bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accelerated hypofractionated hemithoracic intensity modulated radiation therapy (IMRT) followed by extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM): Results of a phase I/II study.
Authors: de Perrot Marc , Feld Ronald , Leighl Natasha B. , Opitz Isabelle , Anraku Masaki , Cho BC John 
Published: March 2020

7526 Background: We developed a protocol with accelerated hypofractionated hemithoracic IMRT followed by EPP for MPM. Advantages include optimal delivery of radiation to the whole tumor bed in a short period limiting the risk of viable tumor cell spread during surgery. Methods: Patients with resectable clinical T1-3N0M0 histology proven MPM were eligible for the study. 25 Gy in 5 daily fractions over 1 week was delivered to the entire ipsilateral hemithorax by IMRT with concomitant boost of 5 Gy to volumes at high risk based on CT and PET scan findings. EPP was performed one week after the end of radiation. Adjuvant chemotherapy was offered to patients with ypN2 on final pathology. The primary end-point was treatment related mortality. Secondary endpoint included overall survival and disease-free survival (DFS). Initial sites of recurrence were also recorded. Results: Twenty five patients were accrued between 11/2008 and 10/2012. Patients had a median age of 64 years (range, 45-75), 76% were males, 64% had epithelioid histology. All patients completed IMRT and EPP. IMRT was well tolerated with no grade 3-5 toxicity. EPP was performed 6±2 days after completion of IMRT. Surgical complications occurred in 18 patients. One patient died from empyema at 88 days. All but one patient (stage IB) had stage III (n=11) or IV (n=13) disease on final pathology. Five out of 13 patients with ypN2 disease underwent adjuvant chemotherapy. After a median follow-up of 19 months (range, 3-51), the estimated 3-year survival reached 62%. Survival was significantly better in epithelioid compared to biphasic pathologic subtypes (83% survival at 3 years vs 19%, respectively; p=0.004). 14 patients remain disease free after a median follow-up of 17 months (range, 3-37). 2-year DFS was 85% in stage III and 37% in stage IV disease (p=0.03). Recurrences occurred in the ipsilateral chest only (n=2), ipsilateral chest and distant sites (n=2), and distant sites only (n=6). Conclusions: Accelerated hypofractionated hemithoracic IMRT followed by EPP is feasible. This treatment could improve survival in selected patients with epithelial subtype. Clinical trial information: NCT00797719.
Intratumoral gene expression of 5-fluorouracil pharmacokinetics related enzymes in stage I and II non-small cell lung cancer patients treated with uracil-tegaful after surgery.
Authors: Eguchi Keisuke , Abiko Tomohiko , Kohno Mitsuo , Sawafuji Makoto , Horio Hirotoshi , Hashizume Toshinori , Nakayama Mitsuo , Kato Ryoichi , Kawamura Masafumi 
Published: March 2020

7536 Background: It is believed through meta-analysis that the adjuvant chemotherapy with oral administration of uracil-tegafur combination drug (manufactured as UFT) yielded better survival than surgery alone in early stage non-small cell lung cancer patients (NSCLC) in Japan. However, no promising bio-marker, which can predict the benefit of UFT use in NSCLC patients, has been found. This clinical trial was designed to evaluate the relationship between the intratumoral gene expression of the five-fluorouracil pharmacokinetics related enzymes such as thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orate phosphoribosyltransferase (OPRT) and thymidine phosphorylase (TP), and clinical outcomes in patients to whom UFT was administered for 2 years after surgery. Methods: From June 2004 to September 2007, 236 NSCLC patients who underwent complete resection of a pathological stage IA (maximum diameter of 2cm or more), IB and II (according to the 1997 UICC TNM classification) were eligible in this study. Other inclusion criteria were age of 20 to 80 years, ECOG PS of 0 or 1 and feasible oral UFT administration within 8 weeks after surgery. Total RNA was extracted from formalin-fixed lung cancer cell sample obtained with micro-dissection method. Gene expression was examined using quantified fluorescence-based real time revers transcription-polymerase chain reaction assay. Results: 131 (63%) patients completed 2 year administration of UFT. 73 (31%) patients had recurrence during 5 years follow-up and 48 (73%) patients among them were treated with chemotherapy including platinum. The 5-year disease free survival (DFS) and overall survival (OS) rates in all patients were 66.7% and 83.7%, respectively. A cox multivariate analysis revealed pathological stage (HR: 0.4463; p=0.034), TS expression status (HR: 0.469; p=0.021) and DPD expression status (HR: 1.956; p=0.048) to be prognostic for DFS but no factors to be prognostic for OS. Conclusions: This study suggested that TS and DPD mRNA expression in the tumor were possible prognostic biomarkers for postoperative adjuvant chemotherapy with UFT in stage I-II NSCLC. Clinical trial information: 15-65-1.
