bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why did the gender difference influence survival in patients with completely resected stage I adenocarcinoma of the lung?
Authors: Tsuboi M. , Kato H. , Ichinose Y. , Ohta M. , Hata E. , Tsubota N. , Tada H. , Wada H. , Hamajima N. 
Published: March 2020

7647 Background: This study evaluates the influence of gender on survival and tumor recurrence in patients with completely resected stage IA and IB adenocarcinoma of the lung based on the analysis of the Japan Lung Cancer Research Group trial, which was a randomized prospective study of adjuvant chemotherapy with uracil-tegaful for stage I pulmonary adenocarcinoma. Methods: Patients were randomized to receive either oral uracil-tegaful (250 mg of tegaful/m2/day) for 2 years postoperatively or no adjuvant treatment. Survival was calculated from randomization until death. Survival estimated using the Kaplan-Meier method, and difference in survival between two groups was compares with the log-rank test. Results: The 5-year survival rate was 88.9% for the 502 women and 84.3% for the 477 men (median follow-up 72 months, p=0.0066). The relative risk of death for men vs women was 0.658 (95% C.I., 0.476–0.910, p=0.011), although the mean age of men was significantly less than that of women (p=0.041). There was no interaction between the gender differences and the efficacy of uracil-tegaful (p=0.657). However men presented with significantly more preoperative complications, more T2 diseases (p=0.0006), less non-papillary growth for histology (p=0.0078), less well differentiated subtype (p<0.001), higher serum carcinoembryonic antigen (CEA) level (p=0.004), and more smoking history than women (p<0.0001). Disease recurrence patterns were similar between the genders. The postoperative mortality showed a tendency to go up in men. Conclusions: Although longer life expectancy for women in Japan may in part explain, gender influences survival after complete resection for stage IA-B lung adenocarcinoma. The reasons for prolonged survival of women with this disease may be related to the several differences in the distribution of preoperative complications, smoking history and tumor biological behaviors such as T descriptor, histologic subtype, and serum CEA level. However cause- specific mortality was difficult to be explained. Further molecular epidemiologic and molecular profiling studies regarding gender as a prognostic and predictive factor for survival should be done. No significant financial relationships to disclose.
IND.175: Phase I study of daily oral AZD2171, a vascular endothelial growth factor receptor inhibitor (VEGFRI), in combination with gemcitabine and cisplatin (G/C) in patients with advanced non-small cell lung cancer (ANSCLC): A study of the NCIC Clinical Trials Group
Authors: Goss G. D. , Laurie S. , Shepherd F. , Leighl N. , Chen E. , Gauthier I. , Reaume N. , Feld R. , Powers J. , Seymour L. 
Published: March 2020

7649 Background: AZD2171 is an oral an inhibitor of the tyrosine kinase activity of all VEGFR subtypes. Objectives: To determine recommended phase II dose (RPTD), dose limiting toxicity (DLT), toxicity, pharmacokinetics and efficacy of AZD2171 with G/C, in pts with untreated ANSCLC. Methods: Eligibility: stage IIIB/IV NSCLC; PS 0–2; no prior chemotherapy (CT) for advanced disease; adequate hematological, biochemical and end-organ function; no significant hemoptysis or bleeding. Treated stable brain metastases were permitted. G 1,250 mg/m2 day 1 & 8 and C 80 mg/m2 day 1 was given q3 weekly with AZD2171 starting day 2 cycle 1. Planned dose levels (DL) of AZD2171 were 30 and 45 mg once daily PK assayed in cycle 1&2, response (RECIST) every 2nd cycle. Results: 14 pts enrolled. 