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Hyperfractionated Radiation Therapy with or without Concurrent Chemotherapy in Stage III Non-small Cell Lung Cancer (NSCLC): Single-institution Experience in 600 Patients
Proceedings of the 50th Annual ASTRO Meeting single-time-point 18F-FDGPET/CT imaging, and 161 by dual-time-point imaging. Therefore, the sensitivity, specificity, diagnostic accuracy, positive predictive value and negative predictive value in the detection of hilar and mediastinal lymph nodes metastasis were 87.3%, 84.0%, 84.8%, 61.9% and 95.7% by single-time-point 18F-FDGPET/CT imaging, versus 94.8%, 92.2%, 92.8%, 78.9% and 98.1%, respectively, by dual-time-point imaging. There was a statistically significant difference in the detection of lymph nodes metastasis between the single-time-point 18F-FDG PET/CT imaging and dual-timepoint imaging. Conclusions: Dual-time-point 18F-FDG PET/CT imaging is more sensitive, specific and accurate than standard single-time 8FFDG PET/CT imaging in the detection of hilar and mediastinal lymph nodes metastasis, and may provide more information for diagnosis, staging and treatment of non-small-cell lung cancer. Author Disclosure: M. Hu, None; J. Yu, None; X. Sun, None; D. Mu, None; Z. Fu, None; X. Xu, None; X. Li, None.
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Association of ATM Single Nucleotide Polymorphisms with Local Advanced Non-small Cell Lung Cancer Patients Treated with Radiotherapy
L. Zhang, M. Yang, N. Bi, W. Ji, L. Zhao, D. Lin, L. Wang Cancer Hospital (Institute), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China Purpose/Objective(s): To examine the possible relationship between single nucleotide polymorphisms (SNPs) in DNA repair, apoptosis and inflammatory cytokine genes with clinical outcomes of patients with local advanced non-small cell lung cancer (NSCLC) treated with radiotherapy. Materials/Methods: 105 non-small cell lung cancer who were inoperable and underwent thoracic radiotherapy at the Cancer Hospital of Peking Union Medical College (PUMC) and Chinese Academy of Medical Sciences (CAMS) between January 2004 and August 2006 were evaluated. All patients consented to blood sampling, SNP analysis and follow-up. We analyzed 37 SNPs in 20 DNA repair, apoptosis and inflammatory cytokine genes including ATM,TP53,ERCC1,XRCC1,XRCC3,XPD,XPC,XPG,NBS1, STK15,ZNF350,ADPRT,FAS,FASL,CYP2D6*4,CASP8,COX-2,TGF-b1,CD14 and ACE using PCR-based restricted fragment length polymorphism (RFLP) analysis. The primary endpoint of the study was to investigate the association between genotypes and survival. The Kaplan-Meier method and log-rank test were used to assess the prognostic significance of the clinical factors and genotypes for overall survival. Cox forward-stepwise regression model was chosen to assess genetic risk factors in multivariate analyses. Results: Median age was 60 years (rang, 26 to 83 years), 38% were female, and there were 64 deaths. All the patients diagnosed stage III with a median follow-up of 26 months were evaluated. Of these patients, 25 were stage IIIA and 80 were stage IIIB. 45 patients received concurrent chemoradiotherapy and 27 patients received sequential chemoradiotherapy. The 1-, 2-, 3-, 4-year overall survival and the median survival were 79.6%, 43.3%, 25.1%, 12.6% and 20.2 months, and the 1-, 2- and 3- year loco-regional progression-free survival were 76.6%, 55.1% and 19.0%. At univariate analysis, the overall survival received benefit from Karnofsky performance status (KPS) $80, three-dimensional conformal radiotherapy, total dose more 60 Gy and ATM 81165C allele. Multivariate Cox regression analysis identified the ATM 81165T allele (ATM 81165TC and -111CC genotypes) as an independent prognostic risk factor (risk ratio = 1.995; p = 0.040; 95%CI = 1.03 to 3.86; adjusted for age, sex, KPS, radiation technique and total dose). Conclusions: Genetic polymorphism in the ATM may be an important prognostic factor in local advanced NSCLC patients treated with radiotherapy. Author Disclosure: L. Zhang, None; M. Yang, None; N. Bi, None; W. Ji, None; L. Zhao, None; D. Lin, None; L. Wang, None.
2600
Hyperfractionated Radiation Therapy with or without Concurrent Chemotherapy in Stage III Non-small Cell Lung Cancer (NSCLC): Single-institution Experience in 600 Patients
B. Jeremic1, B. Milicic2 1
International Atomic Energy Agency, Vienna, Austria, 2University Hospital, Kragujevac, Serbia
Purpose/Objective(s): Institutional experience over the 10-year period of the use of hyperfractionated radiation therapy (Hfx RT) with or without concurrent chemotherapy (CHT) in stage III non-small cell lung cancer (NSCLC) was reviewed. Materials/Methods: Three phase III and two phase II studies have been designed and executed with a total of 600 patients. Hfx RT alone was given in 127 and Hfx RT-CHT was given in 473 patients. Hfx RT doses were 64.8 Gy and 69.6 Gy (1.2 Gy bid) and 67.6 Gy (1.3 Gy bid). CHT consisted of concurrent carboplatin (C) and etoposide (E) in 409 patients and concurrent C and paclitaxel (P) in 64 patients. Results: For all 600 patients, the median overall survival (OS), local progression-free survival (LPFS) and distant metastasis free survival times (DMFS) were 19, 21, and 23 months, respectively. Five-year OS, LPFS and DMFS rates were 19%, 29%, and 35%, respectively. Univariate and multivariate analysis showed that only age did not influence OS and LPFS, while sex, Karnofsky performance status, weight loss, stage, histology, interfraction interval and treatment did. Only age and treatment did not influence DMFS. Acute high-grade ($3) esophageal (p = 0.012), hematological (p \ 0.001) and skin (p \ 0.001) toxicity was significantly increased across the treatment groups but not the bronchopulmonary (p = 0.39) or gastric (p = 0.54) toxicity. Only late high-grade skin toxicity was significantly more frequent across treatment groups. Conclusions: This study reconfirmed superiority of concurrent RT-CHT regimens over the RT alone at the expense of increased acute but not late high-grade toxicity. Author Disclosure: B. Jeremic, None; B. Milicic, None.
