bluuebunny/crossref_metadata_2025_split huggingface dataset:
Costs associated with intravenous (IV) chemotherapy administration in patients with lung cancer
Authors: Skarin A. T. , Duh M. S. , Weiner J. R. , Lefebvre P. , Neary M. P. 
Published: March 2020

18092 Background: The IV method of chemotherapy administration imposes not only a time burden on patients and facilities, but also has cost implications for payers. This study aims to assess the costs associated with the IV administration of chemotherapies for patients with all forms of lung cancer and for a subset of patients with small cell lung cancer (SCLC) in a large employer-payer claims database. Methods: Using medical claims data from 5.5 million beneficiaries between 01/01/1998 and 01/31/2006, we identified 8,605 patients with lung cancer (ICD-9 codes 162.3–162.9, 176.4, or 197.0) receiving IV chemotherapies. We then identified a subset of 942 patients likely to have SCLC by selecting those receiving chemotherapy regimens primarily used to treat SCLC and excluding patients receiving procedures and treatments often associated with NSCLC. Average total costs per day of IV chemotherapy administration (including drug, administration costs, etc.) were computed for all patients and for the SCLC subset based on the actual amount paid. Costs were also computed separately for: IV chemotherapy drugs, IV chemotherapy administration procedures, and other drugs and services such as IV administration of other drugs to treat side effects of chemotherapies, evaluation and management, and laboratory tests. Results: Average total cost per day of IV chemotherapy administration for all patients was $1,112, with $652 (59%) attributable to IV chemotherapy drugs, $85 (8%) to IV chemotherapy administration procedures, and $375 (34%) to other drugs and services. Among patients with SCLC, average total daily cost was $815, with $423 (52%) attributable to IV chemotherapy drugs, $89 (11%) to IV chemotherapy administration, and $303 (37%) to other drugs and services. Conclusions: IV chemotherapy administration procedures and other visit-related services accounted for 42% and 48% of total costs in patients with all forms of lung cancer and those with SCLC, respectively. The increased availability and use of oral chemotherapy drugs in lung cancer should provide savings to payers by avoiding the costs associated with IV administration. No significant financial relationships to disclose.
Prognostic serum markers in malignant pleural mesothelioma: Epidermal growth factor and platelet-derived growth factor
Authors: Betta P. , Libener R. , Orecchia S. , Salvio M. , Schillaci F. , Filiberti R. , Puntoni R. , Paganuzzi M. , Marroni P. 
Published: March 2020

18097 Background: While no previous data has so far shown any difference between the efficacy of serum platelet-derived growth factor (PDGF-AB) and serum epidermal growth factor (EGF) in distinguishing MPM from benign pleural diseases, some pilot studies have shown the potentiality of both these markers in the prognosis of MPM patients. This study investigates this capacity by analyzing survival in a series of MPM patients. Methods: Using an ELISA method, EGF (ng/ml) baseline serum was determined in 83 newly diagnosed MPM patients, and in 62 cases PDGF-AB serum levels were also measured. After a median follow-up time of 11.8 months (range 0.4–52.1 months), the log-rank test was used to compare the survival curves, and Cox’s regression analysis was also performed. Results: Median serum values were 0.56 ng/ml (range 0.09–2.05) for EGF and 43.0 ng/ml (range 0.1–145) for PDGF-AB. Patients with EGF levels higher than the median level of 0.56 ng/ml had an average survival time of 9.4 months (95%CI: 5.7–13.2), while the average survival time of patients with below-median EGF levels was 13.2 months (95%CI: 10.6–15.8); a statistically significant difference (p=0.005). For patients with PDGF-AB levels higher than an assumed cut-off of 49.8 ng/ml, (above 75th percentile of MPM marker concentration) average survival was 7.9 months (95%CI: 4.5–11.3) as against the 14.9 months (95%CI: 10.3–18.7) in patients with below cut-off marker levels, again statistically significant (p=0.02). Cox’s regression analysis was performed on 42 patients in whom data on age, sex, histology, stage and platelet count were available. EGF and PDGF-AB levels higher than the selected cut-offs were confirmed as independent predictors of poor survival (HR=1.49; 95% CI: 1.04–2.13; p=0.03 and HR=1.96; 95% CI: 1.23–3.13; p=0.005, respectively). Conclusions: Our data suggest that circulating PDGF-AB and EGF levels are promising markers for clinical monitoring of MPM patients. No significant financial relationships to disclose.
Hormone replacement use, age, and prognosis for women with non-small cell lung cancer
Authors: Robinson A. , Ayeni M. 
Published: March 2020

