bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biologic markers guiding the treatment of non-small cell lung cancer: RRM-1, class III ß tubulin, and ERCC-1.
Authors: Namal Esat , Bozkurt Mustafa , Ozturk Akin , Planci Kezban Nur , Bassullu Nuray , Pamukcu Ozgul , Dogusoy Gulen Bulbul , Saglam Sezer , Akcali Zafer , Demir Gokhan 
Published: March 2020

e19127 Background: Lung cancer is the most common cause of cancer deaths in the world. Despite the developments in diagnosis and treatment, the high mortality rate in metastatic non small cell lung cancer (NSCLC) is still an important problem. Recent non-targeted standard therapy for NSCLC is the dual therapy regimens which involve platins. Our former knowledge whether these therapies can be effective or not would save the patient from the redundant toxicity and provide us to use more effective drugs formerly. Understanding the biology of NSCLC can allow choosing the effective and appropriate therapy in terms of life quality, survival rate and relapses. There are ongoing studies upon prognostic and predictive values of ERCC1, RRM1 and β tubulin in NSCLC patients. In this study we aimed to investigate the role of β tubulin, ERCC1 and RRM1 expressions as predictive biomarkers. Methods: 47 patients who are on follow up by Bilim University, Medical Oncology Department, were taken to the study. ß tubulin, ERCC1 and RRM1 over expressions were investigated in the biopsy materials of these patients by Pathology Department. Retrospectively, it was evaluated whether there is correlation between these biological markers and patients’ survial rates and responses to antineoplastic therapies. Results: In the literature, there are some studies which show that β tubulin score is a predictive marker for the good response to taxan therapy. On the other hand, it was shown that taxans enhance the platin sensitivity decreasing the β tubulin expressions. Our study was also correlated with these studies in the literature. Furthermore, there was relationship between the β tubulin score and age. 15 patients (%32) were 65 or under 65 and these were accepted as ‘young patient population’; 32 patients were over 65 and were accepted as ‘old patient population’. Most of the patients whose β tubulin score was high (n=29), were young (n=19); and most of the patients whose β tubulin score was low (n=18) were old patients (n=12) (p=0.032). Conclusions: Detecting the levels of β tubulin, ERCC1 and RRM1 before treatment in NSCLC patients, can be predictive to organize the treatment. Unquestionably, it must be supported by the studies involve more patients.
Effect of pretreatment clinical consultation on oncologist prescribing behavior in the initial treatment of NSCLC.
Authors: Fishman Marc L. , Kumar Akhil , Shimp William S. , Bobolts Laura Rose , Krook James Edward , Fishman Val , Davis Sharon , Walton Robert , Huff Dinah , Hrushesky William J. 
Published: March 2020

e19130 Background: Oncology Analytics (OA) promotes evidence-based treatments, based upon objective assessments of efficacy and safety. ASCO guidelines and FDA approval recommend bevacizumab only in combination with carboplatin/paclitaxel, based on E4599 which showed improved OS. NCCN guidelines allow bevacizumab with virtually any approved 1st line chemotherapy (2A). Board certified OA oncologists perform real-time clinical consultations if bevacizumab usage in 1st line is not per level 1 evidence. More recently, those conversations include the Phase III Pointbreak Trial’s failure to show OS advantage with carboplatin/pemetrexed/bevacizumab. Methods: All bevacizumab requests with doublet chemotherapy were tabulated, from 2010 through 2012, and the outcome of pre-treatment clinical consultations were retrospectively analyzed. Results: Bevacizumab with a platinum doublet was requested in 91 patients with non-squamous NSCLC. Of these, 53% (48/91) of requests were for carboplatin/paclitaxel/bevacizumab, consistent with level one evidence, FDA approval and ASCO guidelines. All were approved after confirmation of histology and absence of relative contraindications. Approximately half (47%; 43/91) of the requests were not consistent with level 1 evidence, though compliant with non-evidence-based NCCN guidelines. After clinical consultation, 20 of 43 requests (46%) were revised to evidence-based protocols. Conclusions: These data suggest that nearly half of bevacizumab requests in NSCLC are not in accordance with published level 1 evidence. Pre-treatment clinical consultations can promote evidence based care while reducing costs. National guidelines should be evidence based, especially in common cancers where level 1 evidence is available, since practicing physicians may rely on these guidelines when planning treatment. [Table: see text]
Efficacy and safety of bevacizumab in nonsquamous non-small cell lung cancer with brain metastases.
