bluuebunny/crossref_metadata_2025_split huggingface dataset:
Higher incidence of EGFR exon 19 deletion in younger (age 40 or younger) patients with adenocarcinoma of the lung.
Authors: Sugiyama Eri , Goto Koichi , Ishii Genichiro , Umemura Shigeki , Yoh Kiyotaka , Niho Seiji , Ohmatsu Hironobu , Nagai Kanji , Ohe Yuichiro 
Published: March 2020

7044 Background: The proportion of younger patients (≤ 40 years) with lung cancer is reported to be 2-5%. The most frequent histologic type of them is adenocarcinoma, however little is known about the pathological and molecular characteristics of younger patients with lung adenocarcinoma. Methods: Between July 1992 and April 2011, a total of 7443 patients were diagnosed as lung cancer in National Cancer Center Hospital East and 165 patients of whom (2.2%) who were 40 years or younger were identified. Among them, 44 patients with adenocarcinoma who underwent surgical resection were selected for this study. In addition, 185 elderly patients with > 40 years who underwent surgical resection matching gender and smoking status were selected as a control group. Histological predominant growth pattern and any coexisting variant pattern, the status of EGFR mutations were compared between these two groups. Results: The median age in ≤ 40 years patients was 37 years (range, 21 to 40 years) and that in elderly patients was 68 years (range, 42 to 83 years). Between these two groups, there were no significant differences in the distribution of histological predominant growth patterns (lepidic; 31.8% vs. 26.5%, papillary; 34.1% vs. 37.3%, acinar; 9.1% vs. 16.2%, and solid; 25.0% vs. 20.0%, p=0.78) and the incidence of EGFR mutations (40.9% vs. 45.9%; p=0.55). However, signet-ring cell component were significantly found in the younger patients than elderly (11.4% vs. 0%; p<0.01). The incidence of EGFR exon 19 deletion was significantly higher in younger patients than elderly, in contrast, that of EGFR exon 21 L858R was significantly higher in elderly patients (exon 19 del; 31.7% vs. 18.9%, L858R; 4.6% vs. 25.4%, p=0.0091). Three of 17 adenocarcinomas (17.7%) with EGFR-wild type in younger patients showed positive for ALK translocation. Conclusions: Younger patients with lung adenocarcinoma showed significantly higher proportion of EGFR exon 19 deletion genotype and containing histologically signet-ring cell component comparing with elderly patients. EGFR exon 19 deletion genotype may be related to pathogenesis of lung adenocarcinoma in younger patients.
Molecular profiling of patients with non-small cell lung cancer (NSCLC) using bronchoscopic ultra-micro sampling.
Authors: Sakairi Yuichi , Itoga Sakae , Sato Kenichi , Matsushita Kazuyuki , Yoshida Shigetoshi , Takiguchi Yuichi , Nomura Fumio , Yoshino Ichiro 
Published: March 2020

7046 Background: Genetic information is essential for molecular targeted therapy for personalized medicine, although tissue sampling for genetic analysis remains challenging. In this study, we investigated the utility of bronchoscopic ultra-micro samples compared with conventional histological materials for multiple gene analyses for NSCLC. Methods: Patients with NSCLC proven by on-site cytological examinations during bronchoscopic survey were eligible. Following conventional needle aspiration biopsy by flexible bronchofiberscope (from primary lesion) or convex probe endobronchial ultrasound (from lymph nodes), the used needle was rinsed with 20 ml of saline and this ultra-micro sample (MS) was used for both cytological diagnosis and genetic analysis. DNA and RNA were extracted from each sample. Gene mutations [EGFR (epidermal growth factor receptor), K-ras, BRAF] and anaplastic lymphoma kinase (ALK) fusion genes were examined by high resolution melting analysis and direct sequencing. The results of cytological diagnoses and gene profiles using MS were compared to conventional histological diagnoses. Results: A total of 79 lesions (30 primary and 49 metastatic nodes) from 76 patients were eligible. Adenocarcinoma (N = 46), squamous cell carcinoma (N = 25), and NSCLC (N = 8) were pathologically confirmed in histological lesion cores; however, only 29 malignancies (37%) were detected with MS. DNA and RNA could be extracted from all histological samples and MS. In 35 cases, genetic disorders were identified, including EGFR mutations (N = 12), K-ras mutations (N = 5), BRAF mutation (N = 1), ALK fusion genes (N = 3), and silent mutations (N = 13); these results were identical for both histological samples and MS. Conclusions: Bronchoscopic ultra-micro samples (biopsy needle rinse fluids) are useful for multiple genetic examinations.
