bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicenter prospective study of carboplatin and paclitaxel for advanced thymic carcinoma: West Japan Oncology Group 4207L.
Authors: Takeda Koji , Hirai Fumihiko , Yamanaka Takeharu , Taguchi Kenichi , Daga Haruko , Shimizu Junichi , Kogure Yoshihito , Kimura Tatsuo , Tanaka Kaoru , Iwamoto Yasuo , Ono Akira , Sasaki Hidefumi , Fukuoka Junya , Nishiyama Kenichi , Seto Takashi , Ichinose Yukito , Nakagawa Kazuhiko , Nakanishi Yoichi ,   West Japan Oncology Group
Published: March 2020

7529 Background: Thymic carcinoma (TC) is a rare malignant tumor originated within the thymus gland and is associated with a poor prognosis, differing from thymoma which is the most common type of thymic malignant neoplasm. No results of clinical trials focusing on TC have been reported. This single-arm study evaluated carboplatin and paclitaxel (CbP) in previously untreated patients (pts) with advanced TC. Methods: Pts with Masaoka’s stage III to IVb TC, ECOG PS 0 to 1, and more than 20 years old were eligible. The study treatment consisted of carboplatin (AUC 6) and paclitaxel (200 mg/m2) every 3 weeks for a maximum of 6 cycles. The primary endpoint was objective response rate (ORR) by extramural assessment. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety. All pts were followed-up until 24 months (mo) after last enrollment. Based on the SWOG 2-stage design, the planned sample size of 40 pts was determined to reject the ORR of 20% under the expectation of 40% with a power of 0.85 and a type I error of 0.05. Results: From May 2008 to November 2010, 40 pts were enrolled from 21 centers. Of 39 evaluable for analysis, the median age was 62 years (range, 36–84); 23/16 males/females; 3/10/26 with Masaoka’s stage III/IVa/IVb; 9/11/19 with squamous cell carcinoma/poorly differentiated neuroendocrine carcinoma/other types. The median number of cycles was 6. There was 1/13 complete/partial responses with an ORR of 36% (95% confidence interval [CI], 21-53%; P = 0.031). The median PFS was 8.1 mo (5.4-13.1 mo) while OS did not reach the median value. The 1-year and 2-year survival rates were 85% (95% CI, 69-93%) and 71% (95% CI, 54-83%), respectively. Major adverse event was grade 3-4 neutropenia in 34 pts (87%). Two cases (5%) of grade 3 febrile neutropenia, neuropathy, and arthralgia were observed, respectively. There was no treatment-related death. Conclusions: CbP showed higher efficacy in advanced TC as compared with anthracycline-based chemotherapy which is the current standard for the treatment of thymoma. Our results established that CbP, one of the standard treatments for non-small cell lung cancer, also serves as a key chemotherapy regimen for TC. Clinical trial information: UMIN000001358.
Phase II multicenter clinical trial of isolated lung perfusion (ILuP) with melphalan (MN) in patients (pts) with resectable lung metastases (LM).
