bluuebunny/crossref_metadata_2025_split huggingface dataset:
Favorable outcomes with chemoradiation and surgery for locally advanced non-small cell lung cancer: The BC Cancer Agency Vancouver experience.
Authors: Shan Wen Wen , Sun Sophie , Laskin Janessa J. , Ho Cheryl , Melosky Barbara L. , Carolan Hannah , Goddard Karen , Wu Jonn , Berthelet Eric , Liu Mitchell , Evans Kenneth , Finley Richard , Yee John , Ionescu Diana , Murray Nevin 
Published: March 2020

7020 Background: The role of surgery following concurrent platinum-based chemotherapy and radiation for locally advanced non-small cell lung cancer (NSCLC) remains controversial, with high surgical mortality rates reported in a large randomized clinical trial. In this retrospective study, we evaluated the safety and efficacy of concurrent chemoradiation with or without surgery over an 11 period at the BC Cancer Agency. Methods: Patients were identified by the Vancouver Centre Pharmacy database. Charts were reviewed and data extracted included patient characteristics, weight loss, performance status, and method of mediastinal staging. Outcome measures were overall survival, pathological response rate, and treatment-associated morbidity and mortality. Results: Between January 1999-2010, 177 patients were identified with locally advanced NSCLC (stage IIIA/B) treated with platinum and etoposide and ≥40Gy radiation therapy, with or without surgical resection. The majority of treatment plans were reached by a multidisciplinary conference consensus. 74% (n=131) of patients received chemoradiation alone (bimodality therapy) and 36% (n=46) received chemoradiation followed by surgical resection (trimodality therapy). Among the trimodality therapy group, 16 patients underwent pneumonectomy and 30 lobectomy. Conclusions: In this series, bimodality therapy for patients with locally advanced NSCLC had similar treatment associated mortality and survival outcomes as reported in the literature. Trimodality therapy was associated with low treatment mortality rates and favourable survival. These two groups cannot be directly compared in this retrospective study. However, these results support a multidisciplinary approach to identify and carefully select patients with locally advanced NSCLC to undergo additional surgical resection following concurrent chemoradiation. [Table: see text]
Adjuvant carboplatin, docetaxel, bevacizumab, and erlotinib versus chemotherapy alone in patients with resected non-small cell lung cancer: A randomized phase II study of the Sarah Cannon Research Institute (SCRI).
Authors: Waterhouse David Michael , Hainsworth John D. , Greco Frank A. , Barnes Edward K. , Lobo Christopher F. , Gian Victor , Joseph Mathew John , Peyton James D. , Huh Sang Y. , Daniel Davey B. , Quinn Raven , Burris Howard A. , Spigel David R. 
Published: March 2020

7035 Background: Adjuvant chemotherapy improves overall survival (OS) in patients (pts) with resected non small cell lung cancer (NSCLC). Bevacizumab and erlotinib improve survival in pts with advanced unresectable NSCLC. This randomized phase II multicenter pilot study examined the safety and efficacy of chemotherapy and bevacizumab followed by bevacizumab and erlotinib vs. chemotherapy alone in pts with resected NSCLC. Methods: Eligible pts had completely resected (R0) stage IB, II, or IIIA NSCLC (TNM 6th Ed.), any NSCLC histology, and an ECOG PS 0-1. Pts were excluded for preoperatively