bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of outcome for pemetrexed (Pem) in metastatic NSCLC (mNSCLC).
Authors: Jones Cortney Vanderbilt , Du Lingling , Elson Paul , Mekhail Tarek , Pennell Nathan A. , Hashemi Sadraei Nooshin 
Published: March 2020

e19025 Background: Pemetrexed (Pem) is the first agent showing different efficacy based on histology in the treatment (tx) of NSCLC. Our goal was to identify outcome predictors in patients (pts) with metastatic NSCLC (mNSCLC) treated with pem. Methods: Retrospective data of pts with mNSCLC who received pem were analyzed. Variables included demographics, ECOG performance status (PS), disease sites, pre/post-pem tx, and toxicities. Clinical benefit defined as complete response (CR), partial response (PR), and stable disease (SD) >6 months, progression-free survival (PFS), and overall survival (OS) were analyzed using logistic regression and Cox proportional hazards model. Results: 240 pts were included. 55% male, 84% smokers. 68% adenocarcinomas, 10% squamous/adenosquamous carcinomas. Median age 64 years (range 34-84). Pem was given for a median of 4 cycles (range 1-73), as 1st line in 20% and 2nd line in 50%, given as a single agent in 69%. The most common toxicities were constitutional (50%) and GI related (29%). 31% of pts achieved CR (n=4) or PR, 33% progressed, 36% had SD. Front-line pem use (p=.0003), adenocarcinoma histology (p=.05), and non-pulmonic metastatic sites ≤2 (p=.01) were independent predictors of clinical benefit, with response rate of 71% for pts with all three features, compared to only 7% for pts with none of these features. Multivariable analysis of survival data revealed ECOG PS >1, non-pulmonic metastatic sites>2, and squamous/poorly differentiated histology predicted poor PFS and OS. In addition, interval from diagnosis to start of pem <12 months and male gender predicted poor PFS, while former/current smoker predicted poor OS. Pts with favorable features had a median PFS of 7.7 months, compared to 2.1 months with unfavorable features (p<.0001). A median OS of 16 months was achieved in pts with favorable features, compared to 5.9 months with unfavorable features (p<.0001). Conclusions: Front-line pem use, adenocarcinoma histology, and ≤2 non-pulmonic metastatic sites predict better response to pem. Poor PS, >2 non-pulmonic metastatic sites, squamous/poorly differentiated histology predict poor PFS and OS. An analysis of biomarkers is ongoing.
The predictive role of consecutive measurements of serum CEA for treatment efficacy in advanced non-small cell lung cancer patients harboring epidermal growth factor receptor mutations treated with gefitinib or erlotinib.
Authors: Chung Chi-Li , Chiang Ling-Ling , Yu Ming-Chih , Lin Sey-En , Hsiao Shih-Hsin 
Published: March 2020

e19029 Background: Patients with non-small cell lung cancers (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations dramatically respond to EGFR tyrosine kinase inhibitors (TKIs) with approximately 70% response rate. Carcinoembryonic antigen (CEA) has been suggested to be associated with tumor recurrence, treatment efficacy and prognosis in some specific tumors. However, the role of CEA in NSCLC with EGFR mutations remains unclear. Therefore, we sought to elucidate whether the determination of serum CEA levels can predict the efficacy of EGFR TKIs in NSCLC harboring EGFR mutations. Methods: Medical records of 326 consecutive patients with advanced NSCLC between January 2007 and November 2012 were reviewed and a total of 104 patients with NSCLC harboring EGFR mutations treated with gefitinib or erlotinib ³2 weeks and with available data of serum CEA were identified for analysis. Results: Female, never smokers, adenocarcinoma histology and cases with pretreatment serum CEA ³ 5 ng/ml presented 63%, 76%, 96% and 68% of 104 eligible cases with mean age of 65.4 ± 13.7 years, respectively. The response rate of EGFR TKIs in patients with pretreatment CEA ³ 5 ng/ml was not significantly different (70% vs 91%, P = 0.339), and it was higher in those with reduction of CEA level after treatment than those without (94% vs 35%, RR=2.7, P <0.001). The average change of pre- and post-treatment CEA in respondents and non-respondents was negative 112 ± 181 ng/ml and positive 368 ± 514 ng/ml, P <0.001, respectively. In details, the pre- and post- treatment CEA levels in respondents were 246 and 71 ng/ml, P < 0.001, respectively, and those in non-respondents were 157 and 268 ng/ml, P= 0.019, respectively. Furthermore, the post-treatment CEA level increased by 14% in non-respondents and decreased by 52% in respondents. Conclusions: Reduction or elevation of post-treatment serum CEA can predict the treatment efficacy in NSCLC patients with EGFR mutations treated with gefitinib or erlotinib. Further studies aiming to investigate the value of serum CEA levels in tumor progression and survival are warranted.
Benchmarking population-based EGFR mutation testing in nonsquamous non-small cell lung cancer.
Authors: Shiau Carolyn Jane , Babwah Jesse Paul , Santos Gilda Da Cunha , Sykes Jenna R , Boerner Scott L. , Geddie William R. , Wei Cuihong , Kamel-Reid Suzanne , Hwang David M , Tsao Ming Sound 
Published: March 2020

