bluuebunny/crossref_metadata_2025_split huggingface dataset:
The efficacy of bronchoscopic intratumoral chemotherapy in palliation of inoperable lung cancer.
Authors: El Ghazaly Hesham , Mohammed Tamer , Madkour Ashraf , Koraa Emad 
Published: March 2020

e17556 Background: Endobronchial obstruction is a common complication of advanced-stage lung cancer. Patients presenting with severe bronchial obstruction are at a high risk for developing haemoptysis, post-obstructive pneumonia, or respiratory failure, this often leads to death in weeks to months.Tumor debulking and airway re-canalization has a considerable role in increasing survival in patients with inoperable non-small cell lung cancer (NSCLC). Bronchoscopic endobronchial intratumoral chemotherapy (EITC) is a new intervention to treat airway obstruction. This work aims to determine the efficacy of EITC in palliative care for patients with inoperable NSCLC. Methods: Between April 2009 and June 2011, patients with newly diagnosed non metastatic inoperable symptomatic non-life threatening airway obstruction secondary to NSCLC were selected for tumor debulking via EITC through flexible bronchoscopy. EITC of maximum 20mL cisplatin with the concentration of 50 mg/50 mL was injected into the tumor bulk through flexible needle (weekly for 4 sessions). Patients were followed according to the symptoms, performance and functional status and endobronchial lesions changes after EITC. Results: Forteen male and 1 female were studied in which 7 cases had squamous cell carcinoma, 5 cases had adenocarcinoma and 3 cases had unspecified NSCLC. After 4 sessions of EITC, the involved lumen was considerably opened (> 25%) in 80% of cases in which 7 cases >50% and 5 cases showed a 25–50% luminal opening. Significant improvement was found in dyspnea score, Karnofsky performance scale as well as spirometric and arterial blood gases indices after than before the 4 sessions of EITC. Conclusions: EITC was well tolerated by most of the patients with minimal non systemic complications. In conclusion, EITC is a promising, safe, effective and less invasive procedure for palliative treatment of obstructive non-life threatening endobronchial NSCLC lesions.
Quality of life in poor prognosis patients with locally advanced non-small cell lung cancer (LA-NSCLC) undergoing a phase II study of concurrent cetuximab and definitive thoracic radiotherapy followed by docetaxel and cetuximab.
Authors: Thompson Lora , Extermann Martine , Dilling Thomas J. , Kim Jongphil , Yue Binglin , Stevens Craig William , Antonia Scott , Gray Jhanelle Elaine , Williams Charles C. , Haura Eric B. , Pinder Mary Colleen , Tanvetyanon Tawee , Chiappori Alberto 
Published: March 2020

e17559 Background: A single institution prospective clinical trial was conducted to examine the safety and efficacy of concurrent cetuximab and definitive thoracic radiotherapy followed by docetaxel plus cetuximab. Quality of life (QOL) was assessed as a secondary endpoint. Survival and toxicity data are presented separately. Methods: Eligible pts with unresectable stage IIA or IIIB LA-NSCLC, who also had ECOG PS 2 OR weight loss ≥5% in 3 months OR age >70, completed QOL measures at baseline, after concurrent cetuximab/radiotherapy (recovery), and after docetaxol/cetuximab (consolidation). Scores were calculated for Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Fatigue Symptom Inventory (FSI) worst fatigue, FSI fatigue interference, and Functional Assessment of Cancer Therapy – Lung Trial Outcome Index (FACT-L TOI). FACT-L TOI assessed physical (e.g., nausea) and functional (e.g., difficulty sleeping) well-being as well as lung cancer specific symptoms (e.g., shortness of breath, cough). Descriptive and t-test results are presented. Results: Pts (N = 27) were primarily male (67%) and non-Hispanic Caucasian (96%) with mean age of 73 years. High attrition between recovery (N = 22) and consolidation (N = 10) occurred. Compared to baseline, pts reported higher levels of worst fatigue (p < .03) and fatigue interference (p = .01) at recovery. There was a decline in IADLs (p = .01) but no significant difference in ADLs or FACT-L TOI. Further examination of FACT subscales revealed declines in physical (p < .0001) and functional (p = .02) well-being but improvement in lung cancer specific symptoms (p < .0001). A similar pattern is found for comparisons between baseline and consolidation (ps < .05). There were no significant differences between recovery and consolidation. Conclusions: Although pts experienced declines in QOL across most domains after concurrent cetuximab and radiotherapy, there was improvement in lung cancer specific symptoms. Pts were also able to maintain their ability to perform ADLs. High attrition after recovery is a notable limitation.