Relationship between tumor size and survival in non-small cell lung cancer (NSCLC): An analysis of the Surveillance, Epidemiology, and End Results (SEER) registry.
Authors: Zhang Jianjun , Gold Kathryn A. , Lin Heather , Swisher Stephen , Lippman Scott Michael , Lee J. Jack , Kim Edward S. , William William 
Published: March 2020

7047 Background: Tumor size is a known prognostic factor for early stage (I and II) NSCLC, but its significance in node positive or locally advanced NSCLC has not been determined. We sought to evaluate its prognostic value in early and locally advanced NSCLC and create a nomogram incorporating tumor size and other prognostic variables to predict survival. Methods: The SEER registry was queried for patients (pts) with NSCLC, aged 20-103 and diagnosed between 1998 and 2003. Pts with extra-pulmonary metastases or distant lymph node metastases were excluded. Tumor size was analyzed as a continuous variable. Other demographic variables included age, gender, race, histology, primary tumor extension, node status and primary treatment modality (surgery vs radiation). Log-rank test was performed to evaluate the relationship between these variables and overall survival (OS). Cox proportional hazard model was used to evaluate whether tumor size was an independent prognostic factor. Results: 52,287 eligible pts were divided into 16 subgroups based on primary tumor extension and node status. For example, in group 1, tumor was confined to one lung with no nodes involved; pts in group 12 had tumor invading the mediastinum (T4 by extent) and positive ipsilateral mediastinal nodes. Tumor size had a significant effect on OS in almost all groups after adjustment for age, sex, race, histology, node status, primary tumor extension and primary treatment modality. Our model incorporating tumor size had significantly better predictive accuracy (larger C index) than our alternative model not including this information (p<0.0001). We then developed a nomogram incorporating tumor size, age, gender, race, histology, nodule stage, and tumor extension with the intent to predict OS. In subsequent bootstrap verification, the predicted 2-year OS from the nomogram was almost identical to the actual observed 2-year OS with a very slim biases of estimates. Conclusions: Tumor size is an independent prognostic factor, including pts with node positive or locally advanced NSCLC. We successfully created a nomogram incorporating tumor size and other clinical variables to predict survival.
Breath analysis for early detection of lung cancer.
Authors: Vallabhaneni Geetha D. , Gabram Sheryl G. A. , Lee Kichun Sky , Owonikoko Taofeek Kunle , Brandes Johann Christoph , Kono Scott Arthur , Saba Nabil F. , Khuri Fadlo Raja , Ramalingam Suresh S. , Bayer Charlene W. 
