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Is Radiation Therapy Becoming More Effective in Treating Non-small Cell Lung Cancer?
Proceedings of the 52nd Annual ASTRO Meeting esophageal dose and mean esophageal dose. There were no strong association between grade $3 acute esophagitis and genetic variants studied. Conclusions: XRCC1 280His and the TGF-b1 10 Pro alleles may be protective against development of CTCAE 3.0 Grade 2 or worse esophagitis in patients treated with neoadjuvant chemotherapy and 3D-CRT. Author Disclosure: G. Zhang, None; M. Fan, None; G. Jiang, None; X. Fu, None; J. Chen, None; L. Xie, None; X. Xu, None.
1135
A Phase I Study Demonstrating Manganese Superoxide Dismutase Plasmid Liposome Complex (MnSOD-PL) Reduction of Esophagitis following Standard Chemoradiation in Surgically Unresectable Stage III NSCLC
J. S. Greenberger1, C. P. Belani2, J. D. Leuketich1, A. Argiris1, S. S. Ramalingam3, W. Gooding1, A. Pennathur1, D. Petro1, M. W. Epperly1, A. A. Tarhini1 1
University of Pittsburgh Cancer Institute, Pittsburgh, PA, 2Penn State Hershey Cancer Institute, Hershey, PA, 3Emory University, Atlanta, GA Purpose/Objective(s): Esophageal toxicity has been accepted reluctantly, as a necessary side effect of the benefits of chemoradiotherapy for lung cancer. MnSOD-PL is a genetically engineered therapeutic DNA/liposome complex containing the human MnSOD transgene. Preclinical studies in mouse models have demonstrated that the expression of the human MnSOD transgene confers protection of normal tissues from ionizing irradiation damage. A phase I trial has been completed demonstrating MnSOD-PL may reduce esophagitis following chemoradiation in surgically unresectable Stage III non-small cell lung cancer. Materials/Methods: Chemotherapy (carboplatin AUC = 2 and paclitaxel 45 mg/m2 intravenously) was given weekly (for 7 weeks), concurrently with radiation therapy. MnSOD-PL was swallowed twice a week (total 14 doses), at 3 dose levels: 0.3, 3, and 30 mg. Dose escalation followed a standard phase I design. Esophagoscopy was done at baseline, day 4 and 6 weeks after radiation with biopsies of the squamous lining cells. DNA was extracted and analyzed by PCR for the detection of the MnSOD transgene DNA. Results: Ten patients with AJCC stage IIIA (3) and IIIB (7) completed the course of therapy per study protocol. Five had squamous histology, 2 adenocarcinoma, 1 large cell, and 2 not specified. Patients were treated in 3 different cohorts at 3 dose levels of MnSODPL: 0.3 (3 pts), 3 (3 pts), or 30 mg (4 pts). The median dose of radiation was 77.7 Gy (range 63 - 79.10 Gy). Overall response rate for the standard chemo-radiation regimen was 70% (N = 10). There were no dose- limiting toxicities reported in all 3 dosing tiers. Conclusions: The oral administration of MnSOD-PL is feasible and safe. The phase II recommended dose is 30 mg. Author Disclosure: J.S. Greenberger, None; C.P. Belani, None; J.D. Leuketich, None; A. Argiris, None; S.S. Ramalingam, None; W. Gooding, None; A. Pennathur, None; D. Petro, None; M.W. Epperly, None; A.A. Tarhini, None.