confirmed N2 disease; N2 disease found at surgery was allowed. Pts were randomized 1:1 to carboplatin AUC=5, docetaxel 60 mg/m2, and bevacizumab 15 mg/kg IV d1 q 21 days x 4, followed by maintenance bevacizumab 15 mg/kg d1 and erlotinib 150 mg PO daily x 8 cycles (Arm A) or carboplatin AUC=6 and docetaxel 75 mg/m2 IV d1 q 21 days x 4 (Arm B). The primary endpoint was 1-year disease-free survival (DFS); safety, 2-year DFS, and OS were secondary endpoints. Results: 106 pts were enrolled from 2/2008 to trial closure 1/2012 (A=54; B=52). Baseline features were balanced: age 63 yrs (42–87); 54% male; IB (46%), IIA (8%), IIB (27%), IIIA (18%); adenocarcinoma (61%), squamous (31%). Arm A received a median of 7 cycles (1-12); Arm B 4 cycles (1-4). 1- and 2-year DFS by stage are shown in the table. The 1-year DFS for all stages were 78% (A) and 88% (B) (p=.66). The 3-year OS for all stages were 81% (A) and 63% (B). Neutropenia was the most common grade 3/4 hematologic toxicity (A 18%; B 29%). Severe non-hematologic toxicity was rare: fatigue (A 6%), diarrhea (B 6%). Bronchopleural fistulae occurred in 2 pts (1 per arm), and grade 3 gastrointestinal hemorrhage was seen in 1 pt (A). Conclusions: This pilot study demonstrated that bevacizumab and erlotinib could be safely added to platinum-doublet chemotherapy in the adjuvant setting in all histologies. Larger randomized studies will best define the roles of these agents in pts with resectable NSCLC. [Table: see text]
Intrapleural combination bevacizumab with cisplatin therapy for non-small cell lung cancer caused by non-small cell lung cancer.
Authors: Du Nan , Zhao Hui , Wang Haibin , Li Xiaosong , Ma Junxun , Fan Zhongyi 
Published: March 2020

7036 Background: Malignant pleural effusion (MPE) is a common complicate of advanced non-small cell lung cancer (NSCLC). Bevacizumab, a humanized monoclonal antibody to VEGF, has been shown to be efficient in suppressing the pleural fluid accumulation; however, it has not been reported that whether bevacizumab can be used intrapleurally for the treatment of MPE. The present study is to evaluate the efficacy and safety of combined intrapleural therapy with bevacizumab and cisplatin, an antineoplastic agent, in controlling MPE. Methods: A total of 65 NSCLC patients with MPE were randomly assigned to one of two groups: intrapleural bevacizumab (300mg) with cisplatin (60mg) therapy (n=35) and intrapleural cisplatin (60mg) therapy (n=30). Results: The curative efficacy following combination or cisplatin mono therapy were 85.71% and 56.67%, respectively, being combination therapy group (p<0.05) is significantly higher. In addition, the combination therapy showed a higher efficacy in the patients with VEGF positive (p<0.01). Among the 25 cases that showed initial resistance to chemotherapy, 22 responded well to the combination therapy. Furthermore, combined bevacizumab with cisplatin therapy significantly reduced the VEGF expression, as shown by quantitative RT-PCR. All procedures were well tolerated by the patients, with wwwno severe side effect detected. Conclusions: Intrapleural combined bevacizumab with cisplatin therapy was effective and safe in managing MPE caused by NSCLC; the expression level of VEGF in MPE can be a prognostic marker for bevacizumab therapy.
Amplification of fibroblast growth factor receptor type 1 gene (FGFR1) in samples from 101 NSCLC patients (pts) with squamous cell carcinoma (SCC) histology.
