188 Radiation Oncology, Biology, Physics October 1987, Volume 13, Supplement 1

later years, interstitial steroid infiltration was selectively permitted. Dose-success relationships, post-excision interval (velocity of initiating postoperative irradiation) data, and recurrence intervals will be presented. Recurrence rate after irradiation was low, 9/375 (2.4%). If 7 of 9 recurrences are eliminated for post-irradiation ear lobe repiercing, true recurrence is only 2/375 (0.53%). An additional 5/375 (1.3%) developed subcutaneous nodules < 5 mm. which were neither keloid nor visible. Two others formed flat wide hypertrophic scar without keloid at one pole of their scars. Cosmetic result was considered excellent without recurrence in 92%, favorably improved with hypertrophic scar or persistent hyperpigmentation in 5.6%, and marginally improved with smaller less symptomatic keloid in 2.4%. Complications were limited to transient hyperpigmentation in many, persistent pigment disturbance in a few, pre-irradiation hemorrhage in one (unrelat- ed to radiotherapy), and there were no cases of irradiated incision site failure to heal nor wound dehiscence. Complication statistics will be presented. Our null (0%) carcinogen- icity rate to date and the one-half of one percent true recurrence rate supports continued use of postoperative irradiation to prevent keloid formation in this group of documented troublesome keloid formers. An unexpected finding was 22 of 250 subjects being Caucasian.

187 CONCOMMITTANT CHEMO RADIOTHERAPY IN LIMITED SMALLCELL CARCINOMA OF LUNG: IMPROVED RESPONSE AND MEDIAN SURVIVAL. A SOUTHWEST ONCOLOGY GROUP STUDY. Lalitha M. Janaki, J.D. McCracken, S. B. Taylor, P.G.S. Giri, G. B. Weiss, W. Gordon, Jr., R. B. Vance, and J. Crowley Spohn Hospital, 334 Cape Cod, Corpus Christi, Texas

THE study is designed to use simultaneous Cisplatinum, Etoposide and chest radiation in limited small cell carcinoma of lung. Long term survival in evaluable patient population is imprqssive.

SCHEMA: Radiation therapy to the primary tumor with concommittant chemotherapy to begin on day 1 of the program. 180 rads/day to total tumor dose of 4500 rads. Chemotherapy consisting of Cisplatinum, VP-16 and Vincristine to begin day 1. Prophylactic brain radatio to begin day 57. Consolidation chemotherapy to begin on day85 with Vincristine, Methotrexate, VP-16, Adriamycin, and cyclophomide. After 12 weeks of consolida- tion chemotherapy, patients with CR had all therapy discontinued and observed. The study was opened in December, 1982. Group wide participation began in April, 1985. Toxicity was acceptable and presented pre- viously. A total of 164 patient put on the study. Complete response rate was greater than 55%. The res- ponders have high performance status survival. Local recurrence rate was less than 10%.

The survival curves with relapse rate, response rate to be presented. The following observations were made:

1. The high complete remission rate. 2. The excellent performance status in surviving patients. 3. The long tumor free interval off maintenance therapy. 4. The low recurrence rate. 5. The acceptable toxicity.

These points warrant further use of this program in patients with the diagnosis of LIMITED SMALL CELL CARCINOMA OF THE LUNG.

188 LOCO-REGIONAL FAILURE RATE IN RELATION WITH RADIATION DOSE IN COMBINED MODALITY APPROACH OF MULTIAGENT CHEMOTHERAPY AND RADIOTHERAPY FOR LIMITED STAGF SMALL-CELL LUNG CARCINOMA

Noah C. Choi, M.D! and Robert C. Carey, M.D? Departments of Radiation Medicine+ and Medicine?, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114

Erroneous conclusion can be drawn from inadequate studies. While the role of thoracic radiotherapy (RT) for limited stage small-cell lunq carcinoma (SCLC) has been a subject of the debate based on median survival time (MST) of lo-12 months (M) by either multiaqent chemotherapy (CT) alone or CT plus thoracic RT, radiation dose‘schedules employed in.m&y-studies remain-insufficient. A recent autopsy report, which states that the addition of RT to the orimarv tumor and mediastinum failed to modifv the distribution of residual tumors compared with that of patients treated with CT alone (J Clin Oncol 5:246-254, 1987), prompted us to evaluate the radiation dose-tumor response in modern CT era. As a few ongoing randomized studies are getting matured, it has become clear that thoracic RT continues to remain to play a vital role in achieving long-term survival beyond MST.

Proceedings of the 29th Annual ASTRO Meeting 189

Between 1974 and 1984, 456 patients (226 limited and 230 extensive stages) were treated at this institution. In order to keep multiagent CT at a uniform intensity, patients, who received (a) combined modality approach of both multiagent CT and thoracic RT and (b) > 3 cycles of multiagent CT (> 3 drugs), were chosen for this analysis. There were 126 such patients who-met these strict criteria, a?id the treatment methods for the remaining 100 patients were as follows: (a) CT alone with RT reserved for local failure (42 pts); (b) RT alone (20 pts); (c) surgery + adjuvant CT or RT (21 pts); (d) modified CT plus RT (17 pts). During the lo-year period, therapeutic factors have evolved. Radiation-dose was increased from 30-40 Gy (TDF 49-66) in 1974-1977 to 44-52 Gy (TDF 73-86) in 1978-1984. Target volume for RT included the primary lesion with a 2-cm margin of normal lung and 80% of the mediastinum. CT program also evolved from COP, CAV (1974-1977) to MACC, VCE-VCA, PCE-ACE (1978-1984).

