S750 I. J. Radiation Oncology d Biology d Physics Volume 69, Number 3, Supplement, 2007

Conclusions: An axillary or groin origin for a high grade STS does not confer greater risk for local relapse as compared to moredistal extremity tumors treated with EBRT following limb preservation surgery. A positive margin of resection remains the majorrisk factor for a local relapse.

Author Disclosure: R.P. Phimolsarnti, None; A.M. Griffin, None; P.C. Ferguson, None; C.N. Catton, None; P.W. Chung, None;R.S. Bell, None; J.S. Wunder, None; B. O’Sullivan, None.

2976 Spot Scanning Proton Beam Therapy in the Curative Treatment of Adult Patients With Sarcoma: The Paul

Scherrer Institute Experience

D. C. Weber1,2, G. Goitein2, H. Rutz3, A. Bolsi3, A. Lomax2

1Geneva University Hospital, Geneva, Switzerland, 2Center for Proton Radiation Therapy, Paul Scherrer Institut, Villigen PSI,Switzerland, 3Center for Proton Radiation Therapy, Paul Scherrer Institut, Villigen PSI, Switzerland

Purpose/Objective(s): To assess the safety and efficacy of spot scanning proton beam therapy (PT) in the curative treatment ofsoft-tissue sarcoma (STS) in adults patients.

Materials/Methods: We identified 13 STS patients treated with PT between July 1998 and May 2005 in our institutional database.Tumor histology varied with the most common histologic subtypes including liposarcoma and peripheral nerve sheet tumor. Alltumors were located in vicinity of critical structures, such as the spinal cord, optic apparatus, bowel, kidney or bowel. Six and 5patients received PT either as adjuvant therapy for non-R0 resection or for recurrence, respectively. Two patients received radicalPT for unresectable disease. The median prescribed dose was 69.4 CGE-Gy (range, 50.4–76.0) at 1.8–2 CGE-Gy (median, 1.9) perfraction (CGE = proton Gy X 1.1). Pre-PT anthracycline-based chemotherapy was delivered to 3 patients only. No patient has beenlost to follow-up (median 47.7 months, range, 15.1–99.7).

Results: Of the 13 patients, all but 2 patients were alive. Local recurrence developed in 3 (23%) patients. The administered dose tothese patients was #60 Gy-CGE. Distant control was achieved in all but 2 patients (lung metastasis), one of whom presented witha concomitant local recurrence. The 4-year local control and metastasis-free survival rates were 74.1% and 84.6%, respectively.Late grade $2 toxicity was observed in only 2 patients.

Conclusions: Spot scanning PT is an effective and safe treatment for patient with STS in critical locations. The observed toxicityrate was acceptable.

Author Disclosure: D.C. Weber, None; G. Goitein, None; H. Rutz, None; A. Bolsi, None; A. Lomax, None.

2977 Calreticulin Expression is a Mechanism of Radiation Induced Immune Response in Cancer

L. Geng, T. Tu, H. Onishko, A. Fu, D. E. Hallahan

Vanderbilt University, Nashville, TN

Background/Purpose: Calreticulin regulates dendritic cell activation in cancer and is expressed on cancer cells in response tocytotoxic therapy. Immunotherapy is an effective form of treatment of advanced melanoma. The goal of the present study wasto test the hypothesis that advanced melanoma can benefit from initial radiotherapy prior to resection of the primary.

Materials/Methods: B16F0 melanoma cells were irradiated with 25 Gy and incubated and stained for Calreticulin. FollowingCalreticulin expression irradiated B16 cells were then inoculated subcutaneously into C57 BL6 mice at 6 hours after irradiation.Control group mice received un-irradiated B16 cells. 12 days after tumor vaccine injection, B16F0 tumors were implanted into thehind limb of the mice and tumor growth delay. Tumor tissue was then resected and stained for tumor-infiltrating lymphocytes (TIL)using the CD8 antibody. In a separate experiment, mice inoculated with tumor vaccine were then challenged at day 12 with tail veininjection of B16 cells. Lung metastases were quantified by use of tissue sectioning and counting the number of tumor noduleswithin the lung.

Results: Calreticulin was expressed on the cell membrane surface of B16F0 after irradiated B16F0 vaccine caused 5–7 days tumorgrowth delay as compared to control groups. The CD8+T cell staining showed that tumor-infiltrating lymphocytes significantlyincrease in B16F0 tumor tissues of mice inoculated with irradiated B16F0 vaccine injection. In contrast, control B16F0 tumor tis-sues had very few of CD8 + T cells positive staining. CD8+ T cells staining confirmed that irradiation + surgical remove inducea much stronger immune response against B16F0 metastasis in the lung. Radiation-induced calreticulin expression on the surface ofB16F0 melanoma cells beginning at 6 hours after treatment with maximal expression at 24 hours following treatment. Mice treatedwith the irradiated B16F0 tumor vaccine showed a seven day tumor growth delay as compared to mice treated with untreated con-trol cells. Tumor sections showed CD8+ T cell infiltration into tumors in mice receiving the irradiated tumor vaccine but not in micereceiving untreated control cells. In the lung metastasis model, B16F0 tumor metastases were counted both in the surface of thelung and on tissue sections. Mice receiving the irradiated tumor vaccine was 4.2 ± 2.7 nodules as compared to un-irradiated controltumor vaccine showing 53.2 ± 9.5 tumor nodules and control mice receiving no tumor vaccine at 93.2 ± 17.1 tumor nodules(p \ 0.001).

Conclusions: Irradiated B16F0 melanoma can induce an immune response that diminishes melanoma metastases in mousemodels. Based on these preclinical findings, we have developed a clinical protocol utilizing stereotactic body radiotherapy/high dose rate brachytherapy to stimulate tumor immune response in patients with sentinel lymph node metastasis or oligometa-stasis.

Author Disclosure: L. Geng, None; T. Tu, None; H. Onishko, None; A. Fu, None; D.E. Hallahan, NIH/NCI, R01-CA1256757, B.Research Grant; NIH/NCI, R21-CA128456-01, B. Research Grant; NIH/NCI, R01-CA112385-01, B. Research Grant; NIH/NCI,2R01-CA89674-01, B. Research Grant; NIH/NCi, R01-CA88076-01, B. Research Grant; NIH/NCI, P50-CA90949, B. ResearchGrant.