(P 321) WHOLE ABDOMINAL RADIOTHERAPY IN CHILDREN AND YOUNG ADULTS WITH SARCOMA: A CANADIAN SARCOMA AND CLINICAL COLLABORATION (CANSARCC) STUDY

Objective: Whole abdominal radiotherapy (WART) may be indicated in sarcoma patients with peritoneal implants, malignant ascites or pre- or peri-operative rupture of abdominal tumours. Previous literature is limited and primarily focuses on desmoplastic small round cell tumours (DSRCT). We undertook a multi-centre, retrospective study to describe indications, toxicity and survival outcomes among children and young adults who received WART for sarcoma.

Methods: Following ethics board approvals, we identified patients at 7 institutions from the CanSaRCC database who were age  39 years at diagnosis and received WART for any type of sarcoma between January 1, 2000 to May 1, 2023. Patient and tumour characteristics, treatment and outcome data were collected. Toxicity was graded per the Common Terminology Criteria for Adverse Events (CTCAE) version 5 and categorized as acute (onset < 3 months after WART) or chronic (onset  3 months after WART). Progression-free (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and calculated from start date of WART to first progression / relapse after WART, death from any cause or to date of last follow-up, as applicable.

Results: Twenty patients, median age at diagnosis of 14y (range 0-35y), with DSRCT (n=7), rhabdomyosarcoma (RMS) (n=6), Ewing sarcoma, rhabdoid tumour, endometrial stromal tumour (each n=1) and sarcoma not otherwise specified (NOS) (n=4) were included. Of 17 patients who received WART as part of initial therapy, 10 (58.8%) had abdominal metastases, 6 (35.3%) had malignant ascites/pre-operative rupture and 1 (5.8%) had localized abdominal DSRCT. An additional 3 patients received WART at relapse. For all patients, median WART prescription dose was 22.5 Gy (range 10.5-30) with median 1.5 Gy/fraction (range 1.0 – 2.0). With mean kidney and liver doses of 14.9 and 21.0 Gy (medians), 3 patients had grade 3 acute toxicity; diarrhea (n=2) or elevated creatinine (n=1). None developed chronic kidney disease, hepatitis or other GI toxicity. Four patients, all with DSRCT, also received hyperthermic intraperitoneal chemotherapy (HIPEC). One of these patients had a subsequent relapse (outside WART field); all remain alive at last follow-up and 2 have no evidence of disease. Two RMS patients, neither who received HIPEC, developed second malignant neoplasms (SMN) at 15 months (acute lymphoblastic leukemia) and 133 months (high-grade bladder cancer) after diagnosis (both had prior chemotherapy, neither had undergone germline cancer predisposition testing).

Among 17 patients who received WART in frontline therapy, two year PFS and OS were 66.7% (95% CI 46.6 – 95.3%) and 79.2% (95% CI 61.2 - 100%), respectively. Among patients with RMS or DSRCT and WART in upfront therapy, two year OS was 100% and 62.5% (95% CI 32 – 100%), respectively, and PFS was 80% (95% CI 51.6 – 100%) and 50% (95% CI 22.5 – 100%). Three (17.6%) had recurrence within the RT field (n=2 DSRCT and 1 sarcoma NOS). Five-year cumulative incidence of abdominal recurrence was 33.3% (95% CI 11.4 – 57.3%). Among 3 patients who received WART following initial relapse, all developed subsequent recurrence (n=2 within WART field).

Conclusion: WART is well tolerated among young sarcoma patients with intra-abdominal disease and provided meaningful local disease control in the majority of patients who received it as part of front-line therapy. The role of HIPEC in the management of DSRCT needs further investigation. SMN should be considered as a possible late toxicity of sarcoma therapy that includes WART.

Figure 1. Overall and Progression Free Survival for Sarcoma patients receiving WART as part of initial multi-modal therapy (n=17)