e19032 Background: Epidermal growth factor receptor (EGFR) mutation testing has become critical in the treatment of advanced non-small cell lung cancer (NSCLC) patients. This study involves a large cohort and epidemiologically unselected series of EGFR mutation testing for non-squamous NSCLC patients in a North American population, to determine mutation rates and define factors that influence success in routine clinical EGFR testing. Methods: Data from consecutive cases of Canadian province-wide testing during a 24-month period at a centralized diagnostic laboratory were reviewed. Samples were tested for exon 19 deletion and exon 21 L858R mutations using a validated PCR method with 1-5% detection sensitivity. Results: From 2,651 samples submitted, 2,404 samples were tested with 2,293 samples eligible for analysis. These included 1,780 histology and 513 cytology specimens. The overall test failure rate was 5.4%. Among successfully tested samples, the overall mutation rate was 20.6%. There were no significant differences in the failure rate, mutation rate, or mutation type found between histology and cytology samples. While tumor cellularity was significantly associated with test success or mutation rates in histology and cytology specimens respectively, mutations could be detected in all specimen types. Optimal histology samples contained ≥2 mm2of tumor tissue and ≥30% tumor cellularity. Optimal cytology cell-block samples have at least a few groups of nucleated cells dispersed throughout the block, regardless of tumor cellularity. Samples from metastatic deposits in bone, distant lymph nodes, and pleura showed higher mutation rates than primary lesions. Conclusions: Our current method for EGFR mutation testing is able to detect mutations in small tumor volume biopsies, typical of tissue obtained for initial diagnosis. EGFR mutation testing should be attempted in any type of specimen, histology or cytology. Cases that are suboptimal with a negative EGFR mutation result should be considered for repeat testing with an alternate tumor sample.
Epidermal growth factor receptor mutation (EGFRMUT) in non-small cell lung cancer (NSCLC) in the Middle East.
Authors: Jazieh Abdul Rahman , Jaafar Hassan Nadim , Mustafa Rasha , Rasul Kakil , Zekri Jamal , Gaafar Rabab Mohamed , Al Husaini Hamed Homoud , Azim Hamdy A. , Bamefleh Hanaa , Gasmelseed Ahmed 
Published: March 2020

e19035 Background: EGFR mutation is an important therapeutic marker for the management of NSCLC with known ethnic variations. Our study aims at determining the prevalence of the mutation in the Middle East and its correlation with demographic and clinical features. Methods: A multisite retrospective study was conducted including institutions from Saudi Arabia, UAE, Qatar and Egypt. All consecutive patients (pts) with NSCLC tested for EGFRMUT were eligible. Data were obtained on demographic and disease characteristics, and EGFR test results. Institutional Review Board approval was obtained from all participating sites. Results: Data on 201 patients were obtained. Median age was 61 years (51 - 69), 140 (69.65%) were males and 174 pts were Arab (86.57%) Tumor histology subtypes were adenocarcinoma in 175 patients (87.07%), squamous cell carcinoma in 15 pts (7.46%) and others in 11 pts (5.48%). EGFRMUT was detected in 66 pts, with (36.50%) prevalence in adenocarcinoma. No squamous cell carcinoma harbored EGFRMUT. The most frequent abnormality detected was in exon 19 in 39 pts (57.36%), abnormalities in exon 21 in 22 pts (32.35%) and in exon 18 in 7 pts (10.29%). Two pts had dual mutations on exons 19 and 21. Univariate and multivariate analyses revealed significant predictors for having EGFRMUT to be: female gender (42.42 % vs. 27.7% in males, p= 0.0096), non-smoking status (81.82% vs. 16.21% in smokers, p=0.0001) and adenocarcinoma subtypes (36.25 % vs. 15.38% in others, p=0.035). There was no difference between Arabs and non-Arabs. Conclusions: This is the first study from our region to report the prevalence of EGFRMUT in ME population which seems to be similar to Far East population with similar clinical predictors. Studies about the impact of targeted therapy in our patient’s population are underway.
Evaluation of the prognostic/predictive role of tumor EGFR and KRAS mutations in Greek metastatic non-small cell lung cancer patients treated with first-line chemotherapy.
Authors: Linardou Helena , Kosmidis Paris A. , Kotoula Vassiliki , Karavasilis Vasilios , Eleftheraki Anastasia G , Lazaridis Georgios , Daskalaki Emily , Lakis Sotiris , Charalambous Elpida , Samantas Epaminontas , Pectasides Dimitrios G. , Bafaloukos Dimitris , Fountzilas George 
Published: March 2020

