(P 187) PALLIATIVE LATTICE STEREOTACTIC BODY RADIOTHERAPY FOR PATIENTS WITH SARCOMA

Objective: Metastatic or unresectable disease is the cause of cancer-related morbidity and mortality for approximately 90% of cancer patients. Recent data demonstrates that stereotactic body radiation therapy (SBRT) offers improvements over conventionally fractionated radiotherapy for palliative treatment. SBRT, however, may be associated with increased toxicity and decreased control in larger tumors. Spatially fractionated radiation therapy (SFRT) may address these limitations of traditional SBRT. Unlike conventional radiotherapy, SFRT creates a heterogeneous dose field with high-dose “peaks,” organized throughout a target volume with intervening low-dose “valleys”. Lattice radiotherapy is a form of SFRT that uses a 3-dimensional beam arrangement to target high-dose spherical volumes within the global target. In this prospective trial (NCT04553471) the authors describe the effectiveness of lattice SBRT in local control of large, unresectable lesions with palliative intent.

Methods: Patients >18 years old, ECOG performance status ≤ 2, with histologically or cytologically confirmed sarcoma (including extremity), thoracic cancer, abdominal cancer, or pelvic cancer planning to undergo palliative radiotherapy to a lesion ≥ 4.5 cm were eligible for the Lattice radiation therapy. Exclusion criteria included prior overlapping high-dose radiation therapy, patients with tumors in need of urgent surgical intervention, and those receiving any cytotoxic cancer therapy regimens. Eligible patients underwent Lattice SBRT prescribed to a dose of 20 Gy in 5 fractions with a simultaneous integrated boost of 66.7 Gy in 5 fractions, delivered every other day. The co-primary endpoints of the study were rate of local control of the treated (i.e. target) lesions at 180 days as determined by RECIST v1.1 criteria, and proportion of patients with treatment related grade 3+ CTCAE v5.0 toxicity.

Results: Seventy-seven patients were enrolled in this phase II study. Overall median survival for all patients was 11.5 months, and 13.8 months for 35 sarcoma patients. Median overall progression free survival was 6.8 months for all patients and 8.5 months for sarcoma patients. As local control was greater than 50% for both groups, median time to local failure could not be calculated. In sarcoma patients, at 180 days 88% (16/18) of patients displayed local control of disease by RECIST scoring (66% (12/18) stable disease, 17% (3/18) partial response, and 5% (1/18) complete response. Similarly, for patients with other cancer types at 180 days, 90% (29/32) of patients experienced local control of the target lesions (65% (21/32) stable disease, 21% (7/32) partial response, 3% (1/32) complete response). The therapy was well tolerated with 5 grade 2 toxicities reported, 1 grade 3 toxicity, and 1 grade 5 toxicity (a case of tumor lysis syndrome) possibly, probably, or definitely attributable to Lattice SBRT.

Conclusion: This phase II study demonstrates that Lattice SBRT is a promising treatment option for palliative care in patients with large tumors (≥ 4.5 cm). The trial recorded an impressive local control rate of 90% at 180 days for all patients evaluated by RECIST criteria. Additionally noteworthy was Lattice SBRT’s efficacy in patients with sarcoma with a local control rate of 88% at 180 days. The treatment was generally well-tolerated with minimal severe toxicities reported, suggesting it is a viable treatment option for patients with large tumors. The association of one instance of an attributable grade 5 toxicity (tumor lysis syndrome) with Lattice RT warrants careful consideration and further investigation. Given these encouraging results however, Lattice SBRT in the palliative setting is a safe and effective treatment for patients with large, unresectable tumors.