bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of amrubicin (AMR) and carboplatin (CBDCA) for invasive thymoma (IT) and thymic carcinoma (TC): NJLCG0803.
Authors: Kawashima Yosuke , Inoue Akira , Sugawara Shunichi , Harada Masao , Kobayashi Kunihiko , Kozuki Toshiyuki , Kuyama Shoichi , Sakakibara Tomohiro , Maemondo Makoto , Asahina Hajime , Hisamoto Akiko , Nakagawa Taku , Nukiwa Toshihiro 
Published: March 2020

7530 Background: There has been no standard chemotherapy for advanced thymic malignancies including IT and TC although anthracycline or platinum agents have been commonly used for them. AMR, a new anthracycline agent, was approved for lung cancer in Japan and we had previously conducted some prospective studies of AMR combined with CBDCA for patients with small-cell lung cancer, which revealed this regimen was active with acceptable toxicity. The objective of this study is to evaluate the efficacy and safety of this combination for patients with advanced thymic malignancies. Methods: Patients with histologically confirmed thymic malignancies received AMR (35 mg/m2, day1-3) and CBDCA (AUC 4.0, day1) every 3 weeks. Patients who underwent previous chemotherapy received reduced dose of AMR (30 mg/m2). The primary endpoint was overall response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival and toxicity profile. Assuming that ORR of 75% and 45% would indicate the potential usefulness while ORR of 50% and 20% would be the lower limit of interest, with alpha = 0.10 and beta = 0.20, for IT patients and TC patients, respectively, 18 IT patients and 16 TC patients were at least required. Results: From December 2008 to October 2012, 51 patients (18 IT and 33 TC) were enrolled from 20 institutions in Japan. Patients’ characteristics are as follows; male/female 35/16; median age 66 (range 39-78); performance status 0/1 24/27. The ORR and disease control rate were 17% and 89% in IT, and 30% and 85% in TC. Preliminary median PFS was 7.6 months in both groups. Toxicity was generally moderate and no treatment related death was observed. Conclusions: This is the largest prospective study of chemotherapy for advanced thymic malignancies. AMR combined with CBDCA was effective for TC patients with acceptable toxicities. Clinical trial information: R000001598.
Phase II study of nedaplatin and irinotecan as adjuvant chemotherapy in patients with completely resected non-small cell lung cancer.
Authors: Saito Haruhiro , Murakami Shuji , Kondo Tetsuro , Oshita Fumihiro , Ito Hiroyuki , Nakayama Haruhiko , Yamada Kouzo 
Published: March 2020

7531 Background: The aim of this phase II study was to evaluate the feasibility and safety of a nedaplatin and irinotecan combination regimen in the treatment of completely resected non-small cell lung cancer (NSCLC). Methods: Patients with completely resected pathologically documented stage IB, II or III NSCLC were treated with nedaplatin and irinotecan. Chemotherapy consisted of 4 cycles of nedaplatin at 50mg/m2 and irinotecan 50mg/m2 on days 1 and 8 every 4 -5 weeks. The primary endpoint of this study was the completion rate of 4 cycles. Results: Thirty nine patients were treated, and the patient's demographics were: median age 68 years (range 40-74), gender male (n = 16, 41%)/female (n = 23, 59%), stage IIA (n = 9, 23%), IIB (n = 13, 33%), IIIA (n = 16, 41%), IIIB(n=1,2% ). Thirty six patients (92.3%) received the 4 cycles of the chemotherapy regimen. Among the 3 patients who failed to complete 4 cycles, the reasons for stopping were anaphylaxy (n = 1), G3 infection and diarrhea (n = 2). The main adverse effects were hematological toxicity as well as grade 3/4 neutropenia (which occurred in 36% of the patients). Conclusions: Adjuvant chemotherapy with nedaplatin and irinotecan combination regimen has an acceptable toxicity profile, and the majority of patients completed 4 cycles of therapy.
Survival study of neoadjuvant versus adjuvant chemotherapy with docetaxel combined carboplatin in resectable stage IB to IIIA non-small lung cancer.
Authors: Yang Xue-Ning , Cheng Gang , Ben Xiao-song , Luo Hong-He , Wang Chang-li , Zhong Wenzhao , Ge Di , Qiao Gui-bin , Wang Zheng , Shentu Yang , Yang Jie , Yan Hong hong , Wu Yi Long ,   Chinese Society of Lung Cancer
Published: March 2020