Impact of the presence of EGFR mutation on definitive chemoradiotherapy in patients with locally advanced non-small cell lung cancer: Pattern of relapses and survival analyses in 145 patients.
Authors: Yagishita Shigehiro , Horinouchi Hidehito , Taniyama Tomoko , Nakamichi Shinji , Kitazono Satoru , Mizugaki Hidenori , Kanda Shintaro , Fujiwara Yutaka , Nokihara Hiroshi , Yamamoto Noboru , Sumi Minako , Shiraishi Kouya , Kohno Takashi , Furuta Koh , Tsuta Koji , Tamura Tomohide 
Published: March 2020

7540 Background: EGFR mutational status is an important biomarker in advanced NSCLC patients. However, little is known about the frequency and clinical significance of the presence of EGFR mutation in patients with potentially curable locally advanced NSCLC (LA-NSCLC) eligible for definitive chemoradiotherapy (CRT). Methods: Between Jan 2001 and Dec 2010, we conducted analysis for the presence of EGFR mutations, in consecutive NSCLC patients who were eligible for CRT. The response rate (RR), progression-free survival (PFS), 2-year relapse-free rate, first relapse sites, and overall survival were investigated according to the EGFR mutational status. Results: A total of 528 patients received CRT at the National Cancer Center Hospital during the study period. Of these, 274 were diagnosed as having non-squamous NSCLC, and sufficient specimens for mutational analyses could be obtained from 145 patients. EGFR mutants (EGFR-mt) were found at a frequency of 18% in these patients. In addition to the well-known characteristics of NSCLC patients carrying EGFR mutations (female, adenocarcinoma, and never/ light smoker), the proportion of cases with smaller (T1/2) primary lesions was higher in patients with EGFR-mt than in those carrying wild-type EGFR (EGFR-wt). EGFR-mt showed a slightly better RR (85.7% vs. 72.9%), but similar median PFS (12.2 m vs. 10.6 m) and 2-year relapse free rates (23.8% vs. 29.2%) as compared to EGFR-wt. Local recurrence as first relapse occurred less frequently in EGFR-mt than in EGFR-wt (6% vs. 20%). After disease progression, a majority of EGFR-mt received EGFR-TKIs (62%), and these patients showed longer post-progression survival and a higher 5 year survival rate (60% vs. 40%) than EGFR-wt. Conclusions: Among the LA-NSCLC patients eligible for definitive CRT analyzed, 18% had EGFR- activating mutations. Although definitive CRT was similarly effective in both EGFR-mt and EGFR-wt, slightly better local control rate was noted in EGFR-mt. Treatment with EGFR-TKIs contributed to longer post-progression survival and overall survival in LA-NSCLC patients harboring EGFR mutations.
Scoring system predicting overall survival (OS) in patients (Pts) with non-small cell lung cancer (NSCLC).
Authors: Schild Steven E. , Tan Angelina D. , Wampfler Jason A. , Molina Julian R. , Ross Helen J. , Yang Ping , Sloan Jeff A. 
