bluuebunny/crossref_metadata_2025_split huggingface dataset:
How to deal with second line dilemma in metastatic colorectal cancer? A systematic review and meta-analysis.
Authors: Galvano Antonio , Guarini Aurelia , Cusenza Stefania , Barraco Nadia , Castiglia Marta , Incorvaia Lorena , Rizzo Sergio , Fulfaro Fabio , Beretta Giordano D. , Carreca Ignazio Ugo , Bazan Viviana , Russo Antonio 
Published: May 2019

e15006 Background: Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy in combination with chemotherapy as second line for metastatic colorectal cancer (mCRC). However, there is still a paucity of evidence or guidelines suggesting the right sequential treatment in all RAS (KRAS/NRAS) wild type(wt)mCRC. Therefore, we aimed to evaluate the impact of these targeted therapies by reviewing literature data. Methods: We used Cochrane, EMBASE and Medline databases to select phase III clinical trials containing efficacy and safety data about chemotherapy (CT) or CT + targeted agents combination (Anti-VEGF and Anti-EGFR) in second line mCRC setting. We performed direct comparisons to obtain pooled data for anti-VEGF + CT versus CT and anti-EGFR +CT versus CT comparisons. Then we performed indirect comparisons between anti-EGFR and Anti-VEGF. Outcomes were disease control rate (DCR), response rate (RR), progression-free survival (PFS), overall survival (OS) and most common G3-G5 toxicities. Results: Eight eligible RCTs (6793 pts) were included: 5 studies compared anti-VEGF + CT and 3 anti-EGFR + CT combinations to CT. After direct comparisons, pooled indirect results showed significantly improved OS (HR 0.83, 95% CI 0.72–0.94) and DCR (HR 1.27, 95% CI 1.04–1.54) favouring anti-VEGF combinations in overall population; however, no statistically significant differences in all RAS wt patients was observed (HR 0.87, 95% CI 0.70–1.09). Additionally, anti-EGFR combinations significantly increased ORR in all patients (RR 0.54, 95% CI 0.31–0.96), showing a trend in all RAS wt patients (RR 0.63, 95% CI 0.48–0.83) too. Furthermore, no significant difference in PFS and DCR all RAS was registered. Anti-VEGF combination significantly increased Only a significant asthenia difference (RR 1.34, 95% CI 1.03–1.75) was registered. Conclusions: At our knowledge, our indirect comparisons between anti-VEGF and anti-EGFR combinations showed for the first time better OS and DCR for anti-VEGF combinations, whereas better RR is observed for anti-EGFR combinatory regimens, defining a role of both targeted agents in second line mCRC setting.
Apatinib combined with Raltitrexed in patients with metastatic colorectal cancer after failure of standard therapy (AHEAD-311): A single-arm phrase II pilot trial.
