bluuebunny/crossref_metadata_2025_split huggingface dataset:
RECIST 1.1 versus immune-related RECIST and immune-related response criteria in assessing response to nivolumab in patients with lung, renal, and head and neck cancers.
Authors: Pathak Surabhi , Messinger Marina , Mullane Michael Russell 
Published: September 2018

e14609 Background: Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 is reported to underestimate response to immunotherapeutic drugs. Therefore, immune related RECIST (iRECIST) based on RECIST 1.1 and immune related response criteria (IRRC) based on WHO response criteria have been studied, mainly in patients with melanoma. Whether RECIST 1.1 underestimates responses in other cancers is not well known. Aim of the present study is to assess response rates to PDL-1 inhibitor Nivolumab in lung, renal and head and neck (H&N) cancers using RECIST 1.1, iRECIST and IRRC. Methods: We reviewed patients from 2012 to present with lung, renal, H&N cancers treated with Nivolumab at John h Stroger Jr. Hospital of Cook County. Incomplete charts and those treated for less than 4 cycles of Nivolumab were excluded. Data was analyzed using descriptive statistics and Fisher exact test. Results: 47 charts were reviewed, 27 met the inclusion criteria. 17 lung (14 adeno, 3 squamous), 7 renal (5 clear cell) and 3 H&N cancer patients were included. Average age was 58.2yrs, 20(74%) were male. Average treatment was for 13 cycles. Response was assessed after at least 4 cycles. Disease control rate for lung, renal, head and neck cancer was 70%,58%, 33% respectively with RECIST 1.1 criteria compared to 77%, 71% and 66% respectively using immune RECIST or IRRC (P > 0.05). No patient developed pseudoprogression. Two had progressive disease per RECIST 1.1 but stable disease with iRECIST and IRRC. 26 of the 27 patients showed concordance between iRECIST and IRRC. One patient had stable disease per iRECIST but partial response per IRRC. Average survival after treatment initiation was 8.3 months for lung, 9.1 months for renal and 5.6 months for H&N cancer. Treatment was discontinued in 2 patients based on progression per RECIST 1.1, both patients had stable disease per iRECIST& IRRC. Conclusions: Trend towards underestimation of treatment response using RECIST 1.1 criteria compared to iRECIST or IRRC was observed. Strong concordance was observed between iRECIST and IRRC. Given relative ease of use, iRECIST might be favored over IRRC in response evaluation for immunotherapeutic drugs.
Association between baseline absolute neutrophil count (ANC), derived neutrophil-to-lymphocyte ratio (dNLR), and platelet-to-lymphocyte ratio (PLR) and response to nivolumab (Nivo) in non-small cell lung cancer (NSCLC): A preliminary analysis.
Authors: Russo Alessandro , Scimone Antonino , Picciotto Maria , Toscano Giuseppe , Raiti Fabio , Sava Serena , Battaglia Alessandra , Adamo Vincenzo 
Published: September 2018

e14617 Background: Nivo is a novel therapeutic option in 2nd line NSCLC. However, predictive biomarkers are lacking. The presence of systemic inflammation correlated with poor outcome in many cancer types, including NSCLC. We aimed to evaluate whether there is a correlation between some indicators of inflammation and response in patients (pts) treated with Nivo or Docetaxel (D). Methods: 23 consecutive pts with NSCLC receiving Nivo were analyzed. Baseline white cell count (WBC) and ANC were collected and correlated with tumor response. 27 NSCLC pts treated with D were used as controls. An ANC ≥ 7500 cell/µl was defined neutrophilia. dNLR was calculated as: ANC/(WBC-ANC). Platelet count (PLT) ≥ 450 × 103/μL was defined as thrombocytosis. PLR ratio was defined as PLT/lymphocyte count. dNLR ≥3 and PLR ≥160 were defined high. Results: Baseline characteristics: median age 66 years (range 45-82); sex M 74%; histology squamous 42%, adenocarcinoma 48%, and 10% mixed histology/NOS. Smoking status: 90% smokers/former smokers. Among non-squamous pts, 13,7% were EGFR mutated and 10,3% were KRAS-mutated, with an equal distribution in both treatment groups. Lines of therapies: range 2-8 in Nivo group and 2-3 in D group. Overall response rate (ORR): 13.6% with Nivo vs. 7.7% with D; 9% of pts with Nivo experienced unconventional responses. Baseline neutrophilia (17.4% with Nivo and 27% with D) and thrombocytosis (4.3% and 3.8%, respectively) were not associated with response (ORR 0%). High dNLR (13% and 38% with Nivo and D) correlated with no response (0% ORR), whereas high PLR correlated with no responses to D and reduced ORR to Nivo (10%). Conclusions: The results of this preliminary study suggest that baseline neutrophilia, thrombocytosis and high dNLR are associated with no response to both D and Nivo, whereas high PLR is associated with no response to D and reduced activity with Nivo. Given their relative easy estimation, baseline evaluation of these indicators of inflammation should be included before 2nd line therapy start, especially for highly expensive treatments, such as immunotherapy.
