bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of life and safety profile of pemetrexed-platinum doublet in Indian adult chemo-naive NSCLC patients.
Authors: Gota Vikram , Kavathiya Krunal Vasant , E Damodaran S , Joshi Amit , Noronha Vanita , Prabhash Kumar 
Published: March 2020

e19118 Background: Pemetrexed in combination with cisplatin or carboplatin is commonly recommended for the first-line treatment of patients with locally advanced or metastatic NSCLC of adenocarcinoma histology. The present study explores the safety and the impact of this doublet on the quality of life in adult Indian NSCLC patients. Methods: Patients were enrolled from a single tertiary care cancer hospital in India. Patients were administered pemetrexed 500 mg/m2, cisplatin 75 mg/m2or carboplatin AUC 5 every 3 weekly. All patients received standard folate and Vitamin B12 supplementation. Premedication included dexamethasone, granisetron and ranitidine. Quality of Life (QoL) data was collected at baseline and at completion of 3 cycles using EORTC QLQ-C30 (version 3) and QLQ- LC13 questionnaires. Toxicity was graded using CTCAE v. 4.03. Results: Twenty seven patients were enrolled on the study since July 2012.Twenty received carboplatin and seven received cisplatin. Mean age of the participants was 54.7 years (SD=9.58) with stage (IV=25; III A/B=2) and ECOG performance status (0=1; 1=17; and 2=9). Pemetrexed–platinum doublet caused significant improvement in Global Health Status and dyspnea score at 3 cycles compared to baseline (Table). The treatment also caused marked improvement in the physical function, emotional function, cognitive function and insomnia scales, although not statistically significant (Table). No significant difference compared to baseline was observed for other parameters. Grade 3/4 toxicities include anemia (3), neutropenia (3), hyponatremia (6), vomiting), diarrhea, and dyspnea (1 each). Conclusions: Pemetrexed-platinum doublet was well tolerated and markedly improved the global health status and dyspnoea at the end of three cycles. A higher incidence of hyponatreemia was observed in our cohort that needs to be investigated further. [Table: see text]
Factors associated with survival in non-small cell lung cancer (NSCLC) patients with a solitary metastasis.
Authors: Parikh Ravi , Cronin Angel , Kozono David E. , Oxnard Geoffrey R. , Mak Raymond H. , Jackman David Michael , Lo Peter C. , Baldini Elizabeth H. , Johnson Bruce E. , Chen Aileen B. 
Published: March 2020

e19121 Background: Although palliative chemotherapy is the standard of care for metastatic NSCLC, somepatients with oligometastatic disease may benefit from aggressive local therapy. We investigated factors associated with greater survival among patients diagnosed with a solitary metastatic lesion. Methods: We identified patients diagnosed with stage IV NSCLC who presented with a solitary metastatic lesion based on PET and MRI and who were prospectively consented and enrolled in our institutional database from 2002-2011. Univariable and multivariable Cox proportional hazards models were used to analyze factors associated with overall survival among this cohort. Results: We identified 110 patients (10.7% of stage IV patients) meeting our inclusion criteria. Median age at diagnosis was 61 years, 50% of patients were female, 66% had adenocarcinoma histology, and 35% had N0-1 disease. Median survival from diagnosis was 18.7 months, with a median followup of 31.5 months. On univariable analysis, greater overall survival was associated with ECOG performance status 0-1 vs 2+ (median 21.5 months vs 12.6 months, HR 0.32, p<0.01); weight loss <2 vs >2 kg (22.4 vs 13.8, HR 0.56, p=0.03); and N stage 0-1 vs 2-3 (32.0 vs 17.6, HR 0.52, p=0.02). Adenocarcinoma vs non-adenocarcinoma histology (22.9 vs 13.8, HR 0.65, p=0.07) was borderline significant. Age, gender, race, current smoking, size of primary tumor, and metastatic organ were not significantly associated with survival. On multivariable analysis, adenocarcinoma histology (HR= 0.58, p=0.06); N stage 0-1 (HR= 0.43, p=0.01); and weight loss <2 kg (HR 0.53, p=0.03) were associated with greater overall survival. Conclusions: Select patient and tumor characteristics may predict for improved survival among patients with oligometastatic NSCLC. Future studies will evaluate the impact of aggressive local therapy in these patients.