Published: March 2020

7545 Background: Interpretation of lung cancer clinical trials is complicated by the heterogeneity of the patient population due to disease burden and comorbidities making pre-trial assessment of OS probability challenging. Methods: To create and validate a scoring system to estimate OS and improve the quality of future trials, this study evaluated the pretreatment prognostic factors of 2,442 pts with NSCLC. Univariate (UV) and multivariate (MV) Cox models were used to evaluate the prognostic importance of each baseline factor on OS. Those prognostic factors significant on both UV and MV analyses that were used to develop the scoring system included overall quality of life, age, sex, stage, ECOG performance status, the presence of other cancers, and smoking cessation. The score for each factor was determined by dividing the 5-year OS rate (in %) by 10 and summing these scores to form a total score. Multivariate models and the score for each factor were validated using bootstrapping with 1000 iterations from the original samples. Results: The score for each factor ranged from 1 to 7 points and the total scores ranged between 23 and 39 points. Higher scores reflected better OS. Categorization of the score was delineated first by clinician expert opinion (see Table) and then by multiple statistically defined empirical cut points. All categorization schemes demonstrated successful prognostic power. The bootstrap method confirmed the reliability of multivariate Cox model and score (Spearman correlation coefficient= 0.45). Conclusions: Prognostic factors significantly associated with OS on both UV and MV analysis were used to construct a valid scoring system which can be used to predict survival of NSCLC pts. This scoring system can be used by clinicians in counseling pts and for stratification in future trial design. [Table: see text]
Pulmonary pure ground-glass opacity lesions: Use of computed tomography attenuation for predicting tumor progression.
Authors: Eguchi Takashi , Kondo Ryoichi , Kawakami Satoshi , Matsushita Mina , Takeda Tetsu , Sakaizawa Takao , Tominaga Yoshiaki , Saito Gaku , Hashizume Masahiro , Toishi Masayuki , Shiina Takayuki , Yoshida Kazuo , Amano Jun , Koizumi Tomonobu 
Published: March 2020

7548 Background: Cases with pure ground-glass opacity (GGO) are increasing with the use of computed tomography (CT). In some cases, pure GGO on follow-up CT may represent tumor enlargement or the presence of solid components. We evaluated the natural progression of pure GGO lesions during a long-term follow-up period of more than 2 years. Methods: We retrospectively investigated 95 patients with pure GGO lesions detected between February 2003 and December 2010, in whom these lesions were monitored using CT for more than 2 years. Results: The median follow-up period was 64.7 months (range, 24–114 months). During the follow-up period, areas showing GGO increased in size or appeared to have solid components in 49 patients (group 1) and showed no change in 46 patients (group 2). We compared patient characteristics and tumor properties between the 2 groups. Mean CT attenuation values of the tumors differed significantly between groups 1 (-639.9 ± 88.9 HU) and 2 (-709.2 ± 60.9 HU). In contrast, no significant differences were noted with regard to age, gender, smoking history, lung cancer history, tumor size, and total numbers of GGO lesions between the 2 groups. The difference in the time to tumor growth according to the initial mean CT attenuation value was estimated using the Kaplan–Meier method. The growth incidence at 114 months for lesions with a mean CT attenuation value of -650 HU or more (n = 35) and less than -650 HU (n = 60) were estimated to be 96% and 48%, respectively. The difference between the 2 Kaplan–Meier curves was statistically significant (p < 0.0001). The usefulness of the mean CT attenuation value in predicting the growth of GGO lesions was evaluated using receiver operating characteristic analysis. The sensitivity and specificity was 63% and 87%, respectively, for a mean CT attenuation cutoff value of -650 HU. The area under the curve was 0.76. Conclusions: Many pure GGO lesions have potential for growth as seen during long-term follow-up. CT attenuation is useful in predicting the growth of GGO lesions.
Dose-escalation study of chemoradiotherapy with use of involved-field conformal radiotherapy and accelerated hyperfractionation for stage III non-small cell lung cancer.