The evolving landscape of oncolytic virotherapy (OV) clinical trials (CT): Meta-analysis.
Authors: Park Wungki , Algaze Sandra , Abi Aad Simon , Kwon Deukwoo , Elias Roy , Acquavella Nicolas , Merchan Jaime R. ,   University of Miami/Sylvester Comprehensive Cancer Center/Jackson Health System
Published: September 2018

e14636 Background: The number of new OV CT have been increasing along with the evolution of cancer immunotherapy. The OVs induce direct oncolysis and enhances the host innate and adaptive immunity. There are ongoing efforts to improve the anticancer efficacy of OVs with combinational strategies. However, there has been no direct comparison of OV CTs to evaluate their different dose levels, administration routes, frequencies, and the types of OVs and combinations. Methods: A random-effect meta-analysis was performed to evaluate pooled best ORR of all the existing OV phase II and III trials from publications and presented abstracts from ASCO, AACR, and ASGCT from 1/1/2016 to 12/4/2016. MeSH term “oncolytic” was used in PubMed. The inclusion criteria were: phase II or III, solid tumor, reported ORR. We evaluated the best ORR among different viruses, DNA vs. RNA, intratumoral (IT) vs. intravenous (IV) / intra-arterial (IA), and single vs. combination. Results: From 79 publications and 176 presented abstracts identified, 6 published studies and 12 presented abstracts were selected and pooled (n=875). The best ORRs were: DNA OV 23% (15 ~ 34%) vs. RNA OV 31% (13 ~ 58%), IT 36% (23 ~ 51%) vs. IV/IA 16% (10 ~ 25%), and single agent 22% (16 ~ 31%) vs. combinations 35% (17 ~ 58%). The combination OV CTs were either with chemotherapy (n= 144), chemoradiation (n= 23), or immunotherapy (n= 69). Each OV’s ORR is summarized in the table below. Direct comparison of the secondary endpoints: clinical outcome and adverse events will be presented with the poster. In general, the OV CTs had good overall safety profile and most adverse events were less than grade 3. Conclusions: The antitumor effect of OVs against solid tumors is evident and consistent in many trials. The largest data currently available is with herpes virus and coxsackie virus appears to have the best ORR possibly due to the combination with immunotherapy. The above results confirm the promising clinical activity of novel oncolytic viral vectors both alone and in combination. [Table: see text]
Real-world adherence and treatment discontinuation with trifluridine/tipiracil (FTD-TPI) compared with regorafenib (REG) for the treatment of metastatic colorectal cancer (mCRC).
Authors: Patel Anuj K. , Duh Mei Sheng , Barghout Victoria E. , Yenikomshian Mihran Ara , Xiao Yongling , Wynant Willy , Tabesh Majid , Fuchs Charles S. 