Authors: Martinez Marti Alex , Martinez Pablo , Aura Claudia , Cedres Susana , Sullivan Ivana , Jimenez Jose , Prudkin Ludmila , Montero Maria Angeles , Murtra-Garrell Nuria , Zamora Esther , Navarro Alejandro , Hernandez-Losa Javier , Salcedo Maite , Canela Mercedes , Ramon y Cajal Santiago , Tabernero Josep , Felip Enriqueta 
Published: March 2020

7041 Background: The FGFR1 gene is located in the chromosomal region 8p12 and encodes a transmembrane receptor tyrosine kinase. Amplification of FGFR1 has been reported in lung cancer, predominantly in SCC (in up to ~ 20%) and has been considered a potential target for treatment with anti-FGFR1 agents. Different methods and cutoff levels to determine FGFR1 amplification have been reported but as yet no consensus has been reached on standard method. The aim of this study is to assess FGFR1 amplification determined by FISH analysis in a set of samples from 101SCC pts and to explore their clinical features. Methods: Tumor samples from 101SCC pts diagnosed at our institution from August 2007 to August 2011 were screened for FGFR1 amplification by FISH using the ZytoLight SPEC FGFR1/CEN8 probe. FGFR1 was considered FISH positive with a ratio > 2.2 and FISH FGFR1 was polysomic with 3 or more signals in ≥30% of tumor cells, any other result was considered as negative. For exploratory analyses FGFR1 amplification was considered positive if a median of 6 or more gene copies were identified and FISH were polysomic with more than 2 gene copies but less than 6. Results: Pts characteristics: median age 76 yrs (range 45-80), 91% male, 33% current smokers, 67% former smokers, stage: 8% IA/ 15% IB/ 11% IIA/ 11% IIB/ 24% IIIA, 12% IIIB/ 19% IV. With a median follow up of 48 months, the median overall survival was 18 months. FISH FGFR1 was positive (ratio > 2.2) in 7 (6.9%) pts: 6 were male, 4 former smokers. FISH FGFR1 was considered negative but polysomic (3 or more signals in ≥30% of tumor cells) in 43/94 (45%) pts. If we use for FISH positivity a cutoff of 6 or more copies only 3 patients were considered as positive for FGFR1 amplification (2 were also FISH positive by ratio>2.2). All those 5 patients considered FISH negative by gen copy number (but positive by ratio) were polysomic. Conclusions: In our experience FGFR1 amplification detected by FISH isrelatively uncommon in SCC, although a relevant proportion of FGFR1 FISH negative tumors had polysomy. Standarization of methods to determine FGFR1 amplification and the potential clinical significance of the presence of FGFR1 polysomy are needed.
Outcomes of combined modality treatment in elderly patients with stage III non-small cell lung cancer.
Authors: Cavalcante Ludimila , Kutwak Flavia , Ruiz Ana L. , Fan Tiffany , Samuels Judith , Samuels Michael , Rodriguez Estelamari 
Published: March 2020

7049 Background: The use of combined modality treatment (CMT) has been demonstrated to improve survival in patients with inoperable, locally advanced NSCLC. Elderly patients have been traditionally excluded from prospective clinical trials investigating CMT and thus the optimal treatment strategy for these patients remains unclear. We retrospectively evaluated the outcomes of elderly patients who received concurrent and sequential chemoradiation. Methods: All lung cancer patients age 70 or older who received chemotherapy and radiation treatment at Mt. Sinai Medical Center for stage III NSCLC between 1997 and 2010 were analyzed from tumor registry data. Among 282 lung cancer elderly patients diagnosed with stage III disease, 64 patients (22.7 %) received CMT as part of their treatment. Patients who underwent surgery and palliative radiation were excluded. Statistical analysis was performed by log-rank, Kaplan-Meier methods, and t-test. Results: Median age at diagnosis for the CMT group was 75 years (70-87), male/female: 34/30, TNM: T4N0-1: 12, T3N1: 1, TXN2: 41, TXN3: 10. Concurrent chemoradiation was delivered in 43 cases and sequential in 21 cases. RT doses ranged from 50 to 63 Gy. The most common chemotherapy regimens used were carboplatin and taxol (44 %) and carboplatin and etoposide (15%). The most common treatment-related toxicities were esophagitis (42%), anemia (39%), and pneumonia (24%). Median survival (MST) was 19 months and 11 months in the concurrent and sequential chemoradiation groups (p=0.67). Observed two, three and five-year overall survival (OS) in the CMT group was 49.1%, 27.5%, and 12.5%, respectively. Conclusions: Although CMT is not commonly used in elderly patients with lung cancer, the treatment is feasible and beneficial for selected patients in the community setting. Interestingly, the MST of elderly patients who received CMT in this cohort was comparable to that of younger historical controls with CMT. There was also a trend for increased survival in the concurrent versus sequential chemoradiation group.
