bluuebunny/crossref_metadata_2025_split huggingface dataset:
11C-PD153035 PET/CT molecular imaging of EGFR for evaluation of advanced non-small cell lung cancer (NSCLC) to EGFR-targeted therapy
Authors: Meng X. , Yu J. M. , Yang G. R. , Zhao S. Q. , Sun X. D. 
Published: August 2020

7576 Background: Our previous study suggests that 11C-PD153035, a specific and potent inhibitor of EGFR tyrosine kinase (EGFR-TKI), is a novel PET radiotracer and 11C-PD153035 PET/CT is a promising non-invasive method for in vitro and vivo imaging of EGFR in NSCLC. We report a pilot study evaluating the efficacy of 11C-PD153035 PET/CT imaging as a “molecular fingerprint” to the EGFR-TKI in advanced NSCLC (stage IIIB/IV). Methods: Patients with pathologically proved advanced NSCLC were enrolled. 11C-PD153035 PET/CT was performed before (PET/CT 1) and 4 weeks after (PET/CT 2) received EGFR-targeted therapy (erlotinib) with assessment of maximum standardized uptake values (SUVmax) for correlation with response. Treatment response was also expressed as CT results on the basis of traditional Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Image fusion and calculation of tumor subvolumes was performed on Xeleris workstation. Radioactivity concentrations, derived from regions of interest, were analyzed to the SUVmax. Results: 12 patients (5 men, 7 women; age range, 60–79 years) have been enrolled in this study from August 2008, including 3 cases of squamous cell carcinoma, 1 case of large cell carcinoma, and the other of adenocarcinoma. Tumor uptake of 11C-PD153035 before received therapy was observed in 8 patients and SUVmax ranged from 3.1 to 5.9. There was significant difference in SUVmax (p < 0.01) between tumor and normal tissue. Tumor/lung ratio at 20 min was 4.14 ± 1.80. The SUVmax did not correlate with tumor marker before therapy in our limited data. After 4 weeks therapy, a total of 7 patients underwent the 11C-PD153035 PET /CT again and 5 patients only received CT scanning. Tumor responders had a higher baseline pre-therapy SUVmax than nonresponders (p < 0.01). However, there was no significant difference between pre- and post-therapy SUVmax among 7 patients (p > 0.05). Conclusions: Our data indicated that 11C-PD153035 PET/CT before therapy may play a vital role for identification of patients that could be suitable for EGFR targeted therapies. Thus, it offers opportunities to individualize and optimize target therapy for NSCLC patients. No significant financial relationships to disclose.
The role of extrapleural pneumonectomy in the management of pleural cancers
Authors: Sugarbaker D. J. , Tilleman T. R. , Swanson S. J. , Jaklitsch M. T. , Mentzer S. J. , Mujoomdar A. A. , Bueno R. 
Published: August 2020

7577 Background: We report our experience with EPP for non-mesothelial malignancies. Methods: A retrospective chart review, from June 1994 to October 2007. For all cases, the site of disease involved a single pleura. Results: Sixty-five patients underwent EPP for cancers other than mesothelioma over a 13-year period at our institution. Of these, 32 patients had mediastinoscopy negative T4 lung cancer, 11 had metastases to only one pleura from extrathoracic sites, 10 had unilateral lung sarcomas involving the pleural envelope, 8 had thymomas metastatic to a pleural space, 2 were preoperatively diagnosed as mesotheliomas but at final pathology were determined to be small cell lung cancer and sarcomatoid carcinoma, and 2 represented primary mucoepidermoid and neuroectodermal malignancies. Twenty-eight patients had stage IIIB (T4-N0–1) lung adenocarcinoma representing the largest homogeneous group of patients by cell type and stage. Overall perioperative mortality was 4.6% (3/65). Postoperative morbidity was 44.6% (29/65) with the most common being arrhythmia (n=15), vocal cord paralysis (n=7), and respiratory failure (n=5). Overall survival after surgery was 15.7 months for all the patients. Survival was significantly higher for NSCLC patients with N0 (n=9) on final pathology versus any other nodal status (N1/N2), 52.1 months versus 14.1 months (p=0.0003). Median survival for stage IIIB NSCLC was 16.7 months. Seven of the 8 thymoma patients were alive at last follow-up (median follow-up 22.8 months). Median survival for patients with sarcoma (n=10) or pleural metastases from extrathoracic sites (n=11) was 3.7 and 4.2 months, respectively. Recurrence at follow-up was documented in 21 patients with only 2 (9.5%) occurring in the ipsilateral hemithorax. Conclusions: EPP can be a safe treatment option for some cancers that involve a unilateral pleura. Patients with stage IIIB (T4, N0–1) NSCLC confined to a single pleural cavity or patients with thymoma involving one pleura may benefit from multimodality treatment including EPP. Absence of residual nodal disease at resection is positively correlated with survival in the stage IIIB NSCLC group. Patients undergoing surgical resection for pleural metastases of primary sarcomas or extrathoracic metastasis, however, do not appear to benefit from EPP. No significant financial relationships to disclose.
Feasibility and safety of detection of sentinel node in lung cancer
Authors: Barcelo-Galindez R. , Uribe-Etxebarria N. , Viteri A. , Genollá J. , Jimenez-Maestre U. , Lorenzo-Martín M. , Rios G. , Rojo-Marcos R. , Rumbero-Sanchez J. , Pac-Ferrer J. 
Published: August 2020