Published: September 2018

e15000 Background: FTD-TPI and REG both prolong survival in refractory mCRC. Both agents have the benefit of oral administration but with distinct side effect profiles. This study aims to compare real-world treatment patterns following initiation of FTD-TPI or REG for mCRC in a large, nationally representative US claims database. Methods: Retrospective data from 10/2014 to 7/2016 from the US Symphony Health Solutions’ Integrated Dataverse (IDV®) database were analyzed for patients (pts) receiving FTD-TPI or REG. The index date was the date of first FTD-TPI or REG prescription. Pts were included if: 1) age ≥18 years old, 2) ≥1 CRC diagnosis, 3) no diagnosis of gastric cancer or gastrointestinal stromal tumor, and 4) continuous clinical activity for ≥3 months before and after index date. The observation period spanned from index date to end of data, end of continuous clinical activity, or switch to another mCRC treatment. Medication adherence was assessed by medication possession ratio (MPR), with MPR ≥80% as the defined threshold for adherence, as well as by proportion of days covered (PDC) at 3 months. Between treatment groups, binary endpoints were compared using Chi-square tests and mean and median time to treatment discontinuation (TTD) were compared using t-test and Wilcoxon test, respectively. Results: The study population consisted of 1,630 FTD-TPI pts and 1,425 REG pts. Mean ± standard deviation (SD) age of FTD-TPI pts was 61 ± 11 and REG pts was 63 ± 11 (p < 0.01). Mean ± SD length of observation period in days was 161 ± 59 for FTD-TPI pts and REG pts was 212 ± 113 (p < 0.01). 84% of FTD-TPI and 74% of REG pts reached MPR ≥80% (p < 0.01). FTD-TPI pts had higher mean PDC (71% vs 59%, p < 0.01) than REG pts. Mean and median TTD were significantly longer for FTD-TPI than REG pts (mean: 101 vs. 88 days, p < 0.01; median: 97 vs. 69 days, p < 0.01). Conclusions: In this analysis of real-world medication utilization for mCRC pts, those pts started on FTD-TPI had significantly higher medication adherence and longer TTD than those on REG.
Distribution and pathogenicity of nsSNPs in receptor tyrosine kinases (RTKs) in patients with colorectal cancer.
Authors: Stein Matthew K , Karri Saradasri , Morris Lindsay Kaye , Sareen Srishti , Patel Kruti , Daugherty Ray Scott , Shibata David , Vanderwalde Ari M. , Schwartzberg Lee Steven , Martin Michael Gary 
Published: September 2018

e15012 Background: Non-synonymous single nucleotide polymorphisms (nsSNPs) occur along the entire sequence of RTKs and can promote oncogenic activity. As prior “hot-spot” testing was limited to the tyrosine kinase domain (TKD), next-generation sequencing (NGS) allows the discovery of novel extra-TKD variants. Methods: We analyzed all nsSNPs in 29 RTKs of colon cancer patients (pts) who received tumor profiling (2013-2015) with Caris NGS. Mutations were classified by location including the TKD, extracellular domain (ECD), transmembrane domain (TM), juxtamembrane domain (JM) and carboxy-terminal (CT) regions. nsSNPs underwent in silico analysis using PolyPhen-2 (Harvard) to predict if damaging (pnsSNP). Results: 110 pts were identified with a median age of 58 years (range 37-86); 55% male; 57% white, 41% black. 51 were KRAS+, 12 BRAF+, 5 NRAS+ and 5 were microsatellite unstable (MSI-H); 67 were left-sided, 31 right-sided, 10 transverse and 2 unknown. A total of 171 nsSNPs and 7 pathogenic mutations (Pmut) were detected: ERBB2 (ECD S310F, TKD V777L and TKD V842I), ERBB3 (ECD A232V and TKD Q809R), FGFR2 (ECD S252L) and RET (TKD L790F). 83/110 (76%) pts had ≥1 RTK mutation (median 1; range 0-9). 72/171 (42%) variants were pnsSNPs and found in 50 (45%) pts; 14% of pts had ≥2. All 29 RTKs had nsSNPs with median 6 (range 2-12); 24/29 RTKs had a Pmut or pnsSNP (median 2; range 0-8). RTKs with the most nsSNPs were EPHA5 (8/10 were pnsSNPs), PDGFA (7/8), ALK (6/8), ERBB4 (5/8), NTRK3 (5/6), cKIT (4/9), ROS1 (3/12), PDGFRB (3/6) and FGFR1 (3/6). nsSNPs were distributed across all RTK domains: 50% were ECD (30/86 pnsSNPs), 27% TKD (28/46), 13% CT (7/22), 5% JM (6/9) and 5% TM (1/8). No significant difference was seen between pnsSNP incidence and sidedness or KRAS/BRAF/NRAS status. In MSI-H pts, 13/22 variants were pnsSNPs (median 2; 1-5); 4/5 MSI-H were right-sided (Fisher’s exact p < 0.01). Conclusions: > 70% colon cancer pts had ≥1 mutation in 29 RTKs with > 70% outside the TKD, and > 40% pnsSNPs. MSI-H had a higher incidence of pnsSNPs; further study is warranted to determine their significance and actionability.