7537 Background: Adjuvant chemotherapy is the standard of care for completely resected stage 2-3 non-small cell lung cancer(NSCLC). A few trials suggest neoadjuvant chemotherapy is a promising mode for resectable NSCLC. Indirect comparison meta-analysis of adjuvant versus neoadjuvant therapy showed no difference in survival. This study was conducted to determine whether neoadjuvant chemotherapy or adjuvant chemotherapy prolongs disease-free survival among patients with resectable NSCLC. Methods: Patients with clinical stage IB-IIIA NSCLC were eligible. Patients were randomly assigned to 3 cycles of neoadjuvant DC (Docetaxel: 75mg/m2, Carboplatin :AUC=5 on day 1 every 3wk),followed by surgery 3-6 wk after chemotherapy, or surgery followed by 3 cycles of adjuvant DC at the same schedule. The primary end point was 3 years Disease Free Survival(DFS); secondary end points were 3 years Overall Survival rate (OS) and Safety. Planned sample size is 410. Results: Between March 2006 and May 2011, 198 patients have been accrued, 97 in the neoadjuvant arm, 101 in the adjuvant arm. The neoadjuvant arm had more patients received chemotherapy( 100% v.s 85.1%, P<0.001 ) and received 3 cycles( 91.8% v.s82.6%, P=0.061) than adjuvant arm. Both arms are well tolerated to DC chemotherapy. The most common grade 3/4 adverse event is neutropenia (41.2% with neoadjuvant arm v.s 31.7% with adjuvant arm). One chemotherapy related death in adjuvant arm. One patient die of perioperative pulmonary embolism in neoadjuvant arm. No difference in peri-operative complication between two arms. The 3 years DFS was 45% in the neoadjuvant arm and 53% in the adjuvant arm, HR=0.88 (0.58-1.33), P=0.54. Median survival has not been reached in both arms. Conclusions: Neoadjuvant or adjuvant chemotherapy with docetaxel plus carboplatin in resectable clinical stage IB-IIIA NSCLC is feasible and safe. Preliminary results show similar 3 years DFS in both arms. The OS data has not matured in both arms. Clinical trial information: NCT00321334.
Utilization and impact of adjuvant chemotherapy (AC) in surgically resected stages I-III non-small cell lung cancer (NSCLC).
Authors: Williams Christina D. , Gajra Ajeet , Ganti Apar Kishor , Kelley Michael J. 
Published: March 2020

7538 Background: Clinical trials demonstrating improved survival with AC for stages I-III NSCLC are limited in their applicability to broader populations. We sought to describe the pattern of AC use and its correlation with survival in the population-based VA system. Methods: We conducted a retrospective analysis of pts with stages I-III NSCLC in the VA Central Cancer Registry. Descriptive statistics were used to examine patterns of AC use over an 8 yr period and to obtain survival rates associated with use of AC. Chi-square was used to compare distributions. Results: Among 28,173 pts with stages I-III NSCLC in 2001-2008, 10,043 had surgical resection. The proportion receiving AC was 9% (stage I), 34% (II), and 40% (III). Receipt of AC increased for each stage, with the greatest increase observed in stage II (2001-03: 12%; 2004-05: 41%; 2006-08: 50%). About 90% received a platinum agent; among these carboplatin was most common (77%) but by 2008 43% received cisplatin. For stages II and III in 2001-2003, the 3-year survival rate was similar irrespective of AC use. In latter time periods, survival rates were significantly higher for stage II AC pts (2004-2005: 53 vs 43%, p=0.03; 2006-2008: 58 vs 46%, p=0.001). Stage III AC pt diagnosed in 2006-2008 had a higher 3-yr survival (52 vs 36%, p<0.001). For all stages and years combined, use of cisplatin yielded a better 3-yr survival rate compared to carboplatin (62% vs 55%; p=0.01). 3-yr survival for stage I, II, and III, regardless of AC, increased over time (stage I: 60, 64, and 69%; stage II: 44, 47, 52%; stage III: 33, 40, and 44%). The fraction of lung cancer pts diagnosed at each stage during the 3 time periods was not significantly different. Conclusions: This retrospective study suggests a significant increase in use of AC for NSCLC in the VA, though half of surgically treated pts with stage II and III did not receive AC in 2006-2008. By univariate analysis, AC use is associated with a significantly better 3-yr survival for resected stage II and III NSCLC and the stage-specific 3-year survival for all pts improved over time in association with increasing use of AC. Cisplatin is associated with better survival compared to carboplatin. Multivariate analysis is planned.
Does EGFR mutation define the histological predominant subtype of lung adenocarcinoma?
Authors: Sugiyama Eri , Goto Koichi , Ishii Genichiro , Haruki Tomohiro , Matsumoto Shingo , Umemura Shigeki , Yoh Kiyotaka , Niho Seiji , Ohmatsu Hironobu , Nagai Kanji , Ohe Yuichiro 
Published: March 2020