A survey on Japanese thoracic oncologists’ preference on treatment strategy for EGFR-mutant or EML4-ALK-mutant non-small cell lung cancer (NSCLC).
Authors: Hotta Katsuyuki , Kiura Katsuyuki , Tabata Masarhiro , Takigawa Nagio , Tanimoto Mitsune , Ueoka Hiroshi 
Published: March 2020

e19124 Background: NSCLC pts have become categorized based on two genetic alterations in their tumors, EGFR and EML4-ALK, to provide personalized therapy. In EGFR-mutant NSCLC, EGFR-TKI yields a comparable survival with platinum-based chemotherapy, suggesting either of them can be initiated first, and its choice seems to depend partly on oncologists’ preference. As for the other, EML4-ALK, NCCN guideline recommends first-line crizotinib use despite no relevant survival data. The decision whether to choose crizotinib might be also influenced by oncologists’ preference. We here assessed their preference. Methods: The Japanese thoracic oncologists were asked to complete a self-administered questionnaire at the Japanese meeting specific for thoracic oncology. Results: Of 3,046 subjects, 871 (29%) responded voluntarily to a survey, mainly consisting of medical and surgical oncologists (93%). Majority considered EGFR mutation status should be checked at the time of diagnosis (89%), whereas only 60% and 33% reported EML4-ALK gene status would be assessed at the time of diagnosis and until the initiation of second-line setting, respectively. The subjects also considered pts with EGFR-wild-typed tumor and pts with clinical characteristics possibly related to EML4-ALK rearrangement should selectively receive EML4-ALK gene status check rather than all NSCLC pts (57%, 22% and 16%, respectively). Among the subjects, 52% preferred to choose gefitinib rather than platinum in the first-line setting in EGFR-mutant NSCLC, whilst 44% preferred crizotinib to platinum in the first-line setting in EML4-ALK-positive NSCLC. The major reasons why they chose gefitinib in EGFR-mutant NSCLC were ‘PFS is better’ (36%) and ‘it is easy to improve QOL’ (25%), whereas ‘PFS is better’ (43%), and ‘I want to prescribe when patients are still in good condition’ (19%) were the predominant reasons for choosing crizotinib in EML4-ALK-positive NSCLC. Conclusions: About half of the subjects preferred each molecular-targeted agent to the conventional cytotoxic chemotherapy in first-line setting. They considered better PFS was important in the treatment of EGFR-mutant or EML4-ALK-mutant NSCLC.
Immunohistochemistry to detect EGFR mutation and ALK gene rearrangement in NSCLC bronchoscopic specimens.