Is FOLFOXIRI alone or combined with targeted therapy administered as first-line treatment a reasonable choice for most patients with mCRC? Systematic review and network meta-analysis.
Authors: Zhou Mingyi , Yu Ping , Hernick Dengue , Li Yanrong , Wang Yuanhe , Fu Lingyu , Zhang Jingdong 
Published: September 2018

e15018 Background: Controversy surrounds the question of whether the prognosis of most patients with metastatic colorectal cancer (mCRC) is improved using intensive administration of folinic acid, 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI) alone or combined with target therapy as first-line treatment. Methods: We queried PubMed, the Cochrane Collaboration Central Register of Controlled Clinical Trials, Cochrane Systematic Reviews, ClinicalTrials.gov, the databases of the European Society for Medical Oncology and the American Society of Clinical Oncology to identify abstracts of randomized controlled trials evaluating the efficacies and toxicities of intensive therapies used for first-line treatment of patients with mCRC. The search included articles dated from the inception of these resources until December 31, 2016. We estimated hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and relative risks (RRs) for the objective response rate (ORR), the R0 resection rate, and toxicities. Results: Nine RCTs comprising 2,256 patients were included in this network meta-analysis. The PFS of patients administered FOLFOXIRI plus target therapy experienced prolonged PFS and OS and improved ORRs compared with FOLFOX or FOLFIRI plus target therapy (PFS: HR 0.65, 95% CI 0.46–0.91; OS: HR 0.80, 95% CI 0.65–0.98; ORR: HR 1.70, 95% CI 1.16–2.49; R0 resection rate: HR 2.66, 95% CI 1.86–3.82). There were no significant differences between PFS, OS, ORRs, or R0 resection rates and toxicities of patients administered FOLFOXIRI and FOLFOX or FOLFIRI plus target therapy. Further, FOLFOXIRI plus target therapy did not increase toxicities compared with FOLFOX or FOLFIRI plus target therapy, except for neutropenia. Conclusions: FOLFOXIRI plus target therapy when administered as first-line treatment of patients with mCRC is the best choice and did not significantly increase toxicities. FOLFOXIRI is as effective as FOLFOX or FOLFIRI plus target therapy.
Epithelial circulating tumor cells in portal vein are associated with number of liver metastatic nodules of colorectal cancer.
