bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of liver metastases (LM) with survival in NSCLC patients treated with durvalumab (D) in two independent clinical trials.
Authors: Paz-Ares Luis G. , Shen Kui , Higgs Brandon W. , Morehouse Chris , Rizvi Naiyer A. , Segal Neil Howard , Jin Xiaoping , Zheng Yanan , Narwal Rajesh , Gupta Ashok Kumar , Dennis Phillip A. , Mukhopadhyay Pralay , Ranade Koustubh 
Published: September 2018

3038 Background: Immunotherapies have improved survival in NSCLC but not all pts benefit. Besides baseline PDL1 expression, routinely measured clinical factors may predict clinical outcomes in immunotherapy trials. LM are associated with poor prognosis in melanoma and bladder cancer pts treated with anti-PD1/L1, respectively. We examined correlation between pretreatment LM and survival in D-treated NSCLC pts. Methods: CP1108/NCT01693562 and ATLANTIC/NCT02087423 were nonrandomized phase 1/2 and 2 trials, respectively, of D 10 mg/kg Q2W in advanced NSCLC. As of Oct 24/Jun 3 2016, 304/265 primarily pretreated pts were enrolled in CP1108/ATLANTIC Cohort 2. Cox proportional hazards analysis was conducted, first among LM+/− pts, then LM+/− and PDL1 high/low pts. Both models accounted for tumor stage, ECOG/WHO PS, histology, sex, age, smoking and PDL1 status. PDL1 high was defined as ≥25% tumor cells immunostained for PDL1 at any intensity. Results: LM absence was a positive independent predictor of OS and PFS in both trials. LM− and PDL1 high or low pts had improved OS and PFS vs PDL1 low/LM+; PDL1 high/LM+ pts had improved PFS vs PDL1 low/LM+. An independent tumor kinetic model indicated LM as a predictive covariate of rapid tumor growth in D-treated pts. Conclusions: LM are associated with shorter survival in D-treated NSCLC pts in 2 trials irrespective of PDL1 status. Clinical trial information: NCT02087423 and NCT01693562. [Table: see text]
A phase III trial (ZJBIO009): CMAB009 plus irinotecan versus irinotecan alone as second-line treatment after fluoropyrimidine and oxaliplatin failure in wild-type K-ras metastatic colorectal cancer patients.
Authors: Shi Yuankai , Li Jin , Xu Jianming , Cheng Ying , Liu Wei , Cheng Yigui , Bai Li , Zhang Yiping , He Xiaohui , Luo Yi , Liu Yunpeng , Yao Qiang , Li Yuhong , Qin Shukui , HU Xiaohua , Guo Yajun , Sun Yan 
Published: September 2018

3513 Background: More efficient second line treatment regimen for mCRC is urgently needed. CMAB009, a recombinant human/mouse chimeric monoclonal antibody, is specifically targeting human epidermal growth factor receptor. This study aimed to determine clinical efficacy and safety of CMAB009 plus irinotecan compared with irinotecan alone in wild-type K-ras mCRC patients (pts). Methods: This is a open-label, randomized, phase 3 trial. Patients had histologically confirmed wild-type K-ras mCRC, who previous failure of 5-fuorouracil plus oxaliplatin more than 1 month of the last-dose enrolled in study. Pts were randomly assigned on a 2:1 to receive CMAB009 (initial 400mg/m2 on day 1, and then 250 mg/m2 weekly) plus irinotecan (180mg/m2, every 2 weeks) (A arm) or irinotecan alone (B arm). B arm pts could switch to CMAB009 sequential treatment (C arm) on diseas progression. The primary end point was overall response rate (ORR). The secondary endpoints were PFS, OS, DCR, and DOR (NCT01550055). Results: From May 2009 to December 2012, 512 pts were assigned from 38 sites. Efficacy evaluation could be in 501 pts, ORR were 33.2% (112/337) and 12.8% (21/164) in A arm and B arm ( p <0.0001). C arm had 115 pts, DCR was 63.5% (73/115). DOR in A arm and B arm were 210 days and 109 days ( p=0.001). In C arm, DOR was 148 days . Median PFS was significantly longer in A arm than B arm (169 days vs 95 days; p < 0.0001). In C arm, median PFS was 84 days. Median OS was 425 days in A arm and 401 days in B arm ( p=0.94). 96.2% (484/503) pts experienced at least one adverse event (AE). 55.3%(187/338) and 37.6%(62/165) patients in A arm and B arm had at least one grade ≥3 AE respectively. The most common AE included diarrhea, emesis, leucopenia, neutropenia and fatigue. Adding CMAB009 to irinotecan increased the risk of rash (66.6% vs 5.5%, p <0.001) and paronychia (9.8% vs 0,p < 0.001). Conclusions: CMAB009 plus irinotecan significantly increased ORR and prolonged PFS compared with irinotecan alone. CMAB009 plus Irinotecan were efficient and well tolerated, which could be considered as a standard second-line treatment choice in wild-type K-ras mCRC pts. Clinical trial information: NCT01550055.
Early tumor shrinkage (ETS) and depth of response (DpR) in wild-type (WT) RAS tumors from the phase III trial of panitumumab (pmab) plus best supportive care (BSC) versus BSC in chemorefractory metastatic colorectal cancer (mCRC).
Authors: Kim Tae Won , Elme Anneli , Park Joon Ho , Udrea Anghel Adrian , Manojlovic Nebojsa S. , Guan Xuesong , Jung A. Scott , Vrdoljak Eduard 
Published: September 2018

