134 Radiation Oncology ?? Biology . Physics November 1986, Volume 12, Sup. 1

Immediate RT was given per protocol design (35 cases) or for advanced parameningeal tumors (4). Control was noted in 51% with immediate RT and 71% with RT delayed 1-8 (median = 2) months post-surgery (p =.05). Data supports use of RT at doses of approximately 40 Gy for microscopic disease, continuous RT whenever feasible, and further trials of pre-RT chemotherapy.

84

TREATMENT OF PELVIC SARCOMAS WITH INTENSIVE COMBINED MODALITY THERAPY

B. Stea+, J. Miser*, E. Glatsteini, R. SteisO, 0. LongoO, T. Kinsella+

Radiation Oncology Branch+, Pediatric Branch*, and Medicine Branch', COP, DCT, NCI, NIH, Bethesda, Maryland

The location of the primary tumor and the presence of metastatic disease are the major prognostic vari- ables for patients with pediatric and adolescent sarcomas. Pelvic primaries usually have a larger size and their local failure rate has been reported to be as high as 35%. Furthermore, the proportion of patients with pelvic primaries who present with overt metastatic disease approaches 50%. For these high risk patients, the goals of therapy are both improvement in local control and eradication of either gross or microscopic metastatic disease.

To achieve these goals, we have devised a regimen that utilizes intensive chemotherapy in conjunction with aggressive radiation therapy to the primary as well as to sites of gross metastatic disease. Patients receive 5 cycles of induction chemotherapy (Vincristine, Adriamycin and Cytoxan). Following cycle 3, pa- tients are assessed for tumor response. Two additional cycles of chemotherapy are given with concomitant radiation therapy. The primary receives 55-60 Gy and metastatic (non-pulmonary) sites receive 45-50 Gy using conventional fractionation. CT-assisted treatment planning is used. Patients are then completely re- staged which includes rebiopsy of any persistent soft tissue abnormality. If a complete response is achieved, consolidation therapy consisting of total body irradiation (8 Gy in 2 fractions/2 days), high dose chemother- apy, and autologous bone marrow transplant is given.

23 patients with pelvic sarcomas were treated since l/83. 15 of 23 patients had metastatic disease at presentation. All 23 patients experienced >50% tumor response of measurable disease (excluding bone scans) following the initial 3 cycles of chemotherapy. Of the 19 patients who have completed all treatment, 18 (93%) have achieved a complete response (CR). The median disease-free interval for this group of 19 pa- tients is 19.5 months. There have been 8 relapses among the 18 patients who achieved a CR, but no local failures have been observed. There have been six relapses among the 11 patients who presented with metas- tatic disease, but only 2 of 8 patients with localized disease had a relapse. Disease-free survival is 49% at 18 months. Thirteen of the 19 patients who have completed treatment remain alive with a follow-up of lo-36 months.

This preliminary report shows that with an intensive chemo-radiotherapeutic regimen it is possible to achieve a CR in a very high proportion (93%) of patients with pelvic sarcomas even in the presence of overt metastatic disease. Furthermore, no local failures have been observed so far with this regimen, despite the large size (110 cm) of these tumors at presentation. Although late failures are possible, they are unlikely since most of the local failures occur within 12-18 months from treatment. Acute and late toxicity has been acceptable using this aggressive combined modality approach.

85

TOTAL LYMPHOID IRRADIATION, AN IMMUNOSUPPRESSANT IN GRAFT TOLERANCE: CONVENTIONAL VS. LOW-DOSE-RATE IRRADIATION

Julia E. Blum, Shari DeSilva, Daniel B. Drachman, Stanley E. Order

Departments of Radiation Oncology and Neurology, Johns Hopkins University School of Medicine, Baltimore, Md.

Total Lymphoid Irradiation (TLI) in conventional dose-rates has been successful in inducing immuno- suppression in Lewis rats. Conventional dose-rate TLI requires a prolonged course of therapy (> 3 weeks in rats); low-dose-rate TLI has the potential of reducing treatment time. The immunosuppressant activity of low-dose-rate TLI was compared with conventional dose-rate TLI in prolonging the survival of skin grafts taken from Brown-Norway rats.

Lewis rats were given TLI with Co60. One group was treated with conventional dose-rates (ranging from 80-180 rad/min) and received total doses of 3400 rad in 17 equally divided fractions on a 5 day/week schedule. A second group was treated with low-dose-rates (< 7 rad/min) and received total doses of 800, 1200, 1800, and 2400 rad in up to 4 consecutive days of treatment. Each method of treatment was tolerated well.