7587 Background: Sentinel node (SN) can be detected in the drainage of many primary cancers and is considered a standard procedure in some tumors. For resectable lung cancer its study has began recently and its detection has not yet been standardized. Objective: To study the feasibility and safety of SN detection during surgery for lung cancer. Methods: Patients with non-small cell lung cancer, clinical stage I, amenable to surgery were eligible. Written informed consent was obtained in each patient before the procedure. Technique, as described by Liptay et al, consisted of four injections of albumin labelled with Technetium99, 0,25 mCi each peritumorally, and five minutes later, lobectomy and lymphadenectomy were associated with detection of SN (both in vivo and ex vivo). Results: From Jan 2006 to Nov 2008, the first 37 patients were included. In 35 patients one SN was detected, and in 2 there were two SN. SN was found in the lymphatic stations 10 or 11, except for tumors located in the left upper lobe, where two cases of a SN were found in station 5 and 6 each. In 23 cases of 37, both SN and lymphadenectomy were free of tumor. In seven of 37, SN was positive (in one, micrometastasis was detected with haematoxilin-eosin), and the rest of the nodes were free of tumor. In five of 37, SN and another node were positive. In two of 37, SN was falsely negative as one peribronchial node was positive but masked by radioactivity in the injected lung, one in right lower lobe and another in left lower lobe. Accuracy was 94,6%, sensibility 86%, specificity 100%, positive predictive value 100% and negative predictive value 92%. No relevant prolongation of surgery time was observed (5–15 minutes), and no morbidity or mortality related to this technique were seen. The cost of the materials used was 100 Euro per patient. Recruitment is ongoing. Conclusions: SN can be detected with a very high accuracy in lung cancer. This technique is feasible and safe, and does not add excessive cost or difficulty to the surgery of lung cancer. Modifications of the technique, using metabolic isotopes or new portatil 3D gamma detectors can be incorporated. Its final role in the staging and treatment of lung cancer is still unknown. Supported in part by a grant of the FIS (Fondo de Investigaciones Sanitarias), Spain. No significant financial relationships to disclose.
Gemcitabine-capecitabine in platinum-refractory patients with thymic epithelial tumors
Authors: Palmieri G. , Merola C. , Petillo L. , Merola G. , Federico P. , Leopardo D. , Marino M. , Montella L. 
Published: August 2020