7557 Background: In 2011, invasive adenocarcinomas were newly classified into the five predominant subtypes by IASLC/ATS/ERS: lepidic, papillary, acinar, micropapillary, and solid. The purpose of this study is to investigate the correlation between EGFRmutation and the histological predominant subtype of lung adenocarcinoma. Methods: Among a total of 1,736 patients with lung adenocarcinoma who underwent surgical resection from 2002 to 2011 in National Cancer Center Hospital East, 1,507 were classified into invasive adenocarcinoma. 526 of whom were examined EGFR mutation status. Histological predominant subtypes were evaluated at the maximum cut surface of tumors. The EGFR mutation analysis was performed by PCR-invader method. Treatment efficacy of EGFR-tyrosine kinase inhibitors (TKIs) in 73 relapsed patients with EGFRmajor mutations were also examined. Results: 526 adenocarcinomas were consisted of 95 lepidic (18%), 221 papillary (42%), 80 acinar (15%), 9 micropapillary (2%), and 121 solid predominant subtype (23%). EGFR mutations were detected in 227 adenocarcinomas (43%), and its frequency in the solid subtype (22%) was significantly less than that of other histological subtypes (lepidic 47%, papillary 53%, and acinar 44%; P < 0.01). The proportion of minor mutations, other than exon 21 L858R and exon 19 deletions, were significantly higher in the solid subtype (22%) than that of the others (lepidic 4%, and papillary 12%; P < 0.01). In 73 patients with EGFR major mutations treated by EGFR-TKIs, the response rate was not different between histological subtypes (lepidic 86%, papillary 76%, acinar 89%, and solid 60%). Conclusions: The correlation between histological predominant subtypes of lung adenocarcinoma and the presence of EGFR mutations or the efficacy of EGFR-TKI were not identified in this study. Little is known about the reason why EGFR minor mutations were highly detected in the solid subtype of adenocarcinoma, however it is possibly due to the high frequency of heavy smokers in solid subtype (heavy smoker: solid 67% vs. others 27-44%).
Prognostic role of MET expression in early stage NSCLC.
Authors: John Tom , Murone Carmel , Asadi Khashayar , Morey Adrienne , Knight Simon , Mitchell Paul 
Published: March 2020

7567 Background: The MET receptor tyrosine kinase and its ligand are associated with the malignant phenotype. In non-small cell lung cancer (NSCLC) MET expression increases with disease stage and is involved in de novo and acquired resistance to tyrosine kinase inhibitors. Despite this, in early stage NSCLC small data series have failed to demonstrate MET expression to be prognostic. We investigated a large cohort of patients who underwent curative surgical resection at our institution to determine whether MET receptor or gene amplification was prognostic. Methods: Tissue Microarrays (TMAs) were constructed using 1mm cores of FFPE primary NSCLC tissues in triplicate. TMAs were stained with the SP44 clone (Novus Biologicals) and a H-score calculated based on % cells stained and intensity; (%cellsx1)+(%cellsx2)+(%cellsx3) with a minimum of 0 and maximum of 300. The mean of triplicate values was calculated. MET gene amplification was detected using Ventana’s MET DNP probe with ultraView SISH DNP silver detection, performed on Ventana’s XT autostainer. DNA was isolated and subjected to mutational profiling using Sequenom’s LungCarta panel. Results: Data for 508 patients, 352 (69%) male, were available for analysis including 329 pathological node negative (pN0), 67 pN1, 104 pN2 and 8 patients with resected primaries and solitary brain metastases (M1). Most patients were smokers with only 33 (6%) non-smokers. The median MET H-score was 100 and consistent across N0, N1 and N2 patients, although was higher in M1 patients. Median H-scores were significantly higher in adenocarcinoma compared to squamous cell carcinoma (140 vs 91.5, p<0.0001). Increased MET expression (H-score>100) was seen in 227 (45%) patients and associated with significantly improved overall survival (HR 1.28 95% CI 1.04-1.59; p=0.023). In univariate analyses improved survival occurred in all stages and histologies. DNA and multivariate analyses are pending. MET gene copy number amplification was detected in 11 cases. Conclusions: In contradistinction to advanced NSCLC, increased MET receptor expression is associated with improved survival in a large cohort of early stage lung cancer. Further correlation with mutation status and gene rearrangements will be reported.
Lung adenocarcinoma microRNA-31 expression levels to predict lymph node metastasis and patient survival.
Authors: Lautenschlaeger Tim , Meng Wei , Ye Zhenqing , Cui Ri , Perry James , Huebner Alexander , Dedousi-Huebner Vaia , Stefano Volinia , Hiroshi Nakanishi , Kim Taewan , Suh Sung-Suk , Ayers Leona W. , Ross Patrick , Croce Carlo M , Jin Victor , Chakravarti Arnab 
Published: March 2020