Authors: Si Haiyan , Gou Miaomiao , Zhang Yong , Yan Huan , Qian Niansong , Wang Zhikuan , Shi Yan , Dai Guanghai 
Published: May 2019

e15008 Background: To assess the safety and efficacy of apatinib, an oral vascular endothelial growth factor receptor-2 inhibitor, combined with thymidylate synthase inhibitor raltitrexed in patients with metastatic colorectal cancer (mCRC) as a third- or later-line therapy. Methods: Patients with mCRC after at least 2 lines of chemotherapy were enrolled whenever they previously treated with bevacizumab or not. Apatinib was given orally at 250mg or 500mg daily. Raltitrexed was administered intravenously at 3 mg/m2 on day 1 every 3 weeks. The primary endpoints were progression-free survival (PFS). The second endpoints were objective response rate (ORR), overall survival (OS) and safety. Results: From August 2017 to November 2018, thirty-one patients were enrolled in Chinese PLA General Hospital. After a median follow-up of 6.4 months, the median treatment cycle was 4. four patient achieved partial response(PR), and 11 patients achieved stable disease (SD) and 16 achieved progression disease (PD) in accordance with RECIST version 1.0, illustrating a DCR of 48.4% and an ORR of 12.9% .The Median PFS was 2.4 months and the median OS was 6.4 months. The most common adverse events were hypertension (n=12, 38.7%), nausea and vomiting (n=11, 33.8%), myelosuppression (n=9, 29.0%). The most common grade 3 to 4 adverse events were hypertension (n=2, 6.4%) and hand-foot syndrome (n=2, 6.4%). Grade 3 to 4 hematologic toxicities were rare. One patient died from cardiac arrest after three days treatment. There was no significantly association between PFS or OS, and clinical features including tumor location, KRAS status, and prior surgery or not, and number of metastatic organs. There was no trend showing patients who experienced had hypertension or myelosuppression had longer PFS and OS. Compared to the patients never received bevacizumab, the patients who had previously bevacizumab had the similar PFS and OS (3.9 versus 2.3months, P=0.787; 6.1 versus 6.4months, P=0.287). Grade1-2 nausea and vomiting and age <57 were independent predictors for longer PFS and OS. Conclusions: Apatinib combined with raltitrexed had efficacy but had limited survival benefit in mCRC refractory to standard chemotherapy. This regime showed us a higher risk of adverse event incidence and warrant further exploring of benefit population. Clinical trial information: NCT03344614 .
Clinical efficacy and safety evaluation of nimotuzumab combined with chemotherapy in the treatment of advanced colorectal cancer: A retrospective analysis.
Authors: Bai Sai-xi , Zhang Ruo-rong , Chen Wang-hua , Dong Hongmin , Wang Gang , Li Xiaokai , Wang Ling Wen 
Published: May 2019

e15009 Background: To retrospectively analyze the clinical effects and safety of nimotuzumab combined with chemotherapy as the first-line treatment of advanced colorectal cancer (ACRC). Methods: ACRC patients treated by nimotuzumab combined with chemotherapy (40 cases) or chemotherapy alone (44 cases) were enrolled in this study. Responses were evaluated by Respond Evaluation Criteria in Solid Tumors. Adverse events were evaluated by Common Terminology Criteria for Adverse Events 3.0. Results: The combined treatment group had a slightly higher objective response rate (RR) and disease control rate (DCR) (RR: 55.0% vs 36.4%; DCR: 85.0% vs 75.0%) compared to the chemotherapy alone group, although not statistically significant (P > 0.05). The median progression-free survival (PFS) was 9.89 months in the combined treatment group and 7.86 months in the chemotherapy alone group, respectively. The median survival time was 22.32 months in the combined therapy group and 18.10 months in the chemotherapy alone group, respectively (P = 0.060). There was no statistically significant difference regarding the adverse events between these two groups. Conclusions: The nimotuzumab combined with chemotherapy had similar efficacy and safety to chemotherapy-alone treatment in ACRC. The efficacy and safety of the combined treatment should be further studied with a randomized multicentre trial with a larger number of ACRC patient.
Association between hand-foot skin reaction (HFSR) and survival benefit of fruquintinib in FRESCO trial.