Authors: Wang Mengzhao , Pan Qing qing , Zhu Pei 
Published: March 2020

e19135 Background: The discovery of the E746-A750 and L858R antibodies for mutated epidermal growth factor receptor (EGFR) and the D5F3 antibody for the product of the rearranged anaplastic lymphoma kinase (ALK) gene enables immunohistochemistry(IHC) to be applied to the identification of lung cancer. This study aimed to explore the effectiveness of IHC in small specimens and compare it with standard methods. Methods: We collected bronchoscopic specimens of lung adenocarcinoma that were confirmed by pathology; gathered clinical information, including the basic characteristics of patients, staging and differentiation of the tumor, and the amount and proportion of tumor cells; identified mutant EGFR with E746-A750del and L858R antibodies and rearranged ALK with D5F3 antibody (Cell Signaling Technology, USA); and compared their sensitivity and specificity with standard methods. Results: We collected 92 patients¡&hibar; bronchoscopic specimens. All specimens were successfully detected by the Scorpions-ARMS method£€and exon 19 deletion occurred in 15 specimens (16.3%), and exon 21 L858R mutation in 15 specimens (16.3%). In EGFR-IHC, the positive rates of E746-A750del and L858R were 17.8% (16/92) and 21.4% (19/92), respectively. The sensitivity and specificity of E746-A750del (with Scorpions-amplification refractory mutation system (ARMS) as the standard) were 73.3% (11/15) and 93.3% (70/75), respectively, and those of L858R were 93.3% (14/15) and 93.2% (69/74). Neither method was significantly worse than Scorpions-ARMS (p£½1.000 for E746-A750del, p£½0.219 for L858R). FISH detected 6 positive and 71 negative specimens for ALK rearrangement; the other 15 could not be evaluated for various different reasons. In ALK-IHC, the positive rate was 7.8% (6/77; 13 could not be evaluated). The sensitivity and specificity of D5F3 were 50% (3/6) and 100% (71/71), respectively. ALK-IHC showed no difference with the standard method of fluorescence in situ hybridization (FISH). Conclusions: IHC with E746-A750del and L858R antibodies is an economical and convenient method for EGFR mutation detection in small specimens of NSCLC, as is D5F3 monoclonal antibody for ALK-IHC, especially for the primary screening.
Pulmonary blastoma: A clinicopathologic study of three cases.
Authors: Sandoval-Sus Jose D , Hansra Damien Mikael , Cioffi Lavina Maureen , Patel Ravi , Ponce Mario , Santos Edgardo S , Ikpatt Offiong F 
Published: March 2020

e19140 Background: Pulmonary blastoma (PB) is a rare biphasic neoplasm representing 0.2-0.5% of pulmonary malignancies. Presentation ranges from asymptomatic to symptoms of advanced pulmonary tumors. Surgery is the preferred treatment with no consensus on the role of other adjuvant therapies. Methods: We report the clinicopathologic features of PB in 3 patients (pts). Retrospective review of medical records of pts diagnosed with PB at Jackson Memorial Hospital, Miami, FL since 2009. Staging performed using the 2009 AJCC system for NSCLC. Cases required pathological diagnosis before inclusion. Variables analyzed were demographics, clinicopathologic presentation, treatments and outcomes. Results: Mean age at diagnosis was 53 years old; 2 were male; Hispanic and Caucasian and 1 African American female. Both males were heavy smokers. At diagnosis, all cases were symptomatic; 1 had hypercalcemia of 12.9 mg/dL and 2 were stage IV with metastatic disease (bone and thyroid). 2/3 where treated with surgical resection and both achieved complete remission (CR); Pt with stage IV and resection relapsed in 28 months, received chemotherapy (3 cycles cisplatin/docetaxel) with progressive disease then radiation (37 Gy) without response and died. The other surgical patient remains in CR. The patient with unresectable disease received chemotherapy (6 cycles carboplatin/docetaxel) attaining partial remission. 2/3 patients remain alive at end of this study. Pathologically, all cases showed biphasic morphology composed of multiple glandular structures with atypical pseudostratified columnar epithelium and cellular stromal component. Immunohistochemical analysis revealed positivity in all cases for thyroid transcription factor (TTF-1), keratin, and epithelial membrane antigen (EMA) in the glandular component. Conclusions: All pts were symptomatic at diagnosis and 2 presented with metastatic disease. All pts had similar morphologically and immunophenotypically. Surgery was the most beneficial intervention in regard to CR and PFS. Chemotherapy has shown mixed responses, thus, larger studies are needed to define the role of chemotherapy in the adjuvant and palliative settings.
A phase I feasability study of concurrent fondaparinux (F) with carboplatin (Crb) and paclitaxel (P) for metastatic non-small cell lung cancer (NSCLC): An analysis of coagulation/angiogenic biomarker (CABM) kinetics.