7573 Background: In this study we performed genome-wide microRNA-seqencing (miRNA-seq) in lung adenocacinoma (ADC) patient samples and used bioinformatic analyses to identify novel and annotated microRNAs that are differentially expressed between patients with and patients without lymph node metastasis, as well as examining their potential prognostic value. Methods: Sixty four frozen tissue specimens from lung ADC patients collected between 2003 and 2012 were obtained through the OSUCCC Tissue Procurement Shared Resource, approved by internal review board (IRB). Total RNA samples were processed and loaded on the Applied Biosystems SOLiD 4 sequencing system for data acquisition. 249 patients from the TCGA lung ADC cohort were used for results validation. Human lung ADC cell lines H23 and H1573 were used for in vitro functional assays. Results: We identified several microRNAs that were associated with the presence of lymph node metastasis in primary lung adenocarcinoma tissues using genome-wide miRNA-seq. We confirmed miR-31 to be up-regulated in lung ADC tissues from patients with lymph node metastasis in a separate patient cohort (p=0.009, t-test), and to be expressed higher in ADC tissues than in matched normal adjacent lung tissues (p<0.0001, paired t-test). MiR-31 was then validated as a marker for lymphnode metastasis in an external validation cohort of 233 lung ADC cases of the TCGA that did not have distant metastasis (p=0.031, t-test). In vitro functional assays showed that miR-31 upregulation increases cell migration, invasion, and proliferation. In addition, overexpression of mir-31 increased the expression of markers of epithelial-mesenchymal transition (EMT) and associated with activated ERK1/2 signaling. MiR-31 was a significant predictor of survival in a multivariate Cox regression model even when controlling for tumor stage. In silico analysis showed that low expression of miR-31 was associated with excellent survival for T2N0 patients. Conclusions: In summary, we applied microRNA-seq to study microRNomes in lung ADC tissue samples for the first time and identified a microRNA that could predict the presence of lymph node metastasis and survival outcomes in lung ADC patients.
Total lesion glycolysis (TLG) at baseline FDG-PET/CT compared with maximum standard uptake value (SUVmax) to predict survival in non-small cell lung cancer (NSCLC).
Authors: Li Ling , Kong Feng-Ming (Spring) , Bi Nan , Wang Jingbo , Mahasittiwat Pawinee , Stanton Paul , Ritter Timothy 
Published: March 2020

7579 Background: SUVmaxat baseline FDG-PET has been reported as a significant prognostic factor while recent studies suggest that metabolic tumor volume (MTV) may be more important factor in patients with NSCLC. We hypothesized that TLG is a better prognostic factor than either SUVmax or MTV alone for overall survival (OS) and progression free survival (PFS) in NSCLC because it integrates both volumetric and biologic activity. Methods: The study population included a prospectively recruited cohort of stage I-III NSCLC patients treated with chemoradiation. FDG PET/CT scans were performed within 2 weeks from treatment start. The SUV in the tumor was normalized to that of the background level in the middle of ascending aorta to minimize the confounding effect from inter-scan variation in SUV measurement. MTV was delineated by auto-threshold at 1.5 times background level in the aorta followed by knowledge based manual editing. Mean and maximum SUV normalized to the background level were computed. TLG was calculated as the product of lesion SUVmean and MTV. Results: A total of 96 patients with minimum follow-up of 1 year were eligible. The median follow-up among survivors was 30 months. Univariate analysis demonstrated that MTV and TLG were significant factors for both OS and PFS (all P<0.05). There was a significant correlation between SUVmean and PFS (P=0.013), but there was no significant association between SUVmean and OS. SUVmax was not a significant factor for either OS or PFS (all P>0.05). Under multivariate Cox regression analysis, MTV (HR= 2.62, P= 0.003) and NSUVmean (HR=0.351, P=0.003) were significantly associated with PFS; but only TLG was significantly associated with OS (HR=2.14, P=0.006)adjusted by of TNM stage and other clinical factors. Conclusions: These results support our hypothesis that metabolic tumor volume and biologic average glucose metabolic activity of this volume are more important prognostic factors for overall prognosis than SUVmax in NSCLC patients treated with chemoradiation. Should this be validated by independent studies, future clinical trial should take this into consideration for individualized care.
Independent validation of progression-free survival rate at 9 and 18 weeks (PFSR-18, PFSR-9) as predictor for overall survival (OS) in patients with malignant pleural mesothelioma (MPM): EORTC 08052 study.
Authors: Hasan Baktiar , Pallis Athanasios G. , Gaafar Rabab Mohamed , Greillier Laurent , Van Meerbeeck Jan P. , O'Brien Mary 
Published: March 2020

