Curative Proton Therapy for Infants: At What Cost?

Abstract

Objectives

Infants (age 12 months and younger) are the most difficult population of cancer patients to treat. Historically, radiation would be excluded from treatment options and this view remains prevalent worldwide. New radiation technology may shift this perspective. The purpose of this study is to report the outcomes of infants undergoing treatment with curative-intent proton therapy.

Methods

Between 2006-2023, 15 infants with a median age of 11 months (range, 7-12 months) were irradiated at the University of Florida, constituting 0.75% of all pediatric patients treated with curative intent during this period. Eight patients were male and none had metastatic disease. The diagnoses included rhabdomyosarcoma (7), Ewing sarcoma (2), ATRT (1), ependymoma (1), and pineoblastoma (1). All patients were treated with standard radiation doses for their disease and the mean was 50.4 GyRBE (range, 41.1-54). 14/15 patients received disease-specific multi-agent chemotherapy. Cumulative incidence method was used to estimate overall survival (OS), cause-specific survival (CSS), progression-free survival (PFS), and local control (LC).

Results

With a median followup of 3.5 years (range, 01.-11.2 years), the 5 year OS, CSS, PFS, and LC was 58%, 65%, 58%, and 72%, respectively. Two and 5 patients had leptomeningeal and local recurrence, respectively. One patient died from a 1 metachronous rhabdoid tumor in lungs and kidneys. No patients were lost to follow-up. Four of 7 surviving patients experienced serious toxicity including blindness, deafness, vasculopathy and cataracts requiring surgery, global developmental delay, panhypopituitarism, hemorrhagic cystitis, and severe dentofacial and musculoskeletal problems.

Conclusion

When proton therapy is utilized as part of a multimodality treatment plan in infants with sarcoma and brain tumors, survival is possible but often comes at the cost of major toxicity. Improvements in patient selection may take us farther than improvements in technology.