Authors: Hengst Willem Den , Hendriks Jeroen M.H. , Balduyck Bram , Rodrigus Inez , Vermorken Jan Baptist , Lardon Filip , Versteegh Michel I.M. , Braun Jerry , Gelderblom Hans , Schramel Franz , Van Boven Wim-Jan , Van Putte Bart , Birim Ozcan , Maat Lex , Van Schil Paul 
Published: March 2020

7534 Background: Five-year overall survival (OS) of pts undergoing surgical resection of LM from colorectal cancer (CRC) and sarcoma remains low [20-50%]. Local recurrence rate is high, even after complete surgical resection [48-66%] (Pastorino et al, 1997). Combined modality therapy is currently evaluated. ILuP allows the delivery of high-dose locoregional chemotherapy without systemic exposure. In a previous phase I study maximum tolerated dose of MN was found to be 45mg at a perfusion temperature of 37°C (Grootenboers et al, 2007). Methods: From 2006 to 2011 50 pts, 28 male, median age 57 years [15-76], with LM from CRC [n=30] or sarcoma [n=20] were included in a phase II clinical trial conducted in 4 cardiothoracic surgical centers. In total, 62 ILuP procedures were performed, 12 bilaterally, followed by resection of all palpable LM. Survival was calculated according to the Kaplan-Meier method. Results: Operative mortality was 0%, 90-day morbidity was mainly cardiac [grade 3: 2%] and respiratory [grade 3: 29%, grade 4: 2%]. After a median follow-up of 24 months [3-63 mos] 18 pts died, 2 without recurrence. Seven pts [14%] had their initial recurrence in the perfused lung. Initial progressive disease outside the perfused lung occurred in 23 pts [46%]; contralateral, non-perfused lung 10, liver 3, brain 2, primary site 1 and other location 7. OS and disease-free survival (DFS) are shown in table 1. Lung function data showed a decrease in FEV1 and DLCO of 21.6% and 25.8% after 1 month, and 10.4% and 11.3% after 12 mos, respectively, compared to preoperative values. Long-term quality of life evolution after ILuP and lung metastasectomy was comparable with a standard lung metastasectomy by thoracotomy in one participating center (Balduyck et al, 2012). Conclusions: Compared to historical series of LM resection without ILuP favorable results are obtained in terms of local control without long-term adverse effects. These data support the further investigation of ILuP as additional treatment in pts with resectable LM from CRC or sarcoma. Clinical trial information: 2006-002808-34. [Table: see text]
Appropriateness of imaging in lung cancer in a national cohort.
Authors: Backhus Leah M. , Farjah Farhood , Varghese Thomas K , Cheng Aaron , Zhou Xiao Hua , Wood Douglas E. , Kessler Larry , Zeliadt Steven B 
Published: March 2020

7546 Background: Rising healthcare costs prompt emphasis on quality, appropriate care, and cost containment. Imaging is a source of high healthcare expenditures in cancer. We sought to examine variability of adherence to national guidelines for staging, and appropriateness criteria for imaging for patients with locally advanced lung cancer. Methods: Stage IIB, IIIA, or IIIB lung cancer patients were identified from the national VA Central Cancer Registry from 2004-2008 with linkage to VA data and Medicare claims. Imaging was assessed 180 days pre and post diagnosis per National Comprehensive Cancer Network guidelines and American College of Radiology Appropriateness Criteria for Imaging. Multivariate logistic regression with robust variance estimates (adjusting for within-cluster correlation by facility) was used to control for covariates and results reported as adjusted risk differences (95% confidence intervals [CI]). Results: Recommended imaging was performed in 69.5% of patients for brain imaging and 51.1% of patients for positron emission tomography (PET). Overutilization, with combined bone scintigraphy and PET (BS/PET), occurred in 19.7% of patients and did not vary over time (15.8% to 19.5% p=0.168). Facilities affiliated with a medical school had a 14.8 (CI -25.2, -4.4) percentage point lower utilization of PET. Facility volume and tumor board availability were not associated with variability. Appropriateness of imaging varied significantly by region. New England had the highest rates of imaging. Relative to New England, brain imaging was lowest in the Great Basin Region with 26.9 (-40.0, -14.0) percentage point decrease. Both recommended PET use and overutilization of BS/PET was lowest in the Mississippi Region with 25.0 (CI -49.3, -0.6) and 11.7 (CI – 23.3, -0.1) percentage point decrease respectively compared to New England. Conclusions: A significant proportion of patients do not receive recommended imaging and many undergo excessive imaging for lung cancer. Furthermore, there is substantial regional variation in imaging utilization. These observations are hallmarks of poor quality. A disease-based quality improvement plan aimed at modification via policy and reimbursement initiatives may mitigate poor quality care.
Prognostic significance of α1,6-fucosyltransferase (α1,6-FT) in non-small cell lung cancers (NSCLCs).