Authors: Yoshimura Naruo , Mitsuoka Shigeki , Kimura Tatsuo , Tanaka Hidenori , Suzumura Tomohiro , Nagata Misato , Umekawa Kanako , Nakai Toshiyuki , Hosono Masako Hosono , Tada Takuhito , Hirata Kazuto , Kudoh Shinzoh 
Published: March 2020

7564 Background: To determine a recommended dose (RD) of chemoradiotherapy with use of involved-field conformal radiotherapy and accelerated hyperfractionation (AHF) for stage III non-small cell lung cancer (NSCLC). Methods: Eligible patients had unresectable stage III NSCLC, age of less than 75 years, PS: 0 or 1, V20 of 35% or less. PET was used for staging. Cisplatin (80mg/m2) was administered on day 1 and vinorelbine (20mg/m2) was administered on days 1 and 8 for two cycle. Twice-daily radiation therapy (1.5 Gy per fraction) without elective nodal irradiation started on day 1. Total doses were 60Gy in 40 fractions and 66Gy in 44 fractions at levels 1 and 2 respectively. After concurrent chemoradiotherapy, consolidation chemotherapy regimen was cisplatin (80mg/m2) on day 1 and vinorelbine (20mg/m2) on days 1 and 8 every 4 week for three cycles. The dose-limiting toxicity (DLT) was defined as grade ≥ 3 esophagitis, grade 3 neutropenic fever, grade ≥ 3 other non-hematologic toxicities and interruption of irradiation for more than 2 weeks. DLT was monitored for 90 days. Results: A total of 12 patients were enrolled (6 patients in Level 1, 6 patients in Levels 2). DLTs were noted in 2 patients at Level 1, which were grade 3 esophagitis and grade 3 febrile neutropenia. Radiation dose was escalated up to 66 Gy in 44 fractions (Level 2), and there was no DLT. In principle, Sixty-six Gy in 44 fractions (Level 2) should be the RD. Major toxicities were leucopenia, neutropenia, and anemia. The response rate, the median progression free survival time, and the median overall survival time was 83.3%, 10.4 months, and 36.3 months for all patients, respectively. Conclusions: The RD was 66 Gy in 44 fractions (Level 2). The toxicity of this chemoradiothrapy regimen was manageable and efficacy is promising. The efficacy and safety of this regimen should be confirmed in a phase II study. Clinical trial information: UMIN000003769.
Outcomes of early stage lung cancer treatments in older patients: A SEER database analysis.
Authors: Marr Alissa S. , Shostrom Valerie , Islam K. M , Ganti Apar Kishor 
Published: March 2020

7571 Background: Although the majority of lung cancer patients are over the age of 65, there are limited data on outcomes of treatment options for early stage lung cancer in older patients. Methods: Treatment and outcome data of stage I and II non-small cell lung cancer (NSCLC) patients were obtained from the Surveillance, Epidemiology and End Results (SEER) database. Treatment modalities included no treatment, surgery, radiation, and a combination of surgery and radiation. Patients were divided based on age groups into <65, 65-75, and >75 years old. Multivariate logistic regression was used to compare the likelihood of survival in the three age groups while controlling for gender and race. Results: A total of 10,763 patients diagnosed with stage I and II NSCLC between 1988 and 2007 within the SEER database were analyzed. The age distribution was as follows: <65 (n=3558), 65-75 years (n= 4454), >75 years (n=2751). Patients <65 years of age were more likely than those >75 years of age to be treated with surgery (72.5% vs. 53.5%, respectively; p = <0.0001). Patients >75 years of age were more often treated with radiation alone (23%) or no treatment (18.2%) as compared to those patients <65 (9% and 4.9%, respectively; p = <0.0001). Patients <65 years of age with stage I lung cancer had a statistically significant improved lung cancer-specific 5-year survival with surgery alone as compared to those 65-75 years and >75 years. Lung cancer specific mortality at 5 years was 19%, 26% and 30%, respectively; p= <0.0001. Similar results were seen in stage II patients. When stage I patients received radiation therapy, lung cancer-specific deaths at 5 years were not different between the three groups (66% vs. 63% vs. 66%, respectively; p=0.1263). The 5-year lung cancer- related mortality was lower in younger patients who received no treatment (51% in <65, 56% in 65-75, and 57% in >75 years old; p=0.006). Conclusions: Older patients treated surgically for stages I and II NSCLC have a lower lung cancer-specific survival when compared to younger patients. In contrast, there is no difference in lung cancer-specific survival for patients treated with radiation therapy. Hence, careful selection of older patients for surgical therapy of early stage NSCLC is warranted.