Published: March 2020

7048 Background: Lung cancer (LC) is the leading cause of cancer death worldwide. Early detection is critical to reduce LC related mortality. Breath analysis can be used as a non invasive diagnostic tool in conjunction with CT screening. We assessed the diagnostic value of breath volatile organic compounds (BVOCs) in the alveolar breath of female non-small cell lung cancer (NSCLC) patients. Methods: This is a prospective case-control study that enrolled newly diagnosed NSCLC and cancer-free female controls. The study aims: 1) To compare the BVOC signature in female NSCLC patients to a control group without LC 2) To compare the BVOC signature between NSCLC and breast cancer (BC) patients. The study was restricted to women because the pilot data was generated from female subjects with BC. Consenting eligible patients provided a total of five deep breath samples into a proprietary breath sampler developed at the Georgia Tech Research Institute (GTRI) for collecting alveolar breath. Breath samples were collected five minutes apart from each subject. The collected samples were analyzed for BVOCs using thermal desorption/gas chromatographic/mass spectrometric (TD/GC/MS) technique. Statistical differences in BVOCs in breath samples from cases and controls were assessed using this technique. Support vector machine classification method was employed to compare the BVOCs pattern between LC and BC patients. Results: We enrolled 25 NSCLC and 25 cancer-free subjects. TD/GC/MS analysis identified a total of 422 BVOCs among the controls and NSCLC subjects. 75 unique BVOCs that were significantly different between cases and controls were employed for statistical modeling. This 75 BVOCs signature has a sensitivity of 0.75, a specificity of 0.75 and a classification accuracy of 75% for NSCLC and controls. Statistical analysis on the full BVOCs data set from NSCLC and previously collected BVOCs data from BC patients achieved a classification accuracy of 88%. Conclusions: Unique BVOCs pattern can identify patients with established NSCLC. Future studies in at-risk patients will assess the utility of this approach as a less invasive and minimal risk screening tool for early detection of NSCLC. Supported by the Kennedy Seed Grant awarded by the Winship Cancer Institute of Emory University.
Case-control study of prophylactic cranial irradiation in nonmetastatic non-small cell lung cancer.
Authors: Cheng Simon , Corradetti Michael Nino , Horowitz David Paul , Xanthopoulos Eric , Lusa Amanda , Chao K. S. Clifford , Rengan Ramesh 
Published: March 2020

7050 Background: Prophylactic cranial irradiation (PCI) reduces the incidence of brain metastases in NSCLC patients after primary therapy, but its impact on survival is uncertain. We report on the largest study of survival in patients treated with and without PCI for non-small cell lung cancer (NSCLC). Methods: We reviewed 17 Surveillance, Epidemiology and End Results (SEER) registries for a retrospective study on patients who had PCI as part of their primary treatment for NSCLC from 1988 - 97. Cases were limited to those with non-metastatic (Stage I-III) NSCLC. To balance the cohorts, we matched each PCI patient with four non-PCI patients on stage, histology, race and sex. Associations between treatment type, clinical factors, and demographics were assessed using the Chi-squared test. Survival time was calculated as the number of months from diagnosis to the date of death. Survival was censored as of the last month when patients were known to be alive. Overall (OS) and cancer cause-specific survival (CSS) were investigated using the Kaplan-Meier, competing risks, Cox proportional hazards, and log-rank tests. Results: We found 472 PCI matched to 1,888 non-PCI patients. Characteristics were balanced across groups: race (p = 1.00), sex (p = 0.95), histology (p = 1.00), stage (p = 1.00), and surgery (p = 0.81). PCI group was younger, median age 64 vs 68 (p < 0.01). PCI vs no PCI median OS was 8 vs 10 months (p < 0.01). OS was 14% vs 28% at 2 years and 5% vs 12% at 5 years, PCI vs no PCI respectively (p < 0.01). Stage III OS was also different; 10% vs 21% at 2 years, PCI vs no PCI respectively (p < 0.01). Median CSS was the same at 9 months in both groups. Median follow-up was 14 years. Conclusions: PCI was not associated with improved OS or CSS in these NSCLC patients, and PCI may have a detrimental effect on OS. In limited-stage small cell lung cancer, a retrospective SEER analysis during the 1988 – 97 period showed a survival benefit in treated patients with PCI, which has been confirmed with prospective studies. To date, 4 prospective trials examining PCI for NSCLC have shown a reduced incidence of brain metastases, but the effect on survival is unclear. Further investigation is needed to determine whether PCI for NSCLC increases the risk of other causes of death.
Anatomic segmentectomy versus lobectomy for clinical stage I non-small cell lung cancer: A propensity-matched analysis.