Authors: Honma Rio , Kinoshita Ichiro , Miyoshi Eiji , Tomaru Utano , Matsuno Yoshihiro , Shimizu Yasushi , Takeuchi Satoshi , Kaga Kichizo , Taniguchi Naoyuki , Akita Hirotoshi 
Published: March 2020

7550 Background: Lung cancer is one of the leading causes of cancer death throughout the world. A more sophisticated understanding of the pathogenesis and biology of NSCLCs could provide useful information for predicting clinical outcome and individualizing treatment. α1,6-FT is the only one enzyme responsible for the core α1,6-fucosylation of N-glycans of glycoproteins, including EGF receptor, TGF-β1 receptor, and integrin α3β1. Methods: α1,6-FT expression was studied by immunohistochemistry in a cohort of 129 surgically resected NSCLCs, classified categorically based on the proportion of positively stained cancer cells (high, > 20%; or low, < 20%), and analyzed statistically in relation to various characteristics, including histology, survival and prognosis. Results: High and low expression of α1,6-FT was found in 67 and 62 of 129 NSCLCs, respectively. Multivariate logistic regression analysis revealed a significant association between high α1,6-FT expression and non-squamous cell carcinoma (mostly adenocarcinoma), as compared with squamous cell carcinomas (odds ratio, 3.51; p = 0.008). Patients with tumors having high α1,6-FT expression had significantly shorter survival time than patients with tumors having low expression in potentially curatively resected NSCLCs (p = 0.03) and adenocarcinomas (p = 0.009), as well as in pStage I NSCLCs (p = 0.03) by the log-rank test. Surprisingly, in pStage I adenocarcinomas, 12 of 23 patients with tumors having high α1,6-FT expression died of lung cancer, although none of 15 patients with tumors having low expression died of lung cancer. High α1,6-FT expression was a significant and independent unfavorable prognostic factor in potentially curatively resected NSCLCs (hazard ratio, 1.81; p = 0.047) and adenocarcinomas (hazard ratio 2.39; p = 0.006) and in pStage I NSCLCs (hazard ratio 2.55; p = 0.03) by Cox’s proportional hazards model analysis. Conclusions: These results suggest that α1,6-FT may play a pivotal role for the biological characteristics of NSCLCs. α1,6-FT expression is associated with histology of NSCLCs, and may be a new prognostic marker for overall NSCLCs and adenocarcinomas.
Genomic rearrangements in lung adenocarcinoma: Lineage relationships between the in situ and invasive components.
Authors: Murphy Stephen J , Wigle Dennis A. , Harris Faye R , Lima Joema Felipe , Johnson Sarah H , Eckloff Bruce W , Seto Charlie T , Asiedu Michael , Peikert Tobias , Yang Ping , Aubry Marie-Christine , Vasmatzis George 
Published: March 2020

7568 Background: The molecular events in the initiation and progression of invasive lung adenocarcinoma remain poorly characterized. These tumors are thought to develop through an adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (AD) sequence. The goal of our study was to assess lineage relationships between in situ and invasive components within adenocarcinomas with prominent lepidic growth patterns. Methods: Frozen tissue from fourteen lung adenocarcinomas with mixtures of AD together with an adjacent in situ component (AIS), varying in ratio between 40 to 80%, were selected from our Lung Specimen Registry. Laser capture microdissection (LCM) of each component was performed separately for each tumor. Genomic DNA was isolated using a direct in situ whole genome amplification (WGA) methodology, and Next Generation Sequencing performed using an Illumina Mate Pair (MP) library protocol. MP sequence reads were mapped to the human genome and primers spanning the fusion junctions were used in validation PCRs. Results: Genomic break points identical and unique to a specific patient were identified between the AIS and AD components in 13 (of 14) cases. The total number of events per case ranged from 4-215, and the number of identical events shared between the AIS and AD components ranged from 30 to 90%. Recurrent genomic breakpoints between cases were also observed, with the 2 most common involving 8q24.3 in 5 cases and FAM19A2 on chromosome 12 in 4 cases. PCR validation of selected genomic alterations confirmed the genomic break points identified from sequencing in both the AIS and AD in all cases. Interestingly, we also observed a limited number of genomic alterations present in a zonal distribution of surrounding normal lung around the tumor mass. Conclusions: Our study demonstrates unique chromosomal alterations present in both the AIS and AD components of individual lung tumors with features of lepidic growth. These data provide evidence for lineage relationship and clonal relatedness between the two components, and provide genomic evidence for a model of stepwise progression from AIS to invasive AD in this subset of lung adenocarcinomas.
