bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of survival after resections of synchronous lung cancers located in mutiple lobes: A multi-institutional pooled analysis.
Authors: Tanvetyanon Tawee , Finley David J. , Fabian Thomas , Riquet Marc , Voltolini Luca , Fulp William J , Kocaturk Celalettin , Park Bernard J. , Robinson Lary 
Published: March 2020

7024 Background: Surgical resection is a treatment option for patients with multiple primary lung cancers. However, for synchronous disease, it is often difficult to differentiate this condition from metastatic disease, especially when cancers are distributed in multiple lobes or in both lungs. Some people believe that surgery should be avoided when patients have bilateral cancers or when all cancers have the same histology. To date, however, available evidences are limited by small sample size. Methods: Studies (published 2008-2011) of curative resection for patients with synchronous (< 2-year interval) multiple lung cancers located in ≥ 2 lobes, but without radiographic evidence of distant metastasis, were identified from literature. Corresponding authors were contacted and individual patient data were obtained. Patients with multiple cancers, but localized only to one lobe, were not included. Databases were pooled and multi-variable Cox Proportional Hazard models were fit to adjust for confounders. Results: There were 467 patients included from 6 studies. Median overall survival was 52.0 months (95% CI: 45.6-63.7). Postoperative (30-day) mortality rate was 1.9%. In a multivariable model, study site or having pneumonectomy did not independently impact on survival. However, age, gender, nodal stage, tumor location, and histological similarity were independent predictors of survival. Advanced age increased mortality (p=0.012). Male sex increased mortality compared with female: HR 1.64 (95% CI: 1.23-2.19, p=0.0008). N2 or N1 increased mortality over N0: HR 1.85 (95% CI 1.29-2.66, p=0.0008) and 1.97 (1.43-2.73, p=0.0001), respectively. Unilateral location increased mortality over bilateral location: HR 1.62 (95% CI 1.23-2.13, p=0.0002). Different histology increased mortality over similar histology: HR 1.45 (95% CI 1.11-1.90, p=0.0069). Conclusions: In this largest multi-institutional database of resected multiple lung cancers of multiple lobes to date, we found no evidence of inferior survival among patients having bilateral cancers or having all cancers with the same histology. In fact, the survival among such patients appears superior to their counterparts.
Randomized phase III study comparing etoposide and cisplatin (EP) with irinotecan and cisplatin (IP) following EP plus concurrent accelerated hyperfractionated thoracic radiotherapy (EP/AHTRT) for the treatment of limited-stage small-cell lung cancer (LD-SCLC): JCOG0202.
Authors: Kubota Kaoru , Hida Toyoaki , Ishikura Satoshi , Mizusawa Junki , Nishio Makoto , Kawahara Masaaki , Yokoyama Akira , Imamura Fumio , Takeda Koji , Negoro Shunichi , Harada Masao , Okamoto Hiroaki , Yamamoto Nobuyuki , Shinkai Tetsu , Sakai Hiroshi , Matsui Kaoru , Nakagawa Kazuhiko , Shibata Taro , Saijo Nagahiro , Tamura Tomohide ,   Japan Clinical Oncology Group
Published: March 2020

7028 Background: Four cycles of EP plus AHTRT is the standard treatment for LD-SCLC. IP demonstrated statistically significant overall survival (OS) improvement compared to EP for extensive-stage SCLC (JCOG9511; Noda, et al.NEJM, 2002). EP plus AHTRT followed by 3 cycles of IP is feasible with acceptable toxicities for LD-SCLC (Kubota, et al. CCR,2005). Methods: Eligibility criteria included patients with previously untreated LD-SCLC with measurable lesion, ECOG PS of 0-1, age: 20=<, =<70 years old. Eligible patients received one cycle of EP (etoposide 100 mg/m2 on days 1-3 and cisplatin 80mg/m2 on day 1) plus AHTRT (1.5 Gy b.i.d. total 45 Gy/3 weeks). Patients who achieved CR, good PR, PR or SD with induction EP/AHTRT were randomized to receive either 3 cycles of consolidation EP or IP (irinotecan 60 mg/m2 and cisplatin 60 mg/m2 on days 1, 8, 15). Patients with CR or good PR after consolidation chemotherapy received prophylactic cranial irradiation. The primary endpoint is OS after the randomization. The planned sample size for randomization is 250 with a one-sided alpha of 2.5% and at least 70% power to detect a difference between gruops, 30% in EP versus 42.5% in IP group in 3-year survival. Results: From Sep 2002 to Sep 2006, 281 patients from 36 institutions were registered. After the induction EP/AHTRT, 258 patients were randomized to consolidation EP (n=129) or IP (n=129). Patient demographics were well balanced between the two groups. At the final analysis, the superiority of IP in OS was not demonstrated (hazard ratio of IP to EP, 1.085 [95%CI: 0.80-1.46]; one sided p=0.70, stratifield log-rank test). Grade 3/4 neutropenia (95%/78%), anemia (35%/39%), thrombocytopenia (21%/5%), neutropenic fever (17%/14%), diarrhea (2%/10%) were observed in EP and IP groups, respectively. Conclusions: EP plus AHTRT followed by 3 cycles of IP failed to demonstrate survival advantage over 4 cycles of EP plus AHTRT which still is the standard treatment for LD-SCLC. [Table: see text]
Predictors for locoregional recurrence for clinical stage III-N2 non-small cell lung cancer with nodal downstaging after induction chemotherapy and surgery.
Authors: Lou Feiran , Amini Arya , Correa Arlene M , Baldassarre Randall L , Rimner Andreas , Roth Jack A. , Swisher Stephen , Huang James , Vaporciyan Ara A. , Lin Steven H. 
Published: March 2020