Authors: Ichiki Masao , Yoshida Tsukasa , Nakamura Masayuki , Kumano Tomomi , Hoshino Tomoaki 
Published: March 2020

e19134 Background: Patients (pts) with brain metastases were excluded from bevacizumab (Bev) therapy due to a case of fatal cerebral hemorrhage in 1997. However, several trials showed the safety of Bev in pts with inactive (previously treated or asymptomatic) brain metastases, and Bev therapy was recently permitted as practical care for brain metastases in Japan. Methods: We retrospectively identified pts treated with Bev for inactive brain metastases from NSCLC. CT or MRI scans performed at least 6 weeks after Bev therapy were assessed for response. Results: There were 17 pts. All pts had adenocarcinoma. Median age was 66 (range 57-74), male/female= 8/9, PS0/1/2= 3/10/4, 1st-/2nd-/3rd-/4th-line chemotherapy with Bev = 8/4/4/1, EGFR mutation status; mutated/wild type/unknown=8/7/2; concurrent chemotherapy with Bev: amrubicin (1), pemtrexed (2), cisplatin (carboplatin) + pemetrexed (10), carboplatin + paclitaxel (3), cisplatin + gemcitabine (1); prior chemotherapy: gefitinib (6), erlotinib (3), docetaxel (1), carboplatin + paclitaxel (2), cisplatin + pemetrexed (2), pemetrexed (1); prior therapy for brain metastases: surgery (1), surgery + WBRT (2),WBRT (8), SRS (4), none (2). In 14 pts with evaluable target brain metastases, the response rate for intracranial metastases was 78.6% (95% CI, 49.2-95.4%), and in 15 pts with evaluable target lesions except brain metastases, the response rate for extracranial metastases was 40.0% (95% CI, 16.3-67.7%). Serious toxicities (grade 3/4): hypertension (2/0), proteinuria (0/-). There were 2 bleeding events: one was grade 1 intracraninal hemorrhage, the other was grade 1 bronchopulumonary hemorrhage. Conclusions: Chemotherapy+Bev is effective for pts with inactive brain metastases and is a well-tolerated regimen with a favorable toxicity profile. The updated data including PFS and OS will be presented at the Annual Meeting.
Treatment patterns, biomarker testing, and outcomes in patients with nonsquamous non-small cell lung cancer (NSCLC) receiving second-line treatment in the US Oncology network.
Authors: Pan IWen , Mallick Rajiv , Dhanda Rahul , Nadler Eric S. 
