bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiographic parameters in predicting outcome of patients with nonsquamous non-small cell lung cancer (NSCLC) treated with bevacizumab.
Authors: Kaufman Michael R , Salem Mohamed E. , Aoun Hussein , Kalemkerian Gregory Peter , Kunz Sara , El-Refai Sherif , Ranganath Praveen , Sukari Ammar , Gadgeel Shirish M. , Wozniak Antoinette J. 
Published: March 2020

e19009 Background: Bevacizumab has increased survival in NSCLC patients (pts) when added to standard chemotherapy. However, whether radiographic features at baseline and/or post-treatment can predict benefit from addition of anti-angiogenic therapy to standard chemotherapy remains unknown. In addition, the impact of VEGF-targeted therapy on CT parameters is not fully characterized. Methods: A retrospective review was performed using CT scans of pts enrolled into a prospective phase II clinical trial of pemetrexed, gemcitabine and bevacizumab in stage IV chemo-naïve, non-squamous, NSCLC pts (Wozniak A, et al. IASLC2011). Treatments were repeated every 2 wks (1 cycle). CT scans were obtained at baseline and at the end of every 4 cycles. The radiographic CT features of the primary tumors were retrospectively reviewed at baseline and after first 4 cycles. RECIST 1.1 and Morphology, Attenuation, Size, and Structure (MASS) criteria were used to assess tumor radiographic response. Results: Twenty-four pts (43% males; median age, 62 y [range: 41-82]), were evaluable for this analysis. On baseline CT, median tumor size was 2.9 cm (range: 1.6. to 6.3 cm), median attenuation was 56 HU (range: 31 to 87 HU), 81% of tumors had heterogeneous enhancement, and 50% of tumors demonstrated invasion of adjacent structures. Well-defined margins were noted in 43% of tumors and 81% had < 30% necrosis. On post-4 cycle CT, 63% of tumors had decreased long diameter (median 15% decrease), 81% had decreased attenuation (median 21% HU reduction) and 50% had increased necrosis. RECIST-defined PR was seen in 37%, SD in 56%; and PD in 1 (4%) based on size despite > 75% necrosis. MASS criteria response was favorable in 25% and non-favorable in 75% of tumors. Pts with tumors that demonstrated FR response by MASS after 4 cycles were more likely to have prolonged progression free survival (HR 2.94; p= 0.175). Conclusions: In tumors treated with anti-angiogenic therapy, imaging response criteria that include changes in tumor morphology, attenuation, and size may capture anti-tumor effect more accurately than size-based RECIST criteria alone. These results support the need for prospective investigation of the efficacy of MASS criteria.
Review of 200 consecutive patients with mutation profiling in a lung cancer individualized medicine clinic.
Authors: Asiedu Michael , Molina Julian R. , Jen Jin , Jang Jin Sung , Roden Anja , Aubry Marie-Christine , Peikert Tobias , Maldonado Fabien , Thomas Charles , Edell Eric , Lifeng Wang , Yang Ping , Allen Mark S. , Deschamps Claude , Nichols Francis C , Cassivi Stephen D. , Shen Robert , Wigle Dennis A. 
Published: March 2020

e19013 Background: Mutation profiling to assess for potentially druggable mutations in NSCLC is being offered at an increasing number of cancer centers throughout North America and internationally. Although data continue to accumulate for the potential value of mutation testing in designing chemotherapeutic regimens, the treatment impact of obtaining information beyond assessment of EGFR and ALK status remains unclear. How best to obtain and clinically utilize these data, including information from exome and whole genome sequencing, also remains unclear. Methods: Patients were reviewed electronically in a multidisciplinary conference regarding indications for testing and results of mutation profiling from various methods, including the mass-spec based LungCarta test, targeted NexGen sequencing, exome, and whole genome sequencing. Outcomes of the multidisciplinary review were communicated back to treating physicians. Results: Mutation testing was performed on 200 patients using a variety of approaches. The majority (>150) were surgically resected stage I and II tumors. Mutations in at least 1 major cancer driver gene, including EGFR, KRAS, MET, BRAF and PIK3CA, were found in 47% of all patients tested. EGFR mutations were present in 14.8% of patients tested, KRAS 21.3%, BRAF 2.6%, PIK3CA 3.2%, and MET 4.5%. A total of 8 patients underwent either exome or whole genome sequencing. A limited number of patients (<10) had mutation results that impacted treatment decisions from this cohort. Conclusions: Mutation profiling can influence treatment decisions in NSCLC, but at a low frequency. The role of exome and or whole genome sequencing for patients with NSCLC is evolving and remains undefined.
Prospective cohort study of serum sialylated glycoprotein (KL-6) as a prognostic marker in patients (pts) with non-small cell lung cancer (NSCLC) receiving gefitinib monotherapy: Okayama Lung Cancer Study Group 0703.
Authors: Yoshioka Hiroshige , Hotta Katsuyuki , Oze Isao , Fujiwara Yoshiro , Hayashi Hidetoshi , Nishiyama Akihiro , Korogi Yohei , Takigawa Nagio , Tanimoto Mitsune , Kiura Katsuyuki ,   Okayama Lung Cancer Study Group
Published: March 2020