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2599
Association of ATM Single Nucleotide Polymorphisms with Local Advanced Non-small Cell Lung Cancer Patients Treated with Radiotherapy
L. Zhang, M. Yang, N. Bi, W. Ji, L. Zhao, D. Lin, L. Wang Cancer Hospital (Institute), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China Purpose/Objective(s): To examine the possible relationship between single nucleotide polymorphisms (SNPs) in DNA repair, apoptosis and inflammatory cytokine genes with clinical outcomes of patients with local advanced non-small cell lung cancer (NSCLC) treated with radiotherapy. Materials/Methods: 105 non-small cell lung cancer who were inoperable and underwent thoracic radiotherapy at the Cancer Hospital of Peking Union Medical College (PUMC) and Chinese Academy of Medical Sciences (CAMS) between January 2004 and August 2006 were evaluated. All patients consented to blood sampling, SNP analysis and follow-up. We analyzed 37 SNPs in 20 DNA repair, apoptosis and inflammatory cytokine genes including ATM,TP53,ERCC1,XRCC1,XRCC3,XPD,XPC,XPG,NBS1, STK15,ZNF350,ADPRT,FAS,FASL,CYP2D6*4,CASP8,COX-2,TGF-b1,CD14 and ACE using PCR-based restricted fragment length polymorphism (RFLP) analysis. The primary endpoint of the study was to investigate the association between genotypes and survival. The Kaplan-Meier method and log-rank test were used to assess the prognostic significance of the clinical factors and genotypes for overall survival. Cox forward-stepwise regression model was chosen to assess genetic risk factors in multivariate analyses. Results: Median age was 60 years (rang, 26 to 83 years), 38% were female, and there were 64 deaths. All the patients diagnosed stage III with a median follow-up of 26 months were evaluated. Of these patients, 25 were stage IIIA and 80 were stage IIIB. 45 patients received concurrent chemoradiotherapy and 27 patients received sequential chemoradiotherapy. The 1-, 2-, 3-, 4-year overall survival and the median survival were 79.6%, 43.3%, 25.1%, 12.6% and 20.2 months, and the 1-, 2- and 3- year loco-regional progression-free survival were 76.6%, 55.1% and 19.0%. At univariate analysis, the overall survival received benefit from Karnofsky performance status (KPS) $80, three-dimensional conformal radiotherapy, total dose more 60 Gy and ATM 81165C allele. Multivariate Cox regression analysis identified the ATM 81165T allele (ATM 81165TC and -111CC genotypes) as an independent prognostic risk factor (risk ratio = 1.995; p = 0.040; 95%CI = 1.03 to 3.86; adjusted for age, sex, KPS, radiation technique and total dose). Conclusions: Genetic polymorphism in the ATM may be an important prognostic factor in local advanced NSCLC patients treated with radiotherapy. Author Disclosure: L. Zhang, None; M. Yang, None; N. Bi, None; W. Ji, None; L. Zhao, None; D. Lin, None; L. Wang, None.
2600
Hyperfractionated Radiation Therapy with or without Concurrent Chemotherapy in Stage III Non-small Cell Lung Cancer (NSCLC): Single-institution Experience in 600 Patients
B. Jeremic1, B. Milicic2 1
International Atomic Energy Agency, Vienna, Austria, 2University Hospital, Kragujevac, Serbia
Purpose/Objective(s): Institutional experience over the 10-year period of the use of hyperfractionated radiation therapy (Hfx RT) with or without concurrent chemotherapy (CHT) in stage III non-small cell lung cancer (NSCLC) was reviewed. Materials/Methods: Three phase III and two phase II studies have been designed and executed with a total of 600 patients. Hfx RT alone was given in 127 and Hfx RT-CHT was given in 473 patients. Hfx RT doses were 64.8 Gy and 69.6 Gy (1.2 Gy bid) and 67.6 Gy (1.3 Gy bid). CHT consisted of concurrent carboplatin (C) and etoposide (E) in 409 patients and concurrent C and paclitaxel (P) in 64 patients. Results: For all 600 patients, the median overall survival (OS), local progression-free survival (LPFS) and distant metastasis free survival times (DMFS) were 19, 21, and 23 months, respectively. Five-year OS, LPFS and DMFS rates were 19%, 29%, and 35%, respectively. Univariate and multivariate analysis showed that only age did not influence OS and LPFS, while sex, Karnofsky performance status, weight loss, stage, histology, interfraction interval and treatment did. Only age and treatment did not influence DMFS. Acute high-grade ($3) esophageal (p = 0.012), hematological (p \ 0.001) and skin (p \ 0.001) toxicity was significantly increased across the treatment groups but not the bronchopulmonary (p = 0.39) or gastric (p = 0.54) toxicity. Only late high-grade skin toxicity was significantly more frequent across treatment groups. Conclusions: This study reconfirmed superiority of concurrent RT-CHT regimens over the RT alone at the expense of increased acute but not late high-grade toxicity. Author Disclosure: B. Jeremic, None; B. Milicic, None.
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