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Adjuvant chemotherapy with accelerated radiotherapy effective for high-risk soft tissue sarcoma
WAILEA, Hawaii — Characteristics including tumor size, invasion, necrosis and infiltrative growth helped identify patients with soft tissue sarcoma at high risk for metastasis who benefited from adjuvant chemotherapy plus accelerated radiotherapy, according to prospective, nonrandomized study results presented at the Connective Tissue Oncology Society Annual Meeting.
“Adjuvant chemotherapy is not standard treatment in adult-type soft tissue sarcoma,” Kirsten S. Hall, MD, PhD, of the department of oncology at Norwegian Radium Hospital and Oslo University Hospital in Oslo, Norway, said during her presentation. “There also is no clear consensus on prognostic factors identifying high-risk soft tissue sarcoma.”
To determine whether subpopulations of patients benefit more than others from adjuvant chemotherapy, Hall and colleagues examined the feasibility and efficacy of adjuvant chemotherapy interposed with radiotherapy in patients with specific morphological characteristics previously shown to be associated with high risk for metastasis.
Researchers defined high-risk soft tissue sarcoma as having high-grade morphology and either vascular invasion or at least two of the following: tumor size larger than 8 cm, necrosis and infiltrative growth.
The analysis included 150 patients (median age, 59 years; range, 18-75) who received six cycles of 60 mg/m2 doxorubicin and 6 mg/m2 ifosfamide. Researchers interposed hyperfractionated radiotherapy (36 Gy; 1.8 Gy twice daily) between the third and fourth cycle, with a boost of 9 Gy in the case of intralesional margins.
Patients with subcutaneous tumors excised with a wide margin or radical amputation only received chemotherapy.
Patients included had undifferentiated pleomorphic sarcoma (35%), myxofibrosarcoma (26%), leiomyosarcoma (13%), liposarcoma (12%), synovial sarcoma (8%) and malignant peripheral nerve sheath tumor (6%). Median tumor size was 9 cm (range, 6.6-12).
Median follow-up was 4.4 years (range, 0.2-8.7).
Overall, 70.4% (95% CI, 63.1-78.4) achieved 4-year metastasis-free survival and 76.1% (95% CI, 68.8-84.2) achieved 4-year OS.
Among the 19 patients who only received chemotherapy, rate of 4-year metastasis-free survival reached 72.2% (95% CI, 54.2-96.2) and 4-year OS reached 83.3% (95% CI, 67.8-100).
Among the 119 patients who underwent interposed radiotherapy, researchers reported a 67.2% (95% CI, 58.9-76.5) rate of 4-year metastasis-free survival and 72.9% (95% CI, 64.4-82.5) rate of 4-year OS.
Rates of 4-year metastasis-free survival and OS were each 100% (95% CI, 74.5-100) among the 12 patients who received the radiotherapy boost.
Almost all (91%) of patients received all six chemotherapy cycles. Sixty-five percent of patients experienced grade 3 to grade 4 toxicity, the most common of which included neutropenia without fever (82%), thrombocytopenia (32%) and neutropenia with fever (25%).
Researchers noted that tumor size larger than 10 cm (P = .042), deep-seated tumors (P = .033) and chemotherapy dose intensity less than 70% (P = .018) predicted poorer survival on multivariable analyses.
Hall noted “SING” — or size, invasion, necrosis and growth — can help select patients with high risk for metastatic disease who benefit from this treatment regimen. – by Alexandra Todak
Reference:
Hall KS, et al. Abstract 018. Presented at: CTOS Annual Meeting; Nov. 8-11, 2017; Maui, Hawaii.
Disclosures: The authors report no relevant financial disclosures.