Rapid identification of PIK3CA-mutations in lung cancer by using pyrosequencing.
Authors: Schildgen Verena , Lusebrink Jessica , Engel-Riedel Walburga , Stoelben Erich , Schildgen Oliver , Brockmann Michael 
Published: March 2020

e18000 Background: Phospatidylinositol-3-kinases (PI3K) play an important role in various cell processes. Oncogenic mutations in the PIK3CA gene which codes for the catalytic subunit have been identified in various malignancies and activate the PI3K/AKT/mTOR pathway which is a critical driver of tumorigenesis. Methods: We tested 41 tumor samples with known KRAS, BRAF, and EGFR mutation status for the occurence of mutations in the PIK3CA gene using a new commercial pyrosequencing kit. Results: Pyrosequencing revealed 2 mutations (4.9 %) in the PIK3CA gene, one in exon 9 and one in exon 20. Both mutations have not yet been identified in lung tumor tissue. Conclusions: The screening of our small patient cohort by pyrosequencing identified two mutations (4.8 %) in PIK3CA, on in exon 9 (Q546H) and on in exon 20 (M1043T). Both mutations have not yet been described in lung tumours and seem to be rather uncommon mutations. Future Screening of large patient cohorts with pyrosequencing may contribute to the detection of more mutations in lung cancer due to the low limit of detections of this method and may contribute to a better understanding of the interaction of mutations and tumorigenesis.
Update of a phase III trial of adjuvant vinorelbine plus cisplatin (NP) versus NP plus endostar (NPE) in patients with completely resected stage IB-IIIA non-small cell lung cancer (NSCLC).
Authors: Jie He , Han Baohui , Liu Yongyu , Wu Shi Xiu , Kuang Yukang , Shen Yi , Chen Chun , Wang Qun , Li Qiang , Haitao Ma , Xu Shaofa , Xu Shidong , Wang Ping , Mao Weimin , Pang Zuoliang , Hou Shengcai , Yang Yue 
Published: March 2020

e18013 Background: Adjuvant chemotherapy demonstrated a 5-15% benefit in 5-year survival in early-stage NSCLC. Endostar,a recombinant human Endostatin, could inhibit tumor angiogenesis. In a phase III trial, the addition of Endostar to NP regimen resulted in higher response rate, clinical benefit rate and longer median time to progression compared with NP alone in advanced NSCLC patients. Methods: Completely resected patients (stage IB-IIIA) were randomized to receive adjuvant NP plus Endostar (arm A, Vinorelbine 25mg/m2 on d1 and d8 plus Cisplatin 80 mg/m2 intravenously plus Endostar 7.5mg/m2 per day, iv, for 14 consecutive days. 21 days as one cycle(arm A) or NP regimen alone (arm B) for four cycles. The randomization was stratified by gender, stage and histology. The primary endpoint was OS and the secondary endpoints were RFS and safety. Results: 1037 patients (arm A: 520; arm B: 517) from 43 centers in China were enrolled between 9/2007 and 12/2010. Two arms were well-balanced with regard to age, gender, histology, stage, and resection type. 184 patients in arm A and 202 patients in arm B had relapsed disease or died. The median RFS was 34.1 months in arm A and 30.3 months in arm B (p=0.1573). 79.0% of patients in arm A and 76.0% of patients in arm B received 4 cycles of chemotherapy. Median survival time was not available at this time. Grade 3/4 toxicities in arm A included leukopenia (57.4%), neutropenia (75.0%), anemia (12.9%), nausea (11.3%). Grade 3/4 toxicities in arm B included leukopenia (35.0%) neutropenia (60.5%), anemia (8.5%) and nausea (8.5%). It is worth noting that the incidence of cardiac toxicities in arm A (26.3%) was slightly higher than that in arm B (21.4%). Conclusions: The preliminary result showed that patients in arm A experienced a longer median relapse-free survival time than in arm B (34.1 months vs. 30.3 months), although the difference was not statistically significant by far. The toxicity profiles for both arms were tolerable in this study. The patient follow-up is still ongoing.
