bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety results of pemetrexed administration in non-small cell lung cancers, a multicenter study of the Association of Anatolian Medical Oncology.
Authors: Yasar Nurgul , Unal Olcun Umit , Geredeli Caglayan , Inal Ali , Berk Veli , Sari Ebru , Durnali Ayse , Suner Ali , Ozdemir Nuriye , Budakoglu Burcin , Demirci Umut , Gumussoy Ozge , Uncu Dogan , Boruban Cem Melih , Oztop Ilhan , Ozkan Metin , Gumus Mahmut , Elkiran Tamer ,   Anatolian Medical Oncology
Published: March 2020

e19107 Background: In this study, the efficacy and safety of pemetrexed chemotherapy was evaluated retrospectively in patients who were non-responders to or who have demonstrated progression after the first and/or second line treatments in local advanced and metastatic NSCLC. Methods: 175 patients (139 males, 36 females) were assessed in years 2008 – 2012. Patients were given pemetrexed 500 mg/m2, and the ones receiving combined treatment were given pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 once in every 21 days. Supplementary steroid and vitamin treatment were administered to all patients. Age, gender, performance status (PS), stage, single agent or combined administration of treatment, progression-free survival (PFS) and overall (OS) were investigated. Patients were assessed in terms of treatment efficacy and toxicity. Results: Median follow-up period was 6 months (1 - 25), and median age was 55 years (28 - 83). In 82% of patients, PS was 0 – 1. 73% of patients were at stage 4. 71% of the patients received single agent pemetrexed, and 14% received platinum - pemetrexed combination treatment. 93% of patients received pemetrexed treatment as second line. Median 3 cycles of treatment (1 – 12) were administered. In side effect assessment, while side effects (grade 1 – 4) were observed in 62% of the patients, the most frequently observed side effects were anemia (18%) and nausea-vomiting (15%). Febrile neutropenia was detected in 6 patients (3.4%).In assessment of the response, the disease control ratio was 50% (21% partial response, 29% stable disease). 1- and OS rates were respectively 14% and 41%. Median OS was 10 months (SE:1, 95% CI: 7-12) and median PFS was 3 months (SE:1, 95% CI: 2-4). In multivariate analysis, PS of 0 – 1 and response to treatment were found as factors with prognostic significance (p=0.047, p=0.014, respectively). Conclusions: It is observed that chemotherapy regimen containing pemetrexed in NSCLC treatment is a treatment approach, which provides an efficient disease control with a manageable side effect profile, in patients especially with good performance status and with no platinum resistance, who can receive treatment in combination form.
Adrenalectomy for low-tumor-burden metastatic lung cancer: Results of a single institution experience.
Authors: López-Picazo José María , Martin-Romano Patricia , Zubiri Oteiza Leyre , Gurpide Alfonso , Gil-Bazo Ignacio , Perez-Gracia Jose Luis , Fusco Juan Pablo , Moreno-Jiménez Marta , Carranza Omar Esteban , Martin-Algarra Salvador 
Published: March 2020

e19114 Background: Adrenal gland is a common site of metastasis in lung cancer. Adrenal metastasis (AM) can occur at the time of diagnosis (synchronous AM) or later (metachronous AM). When an AM appears as an isolated site of dissemination it is considered a good-prognosis metastatic disease. Nevertheless few data are available about the prognosis and the optimal management of these patients. Methods: Retrospective analysis of the historical series of adrenalectomies in patients treated of lung cancer at our institution. Results: From April 2002 to April 2011, 30 patients (27m/3f) diagnosed of AM of lung cancer (16 non-squamous, 8 squamous, 6 small-cell; 21 metachronous AM, 9 synchronous AM) were treated with adrenalectomy (26 laparoscopic, 4 open surgery). Median age was 55 years old (range: 42-71). Median size of the AM was 35 mm (range: 12-140). There were no severe complications of surgery in any patient. All the patients had received radical treatment for the primary tumour and for other metatatic sites (8 patients brain metastases, 3 patients other sites) before adrenalectomy. Median overall survival (OS) and disease-free survival from adrenalectomy for the entire group were 44 (95% CI: 10-78) and 15 (95%CI: 7,6-22.3) months respectively. We found an statistical trend (p=0.087) of better OS from adrenalectomy for patients with non-squamous histology compared with squamous histology: 57 (95%CI: 38.4-75.6) and 21 (18.3-23.8) months respectively. The percentage of alive patients at 2 and 5 years was 59.1% and 36% respectively. Conclusions: These results add new data about the prognosis of patients with adrenal metastases into the context of low-tumor-burden metastatic lung cancer. Adrenalectomy is a tolerable procedure which plays a role in the management of these patients.