7043 Background: Pathologic downstaging following induction chemotherapy in patients with stage III-N2 NSCLC is a well-known positive prognostic indicator. However, the predictive factors for locoregional recurrence (LRR) in these patients are largely unknown. Methods: Between 1998-2008, 153 patients with clinically or pathologically-staged III-N2 NSCLC from two cancer centers in the United States were treated with induction chemotherapy and surgery. All patients had pathologic N0-1 disease, and no one received postoperative radiotherapy. LRR were defined as disease recurrence at the surgical site, lymph nodes (levels 1-14 including supraclavicular) or both. Overall survival (OS) was calculated using the Kaplan and Meier method and comparisons were made using the log-rank test. Univariate and multivariate Cox proportional hazards model were used to assess the association of LRR and risk factors. Results: The median follow up time for survivors was 39.3 months. Baseline pretreatment N2 nodal involvement was staged by either pathologic confirmation (18.2%) or PET/CT (81.8%). Overall, the 5 year LRR rate was 30.8% (n=38), with LRR being the first site of failure in 51% (22 of 43). The 5 year OS for patients with LRR compared to those without was 21% versus 60.1%, respectively (p<0.001). Using multivariate analysis, significant predictor for LRR was pN1 versus pN0 disease at time of surgery (p<0.001, HR 3.43, 95% CI 1.80-6.56) and trended for squamous histology (p=0.072, HR 1.93, 95% CI 0.94-3.98). The 5-year LRR rate for N1 versus N0 disease was 62% versus 20%, respectively. Neither single versus multistation N2 disease (p=0.291) nor initial staging by mediastinoscopy versus PET/CT (p=0.306) were predictors for LRR. We found that N1 status was also predictive for higher distant recurrence rate (p=0.021, HR 1.91, 95% CI 1.10-3.30) but only trended for poorer OS (p=0.123, HR 1.48, 95% CI 0.90-2.44). Conclusions: LRR remains high in resected stage III-N2 NSCLC patients after induction chemotherapy and nodal downstaging, particularly in patients with persistent N1 disease. Postoperative radiotherapy may be needed for these high-risk patients.
A phase II trial of induction gefitinib monotherapy followed by cisplatin-docetaxel and concurrent thoracic irradiation in patients with EGFR-mutant locally advanced non-small-cell lung cancer (LA-NSCLC): LOGIK0902/OLCSG0905 intergroup trial.
Authors: Hisamoto Akiko , Sasaki Jiichiro , Takigawa Nagio , Shioyama Yoshiyuki , Kishimoto Junji , Takemoto Mitsuhiro , Hotta Katsuyuki , Tanimoto Mitsune , Ichinose Yukito , Kiura Katsuyuki ,   Lung Oncology Group in Kyushu and Okayama Lung Cancer Study Group
Published: March 2020