Authors: Huang Na , Zheng Siting , Fang Yisheng , Shi Min , Liao Wangjun 
Published: September 2018

e15026 Background: Colorectal cancer has been one of the most diagnosed cancers worldwide, and circulating tumor cells (CTCs), resulting in colorectal liver metastases (CLM), relate to its mortality. Although the mechanism and prognostication of metastasis has attracted a broad interest, the definite relationship between CLM and different phenotype of CTC is still not sufficient. Our objective is to investigate the clinical implication of different phenotype of CTCs. Methods: Twenty-one patients with CLM were enrolled in this study. Peripheral venous (PeV) and portal vein (PoV) blood specimens were collected from each patient. Through real-time ultrasound-guided percutaneous portal vein access, Pov blood was collected. Then CTC detection technology was employed to isolate CTCs for categorization. Results: No difference in the number of total CTCs between PoV and PeV, while strikingly, the number of epithelial CTCs was higher in PoV. In patients with unresected primary lesions, epithelial CTCs in PoV were more than that in PeV, while there was no difference in resected ones. Furthermore, we demonstrate that the percentage of epithelial CTCs in PoV relate to the number of liver metastatic nodules. In addition, the increased percentage of epithelial CTCs in the PoV relates to low amounts of lymphocytes. Conclusions: Our study shows that high proportion of epithelial CTCs in Pov relates to increasing number of liver metastatic nodules in CLM.
Anti-EGFR-based conversion chemotherapy in RAS wildtype colorectal cancer patients: Impact on survival and resection rates.
Authors: Koch Christine , Schmidt Niklas , Winkelmann Ria , Eichler Katrin , Hansmann Martin-Leo , Bechstein Wolf O. , Pession Ursula , Zeuzem Stefan , Trojan Jorg , Waidmann Oliver 
Published: September 2018

e15029 Background: Initially unresectable colorectal liver metastases can become resectable after chemotherapy. Chemotherapy combined with EGF-receptor antibodies has shown consistent high response rates in patients with RAS wildtype tumors. However, the influence of RAS mutations other than exon 2 mutations in the context of a conversion strategy has not been systematically studied yet. Methods: Out of a cohort of 424 patients with mCRC, we identified 30 patients with initially unresectable KRAS exon 2 wildtype colorectal liver metastases who received neoadjuvant chemotherapy including cetuximab or panitumumab between January 2008 and February 2014. In all patients extended RAS analysis (KRAS and NRAS exon 3 codon 59 and 61 and exon 4 codon 117 and 146) was carried out. Resection status (R0, R1 or R2), PFS and OS were recorded in all patients and maximum tumor shrinkage was calculated. Results: RAS mutation analysis identified further KRAS mutations in 4/30 patients (13.3%). No NRAS mutations were found. In none of these four patients a R0 resection could be achieved. In contrast, 15/26 (57.7%) RAS wildtype patients could be R0 resected. Median survival of patients with a RAS wildtype tumor was 64.0 [range: 7.4-98.6] months vs. 28.0 [range: 16.4- 40.6] months in those with a RAS mutation (hazard ratio, HR, 0.53; 95% confidence interval, CI: 0.15-1.81, p = 0.3). Median PFS in patients with a RAS mutation was 8 [range: 6-28.8] months compared to 10.4 [range, 1.7-15.2] months in patients with a RAS wildtype cancer. Median overall survival was > 63.3 months in R0-resected patients vs. 30.0 months in those with a R1 or R2 resection (HR 0.23; [95% CI 0.10- 0.75; p = 0.008). Conclusions: Our data suggest that a RAS wildtype status and a R0 resection are the strongest predictors for overall survival. The extended RAS analysis allows a better patient selection for anti-EGFRbased conversion chemotherapy before secondary resection of colorectal liver metastases.
Differential clinical outcome of metastatic colorectal cancer (MCRC) patients (pts) treated with first line FIr-B/FOx adding bevacizumab (BEV) to triplet chemotherapy according to KRAS, NRAS and BRAF genotype detected by massive parallel sequencing.
