1020

Proceedings of the 31st Annual ASTRO Meeting

TREATMENT OF CANCERS OF THE LIVER AND PORTA HEPATIS WITH EXTERNAL BEAM IRRADIATION AND INTRAARTERIAL HEPATIC FLUORODEOXYURIDINE.*

219

Theodore S. Lawrence, M.D., Ph.D. l, Lynn M. Androff, R.N., B.S.N.1, Suzette C. Walker-Andrews, R.N.3, James C. Andrews, M.D.2, Rebecca J. Tesser, R.T. (T)‘, Ira S. Wollner, M.D.3, Allen S. Lichter, M.D.l, William D. Ensminger, M.D., Ph.D.3

Departments of Radiation Oncologyl, Radiologyz, and Medical Oncology3, University of Michigan Medical Center, Ann Arbor, MI 48109

The role of radiation therapy in the treatment of intrahepatic malignancies has been limited by the low tolerance of the liver to radiation when the entire liver is treated with conventional fractionation. The tolerance of the whole liver to conventional fractionation is approximately 30 Gy, which would not be expected to be tumoricidal in most cases. We hypothesized that in selected patients much higher doses of radiation could be safely delivered as boost treatment to gross tumor within the liver, and that the tolerance of the liver would be determined by the volume of the normal liver that was irradiated. Therefore, we have initiated a prospective study that incorporated the concept of the dose-volume histogram @VH) of normal liver to determine the boost dose.

All patients have a treatment planning CT scan. The volume of the entire liver (L) and the tumor(s) (T) are demarcated, and the volume of normal liver is calculated as L-T. All patients undergo 3-D treatment planning to determine the optimal field arrangements. Non-axial, non coplanar beam arrangements often prove to be superior to standard axial plans. All treatment is given in 1.5 Gy fractions twice a day. If >50% of the normal liver would be treated to encompass the tumor, no boost treatment is given and patients receive 33 Gy to the whole liver, otherwise 30 Gy is given to the whole liver with boost treatment. Boost doses are 15 Gy if 26-50% of the normal liver would be treated and 30 Gy if <25% of the normal liver can be included. All treatment is given with concurrent intraarterial hepatic FdUrd (0.2 mg/kg/d).

Thirty three patients have been entered onto this study between lo/87 and 10/88, and were assessed as of l/1/89. The median age was 56 (range 28-84). There were 20 men and 13 women. The median performance status was 1 (range O-3). Patients had the following primary carcinomas: colorectaI(l6 patients), breast (4 patients), hepatocellular (2 patients), gastric (2 patients), bile duct (2 patients), unknown primary (3 patients) or other (4 patients). Twenty patients received only whole liver radiation and 13 were treated with whole liver plus a 15 Gy (6 patients) or 30 Gy (7 patients) boost treatment. Responses were assessed by CT scan obtained l-2 months after the completion of treatment and by follow-up studies as clinically indicated. Toxicity was assessed by the WHO scale.

Twenty nine patients were evaluable for response (2 patients lost to follow-up; 2 patients with cholangiocarcinoma without measurable disease). There were no complete responses. Fourteen patients had objective partial responses, 13 patients had stable disease, and 2 patients had progressive disease. The median duration of response is 5 months (range l-11+ months). All patients were evaluable for toxicity. The chief toxicities have been fatigue, nausea, gastritis, and diarrhea which were < grade 2 in severity. There was 1 grade 3 thrombocytopenia and 1 patient who developed a gastric ulcer requiring surgery. There were 2 probable cases of mild treatment related hepatitis in patients with progressive systemic disease.

In summary, this appears to be a tolerable, potentially effective approach for this group of patients. Additional studies will be required to determine the optimal combination of these modalities. *Supported by NC1 grant 5MOl-RR00042

1021

Denise R. Tmwbridge, M.D., Linda S. Gemer, M.D., James Neff, M.D.,* Fritz Lin, M.D.,** Eashwer Reddy, M.D., Richard Evans, M.D., Ph.D., Ruth Hassanein, Ph.D.***

t@mrtmnt of Radiation Oncology, *Department of Surgery, Section of OrUqc& 'c -GwY, **rzepment of Pathology, ***Cqxrtmnt of Bicmtry, university of Kansas Medical Center, Kansas City, Kansas 66103

Brachythera~ has been reported by several institutions to be an intportant adjwant to limb sparing surgery in the treatment of soft tissue sarccmias. Twenty-five patients with soft tissue sazcana were treated with Ir192 implants following wide local excision at our institution between 1982 and 1987. Twenty of these patients had a prirrary sarccrua, 4 had a deposit.

recurrent lesion, and 1 had a solitary metastatic External ham radiotheraPy was given in addition to the implant in 16 patients. Doseswere

individualized as follows: typically, patients who received pre- or post-implant external &am radiotherapy were given 45 Gy externally and 20 Gy via implant; patients who received implant only received a dose of 50 Gy; the 3 patients who had implants into previously irradiated tissues received a dose of 30 Gy. Implant closes were Prescribed to the isockxse line which best encompassed the entire tumor volLlme. Four patients also received adjuvant chemotherapy following local treatment.