Published: March 2020

e19139 Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the US, with a 5-year survival rate of < 20%. Treatment patterns and outcomes in late stage NSCLC in US community oncology practices are not well known. Methods: This retrospective study used the iKnowMed database, billing claims, and chart reviews. Eligibility criteria included non-squamous NSCLC, stage IIIB/IV at diagnosis, ECOG status <3, and initiation of second-line therapy (defined as index date) between 1/1/2007-6/30/2011 with > 1 year follow-up. Key outcomes were overall survival (OS), progression-free survival (PFS), time-to-progression (TTP), and time-to-hospitalization (from index date). Progression was defined as change in therapy and/or new metastatic lesion. Kaplan-Meier and Cox proportional hazard models were used to characterize the distribution and predictors of outcomes. Results: 1,168 patients were eligible for the study. The top three second-line therapies were pemetrexed (54.4%), erlotinib-containing regimens (17.6%), and docetaxel (10.0%). OS and PFS were 7.5 (95% CI: 6.6-8.4) and 4.1 (95% CI: 3.7-4.5) months, respectively; 57% of patients were hospitalized post-index date. EGFR testing rates were 2.3% pre-2010, 15.2% in 2010, and 32.0% in the studied 2011 period (p<0.001). Of EGFR-positive patients, 50.0% received erlotinib-containing regimens compared to 16.9% of EGFR-negative patients (p=0.001). Baseline ECOG=1 (HR=1.49; p<0.001) or ECOG=2 (HR=1.79; p<0.001), compared to ECOG=0, existing co-morbid fatigue (HR=1.53; p=0.010) compared to no co-morbid fatigue, and progression (HR=1.78; p<0.001), when it occurred, compared to no progression, increased risk of shorter time to hospitalization, adjusting for other factors. Compared to other second-line treatment, erlotinib-containing regimens prolonged adjusted TTP (HR=0.68; p=0.018). Conclusions: EGFR testing in community practice rose rapidly after 2010 suggesting improved personalized treatment given study evidence that EGFR inhibitors prolonged adjusted TTP. Also, ECOG ≥1 and progression, once it occurred, predicted shorter time-to-hospitalization.
Tumor genotype and clinical outcomes for 229 patients with non-small cell lung cancer.
Authors: Duffy Regan M. , Roesler Grant , Warrick Andrea , Beadling Carol , Schuff Kathryn , Corless Christopher L. , Sandler Alan , Lopez-Chavez Ariel 
Published: March 2020

e19141 Background: Advances in genetic analysis have created a successful paradigm shift in the treatment of advanced lung cancer. Prior studies characterizing molecular profiles in lung cancer have been limited by analysis of a restricted number of genes and lack of clinical outcomes correlation. To overcome these limitations, this study investigates a prospective cohort of lung cancer patients using an expanded molecular profile and evaluates clinical outcomes. Methods: Non-small cell lung cancer (NSCLC) patients enrolled from April 1, 2011 through December 31, 2012 are included in this analysis. Formalin-fixed, paraffin-embedded tumor tissue was analyzed, using mass spectrometry-based panel of multiplexed assays (through July 31, 2012) or using next-generation sequencing detecting hydrogen-ions generated during DNA polymerization (using Ion Torrent from August 1 through December 31, 2012). Clinical information was collected at enrollment and throughout the study. Results: Analysis of 229 enrolled patients revealed 52% women, 95% had ECOG performance status 0-2, 89% Caucasian, and 28% never smokers. Successful molecular analysis (at least one successful analysis) occurred in 178 patients. Fifty-one patients had insufficient tissue for any successful molecular analysis. One hundred twenty-five mutations were detected among ninety-seven patients. The most frequent mutations included KRAS (28%), TP53 (20%), EGFR (13%), ALK translocations (6%), and BRAF (3%). At the time of analysis, 49% of the study population was deceased. Of the deceased, 37% harbored at least one genetic mutation within their tumor sample. Overall survival for those with mutations was 22.7 months, compared to overall survival for those without mutations of 23.3 months. Conclusions: Our analysis contributes to the growing body of data on molecular abnormalities in NSCLC by expanding the knowledge of common and less-commonly documented mutations, as well as characterizing the clinical outcomes associated with the mutations documented. These data emphasize the diversity of mutations and outcomes for NSCLC, and highlight the need for additional research of prognostic genetic markers and improvements in targeted therapies.
Randomized phase III trial of pemetrexed (Pem)+carboplatin (Cb)+bevacizumab (Bev) followed by maintenance Pem+Bev (Pem arm) versus paclitaxel (Pac)+Cb+Bev followed by maintenance Bev (Pac arm) in patients (pts) with stage IIIb/IV nonsquamous non-small cell lung cancer (nsNSCLC) (POINTBREAK): African American (AA) subset.