e19023 Background: Gefitinib is now crucial in the treatment of EGFR-mutant NSCLC. Its anti-tumor activity could be modulated by MUC1 mucins [Cancer Res 2006], similar to KL-6 in the biochemical property, currently used as an indicator for interstitial lung diseases (ILDs). Our preliminary retrospective study showed the elevated serum KL-6 level is a potential negative prognostic value in pts with advanced NSCLC receiving gefitinib therapy [Lung Cancer 2008]. We conducted an observational study to evaluate this issue prospectively. Methods: Consecutive, EGFR-TKI-naïve NSCLC pts who were to receive gefitinib were enrolled and stratified by pretreatment KL-6 levels (< 500 U/ml: normal group [NG] and ≥ 500 U/ml: abnormally elevated group [EG]). The primary endpoint was overall survival (OS). The planned accrual number of pts was 150, assuming an estimated HR of 2.0, α=0.05, ß=0.10). We also evaluated ILD events during the gefitinib treatment. Results: Between 2007 and 2012, 154 pts were registered (NG: 89 [58%] and EG: 65 [42%] with median KL-6 score of 305 and 1,050 IU/mL, respectively). Those with pretreatment pulmonary fibrosis were similarly distributed between the groups. Median follow-up time was 13.7 months. The EG had significantly worse OS in the univariate analysis (log-rank p=0.0011), which was retained in the multivariate analysis (hazard ratio [HR]: 1.95, 95% confidence interval [95% CI]: 1.34-2.81). Exploratory analyses showed an interaction between EGFR-mutation status and KL-6; HR of KL-6 for OS: 1.96, [1.30-2.97], and HR: 4.80, [1.05-21.95] in pts with EGFR-mutant and wild-typed tumors, respectively (interaction p=0.07). As for ILD event it occurred similarly during the gefitinib therapy (HR: 2.76, [0.62-12.33]). Conclusions: The elevated KL-6 level could predict a poor prognosis in NSCLC pts with gefitinib therapy, and this association seemed modulated by EGFR-mutation status. Further studies are needed to clarify the biological behavior of KL-6 expression on tumor progression especially in the EGFR pathway.
Impact of epidermal growth factor receptor mutations on intracranial treatment response and survival after brain metastases in lung adenocarcinoma patients.
Authors: Hsiao Shih-Hsin , Lin Horng-Chyuan , Yu Ming-Chih , Chung Chi-Li 
Published: March 2020

e19030 Background: Brain metastases (BM) commonly occur in patients with lung adenocarcinoma and usually lead to a poor prognosis. Epidermal growth factor receptor (EGFR) mutation is a predictive and prognostic factor for EGFR tyrosine kinase inhibitor (TKI) treatment for lung adenocarcinoma. The present study aimed to elucidate the predictive role of EGFR mutations in BM treatment response and survival after BM in patients with lung adenocarcinoma patients. Methods: From January 2006 through February 2012, 180 of 505 lung adenocarcinoma patients developed BM during their disease course were reviewed for eligibility, and 139 patients, including 89 EGFR mutant and 50 EGFR wild-type patients, were identified for analysis. BM treatment response was assessed radiologically 1 month after start of treatment and survival data was collected. Results: EGFR mutant patients, compared with EGFR wild-type patients, had significantly greater treatment response of BM (85% vs. 53%, P = 0.001) and longer median survival after BM diagnosis (13.2 vs. 6.8 months, P < 0.001). EGFR mutation (P = 0.001) and use of EGFR TKI during treatment (P = 0.037) were independently associated with BM treatment response. Furthermore, EGFR mutation (P = 0.005), good performance status (P < 0.001) and absence of extracranial metastases (P = 0.033) correlated with better survival. Conclusions: EGFR mutation is an independent predictive factor for both BM treatment response and survival after BM in patients with lung adenocarcinoma. Further studies on incorporation of EGFR mutation status into therapeutic strategy and survival prediction system for lung adenocarcinoma with BM are warranted.
Detection of EGFR alterations in circulating cell-free DNA of lung tumor patients: Higher sensitivity obtained with plasma compared to serum.
Authors: Denis Marc G. , Marcq Marie , Hofman Paul , Bizieux-Thaminy Acya , Bennouna Jaafar , El Kouri Claude , Douillard Jean-Yves , Lacroix Herve , Vallee Audrey 
Published: March 2020