7584 Background: The increasing incidence and the plateau of current treatment outcomes in MPM necessitates development of new therapeutic approaches. Reliable and meaningful response assessment is difficult in phase II trials thus a primary endpoint based on progression free survival (PFS) rate at certain time point has been proposed (Greillier et al, 2011). EORTC 08052 was a phase II study in MPM where independent validation of PFSR-18 weeks was foreseen. We extend this to PFSR-9. Methods: Association of PFS and response with OS was assessed at two distinct time points; 9 and 18 weeks after registration. Landmarks method was used, PFS status (CR/PR/SD vs. PD) and response status (CR/PR vs. PD/SD) were determined at those time points. Cox regression and logrank test were performed and the corresponding c-indexes were calculated. Results: Of 82 registered patients, 28.4% achieved CR/PR and 77.8% had disease control (CR/PR/SD) as their best overall response. PFSR-18 and PFSR-9 were both strongly correlated with OS. Patients with no progression at 18 weeks had median OS of 16.9 months compared to 11.9 months in those who progressed at 18 weeks. Hazard ratio [HR] (95 confidence interval [CI]) was 0.46 (0.32-0.67), logrank test was 0.007 and C-index = 0.60. Adjusting for 3 important baseline prognosis factors, histology, performance status and disease stage resulted in PFS-18 as the only significant factor. When 9 weeks landmark was chosen, patients with no progression had median OS of 16.9 months vs. 6.8 months in those who progressed with HR (CI), logrank test and C-index 0.35(0.25-0.49), < 0.0001 and 0.66 respectively. When adjusted by 3 important baseline prognosis factors PFS-9 remained the only significant factor. The results also confirmed that response at 18 weeks and 9 weeks was correlated with OS. Conclusions: PFSR-18 was strongly correlated and discriminated patients with better OS from the poorer prognosis patients. An earlier endpoint, PFSR-9 was also strongly correlated to OS and had a better discriminating capacity. Previous results on correlation between PFSR-9 and PFSR-18 and OS were independently validated.
Genetic analysis of the separate morphologic components in combined small cell lung cancer.
Authors: Lu Hongyang , Ling Zhiqiang , Cheng Qiao-Yuan , Chen Bo , Cai Ju-Fen , Jia Wang Xiao , Lei Lei , Lou CaiJin , Qin Jing , Ye Wei-Wu , Mao Weimin 
Published: March 2020

7590 Background: Combined small cell lung cancer (CSCLC) is currently considered a subset of SCLC and have been reported to account for less than 1-3.2% of all SCLCs. Accurate understanding of CSCLCs is of great importance because treatment strategies are significantly different for NSCLC and SCLC. To address molecular features of different components in CSCLC we analyzed mutation status in CSCLC tumor samples in EGFR signal pathway. Methods: Seven CSCLC samples were included in direct sequencing for mutation analysis of EGFR, KRAS, PIK3CA, BRAF, and PTEN. Results: Mutations were detected in 4 of 7 (57.1%) CSCLC patients. EGFR Exon 18 mutations were identified in two patients among whom the mutation was identified in both adenocarcinoma component and SCLC combined adenocarcinoma component of one patient. The similar situation also happened in another one with PTEN C511T mutations both conventional SCLC component and SCLC combined adenocarcinoma component. Both KRAS and PIK3CA were detected in one SCLC combined adenocarcinoma patient and no mutation in BRAF was identified. Conclusions: Our result is consistent with previous work that the individual components of CSCLC are closely related, despite their distinct morphologic appearances.