Correlation of pretreatment surgical staging and PET SUVmax with outcomes in NSCLC.
Authors: Moscol Giancarlo , Jarrar Doraid , Tran Huyen , Tester William J. 
Published: March 2020

7051 Background: The AJCC staging does not recognize the number of involved mediastinal lymph nodes (LN), nodal stations or PET findings as prognostic factors in non-small cell lung cancer (NSCLC). Most clinical studies report poorer survival with greater number of involved LN and maximal tumor standardized uptake value (SUVmax) > 5. We hypothesized that clinical outcomes can be predicted by (1) number of involved LN, (2) number of involved nodal stations, (3) SUVmax of primary tumor and (4) SUVmax of mediastinum. Methods: Records of patients diagnosed with NSCLC stages I-IIIA from 1/1/99 to 12/31/10 were reviewed. Data collected included age, type of surgery, AJCC stage, number of LN/stations sampled and SUVmax of primary tumor/mediastinum. Primary outcomes were tumor recurrence and death. Descriptive statistics were used to summarize demographics. Prognostic factors were analyzed by a multivariate analysis using Cox’s proportional hazard model. Survival was estimated by the Kaplan-Meier method. Results: There were 369 patients with complete clinical data; 207 underwent surgical staging with mediastinoscopy (62) or VATS/open thoracotomy (145). The median number of LN sampled was 9 (range 1-35) and the median number of stations biopsied was 3 (range 1-9). PET was performed in 89 patients; 59 scans showed tumor SUVmax > 5. A total of 65/207 patients received chemotherapy. With median follow-up time of 29 months (range 1-116), 73 recurrences and 90 deaths were observed. Cox analysis showed greater recurrence risk for patients with 4 or more involved LN (HR= 4.66, CI=1.19-18.18, p=0.027) and higher mortality for patients with tumor SUVmax > 5 (HR=14.83, CI=2.32-94.9, p=0.004). Outcomes did not correlate with the number of involved nodal stations (p=0.76 for recurrence, p=0.51 for mortality) or with SUVmax of mediastinum (p=0.17 for recurrence, p=0.93 for mortality). Conclusions: The number of involved LN was an independent prognostic factor for recurrence but not for mortality. A tumor SUVmax >5 was independently associated with greater mortality. The number of involved stations and the SUVmax of mediastinum did not correlate with worse outcomes. Our results are limited due to the small number of cases with PET/CT scans and short follow-up.
miRNA profiling in resectable NSCLC by multiplex next-generation sequencing.
Authors: Gallach Sandra , Jantus-Lewintre Eloisa , Montaner David , Usó Marta , Sanmartin Elena , Sirera Rafael , Blasco Ana , Guijarro Ricardo , Martorell Miguel , Camps Carlos 
Published: March 2020

7060 Background: Early-stage NSCLC has a relapse rate around 40% within 5 years. With the advent of microRNA (miRNA), which seems to regulate many genes critical for tumorigenesis, there is a growing interest in the characterization of miRNAome in NSCLC specimens and to correlate them with prognosis. Next generation sequencing is a useful tool to study the miRNA content of solid tumors. Here, we applied high-throughput SOLiD transcriptome sequencing to study miRNAs expression in a cohort of early-stage NSCLC patients (tumor vs normal lung). Methods: RNA was isolated from frozen lung specimens (tumor and normal lung) from resectable NSCLC patients (n=35). Samples with a RIN ≥ 7 were analyzed and enriched in the miRNA fraction. miRNAs were sequencing using a bar-code multiplex SOLiD protocol. Data normalization was carried out by rescaling all data according to their counts. Readings were mapped against mature and no-mature miRNAs using miRBase. Statistical analysis was performed with CLCbio software and considered significant when p-adj<0.005. Results: Using the SOLiD high throughput sequencing, we performed a systemic miRNA expression profiling analysis of paired samples (tumor vs normal lung). A total of 1268 miRNAs (mature and no-mature) have been detected in at least one sample. The differential expression between normal and tumor samples shown that 6 miRNAs (miR-193b, miR-182, miR-96, miR-148a, miR-299, miR-590) were upregulated and 7 (miR-145, miR-133a, miR-218, miR-125a, miR-30a, miR-126 and miR-139) were down-regulated significantly in tumor samples compared with normal lung tissues. We are performing studies using qRT-PCR in an independent cohort to further validate these findings. Conclusions: The deep sequencing technology used for differential miRNA expression is useful and novel. The use of barcoding allows multiplexing and lowers cost per sample. Several miRNAs were differentially expressed between tumor and normal tissue, but this point needs to be further validated in an independent cohort. Supported by grants TRA09-0132 (MICINN) and RD06/0020/1024 (ISCIII).