Serum miRNA signature to identify a patient’s resistance to high-dose radiation therapy for unresectable non-small cell lung cancer.
Authors: Bi Nan , Schipper Matthew J , Stanton Paul , Wang Weili , Kong Feng-Ming (Spring) 
Published: March 2020

7580 Background: There is a growing literature on unique profiles of serum micro RNAs (miRNAs) expression to predict clinical outcome of metastatic and early stage non-small cell lung cancer (NSCLC). However, the predictive role of circulating miRNAs in unresectable NSCLC treated with definitive radiation therapy (RT) is unknown. Methods: 134 patients with inoperable/unresectable NSCLC treated with deﬁnitive RT (18-month minimum follow-up) were eligible. Serum samples were collected prospectively before treatment. 100 patients had enough serum and reliable miRNA profile quality, which were randomly divided into training and validation sets (50 patients each). MiRNA profiling was performed using real-time PCR-based array, containing a panel of 84 miRNAs detectable in human bodily fluids. Spiked-in cel-miR-39 was used for normalization. Stepwise regression Cox model building was used to build a miRNA signature on the training set, which was then assessed on the validation set both alone and with clinical factors. Results: The median age was 67 years; 76% were stages III and 79% received chemoradiation; the median physical dose was 70.0 Gy. A serum hsa-miR-885/hsa-miR-7 signature was identified as significant predictors for overall survival (OS) in the training set, which was validated by the validation set (p=0.02). After adjustment for GTV Volume and KPS, the only two significant clinical factors in univariate analysis, this signature remained significant (p=0.04). In the high-dose RT group (>70 Gy, n=45), individuals with low-risk had a significantly longer OS than patients with high-risk (70.7 vs. 18.8 months, p=0.007); while in the low-dose RT group (≤70 Gy, n=55), no significant association was observed (OS, 22.0 vs. 13.3 months, p=0.43). Conclusions: Circulating hsa-miR-885/hsa-miR-7 signature may be used as a putative non-invasive biomarker for predicting survival and radiation resistance in unresectable NSCLC, which may potentially help to select patients who will not benefit from high-dose radiation. Independent validation studies are needed to conﬁrm our ﬁndings. Clinical trial information: NCT01190527.
A novel microRNA-based treatment approach for malignant pleural mesothelioma.