30 mg (5 pts) and 45 mg (9 pts). Pt characteristics (n=13) median age 56; 11 PS 0–1; 9 males. No DLTs seen in initial 3 pts at 30 mg dose; nor in 9 pts at 45 mg dose. Actual median dose intensity for AZD2171 in cycle 1 (C1) was similar to planned in C1 for both DL (200 mg and 300 mg)), but was higher for 30 mg vs 45 mg for subsequent cycles (150 mg vs 134 mg). At the 45 mg DL 13 dose reductions occurred in 9 pts. Grade 3 adverse events occurred in 2 of 3 30 mg pts (1 hypertension (HT), 1 fatigue); at 45 mg 6 pts of 9 pts had grade 3 events (HT, fatigue, diarrhea, voice changes); 2 pts had grade 4 toxicity (1 reversible CNS ischemia, 1 fatigue). PK: no effect of AZD2171 on gemcitabine PK Objective response: 9 pts are evaluable (4 too early At 30 mg-PR 2, SD 1; at 45 mg-PR 3, SD 3. 2 additional patients were accrued at the 30 mg DL. Conclusions: Toxicities of this combination are manageable and predictable. HT was easily controlled with a standardized treatment algorithm. MTD was not reached at the 30 or 45mg dose level, but 30mg of AZD2171 appears better tolerated in combination with G/C and is suggested as the RPTD. Encouraging anti-tumor activity has been observed which does not appear dose dependent at the doses tested. No significant financial relationships to disclose.
Multivariate analysis of prognostic variables associated with survival from a phase III study of cisplatin (P) plus etoposide (E) plus chest radiation (XRT) with or without consolidation docetaxel (D) in patients with unresectable stage III non-small cell lung cancer (NSCLC)
Authors: Ademuyiwa F. O. , Breen T. E. , Johnson C. , White A. , Yiannoutsos C. , Hanna N. 
Published: March 2020

7668 Background: Concurrent chemoradiation is standard treatment against stage III NSCLC. HOG LUN 01–24 examines whether consolidation therapy with D improves overall survival. We present an analysis investigating the association of patient characteristics with overall survival from patients on this study. Methods: Eligible patients had untreated stage III NSCLC, FEV1 ≥ 1 liter, PS of 0–1, and weight loss < 5%. Patients received P 50 mg/m2 days 1, 8, 29, 36 with E 50 mg/m2 days 1–5, 29–33, and concurrent 5,940 cGy XRT. Patients with non-progressive disease were randomized to D 75 mg/m2 q3wk X 3 cycles vs observation. A multivariable parametric accelerated failure time model was performed to identify factors that affected survival and to estimate the treatment effect adjusting for these factors. Results: A multivariate analysis was performed on 203 patients who were the subject of a DSMB interim analysis. Median follow up was 25.6 months. Variables analyzed included age (<70 vs ≥ 70), sex, race, body mass index, PS (0 vs 1), FEV-1 (> 2 vs ≤ 2), smoking status, hemoglobin (≥12 vs <12), and stage. A multivariable parametric accelerated failure time model demonstrated the association of age <70 vs =70 years (p=0.0447), FEV1 >2 vs =2 (p=0.0153), and pre-treatment hemoglobin values (p=0.0083) as independent prognostic factors for overall survival. The median survival for hemoglobin <12 was 16.8 vs 21.5 months for hemoglobin ≥12 (p=0.0432). Similarly, the median survival with FEV >2L was 21.6 vs 18.9 months for FEV =2 L. Survival was not significantly influenced by smoking status, sex, race, PS, stage, or BMI. Conclusions: This analysis suggests that age <70, FEV-1 >2L and higher pre-treatment hemoglobin values are associated with improved overall survival in patients with stage III NSCLC. No significant financial relationships to disclose.
Risk of intracranial hemorrhage and cerebrovascular accidents in non-small cell lung cancer brain metastasis patients
Authors: Srivastava G. , Rana V. , Taylor S. , Debnam M. , Huang Y. , Feng L. , Suki D. , Karp D. , Stewart D. , Oh Y. 