7045 Background: We previously reported efficacy and safety of cisplatin-docetaxel and concurrent thoracic radiotherapy (TRT) for LA-NSCLC (Segawa Y and Kiura K. JCO 2010). However, its cure rate remains unsatisfied, and further improvement in the treatment outcome is strongly warranted. Recently, systemic chemotherapy has been individualized by intensive anti-cancer researches through the discovery of certain molecular targets in the metastatic NSCLC. Especially, gefitinib, EGFR tyrosine kinase inhibitor, is quite active and now one of the standard chemotherapy for untreated metastatic EGFR-mutant NSCLC (Maemondo M and Inoue A. NEJM 2010). Even in the locally advanced setting, approximately 30% of Japanese NSCLC patients possess EGFR-mutant tumors. Given all of these backgrounds, investigation on the role of adding gefitinib monotherapy to the standard concurrent chemoradiotherapy might cause a new paradigm shift in this setting. Methods: Patients have to meet the following eligibility criteria: LA-NSCLC; active tumor EGFR mutations (exons 19 and 21) but without 790M; measurable lesions; performance status (PS) of 0 or 1; age < 75 years; and V20 ≤ 35%. The primary endpoint is set as 2-year progression-free survival (PFS) rate; assuming that 75% in eligible patients would indicate potential usefulness, whereas 60% would be the lower limit of interest (α = 0.05, ß = 0.20), the estimated accrual number is 46 patients. The secondary endpoint includes toxicity, response rate and overall survival. Patients will receive the induction treatment, specified as gefitinib monotherapy (250 mg/body) for 8 weeks. Patients who have not progressed during the induction therapy will receive cisplatin and docetaxel (40 mg/m2; days 1, 8, 29, 36, each) and concurrent three-dimensional conformal TRT (2-Gy, single, daily fractions for 5 consecutive days each week to provide a total dose of 60 Gy). Enrollment began in 2010, and will complete by 2015. UMIN registration number of 000005086.
5-day dosing schedule of temozolomide in relapsed sensitive or refractory small cell lung cancer (SCLC) and methyl-guanine-DNA methyltransferase (MGMT) analysis in a phase II trial.
Authors: Drilon Alexander Edward Dela Cruz , Kyuichi Kadota , Huberman Kety H , Sima Camelia S. , Fiore John Joseph , Yu Helena Alexandra , Varghese Anna M. , Sumner Dyana K. , Travis William D , Heguy Adriana , Ginsberg Michelle S. , Holodny Andrei , Chan Timothy An-thy , Rizvi Naiyer A. , Azzoli Christopher G. , Riely Gregory J. , Kris Mark G. , Krug Lee M. , Pietanza Maria Catherine 
Published: March 2020

7052 Background: MGMT promoter methylation and loss of MGMT activity are associated with improved sensitivity to alkylating agents. We recently reported that the oral alkylating agent temozolomide is active in 2nd- and 3rd-line treatment of relapsed SCLC at 75mg/m2/day for 21 out of 28 days (Pietanza et al, Clin Can Res 2012). Here we evaluate the 5-day dosing schedule of temozolomide in a second cohort of patients and analyze MGMT activity in both cohorts of patients on the same study. Methods: Patients with disease progression after 1 or 2 prior chemotherapy regimens received temozolomide at 200mg/m2/day for 5 out of 28 days (n=25). Those with sensitive (S-SCLC, n=16) and refractory (R-SCLC, n=9) disease were enrolled to assess safety. Available tumor tissue from patients treated according to either schedule was assessed for MGMT promoter methylation status by PCR and MGMT expression by immunohistochemistry (IHC). Results: An overall response rate of 12% was noted (3 partial responses: 1 S-SCLC, 2 R-SCLC). 4 patients had stable disease for at least 3 cycles. Median progression-free survival and overall survival for all patients were 1.3 months and 7.9 months, respectively. Grade ≥3 thrombocytopenia and neutropenia was observed in 20% with a shorter mean duration of myelosuppression compared to the 21-day schedule. Results from MGMT evaluation of tumor samples from both dosing schedules were combined. Promoter methylation of MGMT was not significantly associated with response (p=0.23). However, patients that lacked MGMT expression by IHC had a higher response rate compared to those with MGMT-positive tumors (43% vs. 13%, p = 0.052; see table). Conclusions: The 5-day dosing schedule of temozolomide is both active and safe in patients with relapsed SCLC. A strong trend toward increased response was demonstrated in patients with MGMT-negative tumors compared to patients with MGMT-positive tumors by IHC. A trial combining temozolomide with the PARP inhibitor, ABT888, is planned. [Table: see text]
Prognostic role of FOXP3/CD4 ratio in resectable NSCLC.
Authors: Usó Marta , Sirera Rafael , Jantus-Lewintre Eloisa , Sanmartin Elena , Gallach Sandra , Blasco Ana , Martinez Nieves , Hernando Cristina , Figueroa Santiago , Rolfo Christian Diego , Martorell Miguel , Guijarro Ricardo , Camps Carlos 
Published: March 2020