Plasma microRNA signatures to predict EGFR-TKI resistance in EGFR-mutant advanced NSCLC patients.
Authors: Wang Shuhang , Wang Jie , Bai Hua , An Tongtong , Zhao Jun , Wang Zhijie , Duan Jianchun , Zhuo Minglei , Wang Yuyan , Wu Meina 
Published: March 2020

e19136 Background: EGFR mutation is a strong predictor of EGFR-TKIs (epidermal growth factor receptor tyrosine kinase inhibitor) therapy in advanced NSCLC. However, 20-30% of patients with EGFR mutation are resistant to EGFR-TKIs, suggesting that other determinants of outcome beyond EGFR mutation might exist. We hypothesized that plasma microRNA (miRNA) might play a role. Methods: Training group: 20 advanced NSCLC patients treated with EGFR-TKIs as first-line therapy with EGFR 19 deletion mutation were enrolled, 10 of whom responded dramatically while other 10 are resistant. Matched plasma were collected for miRNA profile detection using TaqMan Low-Density (TLDA). Testing group: Real-time PCR were employed to identify the level of miRNAs found significant differently expressed in training step; bioinformatics was applied to find related miRNAs possibly account for resistance. Validation group: Another cohort with EGFR 19 deletion mutation present dramatically different response to EGFR-TKI was used to analyze the difference of miRNAs expression between responding and resistant group. Results: Training group: 153 miRNAs were found differently expressed between responding and resistant group. Testing group: 3 miRNAs (miR-21, AmiR-27a, and miR-218) were verified significantly higher (P=0.004, A0.009, A0.041, respectively) in resistant group than responding group. Validation group: expression level of these 3 miRNAs was validated to be significantly different (P=0.011, A0.011, A0.026, respectively) between 17 couples advanced NSCLC patients with different response to EGFR-TKI. Conclusions: Higher expression level of miR-21, AmiR-27a, and miR-218 might play the role in the resistance to EGFR-TKI for advanced NSCLC patients who had an EGFR exon 19 deletion mutation treated with EGFR-TKI, which needs further validation.
Phase I dose escalation study of pemetrexed and carboplatin in chemotherapy-naive elderly patients with advanced nonsquamous non-small cell lung cancer.