Authors: Li Jin , Qin Shukui , Bai Yuxian , Deng Yanhong , Yang Lei , Xu Ruihua , Chen Zhendong , Zhong Haijun , Pan Hongming , Guo Weijian , Shu Yongqian , Yuan Ying , Xu Jianming , Shen Lin , Wang Ning , Zhu Chao , Fan Songhua , Gong Wei , Wang Wei 
Published: May 2019

e15012 Background: In phase 3 FRESCO trial, fruquintinib demonstrated a statistically significant and clinically meaningful overall survival benefit in Chinese metastatic colorectal cancer (mCRC) patients. As a known adverse effect of vascular endothelial growth factor receptor (VEGFR) inhibitors, hand-foot skin reaction (HFSR) was commonly reported as a drug-related adverse event (AE) in fruquintinib group. This retrospective analysis explored whether HFSR in fruquintinib group is associated with survival benefit in FRESCO. Methods: This analysis used a subpopulation of intent-to-treat population who at least completed one cycle and entered cycle two of fruquintinib treatment. Patients randomized to receive fruquintinib 5 mg/day during the first 3 weeks of each 4-week cycle were divided into subgroups based on whether they reported HFSR. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method. Hazard ratio (HR) was estimated through Cox proportional hazards model. P-value was generated from log-rank test. Results: Among a total of 255 fruquintinib-treated patients who at least completed one cycle and entered cycle two, 52% (n = 133) reported HFSR of any grade. The median time-to-onset of HFSR (any grade) was 21 days and approximate 75% patients reported HFSR after cycle two treatment completion. The baseline characteristics were well balanced between HFSR reported and non-reported subgroups. Patients who reported HFSR showed both OS and PFS benefit with statistical significant difference comparing with HFSR non-reported patients in fruquintinib group. Fruquintinib significantly decreased 43% death risk in HFSR reported patients and prolonged the median OS to 11.14 months in comparison with HFSR non-reported patients (median: 11.24 vs 7.54 months; HR = 0.57, 95% CI: 0.42-0.78; p < 0.001). Similarly, Patients reported HFSR had a significantly longer PFS than those who did not reported HFSR in the fruquintinib group (median: 5.49 vs 3.48 months; HR = 0.70, 95% CI: 0.54-0.91; p = 0.008). Conclusions: This post-hoc analysis indicates that patients who had HFSR had a greater survival benefit from fruquintinib in Chinese mCRC patients. Clinical trial information: NCT02314819 .
Cost and effectiveness of genetic testing in metastatic colorectal cancer (mCRC) at Montefiore Medical Center (MMC).
Authors: Ashai Nadia , Stuart Matthew , Mejia Saldarriaga Mateo , Zhang Wei , Huang Renee , Narang Rahul , Chuy Jennifer W. , Kaubisch Andreas , Goel Sanjay , Halmos Balazs , Rajdev Lakshmi 
Published: May 2019

e15043 Background: Upfront testing for MSI, and mutations in KRAS, NRAS, and BRAF is recommended. The most cost-effective way of obtaining this information remains unclear. We examined cost of broad next generation sequencing (NGS), in comparison to hotspot (HT) and individual target (IT) testing in patients with mCRC with Medicare (MC) and commercial insurance (CI) at MMC. As a surrogate of effectiveness, we hypothesize that patients with NGS are more likely to enroll in clinical trials. Methods: Cost of individual and hotspot tests were derived from known reimbursement rates with insurances affiliated with MMC. Due to ongoing changes in current procedural terminology for NGS, we used known reimbursement amounts from our patients. We applied these costs to a model population of 1,000,000 people. We then evaluated clinical trial enrollment of patients who had either NGS or hotspot/individual testing. Results: MC costs for IT, HT, NGS testing were $1,504, $752, and $4,680 respectively. CI costs were $1,910, $814, $2,366 for IT, HT, and NGS testing respectively. When applied to our model population, NGS cost $914,604 and $1,131,016 more than individual and hot spot testing respectively for MC patients, and $21,432 and $72,924 more for CI patients. Analysis of effectiveness included 136 patients, wherein 8% of those with NGS (n = 5/61) were enrolled in clinical trials as a result of testing compared to 1% of those with HT/IT (n = 1/75). Conclusions: Broad spectrum NGS costs more than individual or hot spot testing in mCRC. However, patients with NGS testing were more likely to be enrolled in clinical trials, suggesting the need for studies to further evaluate ideal testing modality. [Table: see text]
Predictors of survival in chemorefractory colorectal liver metastases treated with Y90 radioembolization.