Authors: Schuchert Matthew J. , Normolle Daniel Paul , McCormick Kristen N. , Wilson David O , Siegfried Jill , Landreneau Joshua P , Reamer Margaret , Luketich James D. , Landreneau Rodney Jerome 
Published: March 2020

7071 Background: Although anatomic segmentectomy is considered a “compromised” procedure by many surgeons, new information from several retrospective, single-institution series has countered negative premises regarding tumor recurrence and patient survival. The primary objective of this study was to utilize propensity score matching to compare outcomes following these anatomic resection approaches for stage I NSCLC. Methods: Patients undergoing lobectomy (n=392) vs. segmentectomy (n=793) for clinical stage I NSCLC were matched 1:1 using a propensity score that accounted for the potential confounding effects of pre-operative patient variables. Matching based on propensity scores produced 312 patients in each group. Primary outcome variables included recurrence-free and overall survival. Factors affecting survival were assessed by proportional hazards (Cox) regression and Kaplan-Meier survival function estimates. Results: Peri-operative mortality was 1.2% in the segmentectomy group and 2.5% in the lobectomy group (p=0.38). Ninety-day mortality was 2.6% and 4.8% (p=0.20), respectively. At a mean follow-up of 5.4 years, no differences were noted in locoregional (5.5% vs. 5.1%, p=1.00), distant (14.8% vs. 11.6%, p=0.29) or overall recurrence rates (20.2% vs. 16.7%, p=0.30) when comparing segmentectomy with lobectomy. Furthermore, no significant differences were noted in time to recurrence (p=0.415) or overall survival (p=0.258) when comparing the matched groups. Five year freedom from recurrence (95% CI) was: Segment 0.70 [95% CI: (0.63, 0.78) vs. Lobe 0.71 [95% CI: 0.64, 0.78]. Overall survival (95% CI) was: Segment 0.54 [95% CI: (0.47, 0.51) vs. Lobe 0.60 [95% CI: 0.54, 0.67]. Segmentectomy was not found to be an independent predictor of recurrence (HR: 1.11, 95% CI: 0.87, 1.40) or overall survival (HR = 1.17, 95% CI: 0.89.1.52). Conclusions: In this large propensity-matched comparison, anatomic segmentectomy is associated with similar time to recurrence and overall survival rates when compared to lobectomy for clinical stage I NSCLC. These results will need further validation by prospective, randomized trials (CALGB 140503).
Malignant pleural mesothelioma (MPM) in elderly patients: A multicenter survey.
Authors: Grosso Federica , Botta Mario , Zucali Paolo Andrea , Pasello Giulia , La Spina Chiara Maria , Roveta Annalisa , Perrino Matteo , Beretta Giordano D. , Polo Valentina , Santoro Armando , Favaretto Adolfo G. , Ceresoli Giovanni Luca 
Published: March 2020

7082 Background: The incidence of malignant pleural mesothelioma (MPM) in elderly patients (pts) is increasing in Western countries. Elderly pts with MPM are under-represented in clinical trials, and there are no specific guidelines for their management. The aim of this study was to perform a retrospective survey on this patient population in four Oncology Departments with high MPM accrual and expertise. Methods: The clinical records of elderly pts (≥70 years old) with MPM referred to the participating centers from January 2005 to November 2011 were reviewed. For each patient, age and gender, histology, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), Charlson Comorbidity Index (CCI) and treatment modalities were collected. The study endpoint was overall survival (OS). Results: Out of a total of 610 cases, 210 elderly pts were identified (34% of the whole MPM population observed in the study period). Pts characteristics were: median age 75 yrs (range 70-92), M/F 132/78, epithelial/non-epithelial histology 140/70, ECOG-PS 0/1/2/unknown 130/67/9/4. CCI was 0 in 128 pts (61%), ≥4 in 59 pts (28%). Treatment was multimodality therapy including surgery in 16, chemotherapy in 153 (73%) and best supportive care only in 41 pts (19%). Chemotherapy was mainly pemetrexed-based. Median OS was 11.3 months. Non-epithelial histology, age ≥75 yrs and the presence of comorbidities (CCI ≥1, p=.003; CCI ≥4, p<0.0001) were significantly correlated to a shorter OS. Conclusions: Pemetrexed-based chemotherapy is feasible in selected elderly pts with MPM. Comorbidity is a significant prognostic factor, and should be carefully considered in patient selection. Prospective dedicated trials in elderly pts with MPM selected according to comorbidity scales are warranted.