Authors: Yamada Kazuhiko , Takeoka Hiroaki , Zaizen Yoshiaki , Shimamatsu Fumie , Azuma Koichi , Hoshino Tomoaki 
Published: March 2020

e19137 Background: The subgroup analyses in several phase III trials have suggested that overall survival after platinum-doublet chemotherapy in elderly patients with non-small cell lung cancer (NSCLC) can be similar to those in younger patients. The combination of carboplatin (CBDCA) with pemetrexed (PEM) is expected as a suitable treatment for carefully selected elderly patients with advanced non-squamous (non-Sq) NSCLC. Methods: Patients with ≥75 years, PS of 0-1, chemotherapy-naïve advanced non-Sq NSCLC were enrolled in this study. They received escalated doses of CBDCA at AUC 4 (cohort 1) or AUC 5 (cohort 2) and PEM 500 mg/m2 every 3 weeks for six cycles. Dose escalation was decided by dose-limiting toxicity (DLT) occurred in the first cycle of chemotherapy. Study protocol stipulated that additional number of patients, up to maximum of 20 patients, was enrolled to receive the recommended dose of study treatment. The primary objectives were to evaluate feasibility and determine the recommended dose of this combination. Results: A total of 20 patients (6 patients in cohort 1, 14 patients in cohort 2) were enrolled in this study. Median age was 77 (range 75-83). No DLTs were observed in the patients with cohort 1 and the first 6 patients of cohort 2 during the first cycle of chemotherapy, thus the combination of PEM 500 mg/m2 plus CBDCA at AUC 5 was determined as the recommended dose. Median number of cycles was 4 (range 1-6). The major toxicities were neutropenia, thrombocytopenia, anemia. During the entire period of study, 2 and 5 patients needed to have platelet transfusion and RBC transfusion, respectively. Liver dysfunction, fatigue and anorexia were also common, but these were generally manageable. Six partial responses and 9 stable diseases were observed, giving an overall response rate of 30% and a disease control rate of 75%. Median progression-free survival time was 4.8 months (95% CI, 4.1 – 5.4 months). Conclusions: The combination of PEM 500 mg/m2 plus CBDCA at AUC 5 was determined as the recommended dose. This combination therapy is generally tolerable, and may have encouraging antitumor activity in chemotherapy-naïve elderly patients with advanced non-Sq NSCLC. Clinical trial information: UMIN000003231.
First-line chemotherapy (CT) with pemetrexed (PEM) + cisplatin (CIS) + bevacuzimab (BEV) followed by maintenance PEM+BEV for advanced nonsquamous non-small cell lung cancer (NS-NSCLC): Final results of a single-arm phase II study.
Authors: Hillerdal Gunnar N , Sorensen Jens Benn , Hoeffken Gert , Favaretto Adolfo , Perez-Carrion Ramon , Visseren-Grul Carla , Ameryckx Sophie , Soldatenkova Victoria , Bourayou Nawel , Santoro Armando 
Published: March 2020

e19148 Background: 1st line PEM+CIS induction CT followed by PEM maintenance and 1st line BEV-based CT followed by BEV maintenance offer clinical benefit (PFS, OS) in NS-NSCLC. This study explored efficacy and safety of 1st line induction PEM+CIS+BEV followed by maintenance PEM+BEV. Methods: Pts with advanced NS-NSCLC and ECOG 0-1 were planned to receive 4 cycles PEM 500 mg/m2, CIS 75 mg/m2, BEV 7.5 mg/kg, q3w. In absence of PD and with ECOG 0-1, pts could continue on PEM+BEV until PD or unacceptable toxicity. All pts received vitamin supplementation as per PEM label. Primary endpoint was PFS; secondary were OS, response rate, toxicity. Results: 109 pts were enrolled in 5 countries. Characteristics: median age 61 yrs, males/females 59/41%, ECOG 0/1 54/46%, IIIB/IV 9/91%, adenocarcinoma 91%. 72 pts (66%) had maintenance CT. Overall median (max) no of cycles were 6 (34) for PEM+BEV and 2 (4) for CIS. Median PFS was 6.9 m (90% CI 5.7, 8.3). The table gives efficacy and G3/4 AE data. 2 pts died from study-drug related toxicity (GI hemorrhage, pneumonia aspiration; during induction). Conclusions: In this study of PEM+CIS+BEV induction followed by PEM+BEV maintenance median PFS was 6.9 m. Main G3/4 toxicities included neutropenia and fatigue, hypertension was less common. Clinical trial information: NCT01004250. [Table: see text]
Risk of interstitial lung disease and other pulmonary related adverse events among patients taking EGFR inhibitors: A meta-analysis of randomized controlled trials.