The median follow-up in these 25 Patients is 36 months (12 to 75 tnnnt_hs) . Twenty Patients have had no evidence of recurrence following their primary treatment (FFR=80%). Five patients have failed locally; 2 have died, and the other 3 have had salvage prucedures rendering than free of disease. Four of the 5 patients who failed locally did so within 3 years. A multivariate analysis using zuea;as used in o&r to predict failure in 3 years or less.

stepwise logistic Potential predictors examir&

tumor location, primary vs reot.mren t disease, grade, histology, surgical maryins implant only’ vt??&lant plus external beam, and a ratio of the volume of tissue which received 65 r$ (w65) to the ttrtmm volutn? (TV), i.e. (w65/w). The single variable which was significantly associated with 10tzl ftilt_Ke at 3 years or less was m65/w of less than one. Once this variable was entered into the analysis, no other factor prov& significant. !t?“65/m of less than one.

Of the 4 patients who failed within 3 years, 3 bad The fourth had a TV69/TV of 1.06.

220 Radiation Oncology, Biology, Physics October 1989, Volume 17, Supplement 1

Chr data suggest that when attmpting local control of soft tissue sarcomas with brachytherapy the volume of tissue receiving 65 Gy (m65) frm both implant and external beam must exceed the volume ok the excised lesion (TV). Since the volume of a tumor can easily be detemined prior to surgical excision either by CT or MRI scanning, pre-planning of the implant volume could potentially reduce the rate of local failure.

1022 INVASIVE THYMOMA: TREATMENT AND RESULTS OF POSTOPERATIVE RAJIATION THERAPY

Michael R. Kuettel, M.D., Ph.D. and Eva Zinreich, M.D.

Department of Radiation Oncology, The Johns Hopkins Hospital

Invasive thymoma is a rare anterior mediastinal tumor with few reported cases treated with megavoltage radiation therapy to date. We have recently reviewed all cases of thymoma diagnosed at our institution and evaluated a subset of twenty patients with histologically confirmed invasive thymoma treated by radiotherapy from 1975 to 1988.

The preoperative scans and operative reports were reviewed to determine the presence of capsular invasion, tumor extension to adjacent structures, metastasis and completeness of resection. All patients had evidence of invasion. Fifteen patients presented with Stage III disease (invasion into neighboring structures, i.e., pericardium, great vessels, or lung) and five patients presented with Stage IV disease (pleural or pericardial dissemination or metastasis).

Average age at diagnosis was 52 years (range 13 to 75). There were eleven women and nine men. Four patients had myasthenia gravis. The remaining sixteen patients had no known thymoma-associated syndromes. Three patients presented with superior vena cava symptoms.

Surgical management consisted of biopsy only (9), subtotal resection (7) and gross total resection (4). The pathologic classification was as follows: mixed epithelialllymphocytic (lo), predominant epithelial (9); predominant lymphocytic (1).

Megavoltage irradiation consisted of an average of total dose of 47 Gy (range 32-65 Gy) at 1.8 Gy per day. Multiagent chemotherapy was used in five cases with metastasis and/or progression of disease.

Actuarial overall survival was 50% at five and ten years. Adjusted survival was estimated by calcu- lating actuarial survival with non-cancer related deaths censored. This adjusted survival was 77% at five and ten years. Myasthenia did not have an unfavorable effect on prognosis with three of four patients alive without evidence of disease (median follow-up 6.5 years). Three of four patients who died from disease received ~40 Gy to the mediastinum. Five of six patients who received >50 Gy, however, remain alive and disease free. Favorable prognostic indicators included Stage III disease, gross total resection and >50 Gy to the mediastinum.

1023 TEN YEARS EXPERIENCE WITH DEFINITIVE IRRADIATION IN PROSTATE CANCER (A2, 5, B2, C) LYMPH NODE NEGATIVE

James D. Easley, M.D., John H. Wilbanks, M.D., W. Sam Dennis, Ph.D., M.D.

Department of Radiation Oncology; Baylor College of Medicine

This study is a University retrospective review to evaluate the efficacy of definitive radiation treatment in 295 patients with stage A2, B, C carcinoma of the prostate who had been staged with the following criteria: Negative pelvic lymphadenectomy, negative bone scan, normal serum acid phosphatase and in the course of their treatments and follow-ups, underwent no hormonal manipulations prior to documented disease.

The end point of analysis was the probability of progression to distant metastases. The excellent results of the analysis for all the stages is as follows in the table below.

Table 1. Distant Disease Free Survival

Stage # % 5 years S.E. % 10 years S.E.

A2 82 92 .03 91 .033

B1N 19 95 .05 84 .08

B1 91 87 .03 68 .06

I32 53 82 .05 63 .08

C 50 74 .06 46 .lO

Total 295