Authors: Reid Glen , Pel Marcella , Kirschner Michaela , Cheng Yuen Yee , Mugridge Nancy , Weiss Jocelyn , Williams Marissa , Wright Casey , Klebe Sonja , Brahmbhatt Himanshu , MacDiarmid Jennifer , Van Zandwijk Nico 
Published: March 2020

7586 Background: Malignant pleural mesothelioma (MPM) is recalcitrant to treatment and new approaches are needed. The microRNA miR-16 has been implicated as a tumor suppressor in a range of cancer types, and restoration of miR-16 expression has been shown to inhibit tumor cell proliferation. The miR-16 status in MPM is largely unknown. Methods: MicroRNA expression was analysed by TaqMan-based RT-qPCR in 10 MPM cell lines and 60 tumour specimens consisting of archival blocks from patients undergoing surgery. MicroRNA expression was restored in vitro using mimics corresponding to the sequence of the mature microRNA, and effects on proliferation and target genes were assessed with standard methods. Human xenograft-bearing mice were treated with miR-16 mimics packaged in minicells targeted with EGFR-specific antibodies. Results: Expression of miR-16 was consistently down-regulated in MPM cell lines and MPM tumor specimens as were the co-expressed miR-15a and miR-15b. A decrease of 2- to 5-fold in miR-16 expression was found when MPM cell lines were compared with the normal mesothelial cell line MeT-5A. When tumor specimens were compared with normal pleura, the down-regulation of miR-16 was in the order of 10-fold. Using synthetic miR-16 mimics to restore miR-16 expression in MPM cell lines led to time- and dose-dependent growth inhibition in a panel of MPM cell lines but did not affect growth of MeT-5A. Growth inhibition correlated with cell cycle arrest and concordant down-regulation of miR-16 target genes including Bcl-2 and CCND1. In a series of experiments with nude mice bearing MPM (MSTO-H211) xenografts, intravenous administration of miR-16 mimics packaged in minicells led to consistent and dose-dependent inhibition of tumor growth. Conclusions: Restoring miR-16 expression represents a novel approach to treatment for MPM. Preparations are being made to test miR-16 packaged in minicells as a new treatment approach for patients with recurrent MPM and NSCLC.
Circulating tumor cells as a prognostic factor in patients with small cell lung cancer.
Authors: Igawa Satoshi , Sasaki Jiichiro , Masuda Noriyuki 
Published: March 2020

7592 Background: Research on the detection of circulating tumor cells (CTCs) in peripheral blood is currently an important field of research. The aim of this study was to evaluate a new method of detecting CTCs in the peripheral blood of small cell lung cancer (SCLC) patients by using the telomerase-specific replication-selective adenovirus OBP-401. Methods: We prospectively enrolled 30 consecutive newly diagnosed SCLC patients who were being started on chemotherapy or chemoradiotherapy as the subjects of this study. We collected peripheral blood specimens from the SCLC patients and detected viable CTCs in them after incubation with a telomerase-specific, replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein (GFP) gene. We also investigated whether the CTC count per 7.5 ml of peripheral venous blood was associated with the outcome of SCLC. Results: CTCs were detected in 96% of the patients (29 of the 30 patients). The group of 22 patients with a CTC count of < 2 before treatment (baseline) had a significantly longer median survival time than the group of 8 patients with a CTC count of ≥ 2 before treatment (14.8 months and 3.9 months, respectively, P = 0.001). The results of a multivariate analysis showed that the baseline CTC count was an independent prognostic factor for survival (hazard ratio = 5.11, P = 0.038). Conclusions: CTCs in the peripheral blood of SCLC patients can be detected by the OBP-401assay, and based on the results of this study the CTC count before treatment appears to be a strong prognostic factor.
Prospective molecular evaluation of small cell lung cancer (SCLC) utilizing the comprehensive mutation analysis program at Memorial Sloan-Kettering Cancer Center (MSKCC).
Authors: Pietanza Maria Catherine , Varghese Anna M. , Won Helen H. , Wang Lu , Rekhtman Natasha , Krug Lee M. , Paik Paul K. , Riely Gregory J. , Zakowski Maureen Frances , Ladanyi Marc , Berger Michael F. , Kris Mark G. 