Predictive value of BRCA1, ERCC1, ATP7B, PKM2, TOPO-I, TOPO-iia, TOPO-iib, and c-MYC genes in patients with small cell lung cancer (SCLC) who received first-line therapy with cisplatin and etoposide.
Authors: Papadaki Chara , Karachaliou Niki , Lagoudaki Eleni , Trypaki Maria , Sfakianaki Maria , Koutsopoulos Anastasios , Mavroudis Dimitrios , Stathopoulos Efstathios , Georgoulias Vassilis , Souglakos John 
Published: March 2020

7594 Background: to evaluate the predictive value of genes correlated with cisplatin-etoposide (EP) metabolism or mode of function in patients with SCLC. Methods: Tumor samples from 184 patients, with SCLC were analyzed for ERCCI, BRCA1, ATP7B, TOPOI, TOPOIIA, TOPOIIB PKM2 and C-MYC mRNA expression by quantitative real-time PCR, from microdissected cells derived from patients’ primary tumors. All patients were treated with EP (plus radiotherapy for patients with limited disease-LS) in the department of Medical Oncology of the University Hospital of Heraklion. Results: The median age of the patients was 63 years (min-max: 33-78). One hundred-twenty (65%) patients presented with extended stage (ES), LDH was above the UNL in 75 (41%), while ECOG performance status was 0-1 in 131 (71%) of them. Shorter progression free survival (PFS) was observed in patients with LS-SCLC whose tumors expressed high ERCC1 (p=0.028), PKM2 (p=0.046), TOPO-I (p=0.008), TOPO-IIA (p=0.002) and TOPO-IIB (p<0.001) expression. High expression of ERCC1 (p=0.014), PKM2 (p=0.026), TOPO-IIA (p=0.021) and TOPO-IIB (p=0.019) was correlated with shortened median overall survival (OS) in LS-SCLC patients. In patients with ES-SCLC, only high TOPO-IIB expression was associated with decreased OS (p=0.035). The favorable genotype (low expression of ERCC1, PKM2, TOPO-IIA and TOPO-IIB) was correlated with significantly improved PFS in both LS-SCLC (p<0.001) and ES-SCLC (p=0.007) patients as well as with improved OS in the LS-SCLC (p=0.007) and ES-SCLC (p=0.011) group. Unfavorable genotype was independent predictor of poor PFS (HR: 3.18; p=0.002) and OS (HR: 4.35; p=0.001) in LS-SCLC as well as for both PFS (HR: 3.14; p=0.021) and OS (HR: 3.32; p=0.019) in ES-SCLC. Conclusions: Single gene’s expression analysis as well as the integrated analysis of ERCC1, PKM2, TOPO-IIA and TOPO-IIB may predict treatment outcome in patients with SCLC. The results of our study, if validated prospectively, may help in selecting patients for personalized therapeutic strategies.
Oral (O) versus intravenous (IV) etoposide and platinum in the treatment of extensive-stage small cell lung cancer (SCLC).
