bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of statins may prolong survival of non-small cell lung cancer patients: Final update from 1,205 cases
Authors: Hanbali A. S. , Wang D. , Jankowski M. , Urbaez E. , Syed A. , Farhan S. 
Published: March 2020

7638 Background: Hypercholesterolemia is one of the most common morbidities in United States. Statins have been proven as effective cholesterol-lowering agents and have been widely used in this country. They have been reported reducing the incidence and risk of various cancer types. However, the impact of using statins on the survival of 407 patients with diagnosed non-small cell lung cancer (NSCLC) was initially reported (Wang, et al. Abstract #7149, ASCO Meeting 2006). Methods: 1,233 patients with diagnosed non-small cell lung cancer were identified from the Tumor Registry at Henry Ford Health System between January 1999 and December 2004. The data from 1,206 patients were extracted from their available electronic medical records. Statistical analyses were performed and stratified for statin users versus non statin users. Results: Data from 1,205 eligible patients were included in this updated report. There were 391 patients with hypercholesterolemia, 250 of them were statin users at the time of their non-small cell lung cancer diagnosis. Average age was 68 (range 46–90) years for statin users and 65.9 (range 29–94) years for non statin users. Overall median survival of 1,205 subjects was 9.85 months. After stratifying for statin use, the median survival of statin users was 13.9 (95% C.I. 9.9 - 17.4) months while the median survival of non statin users was 9.6 (95% C.I. 8.1 - 10.4) months, with a P value of 0.0001. After having several prognostic variables (age, stage, co-morbids, other cancers, performance status, anti-cancer therapies, and serum albumin, etc.) adjusted, statin use still demonstrated protection from death with a hazard ratio of 0.74 (95% C.I. 0.59 - 0.95, P=0.017). Conclusion: The trend of survival benefit from NSCLC among statin users was shown in our previous report and it has maintained with further enhanced statistical significance in this update. Though statin use will unlikely become an independent anti-cancer regimen by itself, the choice of continuation of statin among NSCLC patients may still provide survival benefit to this population. The favorable impact of statin use on NSCLC patients is intriguing; a prospective study of co-morbidity management with statins in patients with non-small cell lung cancer is warranted. No significant financial relationships to disclose.
XPD 312 single nucleotide polymorphism (SNP) in stage IIIA-B non-small cell lung cancer (NSCLC) patients (p) <59 years (y) treated with chemotherapy followed by surgery
Authors: Santarpia M. , Garrido P. , Gonzalez-Larriba J. , Azagra P. , Cardenal F. , Ramirez J. , de Aguirre I. , Sanchez-Ronco M. , Taron M. , Rosell R. 
Published: March 2020

7652 Background: SNPs in DNA repair genes may affect response to cytotoxic therapy. We investigated SNPs in XPD codons 751 and 312 and in RRM1 −37 in 109 stage IIIA (N2) and IIIB NSCLC p treated with neoadjuvant chemotherapy and correlated results with event- free (EFS) and median (MS) survival. Methods: p eligible for surgery received cisplatin day (d) 1, gemcitabine d 1,8, docetaxel d 1,8,15, every 3 weeks for 3 cycles, followed by thoracotomy. DNA was extracted from baseline peripheral lymphocytes and genotyping was performed by Taqman. Results: Median age, 60 y (range 31–77); 92 males (84%); 45 squamous cell (41%). 4 p (3.9%) attained complete response; 55 (53.9%) partial response. 75 p underwent surgery (62 complete, 13 incomplete resection); remaining 34 p were unresectable. Median follow-up was 15.7 months (m) (range, 0.5–74). MS for p still alive is 49.8 m (range, 6.7–74). MS: 48 m with complete resection, 13 m with incomplete resection, 17 m for unresected p. In the univariate analysis of survival, age <59 y (P=0.03), resection (P<0.001) and XPD312 AspAsp (P=0.05) emerged as predictive markers of longer survival. For all 109 p, those with XPD312 AspAsp had longer EFS and MS than p with Asn variants ( Table ). In addition, for 51 p <59 y, EFS was longer for 24 p with XPD312 AspAsp (36.4 m) than for 27 p with Asn variants (9.8 m) (P=0.009); MS in this group of younger p was 45.4 m for AspAsp vs 15.8 m for Asn (P=0.04). No other significant correlation between SNPs and survival was observed ( Table ). Conclusions: Interaction between SNPs, age and risk of lung cancer has previously been described. XPD312 AspAsp in p <59 y predicts longer survival in stage IIIA (N2) and IIIB NSCLC treated with neoadjuvant chemotherapy. No significant financial relationships to disclose. [Table: see text]
A phase II study of nedaplatin (CDGP) and docetaxel (TXT) in patients with advanced non-small cell lung cancer (NSCLC)
Authors: Fujino S. , Asada Y. , Nakano Y. , Suzumura Y. , Inoue S. , Nagao T. , Hajiro T. , Tezuka N. , Sawai S. 
Published: March 2020