1136
Is Radiation Therapy Becoming More Effective in Treating Non-small Cell Lung Cancer? 1
B. E. Lally , J. L. Wright1, L. G. Koniaris1, O. Mahmoud1, J. Gomez1, D. Nguyen1, T. Baxter1, C. R. Thomas2, M. Abramowitz1, M. Abramowitz1 1
University of Miami, Miami, FL, 2Oregon Health & Science University, Portland, OR
Purpose/Objective(s): Over time the management of patients with non-small cell lung cancer (NSCLC) has evolved, and aggregate outcome of these patients may have improved. The specific aim of this analysis if to determine if an improvement in survival over time in pts receiving radiotherapy (RT) from the Surveillance, Epidemiology, and End Results (SEER) database may be observed. Materials/Methods: Patients with incident NSCLC aged 21 yrs and older diagnosed from 1988-2002 and followed through 2006 were examined. All pts were censored at 5 years survival. Cox proportional Hazard model was used. Results: Overall, 158813 patients were identified. The number of pts with stage I, II, IIIa, IIIb, and IV were 41159 (26%), 7456 (5%), 16694 (11%), 34700 (22%), and 58804 (37%), respectively. 58,557 (37%) of these patients received definitive RT. For the total cohort, more recent year of treatment (HR = 0.993; CI: 0.992-0.994) and female gender (HR = 0.831; CI: 0.822-0.840) were associated with better survival. Conversely, increasing age (HR = 1.006; CI: 1.006-1.006), and African American race (HR = 1.171; CI: 1.151-1.191) were associated with worse survival. With respect to squamous histology (HR = 1.00 (Ref.)), large cell carcinoma (HR = 1.315; CI: 1.290-1.341) and adenocarcinoma (HR = 1.072; CI: 1.059-1.085) were associated with worse survival, while bronchioalveolar carcinoma (HR = 0.447; CI: 0.434-0.461) was associated with the best survival. Subset analysis was performed for only pts receiving definitive RT. Overall survival improved with more recent yr of treatment across all stages: Stage I (HR = 0.981; CI: 0.973-0.989), II (HR = 0.968; CI: 0.948-0.988), IIIA (HR = 0.983; CI: 0.977-0.989), IIIB (HR = 0.978; CI: 0.975-0.982), and IV (HR = 0.987; CI: 0.985-0.990). Conclusions: The survival for pts with NSCLC has improved over time in all stage categories and specifically in those receiving RT. We hypothesize that the benefit seen in stage I and IV NSCLC is driven by improved staging. The benefit in stage II/IIIA/IIIB may represent not only an improvement in staging, but also improvements in RT as well as the widespread adoption of combinedmodality treatment. Author Disclosure: B.E. Lally, None; J.L. Wright, None; L.G. Koniaris, None; O. Mahmoud, None; J. Gomez, None; D. Nguyen, None; T. Baxter, None; C.R. Thomas, None; M. Abramowitz, None; M. Abramowitz, None.
1137
IMRT vs. Passively Scattered Proton Therapy (PSPT) for Locally Advanced Non-small Cell Lung CA (LA NSCLC) Randomized Trial - Is there Equipoise?
R. Mohan1, X. Zhang1, J. Matney1, J. Bluett1, L. Dong1, P. Balter1, M. Engelsman2, N. Choi2, R. Komaki1, Z. Liao1 1
M.D. Anderson Cancer Center, Houston, TX, 2Massachusetts General Hospital, Boston, MA
S201
1135
A Phase I Study Demonstrating Manganese Superoxide Dismutase Plasmid Liposome Complex (MnSOD-PL) Reduction of Esophagitis following Standard Chemoradiation in Surgically Unresectable Stage III NSCLC
J. S. Greenberger1, C. P. Belani2, J. D. Leuketich1, A. Argiris1, S. S. Ramalingam3, W. Gooding1, A. Pennathur1, D. Petro1, M. W. Epperly1, A. A. Tarhini1 1
University of Pittsburgh Cancer Institute, Pittsburgh, PA, 2Penn State Hershey Cancer Institute, Hershey, PA, 3Emory University, Atlanta, GA Purpose/Objective(s): Esophageal toxicity has been accepted reluctantly, as a necessary side effect of the benefits of chemoradiotherapy for lung cancer. MnSOD-PL is a genetically engineered therapeutic DNA/liposome complex containing the human MnSOD transgene. Preclinical studies in mouse models have demonstrated that the expression of the human MnSOD transgene confers protection of normal tissues from ionizing irradiation damage. A phase I trial has been completed demonstrating MnSOD-PL may reduce esophagitis following chemoradiation in surgically unresectable Stage III non-small cell lung cancer. Materials/Methods: Chemotherapy (carboplatin AUC = 2 and paclitaxel 45 mg/m2 intravenously) was given weekly (for 7 weeks), concurrently with radiation therapy. MnSOD-PL was swallowed twice a week (total 14 doses), at 3 dose levels: 0.3, 3, and 30 mg. Dose escalation followed a standard phase I design. Esophagoscopy was done at baseline, day 4 and 6 weeks after radiation with biopsies of the squamous lining cells. DNA was extracted and analyzed by PCR for the detection of the MnSOD transgene DNA. Results: Ten patients with AJCC stage IIIA (3) and IIIB (7) completed the course of therapy per study protocol. Five had squamous histology, 2 adenocarcinoma, 1 large cell, and 2 not specified. Patients were treated in 3 different cohorts at 3 dose levels of MnSODPL: 0.3 (3 pts), 3 (3 pts), or 30 mg (4 pts). The median dose of radiation was 77.7 Gy (range 63 - 79.10 Gy). Overall response rate for the standard chemo-radiation regimen was 70% (N = 10). There were no dose- limiting toxicities reported in all 3 dosing tiers. Conclusions: The oral administration of MnSOD-PL is feasible and safe. The phase II recommended dose is 30 mg. Author Disclosure: J.S. Greenberger, None; C.P. Belani, None; J.D. Leuketich, None; A. Argiris, None; S.S. Ramalingam, None; W. Gooding, None; A. Pennathur, None; D. Petro, None; M.W. Epperly, None; A.A. Tarhini, None.