Clinical profile and patterns of progression (PD) of patients (pts) with advanced nonsquamous non-small cell lung cancer (nsNSCLC) treated with first-line bevacizumab (B): AVVA study.
Authors: De Castro Javier , Domine Manuel , Garcia-Bueno Jose Maria , Saura Salvador , Garcia-Gomez Ramon , Sereno Maria , Juan Oscar , Pujol Eduardo , Rubio Belen , Cobo Manuel 
Published: March 2020

e18015 Background: B in combination with platinum doublets prolongs survival and delays PD in chemo-naïve pts with advanced nsNSCLC and its safety profile has been widely described in clinical trials. In this study we aim to evaluate the behavior, clinical profile and patterns of PD of real-life nsNSCLC pts treated with B in 44 Spanish institutions. Methods: AVVA is a multicenter, epidemiological study to define the clinical profile (gender, age, PS, histology, stage, comorbidities, tumor load, Tx, response and tolerability) and describe the patterns of PD. Pts diagnosed with advanced nsNSCLC and evidence of PD after treatment (Tx) with standard chemotherapy (CT) plus B up to 6 cycles followed by maintenance B were included. Results: Data of 158 pts are presented. Clinical profile was: median age 58 years (range 34-79); male 65%; stage IV 91%; adenocarcinoma 77%; ECOG PS 0/1/≥2 (%): 35/56/9; never/current/former smokers (%): 23/40/37. 64% of pts presented relevant concomitant disease at baseline (27% cardiovascular disease, 24% pulmonary disease). Tx received: B plus carboplatin-doublet/cisplatin-doublet/other (%) 70/25/5. Median no. of cycles for CT/B: 6/9. Patterns of PD: 44% presented high tumor load (tumor diameter ≥55mm and ≥5 lesions); 97% of pts presented intra-thoracic disease, 53% presented extra-thoracic disease and 13% only pulmonary disease. High tumor load was associated with extra-thoracic disease (p<0.05). ORR was 53% (95% CI: 45-61) and disease control rate was 85%. Best response was achieved after a median of 4 cycles (range 1-16). ECOG 0/1 at PD (%): 15/50. Median PFS was 7.7 months (95% CI: 7.3-8.1). No differences were found in ORR or PFS according to tumor load and intra/extra-thoracic disease. Grade 3/4 toxicities were: venous thrombosis (3.2%/0), proteinuria (0.6%/0), hemoptysis (0.6%/0), pulmonary embolism (0/0.6%) and mucositis (0.6%/0). Conclusions: B was effective in this real-life patients’ population, irrespective of tumor load and location of the disease. These results confirm the well-established safety profile and the efficacy of B as frontline Tx in nsNSCLC.
EGFR mutation analysis from REASON: A registry for the epidemiologic and scientific evaluation of EGFR mutation status in newly diagnosed NSCLC patients stage IIIB/IV.
