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Limited-margin radiotherapy induces tumor control for pediatric sarcoma subtype
Limited-margin radiotherapy using conformal external-beam radiotherapy or brachytherapy provided a high rate of local tumor control without increased marginal failures among children and young adults with nonrhabdomyosarcoma soft tissue sarcoma, according to the results of a phase 2 study published in Cancer.
“Limited numbers of prospective clinical trials specific to pediatric nonrhabdomyosarcoma soft tissues sarcoma (NRSTS) have been conducted, and indications and techniques of adjuvant therapies have been derived largely from adult studies,” Christopher L. Tinkle, MD, PhD, assistant member of the radiation oncology department at St. Jude Children’s Research Hospital, and colleagues wrote. “However, concern regarding long-term treatment-related morbidity remains, particularly related to normal tissue radiation exposure.”
Soft tissue sarcomas are rare tumors that represented about 0.7% (n = 12,310) of all new cancers reported in the United States in 2016. However, soft tissue sarcomas comprise about 7% of all childhood cancers, and NRSTS represents about half of those pediatric cases, with more than 500 children and adolescents diagnosed annually.
Long-term treatment-related morbidity, especially related to normal tissue radiation exposure, remains a concern for these patients.
To limit normal tissue exposure while maintaining critical local tumor control among pediatric and young adult patients with NRSTS, researchers assigned 62 patients aged 3 years to 22 years with predominantly high-grade or locally recurrent NRSTS to an anatomically constrained margin of 1.5 cm to 2 cm of conformal external-beam radiotherapy and/or brachytherapy. Disease control, patterns of disease failure, predictors of local failure and survival, pathologic and imaging-based responses to neoadjuvant therapy, survival outcomes, and acute and late toxicity served as study outcome measures.
At a median follow-up of 5.1 years (range, 0.2-10.9 years), nine patients experienced local failure after a median time of 9.2 months. The 5-year overall cumulative incidence of local failure was 14.8% (95% CI, 7.2-25); all but one local failure occurred outside the highest-dose irradiation volume.
Multivariable analysis showed younger age was the only independent predictor of local recurrence (P = .004).
Five-year Kaplan-Meier estimates placed EFS at 49.3% (95% CI, 36.3-61.1) and OS at 67.9% (95% CI, 54.2-78.3). Patients who had metastatic disease at the time of diagnosis had significantly lower 5-year EFS (27.3% vs. 50%) and OS (9.1% vs. 80.9%; P < .0001 for both) rates than nonmetastatic patients.
Multivariable models showed metastasis predicted poorer EFS (HR = 1.78; 95% CI, 2.04-17.11) and OS (HR = 1.97; 95% CI, 2.12-24.13).
The 5-year cumulative incidence of grade 3 or grade 4 late toxicity was 15% (95% CI, 7.2-25.3). Researchers observed seven acute grade 3 or grade 4 radiation-related toxicity events among six patients, related largely to radiotherapy dermatitis and associated pain. All but one patient reported resolution within 3 months.
“It is noteworthy that [these results] appear to have been accomplished without an increased incidence of marginal failures, with all but one patient with a local recurrence within the highest-dosed irradiated volume,” Tinkle and colleagues wrote. “Although long-term, significant, treatment-related toxicity appears to be manageable at 15% at 5 years, it still represents a significant morbidity to bear in a population expected to continue to age and develop.” – by Chuck Gormley
Disclosures: The NCI, American Lebanese Syrian Associated Charities and Lance Armstrong Foundation funded this study. The authors report no relevant financial disclosures.