Authors: Mooney David James , Miley Debi , Jerome Mary , Grant Stefan C. , Robert Francisco 
Published: March 2020

e19143 Background: There is an association between risk of thrombosis and metastatic cancer. Chemotherapy (C) also independently increases thrombotic risk. This increased risk is multifactorial, including endothelial damage and release of angiogenic cytokines. We hypothesized that adding anticoagulation to C may decrease thrombotic risk and also, potentially, have anti-tumor effect. Methods: The primary aim of this study was to determine the tolerability and safety (bleeding events) of the combination of F with 21-day cycle chemotherapy (Crb AUC 6 + P 200 mg/m2) in two cohorts of untreated patients (pts) with stage IV NSCLC. The secondary objectives were to determine incidence of venous thrombosis (VT), changes in CABM parameters during treatment, and clinical efficacy endpoints. Two cohorts of pts received F from cycles 2-4 with Crb+P. Cohort A received 2.5 mg F daily from cycle 2-4. Cohort B received 7.5 mg of F on day 1, 2 of cycle 2-4 and 2.5 mg F on day 3-21. Results: Clinical data from 19 evaluable pts are as follows: median age 55 years, 63% male, and 32% adenocarcinoma. There was no major bleeding event (BE) in either cohort, and 5 pts had a minor BE. There was no VT. Median time to progression was 5 months (3.8-6.2 months), and overall survival was 10 months (4.3-15.6 months). Baseline values of sensitive markers of activated coagulation (D-Dimer, Thrombin Anti-Thrombin Complex) were above the normal range in most patients. These biomarkers tended to increase during the first cycle (without F); whereas the same markers decreased during the second cycle (with F). A reduction of the angiogenic biomarkers during therapy was observed with VEGF, TGF-β1, and Angiopoietin-1. Conclusions: Concurrent treatment with F and chemotherapy for metastatic NSCLC is feasible with no major bleeding and little minor bleeding. During chemotherapy, coagulant and angiogenic biomarkers tended to increase, perhaps suggesting an increase in thrombogenic state. When F was added, these markers trended downward, suggesting that the proangiogenic state associated with cancer may be significantly altered by anticoagulation. Clinical trial information: NCT00476216.
Risk of interstitial lung disease with gefitinib and erlotinib in advanced non-small cell lung cancer: A systematic review and meta-analysis of clinical trials.
Authors: Shi Liang , Liu Zhe , Tang Junfang , Tong Li 
Published: March 2020

e19149 Background: Gefitinib and erlotinib are oral EGFR-TKIs widely used in advanced NSCLC. The reported incidence and risk of interstitial lung disease (ILD) events associated with gefitinib and erlotinib varies widely and has been inconsistently reported in trials. Therefore, we performed a systematic review and meta-analysis to determine the incidence and the relative risk (RR) associated with the use of gefitinib and erlotinib. Methods: PubMed databases were searched for articles published from January 2000 to October 2012, and abstracts from ASCO and ESMO meetings (2000-2012) were searched for relevant studies. Eligible studies included randomized controlled trials with gefitinib and erlotinib in advanced NSCLC patients. Summary incidence rates, RRs, and 95% CIs were calculated using fixed-effects or random-effects models, depending on the heterogeneity of the included studies. Results: 15,618 patients from 29 randomized controlled trials were selected for this meta-analysis. The overall incidence for all-grade ILD events was 1.2% (95% CI, 0.9% to 1.6%) among patients receiving gefitinib and erlotinib, with a mortality of 22.8% (95% CI, 14.6% to 31.0%). The summary incidence of fatal ILD events was 0.2% (95% CI, 0.1% to 0.3%) in 26 trials with available data. Compared with controls, the RR of all-grade and fatal ILD events was 1.53 (95% CI, 1.13 to 2.08; P = 0.006) and 1.96 (95% CI, 1.03 to 3.72, P = 0.041), respectively. After stratifying patients by study location (Asian versus non-Asian), the RR of all-grade ILD events was 2.00 (95% CI, 1.23 to 3.25) and 1.30 (95% CI, 0.88 to 1.91) for Asian studies and non-Asian studies, respectively. The analysis was also stratified for drug type, trial phase, treatment line, and studies quality, but no significant differences in RRs were observed in all subgroup analyses. Conclusions: Treatment with EGFR-TKIs gefitinib and erlotinib is associated with a significant increase in the risk of developing both all-grade and fatal ILD events in advanced NSCLC.
