256 1. J. Radiation Oncology l Biology l Physics Volume 48, Number 3, Supplement, 2000

10 17 Eye-preserving proton radiation therapy (PRT) for medium and large choroidal melanoma

M. Fuss,’ L. Loredo,’ R. Grove,* J. Slate?

‘Universify of Heidelberg, Heidelberg, Germany, “Loma Linda University, Lomn Linda, CA

Purpose: Enucleation of uveal melanoma containing eyes has been standard treatment for decades. Recent COMS-protocols compare enucleation with plaque radiotherapy for medium size tumors and percutaneous radiotherapy prior to enucleation in large tumors. However, preservation of the organ and its function, as well as cosmetics are important and growing numbers of patients are searching for treatment alternatives to avoid enucleation. This study aimed to evaluate the efficacy and safety of proton radiation therapy (PRT) for medium and large size choroidal melanoma with focus on preservation of the eye and its function. We also calculated local tumor control and survival rates.

Methods: Retrospective review of 78 patients with 60 medium and 18 large size choroidal melanomas at a median follow-up of 34 months. Tumors were treated with 70.2 CGE (Cobalt Gray Equivalent) in five fractions in typical technique. Target volume was the gross tumor volume (surgically marked by tantalum-clip placement) and a safety margin of 15 to 2 mm.

Results: The 5-year actuarial data for local control, metastases free survival, and disease specific survival were 90.5 -C 3.7%, 76.2 + 6.7%, and 75.6 t 7.6%, respectively. Eye preservation was achieved in 75.3% of patients, with useful (better than 20/200) visual acuity in 49.1% of patients alive. Both local failure and complications let to enucleation. Prognosticators for subsequent eye-loss were tumor close to the optic disc (P = 0.003) large tumors involving the ciliary body (P = 0.041), and local failure (P < 0.001). Prognostic factors for visual acuity following PRT were initial visual acuity (P = O.OOl), doses to optic disc (P = 0.001) and fovea (P = 0.022) higher than 35 CGE (Cobalt Gray equivalent), tumor close to the optic disc (P = 0.034), and retinal detachment (P < 0.001). Tumor basis diameter was significantly related to metastases free survival (P = 0.02) overall survival (P = 0.033), and disease specific survival (P = 0.017), but did not impair local tumor control, rate of enucleation and visual acuity.

Conclusion: The present data suggest that PRT is an effective and safe treatment for medium and large size choroidal melanoma. PRT can preserve the eye and its function in a reasonable percentage of patients. Whereas PRT can be recommended for medium size tumors, the patient has to be informed that treatment of large tumors is comparable in terms of local tumor control but may be associated with a distinctly higher rate of distant metastases and subsequent impaired survival rates.

10 18 Gliadel followed by radiotherapy for newly diagnosed malignant glioma: Safety results, pathologic findings, and survival

J. Weingart, H. Brem, S. A. Grossman, P. Burger, M. D. Wharam, L. Kleinberg

Johns Hopkins, Baltimore, MD

Purpose: To describe toxicity, pathologic findings, and survival after gliadel wafer inplantation followed by radiotherapy for newly diagnosed malignant glioma. Gliadel (BCNU impregnated wafers) are FDA approved for use in recurrent glioblastoma and are used with increasing frequency in the therapy of newly diagnosed malignant glioma patients prior to radiotherapy, although there is only limited information about the safety and efficacy of this approach. The rationale for the use of Gliadel in newly diagnosed patients includes administration of BCNU without systemic toxicity, improved median survival demonstrated in patients with recurrent disease, and a 32 patient randomized trial conducted in Europe that demonstrated a survival increase from 9.3 months to 12.2 months in patients with newly diagnosed glioblastoma- (Valtonen, p = ,008).

Materials and Methods: 45 patients received gliadel followed by radiotherapy for newly diagnosed malignant glioma (89% GBM) in the years 1990-91 and 1997-99. One patient was lost to follow-up. The remainder are evaluable for survival and pathology at reoperation. All reoperations, except 1 with pathology of recurrent tumor, were performed at Johns Hopkins, 27 patients who received radiotherapy at Johns Hopkins are evaluable for toxicity experienced during and one month after completion of RT. Radiotherapy was 60 Gy/30 fractions for 21 patients and 5 1 Gy/17 fractions for 6 patients. The median age is 57 years and median follow-up of surviving glioblastoma patients is 12.6 months.

Results: Full dose radiotherapy was tolerable after gliadel implantation, with l/27 developin g neurologic complications

requiring admission and responding to dexamethasone. 5 patients developed neurologic symptoms during radiotherapy responding to increased steroids and/or anticonvulsants, whereas an additional 8/27 developed neurologic symptoms during dexamethasone taper that responded to increases in dexamethasone dose. At one month after RT, 58% of surviving patients were still on dexamethasone despite attempted taper. 15/44 (35%) pts. underwent reoperation or biopsy for a new local contrast enhancing lesion. In 8/l 5 (54%) the reoperation revealed necrosis or treatment effect with or without ‘foci’ of glioblastoma. The remainder had recurrent tumor. For the 27 patients with available RT records (27 pts treated at Johns Hopkins), necrosis/ treatment effect at reoperation was observed in 2/5 patients (2/3 reoperations) treated with 5 1 Gy/17 fractions and in l/22 patients (l/6 reoperations) treated with conventional fractionation. The Kaplan-Meier median survival for the glioblastoma patients is 12.5 (95% CI 7.7, 17) months, similar to the median survival of the GBM patients in the gliadel arm of the European randomized trial described above. For glioblastoma patients under 55 years old, median survival is 14.1 (12.5, 15.5) months whereas for older patients it is 9.2 (8.3, 10.6) months.

Conclusions: Gliadel followed by full dose standard radiotherapy is acutely well tolerated although close supervision should be emphasized during dexamethasone taper. The favorable median survival in excess of one year suggests that there are not complications resulting in overall premature death. Clinicians should be aware that new contrast enhancing lesions in the resection bed may represent treatment effect/necrosis as well as recurrent disease, and we recommend that such patients not be enrolled in experimental protocols for recurrent disease without histologic confirmation.