Outcomes of sarcomatoid malignant pleural mesothelioma, a distinct clinical entity.
Authors: Gattoni Elisabetta , Grosso Federica , Roveta Annalisa , Libener Roberta , Degiovanni Daniela , Mancuso Maurizio , Piccolini Ezio , Ferretti Gabriele , Botta Mario , Betta Pier Giacomo 
Published: March 2020

7084 Background: Sarcomatoid malignant pleural mesotheliomas (SMPM), accounting for 10% of MPM, are resistant to chemotherapy (CT) with median survival in the range of 6 months. Here we report on clinical outcome of a large series of SMPM patients treated at our Oncological Department, located in a particularly asbestos-polluted area in Piedmont (Italy). Methods: Patients consecutively diagnosed, treated and included in our MesoDB between 1993 and 2010 were considered for this study. Clinical and pathological data, treatments, response to CT and outcomes were analyzed for the present study. Diagnosis was always confirmed by the same expert pathologist. Results: Data of 672 patients were considered for the analysis. Among these, 53 (8%) were diagnosed with SMPM (17F/36M). Median age was 67,6 years. Asbestos exposure was occupational certain in 12, possible in 15, domestic in 3 and environmental in 23. The predominant symptom at diagnosis was thoracic pain in 34 patients (64%), followed by dyspnea in 16 (30%), fatigue and weight loss in 2 and palpable mass in 1. The predominant radiological finding at diagnosis was diffuse pleural thickening in 23 patients (43%), pleural effusion in 14 (26%), pleural effusion and pleural thickening in 10 (19%), localized mass in 4 (8%), unknown in 2 (4%). Forty-eight patients received first line CT with the following regimens: carboplatin/cisplatin and pemetrexed in29, pemetrexed in 8, cisplatin and raltitrexed in 3, cisplatin and gemcitabine in 3, gemcitabine in 2, doxorubicin based combination in 3 patients. The median number of cycles was 4. Overall response rate to first line CT was as follows: 11 SD (21%), 31 PD (58%) and 6 (11%) patients were not evaluable for response. Median progression free survival was 3.3 (95%CI 2.6-4.1) months. Eleven patients received a second line CT and no responses or disease stabilization was observed. Median OS was 7.6 months. Conclusions: This large series of SMPM suggests that standard CT has only negligible impact on the prognosis, underlying a highly unmet clinical need. SMPM patients should be treated within phase I-II studies with investigational agents. Research should focus to a deeper knowledge of tumor biology and to the identification of druggable targets.
Phase II study of amrubicin (AMR) combined with carboplatin (CBDCA) for refractory relapsed small cell lung cancer (SCLC): North Japan Lung Cancer Group 0802.