18099 Background: Lung cancer is the leading cancer cause of mortality in women. A recent report by Ganti et al, presented at ASCO, suggested that women who had been taking hormone replacement therapy (HRT) had significantly decreased survival after a lung cancer diagnosis. In addition, in women fit enough to be enrolled on randomized controlled trials in advanced lung cancer, younger women (under age 60) may have a worse prognosis than older women. The purpose of this current study was to do an institutional review on women diagnosed with lung cancer to determine whether these novel prognostic factor results could be duplicated. Methods: All female patients who were diagnosed with lung cancer between January 1999 and December 2003 were reviewed for age at diagnosis, stage, treatment, smoking history, hormonal therapy, performance status, weight loss, age at menopause, and overall survival. Patients were excluded if they had small cell lung cancer, were unknown primary, or had previous or synchronous non-lung, non-skin, cancers. Statistics were performed using Chi- Squared tests for categorical variables, while the Kaplan-Meier method and Cox-Regression models were used for univariate and multivariate analysis of overall survival. Results: Of 397 patients, the majority (68%) were stage 3 or 4. There were very few never smokers (5%). Twenty-nine percent of patients had prior HRT, with no effect on overall survival, with median survivals of 13 months in the non- HRT group and 14 months in the HRT group. The most powerful predictors of overall survival were: Stage, Performance Status, and Weight Loss. Patients aged 60–75 did as poorly as younger patients (median survival 10 months for stage 4 disease). Conclusions: Stage, performance status, and weight loss, are the most powerful predictors of survival for women with lung cancer. Patients with prior HRT use do not have inferior outcomes compared to non-HRT users. In a non-clinical trial population, patients under age 60 have similar outcomes as women aged 60 to 75. No significant financial relationships to disclose.
Preoperative docetaxel and gemcitabine in resectable non-small cell lung cancer: A phase II trial of the Minnie Pearl Cancer Research Network
Authors: Thompson D. S. , Spigel D. R. , Greco F. A. , Yardley D. A. , Burris H. A. , Vazquez E. , Erland J. , Shipley D. L. , Spremulli E. , Hainsworth J. D. 
Published: March 2020

18100 Background: Preoperative chemotherapy may improve outcomes for patients (pts) with resectable non-small cell lung cancer (NSCLC) compared with surgery alone. This multicenter community-based phase II trial examined the role of preoperative gemcitabine (G) and docetaxel (D) in pts with resectable NSCLC. Methods: The primary endpoint was to assess the pathologic response rate of G/D in pts with potentially resectable clinical stages IB, II, and selected III NSCLC [T3N1, T1–3N2 (1 nodal station = 2 cm), T4N0, T4N1 excluding vascular, tracheal, esophageal, vertebral disease, or malignant effusions]. Additional eligibility criteria: measurable disease, ECOG PS 0–1, and informed consent. Treatment: G 1,000 mg/m2 and D 30 mg/m2 days 1, 8 every 21 days x 3 cycles. Pts were restaged after treatment and resected 3–6 weeks later. If pts were inoperable, had incomplete resections, or N2 disease, D 20 mg/m2, carboplatin AUC=1.5 weekly x 7, and radiation to 63 Gy were administered. Analysis was by intent to treat. Results: Between April 2004 and September 2005, 75 pts were enrolled. Median age was 62 years. 92% of planned preoperative therapy was administered and 38 pts (51%) underwent resection. The clinical objective response rate was 30% (95% CI 20%-42%). No pathological complete responses were observed. 26 pts went on to receive chemoradiotherapy. Median progression-free survival was 9.8 months (95% CI 5.9–13.9). Median overall survival was 18 months (95% CI 14.8- 21.3). 71% of pts were alive at 1 year. Grade 3/4 hematologic toxicity with preoperative therapy included neutropenia (28%), anemia (4%), and thrombocytopenia (7%). Grade 3/4 non-hematologic toxicity was limited. Conclusions: G/D is a well tolerated preoperative regimen for pts with resectable NSCLC, however did not result in pathologic complete responses. There is no suggestion that G/D is more active than other tested combined modality regimens. The role of preoperative therapy in NSCLC remains undefined. Additional studies comparing preoperative and adjuvant treatment are warranted. No significant financial relationships to disclose.
A pilot study of weekly docetaxel and daily trofosfamide as metronomic second-line chemotherapy in the treatment of metastatic non-small cell lung cancer (NSCLC)
Authors: Gorn M. , Habermann C. , Thom I. , Schuch G. , Andritzky B. , Brandl S. , Burkholder I. , Hossfeld D. K. , Bokemeyer C. , Laack E. 
Published: March 2020