3561 Background: Activating RAS mutation is a negative predictor of anti-EGFR therapy. In the final analysis of 20100007, the first phase 3 study to prospectively evaluate efficacy and safety of WT RAS ( KRAS and NRAS exons 2, 3, 4 ) mCRC, pmab + BSC continued to show improved survival (OS and PFS) and ORR. Recent data suggest that tumor burden reduction and ETS may contribute to improved OS. Previous studies have shown that pmab plus chemotherapy results in ETS, which correlates with OS benefit (Douillard et al, EJC, 2015; Rivera et al, JCO, 2015; Mansmann et al, JCO 2013). Here we report analyses of ETS and DpR and the effect on OS in patients (pts) with WT RAS mCRC treated with pmab monotherapy in the ‘0007 trial. Methods: Anti-EGFR naïve pts with WT KRAS exon 2 mCRC were randomized 1:1 to pmab + BSC or BSC. Pt tumors were further evaluated for RAS status, and DpR (percent tumor shrinkage at nadir or progression) and ETS (≥/< 0% or ≥/< 20% by week 8) were analyzed in WT RAS pts. OS and PFS were compared for each ETS group. Results: Of 377 pts with WT KRAS exon 2 mCRC, 270 were WT RAS (142 pmab + BSC, 128 BSC alone). In the pmab + BSC arm, 69.5% and 38.2% of pts had ≥0% and ≥20% ETS, respectively, and median (Q1, Q3) DpR was 16.9% (0%, 37.5%). OS was improved in pts with higher ETS (≥0% or ≥20%) compared with lower ETS (<0% or <20%; Table). Conclusions: In this post-hoc analysis, pmab monotherapy provided any ETS benefit (≥0%) in 69.5% of WT RAS mCRC pts, and ETS was associated with improved PFS and OS. Pmab should be considered both in combination and as monotherapy for its significant impact on OS and also for its ability for substantial ETS in pts with WT RAS mCRC. Validation is necessary to investigate the value and cutoff of ETS in a prospective study. Clinical trial information: NCT01412957. [Table: see text]
Neoadjuvant chemotherapy with mFOLFOXIRI alone for cT4 and fixed cT3 rectal cancer: Results from a single arm phase II study (FORTUNE).
Authors: Zhang Jianwei , Cai Yue , Hu Huabin , Chen Dianke , Xiao Jian , Ling Jiayu , Wenjing Wang , Lan Ping , Wang Lei , Huang Meijin , Wu Xiaojian , Kang Liang , Wang Jianping , Deng Yanhong 
Published: September 2018