Authors: Dorroh Scott Alan , Siegel Eric R , Govindarajan Rangaswamy 
Published: March 2020

7597 Background: Platinum and etoposide chemotherapy is the treatment for patients with SCLC. O etoposide is substituted for IV by many clinicians at twice the dose for bioavailability but the outcome of these subjects has not been studied. To compare the efficacy of O vs. IV etoposide in extensive stage SCLC, a retrospective analysis of subjects treated in the VISN 16 network of 10VA hospitals was undertaken. Methods: Subjects with SCLC diagnosed between 10/1/1996 and 9/30/2010 were identified from the VISN-16 tumor registry. Study was limited to extensive disease by excluding those treated with radiation therapy. Chemotherapy details were obtained from the pharmacy data in the VISN 16 database. Overall survival (OS) was computed as the time in months from the first etoposide issue date to the date of death or last contact. Kaplan-Meier methods were used to compute median OS, and etoposide groups were compared via log-rank test. Results: 300 subjects were eligible for analysis, with median age 67 yrs (range 45-84). 295 deaths were observed during 2,419 total months of follow-up. The median OS of all subjects was 6.3 months (interquartile range (IQR) 2.0-11 months). In addition to platinum, 153 subjects received only O etoposide, 147 received some form of IV etoposide. The median duration (IQR) of therapy for all subjects was 29 (1-110) days; 23 days for those who received any IV etoposide and 43 days for those who received only oral etoposide. The median OS was 7.6 months for those who received only O etoposide vs. 5.4 months for any IV etoposide (P<0.0001). In the latter group, those receiving purely IV etoposide had only 1.5 months’ median OS vs. 8.8 months for those receiving both O and IV etoposide (P<0.0001). Conclusions: Survival of subjects with SCLC treated with O etoposide is comparable to those who received a combination of O and IV therapy. Poor OS for those with only IV therapy may be due to selection bias of poor-performance subjects. [Table: see text]
Molecular profiling of small cell lung cancers in Japanese patients.
Authors: Wakuda Kazushige , Kenmotsu Hirotsugu , Serizawa Masakuni , Koh Yasuhiro , Isaka Mitsuhiro , Takahashi Toshiaki , Murakami Haruyasu , Naito Tateaki , Taira Tetsuhiko , Shukuya Takehito , Ono Akira , Akamatsu Hiroaki , Imai Hisao , Mori Keita , Endo Masahiro , Nakajima Takashi , Ohde Yasuhisa , Yamamoto Nobuyuki 
Published: March 2020

7599 Background: Molecular abnormalities discovered in the last decade have led to a paradigm shift in the diagnosis and treatment of lung adenocarcinoma. But there have been few reports about molecular profiling of small cell lung cancers (SCLC). We conducted the Shizuoka Lung Cancer Mutation Study to analyze driver mutations in patients with thoracic SCLC malignancies. Methods: We collected molecular profiling data of SCLC from the biobanking system in conjunction with the clinic, including the pathology lab, where 23 mutations in 9 genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN and HER2), EGFR, MET, PIK3CA, FGFR1 and FGFR2 amplifications, and EML4-ALK translocations were assessed using pyrosequensing plus capillary electrophoresis, qRT-PCR, and RT-PCR, respectively. To evaluate mutation status for SCLC patients, we collected patient characteristics data from medical records. Results: Between July 2011 and July 2012, fifty small cell lung cancer patients were assessed in our biobanking system. Patient characteristics were as follows: median age (range) 70 (43 - 82) years; male 82%; smoker 96%; limited disease/extended disease 56/44%; small cell carcinoma/combined small cell carcinoma with adenocarcinoma 94/6%; surgically resected snap-frozen samples 8, formalin-fixed paraffin-embedded samples 40 and pleural effusion 7. We detected driver mutations in 8 cases (16%). Mutations found: EGFR 1 (2%), KRAS 1 (2%), PIK3CA 2 (4%), AKT1 1 (2%), MET amplification 1 (2%), PIK3CA amplification 6 (12%). EGFR and KRAS mutation were found in combined small cell carcinoma with adenocarcinoma. No significant differences in age, sex, disease extent at diagnosis or smoking status were found between patients with mutations and those without mutations. But serum neuron-specific enolase (NSE) levels were significantly higher in patients without mutations (p=0.03). Conclusions: In our analysis, driver mutations were found in 16% of SCLC patients and PIK3CA amplification seemed to be relatively frequent in SCLC. Our results suggest that PIK3CA might become a target of treatment for SCLC patients.