e19048 Background: KRAS mutations are reported in 20-25% of non-small cell lung cancer (NSCLC). Little is known about the prognostic/predictive role of KRAS in advanced NSCLC, with conflicting results among small studies. Recent evidence showed that KRAS mutations could predict for worse outcome in patients treated with platinum-based adjuvant chemotherapy. Methods: KRAS and EGFR genotypes were evaluated in 414 NSCLC patients with available clinical data, diagnosed from March 2000 to December 2012 (tissue blocks from the HeCOG tumor repository). KRAS and EGFR mutations were associated with clinicopathological parameters (mutated vs. wild-type). Outcome comparisons were performed in 214 metastatic patients with treatment data available, following 1st-line chemotherapy without tyrosine kinase inhibitors. Results: The majority of the patients were male (80%), current smokers (53%), with adenocarcinoma (AC) histology (65%). EGFR mutations were found in 10% and KRAS mutations in 17% of all histological types, while in AC they were 14% and 21%, respectively. Most EGFR mutations were classical (79%), while most common KRAS mutations were p.G12C (39%), p.G12D (30%) and p.G12V (15%). Two tumors had concurrent EGFR and KRAS mutations. EGFR mutations were significantly associated with female gender, AC histology and non-smoking status, as previously described. KRAS mutations were associated with AC histology and younger age (<60). At a median follow-up of 31 months, EGFR status did not show any significant associations with OS or PFS, while KRAS mutations were prognostic for worse OS compared to KRAS and EGFR wild-type tumors (HR=1.67, CI=1.08-2.59, p=0.021). This effect was also significant (p=0.022) in the presence of treatment type, with platinum-based therapy being a positive prognostic factor for OS (HR=0.62, CI=0.4-0.92, p=0.019). The association of KRAS mutations with PFS was not significant. Conclusions: EGFR and KRAS genotype incidences are presented for the first time for Greek metastatic NSCLC patients. In this setting, the presence of KRAS mutations significantly increases and platinum 1st-line treatment decreases the risk of death.
Model-based estimates of tumor growth inhibition (TGI) metrics to predict for overall survival (OS) in first-line non-small cell lung cancer (NSCLC).
Authors: Claret Laurent , Mancini Pierre , Sebastien Bernard , Veyrat-Follet Christine , Bruno Rene 
Published: March 2020

e19049 Background: A survival model using change in tumor size at week 8 from baseline (CTS) (Clin Pharmacol Ther 86:167-174, 2009) was used to predict OS of the motesanib phase III study in NSCLC (Clin Pharmacol Ther 92:631-634, 2012). However CTS may not fully capture treatment effect on OS. We investigated other TGI metrics to predict OS using historical phase III data. Methods: Various TGI metrics, CTS, time to growth (TTG), and tumor growth rate (G), were estimated using two longitudinal tumor size models (Clin Cancer Res 17:907-917, 2011, PAGE 21 [www.page-meeting.org/?abstract=2328], 2012, JCO in press, 2013) developed from phase III data (1218 1st-line patients with NSCLC treated with doxetaxel (D) plus cisplatin (Cs) or carboplatin (Cb) or vinorelbine (V) plus Cs) (J Clin Oncol, 21:2016-3024, 2003). TGI metrics and baseline prognostic factors were assessed in univariate Cox and multivariate parametric survival models. Alternative models were qualified by simulating OS distributions in 1000 replicates of the phase III study and checking that observed OS distribution belongs to the 95% prediction intervals. Results: In a univariate analysis all TS metrics were strong predictors of OS (p<0.0001). TTG and G were similar and much better than CTS (likelihood ratio test). OS was best described by a log-normal distribution and the influence of the covariates was assessed based on linear regression of the logarithm of OS (days). Parameter estimates of the best multivariate model are shown in the Table. The model was qualified in predicting OS distributions in the 3 arms (D+Cs, D+Cb, V+Cs). Conclusions: With further external validation, this model could be used to analyze longitudinal NSCLC tumor size data and their relationship to OS, in phase II studies of new agents and support end-of-phase-II decisions. [Table: see text]
The association between COX-2 polymorphisms and hematologic toxicity in patients with advanced non-small-cell lung cancer treated with platinum-based chemotherapy.
Authors: Fei Zhou 
Published: March 2020