e19046 Background: Detection of EGFR alterations is critical for predicting the response to tyrosine kinase inhibitors (TKI) in patients with non-small-cell lung cancer (NSCLC). In clinical practice, molecular testing is performed on tumor tissues when available. We investigated the use of circulating cell-free DNA for the detection of EGFR alterations in patients with NSCLC. Methods: Serum and plasma were obtained by centrifugation (10 min, 2,000 g, 20°C) performed within 3 hours following blood collection. Cell-free DNA was extracted using the QIAamp Circulating Nucleic Acid kit (Qiagen). Detection of EGFR alterations was performed using the approved Therascreen EGFR RGQ kit (Qiagen). Samples were tested positive for EGFR mutation when the ΔCt value (Ct of the mutation specific PCR – Ct of the control PCR) was lower than 12 for exon 19 deletions, and below 14 for L858R mutation. Results: No EGFR alteration was detected in samples collected from healthy donors (n=6), NSCLC patients with a wild type EGFR (n=60), and early stages NSCLC patients presenting an EGFR mutation in their tumor (n=11). Thirteen metastatic patients presenting an EGFR mutation in their tumor were tested before initiation of TKI treatment. When available, both serum and plasma were analyzed. Nine of these patients (9/13; 69.2%) were tested positive in their serum. The ΔCt values obtained were lower for plasma than for serum in most cases, and more patients (10/11; 90.9%) were EGFR mutation positive when plasma was tested. Finally we tested 3 patients during TKI treatment on a monthly basis. For 2 patients we were unable to detect the mutation initially found in pretreatment samples. Clinically, both patients were partial responders. The third patient did not respond to TKI, and we detected the EGFR mutation with stable ΔCt values at all points tested. Conclusions: EGFR alterations can be found in patients presenting an EGFR mutation in a metastatic NSCLC. Plasma samples allowed a better detection rate. Our results suggest that DNA circulating in plasma is a useful alternative source of tumor DNA that could be used for determining EGFR mutation status, and for follow-up of treatment. Supported by a grant from Astra-Zeneca.
Feasibility study of pemetrexed (PEM) plus bevacizumab (BV) as the first-line treatment for elderly advanced or recurrent non-squamous (non-Sq) non-small cell lung cancer (NSCLC): TORG1015.
Authors: Kozuki Toshiyuki , Nogami Naoyuki , Kitajima Hiromoto , Shinkai Tetsu , Kato Fumiaki , Sakaida Emiko , Takiguchi Yuichi , Ikeda Satoshi , Yoshida Masahiro , Enomoto Yasunori , Kato Terufumi , Ogura Takashi , Miyamoto Shingo , Morita Satoshi , Watanabe Koshiro ,   Thoracic Oncology Research Group
Published: March 2020

e19054 Background: The addition of BV to cytotoxic agent(s) prolonged survival for non-Sq NSCLC patients (pts). However, there is no definitive evidence for the cytotoxic agent(s) plus BV is superior to the cytotoxic agent(s) alone for elderly non-Sq NSCLC. We conducted the feasibility study of PEM plus BV as the first-line treatment for elderly advanced or recurrent non-Sq NSCLC. Methods: Major eligibility and exclusion criteria were followings; chemotherapy-naïve; unfit for bolus combination chemotherapy; stage III/IV or relapsed non-Sq NSCLC; age≥70; PS 0-1; no evidence of brain metastasis; no history of hemoptysis and irradiation for thorax. PEM (500 mg/m2) and BV (15 mg/kg) were administrated intravenously on day 1 every 3 weeks. The primary endpoint was toxicity and the secondary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the percentage of pts who completed more than 3 cycles. Results: From November 2010 to April 2012, total 12 pts were enrolled. Patients characteristics were following; male/female=6/6; Median age (range) 78 (72-81); histology was all adenocarcinoma; activating EGFR mutation no/yes/unknown=9/2/1; stage IIIB/IV/recurrence=2/8/2; ECOG PS 0/1=6/6; smoking history yes/no=6/6. Severe toxicities (Grade 3≥) were leukopenia (25%), neutropenia (25%), anemia (8%), thrombocytopenia (8%), febrile neutropenia (8%), anorexia (8%), hypertension (8%), fatigue (8%), nausea (8%), and perforation (colon) (8%). No dose-limiting toxicity and treatment-related death was occurred. Three patients achieved PR and the ORR was 25%. The median PFS and OS were 5.6 months (mo) (95% C.I. 1.1-7.9 mo) and 10.3 mo (95% C.I. 6.9-15.6 mo) in 11 evaluated pts, respectively. The 1-year survival rate was 49% (95% C.I. 12-79%). Seven of 12 pts (58%) received more than 3 cycles. Conclusions: PEM plus BV as first-line treatment for elderly non-Sq NSCLC was well tolerable and promising. Clinical trial information: UMIN000004263.
EGFR-TKI after disease progression with central nervous system metastasis in advanced non-small cell lung cancer with EGFR mutations.
Authors: Sone Takashi , Kasahara Kazuo , Kurokawa Koji , Sakai Asao , Kita Toshiyuki , Nishikawa Shingo , Watanabe Kazuyoshi , Shirasaki Hiroki , Yoneda Taro 
Published: March 2020