Published: March 2020

7671 Background: Brain metastases confer significant morbidity and a poorer survival in non-small cell lung cancer (NSCLC). Vascular endothelial growth factor-targeted antiangiogenic therapies (AAT) have demonstrated benefit for patients with metastatic NSCLC and are expected to directly inhibit the pathophysiology and morbidity of brain metastases, yet patients with brain metastases have been excluded from most clinical trials of AAT for fear of intracranial hemorrhage (ICH). This is a low suspected risk, but needs to be quantitated to plan clinical trials of AAT for NSCLC brain metastases. Methods: Data from MD Anderson Cancer Center Tumor Registry and electronic medical records from January 1998 to March 2006 was interrogated. 2143 patients with metastatic NSCLC registering from Jan 1998 to Sept 2005 were followed till March 2006. 776 patients with and 1367 patients without brain metastases were followed till death, date of ICH, or last date of study, whichever occurred first. Results: The incidence of ICH seemed to be higher in those with brain metastasis compared to those without. However, the rates of symptomatic ICH were not significantly different. All ICH patients with brain metastasis had received radiation therapy for them and were not anticoagulated. Most of the brain metastasis-associated ICH's were asymptomatic, detected during radiologic surveillance. The rates of symptomatic ICH, or cerebrovascular accidents were similar and not significantly different between the two groups. The following table depicts the rates of CVA and/or ICH in metastatic NSCLC patients. Conclusions: In metastatic NSCLC patients, the incidence of spontaneous ICH appeared to be higher in those with brain metastases compared to those without, but was very low in both groups nonetheless without a statistically significant difference. These data suggest minimal risk of clinically significant ICH for NSCLC brain metastasis patients and justifies for them clinical trials of AAT. No significant financial relationships to disclose. [Table: see text]
Cost-effectiveness analysis (CEA) of third-line erlotinib therapy compared to best supportive care for advanced non-small cell lung cancer (NSCLC) in British Columbia (BC)
Authors: van der Hoek K. , Taylor S. C. , Peacock S. , Johnston K. , Melosky B. L. 
Published: March 2020

7678 Background: Erlotinib was approved for funding as a systemic therapy treatment for 3rd line management of advanced NSCLC by the BC Cancer Agency (BCCA) in April 2004. BCCA patient outcome and cost data are routinely collected to verify the therapeutic effectiveness and cost-effectiveness of systemic treatment policies. Methods: This was a pragmatic retrospective analysis of all patients who received 3rd line erlotinib compared to a historical group treated with 2nd-line docetaxel then no further active treatment, both according to BCCA protocol. The primary end-point was cost-effectiveness, measured in terms of cost per-life-year-gained. Secondary end-points included: median overall survival (MOS); overall survival (OS) at 1 year; and comparison to phase III efficacy results. Data was retrieved from the Cancer Agency Information System (CAIS) and Systemic Therapy Data Warehouse. Life-years- gained were calculated from the area under the survival function curve. CEA took the BCCA perspective and costs included all direct drug costs for treatment of advanced disease. Sensitivity analyses included varying life expectancy across its 95% CI, cost to the extremes of ranges, and start date for length of survival: method 1. progression after 2nd line therapy or 3 weeks post last dose of chemotherapy for control group and start date of erlotinib for treatment group; method 2. last date of 2nd line therapy for both groups Results: 75 control and 70 erlotinib patients were included in the analysis. Results are presented in the table . The Incremental Cost-Effectiveness Ratio (ICER) was $28,516 per life-year-gained under method 1, and $17,632 under method 2. The erlotinib group had similar 1-year OS compared to literature (36 vs. 31%). Conclusions: Erlotinib appears to be cost-effective in terms of life-expectancy under a range of assumptions. No significant financial relationships to disclose. [Table: see text]
Randomized phase II study of erlotinib alone and in combination with bortezomib in previously treated advanced non-small cell lung cancer (NSCLC)
Authors: Lynch T. J. , Fenton D. W. , Hirsh V. , Bodkin D. J. , Middleman E. , Chiappori A. , Halmos B. , Liu H. , Eton O. , Shepherd W. F. 