Phase II study of concurrent cetuximab (C225) plus definitive thoracic radiotherapy (XRT) followed by adjuvant docetaxel in poor prognosis patients with locally advanced non-small cell lung cancer (LA-NSCLC).
Authors: Dilling Thomas J. , Extermann Martine , Kim Jongphil , Thompson Lora , 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

7065 Background: Recursive partitioning analysis has shown that ECOG PS ≥ 2, male gender, or age > 70 are prognostic of poor outcome in LA-NSCLC pts. Concurrent chemoradiotherapy improves survival, but toxicity is concerning in this frail pt cohort. We therefore opened this trial of concurrent definitive-dose XRT (70 Gy in 35 fractions) and C225 (250 mg/m2/dose), followed by adjuvant C225 and docetaxel (60 mg/m2 q3weeks x 3 cycles). Methods: Eligible patients had pathologically-proven LA-NSCLC (stage IIA – “dry” IIIB), not surgically resectable. They had ECOG PS 2 OR weight loss ≥5% in 3 months OR age >70. The primary objective was progression-free survival (PFS). Secondary objectives included overall survival (OS) and overall response rate (ORR). Results: From 5/2008 to 11/2010, 32 pts were evaluated for our single-institution, IRB-approved prospective clinical trial. 3 pts were screen-failures and 2 more withdrew consent prior to treatment, leaving 27 evaluable patients. 1 was removed due to poor therapy compliance and 2 were taken off trial due to grade 3 toxicity from the C225 loading dose, but were followed under intent-to-treat analysis. Median follow-up and OS was 10.5 months. Median PFS was 7.8 months. ORR = 59.3%. 8 early/sudden deaths were reported, so the trial closed early: radiation pneumonitis (RP) was the apparent cause in 1 and probably/possibly in 4 others, with insufficient information in 2 additional pts; 1 pt died of failure to thrive. Of the remaining pts, 3 developed grade 3+ RP and 2 had grade 2 RP. Conclusions: Pts enrolled on this trial had improved OS compared with poor-PS historical controls (10.5 vs 6.3 months) and comparable OS compared with good-PS historical controls (10.5 vs 11.9 months) treated with RT (Werner-Wasik M et al. Int J Radiat Oncol Biol Phys. 2000;48:1475-82). However, pulmonary toxicity is a concern. Analysis of RP events is ongoing. Updated results will be presented at the meeting.
Preoperative survivin, ERCC1, and PTEN expression in stage III non-small cell lung cancer (NSCLC) patients (pts) treated with neoadjuvant and definitive chemoradiation and association with overall survival (OS).
Authors: Batus Marta , Fidler Mary J. , Walters Kelly Kaiser , Pool Mark , Mahon Brett , Basu Sanjib , Borgia Jeffrey Allen , Sher David , Bonomi Philip D. 
