S484 I. J. Radiation Oncology d Biology d Physics Volume 69, Number 3, Supplement, 2007

Materials/Methods: 278 Consecutive Patients who underwent a definitive Surgical Resection ± adjuvant chemotherapy forNSCLC from 2000–2004 were qualified for analysis if they did not receive any adjuvant/neo-adjuvant Radiotherapy, had at leastthree months of follow-up, and did not have a history of other cancers within 5 years of the diagnosis of their NSCLC. Univariateand Multi-variate analysis were performed to assess risk factors for brain metastases as the only site of metastatic relapse in order todefine a high-risk group that could benefit from screening with serial MRI exams after definitive surgical resection.

Results: After a median follow-up of 39 months, 46 patients developed distal recurrences. 10 of these patients presented withisolated Brain metastases as the only site of metastatic disease. Multi-variate analysis revealed that isolated CNS metastaseswere significantly associated with Tumor Stages T2NO and T3N0 as well as present smoking. Non-CNS Distal Recurrenceswere significantly associated with tumor histology (tumors with neuroendocrine features, NSCLC-NOS), performance of a pneu-monectomy, and cough by multi-variate analysis.

Conclusions: Isolated CNS metastases have distinctly different risk factors than non-CNS distal recurrences. If these results areconfirmed in prospective trials, patients who continue to smoke and present with T2-3N0 tumor stages may benefit from periodscreening with Brain imaging to prevent symptomatic recurrences from developing.

Author Disclosure: L. Medford-Davis, None; J. Varlotto, None; M. Nikolov, None; M. DeCamp, None.

2510 High Dose of Low Molecular Weight Catalytic Metalloporphyrin Antioxidant AEOL 10150 Protects Lungs

From Fractionated Radiation

F. Salahuddin1, Z. Rabbani2, P. Yarmolenko2, I. Batinic-Haberle2, B. Thrasher2, B. Gauter-Fleckenstein2, M. Dewhirst2,

M. Anscher3, Z. Vujaskovic2

1Department of General Internal Medicine, Durham Regional Hospital/Duke University Medical Center, Durham, NC,2Department of Radiation Oncology, Duke University Medical Center, Durham, NC, 3Department of Radiation Oncology,Medical College of Virginia/Virginia Commonwealth University, Richmond, VA

Purpose/Objective(s): To determine whether administration of a catalytic antioxidant, Mn(III) tetrakis(N,N’-diethylimidazolium-2-yl) porphyrin, AEOL10150, reduces the severity of long-term lung injury induced by fractionated radiation (RT).

Materials/Methods: Fisher 344 rats were randomized into five groups, receiving the following treatments: RT+AEOL10150 (2.5mg/kg BID), AEOL10150 (2.5 mg/kg BID) alone, RT + AEOL10150 (5 mg/kg BID), AEOL10150 (5 mg/kg BID) alone and RTalone. Animals received five 8 Gy fractions of RT to the right hemithorax. AEOL10150 was administered 15 minutes before RTand 8 hrs later during the period of RT treatment (5 days), followed by subcutaneous injections for thirty days, twice daily. Twenty-six weeks after RT, lung sections were histologically analyzed for factors associated with hypoxia (HIF1a, CA IX), angiogenesis(VEGF,CD31), oxidative stress (8-OHdG,3-nitrotyrosine), inflammation (activated macrophage marker:ED1) and fibrosis path-way (TGFb1, Smad3, p-Smad2/3) to determine the extent of lung injury.

Results: There was no significant difference in lung damage and immunohistochemistry studies between the RT alone andRT + AEOL10150 (2.5 mg/kg BID). Lung histology at 26 weeks revealed a significant decrease in structural damage (p =0.003) and collagen deposition (p = 0.009), in animals receiving RT + AEOL10150 (5 mg/kg BID), in comparison to RT alone.Lung immunohistochemistry revealed a significant reduction in HIF1a stabilization, tissue hypoxia and angiogenic response inanimals receiving RT + AEOL 10150 (5 mg/kg BID) (p\0.05). Intrapulmonary inflammation and oxidative stress were also sig-nificantly reduced in RT + AEOL10150 (5 mg/kg BID) animals (p \ 0.05). RT + AEOL10150 (5 mg/kg BID) treatment signif-icantly reduced TGFb1 activation and its signal transduction down the fibrosis pathway (p \ 0.05).

Conclusions: Administration of AEOL10150 at a dose of 5 mg/kg BID during and after RT, results in a significant protective effectfrom long-term RT-induced lung injury. Low dose delivery of AEOL10150 has no beneficial radioprotective effects.

Author Disclosure: F. Salahuddin, None; Z. Rabbani, None; P. Yarmolenko, None; I. Batinic-Haberle, None; B. Thrasher, None;B. Gauter-Fleckenstein, None; M. Dewhirst, None; M. Anscher, None; Z. Vujaskovic, None.

2511 Determination of Patient-Specific Intra-Fractional Respiratory Motion Envelope of Tumors From

Maximum Intensity Projections of 4D CT Datasets

M. Ezhil, S. Vedam, B. Choi, G. Starkschall, P. Balter, J. Chang

University of Texas M.D. Anderson Cancer Center, Houston, TX

Purpose/Objective(s): Recent developments in multislice CT technology and 4D CT imaging have enabled patient-specific de-termination of intra-fraction gross tumor volume (GTV) position and motion throughout the respiratory cycle. Image processingtools such as the maximum intensity projection (MIP) of 4D CT datasets have increased efficiency of such a process. Althoughapplicability of such tools in estimating GTV respiratory motion envelopes has been evaluated for some early stage lung tumors,further evaluation is required to prove that such tools ensure adequate coverage of the GTV volume throughout the range ofrespiratory motion.

Materials/Methods: 27 patients with NSCLC (17 stage I and 10 stage III) who received definitive radiotherapy in our institutionwere studied. 4D CT datasets were acquired for all patients for treatment planning. The GTV was contoured manually on eachrespiratory phase (0–90%) of the 4D CT dataset and also on the MIP of the 4D CT dataset. The envelope of respiratory motionof the GTV was determined based on (a) combining the GTV contours from all phases of the 4D CT dataset (GTVAllPhases) (b)combining the GTV contours from two extreme respiratory phases (0 and 50%) of the 4D CT dataset (GTV2Phases) (c) definingthe GTV contour as the MIP of the 4D CT dataset (GTVMIP) and (d) defining the GTV contour as the MIP of the 4D CT datasetfollowed by subsequent modification based on visual verification of coverage in each individual phase of the 4D CT dataset(GTVMIP_Modified). Using the respiratory motion envelope determined from contouring all phases of the 4D CT dataset(GTVAllPhases) as the reference GTV, we compared volumes and their corresponding matching indices (ratio of intersection tothe union of any two volumes) for each of the other methods of respiratory motion envelope determination.