185 - Low Rates of Marginal Failure in Pediatric Patients Treated with Pencil Beam Scanning Proton Therapy: Results from a Single Institution Phase IV Surveillance Trial
Presenter(s)
J. G. Roubil1, H. Worrall2, J. Becksfort2, T. T. Patni2, V. T. Groben2, E. Burghen2, H. T. Ruleman2, M. Marker2, N. D. Sabin2, S. Kaste2, G. T. Armstromg2, M. M. Hudson2, O. Ates2, C. H. Hua2, Y. Li2, C. L. Tinkle2, M. Krasin2, T. E. Merchant3, and J. T. Lucas Jr3; 1Massey Comprehensive Cancer Center, VCUHealth, Virginia Commonwealth University, Richmond, VA, 2St. Jude Children's Research Hospital, Memphis, TN, 3Department of Radiation Oncology, St. Jude Children’s Research Hospital, Memphis, TN
Purpose/Objective(s): Disease control concerns regarding the use of intensity modulated pencil beam scanning proton radiotherapy (PBS-PT) in children include the potential for marginal misses, and interplay effect (motion) related concerns. We sought to estimate the risk of marginal failures with PBS-PT in children in this single-institution Phase IV clinical trial.
Materials/Methods: SJPROTON1 screened 1,000 children from July 2017 to January 2022, of which 995 were eligible for enrollment and PBS-PT. Co-enrollment on a therapeutic study occurred in 56.4% of patients. The median follow-up was 4.1 years (IQR 2.8-5.7, range 0.2-8.72). 2,916 irradiated sites were treated. Sites prone to motion were assessed with 4DCT and/or 4DMRI. Dynamic targets were assessed with weekly MRI, while daily cone-beam CT was used for all cases. Failure was defined by the therapeutic protocol or disease-specific criteria. Local failures were assessed dosimetrically (central, in-field, marginal, and out-of-field). The cumulative incidence (CI) of events were calculated using the Aalen-Johansen estimator, and the Fine-Gray subdistribution hazard model was used to evaluate predictors of treatment failure.
Results: The distribution of treatment sites for 995 patients was CNS (n=711, 71.5%), head and neck (n=80, 8%), abdomen (n=65, 6.5%), pelvis (n=49, 5%), chest (n=46, 4.6%), and musculoskeletal (n=44, 4.4%). CNS disease categories included embryonal (n=267, 26.7%), ependymal (n=124, 12.4%), sellar (n=123, 12.3%). The remaining categories included skeletal muscle sarcoma (n=84, 8.4%), neuroblastic (n=52, 5.2%), bone sarcomas (n=13, 2.8%) other solid tumor and Hodgkin lymphoma (n=43, 4.3%), ALL (n=7, 0.6%), and AML (n=2, 0.2%). Repeat radiotherapy was utilized in 73 (7.6%) patients. Mixed PBS-PT/photon was used in 12.4%. 17.6% received concurrent chemotherapy. Conventional, SBRT, and accelerated fractionation schedules were used in 99.3, 0.44, 0.27% respectively. Residual disease was present in 53.7% (373/694), 57.9% (143/247), 57.7% (26/45), and 37.5% (3/8) of CNS, solid tumor, lymphoma and leukemia patients prior to PBS-PT. The 4 yr CI of distant and local failure was 21.1% (95% CI 18.6-23.9) and 13.8% (95% CI 11.7-16.2), respectively. The hazard for local/regional failure was increased in retreatment patients HR 2.8 (1.7-4.59, p<0.001) and cases of residual disease HR 6.37 (95%CI 1.48-27.3, p=0.013), but not in patients with motion prone sites. Concurrent chemotherapy did not modify the hazard for local failure. Local failures were central, in-field, marginal, and out-of-field in 58.7% (81/138), 18.1% (25/138), 12.3% (17/138), and 6.5% (9/138), respectively. 651 patients remain disease free.
Conclusion: Children treated with PBS-PT experience a low rate of marginal failure; however, specific subsets may be at increased risk.