18105 Background: An emerging notion for the treatment of advanced solid malignancies in adults is to manage it as a chronic disease and aim to keep tumor burden and associated symptoms at the lowest possible level. One of the most promising strategies to achieve this is to target the tumor vasculature using modified, “metronomic”, dosing schedules. We conducted a pilot study of weekly docetaxel in combination with daily trofosfamide as a metronomic second-line regimen in patients (pts) with metastatic non-small cell lung cancer (NSCLC). Methods: From March 2003 to November 2005, 21 pts with stage IV disease who had one prior chemotherapy were enrolled. Pts received docetaxel 25 mg/m2 on days 1, 8 and 15, every 4 weeks plus trofosfamide 50mg per day. Results: Median age: 60 years; gender: 18 male (85.7%), 3 female (14.3%); median Karnofsky PS: 80%; histologic subtypes: 8 squamous cell carcinomas (38.1%), 7 adenocarcinomas (33.3%), 6 large cell carcinomas (28.6%); previous chemotherapy: platinum-based in 15 pts (71.4%), platinum-free in 6 pts (28.6%). A total of 62 chemotherapy cycles were administered. The median number of cycles per pt was 3 (range 1 - 8). The intent-to-treat overall response rate was 19% (95% CI 5.5 - 41.9) 1 CR (4.8%), 2 PR (14.3%), 9 SD (42.9%), 8 PD (38.1%). The median overall survival from onset of second-line therapy was 6.9 months (95% CI 5.0 - 13.9 months), the median progression-free survival 2.9 months (95% CI 1.58 - 6.28 months), the 1-year survival rate 28.6% (95% CI 14.5 - 56.2%), and the 2-year survival rate 7.1% (95% CI 1.26 - 40.6%). Hematological and non-hematological toxicities were mild. No grade 4 toxicity was observed. Conclusions: To the best of our knowledge, this is the first trial that combines docetaxel and trofosfamide for the treatment of NSCLC. Our results suggest that the concept of metronomic chemotherapy is a valuable addition to the treatment of NSCLC. The combination of docetaxel and trofosfamide is active and well tolerated as second-line therapy in pts with metastatic NSCLC. No significant financial relationships to disclose.
Renal safety of sustained pemetrexed (P)/platinum treatment for advanced malignant mesothelioma (MM)
Authors: Karthaus M. , Hornych K. , Wiegand U. , Pfeil N. , Baysal F. , Trapp M. , Tagizadeh K. 
Published: March 2020

18106 Background: MM is a very rare and aggressive neoplasm with a short life expectancy. Standard care of MM is P + cisplatinum (DDP). The optimal duration of chemotherapy(ctx) for MM is undetermined. The feasibility of maintenance with P/DDP has not been reported. A major obstacle to sustained P/DDP for MM is renal safety beside neurotoxicity. At present, there are no data regarding renal safety in pts receiving ≥ 6 cycles of P/DDP in MM. Methods: We evaluated long term renal function of P(500 mg/m2)/DDP(75 mg/m2) for MM prospectively. Ctx on d1 was repeated on d22 until disease progression or toxicity. Pts with impairment of renal function (creatinine-clearance <60 ml/min) switched to P/carboplatin (CP) AUC 5 for further ctx. P ctx was stopped if creatinine-clearance (CrCl) <45 ml/min. Routine folinic acid and vitamine B12 was administered to prevent AE. Study endpoint was long term renal function for sustained therapy of P/DDP followed by P/CP and/or P-mono. Results: Between 12/02 and 05/06 86 consecutive MM pts were treated. Staging revealed peritoneal MM in 19, and pleural MM in 67 pts. Five pts did not receive ctx. First-line ctx was P/DDP in 66 pts (prior s-crea 0.85; SD 0.17) given a mean of 4.9 cyles (range 1–11) for a mean of 120 d (21–397 d) and a mean of 138 mg DDP/cycle. 28 pts received CP/P sequentially for further maintenance up to 27 cycles (mean 6.4). A change from P/DDP to P/CP was necessary due to a worsening renal function in all of those pts. Mean s-crea/CrCl prior to DDP ctx in those pts was 0.87 mg/dl (SD 0.17)/96.0 ml/min (SD 26) and 1.01 mg/dl (SD 0.29)/73.4 ml/min (SD 22) at the end of P/DDP. Mean given CP dose was 425 mg/cycle (range 175 - 725 mg). Pts subsequently receiving P/CP had a s-crea of 1.16 mg/dl (CrCl 73.4 ml/min) prior to ctx that did not change during P/CP (1.13 mg/dl/CrCl 73.2 ml/min). 13 pts received P- mono with a mean of 8 cycles (1–26) subsequently. Renal function showed a s-crea(CrCl) of 1.13 mg/dl (71.2 ml/min) prior and 1.11 mg/dl (70.8 ml/min) at the end of P ctx. Conclusions: Long term maintenance P/DDP of MM is limited by renal impairment due to DDP, while subsequent P/CP or P-mono was feasible and not associated with further deterioration of renal function. Further trials with sustained P/CP or P ctx for MM are warranted to evaluate the efficacy of maintenance for advanced MM. No significant financial relationships to disclose.
Possible correlation between SOCS1 methylation and EGFR exon 19 mutation but not exon 21 mutation in Chinese NSCLC patients
Authors: Lee S. , Mok T. , Li H. , Yim A. , Wan I. , Lam K. C. , Chan A. , To K. F. , Tao Q. 
Published: March 2020