Forty of 126 patients (32%) developed loco-regional recurrence (infield failure) and 95% (38/40) of these patients exhibited this within 3 years. Survival data of 126 patients were as follows: a) MST was 12 M; b) actuarial survival rates at 2 and 5 years were 21% and 8% respectively.

Fifty percent of these patients died within 12 months (MST 12 M) and were not exposed to the full length of the risk period for loco-regional failure. In order to take into account the duration of exposure to the risk period, actuarial method was employed to measure the probability of loco-regional failure. Loco-regional failure rates at 3 years were 36X, 39%, 43%, 79%, and 100% for 50 Gy, 45 Gy, 40 Gy, 35 Gy, and 30 Gy respectively, (Fig. 1). Although the recurrence rates of 36% and 43% by 50 Gy and 40 Gy were not statistically different, the difference between the recurrence rates of 36% and 79% by 50 Gy and 35 Gy was statistically siqnificant, p < 0.01. The time to recurrence seems also shorter with lower radiation-dose than that of higher RT doses.

Current RT schedules employing 45 Gy to 50 Gy (TDF 75-82) are still associated with 36% to 40% of loco-regional failure rates, and these data urge trials employing radiation-doses higher than 50 Gy or altered fractionation schedules to achieve the best possible rate of loco-regional control of SCLC.

189 CONCURRENT TWICE-DAILY RADIOTHERAPY (XRT) - PLATINUM (DDP) - ETOPOSIDE (VP-16) FOR LIMITED SMALL CELL LUNG CANCER (SCLC): UPDATE 1987

Andrew T. Turrisi, III, M.D.,1 Donna .J. Glover, M.D.,2 and Bernard Mason, M.D.3

Departments of Radiation Therapy1 and Medicine,2 Department of Medicine,3

Hospital of the University of Pennsylvania, and Presbyterian-University of Pennsylvania Medical Center, Philadelphia, PA

Local control (LC) and long term survival (LTS) remain problems in the treatment of limited SCLC. Many integrations of XRT and chemotherapy have improved response rates and LTS, but intensified toxicity. Twice daily XRT plus simultaneous DDP/VP-16 chemotherapy attempts to address these issues. Since SCLC has little to no shoulder on survival curves, a large growth fraction and rapid doubling-time, two XRT fractions per day may be more effective. Normal tissues have broader shoulders. Lung, heart, esophagus, and spinal cord have not been reported to express toxicity to DDP/VP-16. DDP/XRT interaction has generated considerable lab interest, particularly against hypoxic cells, of which SCLC has a substantial proportion.

Since 7/84 the University of Pennsylvania has entered 23 patients with limited SCLC. Patients were selected by performance status < ECOG 1, FEVlL 1 liter, no prior cancer and staged with CXR, bronchoscopy, CT's chest, head and abdomen, bone scan and bone marrow bx. and aspirate. Histologic or cytologic proof of SCLC or variant SCLC were identified before entry. The 23 patients consisted of 12 males and 11 females, 21 whites 2nd 2 blacks, DDP-60mglM days 1,

with a mean an< median age of 57.9 and 56 (range 45-80). Induction (weeks l-6): 22; VP-16-120 mg/M days 4, 6, and 8; 25, 27, and 29. XRT starts on day 1 and delivers

150 cGy 2x/d over the course of 21 days, Monday through Friday, total dose 4500 cGy (uncorrected). Week 1 XRT gives AP/PA parallel opposed treatment to both sessions, but weeks 2 and 3 administers obliqued parallel opposed therapy in order to exclude the spinal cord from the PM session during weeks 2 and 3 without using a direct posterior cord block. After week 6, complete restaging assesBes for response. To those responding (between weeks 7-24) 6 cycles of alternating CAV (1000/45/2 mg/M ) and DDP/VP-16 (60/120 mg/M ) are administered. Prophylactic cranial irradiation (PCI) begins post re-staged CR at week 26 and after completion of all chemotherapy. PC1 schedule and dose varied to give 2400-2500 cGy, 8-12 fractions over 2 to 3 weeks.

At this writing all 23 patients are evaluable for toxicity and response evaluation, with median 22 months, minimum 4 months follow-up. Acute toxicity: observed: a) esophagitis: 73% (3 severe); b) myelotoxicity: _ < 2000 WBC 65% (4 < 1000) platelets < 100,000 13%. No acute pulmonary toxicity. One non-cancer death day 93 from strep. sanguis pneumonia and sepsis with normal blood parameters. Response: overall, 91% CR: pure small cell 20/21 (95%) @ 6 weeks, 21/21 (100%) @ 6 months; O/2 variant SCLC responded, both had persistence in chest, disseminated and died. Six initial responders progressed--all systemically. No responder has relapsed in field. Overall local control is 91%; 100% in initial responders with pure SCLC. Survival: with median follow up of 22 months, median survival not reached. The 24 month actuarial survival and disease free survival is 56%.

Excellent response, local control and survival can be achieved in limited SCLC. While toxicity is formidable, for the most part, it is tolerable and reversible. An ECOG pilot of multiple institutions is underway as prologue to prospective randomized trial.