7660 Background: Nedaplatin (CDGP) is a cisplatin derivative developed in Japan. In non-small cell lung cancer (NSCLC), its response as monotherapy has been reported to be 20.5%, while when used in combination with vindesine, its efficacy is similar to cisplatin (CDDP). With respect to adverse effects, it causes less nausea/vomiting and nephrotoxicity compared to CDDP. By these data, we conducted a phase II study of combination treatment with CDGP and docetaxel (TXT) in advanced NSCLC. Methods: Forty six patients (Male/Female 39/7, median age 65 years (40–79), IIIB/IV 20/26) were enrolled from March 2004 to March 2006. Eligibility criteria included signed informed consent, age over 20 and under 80, measurable disease, ECOG PS 0–1, adequate bone marrow reserve, no previous chemotherapy or radiotherapy, and life-expectancy of at least 12 weeks. Treatment consisted of 80 mg/m2 CDGP and 60 mg/m2 TXT on day one with about 1,000 ml of hydration every 3–4 weeks. Results: One hundred and forty four cycles were given to 46 pts (mean cycles 3.1) and the mean dosages actually administered were 75.5±6.1 mg/m2 for CGDP and 57.7±4.6 mg/m2 for TXT. An over all response rate was 52.2% (squamous cell carcinoma 66.7%, adenocarcinoma 44.0%), median survival time was 12 months and 1-year survival rate was 50%. NCI-CTC grades 3–4 leukopenia, neutropenia, nausea/vomiting and appetite loss occurred in 44 (29.2%), 50 (34.7%), 5 (3.5%), 6 (4.2%) cycles, respectively. There was no grade 3–4 anemia, thrombocytopenia and neuropathy. Conclusions: This combination of chemotherapy was well tolerated, and its activity and survival for advanced NSCLC were acceptable. The update data will be presented at the meeting. No significant financial relationships to disclose.
Investigating gender specific metabolic differences in non-small cell lung cancer by F-18 FDG PET
Authors: Howard G. , Zakalik D. , Vashist P. , Wong C. O. 
Published: March 2020

7663 Background: Lung cancer is the leading cause of cancer death in women, killing more women than breast, ovarian, and uterine cancers combined. Recent evidence suggests differences in lung cancer between the sexes. Women have better rates of survival, different histology, genetic, and molecular factors as compared to men. Metabolic characteristics of lung cancer have prognostic value. The use of F-18 FDG Positron Emission Tomography (PET) has been demonstrated in multiple studies to better determine outcome, improve diagnostic and staging techniques. Methods: 251 (M:F=101:150) patients with newly diagnosed biopsy proven NSCLC and evaluated by F-18 FDG PET(CT), without other malignancies, prior radiation or chemotherapy, were analyzed retrospectively from our institution. PET scans were obtained 1 hour after injection of 370 MBq F-18 FDG using a dedicated whole body PET-CT or PET scanner. The PET images were reconstructed with attenuation correction by either radioisotope or CT transmission scan. The SUV, defined as tumor activity divided by dose injected per lean body mass, from the PET cameras had been cross validated to produce the same value in a given phantom and patient. The maximum SUV was measured by searching the maximum value within a volume of known primary cancer. Results: The two groups were matched for age. Females had significantly less squamous cell carcinomas (18% vs. 29%, p=0.025) and more adenocarcinomas (41% vs. 30%, p=0.041) than males. Although there were no significant differences stage by stage between males and females, there was gradual transition or increment of SUV by stage in all female NSCLC with the SUV of stage I NSCLC being lower than that of cancers in stages II, III or IV (p=0.00022, 0.0088, and 0.0026 respectively). However, there were no such distinctions among male patients. There were no differences in SUV among various histological types of NSCLC between the sexes. Conclusions: The study suggests there are gender differences in the metabolic properties of NSCLC with distinctively more metabolically aggressive NSCLCs upon advancing stage in women but not in men. This gender specific metabolic difference is another discriminator besides other known gender factors and is potentially useful in the management of early stage NSCLC in women. No significant financial relationships to disclose.
Cost-effectiveness of erlotinib vs. docetaxel or pemetrexed in the treatment of refractory non-small cell lung cancer (NSCLC)
Authors: Carlson J. , Oestreicher N. , Lubeck D. P. , Ramsey S. D. , Veenstra D. L. 
Published: March 2020