7590 Background: Platinum based combination chemotherapy is the actual standard of care for advanced and recurrent Thymic epithelial tumours-TET (thymoma and thymic carcinoma). Additional agents are needed in this setting. We have designed a pilot study, phase II multicenter, to evaluate the efficacy and safety of no tested schedule gemcitabine-capecitabine in patients refractory to platinum based chemotherapy. Methods: Eligible patients had pathologically confirmed TET and were treated with at least 2 lines of chemotherapy, one of this being a platinum based schedule. From January 2007 to September 2008 twelve pts were enrolled. Treatment Schedule: Gemcitabine 1,000 mg/m2 by 30-minute infusion on days 1 and 8 every 3 weeks plus oral capecitabine 650 mg/m2 twice daily on days 1 to 14. Response was evaluated at 3 and 6 cycles. Results: Pts Characteristics: 12 pts (7 M-5F, Median Age 51,3 yrs,range 27–76). 7 pts had received Thymectomy and 4 of this had received also surgery for metastatic disease. 5 pts have received only thymic biopsy. Performance status sec. Karnofsky was 90% (range 80–100). Site of disease: liver, lung, bone, nodal, pleural and pericardium. All pts were staged IVB sec. Masaoka. Tumors were classified by WHO classification as follows: 4-B2, 8-B2/B3. All pts were evaluated as concerns performance status and all had Karnofcky 90% (range 80–100). Sites of metastatic disease were: liver,lung,bone,nodal, pleural and pericardium. Associated paraneoplastic syndromes were: myasthenia in 7 pts, B-lymphopenia 11 pts. The minimum number of cycles administered on study was 3 (range 3–8).Among the 12 enrolled pts there were 10 objective response: 2 CR, 8 PR. 2 pts had SD. Prolonged maintenance of absence of disease was obtained in the 2 pts reporting a CR (more than 6 months in 1 patient). Treatment was well tolerated, no grade 4 toxicities was registered. Conclusions: The combination schedule gemcitabine-capecitabine have an high activity in Thymic malignancies in pts heavily pretreated with advanced recurrent TET and appears to be a safe option in platinum-refractory TET pts. This schedule must be proposed to be used also in randomized clinical trial compared with platinum based treatment. No significant financial relationships to disclose.
Prognostic value of microRNAs (miRNAs) profiling in early-stage squamous cell lung cancer (SqCLC)
Authors: Skrzypski M. T. , Szymanowska A. , Jassem E. , Rzepko R. , Pawlowski R. , Wyrwicz L. , Goryca K. , Marjanski T. , Rzyman W. , Jassem J. 
Published: August 2020

7594 Background: About 50% of NSCLC patients (pts) will develop distant metastases following pulmonary resection. Currently, apart from clinical stage at diagnosis, there are no reliable clinical factors to select high risk pts for adjuvant chemotherapy. miRNAs profiling is expected to indicate pts with aggressive disease and to provide prognostic information. Confounding effect of NSCLC pathology heterogeneity justifies searching for prognostic miRNAs separately in SqCLC and adenocarcinoma. Methods: Fresh frozen tumor tissue was obtained from 30 SqCLC stage I-II pts during curative pulmonary resection. Of those, 15 pts developed distant metastases and 15 had no relapse after a median follow-up of 5.4 years (range, 3.1–6.9 years). RNA was isolated from tumor sections containing ≥60% of tumor cells per section. Expression of 380 miRNAs was analyzed by RT-PCR arrays (TLDAs-Appliedbiosystems). Raw data were normalized vs. the expression of U6 RNA and calibrated by ΔΔCt method. Results: Expression of 300 miRNAs was detected in tumor tissues. Expression of three miRNAs (193a[5p], 146b[5p] and 10b) differed between groups with and without metastases (t-Student test, p<0.05). Due to the limited number of samples, proportional hazard regression for survival (Cox analysis) could not be performed on the full data set of 300 variables. Cox analysis performed for the top 5 miRNA identified with t-Student test showed significant correlation for 10b (p<0.02). The internal consistency of data sets was tested using PCA, and three samples were excluded. In this modified test set, the top 10 miRNAs (ranked according to p-value of t test) revealed two significantly correlated miRNAs in Cox analysis: 484 and 146b (5p). Similar results were obtained for miRNAs expression defined as continuous or categorized variables. Conclusions: Four miRNAs: 10b, 146b, 193a(5p) and 484 are potentially related to high metastatic propensity of early stage SqCLC. Further validation is necessary to confirm their prognostic relevance in this tumor. No significant financial relationships to disclose.
A randomized placebo-controlled phase III study of docetaxel/carboplatin with celecoxib in patients (pts) with advanced non-small cell lung cancer (NSCLC): The NVALT-4 study
Authors: Groen H. , Hochstenbag M. M. , van Putten J. W. , Vincent A. , Dalesio O. , Biesma B. , Smit H. J. , Termeer A. , van den Borne B. E. , Schramel F. M. 
Published: August 2020