Authors: Reynolds Craig H. , Patel Jyoti D. , Garon Edward B. , Olsen Mark R. , Bonomi Philip D. , Govindan Ramaswamy , Obasaju Coleman K. , Pennella Eduardo J. , Liu Jingyi , Guba Susan C. , Spigel David R. , Hermann Robert C. , Socinski Mark A. 
Published: March 2020

e19150 Background: AAs with lung cancer (LC) have shorter survival than Caucasians (Cs). Despite a higher LC incidence among AAs than Cs (74.7 vs 64.4/100,000), AAs are underrepresented in clinical trials. There are no reports of randomized LC prospective trials reporting AA results. In POINTBREAK, we enrolled AAs at the same rate as the US incidence of NSCLC in AAs. We report efficacy/safety of AAs in both arms and efficacy/safety of AA and C within the Pem Arm. Methods: Data from AAs and Cs enrolled in POINTBREAK were analyzed. AAs in both arms were evaluated in a pre-specified analysis. Hazard ratio and p-values were derived from a multivariate Cox-PH model by adjusting stratification factors. Results: Of 939 randomized pts, 94 were AA and 805 were C. Demographics were comparable between AA/intent-to-treat populations (%): 56/53 male, 65/52 ≤65 years, 87/88 ever smoker, 86/90 stage IV, 43/44 Eastern Cooperative Oncology Group performance status 0. The table shows efficacy results. Among AAs, drug-related grade 3/4 adverse events (AEs) include (Pem Arm %/Pac Arm %): anemia (7.3/0), thrombocytopenia (9.8/4.0), fatigue (4.9/4.0), neutropenia (31.7/44.0), febrile neutropenia (0/4.0). Within Pem Arm, drug-related grade 3/4 AEs (AA%/ C%) were anemia (7.3/15.9), thrombocytopenia (9.8/25.5), fatigue (4.9/11.5), neutropenia (31.7/25.3), febrile neutropenia (0/1.6). Conclusions: Median OS for Pem Arm was not superior to Pac Arm in AAs. Within Pem Arm, there were no significant differences between AAs and Cs for efficacy outcomes. Both regimens were tolerable in AAs. Clinical trial information: NCT00762034. [Table: see text]
Prognostic significance of minimal pleural effusion in non-small cell lung cancer patients.
Authors: Ryu Jeong Seon , Lee Si-Nae , Ryu Hyo-Jin , Nam Hae-Seong , Memon Azra , Kim Hyun-Jung , Lim Joo Han 
Published: March 2020

e19152 Background: Malignant pleural effusion (MPE) was defined by the presence of malignant cells in pleural space. Accurate characterization of pleural effusion (PE) is an essential part in staging the disease for adequate management. At diagnostic evaluation, minimal pleural effusion (mPE) that is too small amount PE to examine the presence of malignant cells through thoracentesis is present outside scope of current staging system. Therefore whether mPE has prognostic impact or not is an important clinical issue needed to be investigated. Methods: 1,382 consecutive stage IIIB, IV NSCLC patients were retrospectively enrolled from Inha Lung Cancer Cohort. Information regarding smoking habits, ECOG PS, Charlson comorbidity index score, weight loss in 6 months before diagnosis, levels of hemoglobin, albumin, alkaline phosphatase and calcium at the time of diagnosis, treatment, followed-up and survival status was analyzed as potential confounding factors. All patients were performed staging work-up and followed-up at Inha university hospital. The mPE was defined as less than 1 cm of maximal thickness on contrast enhanced chest CT scan at diagnosis and its presence was not considered in staging the disease. Results: According to status of PE at diagnosis, patients were classified into no PE, mPE and MPE. No PE was presented in 614 patients (44.4%); mPE in 339 patients (24.5%); malignant PE in 356 patients (25.8%). PEs of 73 (5.3%) patients was not evaluated. Overall survival of patients with mPE or MPE was shown to be significantly shorter than those of patients with no PE (MST, 9.67 for no PE, v 6.60 for mPE v 5.37 months for MPE, log-rank p<.0001), even after adjustment for age, smoking habits, ECOG PS, Charlson comorbidity index score, weight loss, hemoglobin, albumin, alkaline phosphatase, calcium, histology, T subset, N subset, M subset, and treatment status (hazard ratios, 95% CIs and Cox p: 1.18, 1.023 to 1.373 and .024 for mPE; 1.545, 1.314 to 1.816 and <.0001 for MPE). Conclusions: The mPE is commonly encountered clinical situation in advanced stage NSCLC patients. These results suggest that presence of mPE at diagnosis confers grave prognosis like MPE, in spite of its nature.