Efficient detection of EGFR, KRAS, and BRAF mutations in cell-free DNA from pleural effusions.
Authors: Sagan Christine , Vallee Audrey , Denis Marc G. 
Published: March 2020

e19151 Background: Detection of EGFR gene alterations is critical for predicting the response to tyrosine kinase inhibitors in patients with non-small-cell lung cancer. Analysis of other biomarkers might also be mandatory in the future, requiring more biological material. In routine practice, molecular testing is usually performed on tissues such as bronchial or transthoracic biopsies and surgical resections. We investigated the feasibility of using both cytology cell blocks and cell-free DNA from pleural effusions. Methods: Pleural effusion samples were centrifuged to form a pellet, fixed in formaldehyde, and processed as a cell block. DNA was extracted from 10-µm sections after paraffin removal using the Forensic kit and an iPrep system (Invitrogen). Cell-free DNA was extracted from the centrifugation supernatants using the QIAamp Circulating Nucleic Acid kit (Qiagen). Detection of molecular alterations were performed by allele-specific PCR (EGFR p.L858R mutation, BRAF p.V600E mutation), fragment size analysis (EGFR exon 19 deletions), and Sanger sequencing (KRAS mutations, codons 12 and 13). Results: Between January 2010 and December 2012, we tested 65 cell pellets (32 women and 33 men) and collected 34 paired supernatants. With the cell pellets, all the EGFR status were successfully determined (13 mutations; 20%), 9 mutations of KRAS on the 42 cases sequenced (17.6%), and 2 BRAF mutations on the 50 samples tested (4%) were found. We next investigated the potential use of the cell-free DNA from supernatants. Quantification by real-time PCR revealed significant amounts of DNA (mean = 306 ng extracted from 2 ml). EGFR, KRAS and BRAF tests were contributive for all these samples: 2 EGFR p.L858R mutations, 6 KRAS mutation (p.G12C, n=2; p.G12D, n=2; p.G13C, n=1 and p.G12F, n=1) and 1 BRAF p.V600E mutation were found. Most interestingly, the molecular status of the cell-free DNAs perfectly matched those obtained with the corresponding cell pellets. Conclusions: Pleural effusions provide high quality material for molecular testing and are suitable samples for routine practice. Cell-free DNA can also be successfully tested thus saving material for morphological / immunohistochemical / FISH analysis.
Clinical significance of ERCC2 haplotype-tagging single nucleotide polymorphisms in patients with unresectable non-small cell lung cancer treated with first-line platinum-based chemotherapy.