e19083 Background: Several retrospective studies have reported that continued treatment with EGFR-TKI after developing progressive disease (PD) by RECIST improved survival compared to TKI-free treatment in NSCLC patients with EGFR mutations. However, it is unclear which patients would benefit from EGFR-TKI after PD. We hypothesized that patients with CNS progression only, without systemic deterioration, would show a good prognosis with EGFR-TKI after PD. Methods: In order to clarify the survival benefits in patients treated by EGFR-TKI after developing PD, particularly patients with CNS metastasis alone, NSCLC patients with EGFR mutations who were treated with EGFR-TKI and showed progression were analyzed retrospectively. The patients were categorized into two groups: patients continuing with EGFR-TKI treatment after progression (continuation group) and patients switched to chemotherapy or BSC (discontinuation group). Patients were also classified into two groups by site of progression: patients who showed deterioration involving only CNS metastasis (CNS group) and patients who showed progression of the primary lesion, lymph nodes, bone, liver, adrenal glands, CNS, or other sites (systemic group). Differences in post-EGFR-TKI progression survival (PPS) and overall survival were compared between the groups. Results: A total of 75 patients, including 54 women, 56 never smokers, 73 patients with adenocarcinomas, and 57 patients with good PS (0, 1), were analyzed. There were 40 patients with deletions in exon 19, 29 patients with L858R, and 6 with minor mutations. The continuation group (n=36) had a significantly longer PPS than the discontinuation group (n=39) (16.2 m vs. 8.5 m, p<0.01). Although it was not significant, the CNS group (n=14) showed longer PPS than the systemic group (n=61) (17.3 m vs. 9.2 m, p=0.10). The PPS of 9 patients (continuation and CNS groups) was 21.0 m, while PPS of 34 patients (discontinuation and systemic group) was 7.2 m. Conclusions: In this retrospective analysis, continued treatment with EGFR-TKI after PD resulted in longer PPS. A prospective study of patients with progression involving only CNS metastasis treated with EGFR-TKI is needed.
Effect of sequential chemotherapy and gefitinib on survival outcome in advanced NSCLC with acquired gefitinib resistance.
Authors: Huijuan Wang , Mina Zhang , guo Wei Zhang , Hui Zhu , Qiming Wang , Peng Li , Xiangtao Yan , Shaomei Li , Yong Ma Zhi 
Published: March 2020

e19085 Background: As one of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), gefitinib has been proven to be highly effective for patients with advanced NSCLC. However, almost all patients who experienced remarkable improvement eventually develop acquired resistance. There are no approved therapies after disease progression on gefitinib. Subsequent therapeutic modalities are needed. Methods: From September 2007 to July 2012, 74 patients with pathologically confirmed advanced NSCLC who had had disease control with gefitinib more than 6 months were retrospectively reviewed. After acquired resistance to gefitinib, 38 (51%) patients received systemic chemotherapy and sequential gefitinib, 14 (20%) received local treatment and continued gefitinib, and 22 (29%) received best supportive care (BSC) only.Our objective was to assess the survival outcome of different subsequent therapy after acquired resistance to gefitinib. Results: In chemotherapy group, Patients achieved higher response rate and disease control rate, respectively 39% and 82%. The median overall survival (OS) and progression free survival (PFS) from the time of gefetinib resistance in the subsequent chemotherapy group (13.9 m and 5.2 m, respectively) were longer than the local therapy group (7.1 m and 3.1 m, respectively) and the BSC group (3.7 m and 1.1 m, respectively; P < .01). Furthermore, we found that patients who accepted subsequent therapy and continued gefitinib at the same time got better PFS and OS. Local therapy and in combination with continuation of gefitinib treatment could prolong time from local progress to distant metastasis. Conclusions: Subsequent therapy, especially sequential chemotherapy and gefitinib could bring gefetinib resistance NSCLC better survival outcome. Local therapy could also be a reasonable choice for local progress or metastasis patients during gefitinib treatment.
TTF1 status as a better predictor of benefit to erlotinib (E) in metastatic non-small cell lung cancer (NSCLC) than sex, histology, and smoking status.
Authors: Charalambous Charalambos Haris , Charalambous Charis , Vomvas Dimitrios , Katodritis Nikos , Decatris Marios P. 
Published: March 2020