Authors: Garcia Salvador Ricardo , Donath Elie , Ortega-Parra Camilo A. , Jacobson Robert J. 
Published: March 2020

e19155 Background: Epidermal growth factor receptor (EGFR) inhibitors are suspected of being a potential cause of interstitial lung disease (ILD). This speculation is based largely on case reports and series in which it is difficult to establish causality. In this meta-analysis we evaluated randomized controlled trials (RCTs) involving EGFR inhibitors to verify if a relationship exists between exposure to EGFR inhibitors and development of ILD and other pulmonary-related events. Methods: EMBASE and Medline were searched for all RCTs evaluating cetuximab, gefitinib or erlotinib in non-small cell lung cancer (NSCLC). Studies were disqualified if the control contained any EGFR inhibitor or drug known to cause ILD. Thirty-one RCTs with 15,736 patients were identified. The primary outcome was ILD incidence. ILD is poorly defined and there is overlap with other pulmonary related outcomes including pneumonia, acute respiratory failure (ARF) and pneumonitis, and these were therefore secondary outcomes of interest. For all outcomes, a fixed-effects meta-analysis was performed. Results: For the primary outcome, there is a 173% increased risk of ILD among patients given EGFR inhibitors (RR 2.73, 95% CI: 1.74-4.23, p<0.001) across 15 RCTs that report on ILD incidence. Among secondary endpoints, there is an 86% increased risk of pneumonia (RR 1.86, 95% CI 1.36-2.53, p<0.001), a 19% increased risk of pneumonitis (RR 1.19, 95% CI: 0.62-2.27, p=0.59) and a 33% increased risk of ARF (RR 1.33, 95% CI: 0.65-2.72, p=0.44) among patients given EGFR inhibitors. There is minimal heterogeneity across trials for all above outcomes. Conclusions: EGFR inhibitors play a direct role in causing or contributing to ILD progression in patients with NSCLC who are susceptible to alveolar damage from prior chemoradiation therapy. Additionally, EGFR inhibitors seem to be associated with an increased risk for other pulmonary related events.This research suggests that caution should be undertaken in administering EGFR inhibitors to patients with poor baseline lung function or pre-existing pulmonary disease.
Variables impacting the number of palliative chemotherapy lines administered to patients with advanced non-small cell lung cancer (NSCLC) in a common daily practice setting.
Authors: Roa-Garcia Diana Marcela , Muñoz Silvia , Baste Neus , Holguin Francia , Sais Elia , Urbano Cristina , Quer Nuri , Guerra Silvia , Cufi Silvia , Vazquez-Martin Alejandro , Oliveras-Ferraros Cristina , Corominas-Faja Bruna , Menendez Javier A. , Brunet Joan , Garcia-Velasco Adelaida , Izquierdo Angel , Porta Rut , Bosch-Barrera Joaquim 
Published: March 2020

e19159 Background: Palliative chemotherapy (CT) can increase survival and quality of life for advanced non-small cell lung cancer (NSCLC) patients (pts). It has been observed in phase III clinical trials that not all pts are able to receive second or further lines of CT. We have analyzed the number of CT lines that pts with advanced NSCLC do in our institution and factors that could have an impact on it. Methods: All pts treated during 2010 for advanced NSCLC in our institution were analyzed (n=124). Quantitative data were compared by Student’s t test. Overall survival (OS) was estimated by Kaplan-Meier analysis and differences were assessed with the log-rank test. Results: Most pts (75.8%) were men. Median age was 66 years. The 67.7% of patients received up to 2 lines of CT, 38.7% 3 lines, 15.3% 4 lines, 8% 5 lines, and 2.4% received up to 6 lines. The higher the number of lines of CT were administered, the higher the median of OS obtained from one line of CT to up to six lines respectively (4.4 vs 10.9 vs 15.6 vs 19.2 vs 31.1 vs 54.3 months, p<0.0001). Women presented a higher median of OS than men (18.7 vs 12.1 months, p=0.015), but without a significant higher number of CT lines (2.6 vs 2.17, p=0.159). Adenocarcinoma pts (54.0%) received greater numbers of CT lines than squamous cell carcinoma pts (26.6%) (2.54 vs 1.58, p=0.007), with a trend towards significant increase in the median OS (14.7 vs 11.6 months, p=0.072). Pts receiving cisplatin-based CT as first line (40.3%) received more lines of treatment than carboplatin-based (46.0%) (2.88 vs 2.04, p=0.001) and were also younger (59.6 vs 65.8 years, p=0.003), but these differences did not have a statistically significant impact on median OS (14.0 vs 11.6 months, p=0.375). Conclusions: In our series, pts with adenocarcinoma histology and cisplatin-based first line treatment received a higher number of lines of CT. Women had better median OS. The number of lines of CT received may have an impact on median OS.