18113 Background: Suppressor of cytokine signaling-1 (SOCS1) and -3 (SOCS3) interact with the epidermal growth factor receptor (EGFR) to bring about the ubiquination and degradation of the receptor. Silencing of SOCS1 and SOCS3 by methylation was postulated to regulate the IL-6R/JAK-mediated STAT3 activation. Its relationship to EGFR and EGFR mutations in lung cancer remains unclear. Here, we examined the relationship between EGFR mutations and methylation of SOCS1 and SOCS3 in Chinese NSCLC patients. Methods: EGFR mutations were assessed in DNAs from microdissected tumor cells. PCR products were purified and sequenced using the BigDye Terminator Cycle Sequencing Kit (Applied Biosystem) and the ABI 3100 Genetic Analyzer. For methylation analyses of SOCS1 and SOCS3, DNAs were extracted from paraffin sections of tumor tissues, bisulfite treated and analyzed by methylation- specific PCR (MSP). Results: Data is available from 9 lung cancer cell lines and 20 tumor samples. Five EGFR-wild type cell lines had methylation for SOCS1. We found EGFR exon 19 mutation in 5 (25%) tumors, exon 21 mutation (L858R) in 2 (10%) tumors, and 1 (5%) tumor had double mutations. Four of 5 (80%) tumors with exon 19 mutation and none (0%) of the tumors with exon 21 mutation had SOCS1 methylation, comparing to only 2 of 12 (17%) EGFR-wild type tumors had SOCS1 methylation. SOCS3 methylation was not detected in any of the primary tumors or cell lines. Conclusions: Our preliminary findings suggest that SOCS1 methylation might be positively correlated with EGFR exon 19 mutation but exclusive from exon 21 mutation. A following study with larger sample size is currently under way. SOCS1 methylation may explain the better tumor response associated with EGFR exon 19 mutation. No significant financial relationships to disclose.
Disease stabilization (SD) as a surrogate end-point in advanced non-small cell lung cancer (NSCLC) patients treated with erlotinib (E) or gefitinib (G)
Authors: Pronzato P. , Loprevite M. , Brianti A. , Defferrari C. , Catania G. , Grossi F. 
Published: March 2020

18115 Background: One retrospective study (Hotta K, Ann Oncol 2005), investigating the prognosis of patients (pts) obtaining SD as best response with G treatment, has demonstrated that both progression-free survival (PFS) and survival (S) were significantly longer than those in pts with progressive disease (PD). The aim of this retrospective study was to compare the PFS and S outcome in pts with advanced NSCLC who achieved SD or partial response (PR) after treatment with E or G. Methods: Pooled data from 62 pts, entered into an open label phase II program of E (n=31) and a compassionate-use program of G (n=31), were retrospectively analyzed. E and G were given orally at 150 and 250 mg per day respectively and were continued until disease progression, development of unacceptable toxicity or patient’s refusal. Results: Pts characteristics: median age 69 years (42–85); females= 21 pts (34%); never/former smokers= 16/38 pts (26/61%); adenocarcinoma/BAC= 35/10 pts (56/16%); PS 0/1= 18/38 pts (29/61%). In 16 pts (26%) E or G were given as first-line therapy; 21 pts (34%) had received =2 prior lines of chemotherapy. Six pts (10%) achieved a PR and 18 pts (29%) obtained SD. TTP and OS in pts obtaining PR and SD were comparable: 7 vs 5.5 and 9.7 vs 9.1 months respectively. In progressing pts median TTP and OS were 1.7 and 3.7 months. Conclusions: Our findings indicate the importance of achieving disease control with both E and G treatment. Pts obtaining SD had a similar PFS and S compared with those having PR. An analysis of the role of mutational status and other biomarkers in predicting clinical outcome is currently underway. No significant financial relationships to disclose.
Clinical significance of altered expression of the retinoid acid receptors alfa and beta (RAR a and b) and the cellular retinol binding protein (CRBP-1) in stage I non-small cell lung cancer
Authors: Pallotta M. G. , Mauro L. , Beguelin G. Z. , Dallurzo L. M. , Smith D. , Lastiri J. M. , Vasallo B. , Val De Kier Joffé E. , Puricelli L. 
Published: March 2020