3607 Background: Although neoadjuvant chemoradiotherapy achieves low local recurrence rates in locally advanced rectal cancer (LARC), it delays administration of systemic chemotherapy. About 30% of patients still developed distant metastases, which is the main obstacle for improving survival of LARC. Besides, preoperative radiation causes lots of concerns about anal and sexual functions. We aimed to explore the efficacy of preoperative chemotherapy with mFOLFOXIRI in LARC rather than consistent use of chemoradiotherapy. Methods: Patients with fixed cT3 or cT4 rectal cancer evaluated by pelvic MRI participated in this trial. All candidates were to receive 4-6 cycles of mFOLFOXIRI. MRI will be performed to assess clinical responses. Patients with stable/progressive disease were to have radiation before surgery, whereas responders were to have immediate total mesorectal excision (TME). Postoperative radiation was planned if R0 resection was not achieved. Postoperative FOLFOX was recommended. The primary endpoint is the ratio of tumor downstaging to ypT0-2N0M0.The secondary endpoint included pathologic complete response rate, 3-year disease free survival rate and safety. Results: Between August 2014 and September 2016, 83 patients were enrolled and 80 participants had received TME. Three refused surgery after chemotherapy, because the tumor location is too low to perform sphincter-preserving operation. Of 80 patients completing at least 4 cycles of preoperative chemotherapy, two received short-term radiation before TME, and 10 patients underwent long-term chemoradiotherapy after MRI evaluation. The pCR rate of the whole group was 15 of 80 (18.8%) and the tumor downstaging rate was 43.8%. Among patients without chemoradiotherapy, the pCR rate and tumor downstaging were 14.3% and 41.4%, respectively. And the chemo-related toxicity was all tolerable. Conclusions: Neoadjuvant chemotherapy with mFOLFOXIRI and selective radiation does not seem to compromise outcomes in LARC. The result was promising and further phase III study is warranted to validate this experience. Clinical trial information: NCT02217020.
Phase III study of individualized intraperitoneal/intravenous/oral chemotherapy compared with standard intravenous/oral chemotherapy in patients with advanced gastric cancer.
Authors: Yang Yang , Wei Jia , Du Juan , Yu Lixia , Qian Hanqing , Yang Yan , Qian Xiaoping , Liu Baorui 
Published: September 2018

4021 Background: Tumor mRNA expression levels may have a promising role as potential predictive biomarkers for chemotherapy. Intraperitoneal (IP) chemotherapy provides sustained high local concentrations, and its efficacy has been shown in ovarian cancer and gastric cancer patients with peritoneal metastasis. We developed a regimen combining IP/intravenous(IV)/oral chemotherapy for the treatment of advanced gastric cancer patients with individualized chemotherapeutics according to mRNA expression. This multicenter phase III study evaluated the efficacy of individualized multi-route chemotherapy compared to standard systemic chemotherapy. Methods: Eligibility criteria included pathologically confirmed advanced gastric adenocarcinoma, and no prior chemotherapy. Patients were randomized 3:1 to an individualized arm (IN) and standard arm (ST). Randomization was stratified by center. Patients in individualized arm first underwent mRNA expression (BRCA1/TOPO1/TS) to choose sensltive chemotherapeutics from oxaliplatin/cisplatin/docetaxel/irinotecan/S-1 and then received individualized IP/IV/oral chemotherapy. The primary endpoint was overall survival (OS). Secondary endpoints were response rate, progression-free survival (PFS), and safety. Results: Between April 2013 and December 2015, 231 patients were enrolled, and 218 patients were included in the efficacy analysis. Baseline patient characteristics were balanced between the two arms. The median OS for IN and ST were 16.3 and 14.1 months, respectively (adjusted hazard ratio [aHR] 0.77, 95% confidence interval [CI] 0.61-0.98, p < 0.05). The overall response rate was 44.0% in the IN arm, and 33.9% in the ST arm (p < 0.05). Both regimens were tolerable. Conclusions: The primary analysis showed the statistical superiority of the individualized multi-route regimen. It suggested clinical efficacy of this regimen in patients with advanced gastric cancer. Clinical trial information: ChiCTR-IPR-15006201.
The prognostic role of metastatic lymph node ratio-staging system in gastric cancer patients: Analysis of the National Cancer Database.
Authors: Naffouje Rand , Salti George I. 
Published: September 2018

4044 Background: The NCCN recommends retrieval of at least 15 lymph nodes for adequate nodal staging in gastric cancer. There is an ongoing debate about the accuracy of the classification systems for nodal involvement based on the absolute number of positive nodes (AJCC-N) vs. the ratio of positive nodes (rN). In this study, we aim to assess the accuracy of each system in the prediction of 5-year survival using the National Cancer Data Base (NCDB) for gastric cancer. Methods: The database included 168,377 gastric cancer patients between 2004-2014. Patients who were approached with palliative intent, or had metastatic disease were excluded from the analysis. Only patients who had at least one regional node examined were included. A univariate and multivariate regression analysis were conducted to identify significant predictors of the 5-year survival among the perioperative patients’ characteristics. Bayesian Information Criterion (BIC) was used to compare the model fitting when the AJCC nodal staging is applied to that of the ratio nodal staging. Results: 48,126 patients were included in the final analysis. 23,102 (48%) patients had ≥15 nodes examined. The univariate and multivariate regression analysis identified age, male gender, Caucasian race, and presence of comorbidities as significant demographic predictors. TNM T-stage, N-stage, and rN-stage were significant predictors with worsening prognosis as the stage increases. Overall, BIC demonstrated that the model using rN had a better fit (rN = 30321 vs. AJCC-N = 30619). However, subgroup analysis showed that the AJCC-N functioned better when < 15 nodes were examined (rN = 17367 vs. AJCC-N = 17311), whereas rN functioned better when ≥15 nodes were collected (rN = 16776 vs. AJCC-N = 16831). Conclusions: Both AJCC-N and rN are valid systems for nodal staging in terms of survival prediction in gastric cancer. When at least 15 nodes are resected in line with the current NCCN guidelines, the rN staging system for nodal metastasis appears to function more accurately in survival prediction. It might be advisable to consider the ratio of positive lymph nodes when a large number of nodes are collected to avoid over-staging and stage migration.
Long term cardiac outcomes and anthracycline exposure in breast cancer survivors: A retrospective cohort data linkage and competing risks analysis.
Authors: Rust Kelly , Walker Jeremy , Stoker Richard , Wild Sarah , Henriksen Peter , Cameron David A. , Maclennan Marjory , Simpson Maighread , Lilley Christina , Hall Peter 
Published: September 2018