Authors: Dabrowiecki Alexander Michael , Sankhla Tina , Shinn Kaitlin , Bercu Zachary Louis , Ermentrout Robert Mitchell , Newsome Janice , Shaib Walid Labib , Cardona Kenneth , Kokabi Nima 
Published: May 2019

e15044 Background: The aim of the study was to evaluate molecular signatures and timing of yttrium-90 (Y90) as prognostic factors of survival following Y90 radioembolization (RE) in patients with chemorefractory colorectal liver metastases (CRLM). Methods: In a retrospective single-institution study, patients with unresectable, chemorefractory CRLM who had undergone genomic analysis prior to Y90 RE from 2013 to 2018 were identified. Timing of Y90 (following failure of first line vs following multiple lines of chemotherapy) and oncogenic mutation status (MAPK and PI3K pathways) were evaluated as predictors of survival length following Y-90. Survival was measured from first Y90 using Kaplan-Meier estimation and predictors of outcome were identified using log-rank analysis. Results: Overall, 58 patients with chemorefractory CRLM who underwent genomic analysis prior to Y-90 were identified. Of these, 26 (44.8%) had MAPK mutations, and 2 (3.5%) had PI3K mutations. Median survival after first Y-90 RE was 12.9 months. There was significantly prolonged overall survival (OS) in patients receiving Y90 immediately following failure of the first line of chemotherapy (FOLFOX ± bevacizumab) versus patients who underwent multiple lines of chemotherapy prior to Y90 (median OS of 16.9 vs 11.4 months for others; p = 0.023). When stratifying the cohort based on the timing of Y90, patients with WT-MAPK (n = 8) had prolonged OS if they underwent Y-90 following failure of the first line of chemotherapy (median OS of 22.3 vs 12.9 mo; p = 0.019). Patients with WT-PI3K (n = 19) had prolonged OS if they underwent Y90 following failure of the first line of chemotherapy (median OS of 16.9 vs 12 mo; p = 0.037). When analyzing the entire cohort non-stratified by timing of Y90, genetic mutation was not found to be a predictor of prolonged OS. Conclusions: Y90 RE after failure of first line of chemotherapy in CRLM appears to confer prolonged survival specifically for WT-MAPK and WT-PI3K oncogenes. Conversely, the prognosis of more favorable genetic status appears to be negated if Y90 RE is performed after failure of second or third line chemotherapies.
Outcomes of metastatic colorectal cancer over fifteen years from an Indian tertiary care center: A retrospective analysis.
Authors: Sharma Vinod , Sharma Atul , Pathy Sushmita , Shukla Nootan Kumar , Deo S V Suryanarayana , Thulkar Sanjay , Kumar Sunil , Sahoo Ranjit 
Published: May 2019

e15050 Background: Management of metastatic colorectal cancer (CRC) has revolutionised over the past 2 decades and a number of drugs are part of active disease management including biologicals. Published large database on metastatic CRC outcome has been lacking from India. Methods: A retrospective data analysis of metastatic CRC from prospectively based database was performed from the year, 2001-2015. All patients who have received at least 1 cycle of chemotherapy were enrolled. Kaplan Meier analysis was done for overall survival (OS). Cox-regression model was done to determine prognostic factors of OS. Results: A total of 288 patients including upfront metastatic (n = 197, 68%) and relapsed (n = 91, 32%) with male to female ratio of 1.4:1 and median age of 46 years were studied. CEA was high in 78% with median level of 20 ng/ml. Most common site of primary tumor location was rectum (47%). Proportions of left side, right side and transverse colon was 75%, 20% and 4.2%. Mucinous and signet histologies were seen in 24% and 9.2% of patients. Most common sites of metastases being liver (43%), peritoneum (31%) and lung (18%). Oxaliplatin based therapy was used 71% of patients as 1st line. Median chemotherapy cycles for both 1st and 2nd line regimen was 6. Biologicals were part of 1st line regimen in only 12.5% of patients. Median OS of our cohort was 18.5 months. Predictors of poor OS were ECOG PS > 1 (HR 2, CI: 1.3-3.3, p value = 0.003), high CEA ( > 5ng/ml, HR 2.5, CI: 1.3-4.6, p value = 0.004), low albumin (< 3.5 g/dl, HR 1.7, CI: 1.03-2.9, p value = 0.045), < 2 lines of chemotherapy received (HR 2, CI: 1.3-3.3, p value = 0.001). Conclusions: Outcomes of metastatic CRC in our cohort with use of doublet chemotherapy (small proportion with biologicals) is comparable to published literature worldwide. We have higher proportion of younger population, rectum cancer, signet and mucinous histology and higher incidence of peritoneal involvement.