Published: March 2020

7680 Background: Treatment options for previously treated NSCLC are limited, warranting consideration of novel combinations. This study evaluated the activity and toxicity of erlotinib with bortezomib, a proteasome inhibitor. Dosing was based on the approved indication for erlotinib and on phase I data for the combination. Methods: Patients (pts) with Stage IIIB/IV NSCLC who progressed following one prior line of chemotherapy, with no prior exposure to an EGF-receptor inhibitor and ECOG performance status 0 or 1 were randomly assigned to erlotinib 150 mg po daily alone (arm A) or in combination with bortezomib 1.6 mg/m2 iv on days 1 and 8 (arm B) of a 21-day cycle. Response was evaluated by RECIST and toxicity was graded using NCI CTCAE 3.0. A Simon optimal two-stage design was used to evaluate anti-tumor activity in response-evaluable pts. Results: Fifty pts were treated at 17 sites (January-June 2006); baseline characteristics and treatment intensity were comparable in both arms. Among 24 response-evaluable pts in each arm, there were 3 partial responses (PR) and 1 complete response in arm A and 2 PR in arm B. Median progression-free survival (PFS) was 2.7 and 1.4 months in arms A and B, respectively. The study was halted as required at the planned interim analysis due to insufficient clinical activity in arm B. Activity and toxicity in arm A were consistent with published reports for erlotinib alone. Adverse-event profiles were as expected in both arms, with no significant additivity. In arm B, one pt died of pneumonia. The most common grade 3 treatment-related toxicity was skin rash (12% arm A and 8% arm B), and rash severity correlated with PFS: grades 2/3, 2.8 months PFS (20 pts); grades 0/1, 1.4 months PFS (28 pts), p=0.032. In arm B, one pt each had grade 3 anorexia, hypokalemia, and worsened peripheral sensory neuropathy compared with baseline. There were no grade 4 treatment related toxicities in either arm. Conclusions: The combination of erlotinib and bortezomib in the doses and schedules used in this trial was well tolerated but did not show sufficient activity at this dose and schedule to warrant further development. No significant financial relationships to disclose.
Enhanced detection of EGFR mutations in plasma from non-small cell lung cancer (NSCLC) patients using Scorpion primers
Authors: Holland W. , Davies A. M. , Farneth N. C. , Gautschi O. , Lara P. N. , Gandara D. R. , Mack P. C. 
Published: March 2020

7682 Background: Activating epidermal growth factor receptor (EGFR) mutations identified in NSCLC patient tumors are often associated with rapid and profound response to EGFR tyrosine kinase inhibitors (TKIs). Conventional detection methods are cumbersome and may underestimate mutations frequencies due to limited sensitivity. We and others have shown that tumor-specific mutations such as KRAS can be detected in tumor DNA shed into patient plasma (Kimura, Ann N Y Acad Sci, 2004). Here we describe the performance of an allele- specific real-time PCR system utilizing Scorpion primers (kindly provided by DxS, UK) to detect EGFR mutations in plasma. Methods: DNA was extracted from archival tumor blocks, slides and plasma obtained from consenting patients. In order to determine the sensitivity of this technique both in terms of the ratio of mutant-to-wild-type genomic DNA as well as the minimum amount of DNA required for detection, a dilution experiment was conducted. Genomic DNA from cell lines containing either the exon 21 L858R point mutation or the exon 21 E746–750 deletion was diluted with wild-type genomic DNA at ratios ranging from 1:2 to 1:10,000. Clinical specimens including plasma and/or tissue from 35 advanced stage NSCLC patients treated with EGFR-TKIs were examined. Results: Mutant DNA was successfully detected when it comprised as little as 0.1% of the total sample or as low as 25 pg of mutant-positive genomic DNA in a pool of 2.5 μg of total DNA. EGFR mutations were identified by this approach in both plasma and tissue of 2 patients who were complete responders to EGFR-TKI therapy, only one of which was detectable by direct sequencing. For the 7 patients where only tissue was available, two were positive both with the Scorpion primers and direct sequencing while the rest were wild-type. Of 21 patients where only plasma was available, 6 mutations were detected using the Scorpion primers. Conclusions: Allele-specific Scorpion technology is 1) highly specific and sensitive for EGFR mutation analysis, 2) able to detect mutations that were not observable by direct sequencing in plasma and tissue, 3) capable of detecting mutations in shed tumor DNA in plasma of advanced NSCLC patients and 4) may be suitable for monitoring response or detecting recurrence. No significant financial relationships to disclose.