553 Background: Anthracycline chemotherapy is used frequently in adjuvant breast cancer treatment but there is clinical trial evidence of cardiac toxicity. Attempts to quantify this risk in routine care have been limited by follow up time & confounding factors. The aim of this project was to exploit rich Scottish NHS datasets for this purpose. Methods: Patients treated surgically for stage I-III invasive breast cancer between 2000 & 2010 were identified from a local cancer database (Edinburgh Cancer Centre). Outcomes were captured by linkage to the Scottish Morbidity & death Records. Follow-up was until March 2016. The primary outcome was a cardiac event or cardiac death, identified from coding. Analysis used the Latouche approach (estimating cause-specific hazards & sub-distribution hazards) for the primary outcome & the competing risks of death from breast cancer & death from other causes. Results were adjusted for age, deprivation (SIMD), co-morbidity (Charlson), year of diagnosis, side of radiotherapy, cancer stage, grade, ER & HER 2 status. Results: 4080 patients were identified, 1658 received an anthracycline containing regime, 297 received non-anthracycline chemotherapy & 2125 received no chemotherapy. A total of 33946 women years were analysed. During median follow up of 8.2 years there were 448 cardiac events & 559 breast cancer deaths. After adjustments there was no association between anthracycline use & cardiac outcomes (HR 0.9, 95% CI 0.67-1.21). There was an increased risk of breast cancer death (HR 1.66, 95% CI 1.28-2.16).Age & Charlson score were associated with an increased cardiac risk. Stage & grade were statistically associated with breast cancer death. Conclusions: No increased risk of cardiac events was seen in women treated with anthracyclines, they can be safely used in carefully selected patients. This data suggests selection may be over-cautious, a lower threshold for treatment may lead to improved breast cancer outcomes. Rich routine health datasets & appropriate analysis methods make outcomes monitoring feasible in Scotland. Oncologists are skilled at assessing both cardiac risk factors & breast cancer risk.
Prediction of radiation therapy response in breast cancer patients.
Authors: Arora Divya , Hasan Salman , Jebakumar Deborah , Munoz Yolanda , Ford John , Ord Celine , Rao Arundhati , Deb Niloyjyoti 
Published: September 2018

565 Background: While radiation portals are tailored to a patient’s unique anatomy and the selection of systemic agents routinely employs biomarker data, the selection of radiotherapy based on a patient’s tumor biology is not routinely utilized in breast cancer. The purpose of this study was to identify which genetic markers are possible predictors for local recurrence as a surrogate for radiation response. Methods: We identified 200 patients who received radiotherapy for breast cancer. Selected tumor markers included: Androgen receptor (AR), Hypoxia Inducible Factor 1-α (HIF-1), Phosphotidylinosotol-4,5-bisphosphate 3-kinase (PI3K), and Interleukin 13 (IL-13). Biomarkers were analyzed in terms of “extent” and “intensity” on a scale of 0-3 and scored by 2 separate pathologists. The primary endpoint of local recurrence (LR) & secondary endpoint of overall survival were analyzed using Kaplan-Meier survival curves, log-rank test for differences, and Cox regression models. Results: Median follow up was 7.98 years. At 5 years, the rate of LR was 92.6% and overall survival was 89.4%. On multivariate Cox regression analysis, a one unit increase in IL-13 extent increased the hazard of LR by 73%. A one unit decrease in AR extent increased the hazard of LR by 134%. The hazard of death increased 3.2 times for each unit increase in HIF1 extent. The hazard of death increased 1.5 times for each unit increase in PI3K extent. PI3K extent and intensity was increased, and AR extent and intensity was decreased in triple negative breast cancer (TNBC) (n = 68) vs non-TNBC (p < 0.0001). African Americans had a 4.2 times hazard of LR vs Caucasians. Conclusions: Expression of IL-13 was associated with a higher risk of LR; expression of AR was associated with decreased LR. These two markers may be instrumental in predicting radiation response. If this study is validated, cancers that express more IL-13 may require higher doses or targeted therapy. In contrast, those cancers expressing AR may not require as aggressive therapy. Lastly, PI3K and HIF1 α expression were significant predictors of worse overall survival. The clinical implications of these biologic markers are significant as they may help to guide biologically-driven, personalized breast cancer radiotherapy.
Relationship between out-of-pocket spending and drug value for oral oncolytics reimbursed by commercial insurers: 2007-2014.
Authors: Rotenstein Lisa , Dusetzina Stacie , Keating Nancy Lynn 
Published: September 2018