8005 Background: Cox-2 is overexpressed in NSCLC tumors and has a negative impact on survival. It is involved in proliferation and angiogenesis. The hypothesis is that celecoxib by inhibiting Cox-2 enzyme will prolong survival and may increase response to chemotherapy. Methods: We performed a phase III study with planned sample size of 540 pts. Included were pts with pathologically proven NSCLC, no prior chemotherapy, PS=0–2, measurable disease, adequate organ functions. Excluded were pts with CHF NYHA class II-IV, atherosclerotic diseases, gastrointestinal bleeding, symptomatic brain metastases and chronic use of NSAIDs (defined as 1 wk for >3 wks per yr or more than 21 days throughout the year). Acetylsalicylic acid (ASA) ≤ 150 mg/d was allowed. Pts were treated with docetaxel 75 mg/m2;, carboplatin (AUC = 6 mg/ml.min) every 3 wks for 5 cycles and randomized for celecoxib (cel) 400 mg bd, starting on day 1 for 3 years or placebo (plac) 400 mg bd. Stratification was by WHO PS (0–1 vs. 2), stage (IIIB vs. IV), ASA (yes vs. no) and hospital. Primary endpoint was overall survival. Results: From July 2003 until Dec 2007 561 pts were randomized (cel 281 pts, plac 280 pts). Median follow-up was 36 months (mo). Median (range) age 61 yrs(33–84), M/F 63/37%, PS 0/1/2 45/48/6%, adeno/large cell/squamous/other 48/27/18/7%, stage IIIB/IV 17/83%, 11% of pts used acid ≤ 150 mg/day. Reason to end treatment (cel/plac arm) was therapy completed (51/45%), PD (17/22%), adverse events (8/10%), death (8/8%). Toxicity was mild and no increase in cardiovascular events were observed in cel arm. CR, PR, SD, PD in cel/plac arm was 0/1%, 33/26%, 35/40%, 14/19%, respectively. Response rate in evaluable pts was better in the cel arm (p=0.05). Median PFS (95% CI) was 5,5 mo ( 4,3 - 6,8), OS was 8,3 mo (7,5 - 8,8), not different for both arms. HR stratified by ASA and PS for PFS and OS was 0,94 (0.79–1.13) and 0.95 (0.79–1.15), respectively. Conclusions: Addition of celecoxib to first line chemotherapy improves response rate but not progression-free interval or overall survival. No significant financial relationships to disclose.
A phase II trial of salirasib in patients with stage IIIB/IV lung adenocarcinoma enriched for KRAS mutations
Authors: Johnson M. L. , Rizvi N. A. , Ginsberg M. S. , Miller V. A. , Kris M. G. , Pao W. , Riely G. J. 
Published: August 2020

8012 Background: KRAS mutations are present in 30% of lung adenocarcinomas and are associated with primary resistance to erlotinib and gefitinib. Salirasib severs RAS proteins from the membrane, decreasing function of all RAS isoforms. Salirasib inhibits KRAS-dependent growth in cell lines and xenograft models. This phase II study was designed to determine the activity of salirasib in patients (pts) with advanced NSCLC enriched for KRAS mutations. Methods: Two cohorts of pts with stage IIIB/IV NSCLC were eligible. Group A: pts with KRAS mutations previously treated with chemotherapy. Group B: previously-untreated pts with ≥15 pack-year smoking history. Salirasib was given orally, for days 1–28 of a 35 day cycle, with response assessment on day 28, day 63, and every 10 weeks (wks) thereafter. The primary endpoint was rate of RECIST non-progression at 10 wks. Secondary endpoints were response rate (RR), time to progression (TTP), overall survival (OS) and toxicity. Results: From August 2007-December 2008, 33 pts were enrolled (20 women); median age 68 (range 46–79). Pts in Group A had received a median of 2 lines of prior chemotherapy. All 23 pts in Group A and 7/10 pts in Group B had KRAS mutations. Of the 30 pts with KRAS mutations, 7 were never smokers or smoked ≤15 pack-years. Three pts withdrew due to drug-related diarrhea in the first 10 wks of therapy. Four pts have not reached 10 wks of therapy. After 10 wks of salirasib, 5/18 (28%) previously treated pts with KRAS mutations and 3/8 (38%) previously untreated pts showed no progression. The RR in pts was 0/18 for Group A and 0/8 in Group B. For all pts with KRAS mutations, the RR was 0/23. The median TTP was 1 month (mo) and 2 mo in Groups A and B, respectively. The median OS was 13 mo for Group B and not reached in Group A (median follow-up 3 mo). Grade 3 diarrhea and fatigue were the most common toxicities. Conclusions: After 10 wks of salirasib, 28% of previously treated pts with KRAS mutations and 38% of untreated pts had stable disease. No partial or complete responses were seen in pts with KRAS mutations. The successful enrollment over 15 months of 29 pts with tumors with known KRAS mutations demonstrates that trials of a KRAS-specific genotype in lung cancer are feasible, and should be standard in future studies targeting the KRAS pathway. [Table: see text]
Biomarker analyses from the phase III placebo-controlled SATURN study of maintenance erlotinib following first-line chemotherapy for advanced NSCLC
Authors: Brugger W. , Triller N. , Blasinska-Morawiec M. , Curescu S. , Sakalauskas R. , Manikhas G. , Mazieres J. , Whittom R. , Rohr K. , Cappuzzo F. 
Published: August 2020