Patterns of practice in radiation therapy for non-small cell lung cancer among members of American Society of Therapeutic Radiology and Oncology
Authors: Kong F. , West B. , Bonner J. , Choy H. , Gaspar L. E. , Komaki R. , Sun A. , Morris D. , Wang L. , Sandler H. M. , Movsas B. 
Published: March 2020

7693 Purpose: To investigate the dominant pattern of current practice in radiation therapy (RT) for lung cancer among members of American Society of Therapeutic Radiology and Oncology (ASTRO). Methods: A 35-item survey was designed by a panel of 8 board certified radiation oncologists regarding RT for lung cancer. Surveys were sent through email to 3,800 radiation oncologist members on September 10, 2006, with the results collected online on December 10, 2006. Here we report results on radiation decisions for non-small cell lung cancer (NSCLC). Results: The response rate was 19% (n = 727). The respondents saw an average of 8 consults (ranged 1–25) monthly during the survey time (summing up to a total of >60,000 new cases yearly). For stage I peripherally located NSCLC, 33%, 10% and 20% of respondents reported conventional fractionated, hypofractioned and stereotactic RT, respectively. Another 25% of respondents would have offered stereotactic RT if this technique were available at their center. For stage I centrally located tumors, 78% of respondents did not agree with, but 10% selected, stereotactic RT. For stage II and III, 76% of respondents selected 60–70 Gy in 1.8–2 Gy with chemotherapy. With regard to the combined modality approach for stage II and III disease, 76–77% of respondents selected concurrent chemoRT followed by adjuvant chemotherapy, and 11–16% sequential followed by concurrent chemoRT for patients with good performance status. For stage IV NSCLC with remarkable local disease, the consideration of RT ranged from 0 Gy, 3 Gyx10, 3 Gyx15, 2.5 Gyx20, to 2 Gyx30 in 27%, 17%, 8%, 13%, and 21% of respondents, respectively. Conclusions: The dominant pattern of practice for stage II/III disease is concurrent chemoRT, consistent with results of phase III trials. The treatment decisions for stage I and IV disease are diverse, partially due to technology advancement and the lack of large phase III trials. No significant financial relationships to disclose.
A clinical trial design applying Bayesian adaptive randomization for targeted therapy development in lung cancer: A step toward personalized medicine
Authors: Zhou X. , Kim E. S. , Herbst R. S. , Liu S. , Wistuba I. I. , Mao L. , Lewis J. , Lippman S. M. , Hong W. K. , Lee J. J. 