Safety and efficacy results of a phase IV, open-label, multicenter, safety-monitoring study of icotinib in treating advanced non-small cell lung cancer (NSCLC): ISAFE study.
Authors: Tan Fenlai , Gu Aiqin , Zhang Yiping , Jiao Shun Chang , Wang Chang-li , He Jintao , Jia Xueke , Zhang Li , Peng Jiewen , Wu Meina , Ying Kejing , Wang Junye , Ma Kewei , Zhang Shucai , You Changxuan , Ding Lieming , Wang Yinxiang , Shen Haijiao , Wan Jiang , Sun Yan 
Published: March 2020

e19161 Background: The phase III ICOGEN trial established the non-inferiority of icotinib to gefitinib in terms of progression-free survival (PFS), based on which icotinib was approved by State Food and Drug Administration of China. We conducted a safety-monitoring study to assess the safety and efficacy of icotinib in a broad range of patients with advanced non-small-cell lung cancer (NSCLC) across China. Methods: This study was a single-arm, open-label, multi-center trial in advanced NSCLC patients who were suitable for treatment with oral icotinib 125 mg three times daily. Endpoints included safety, objective response rate (ORR) and disease control rate (DCR), were investigated overall and in subgroups. EGFR mutation analysis was performed retrospectively. Results: Between August, 2011 and August, 2012, 6,087 advanced NSCLC patients were registered with a median age of 63 years (range: 21-95 years), and 5,549 patients were evaluable for safety and tumor response. Baseline characteristics (%) were: male/female 50.8/49.2; non-smoker/ex- or current-smoker/no data 67.2/32.7/0.1; adenocarcinoma/non-adenocarcinoma/other 78.6/15.4/6.0; stage IIIB/IV/other 7.4/90.2/2.4; and 1,571(28.3%) patients were ≥ 70 years of age. The overall incidence of drug-related adverse events (AEs) of any grade was 31.5%, in which the most common drug-related AEs including rash (17.4%) and diarrhea (8.5%), and 3 patients experienced with interstitial lung disease (ILD) associated with icotinib. ORR and DCR were 30.0% and 80.6%, respectively. The safety in the elder patients (age ≥70, n=1,571) were similar to that in the overall population, the incidence of drug-related AEs of any grade was 30.6%, most of which were grade I or II. Among 989 patients who undertook EGFR mutation detection, 738 (74.6%) patients were mutation-positive with an ORR of 49.2% and a DCR of 92.3%. Moreover, in 251 (25.4%) wild type patients, the ORR and DCR were 17.8% and 75.7%, respectively. Conclusions: The data from over 6,000 patients was consistent with the results of the ICOGEN study. Icotinib demonstrated efficacy and a favorable toxicity profile in the routine clinical setting.
A meta-analysis of comparing EGFR-TKI with chemotherapy as the second-line treatment of NSCLC patients with wild-type EGFR.