7664 Background: Multiple treatment strategies are now available for stage IIIB/IV non-small cell lung cancer (NSCLC) after failure of 1st line treatment, but their relative economic and clinical value is not clear. Methods: We developed a health state transition model with 3 health states (progression free, disease progression, and death) to estimate the direct medical costs and quality-adjusted life-years (QALYs) of treating refractory NSCLC from the US healthcare system perspective. The treatments considered were erlotinib, docetaxel, and pemetrexed, and the time horizon was 2 years. Mean survival and progression free survival were assumed equal for all three treatments based on published pivotal clinical trials; side effect data were derived from the same studies. Utilities were obtained from a recent community-based study performed in the UK. Costs were obtained from published sources, and costs and effects were discounted at 3%. Sensitivity analyses were performed to evaluate uncertainty in the results. Results: Total costs in the base case were $31,000 for erlotinib, $33,700 for docetaxel, and $38,200 for pemetrexed. Drug acquisition and administration costs were $11,800, $12,200, and $18,700, respectively. Adverse event costs were $200, $2,500, and $500 on average per patient, and disease costs were equivalent at $19,000. QALYs were slightly greater for erlotinib versus docetaxel and pemetrexed (an increase of 0.02 and 0.01, respectively), due to differences in side effect profiles. The cost differences were robust to sensitivity analyses; when the utility for IV vs. oral therapy were assumed equal, erlotinib had 0.1 greater QALY than docetaxel and equivalent QALYs to pemetrexed. Conclusions: The results of our study suggest erlotinib in the treatment of refractory NSCLC in the United States is cost-saving compared with alternative treatments, with a slight improvement in patient quality of life. The results of ongoing comparative clinical trials will be useful for further evaluation of potential survival benefits. [Table: see text]
E2F1 overexpression associated with TS and survivin gene expressions in non-small cell lung cancer
Authors: Huang C. , Liu D. , Nakano J. , Ishikawa S. , Yokomise H. , Ueno M. 
Published: March 2020

7669 Background: The thymidylate synthase (TS) expression is related to 5-FU sensitivity. The survivin expression is associated with tumor apoptosis, an indicator to predict the efficacy of chemotherapy. Recently, TS and Survivin have been reported to be E2F1 target genes. We investigate the clinical significance of the E2F1 gene expression in relation to gene expressions of TS and Survivin among non-small cell lung cancer (NSCLC). Methods: One hundred and twenty-seven NSCLC patients were investigated. Quantitative RT-PCR was performed to evaluate gene expressions of E2F1, TS, and survivin. The Ki-67 proliferation index and the apoptotic index using TUNEL method were also evaluated. Results: The E2F1 gene expression was significantly higher in stage II to III tumors than in stage I tumors (p=0.006). The E2F1 gene expression significantly correlated with the Ki-67 proliferation index (p<0.001), while no correlation was observed between the E2F1 gene expression and the apoptotic index. Regarding E2F1-target genes, the E2F1 gene expression significantly correlated with the TS gene expression (p<0.001). The E2F1 gene expression also significantly correlated with the survivin gene expression (p<0.001). The TS expression and the survivin expression significantly correlated with the Ki-67 proliferation index (p<0.001 and p<0.001, respectively). There was a significant inverse relationship between the survivin expression and the apoptotic index (p<0.001). The overall survival was significantly lower in patients with high-E2F1 tumors than in those with low-E2F1 tumors (p=0.002), especially among patients with stage II to III NSCLCs (p=0.018). The Cox regression analysis demonstrated that the E2F1 status was a significant prognostic factor for NSCLC patients (p=0.026). Conclusions: The present study revealed the E2F1 gene expression to correlate with TS and survivin gene expressions, and tumor proliferation. E2F1 overexpression could occur to produce more aggressive tumors with high proliferation rate and chemo-resistance during progression of NSCLCs. The suppression of E2F1 by RNA interference would be a useful strategy for cancer gene therapy. No significant financial relationships to disclose.
Clinical significance of epidermal growth factor receptor gene mutations on treatment outcome after cytotoxic chemotherapy in Japanese patients with non-small cell lung cancer (NSCLC)
Authors: Hotta K. , Kiura K. , Toyooka S. , Takigawa N. , Soh J. , Fujiwara Y. , Tabata M. , Uno M. , Date H. , Tanimoto M. 
Published: March 2020