Authors: Schuette Wolfgang , Eberhardt Wilfried Ernst Erich , Graf von der Schulenburg J.-Mathias , Dietel Manfred , Schirmacher Peter , Zaun Silke , Thomas Michael 
Published: March 2020

e18016^ Background: Somatic mutations in the EGFR gene predict for sensitivity to EGFR TKI in patients with adv. NSCLC, yet limited data exists on EGFR mutation rates of all 4 exons in all NSCLC histologies. Methods: The REASON study (NCT00997230) aims to generate data on EGFR mutation (M) status, association of EGFR-M status with clinico-pathological parameters, treatment decisions and clinical outcomes for EGFR M+ patients from a large sample of stage IIIB/IV NSCLC patients in Germany. 4279 subjects for whom EGFR M testing was planned were enrolled at 151 sites (85% hospital based) in Germany. Standard test method was Sanger sequencing. While analysis of exons 19 and 21 was obligatory, exons 18 and 20 were not routinely done at all labs. Primary objectives are epidemiological data on EGFR M status and correlation with clinico-pathological features. Secondary aims are clinical outcome of all EGFR M+ patients (PFS, OS, DCR), clinical management and pharmaco-economic data associated with diagnosis and treatment of EGFR M+ patients. Results: A 2nd interim analysis provided baseline data on 3973 patients. 63% were male; 82% ever-smokers, 18% never-smokers. Adenocarcinoma is most frequent (69%), followed by squamous epithelial carcinoma (19%). 379 patients had EGFR mutations (9.9%) with 9.5% predicting TKI sensitivity and 0.4% resistance. Most common were exon 19 deletions (50%; with 35% DelE746-A750) followed by exon 21 mutations (36.8%; with 72% L858R). Multivariate analysis revealed association of gender, smoking status and histological subtype with EGFR M status (Table). 50% of M+ patients received 1st line TKI vs. 48% doublet CTX. Conclusions: REASON provides the largest data base yet on EGFR M status in Caucasian patients with newly diagnosed stage IIIB/IV NSCLC. Smoking followed by adeno-carcinoma was the strongest predictive factor for EGFR M. Only 50% of EGFR M+ patients received 1st line TKI. [Table: see text]
Retrospective analysis of the impact of age on overall survival in patients with non-small cell lung cancer.
Authors: Luu Dai Chu Nguyen , Mamet Rizvan , Zornosa Carrie C. , Niland Joyce C. , D'Amico Thomas A. , Kalemkerian Gregory Peter , Koczywas Marianna , Pisters Katherine , Rabin Michael S. , Otterson Gregory Alan 
Published: March 2020

e18018 Background: Clinical trials have failed to demonstrate that age is a significant prognostic indicator among patients treated for non-small cell lung cancer (NSCLC). Clinical trials do not necessarily represent real-world experience, however. We sought to analyze the impact of age on survival in patients in the National Comprehensive Cancer Network (NCCN) NSCLC Outcomes Database. Methods: We performed a retrospective analysis of 6,834 NSCLC patients from the NCCN NSCLC Database representing 8 NCCN institutions. Of this population, 4,943 patients were eligible for our analysis. Exclusion criteria included the following: alive patients with < 180 days of follow-up, patients with incomplete staging, and patients with a prior cancer diagnosis. The study population was separated into five age quintiles with equal number of patients in each group. Variables included institution, smoking status, gender, race, Charlson comorbidity score, ECOG performance status (PS), histology, stage, and receipt of resection, drug and radiation therapy. Multivariable Cox model was performed for the effect of age on survival after adjusting for the above variables. Model assumptions were evaluated via graphs and residual tests. Results: Across the five quintiles (< 54, 54-60, 61-66, 67-72 and ≥ 73) there was a trend towards lower stage and higher Charlson score with increasing quintile. In addition, there was an increased proportion of patients with squamous cancer in the older age group. In the adjusted Cox model, there was a statistically significant longer survival in each of four younger quintiles compared to the reference group of ≥ 73 years of age (p=0.01). The adjusted hazard ratio of death for patients < 54 was .82 (95% CI = .72 to .94), for patients 54-60 was .86 (95% CI = .76 to .97), for patients 61-66 was .84 (95% CI = .74 to .95), and for patients 67-72 was .84 (95% CI = .74 to .95). There were no statistically significant pairwise interactions among age, smoking status and stage. Conclusions: Even after adjusting for institution, comorbidity scores, smoking status, race, gender, ECOG PS, histology, stage and treatment, NSCLC patients who were ≥ 73 years of age had a worse survival when compared to younger age groups.