Published: March 2020

7600 Background: Oncogenic events in adenocarcinoma and squamous cell cancers of the lung are well described. In contrast, the repertoire of possible molecular targets in SCLC is still unclear. Recent studies using next generation sequencing on rare resected SCLC specimens have provided insights into the molecular heterogeneity of this disease. Comprehensive, prospective molecular profiling of patients with SCLC using the small biopsy specimens available in clinical practice has not been performed. Methods: Utilizing an IRB-approved protocol to prospectively test SCLC tumors (Small Cell Lung Cancer Mutation Analysis Program, “SC-MAP”), these biopsies are evaluated by: FISH for FGFR1 and MET amplification; immunohistochemistry for MGMT and PTEN loss; point mutation genotyping with Sequenom for PIK3CA (and others); and next-generation sequencing with our MSK-IMPACT assay (Integrated Mutation Profiling of Actionable Cancer Targets). MSK-IMPACT uses exon capture followed by massively parallel sequencing to profile all protein-coding exons and select introns of 279 cancer-associated genes, enabling the identification of mutations, indels, and copy number alterations of these genes. We tested the feasibility of this approach in a series of patients with SCLC. We performed next generation sequencing with MSK-IMPACT, with findings confirmed by FISH. Results: We identified 11 patients with SCLC with FFPE samples available from both matched normal tissue and small tumor biopsies, including 3 core biopsies and 8 fine needle aspirations. 9/11 patients had adequate tissue for MSK-IMPACT, which revealed recurrent mutations in Rb1 (N=7) and p53 (N=7), FGFR1 amplification (N=2), and MET amplification (N=1), using as little as 15 nanograms of DNA. FGFR1 and MET amplification were confirmed by FISH testing. We have initiated this prospective SC-MAP program for our patients with SCLC. Conclusions: Comprehensive molecular evaluation of SCLC is feasible on clinically available, small samples. Such analyses will allow us to characterize the molecular diversity of this disease and identify patients who will be candidates for targeted therapies.
A phase III study of pemetrexed (Pem) plus carboplatin (Cb) plus bevacizumab (Bev) followed by maintenance pem plus bev versus paclitaxel (Pac) plus cb plus bev followed by maintenance bev in stage IIIb or IV nonsquamous non-small cell lung cancer (NS-NSCLC): Overall and age group results.
Authors: Socinski Mark A. , Patel Jyoti D. , Garon Edward B. , Govindan Ramaswamy , Reynolds Craig H. , Spigel David R. , Olsen Mark R. , Liu Jingyi , Guba Susan C. , Bonomi Philip 
Published: March 2020

8004 Background: This study compared Pem+Cb+Bev followed by Pem+Bev maintenance (Pem arm) to Pac+Cb+Bev followed by Bev maintenance (Pac arm). The primary endpoint of improved overall survival (OS) for the Pem arm was not met. Methods: Advanced NS-NSCLC pts, ECOG PS 0/1, were randomized to 4 cycles of induction Pem+Cb+Bev with folic acid+vitamin B12 or Pac+Cb+Bev (Pem 500 mg/m2or Pac 200 mg/m2; Cb AUC 6; Bev 15 mg/kg) every 3 weeks. Eligible pts received maintenance Pem+Bev or Bev. OS, progression-free survival (PFS), overall response (ORR), and toxicity were evaluated. A hazard ratio (HR) of 0.80 required 676 OS events/900 pts with 2-sided type-I error .05 and at least 80% power for superiority of Pem over Pac arm. Exploratory Cox models estimated treatment HRs with 95% confidence intervals (CIs) for each age subgroup analyzed: ≤ or >65, 70 (prespecified) and ≤ or >75 yrs (not prespecified). Results: 939 pts (median age, 64.7) were randomized. Median (m) OS for ITT pem and pac arms was 12.6 vs 13.4 mos (HR 1.00, p=0.949); mPFS was 6.0 vs 5.6 mos (HR 0.83, p=0.012) Subgroup efficacy is shown in the Table; ≤ or >65 data were similar to ITT. Pem pts had significantly more drug-related grade 3/4 thrombocytopenia, anemia (except >75 yrs) and fatigue (except >70 and >75 yrs). Pac pts had significantly more grade 3/4 neutropenia (except >70 and >75 yrs), sensory neuropathy (except >75 yrs) and grade 1/2 alopecia. Results parallel overall safety data. Conclusions: OS was not significantly different in any of the age subgroups. PFS was significantly longer in Pem arm overall and for pts ≤70, but was similar for pts >70, >75 yrs. Toxicity profiles differed; subgroup safety data paralleled overall data. Clinical trial information: NCT00762034. [Table: see text]