Evaluation of long term survival in pretreated metastatic colorectal cancer patients undergoing GOLFIG chemoimmunotherapy regimen.
Authors: Correale Pierpaolo , Giannicola Rocco , Staropoli NIcoletta , Ciliberto Domenico , Azzarello Domenico , Tripepi Giovanni , Agostino Rita Maria , Strangio Alessandra , Altomonte Maria , Nesci Antonio , Francini Guido , Pastina Pierpaolo , Tassone Pierfrancesco , Pirtoli Luigi , Caporlingua Nadia , Falzea Antonia Consuelo , Tagliaferri Pierosandro 
Published: May 2019

e15057 Background: In the last few years, there has been a renewed interest on the potential use of immunotherapy alone or combined to chemotherapy (CHT) for mCRC patients. GOLFIG regimen (biweekly Gemcitabine+FOLFOX and IL2 and GM-CSF) was designed to enhance immunomodulating effects of selected cytotoxic drugs by combining them with cytokines able to promote priming and effector phases of the immune-response. This regimen has been tested in two different phase II and III clinical trials in mCRC patients, whose successful results have been published. Here we present the results a retrospective analyses including all the patients treated in a period of 16 years. Methods: This is a multi-institutional retrospective study including 179 mCRC patients (106 men, 73 women). They received a median of 12 courses of GOLFIG regimen (treated between June 2002 and November 2018). K-RAS mutational status has also been evaluated in 74 pts (41 wild type and 33 mutated); as for sidedness 112 pts had a left disease and 67 pts right disease; 71 pts received only one previous CHT line and 100 more than two lines. PFS and OS were evaluated by Kaplan-Meier curves and Cox-regression analyses in different subgroups (RAS mutational status, sidedness, previous CHT lines) to estimate their effect on survival endpoints. Results: We recorded a mean PFS and OS of 15,28 [95%CI:10,36-20,20] and 24,61 [95%CI:19,07-30,14] months, respectively, with no difference in efficacy outcomes observed among the different subgroups (one vs. more than one previous CHT lines; left vs. right primary side; k-ras status mutated vs. wt). Finally, we recorded a 2, 5 and 10 year OS-rate, in 42, 17 and 14 percent of the patients, respectively. The occurrence of self-limiting autoimmunity was confirmed as highly predictive of longer survival. Conclusions: These results confirm that GOLFIG regimen has strong efficacy in mCRC pts and may represent a reliable option in pretreated setting without evident effect of known prognostic variants. Such data offer a strong basis for future clinical trials in mCRC patients, where GOLFIG may represent a scaffold for combinatory immunotherapy approaches with immune-checkpoint blocking drugs.
FOLFOXIRI versus doublet-regimens in the first-line therapy of MSI-S right-sided (RS) metastatic colorectal cancer (mCRC): A survival analysis.