Efficacy of fexofenadine in preventing tyrosine kinase inhibitor (TKI)-induced interstitial lung disease.
Authors: Ko Ryo , Sasaki Shinichi , Namba Yukiko , Ishimori Ayako , Yoshioka Masakata , Yoshioka Yasuko , Tominaga Shigeru , Takahashi Kazuhisa 
Published: March 2020

e18019 Background: Tyrosine kinase inhibitors (TKIs; gefitinib and erlotinib) are widely indicated in NSCLC patients, especially those harboring an active mutation of EGFR, and have shown excellent efficacy. However, severe interstitial lung disease (ILD) can occur as an adverse event with TKIs, and is sometimes fatal. Fexofenadine has been used to prevent TKI-induced skin rash in all patients, who received EGFR-TKIs, since April 2009 in our hospital, and seems to reduce the incidence of ILD. Therefore, we retrospectively analyzed the efficacy of fexofenadine in preventing TKI-induced ILD. Methods: 145 NSCLC patients, in whom TKIs were administered, were analyzed in the study, comprising 54 and 91 patients with and without concomitant administration of fexofenadine, respectively. Univariate and multivariate analyses with logistic regression model were used to investigate whether fexofenadine could prevent EGFR-TKIs-induced ILD or not. Results: ILD occurred in 21 patients (14.5%), and was fatal in 5 (3.4%). The number of ILD patients with/without fexofenadine was 4 out of 54 (8.5%)/17 out of 91 (18.7%), and the mortality was 1 out of 54 patients (1.9%)/4 out of 91 (4.4%), respectively. Fexofenadine appears to reduce the ILD event (p=0.062). Interestingly, severe ILD events (grades 2, 3, 4, or 5) were significantly reduced in patients with fexofenadine compared to patients without fexonadine (p=0.031, Table). Although the administration of fexofenadine was not independent predictive factor for EGFR-TKIs-induced ILD according to multivariate analysis, it seems to reduce the ILD events (p= 0.061). Conclusions: Our data suggest that fexofenadine seem to reduce the incidence of TKI-induced ILD. However, the prospective study needs to be performed to confirm our result. [Table: see text]
Survival post-progression (SPP) in phase III trials of chemotherapy in advanced NSCLC: Its potentially different impact on OS in the first-line and salvage settings.