6524 Background: With total and out-of-pocket (OOP) spending for oral oncolytics rising, there is increased interest in choosing oncology treatments based on their clinical value relative to cost. We sought to determine if OOP spending varied for higher versus lower-value oral oncology drugs reimbursed by commercial insurers. Methods: This was a retrospective analysis of commercial insurer prescription drug claims filed between 2007-2014 for 13 oral oncolytics approved before 2009. We calculated mean monthly OOP payments for each patient. We then categorized oral oncolytics by their overall and progression-free survival benefits for each FDA-approved indication, using evidence from published studies. We assessed the relationship of survival benefit with mean monthly OOP payment, adjusting for demographic and plan characteristics. Results: Our population included 44,109 patients ages 18-65 (mean age = 52.5 years, SD = 9.4 years) with a cancer diagnosis who filled 731,261 prescriptions. The most commonly represented oncolytics were imatinib (37.4% of fills) and lenalidomide (17.7% of fills). Approximately 57.6% of fills were for drug-indication pairs with an overall survival benefit of 5+ months. In adjusted analyses, there was no significant difference in mean monthly OOP payment between drugs without evidence of benefit and those with 0-5 months progression-free survival benefit or 5+ months of overall survival benefit (p > 0.05). Meanwhile, drugs with 5-10 months progression-free survival benefit or 0-5 months overall survival benefit had higher OOP payments than those without benefit (p < 0.01). Conclusions: OOP payments for oral oncolytics were not clearly related to indication-specific value. This suggests that despite increased attention to value- and indication-based drug pricing, cost-sharing for oral oncolytics does not currently reflect these goals.
Prevalence and estimated trend in chemotherapy use near death from population-based studies on cancer patients: A systematic review and meta-analysis.
Authors: Chou Pei-Chun , Chen Chen Hsiu , Liu Tsang-Wu , Tang Siew Tzuh 
Published: September 2018

6590 Background: Chemotherapy (CMT) use near death, based on US national guidelines, is an indicator of aggressive treatment and poor quality of end-of-life (EOL) care. US law also decreased Medicare payments for outpatient CMT since 2005-2006. To evaluate the impact of US payment reform and guidelines on CMT use at EOL, we estimated and compared the overall prevalence of CMT use at EOL in the US and other countries as well as before and after 2007 in the US. Methods: Six databases were systematically searched to January 2017 for population-based studies of CMT use at EOL for patients in all cancer groups. Two reviewers independently extracted data.Overall CMT use prevalence was pooled by a random-effects model. Differences in prevalence of CMT use were compared by meta-regression between subgroups (US vs non-US countries; before and after 2007 in the US). Results: We identified 9 and 7 articles from the US and non-US countries, respectively. CMT was provided to 28.9% [95% confidence interval (CI) 26.2%-31.8%], 23.2% [95% CI 21.7%- 24.8%], 10.0% [95% CI 8.5%-11.8%], and 4.5% [95% CI 3.9%- 5.2%] of cancer patients in their last 6, 3, and 1 months as well as 14 days of life, respectively. CMT use in the last 6 months was more common in the US than in non-US countries (32.4% vs. 26.2%, p = 0.015) but similar to that of other countries in the last month (9.3% vs.11.2%, p = 0.179) and last 14 days (4.6% vs.5.6%, p = 0.683) of life. Prevalence of CMT use in the last 14 days of life in the US did not differ significantly before and after 2007 (5.1% vs. 5.2%, p = 0.967). Conclusions: Many cancer patients worldwide receive CMT at EOL, and the prevalence of CMT use in US patients’ last 14 days of life was virtually unchanged over time. Effective interventions should be developed and provided to offset the trend of continuing CMT use at EOL.