Authors: Saito Ryota , Inoue Akira , Sugawara Shunichi , Oizumi Satoshi , Maemondo Makoto , Okudera Koichi , Suzuki Toshiro , Usui Kazuhiro , Harada Masao , Morikawa Naoto , Hasegawa YUkihiro , Ishimoto Osamu , Sakakibara Tomohiro , Asahina Hajime , Nukiwa Toshihiro 
Published: March 2020

7086 Background: AMR, a new anthracycline agent, has achieved some promising results for advanced SCLC both in the first-line and the second-line setting. However the efficacy of AMR alone against refractory relapsed SCLC was relatively low in previous studies. This study was conducted to evaluate the safety and efficacy of the combination of AMR plus CBDCA in patients with refractory relapsed SCLC. Methods: Patients with advanced SCLC who relapsed within 90 days after the completion of first-line chemotherapy received AMR (30 mg/m2, day1-3) and CBDCA (AUC 4.0, day 1) every 3 weeks. The primary endpoint of this study was overall response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival and toxicity profile. Assuming that ORR of 45% in eligible patients would indicate potential usefulness while ORR of 20% would be the lower limit of interest, with alpha = 0.10 and beta = 0.10, at least 24 patients were required. Results: From September 2008 to May 2011, 30 patients were enrolled from 10 institutions. One patient was excluded because of ineligible histology. Patient characteristics were: Male/Female 26/3; median age 67 (range 50-81); Performance status 0/1/2 9/16/4. The median number of treatment cycles were 4 (range 1-7). The objective responses evaluated by RECIST were: CR 0, PR 10, SD 14, PD 5. The ORR was 34% and the disease control rate was 83%. Median PFS was 3.5 months and median survival time was 7.3 months. Grade 3-4 neutropenia was observed in 23 patients (79%) and grade 3-4 thrombocytopenia was observed in 7 patients (24%). One patient (3%) suffered from grade 3-4 febrile neutropenia. Other grade 3 non-hematological toxicities such as infection, interstitial lung disease, hyponatremia, hypoglycemia, were observed in 7 patients (24%). No treatment related death was observed. Conclusions: This is the first prospective study of AMR combined with CBDCA for refractory relapsed SCLC, which was effective and well tolerated. Further investigation of this treatment is warranted.
Genome-wide association study of survival in small cell lung cancer patients treated with irinotecan and cisplatin chemotherapy.
Authors: Han Ji-Youn , Shin Eun Soon , Lee Yeon-Su , Kim Sook-Young , Hong Seung-Hyun , Kim Jin Young , Lee Jin Soo 
Published: March 2020

7089 Background: The prognosis of patients with extensive-disease small-cell lung cancer (ED-SCLC) remains poor. Despite a high initial response rate to chemotherapy, most patients die from rapid recurrence. We conducted a genome-wide analysis study (GWAS) to examine whether germline genetic variations are prognostic factors in ED-SCLC patients treated with irinotecan and cisplatin (IP) chemotherapy. Methods: We prospectively collected blood samples from 139 patients who participated in two phase II studies of IP chemotherapy as first-line therapy and conducted a GWAS using overall survival (OS) as the endpoint. Germline DNA was genotyped using the Affymetrix 5.0 or 6.0 array sets. Associations between OS and single nucleotide polymorphisms (SNPs) were investigated using multivariate Cox regression analysis. Adjustments for age, performance status (PS) and gender were made. We selected most promising SNPs with p<1×10−6 in the GWAS allelic association analyses. Results: A total of 426,019 SNPs were genotyped and 343,530 SNPs passed quality control (HWE, p<10-7, minor allele frequency>1%). We found 7 SNPs showing a significant association with OS. Patients harboring rs16950650 CT, rs7186128 AG or GG, rs17574269 AG, rs8020368 CC, rs4655567 CC, rs2166219 TT and rs2018683 TT genotypes showed shorter OS compared to patients with control alleles. Hazards ratios of death for each risk variants were 30.2 (95% CI, 8.3-109.0, p=2.1X10-7), 2.5 (95% CI, 1.7-3.5, p=3.8X10-7), 7.6 (95% CI, 3.4-16.6, p=4.5X10-7), 3.4 (95% CI, 2.1-5.5, p=3.5X10-7), 4.9 (95% CI, 2.7-9.0, p=3.1X10-7), 5.8 (95% CI, 2.9-11.7, p=8.4X10-7) and 7.8 (95% CI, 3.4-17.7, p=8.0X10-7), respectively. Among these SNPs, rs4655567, rs8020368, rs2018683 and rs17574269 were significantly associated with a refractory relapse. In multivariate logistic analysis including age, gender and PS, rs8020368 CC genotype showed higher risk of refractory relapse than patients with TT or TC genotype (HR=14.9 [95% CI, 1.9-114.8], p=0.010). Conclusions: This exploratory GWAS identified several candidate SNPs that might predictive for the outcome of patients with ED-SCLC receiving IP chemotherapy.