8020 Background: The SATURN (BO18192) study investigated whether erlotinib maintenance therapy improved PFS in patients (pts) with advanced NSCLC who had obtained clinical benefit from 1st-line chemotherapy. This study included a prospective analysis of the prognostic/predictive value of several molecular markers. Methods: 889 pts with advanced NSCLC whose disease had not progressed following 4 cycles of 1st-line platinum-doublet chemotherapy were randomized to erlotinib 150 mg/day or placebo. Mandatory tumor specimens were collected at baseline and tested for EGFR protein expression using immunohistochemistry (IHC), EGFR gene copy number using fluorescent in-situ hybridization (FISH), and EGFR and KRAS somatic mutations using DNA sequencing. Pts were stratified according to EGFR IHC status (any membranous staining in ≥10% tumor cells used as cut-off); the co-primary endpoint was PFS in EGFR IHC+ pts. Baseline whole blood samples were obtained for genotyping of EGFR (intron 1 CA-repeat polymorphisms). Results: In the overall population, erlotinib significantly prolonged PFS vs placebo (HR 0.71, p<.0001; primary endpoint). The co-primary endpoint was also met, with erlotinib significantly improving PFS in the EGFR IHC+ group (HR 0.69, p<.0001). Many tumor samples were assessable for molecular marker status (see table). Biomarker data suggest that patients derived a PFS benefit with erlotinib irrespective of EGFR FISH or EGFR intron 1 CA-repeat status. The magnitude of benefit with erlotinib was similar in both KRAS-mutant and KRAS wild-type pts. Conclusions: This is the largest biomarker analysis performed for erlotinib in a randomized, placebo-controlled setting, and answers key scientific questions regarding the prognostic and predictive value of potential biomarkers of efficacy. Full data will be presented. [Table: see text] [Table: see text]
KRAS mutation analysis in cetuximab-treated advanced stage non-small cell lung cancer (NSCLC): SWOG experience with S0342 and S0536
Authors: Mack P. C. , Holland W. S. , Redman M. , Lara P. N. , Snyder L. J. , Hirsch F. R. , Franklin W. A. , Kim E. S. , Herbst R. S. , Gandara D. R. 
Published: August 2020

8022 Background: KRAS mutations occur in NSCLC with a frequency of 15–25% and have been associated with a poor response to EGFR tyrosine kinase inhibitors. In colorectal cancer, benefit from the EGFR-targeted monoclonal antibody cetuximab is largely limited to patients (pts) whose tumors are KRAS wild-type (WT). However, in cetuximab-treated NSCLC, a predictive role for KRAS mutations has not been established. We evaluated KRAS status in specimens from two cetuximab-based front-line multicenter SWOG phase II trials in advanced NSCLC. Methods: DNA extracted from archival tumor and plasma specimens from S0342 (carboplatin-paclitaxel plus sequential vs. concurrent cetuximab) and S0536 (carboplatin-paclitaxel-cetuximab-bevacizumab) was analyzed for KRAS mutations by micro-dissection/sequencing and/or Scorpion-ARMS (DxS LTD). Results: For S0342, 45 archival tissues and 90 plasma specimens were analyzed. Combined, KRAS mutations were detected in 24% of pts. No differences between mutant and WT tumors were observed for response rate (p=0.62) or progression-free survival (PFS; p=0.65). Overall survival (OS) was non-significantly higher for pts with WT vs. mutant KRAS [median OS: 11 vs. 8 mo.; p=0.39]. When evaluated with EGFR copy number analysis conducted previously (JCO 10:3351, 2008), pts with both low EGFR copy number and mutant KRAS trended towards a worse OS [7 mo. vs. 17 mo. for all others, p=0.08, n=31]. For S0536, 6/26 pt specimens (23%) harbored KRAS mutations. In the limited sample set available from S0536, no associations were observed between KRAS status and clinical outcome [response rate: p=0.83; PFS: p=0.93; OS p=0.89]. Conclusions: These data suggest that KRAS mutations may not play a significant predictive role for cetuximab-based therapy in NSCLC, contrary to colorectal cancer. KRAS analysis in recently completed phase III trials of chemotherapy ± cetuximab will be of interest to confirm these observations. Trends in favorable OS in pts with WT KRAS may reflect prognostic effects of KRAS mutations. [Table: see text]