Authors: Kim Seok-Hyun , Lee Gyeong-won , Jeong Yi Yeong , Kim Ho-Cheol , Lee Jong Deog , Hwang Young Sil , Kim In-Suk , Lee Suee , Oh Sung Yong 
Published: March 2020

e19156 Background: DNA repair pathway is a crucial molecular mechanism potentially involved in resistance to platinum-based chemotherapy in the unresectable non-small cell lung cancer. Furthermore, single nucleotide polymorphisms (SNPs) and haplotypes in the ERCC2 gene are thought to be associated with the risk of developing lung cancer and clinical outcomes. Methods: We genotyped 8 ERCC2 htSNPs for 129 unresectable NSCLC (stage IIIA, 12; stage III, 36; stage IV, 82) cases treated with first-line platinum-based chemotherapy. Clinical characteristics, treatment outcomes, and predictive value of htSNPs in patient response, survival, and chemotherapy-related adverse events were analyzed according to each ERCC2 htSNP using chi-square test, Kaplan-Meier method, and Cox proportional hazard model. Results: No differences were observed in patient or disease characteristics and response according to ERCC2 htSNPs. In a survival analysis, rs50872 was significantly related to overall survival (OS) (log-rank test, p=0.014). The median survival duration of rs50872 G/G, A/G, and A/A genotypes was 35.75 (95% confidence interval [CI] 21.05-50.45), 36.07 (hazard ratio[HR] 1.02, 95% CI 25.20-46.94), and 16.75 (HR 3.49, 95% CI 5.73-27.77) months, respectively. A significant association was observed between grade 3-4 infections and poor survival: OS in patients with a grade 0-2 infection: 35.75 months (95% CI 28.15-43.35); OS in patients with a grade 3-4 infection: 12.86 months (95% CI 8.99-16.72, HR 3.57) (log-rank test, p<0.001). In a subgroup analysis, rs238405 genotype was significantly related to OS in the taxane-based group. However, rs238416 genotype was significantly associated with OS in the gemcitabine-based group. Conclusions: ERCC2 htSNPs rs50872 (overall), rs238405 (taxane-based group), and rs238416 (gemcitabine-based group) and infection related to first-line chemotherapy were associated with OS in unresectable NSCLC patients treated with first-line platinum-based chemotherapy. However, additional large prospective studies focusing on the role of ERCC2 htSNPs in unresectable NSCLC are needed.
Evaluation of spot urine protein to creatinine ratio and 24-hour urine protein quantification for proteinuria in patients with plasma cell dyscrasia.
Authors: Apuri Susmitha , Nishihori Taiga , Lin Karen Yin , Baz Rachid C. , Kim Jongphil , Shain Kenneth H. , Doumit Elias , Ochoa-Bayona Jose L. , Sullivan Daniel , Alsina Melissa , Djulbegovic Benjamin 
Published: March 2020

e19516 Background: Though cumbersome, a 24-hour urine collection remains crucial for diagnosis and monitoring in plasma cell dyscrasias (PCD). Nephrology guidelines recommend replacement of 24-hour urine collection with spot urine protein/creatinine (Pr/Cr) ratio for proteinuria. Only limited data exist on accuracy of spot urine Pr/Cr ratio in PCD. Methods: From 04/2012 to 01/2013, a total of 67 PCD patients were prospectively enrolled. Oliguria or dialysis were considered ineligible. Spot urine was collected on the day of 24-hour urine collection. Spot urine Pr/Cr ratios were compared to 24-hour urine on (1) total protein and (2) monoclonal protein (M-spike). Results: Fifty-two of 67 patients were evaluable (missing samples in 9; no Pr/Cr ratios in 4; protein below the level of detection in 2). A median age was 66 (range, 36 - 82), 62% were male, and 81% were Caucasian. Primary diagnoses were myeloma (n=47), amyloidosis (n=2), plasmacytoma (n=2), and MGUS (n=1). Comorbidities included hypertension (58%), chronic kidney disease (27%), diabetes (19%), and congestive heart failure (2%). A median serum creatinine was 0.9 mg/dL (range, 0.5 - 5.1). A median spot urine Pr/Cr ratio was 140 mg/g creatinine (range, 32 - 21,447), a median 24-hour urine protein was 130 mg (range, 31 - 15,092: n=49), and a median urine M-spike was 1.9 mg (range, 0 - 8,099). Most spot urine samples were collected in the morning (65%). There were strong correlations between (1) spot urine Pr/Cr ratio and 24-hour total urine protein (Spearman correlation coefficient=0.91, p < 0.0001), and (2) spot urine Pr/Cr ratio and 24-hour urine M-spike (Spearman correlation coefficient=0.73, p < 0.0001). The timing of spot urine sample collection had no significant effect (p = 0.274 by Wilcoxon rank-sum test). Conclusions: Spot urine Pr/Cr ratio strongly correlates with proteinuria measured in 24-hour urine collection and may predict the quantity of urine M-spike in non-oliguric PCD population. Spot urine Pr/Cr ratio may be useful as a monitoring tool for estimation of proteinuria. The study is ongoing and updated result will be provided.