7670 Background: The relationship between EGFR mutation status and clinical outcome has not fully been assessed in NSCLC patients receiving cytotoxic agents. The aim of this study was to clarify its association. We also examined if this association could be affected by the prior gefitinib treatment or not. Methods: Patients with advanced or postoperative recurrent NSCLC who received both cytotoxic chemotherapy and gefitinib monotherapy through their treatment course and whose tumors were assessable for EGFR mutation analysis were included in this study. EGFR mutation was determined in exons 19 and 21 by direct sequencing. Results: Sixty patients were included in the study, including 6 (10%) patients who received the first-line gefitinib monotherapy followed by cytotoxic chemotherapy in the second-line or later settings. Of the 54 (90%) patients, 22 also underwent subsequent cytotoxic chemotherapy after the relapse to gefitinib monotherapy. EGFR mutations were detected in 17 (28%) patients. In the first-line cytotoxic chemotherapy setting (n=54), EGFR mutations significantly affected progression-free survival (PFS) with 6-month PFS rates of 45.8 vs. 21.9% (p=0.05). This was also observed in the multivariate analysis (HR=0.42, p=0.04). EGFR mutation was also significantly correlated with overall survival (OS) in the multivariate analysis (HR=0.26, p <0.01). Contrary, in the 28 (47%) of 60 patients who received cytotoxic chemotherapy after gefitinib monotherapy, there were no differences in PFS stratified by EGFR mutation status. The sensitivity to gefitinib was, however, correlated with EGFR mutation status and its sensitivity was retained even in the second-line setting in patients with EGFR mutations. Conclusion: EGFR mutation was significantly associated with better PFS in the first-line cytotoxic chemotherapy regimens. However, its association was not observed in the cytotoxic regimens administered after the relapse to gefitinib monotherapy, while the sensitivity to gefitinib was associated with EGFR mutation even in the second-line or later setting. No significant financial relationships to disclose.
Predictors and impacts of second-line chemotherapy on survival after progression in patients with advanced non-small cell lung cancer (NSCLC)
Authors: Teramukai S. , Nishimura T. , Nakagawa M. , Kawahara M. , Kubota K. , Furuse K. , Fukushima M. 
Published: March 2020

7675 Background: Survival after progression (SAP) was longer (median: 8 months) than progression-free survival (median: 6 months) in a phase III randomized trial in patients with stage IIIB or IV NSCLC (SWOG-Japan Common Arm Trial, the Japan Multinational Trial Organization LC00–03, Kawahara, PASCO 2006, #7013). The overall survival in the trial was longer than that in the US populations (median: 14 months vs. 9 months in the paclitaxel/carboplatin arms, Crowley, PASCO 2006, #7050). The aims of this study were to identify predictors and to assess impacts of second-line chemotherapy on SAP of advanced NSCLC. Methods: To identify independent predictors and to estimate hazard ratios (HR) for SAP, we used the Cox proportional hazards model. We evaluated survival benefit of second-line chemotherapies after adjustment for baseline factors and regimens of first-line therapy, types of progression, and time to progression. Results: Out of 393 patients in the LC00–03 trial, 340 patients had progressive disease during the follow-up period. The identified independent significant predictors for SAP were PS (HR: 2.19, p<0.001), weight loss (HR: 1.48, p=0.020), smoking (HR: 1.36, p=0.025), and LDH (HR: 1.37, p=0.032) as baseline factors. Lymph node metastases (HR: 2.17, p<0.001) and bone metastases (HR: 1.75, p=0.004) were poor predictors and relapse in primary lesion was a good predictor (HR: 0.74, p=0.027). Time to progression was correlated with SAP (p=0.008). The median SAP according to second-line treatments were 13 months in gefitinib treatment (response rate: 23%, n=67) and 9 months in other chemotherapies (n=174). The difference is not statistically significant after adjustment for the confounding factors (HR: 0.96, 95%CI: 0.65–1.41), although gefitinib was used after third-line at a constant proportion. Conclusions: Our study shows that baseline factors (PS, weight loss, smoking, LDH) and types of metastases at progression (lymph node, bone) are important prognostic factors for SAP, suggesting minimal effect of selecting gefitinib as a second-line treatment on SAP. [Table: see text]
A surgical predictive risk model of in-hospital mortality for primary resectable lung cancer: Statistical analysis of 8,796 patients from a nationally representative database
Authors: Falcoz P. , Brouchet L. , Conti M. , Chocron S. , Puyraveau M. , Mercier M. , Etievent J. , Dahan M. 
Published: March 2020