Single institution experience of brentuximab vedotin (SGN-35) impact on allogeneic transplant in patients with relapsed/refractory CD 30 positive lymphoma.
Authors: Parsons Benjamin Marshall , Stiff Patrick J. , Smith Scott E. 
Published: March 2020

e19511 Background: Case series to date (Chen and Gopal) have reported safety and efficacy of b. vedotin prior to allo-SCT. We report our experience using b. vedotin prior to allo-SCT. Methods: Patients were treated with b. vedotin through Seattle Genetics trials and identified retrospectively using a registry of b. vedotin use and subsequent allo-HCT. Patients were treated per study protocol and received 1.8 mg/kg b. vedotin administered every 3 weeks for up to 16 cycles. Patients were followed for response, survival/disease status and subsequent therapy. Results: 7 patients were identified with a median of 5.7 prior therapies. Of these patients 5 had HL histology and 2 had ALK+, ALCL histology. The median age was 37.0 years. The median time since initial diagnosis was 60.4 months. All 7 patients had previously received an autologous SCT. Patients with primary refractory disease accounted for 42% of patients. Patients received a median of 8.6 cycles of b. vedotin and 86% of patients achieved an objective response; best response was CR for 3 patients and PR for 3 patients. Median maximum tumor reduction was 43%. Median time from b. vedotin to transplant was 7.6 months. Three patients received additional chemotherapy post b.vedotin and prior to allo-SCT. The PFS and OS are 86% with 6 patients alive and without relapse in follow-up post allo-SCT. There was 1 transplant related death at induction which did not appear related to b. vedotin. The median follow up is 17.5 months. The median time to neutrophil engraftment was 12.3 days. The median time to platelet engraftment was 21.6 days. Their were no episodes of aGVHD and 33% of patients developed cGVHD all Grade I/II. No increase in infections was observed. Conclusions: Treatment with b.vedotin provided significant decrease in tumor volume in patients with relapsed CD30+ lymphoma, and allowed for allo-SCT. There was no evidence of a delay in engraftment, aGVHD, cGVHD, or post transplant infectious complications. Our results add to prior reports that b. vedotin is a safe and effective option for reducing tumor burden to facilitate a potentially curative allo-SCT and warrants further study.
Evaluation of protocol mandated testing in E4A03, a randomized phase III study of CC-5013 plus dexamethasone versus CC-5013 plus low-dose dexamethasone in multiple myeloma (MM).