Published: March 2020

7697 Background: Multiple axes of signaling pathways are associated with lung carcinogenesis. These signaling axes are different in pts (pts) and their cancers. Utilization of molecularly targeted agents may inhibit these specific aberrant pathways and lead to clinical efficacy. Biomarkers expressions can be used as indicators for the aberrant signaling to identify effective targeted therapy. Methods: The program, “Biomarker-integrated Approaches of Targeted Therapy of Lung Cancer Elimination (BATTLE),” consists of an umbrella screening trial and 4 parallel phase II targeted therapies trials (with erlotinib, sorafenib, vandetanib, and the combination of erlotinib and bexarotene) in advanced non-small cell lung cancer pts with prior chemotherapy. All pts will have biopsy samples taken for biomarker profile assessment prior to the randomization. A ‘surrogate response‘ to treatment is defined as progression free at 8 weeks after randomization. The Bayesian ordinal probit model is used to characterize the response rate. Pts with certain biomarker profile will be adaptively randomized (AR) to one of the 4 treatment arms with the randomization rate based on the updated response rate based on accumulated data in the trial. For each biomarker profile, better performing arms will have higher randomization rates and vise versa. Early stopping rules are set so that low-performing arms may be suspended for new patient entry. Results: Based on extensive simulation studies, the proposed design with a total of 200 pts has desirable operating characteristics to: (1) identify effective agents with high probability; (2) suspend ineffective agents; and (3) treat more pts with effective agents according to their biomarker profiles. The Bayesian design incorporates prior data and findings from the current pts to form better estimates of the treatment efficacy for pts with different biomarker profiles. The design continues to “learn” and improve the estimates as the trial moves along. Conclusion: The Bayesian AR design is a smart and ethical design and ideally suitable for the development of targeted therapy. It may help in identifying effective agents based on pts’ tumor biomarker profile and thus treat more pts with effective therapies. No significant financial relationships to disclose.
Safety assessment for the combination of docetaxel, carboplatin, and thoracic radiotherapy in unresectable stage III non-small cell lung cancer (NSCLC): A report of the first 100 patients treated with chemoradiation on D0410
Authors: Rigas J. R. , Rubin M. S. , Waples J. M. , Dragnev K. H. , Zimmerman D. M. , Reimer R. R. , Droder R. , Rathmann J. , Green N. B. , Carey M. 
Published: March 2020

7701 Background: Concurrent chemoradiotherapy (chemoRT) is the preferred treatment for patients with unresectable stage III NSCLC. Limited safety information is available on the use of concurrent docetaxel, carboplatin and thoracic RT. We report the safety information on the initial 100 patients (pts) treated with this chemoRT as part of an ongoing US randomized phase III trial (D0410) evaluating the role of erlotinib/placebo following this concurrent chemoRT treatment. The sample size is 400 pts and the primary endpoint is progression-free survival. Methods: Pts with unresectable pathologically confirmed stage III NSCLC are randomized to receive either erlotinib 150 mg or placebo orally daily for 2 years following concurrent chemoRT with docetaxel 20 mg/m2, carboplatin AUC=2 intravenously weekly for 6 wks with thoracic RT of at least 61 Gy in 33 fractions over 6.5 weeks. The planned total lung volume exceeding 20 Gy (V20) was less than 32%. Only the chemoradiation safety information is being reported. This data was reviewed by an independent safety and data monitoring committee. Results: Pt characteristics; 59% males, median age 69 years (range 38 to 86), 21% adenocarcinoma, 48% squamous cell, 94% ECOG PS0–1, 49% stage IIIA, 15% weight loss = 10%. Of 600 planned chemotherapy treatments, 492 were administered (93 wk 1, 85 wk 2, 82 wk 3, 81 wk 4, 77 wk 5, 74 wk 6). There were 25 chemotherapy dose reductions; most commonly for esophagitis (8), neutropenia (5), renal dysfunction (3), hypersensitivity (2). There were no treatment-related deaths. There were 25 grade 3 and 3 grade 4 treatment-related adverse events. The most common grade 3/4 events were esophagitis (6), fatigue (3), odynophagia (2), neutropenia (1), thrombocytopenia (1), dematitis (1). Conclusions: This concurrent chemoradiation regimen appears to be safe. Enrollment to the phase III trial continues. There is a planned interim efficacy evaluation at 150 events (deaths or disease progression). Funded in part by Sanofi- Aventis, Genentech, and OSI Pharmaceuticals. [Table: see text]