Authors: Jacome Alexandre A , Kee Bryan K. , Fogelman David R. , Shureiqi Imad , Dasari Arvind , Raghav Kanwal Pratap Singh , Morris Van K. , Johnson Benny , Wolff Robert A. , Overman Michael J. , Kopetz Scott , Rogers Jane , Ahmed Shahab U. , Mehdizadeh Amir , Eng Cathy 
Published: May 2019

e15060 Background: Microsatellite stable (MSI-S) RS mCRC patients (pts) have a worse prognosis relative to left sided tumors for overall survival (OS). The present analysis aims to test the hypothesis that a triplet-regimen is superior compared to doublet-regimens (DR; FOLFOX or FOLFIRI) for OS. Methods: Pts with treatment-naive RS mCRC at MD Anderson Cancer Center between January/2011 to December/2018 were selected. We compared the progression-free survival (PFS) and OS of mCRC pts treated with FOLFOXIRI versus DR. Pts treated with anti-EGFR therapy were excluded. Results: A total of 37 pts were treated with FOLFOXIRI and 111 pts with DR. There were no statistical difference between groups regarding gender, KRAS and BRAF mutations, peritoneal metastasis and bevacizumab use. There were statistical difference in age (median: 46y vs 59y) and metastasectomy rates (14% vs 32%) (p < 0.001). KRAS mutation was found in 65% of the population. Median follow-up was 55.3m. Median PFS was 6.5m vs 11.2m (HR: 1.30 95% CI 0.85 – 1.99) and median OS was 17.0m vs 26.3m (HR: 1.01 95% CI 0.60 – 1.68). By univariate analysis, pts who have undergone metastasectomy had superior PFS (14.9m vs 9.2m; p<0.001) and OS (32.4m vs 22.9m; p=0.003). By multivariate analysis adjusted for age, BRAF mutation, metastasectomy, bevacizumab use and, treatment regimen, only age and metastasectomy had prognostic influence for PFS (p=0.039 and p=0.026, respectively). Conclusions: Despite RS having a poor prognosis for OS, our study does not suggest that RS mCRC pts benefit from intensive treatment. Randomized clinical trials may suggest more individualized therapies.
The efficacy and safety of irinotecan plus raltitrexed as second-line treatment in advanced colorectal cancer (ACC) patients: An interim analysis of a multicenter, phase II trial.
Authors: Liu Yunpeng , Teng Zan , Qu Xiujuan , Zhang Yan qiao , Zheng Zhendong , Wen Fugang , Bai Yuxian , Piao Ying , Wang Ying , Teng Yuee , Zhao Mingfang , Jin Bo , Li Xin , Shi Jing , Yu Ping , Qu Jinglei , Luo Ying 
Published: May 2019

e15061 Background: There are limited therapeutic options for the treatment of advanced colorectal cancer which fail first-line chemotherapy. Phase I studies have shown that the combined application of the irinotecan (CPT-11) and raltitrexed has significant synergistic effect and acceptable toxicity. The aim of this multicenter study was to assess the efficacy and toxicity of second-line raltitrexed plus irinotecan in Chinese patients with advanced colorectal cancer. Methods: This is an open-label,single-arm, multicenter, phase II trial (Registered in clinicaltrials.gov with NCT03053167).Brief inclusion criteria: patients were aged 18 to 75 years with locally advanced or metastatic colorectal cancer after failure of oxaliplatin and fluorouracil therapy. Enrolled patients received CPT-11 (180 mg /m2 , d1) and raltitrexed (3 mg/m2, d1) each 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were disease control rate (DCR), objective response rate (ORR), overall survival (OS), quality of life (QOL) and safety. In all, 100 patients were required for primary point testing. Results: Between November 2016 and December 2018, a total of 70 patients were screened for enrollment and 53 patients reached the primary endpoint. Nine patients achieved a partial response and twenty-seven stable disease. The overall response rate was 17% (9/53) and the disease control rate was 67.9% (36/53). Median progression-free survival (mPFS) was 4.3 months and median overall survival was not observed. The most common adverse events were elevated transaminases (21/53), fatigue (14/53), diarrhea (12/53), neutrocytopenia (10/53), erythrocytopenia (9/53), hypohemoglobin (8/53) and leukocytopenia (6/53). The total incidence of grade 3/4 toxicity was 17% (9/53) , mainly diarrhea (2/53), neutrocytopenia (2/53) and elevated transaminases (2/53). There were no treatment-related deaths. Conclusions: We have demonstrated that CPT-11 plus raltitrexed is active and feasible in patients with second-line treatment in advanced colorectal cancer. This trial will progress as planned. Clinical trial information: NCT03053167.