7058 Background: Tregs play a critical role in immune tolerance to tumor cells and have been related to prognosis. The aim of this study was to determine the expression of Tregs makers genes by RT-PCR and to correlate them with clinico-pathological and prognostic variables in NSCLC. Methods: RNA was isolated from frozen lung specimens (tumor and normal lung) from resectable NSCLC patients (n=175). RT-PCR was performed to analyze the expression of: CD4, CD8A, CTLA-4, FoxP3, IL-10, CD25, CD127 and TGFβ-1. Relative expression was normalized by an endogenous gene (GUSB) using the Pfaffl formulae. Statistical analyses were considered significant at p<0.05. Results: Tumor samples had significantly lower expression of CD127 (x0.45) and a tendency toward higher expression of CD25 (x1.81), FoxP3 (x1.57) and CTLA-4 (x1.53) compared to normal lung tissues, reflecting a Treg phenotype infiltrating the tumor. Survival analyses revealed that patients with higher FoxP3 expression had reduced OS (median 29.8 vs 67 months, p= 0.026). We also found that those patients with high levels FoxP3/CD4 ratio had worse TTP and OS (median 22.1 months vs NR, p= 0.021 and 29.8 vs NR months, p=0.003, respectively). A multivariable Cox regression model for TTP and OS was built using variables that were found significant in the univariate analysis (nodal involvement, histology, tumor size, PS, and FoxP3/CD4 ratio). This analysis revealed that FoxP3/CD4 ratio was an independent prognostic marker for both TTP and OS (see table). Conclusions: FoxP3 is a transcription factor necessary and sufficient for induction of the immunosuppressive functions in Tregs. In concordance, our results indicate that higher levels of FoxP3/CD4 ratio in tumor samples is a poor prognostic markers for TTP and OS. Furthermore, the multivariable COX regression analysis showed that FoxP3/CD4 ratio is an independent prognostic marker. Therefore, this ratio could be used as a new biomarker of prognosis in resectable NSCLC. Supported by grants PS09-01149 and RD06/0020/1024 from ISCIII. [Table: see text]
A systematic analysis of high-dose radiation in the treatment of surgically unresectable, locally advanced non-small cell lung cancer.
Authors: Behera Madhusmita , Beitler Jonathan Jay , Bhimani Chandar , Higgins Kristin , Chen Zhengjia , Kim Sungjin , Deng Xingming , Curran Walter J. , Khuri Fadlo Raja , Ramalingam Suresh S. , Owonikoko Taofeek Kunle 
Published: March 2020

7059 Background: The 5-year survival rate for locally advanced non-small cell lung cancer (NSCLC) is < 25% with concomitant chemoradiotherapy. High-dose radiation appears to confer additional benefit based on surrogate endpoints from relatively small clinical trials. However, survival advantage of higher-dose radiation delivered by conventional fractionation of 1.8-2 Gy is unclear. We conducted a systematic review of pooled outcome data from published results of studies that evaluated the role of high-dose radiation in the management of locally advanced NSCLC. Methods: A detailed search of published clinical trials was conducted using computerized databases (MEDLINE, EMBASE, Cochrane library) and meeting proceedings. Single arm studies using high dose (>66Gy) or randomized trials of high versus standard radiation dose (60-63Gy) for locally advanced NSCLC were selected. A systematic analysis of extracted data was performed using Comprehensive Meta Analysis (Version 2.2.048) software under the random effect model. Clinical outcome in patients treated with high versus standard radiation dose was compared using point estimates for weighted values of median overall survival (OS), progression free survival (PFS), and response rate (RR). Treatment-related toxicities data between the two arms was compared using T-test and chi-square test. Results: Analytic data was retrieved from the results of 44 eligible studies reported between 1994 and 2012. The studies enrolled 3699 patients, 62% males, 2095 and 1604 treated with standard and high dose radiation respectively. The weighted median age was 63 and 61 years (p=0.66) for standard and high dose patients respectively. The weighted median OS was 19.1 vs. 16.4 months (p= 0.97); weighted RR of 76% vs. 70% (p=0.79) and survival rates after up to 3 years of follow up of 39% vs. 46% (p=0.45) for standard and high dose arms respectively. There was no significant difference in the rate of grade ≥3 toxicities between the two treatment groups. Conclusions: High-dose radiation therapy does not result in improved survival over standard radiotherapy dose in patients with locally advanced NSCLC.
SOX2 and FGFR1 gene copy number in surgically resected non-small cell lung cancer (NSCLC).
Authors: Toschi Luca , Finocchiaro Giovanna , Nguyen Teresa T. , Skokan Margaret , Giordano Laura , Gianoncelli Letizia , Perrino Matteo , Siracusano Licia , Destro Annarita , Infante Maurizio , Alloisio Marco , Terracciano Luigi , Roncalli Massimo , Santoro Armando , Varella-Garcia Marileila 
Published: March 2020