1136
Is Radiation Therapy Becoming More Effective in Treating Non-small Cell Lung Cancer? 1
B. E. Lally , J. L. Wright1, L. G. Koniaris1, O. Mahmoud1, J. Gomez1, D. Nguyen1, T. Baxter1, C. R. Thomas2, M. Abramowitz1, M. Abramowitz1 1
University of Miami, Miami, FL, 2Oregon Health & Science University, Portland, OR
Purpose/Objective(s): Over time the management of patients with non-small cell lung cancer (NSCLC) has evolved, and aggregate outcome of these patients may have improved. The specific aim of this analysis if to determine if an improvement in survival over time in pts receiving radiotherapy (RT) from the Surveillance, Epidemiology, and End Results (SEER) database may be observed. Materials/Methods: Patients with incident NSCLC aged 21 yrs and older diagnosed from 1988-2002 and followed through 2006 were examined. All pts were censored at 5 years survival. Cox proportional Hazard model was used. Results: Overall, 158813 patients were identified. The number of pts with stage I, II, IIIa, IIIb, and IV were 41159 (26%), 7456 (5%), 16694 (11%), 34700 (22%), and 58804 (37%), respectively. 58,557 (37%) of these patients received definitive RT. For the total cohort, more recent year of treatment (HR = 0.993; CI: 0.992-0.994) and female gender (HR = 0.831; CI: 0.822-0.840) were associated with better survival. Conversely, increasing age (HR = 1.006; CI: 1.006-1.006), and African American race (HR = 1.171; CI: 1.151-1.191) were associated with worse survival. With respect to squamous histology (HR = 1.00 (Ref.)), large cell carcinoma (HR = 1.315; CI: 1.290-1.341) and adenocarcinoma (HR = 1.072; CI: 1.059-1.085) were associated with worse survival, while bronchioalveolar carcinoma (HR = 0.447; CI: 0.434-0.461) was associated with the best survival. Subset analysis was performed for only pts receiving definitive RT. Overall survival improved with more recent yr of treatment across all stages: Stage I (HR = 0.981; CI: 0.973-0.989), II (HR = 0.968; CI: 0.948-0.988), IIIA (HR = 0.983; CI: 0.977-0.989), IIIB (HR = 0.978; CI: 0.975-0.982), and IV (HR = 0.987; CI: 0.985-0.990). Conclusions: The survival for pts with NSCLC has improved over time in all stage categories and specifically in those receiving RT. We hypothesize that the benefit seen in stage I and IV NSCLC is driven by improved staging. The benefit in stage II/IIIA/IIIB may represent not only an improvement in staging, but also improvements in RT as well as the widespread adoption of combinedmodality treatment. Author Disclosure: B.E. Lally, None; J.L. Wright, None; L.G. Koniaris, None; O. Mahmoud, None; J. Gomez, None; D. Nguyen, None; T. Baxter, None; C.R. Thomas, None; M. Abramowitz, None; M. Abramowitz, None.
1137
IMRT vs. Passively Scattered Proton Therapy (PSPT) for Locally Advanced Non-small Cell Lung CA (LA NSCLC) Randomized Trial - Is there Equipoise?
R. Mohan1, X. Zhang1, J. Matney1, J. Bluett1, L. Dong1, P. Balter1, M. Engelsman2, N. Choi2, R. Komaki1, Z. Liao1 1
M.D. Anderson Cancer Center, Houston, TX, 2Massachusetts General Hospital, Boston, MA
S201