Authors: Gao Guanghui , Ren Shengxiang , Li Aiwu , He Yayi , Chen Xiaoxia , Li Wei , Zhou Fei , Li Shuai , Zhou Caicun 
Published: March 2020

e19166 Background: The efficacy of comparing the EGFR-TKI with standard chemotherapy in the second-line treatment of advanced NSCLC with wide-type EGFR were still controversial. To derive a more precise estimation of the two regimens, a meta-analysis was performed. Methods: Medical databases and conference proceedings were searched for randomized controlled trials which compared EGFR-TKI (gefitinib or erlotinib) with standard second-line chemotherapy (docetaxel or pemetrexed) in patients with NSCLC. Endpoints were overall survival, progression-free survival and overall response. Results: Three eligible trials (INTEREST, TITAN and TAILOR) were identified. Lacking for data of overall survival of TAILOR trial, So we only make a preliminary meta-analysis for overall survival. The intention to treatment (ITT) analysis demonstrated that the patients receiving EGFR-TKI had a significantly shorter progression-free survival (PFS) than patients treated with chemotherapy (hazard ratio (HR) = 1.31; 95% conﬁdence intervals (CI) = 1.10-1.56; P = 0.002). The overall survival (OS) and overall response rate (ORR) were coparable between this two groups (HR = 0.96; 95%CI = 0.77-1.19; P = 0.69; relative risk (RR) = 0.37; 95%CI = 0.09-1.54; P = 0.17). Conclusions: Although chemotherapy had a clear superiority in PFS as second-line treatment for patients without EGFR mutations compared with EGFR-TKI, OS and ORR were equal in this two regimens. The toxicity proﬁles might play an important role in the decision to choose EGFR-TKI or chemotherapy. These findings still need to be verified in larger confirmatory studies in future.
Impact of body surface area (BSA) on efficacy of gefitinib in patients with non-small cell lung cancer (NSCLC).
Authors: Kudo Kenichiro , Hotta Katsuyuki , Yoshioka Hiroshige , Kunimasa Kei , Tsubouchi Kazuya , Iwasaku Masahiro , Oze Isao , Ichihara Eiki , Tanimoto Mitsune , Kiura Katsuyuki 
Published: March 2020

e19167 Background: Drug dosing of chemotherapeutic agents has traditionally been based on an estimated BSA to reduce the pharmacokinetic inter-patient variability. However, the approved dose of gefitinib was fixed at 250 mg/body/day. Our preliminary retrospective study showed a potential association between BSA and progression-free survival (PFS) in the gefitinib monotherapy in advanced NSCLC [ASCO 2012, #2607]. Here, we investigated the influence of BSA on efficacy of gefitinib, using data from a prospective cohort of NSCLC patients receiving gefitinib. Methods: The subjects were 154 consecutive, EGFR-tyrosine kinase inhibitor (TKI)-naïve NSCLC patients who were to receive gefitinib monotherapy between 2007 and 2012. Baseline BSA was estimated by height and weight in each patient. The association between BSA and survival time was assessed using log-rank test and stepwise multivariate Cox proportional hazard model. Results: Median BSA of the subjects was 1.42 m2 (range: 0.98-1.95). At the cutoff level in BSA of 1.50 m2, overall survival (OS) and PFS in the large BSA group were not different from those in the small BSA group in the univariate analysis, which was also shown in multivariate analysis (hazard ratio: 1.12, 95% confidence interval: 0.66-1.92 and 1.67, 0.86-3.44, respectively). Among subjects with EGFR-mutant tumors (n=125; 81%), BSA had no association with OS, but patients with larger BSA had significantly worse PFS in the multivariate analysis (1.59, 1.01-2.51). The association of BSA with PFS was highly sensitive to increase or decrease in the cutoff level of BSA: BSA ≥ 1.45 m2 vs. <1.45 m2, [1.18, 0.80-1.75]; BSA ≥ 1.55 m2 vs. <1.55 m2, [1.75, 1.11-2.78]; BSA ≥ 1.60 m2 vs. <1.60 m2, [1.32, 0.82-2.11]. Conclusions: In this cohort, PFS was significantly associated with BSA in EGFR-mutant NSCLC when BSA level was cut off by around the median score. Our findings might suggest the need for further investigation of dose finding PK/PD study stratified by BSA level in gefitinib therapy in EGFR-mutant NSCLC.