7061 Background: SOX2 is a member of the SRY-related HMG-box family of transcription factors and has been shown to be frequently amplified and overexpressed in squamous cell lung cancer, with conflicting results regarding its prognostic relevance. Similarly, FGFR1, a transmembrane tyrosine kinase receptor belonging to the fibroblast growth factor receptor family, has been recently reported to be amplified in squamous cell lung carcinomas, suggesting a potential role for FGFR1 as a therapeutic target in NSCLC. Aim of the present study is to evaluate SOX2 and FGFR1 gene copy number in surgically resected NSCLCs, to investigate their prognostic relevance and their association with clinico-pathological characteristics. Methods: SOX2 and FGFR1 gene copy number was assessed by fluorescence in situ hybridization (FISH) in tissue microarray cores from 447 surgically resected NSCLCs. Each patient was given a score ranging from 1 to 6 according to increasing mean copy number per cell of each gene, with 6 indicating true gene amplification. Results: SOX2 and FGFR1 FISH was successfully performed in 445 patients (pts), which were grouped as + (score 5-6) and - (score 1-4). Using this scoring system 105 (23.6%) pts tested SOX2+, while 74 (16.6%) pts resulted FGFR1+. True gene amplification for SOX2 and FGFR1 was observed in 19 (4.3%) and 37 (8.3%) cases, respectively. SOX2+ and FGFR1+ status was significantly associated with squamous histology (p<.001). Additionally, SOX2+ pts had a significantly higher chance of being former/current smokers, male and FGFR1+. FGFR1 gene status had no prognostic impact in the whole population and in the squamous cell carcinoma subgroup. Conversely, SOX2+ pts had significantly longer overall survival compared with SOX2- pts (HR 0.68, p=.020). When restricting survival analysis to squamous cell histology, stage I-II SOX2+ pts had a significant survival advantage compared with SOX2- group (HR 0.38, p=.006), while no difference was observed in stage III-IV pts. Conclusions: Increased SOX2 and FGFR1 gene copy number is a common event in lung cancer pts with squamous cell histology. SOX2 gene gain is a favorable prognostic factor in surgically resected pts, particularly in early stage squamous cell cancers.
Survival following segmentectomy and lobectomy for stage I non-small cell lung cancer.
Authors: Smith Cardinale B. , Wisnivesky Juan P. 
Published: March 2020

7064 Background: Although lobectomy is considered the standard surgical treatment forstage IA non–small cell lung cancer (NSCLC), limited resections are frequently performed for patients with poor lung function or high operative risk. Recent studies suggest that segmentectomy may be the superior limited resection procedure. The objective of this study was to compare survival among patients with stage IA (≤3cm) NSCLC undergoing lobectomy vs. segmentectomy. Methods: Using the Surveillance, Epidemiology and End Results registry we identified 15,180 cases of stage IA NSCLC that underwent lobectomy or segmentectomy. We used logistic regression to determine propensity scores for patients undergoing segmentectomy based on the patient’s preoperative characteristics. Overall and lung cancer-specific survival of patients treated with lobectomy versus segmentectomy was compared after adjusting, stratifying, or matching patients based on their propensity score. We also performed secondary analyses in subgroups of age (≤70 vs. >70 years) and tumor size ≤2 cm. Results: Overall, 1,200 (8%) patients underwent segmentectomy. Among the entire cohort, analyses adjusting for propensity scores did not demonstrate a difference in outcomes among patients treated with lobectomy versus segmentectomy, (adjusted hazard ratio [HR] for overall survival 1.11, 95% confidence interval [CI]: 0.94 – 1.30 and lung cancer-specific survival 1.11, 95% CI: 0.98 – 1.25). Similarly, secondary analyses showed no difference in overall (HR: 1.12, 95% CI: 0.90 – 1.40) and lung cancer-specific survival (HR: 1.04, 95% CI: 0.88 – 1.24) among patients with tumors ≤2 cm (T1a tumors). For patients ≤70 years of age, no difference in overall survival was observed (HR: 0.97, 95% CI: 0.73 – 1.28); however, a lung cancer-specific survival advantage of lobectomy was observed (HR: 1.19, 95% CI: 1.00 – 1.40). Finally, among those >70 years overall survival (HR: 1.03, 95% CI: 0.87 – 1.22) and lung cancer-specific survival (HR: 1.18, 95% CI: 0. 97 – 1.44) showed equivalence of the two surgical groups. Conclusions: Segmentectomy and lobectomy may lead to equivalent survival rates among patients with stage IA NSCLC. These study findings should be confirmed in prospective studies.