16 Second malignancies after treatment for Ewing's Sarcoma

142

I. J. Radiation

Oncology@Biology@Physics

Volume

39, Number

2, Supplement,

1997

15 THE ROLE OR RADIATION THERAPY (RT) IN THE MANAGEMENT OF LOCALIZED SOFT TISSUE SARCOMAS (STS) IN CHILDREN A REPORT OF THE INTERNATIONAL SOCIETY OF PEDIATRIC ONCOLOGY (SIOP) J.L. HABRAND, D. SPOONER, A RN, A BARRETT, M. STEVENS, 0. OBERLIN On behalf of the SIOP committee for Malignant Mesenchymal Tumors PURPOSE : Since 1984, SIOP has conducted 2 successive studies in which the mainstay of treatmsnt has been represented by polychemotherapy and local treatment, especially RT, confined to *high risks’ groups of children. This strategy has been condkioned by the high chemo sensttivfty of most STS in this age group, along with their propensity for rapid disseminatfon and the substantial risk of deleterious side effects induced by high dose RT. This is a report on the role of RT in the second MMT 89 study. MATERlALS AND KWODS: From January 1989 through November 1995,308/813 children (38 %) received RT as part of their treabnent RT was administered I/ systematically following 3 courses of the IVA regimen (Ifosfamide, Vincristin, Actinomycin D) in parameningeal sites (126 patients) and 2/ at completion of chemotherapy (generally 6 IVA) in other children if residual disease was still present (182 patients). Total median dose was 45 Gy + boost administered &Jter with a conventional regimen (ClD = 5 daily sessions of 1.8 to 2 Gy 77 % cases) or, opgonnaily, with an hyperfractionated accelerated one (BID = 10 daily sessions oft.5 Gy = 15 % cases). The BID fractionatfon Was expected to improve local control without increasing long term toxicity, LDR brachytherapy (BT) was also used in selected sites (8 % cases). Clinical and technical informations were centrally collected. q

RESULTS : Sites irradiated concerned the parameningeal (PM) area (51 %), extremities (12 %) orbit (10 %), Head and Neck non PM (7 %), GU (6 %). others (13 %). 75 % sarcomas were of the Rhabdomyosarcoma (RMS) histological type (embryonal mainly). Median dose for QD was 46 Gy and BID 45 Gy, protractfon 37 and 25 days respectively. A severe immediate toxicity was significantly correlated with the BID regimen (cutaneous 36 %, mucosal50 %), compared with QD (15 and 13 %) (p 0.001). Despite a median 12 day-gain in the BID regimen, and after adjustment for site, no advantage was recorded at 4 years for this regimen in terms of survival (QD = 67 36, BID 55 % pNS) or EFS (QD = 57 %, BID = 48 % pNS). Local regiond failures represented 14 % (421398) patients either local (28). nodal (lo) or both (4)Signiticant risk factors for local failure were the inadequate coverage of the primary in PM sites (p 0.01) and for nodal failure the alveolar subtype of RMS (p 0.03). According to the site, exbemkies failed in 25 % cases, Head-Neck non PM in 21 %, PM in 15 %, orbit in 8 %, GU in 7 % and ‘others’ in 11 % (pNS). According to the histology, alveolar RMS faged in 19 %, embryonal RMS in 15 % and non RMS in 14 % @NS). Afthough it didn’t reach stat&ical significance, a dose effect relationship was suspected at the 50 Gy level (LRF = < 50 Gy = 15 %, > 50 Gy = 9 %).

CONCLUSlON: Although directed to unfavorable cases, RT in the SIOP MMT 89 protocol, has pmvided an excellent survival. HART failed to improve the outcome at the price of an increased acute toxicity but concerned a small subset of patienk only. In our approach PM sites outcome has dramatically improved for the past decade mainly due to the administration of early irradiation to a carefully designed target vofurne (inlal primary + base of the skull). Future evaluations should explore sites at higher risks like extremities, and alveolar subtypes, also a possible dose-effect relationship and new strategies for quality control.

16 SECOND MALIGNANCIES

AFTER TREATMENT

Susanne Ahrens, Jiirgen Dust, Christian Dept. of Radiotherapy, Martin-Luther-University C+=Y

Riibe,

FOR EWING’S

SARCOMA

Michael Paulussen, Christine Hoffmann, Herbert Halle-Wittenberg and Dept. of Pediatric Hematology

Jiirgens and Oncology,

University

of Miinster,

Background: Some former retrospective studies have suggested that patients with Ewing’s sarcoma might have a very high risk for developing secondary sarcomas if treated with radiotherapy. We have evaluated the risk of second malignancies (SM) in patients treated in tbe German Cooperative Ewing’s Sarcoma Studies CESS 81 and CESS 86. Materials & methods: From Janua~~ 198lthmugh June 1991, a totalnumber of 674 patients was registered in the two multicentric Ewing’s sarcoma trials CESS 81 (1981 through 1985) and CESS 86 (1986 through June 1991). The systemic treatment consisted in both studies of a four-drugchemotherapy (VACA= v&xi&e, actinomycin D, cyclophosphamide and adriamycin; or VAIA= vim&tine, actinomycin D, ifosfamide and adriamycin) and a total number of four courses, each lasting tie weeks, was recommended by tbe protocol. Local therapy was either complete surgery or surgery plus postoperative radiotherapy with 36-46Gy or definitive radiotherapy with 46 to 60Gy. The median follow-up at the time of this analysis was 7 years, the maximum follow-up 16 years. Results: Eight patients developed a SM, 4 were acute myelogenic leucemias, three sarcomas and one benign ncminoma. One of the sarcomas was considered as radiation-induced because of its location in the former radiation field. The intervalI between diagnosis of Ewing’s sarcoma and the diagnosis of the SM was 17 to 78 months for the four ,&KS and 82 to 136 months for the three sarcomas. All solid second tumors occurred in irradiated patients. The cumulative risk of a SM is given ia table 1. Three patients (aU with Ah4L) died oftheir SM, the other 6ve were s&age by subsequent treatment and are in cl&al remission with a median follow-up of 1 to 10 years. Conclusions: The risk of leucemia atier treatment for Ewing’s sarcoma is probably low in the range of l-2% or less and accounts for about 1% of alI deaths. There was no risk of solid tumors in surgically treated patients. Irradiated patients seem to be at low risk for solid tumors within the first ten years after treatment but have a 5%-risk of developing any solid tumor after 15 years. However, there have been no deaths due to secondary aarcmnas up to now. Cumulative Type of local treatment

All patrents Surgery Surgery + postop Definitive

XRT

XRT

risk of any SM

after 10 years

after 15 years

28%

4.6%

Cumulative

risk of leucemias

after 10 yeras 1%

Cumulative

risk of any secondary

solid tumors

after 10 years

after 15 yeras

1 8%

36%

09%

0.9%

09%

0%

0%

1.4%

6.1%

0.4%

1 0%

5.7%

6.7%

6.7%

1.9%

48%

4.8%