The mean survival of Brown-Norway skin grafts in untreated (control) rats was 15 days. Conventional TLI (17 fractions x 200 rad/day) prolonged skin graft survival to 60 days. Low-dose-rate TLI given as

Proceedings of the 28th Annual ASTRO Meeting 135

800 rad had only minimal effect in prolonging graft survival (18 days). Incremental increases in radia- tion dose resulted in increasing skin-graft survival with grafts intact for over 30 days in rats treated with 2400 rad.

Both conventional dose-rate TLI and low-dose-rate TLI significantly prolonged skin graft survival. A dose response curve appears to exist for low-dose-rate TLI and is being further characterized.

Total lymphoid irradiation using a low-dose-rate allows shortening of total treatment time and appears to be an effective means for induction of immunosuppression in laboratory animals. Translation of the above data into imnunosuppression protocols for clinical use would have the advantage of a reduction in facility needs and patient time.

86

PHASE I-II TRIALOFWIDEFIELDLCWFRACYIONAL DXE 'JXXALLYiWHOID IRRADIATION INACANINF,i%D~

A.G. Meek, F.T. Rappaport, S. btiura, F. Kimmzlstiel

Radiation oncOlcgy Service & Transplant Service, SUNY at Stony Brook, Stony Brook, NY 11794

Total Lphoid Irradiation (TLI) has proven to be a safe agent for the induction of immnological tolerance in small animals. Limited applications of TLI in larger animals andhmanshave providedmixed resultswithuncertainty as to the optiml treatment regimen. A study has been undertaken in a canine model to further elucidate treatment factors which my lead to greater success of TLI as part of a preparative regimen for allogeneic organ transplantation in this species.

Beagledogs ofknownDI.Agenotype andpsdigreeweretreatedwithwide field%1 (shieldingofportions of lungs and liver only) three times weekly, with daily fractional doses between 70 and 100 cgys to total doses betwem 1750 and 2100 cgys over 9 to 11 weeks. Following the TLI, the dogs were given a lo-12 day comse of rabbit anti-dog thymxyte globulin (4rqm/kg/day) (A%).

Four dogs who received DLA identical passenger cell (PC) free real allografts all appear to have develop&long tennunresponsiveness to their graft. Cmeof fourwho receivedDLAidenticalbut PC containing renal allcgrafts developed long term unresponsiveness.

l'hree dcgs not treated with TLI and A!IG who received DLA identical PC free renal allcgrafts rejected their grafts within 60 days. !lXrteendcx~s nottreatedwitb TLI and.ATGwho receivedDIAidentica1 FC containing renal allcgrafts all rejected their grafts within 38 days.

these results support the efficacy of low fractional dose wide field TLI as well as suggest a synergistic effect of !t'LI and elimination of allcgeneic FC.

Supported by NIB Grant AI-14453-08.

87

HISTOPATHOLOGIC RESPONSES TO UPPER HALF-BODY IRRADIATION

Hubert A. Eddy, Omar M. Salazar, Elizabeth K. Balcer-Kubiczek, William R. Redwood

Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Ma.ryland

The value of half-body irradiation (HBI) with single high doses (600 rad) for the palliation of multiple symptomatic bone metastases and in the control of cancer pain has been well established. As these unconventional radiation delivery systems (e.g., half-body irradiation, hypofractionation, hyperfractionation) begin to be used in earlier stage cancer and when they begin to be mixed among themselves or with conventional fractionation schedules, then the problem of exceeding normal tissue tolerance becomes the prime consideration. However, little is known about the biological response equivalencies of these unconventional dose delivery systems. Preliminary studies have been conducted in C H mice using upper hemibody irradiation (UHBI) to determine and compare lethality and pathologic

a resp rises to single doses, to conventional fractionated doses and to unconventional dose schedules (two fractions given one week apart, increasing doses; and increasing numbers of fractions given one week apart, fixed doses).

Mortality data were well fitted by the linear quadratic equation. The&/Pratio at both 24 and 48 weeks was approximately 8 to 9 Gy which is notably larger than the ratio of 2 to 6 Gy reported for late responding tissue after localized multifraction irradiation of single organs. After single doses of UHBI, the cause of death appears related 'co a combination of both lung alterations and bone