7677 Background: The aim of this study was twofold: to identify factors associated with in-hospital mortality among patients operated on for primary resectable lung cancer and to construct a risk model that could be used prospectively to inform decisions and retrospectively to enable comparisons and outcomes. Methods: Data from a nationally representative thoracic surgery database were collected prospectively in 59 hospitals between June 1, 2002 and December 1, 2006. Only adult patients with more than 95% of completed data were selected for the final analysis (n = 8,796 patients). Logistic regression analysis was used to predict the risk of in-hospital mortality. A risk model was developed with a training set of data (50% of patients) and validated on an independent test set (50% of patients). Its fit was assessed by the Hosmer-Lemeshow test (larger p value signifies greater reliability), and predictive accuracy was indicated by the area under the receiver operating characteristic curve (c-index). Results: Of the 8,796 original patients, 255 (2.9%) died during the same hospital admission. Within the data used to develop the model, the factors found to be significantly associated with the occurrence of in-hospital mortality in a multivariate analysis were: age, gender, performance status (World Health Organization) classification, side, class of procedure (lobectomy or wedge resection versus pneumonectomy), tumor histology, TNM stages and presence of co-morbid disease. The model was reliable (Hosmer-Lemeshow test = 8.94; p = 0.35) and accurate: the c-index (95% confidence interval) = 0.83 (0.81 to 0.85) for the training set and 0.82 (0.79 to 0.85) for the test set of data. The correlation between the expected and observed number of deaths was 0.99. Conclusions: The validated multivariate model for risk of in-hospital mortality among adult patients requiring surgery for primary resectable lung cancer described in this report was developed with national data, uses only 8 variables and has good performance characteristics. It would be useful both for calculating the mortality risk of an individual patient and contrasting expected and observed mortality rates for an institution or independent clinician. No significant financial relationships to disclose.
Prognostic value of preoperative serum tumor markers, including CEA, Cyfra21–1, SCC, CA19–9, SCC, CA125, TPA, NSE, and SLX, in patients with completely resected pathological stage I non-small cell lung cancer
Authors: Matsuguma H. , Suzuki H. , Ishikawa Y. , Kondo T. , Nakahara R. , Kamiyama Y. , Mori K. , Kodama T. , Honjo S. 
Published: March 2020

7681 Background: Recent randomized control trials have shown a survival benefit of adjuvant chemotherapy in patients with stage II or more advanced NSCLC, while surgery alone is still the standard therapy for stage I patients. There is, however, a subgroup of patients among the stage I patients who have a poor prognosis, for whom adjuvant chemotherapy can be as effective as has been observed for the patients with more advanced disease. Preoperative serum CEA level has been reported to be an independent prognostic factor for stage I NSCLC. However, many other tumor markers have also been reported as prognostic indicators in different studies using different tumor markers. It is unknown which tumor marker is the most effective for selecting poor prognostic subgroup of patients with stage I NSCLC for which adjuvant chemotherapy can be applied. Methods: A total of 355 patients underwent complete resection, and were diagnosed as having stage I NSCLC from 1995 to 2003. Analyzed tumor markers included CEA, Cyfra21–1, SCC, CA19–9, SCC, CA125, TPA, NSE, and SLX. Cut-off values for each tumor marker are listed in the table . Clinicopathologic factors including age, gender, histology, vessel invasion, pleural invasion, and pathologic T indicator are also analyzed in the multivariate analysis. Results: Among the 355 patients, 211 patients were male, 249 had adenocarcinoma, 82 had squamous cell carcinoma, and 253 had pathologic T1 tumors. Percentages of elevated value for each tumor marker are listed in the table in combination with related survival data. Cox proportional hazard model demonstrated age, pleural invasion, histology, and CEA were significantly independent prognostic factors. Conclusions: CEA is thought to be the best tumor marker for selecting the poor prognostic subgroup of patients with resected stage I NSCLC because of its high percentage of abnormal value and high ability to differentiate prognostic subgroups. No significant financial relationships to disclose. [Table: see text]