Authors: Hotta Katsuyuki , Takigawa Nagio , Fujiwara Yoshiro , Hisamoto Akiko , Ichihara Eiki , Tabata Masahiro , Tanimoto Mitsune , Kiura Katsuyuki 
Published: March 2020

e18027 Background: We previously demonstrated that in advanced NSCLC, survival after progression to first-line chemotherapy (SPP-1) has significantly improved and has become more closely associated with OS after the initiation of first-line chemotherapy (OS-1), potentially because of the recent development of active agents even in salvage settings (Plos One 2011). We conducted a literature survey to examine time trend in survival after progression to second- or third-line chemotherapy (SPP-2/3) and its potential correlation with OS after the initiation of second- or third-line chemotherapy (OS-2/3). Methods: SPP-2/3 was pragmatically defined in each second- or third-line chemotherapy trial as the interval of MST (OS-2/3) minus median PFS time (PFS-2/3) (OS-2/3 = PFS-2/3 + SPP-2/3). The relationship between PFS-2/3 and OS-2/3 or SPP-2/3 and OS-2/3 was assessed in the regression analysis using the coefficient of determination (r2); higher r2 means a higher correlation. Results: Twenty trials of the second- or third-line chemotherapy initiated between 2001 and 2009, were defined (14,951 patients, 37 chemotherapy arms). Contrary to our previous findings regarding SPP-1, SPP-2/3 has not been significantly prolonged over the years (8.0-day increase per year; p = 0.161) despite a steady increase in OS-2/3 (17.2-dayincrease per year; p = 0.003) and PFS-2/3 (9.8-day increase per year; p = 0.005). Overall, a moderate association was observed between OS-2/3 and SPP-2/3 (r2 = 0.6755), suggesting SPP-2/3 could predict 68% of the variation in OS-2/3. Interestingly, the association between OS-2/3 and SPP-2/3 became less close over the years (r2 = 0.9849, 0.8280, and 0.5667 in 2001–2003, 2004–2006, and 2007–2009, respectively). Conclusions: During the period SPP-2/3 seemed stable, and the association between SPP-2/3 and OS-2/3 has become unclear probably because of recent survival improvement in PFS-2/3 rather than SPP-2/3. This seems in contrast with our previous report that SPP-1 has become more tightly associated with OS-1 over the year, potentially due to the establishment of active post-study treatments just in second- or third-line setting.
Bevacizumab (B), cisplatin (C), and pemetrexed (P) plus maintenance B in chemonaive patients (pts) with advanced nonsquamous non-small cell lung cancer (nsNSCLC): A phase II study.
Authors: Lopez-Vivanco Guillermo , Carrera Sergio , Sancho Aintzane , Marrodan Ines , Azcona Eider , Iruarrizaga Eluska , Rubio Itziar , Muñoz Alberto , Cardona Jose Vicente 
Published: March 2020

e18031 Background: B in combination with platinum doublets followed by continuation maintenance with B prolongs survival and delays progression in chemo-naïve pts with advanced (nsNSCLC). P in combination with C is efficacious in advanced nsNSCLC as frontline treatment. This phase II study aims to evaluate the efficacy and safety of B, C and P plus maintenance B in chemo-naïve pts with advanced nsNSCLC. Methods: Chemo-naïve pts with unresectable stage IIIB or IV nsNSCLC were treated of C (75 mg/m2), P (500 mg/m2), and B (7.5 mg/kg) on day 1 every 21 days up to 6 cycles. Pts with response or stable disease (SD) received maintenance B (7.5 mg/kg) every 21 days until disease progression or unacceptable toxicity. The primary endpoint was median progression free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), safety and analysis of K-ras mutations and plasma VEGF levels. Results: From 4/09 to 12/11, 27 pts were enrolled in the study. Data of 21 pts are presented. Median age was 58 years (range 42-74); male/female (%): 81/19; ECOG 0/1 (%): 5/95; adenocarcinoma/large cell carcinoma (%): 95/5. Median follow-up is 4.7 months. 53% of pts received at least 6 cycles of treatment and 20% received up to 12 cycles. Among the 15 pts assessable for response, the ORR was 47% (95% CI, 21-73) and disease control rate was 87%. Median PFS was 6.0 months (95% CI, 1.9-7.5). Grade 3/4 hematologic toxicity was neutropenia (9%/0). Most frequent grade 3/4 non-hematologic toxicities were fatigue (29%/0), venous thrombosis (14%/0), pulmonary embolism (9%/0) and dyspnea (5%/5%). There were no grade 3/4 hemorrhagic events. Data on survival and the analysis of K-ras mutations and VEGF levels will be presented. Conclusions: Treatment with B, C and P plus maintenance B is feasible and effective as front-line treatment of pts with advanced nsNSCLC. These data provide further evidence that B may be used in combination with multiple standard, platinum-based doublets in this setting.