Authors: Bruera Gemma , Pepe Francesco , Malapelle Umberto , Pisapia Pasquale , Dal Mas Antonella , Marchetti Paolo , Calvisi Giuseppe , Troncone Giancarlo , Ricevuto Enrico 
Published: September 2018

e15041 Background: KRAS/NRAS/BRAF genotypes guide tailoring of first and subsequent lines of MCRC treatment strategy. First line triplet chemotherapy/BEV associations significantly improved progression-free survival (PFS) and overall survival (OS) in overall MCRC patients. OS may be significantly worse in the prevalent KRAS c.35 G > A and BRAFmutant (mt). Evaluation of differential clinical outcome in overall MCRC patients will help identify clinically relevant biomarkers to personalize treatment strategy. Methods: Tumoral samples of 67 MCRC pts treated with FIr-B/FOx (77% overall) were analyzed through a 50 genes panel (PGM/Colon Lung Cancer) by ION Torrent: 58 (86.5%) primary, 9 (13.4%) metastatic samples; 60 (89.5%) pre-, 7 (10.4%) post-treatment. KRAS, NRAS and BRAFcoding frames were analysed. Molecular diagnostic criteria for mutation detection: > 50% coverage; > 1% mutant allelic fraction. Clinical outcomes (PFS and OS) were evaluated and compared by log-rank. Results: Mutant KRAS2-4/ NRAS2-4/ BRAF MCRC patients were 49 (73.1%): KRAS 42 (62.6%), NRAS 15 (22.3%), BRAF 5 (7.4%). BRAF mutations were all atypical and concomitant with KRAS and/or NRAS mutations. At median follow-up 21 months (m), overall PFS and OS were 13 and 27m, and KRAS exon 2 wild-type (wt)/mt PFS 14/12m, and OS 28/21m, respectively, consistent with previously reported, and not significantly different. KRAS2-4/ NRAS2-4/ BRAF wt/mt, PFS 18/12m, OS 28/22m, not significantly different: KRAS2-4 wt/mt, PFS 13/12m, OS 27/27m, not significantly different; NRAS2-4 wt/mt, PFS 16/12m, OS 28/22m, not significantly different; c.35 G > A KRAS mt showed trendy worse PFS/OS 8/14m, respectively; BRAFmt/wt trendy worse PFS 8 vs 14m and OS 11 vs 28m. Conclusions: Retrospective analysis of clinical outcome of MCRC patients treated with intensive first line BEV added to triplet chemotherapy FIr-B/FOx seems to be not significantly affected by KRAS/ NRAS/ BRAF genotype.
Prognostic impact of tumor deposits in colorectal cancer with lymph nodes metastasis.
Authors: Liu Fangqi , Zhao Jiang , Yang Li , Zhu Ji , Xu Ye 
Published: September 2018

e15051 Background:The TNM classification system was widely used in managing many kinds of cancer including colorectal cancer. However, there is one undefined aspect that is the value of tumor deposits (TDs) in the condition of TDs and lymph nodes metastasis (LNM) coexisting. This research aims to clarify the prognostic impact of TDs in colorectal cancer especially for the condition of TDs combined with LNM. Methods: An analysis was performed to evaluate the prognostic significance of TDs in stage Ⅰ to Ⅳ colorectal cancer patients from 2010 to 2013 using Surveillance Epidemiology and End Results (SEER) database as a training cohort (N = 65, 537). An additional 3, 719 patients from Fudan University Shanghai Cancer Center were enrolled between 2006 and 2014 as a test cohort to validate the results. Results: TDs were observed in 6.32% of patients in training cohort and 14.7% in test cohort. A significantly reduced overall survival was observed for TDs positive in LNM positive and negative colorectal cancer patients (hazard ratio [HR], 1.65; 95% CI, 1.54 to 1.76). Further analysis combining TDs with LNM shows that there is no considerable difference in the impact on overall survival between N1 and N1c or between N1 with TDs (N1TD) and N2. The 3-year survival rate was 82.3%, 72.0%, 69.9%, 55.7%, 52.1%, 39.4% for N0, N1, N1c, N1TD, N2 and N2 with TDs (N2TD) respectively. Similar results were observed in the test cohort. Conclusions: These results support the 7th and 8th TNM system in which N1c was integrated into pathological N classification. However, LNM with positive TDs should be also considered into the TNM classification system because of the high prognostic impact of TDs, which was not mentioned in the current TNM system.