e19059 Background: Overexpression of COX-2 is thought to contribute to tumor promotion and carcinogenesis through stimulating cell proliferation, inhibiting apoptosis, and enhancing the invasiveness of cancer cells. Apoptosis-related molecules are potential predictive markers of survival and toxicity outcomes for platinum treatment. This study aimed to investigate the association between COX-2 polymorphisms and the occurrence of grade 3 or 4 toxicity in advanced non–small cell lung cancer patients treated with platinum-based chemotherapy. Methods: Two hundred and twelve patients with inoperable stage IIIB-IV receiving first-line chemotherapy between 2007 and 2009 were recruited in this study. Four functional COX-2 polymorphisms were genotyped by PCR-based restriction fragment length polymorphism (RFLP) methods. Results: The incidence of grade 3 or 4 hematologic toxicity was significantly higher in G allele carriers of the COX-2 −1195G/A (rs689466) polymorphism compared to wild-type homozygotes AA (P value = 0.013; odds ratio, 2.30; 95% confidence internal, 1.20-4.42) and still significant after a Bonferroni correction. More statistically significant difference was found in grade 3 or 4 leukocytopenia (P value = 0.010; OR=2.28; 95%CI=1.28-6.05). No other significant association between genotype and toxicity was observed in the study. The haplotype analysis showed the haplotype AGG was associated with a reduced risk of grade 3 or 4 hematologic toxicity (P value= 0.015; OR= 0.61; 95%CI =0.41-0.91) while the haplotype GGG was associated with an increased risk of grade 3 or 4 hematologic toxicity (P value=0.008; OR=1.71; 95%CI=1.15-2.54), global X2= 6.9825, df =2, P = 0.030. Conclusions: This investigation, for the first time, suggests that polymorphism in COX-2 −1195G/A may be a useful bio-marker to predict severe hematologic toxicity in NSCLC patients after platinum-based chemotherapy.
The prognostic value of gene expressions of ERCC1 and RRM1 in non-small cell lung cancer.
Authors: Hasturk Serap , Olgunus Ozlem , Tuli Abdullah , Dundar Ebru , Unlu Emine Ozgur 
Published: March 2020

e19071 Background: Non small cell lung cancer is the most common cause of death due to cancer in the world. The role of ERCC1 and RRM1 genes has been researched in prediction of lung cancer prognosis and response of patients to chemotheraphy. We aimed to evaluate the effects of ERCC1 and RRM1 gene expressions profiles on the prediction of the prognosis and the treatment on bronchoscopy specimens of advanced stage NSCLC patients. Methods: The levels of ERCC1 and RRM1 gene expressions were studied for 76 patients which were diagnosed by bronchoscopic biopsy parafin embedded tissue samples. The RRM1 and ERCC1 gene expression profiles were examined by RT-PCR method. Forty were diagnosed with squamous cell cancer, 24 with adenocarcinoma, 12 with NOS NSCLC. Thirty patients were chemotherapy native, 33 were received gemcitabine-cisplatin and 13 were received docetaxel- cisplatin doublets chemotherapy. Results: The mean age of the patients in the study was 59.8±9.3 (years ± SD). The levels of gene expressions of ERCC1 and RRM1 were found to be 2-9 (median 4.9), and 1.3-17.7 (median 6.8). No significant difference was detected between ERCC1 and RRM1 levels and age, gender, histologic type, ECOG, weight loss when the median gene expression levels were used as cut off value. Also, no significant difference was observed for survival analysis among the patients that have low ERCC1 mRNA level (p=0.41). The level of gene expression of ERCC1 was lower in patients with advanced stage (p=0.06). In addition, no significant difference was detected for the survival analysis within the patients that have the low and high RRM1 mRNA levels (p=0.43). When the survival analyses were evaluated between the patients who had chemotherapy and the ones who did not; no significant difference was detected according to ERCC1 and RRM1 levels. Conclusions: We conclude that the analysis of ERCC1 and RRM1 gene expression profiles based on bronchoscopy obtained samples appeares feasible, but the methodology and cut off points that was used to classify expression level as ‘high’ or ‘low’ would require further optimization. These two gene signature proposed for advanced stage NSCLC may not be useful, particularly not ready for clinical application.
Association of brain metastasis in non-small cell lung cancer.
Authors: Zhao Yu , Guo Huiqin , Lu Jiangyang , Christiani David C. , Lin Xihong , Wang Zhaoxi 
Published: March 2020