Authors: Callander Natalie Scott , Jacobus Susanna J. , Weiss Matthias , Kumar Shaji , Fonseca Rafael , Siegel David Samuel DiCapua , Katz Michael S. , Abonour Rafat , Williams Michael E. , Greipp Philip R. , Rajkumar Vincent ,   Eastern Cooperative Oncology Group
Published: March 2020

e19517 Background: Investigators cite complicated test (T) schedules as barriers to the conduct of clinical trials, especially T that do not contribute to outcome or pt safety. In MM protocols, some T are prone to being done inaccurately (e.g. UPEP, 24 hour urine collections), or are not useful (e.g. uric acid, AST/ALT) in determination of response (R) or safety. These T lead to increased cost, protocol violations, and do not enhance outcome. Methods: We analyzed data submitted for pts on E4A03 to examine frequency of missing data for R T: serum and urine (U) PEP, immunofixation (IFE) bone surveys (BS), and safety labs for C1-4. Results: Table outlines % pts with completed T. Most had T for serum M protein, as well as heme T but serum and U PEP, and IFE dropped off by C4. Other T e.g. uric acid were completed in 77%. Only 79% of pts had a BS repeated at C4. Incorrect or missing U data led to categorization of 16/445 (3.6%) pts as ineligible and was most frequent reason for ineligibility (69%). Missing U data led to 13/26 pts not evaluable. Analysis of SAE during the C1-4 revealed no SAE for hyperuricemia and < 5 SAE for AST/ALT. Only 5% of pts had lab-based SAE filed in 4 C. Conclusions: Required U T and BS to assess R in E4A03 were missing or completed inadequately and caused pts to be ineligible and or not evaluable. Such T need to be eliminated or replaced. Strategies to monitor data submission in real time may reduce subject loss due to T error. The requirement for routine T should be reassessed to create simpler trial design. Clinical trial information: NCT00098475. [Table: see text]
Retrospective analysis of treatment-induced peripheral neuropathy (TIPN) in multiple myeloma (MM).
Authors: Martin Thomas , Panjabi Sumeet , Imani Robert , Anum Emmanuel , Lubeck Deborah P. 
Published: March 2020

e19530 Background: Peripheral neuropathy (PN) is commonly present at MM diagnosis and exacerbated or induced by MM treatments. TIPN poses significant morbidity, and may result in therapy modifications (TM). We examined the “real-life” onset and severity of TIPN in newly diagnosed patients (pt) receiving anti-MM therapies. Methods: Medical records from a US community oncology network were reviewed. Newly diagnosed MM pt treated between 1/1/08 and 7/1/10, ≥18 years, and followed for ≥24 months were eligible. The protocol pre-defined inclusion of an equal number of TIPN and non-TIPN cases. Regimen-related TIPN was based on clinician judgment and/or correspondence of TIPN with regimen start/end dates. Uni- and multi-variate (MV) analyses examined association of demographic and regimen characteristics with TIPN, TIPN severity, and TM. Results: In all, 716 MM records were screened; 367 were deemed ineligible or incomplete. Of 349 eligible records, 229 were abstracted, 10 had unusable data, and 219 formed the analytic set; 120 records were excluded since the accrual target (N=225) had been met. Average age of pts was 67.0 years, 49.3% were female, 57.5% Caucasian, and 36.0% African-American (AA). A majority (56.6%) had 1 regimen prior to 1st disease progression, 26.0% had 2 and 17.4% had >2 regimens. Overall, 138/219 (63.0%) developed PN, 123/219 (53.7%) with documented TIPN. TIPN developed during 1st line therapy in the majority 110/123 (89.4%). Univariate analysis revealed that TIPN pt were younger, more likely to be AA, and treated more frequently with bortezomib-based regimens BTZ-BR (63.3 v 9.3%). MV analysis showed TIPN was associated with BTZ-BR (OR=14.5, 95% CI=6.5-32.2), but not age, race, gender, and diabetes. BTZ-BR compared to non BTZ-BR were associated with severe and grade 3/4 TIPN (79.3 v 20.7%; χ2=5.36, p=0.02), and TM (65.7 v 34.3%, χ2=5.57, p=0.02). Notable TM included dose reductions (66.7 v 33.3%) and delays (83.3 v 16.7%). Conclusions: In this study of newly diagnosed MM pt, TIPN developed frequently during 1st line therapy. BTZ-BR were associated with TIPN that was severe and resulted in greater TM. While this analysis represents a small pt population, the results are provocative and warrant further study.