Integration of Adaptive Proton Therapy in Pediatric Solid Tumors and Hodgkin's Lymphoma

Pediatric patients receiving proton therapy for solid tumors or Hodgkin's lymphoma may experience anatomical changes during treatment that can affect proton therapy accuracy. This prospective single-arm study uses regular low-dose imaging to monitor these changes and adjust treatment plans as needed. Participants will receive weekly or every-other-week CT scans, with MRI when appropriate, to assess whether the original plan remains accurate. Treatment plans will be updated if tumor coverage decreases by more than 5% or if radiation dose to normal tissues increases by more than 10%; otherwise, the original plan will continue. The study aims to determine how often plan adjustments are needed and to identify which disease sites are most likely to experience significant anatomical changes during treatment.

Primary Objective:

• Define the frequency of replanning necessary to ensure tumor coverage never falls below 95% (or 5% drop) of the prescribed daily dose in participants with intact (gross) tumors to keep the tumor control optimal throughout the multi-week treatment regimen.
• Define the frequency of replanning necessary to ensure organs-at-risk (critical organs) do not deviate by more than 10% of the initially approved dose constraints to keep the normal tissue complication minimal throughout the multi-week treatment regimen.

Secondary Objectives

• Establish a cone beam CT (CBCT)-based framework for quantifying body surface changes throughout the treatment course. This goal will be achieved by developing a novel algorithm that detects and tracks external anatomical variations longitudinally, without requiring CBCT image enhancement, enabling precise assessment of daily participant setup consistency and anatomical stability.
• Overcome daily CBCT quality limitations by generating synthetic CT images that accurately represent daily anatomy and support proton dose recalculation or verification planning. This goal will be achieved by developing a hybrid pipeline that integrates deep learning models with the deformable image registration algorithm, trained and validated on disease site-specific data. This will enable precise dose mapping and tissue density estimation, directly supporting adaptive planning decisions without the need of diagnostic- quality CT images.

Study Overview

• Status: Not yet recruiting
• Conditions: Soft Tissue Sarcoma; Hodgkin Lymphoma; Osteosarcoma; Ewing Sarcoma; Rhabdomyosarcoma; Bone Tumor; Pediatric Solid Tumors
• Intervention / Treatment: Radiation: Proton Therapy (Adaptive)

Detailed Description

Proton therapy is a type of radiation treatment that can target tumors very precisely while protecting healthy organs. This is especially important for children. However, during the several weeks of treatment, a child's body and tumor can change. These changes may cause the radiation dose to miss part of the tumor or give too much dose to nearby organs.

In usual care, proton therapy plans are based on one CT scan taken before treatment starts. New scans are only done if the care team thinks a change has occurred. There is no standard process to regularly check whether the treatment plan is still accurate during therapy.

This study tests a structured approach to monitoring and adjusting proton therapy plans during treatment in children with solid tumors or Hodgkin's lymphoma.

About 100 pediatric patients receiving proton therapy at St. Jude Children's Research Hospital will take part. All patients will receive their prescribed proton therapy as usual. The study does not change the radiation dose or schedule.

Participants will receive additional CT scans, and MRI when needed, during treatment. Imaging will be done weekly or every other week to check whether the original treatment plan still provides good tumor coverage and protects healthy organs.

The treatment plan will be updated if:

• Tumor coverage drops by more than 5%, or
• Radiation dose to normal organs increases by 10% or more.

If these changes are not seen, the original plan will continue. The extra imaging uses a low radiation dose.

The goal of this study is to learn how often proton therapy plans need to be adjusted to keep treatment accurate and safe. Results may help improve proton therapy care for children in the future.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ozgur Ates, PhD; Phone Number: 888-226-4343; Email: referralinfo@stjude.org

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
      • Contact: Ozgur Ates, PhD; Phone Number: 888-226-4343; Email: referralinfo@stjude.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants diagnosed with solid tumors, including Rhabdomyosarcoma, Osteosarcoma, Ewing sarcoma, other sarcomas and carcinomas or also Hodgkin's lymphoma.
• Participants who receive proton radiation therapy at St. Jude Children's Research Hospital.
• Research participant or legal guardian/representative gives written informed consent.

Exclusion Criteria:

• Participants who are not diagnosed with solid tumors or Hodgkin's lymphoma.
• Participants who are diagnosed with Wilm's tumor or neuroblastoma
• Participants who do not undergo proton therapy.
• Participants who are prescribed equal or less than 5 fractions of proton therapy.
• Participants with severe comorbid conditions that may impact imaging feasibility.
• Inability to obtain written consent from research participant or legal guardian/representative.
• Females of child-bearing potential cannot be pregnant or breast-feeding. Female participants >10 years of age or post-menarchal must have a negative serum or urine pregnancy test

All participants receiving proton therapy at St. Jude Children's Research Hospital will be screened for participation on this research protocol based on the Inclusion Criteria and the Exclusion Criteria. Qualified candidates will be selected during the consultation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Adaptive Proton Therapy With Systematic On Therapy Imaging; All enrolled participants receive standard of care proton therapy combined with systematic on therapy imaging (CT and/or MRI) during treatment. Imaging is used to generate verification plans to assess dose delivery relative to the original plan. Adaptive replanning is implemented if predefined dosimetric thresholds are exceeded.

Radiation: Proton Therapy (Adaptive); Proton beam radiation therapy delivered per standard disease or site specific protocols, with additional on therapy CT and/or MRI imaging performed weekly or bi weekly during treatment. Verification planning is conducted using updated imaging, and treatment plans are adaptively replanned when tumor coverage decreases by ≥5% or organ at risk dose increases by ≥10% compared with the originally approved plan. Total dose, fractionation, and treatment schedule follow standard of care and are determined by the treating physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Replanning Treatment	Descriptive statistics for number of cases replanned during treatment course will be reported	Captured during on-therapy imaging (occurring either weekly or bi-weekly) for the duration of the patient's treatment course (varies depending on individual cases, anywhere from roughly 6 weeks to 10 weeks)
Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP)	Descriptive statistics for V95% (tumor coverage) and OAR (organs-at-risk) will be reported, as well as signed-rank tests to evaluate adaptive planning effectiveness	Captured during on-therapy imaging (occurring either weekly or bi-weekly) for the duration of the patient's treatment course (varies depending on individual cases, anywhere from roughly 6 weeks to 10 weeks)
Correlation between tissue discrepancies and changes in proton range, and deviations from intended plan quality	Spearman correlation will be reported, assessing the associations between factors	Captured during on-therapy imaging (occurring either weekly or bi-weekly) for the duration of the patient's treatment course (varies depending on individual cases, anywhere from roughly 6 weeks to 10 weeks)

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Investigators: Principal Investigator: Ozgur Ates, PhD, St. Jude Children's Research Hospital

Publications and helpful links

Helpful Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2031

Study Registration Dates

• First Submitted: March 31, 2026
• First Submitted That Met QC Criteria: March 31, 2026
• First Posted (Actual): April 7, 2026

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Neoplasms by Site; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Myosarcoma; Hemic and Lymphatic Diseases; Sarcoma, Ewing; Sarcoma; Hodgkin Disease; Rhabdomyosarcoma; Osteosarcoma; Bone Neoplasms; Therapeutics; Radiotherapy; Heavy Ion Radiotherapy; Proton Therapy
• Other Study ID Numbers: SJPROTON3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No