e19110 Background: Erlotinib (E) is currently indicated as first line therapy in patients with EGFR mutations, and as second and third line treatment for patients with advanced metastatic NSCLC. In Cyprus comprehensive EGFR testing started in January 2011. In this study we reviewed all the patients that received E between 2007-2010, without having undergone EGFR mutation testing, looking at predictive factors for benefit. Methods: 100 consecutive patients are included. 3 patients received this as 1st line, 49 patiens as 2nd line and 48 patients as 3rd line and beyond. Previous treatments gemcitabine platinum doublet as first line, and either pemetrexed or docetaxel as 2nd line therapy. Patients had regular Chest x-rays (every 2-3 months) and CT scans (every 4-6 months). Results: 40 female and 60 male, with 9 patients still alive and on treatment. Median age is 66 years (range 32-79). 45 patients were WHO performance status (PS) 0-1, 47 PS 2-3, 8 patients PS not recorded. Median progression-free survival (PFS) for all patients was 95 days( 95% CI 68-118). Median overall survival (OS) from starting E was 144 days (95% CI 103-185). Ten (10) patients had a partial response and 34 stable disease. Subset analyses were undertaken based on smoking status, sex, histology type and TTF1. Univariate analysis for PFS using KM plots showed a statistically significant difference for sex, smoking and TTF1. On Cox regression only gender and TTF1 were statistically significant (0.007 and 0.006). There was a striking difference in both median PFS and median OS between patients with TTF1-ve tumours (33 days) and TTF1 +ve tumours (149 days). Conclusions: TTF1 is a better predictor of benefit to E than histology, sex and smoking status. The very low median PFS and OS for patients with TTF1 –ve tumors would suggest that such patients derive little or no benefit from E. [Table: see text]
Review of end points of phase III clinical trials with combination chemotherapy regimens for non-small cell lung cancer evaluating importance of quality of life.
Authors: Prabhash Kumar , Divekar Ganesh , Jain Minish Mahendra , Bhosale Bharatsinha Baburao 
Published: March 2020

e19119 Background: Systemic combination chemotherapy is accepted as a standard of care for patients with advanced non-small cell lung cancer (NSCLC). Substantial similarities in terms of treatment efficacy and survival have emerged over the years between the different systemic chemotherapy regimens used. Quality of life (QOL) analysis will help to customize chemotherapy to improve outcome in NSCLC patients. Methods: Using PUBMED database, a review of randomized controlled phase III trials of advanced NSCLC published in last 5 years reporting comparative safety and efficacy between chemotherapeutic regimens as end points was conducted. An evaluation of end points, difference in efficacy endpoints, QOL analysis, and final conclusion was conducted. Results: The search criteria identified 51 trials (33,481 patients). Out of these 51 clinical trials, 16 trials showed difference in efficacy (13 survival endpoint, 1 ORR (objective response rate), 2 survival without grade 3/4 toxicity) and 11 trials used validated QOL instruments and were included for review. Two trials; one comparing pemetrexed/cisplatin with gemcitabine/cisplatin, and other comparing cisplatin/weekly vinoralbine with cisplatin/vinoralbine on day 1 and 8; showed difference with QOL; though not statistically significant. The QOL reporting/analysis techniques were heterogeneous. Two trials used QOL as primary endpoint. Safety reporting included percentage adverse events with treatment arms. Conclusions: Based on our review, it seems critical to have QOL as an endpoint while evaluating newer combination chemotherapeutic regimens for NSCLC. Secondly, it is unlikely that a major difference exists in the global QOL associated with standard chemotherapy regimens for NSCLC. An effort to have uniform QOL assessment across trials evaluating newer combination regimens for NSCLC will help to customize treatment.