e19081 Background: Brain metastases are the main cause of non-small cell lung cancer (NSCLC) relapse and death. However, it is difficult to predict which NSCLC patient will develop brain metastasis. We have observed and summarized the relationship between the clinical and molecular biological features including EGFR mutation status and brain metastases in a prospectively enrolled case series, and developed a multivariable model in this study. Methods: The study enrolled 184 Chinese NSCLC patients with at least 18 months follow-up period. Clinical information including age, smoking history, lymph node status, pathological stage, primary location and histological type of the tumor and EGFR (including exon 19 and 21) and KRAS mutation status were collected and analyzed. Univariate and multivariate Cox regression analysis was run to investigate risk factors of brain metastasis from these features. A risk model based on these risk factors was constructive. Results: 13.0% (24/184) patients were diagnosed as brain metastasis. EGFR mutation (P=0.026), younger age (P=0.034) and lymph node metastasis (P=0.038) were associated with brain metastasis. A Cox model based on these 3 factors was founded and the risk of brain metastasis was 1.9% (1/53), 8.3% (5/60) and 25.4 % (18/71) in low, intermediate and high risk group, respectively (P<0.001). Conclusions: EGFR mutation, younger age and lymph node metastasis are associated with brain metastasis in NSCLC patients. If confirmed in clinical trials, high risk patients may be considered for prophylactic cranial irradiation therapy in future clinical trials
Treatment strategies after failure to reversible tyrosine kinase inhibitors (rTKI) in EGFR mutant (mut) non-small cell lung cancer (NSCLC) patients (p): A retrospective analysis of 41 Spanish p.
Authors: Remon Jordi , Moran Teresa , Alcaraz Diego , Capdevila Laia , Porta Rut , Reguart Noemi , Lianes Pilar , Carcereny Costa Enric , Bosch-Barrera Joaquim , Rosell Rafael 
Published: March 2020

e19089 Background: Different therapeutic approaches have been used in the clinical setting in NSCLC p harbouring EGFR mutations progressing to rTKI, although the standard of care in this situation is still not well established. Methods: A multi-institutional database from four different centers in Spain was review to identify EGFR mut p with acquired resistance to rTKI in order to evaluate the therapeutic strategies after rTKI failure and the effect on the post-progression survival (PPS) of these treatments. Results: 41 p with acquired resistance to rTKI were identified: 63% female; median (m) age 62 ±11 yrs; 95% Caucasian; del19 76%, never or light former smokers 100%; 90.2% adenocarcinomas; 51 % received TKI as first line therapy; 85% were initial stage IV .mPFS for the rTKI was 8.4 months (mo) and mOS was 29.7 mo for the entire population. P were treated with a median of 2 therapeutic strategies after the rTKI failure. 6 therapeutic strategies have been identified. As immediate approach, 16 p were switched to chemotherapy (CT) with a mPPS of 3 mo. 9 p were switched to an irreversible TKI obtaining a mPPS of 3.9 mo. rTKI plus other drug was maintained in 11 p: rTKI plus CT in 9 p with a mPPS of 4 mo and rTKI plus other drug different to CT in 2 with a mPPS of 2 mo. Despite the progression, rTKI was maintained in 2 p considered slow progressors and local therapy, in addition to the rTKI, was administered in 3 p with oligoM1progressive disease obtaining a mPPS of 1.4 and 36 mo, respectively. 8 p were treated sequentially with ≥5 strategies. These p attained a mOS of 27.7 mo. Conclusions: The combination of different strategies when treating EGFR mut p after rTKI failure may impact the survival especially when p are candidates to receive some of this treatments sequentially. These strategies may reflect different subsets of EGFR mut disease.