetan 
Published: September 2018

e15034 Background: The clinical benefit of double-front-line therapy (including oxaliplatin or irinotecan or bevacizumab plus 5FU or capecitabine) compared to monotherapy (5FU or capecitabine) in elderly ( > 70 years) patients with metastatic colorectal cancer (MCRC) is controversial. We performed a meta-analysis of published randomized studies. Methods: The selection of the studies was carried out using PubMed with the following keywords: "metastatic colorectal cancer", "elderly", "oxaliplatin", "irinotecan", "bevacizumab", "survival". The efficacy endpoints were overall survival (OS) and progression-free survival (PFS). Hazard Ratios (HRs) with their 95% confidence intervals (CIs) were collected from the studies and pooled. By convention, a HR < 1 was a result in favor of bitherapy. Results: This meta-analysis (MA) included nine studies: three assess irinotecan (FFCD 2001-02, CAIRO and an already published MA); three others assess oxaliplatin (FOCUS2, FFCD 2000-05 and FOLFOX pivotal trial) and the last three ones assess bevacizumab (AVEX, AGITG-MAX and AVF2192g). Our MA included 1600 patients (62% of men). Concerning age, we chose a cut-off of 70 years or a cut-off of 75 years, corresponding to the available data for each study. The performance index (PS) was 0-1 for about 90% of patients, with the exception of FFCD 2001-02 and FOCUS2 which included 30% of patients with PS2. Overall, the addition of bevacizumab to fluoropyrimidin statistically improved both OS and PFS (HR = 0.78; CI: 0.62–0.98 and HR = 0.51; CI: 0.41–0.64, respectively). The addition of oxaliplatin statistically improved PFS (HR = 0.81; CI: 0.67–0.97) but not OS (HR = 0.99; CI: 0.85–1.17) as well as the addition of irinotecan (HR = 0.83; CI: 0.68–1.00 and HR = 1.01; CI: 0.84–1.22, respectively). Conclusions: In previously untreated elderly patients with MCRC, the addition of bevacizumab to fluoropyrimidin appears more effective in terms of OS or PFS than the addition of oxaliplatin or irinotecan.
Safety of trifluridine/tipiracil for metastatic colorectal cancer in African American patients participating in an expanded access program.
Authors: Philip Philip Agop , Smaglo Brandon George , El-Rayes Bassel F. , Lesuisse Christian , Makris Lukas 
Published: September 2018

e15039 Background: A Phase 3 clinical trial (RECOURSE) showed that trifluridine/tipiracil (FTD/TPI) was effective in the treatment of refractory metastatic colorectal cancer (mCRC) (Mayer et al. NEJM 2015;372:1909-19). An expanded-access program (EAP) for patients with refractory mCRC assessed FTD/TPI safety in a real-world setting. One limitation of RECOURSE was the small number of African-American (AA) patients enrolled in the study (n=8). The EAP enrolled 45 AA patients, enabling assessment of FTD/TPI safety in this population. Methods: Patients aged ≥18 years with refractory mCRC resistant to ≥2 regimens of standard chemotherapy and an ECOG performance status of 0 or 1 were enrolled in this open-label EAP. Patients received FTD/TPI 35 mg/m2 twice daily for 5 days followed by 2 days’ rest repeated twice followed by 14 days’ rest over a 28-day treatment cycle until drug discontinuation. We investigated duration of exposure to FTD/TPI and associated adverse events (AEs) in AA patients to compare them with non-AA and US patients from RECOURSE. Results: Median duration of FTD/TPI therapy for AA patients in the EAP was 9.7 weeks, similar to non-AA patients in the EAP (9.7 weeks) and US patients in RECOURSE (8.9 weeks) (differences not statistically significant). 73.3% of AA patients (n=33) in the EAP discontinued treatment due to disease progression and 8.9% (n=4) discontinued due to AEs. AEs related to FTD/TPI are summarized in the table. Conclusions: Lung cancer patients in Eastern North Carolina possess a strikingly poor inflammatory signature with significant implications for quality of life and survival. Clinical trial information: NCT02286492. [Table: see text]
TAS 102 in refractory metastatic colorectal cancer: UK Expanded Access Programme experience.
Authors: O'Brien Ciara , Callaghan Sophia , Papaxoinis George , Bennett James , Lee Chern Siang , Evans Rhiannon Mai , Iveson Tim , Adams Richard , Mullamitha Saifee 
Published: September 2018

e15043 Background: Trifluridine/tipiracil (TAS-102), an oral combination of a nucleoside analogue and thymidine phosphorylase inhibitor, showed significant survival benefit in the RECOURSE study. We assessed TAS-102 clinical activity in an unselected patient population with refractory metastatic colorectal cancer in the UK Expanded Access Programme (EAP). Methods: Pharmacy databases were used to identify patients treated with TAS-102 on the UK EAP at three tertiary referral Cancer Centres (Manchester, Cardiff and Southampton) between December 2015 and December 2016. Case notes, laboratory tests and histopathology were reviewed to ascertain survival data and prognostic variables. Results: Of the 78 patients treated with TAS-102, median ECOG PS was 1, 56% of patients were male and median age was 64 years (range 27- 80 years). 31 patients had 3 or more metastatic sites of disease. 26 patients were RAS mutant and 1 patient was B-RAFmutant. Median number of cycles of TAS-102 was 2 cycles (range 1-11 cycles) with one third of patients requiring a dose reduction due to toxicity. 39% of patients developed grade 3 or 4 neutropenia and 12% febrile neutropenia. Response assessment was not performed in 12 patients due to death prior to assessment (6 patients) or withdrawal of patient consent for TAS-102 treatment (6 patients). Where best disease response was assessed by RECIST 1.1 criteria, 26.6% patient showed clinical benefit (stable disease or partial response) whereas 73.3% of patients had confirmed progressive disease. Median follow-up period was 5.2 months with 45 deaths in the study period. Median overall survival (OS) was 6.6 months. OS was significantly worse for patients with hypoalbuminemia (Albumin < 30g/dl) at cycle 1 day 1 TAS-102 (p = 0.028). Anaemia, renal or liver impairment and number of metastatic sites of disease had no impact on patient survival. RAS mutant colorectal cancer patients showed a trend to improved outcome on TAS-102 which did not reach statistical significance within the study follow-up period. Conclusions: TAS-102 shows modest clinical benefit in treatment refractory metastatic colorectal cancer patients on the UK expanded access programme.