Published: March 2020

7067 Background: Thoracic radiation and concurrent chemotherapy consisting of platinum based doublets has produced modest improvement in long term survival for patient with locally advanced (LA) NSCLC. There is relatively little information regarding molecular profiles and outcome in LA-NSCLC patients (pts) treated with chemoradiation. The objective of this retrospective study is to evaluate potential relationships between expression of DNA repair enzyme ERCC1 and enzymes involved in cell survival – survivin and PTEN. Methods: Stage III NSCLC pts who were treated with chest radiation (40-60Gy) and concurrently with platinum doublet and who had sufficient pretreatment tissue were included in this study. Immunohistochemistry was used to detect nuclear and cytoplasmic expression (frequency 0-4 and intensity 0-4) of survivin, and PTEN, and for nuclear expression of ERCC1. Product of intensity and frequency was calculated for all markers and correlated with overall survival (OS). Results: 97 pts had adequate tumor samples for analysis. 53 women, median age 67. 48 pts with ERCC1 prod <=6 had longer OS than 41 pts with ERCC1 prod >6 (19.6 vs 1.0 months, p=0.034). 16 pts with ERCC1 prod >6, PETN prod <=6 and survivin prod >4 had significantly lower OS than 68 pts with ERCC1<=6, PETN >6 and survivin <=4 (17.2 vs 40.2 months, p<0.001). Conclusions: The association of inferior survival in LA-NSCLC pts whose tumors express high survivin, low PTEN, and high ERCC1, suggests that combining inhibitors of survivin and or of PI3KCA with chemoradiation and developing strategies to inhibit DNA repair might improve outcomes in this group of pts.
Phase II trial: Concurrent chemotherapy and radiotherapy with nitroglycerin in locally advanced non-small cell lung cancer patients.
Authors: De la Mata Dolores , Blake Monika , Moreno Jesus Zamora , Pena Omar , Flores-Estrada Diana , Turcott Jenny , Arrieta Oscar 
Published: March 2020

7068 Background: The treatment of choice for locally advanced non small cell lung cancer (NSCLC) is concurrent chemoradiation (CRT). However, efforts to improve treatment results include targeted therapy and the use of radiosensitizers. Nitroglycerin (NTG), a nitric oxide (NO) donor agent, reduces expression of Hypoxia-Induced Factor, which is associated to both chemo and radio resistance. Methods: This is phase II trial in patients with locally advanced NSCLC treated with chemotherapy (CT) based on cisplatin and vinorelbin with NTG concurrent with radiation therapy. A 25 mg NTG patch was administered to the patients during the first 5 days of each induction treatment cycle and during chemo-radiotherapy. Blood samples of VEGF were taken before any treatment and after two cycles of CT. The protocol is registered with ClinicalTrials.gov, number NCT00886405. Results: 35 patients were enrolled in this trial. Median Follow up was 16.6 months (SD ±13.6). Mean age was of 59.9 years (±10.8), 68.6% of the patients were smokers. ECOG status was 0 in 22.9%, 1 in 65.7% and 2 in 11.5%, respectively. Histopathology was adenocarcinoma in 68.6%, epidermoid in 17.1% and undifferentiated in 14.3%. Stage distribution was: IIIa, 57.6% and IIIb, 42.5%. All patients completed CRT treatment and four underwent surgical treatment. Toxicity profile related to NTG was grade 1 and 2 headache in 17.1%. Grade 3 and 4 toxicities were esophagitis (17.1%), neutropenia (62.9%), and nausea (5.7%). Sixty-four per cent of patients achieved partial response after CT and 75.8% after CRT. PFS was 11.8 months (95%, IC 7.8-15.6) and OS was 42.9 months (95%IC 31.3-52.1). After two cycles of CT, plasma VEGF levels were significantly lower (Median 132±79 vs. 53±78 pg/ml, p<0.001). No differences on PFS and OS were found between patients with a reduction ≥ 93 pg/ml (median of differences between VEGFR before and after chemotherapy). Conclusions: The addition of NTG to induction CT, and concurrent CRT on locally advanced NSCLC patients seems to increase the response rate, PFS and OS with an acceptable toxicity profile. A prospective trial is warranted to confirm these findings.