18117 Background: Retinoids, a group of natural and synthetic Vitamin A analogues, are known to play a major role in regulating growth, differentiation and apoptosis of many cell types. Its role as prognostic factors in non-small cell lung cancer (NSCLC) is poorly known. Methods: Patients who underwent a successful surgical resection for stage I NSCLC were elegible. Antigen expression was analyzed by immuno histochemistry on histological samples of the tumor to investigate the expression pattern of RARa, RARb and CRBP-1. 51 NSCLC patients stage I (18 Stage Ia and 33 Stage Ib) were tested . A case was considered positive when more than 10% of cells presented specific staining for the antigen. Prognostic evaluation was performed with the Log-Rank test and the multivariate proportional hazard model. Results: About 40% of cases were positive for RARa. In the case of RARb 58.3% NSCLC showed cytoplasm staining, while only 18% showed nuclear immunopositivity. Taken together, the 81.5% of NSCLC tumors expressed at least one RA receptor (RARa or RARb or both). CRBP-1 staining was observed in 52% of the lung tumors. No relationship was found between the number of cells expressing the studied molecules and clinical pathological features, including sex, T stage, histopathology, adjuvant therapy, smoking habit or the presence of tumor cells in the pleural fluid. The only exception was that a higher percentage of adenocarcinomas were positive for RARa as compared with epidermoid tumors (50.0 vs 14.3%, p=0.05). On the other hand RARb was expressed preferentially in epidermoid tumors (81.3% vs 42.9 %, p<0.05). Univariate analysis showed a significant association between positive expression of RARb with shorter overall survival (log-rank test 3.7, p<0.05). However, the multivariate study indicated that RARb expression was influenced by other clinical pathological parameters, suggesting that this antigen would not be able to predict cancer-specific survival in an independent way. Conclusions: A high number of stage I NSCLC express RARs and CRBP. This suggests that retinoid expression could harbour relevant prognostic information at an early stage of the disease. No significant financial relationships to disclose.
Clinical predictive factors for mutations in epidermal growth factor receptor (EGFR) exon 19 and 21 in Japanese patients with lung cancer
Authors: Goto K. , Kim Y. , Yoh K. , Niho S. , Ohmatsu H. , Kubota K. , Nishiwaki Y. , Saijo N. 
Published: March 2020

18131 Background: It has been reported that lung cancer with activating mutations of EGFR are highly sensitive to gefitinib or erlotinib. Furthermore, the incidence of EGFR mutations is significantly higher in adenocarcinoma, female, never-smoker, Japanese patients. However, it is difficult to take sufficient amount of biopsy specimen of lung cancer with advanced disease for mutation analyses in clinical practice. Therefore, in this study, clinical predictive factors for EGFR mutations in Japanese patients with lung cancer were clarified. Methods: EGFR exon 19 and 21 mutation status was determined in 284 tumor samples using direct sequencing, polymerase chain reaction. To identify clinical independent predictive factors for EGFR mutation, the logistic regression analysis was performed. Results: 131 tumors of them could be analyzed for mutations in EGFR exon 19 and 21. EGFR mutations were detected in 38 tumors (29%). Median age of patients with EGFR mutations was 62 years (rage 43–84); 19 male and 19 female; 18 stage I, 15 stage II, and 5 stage III disease. Cigarette- smoking history of patients with EGFR mutations included non-smoker in 20 patients, light smoker (< 10 pack-years smoker) in 4, and heavy smoker (> 10 pack-years smoker) in 14. Multivariate analyses showed that non-smoker or light smoker (p=0.007) and adenocarcinoma (p=0.044) were the significant predictive factors contributing to EGFR mutations. Gender, serum CEA level, and clinical stage were not associated with EGFR mutations. Seventy patients treated with gefitinib and 25 PR were observed, and the overall response rate was 36%. The response rate to gefitinib in patients with and without EGFR mutations were 76% and 7%, respectively. In addition, EGFR mutations were detected in 51% (19/37) of patients with adenocarcinoma and light smoker, and the response rate to gefitinib of them was 49% (18/37). Conclusions: In Japanese patients with lung cancer, non-smoker or light smoker and adenocarcinoma were significant predictive factors for mutations in EGFR exon 19 and 21. No significant financial relationships to disclose.