Proton Beam Radiotherapy for Medulloblastoma and Pineoblastoma

Proton Beam Radiotherapy for Medulloblastoma and Pineoblastoma: An Assessment of Acute Toxicity and Long Term Neurocognitive, Neuroendocrine and Ototoxicity Outcomes

There are two types of external radiation treatments (proton beam and photon beam). As part of the participant's treatment, they will receive radiation to the entire central nervous system (CNS); this is known as craniospinal irradiation (CSI). In the past, photon radiation therapy has been used for CSI. In this study we will be examining the effects of proton beam radiation therapy. Studies have suggested that this kind of radiation can cause less damage to normal tissue than photon radiation therapy. The physical characteristics of proton beam radiation let the doctor safely deliver the amount of radiation delivered to the tumor that is normally delivered through standard therapy but spare more normal tissue in the process.

Study Overview

• Status: Completed
• Conditions: Brain Tumor; Medulloblastoma; Pineoblastoma
• Intervention / Treatment: Radiation: proton beam radiation

Detailed Description

• Before beginning radiation therapy, participants will have scans done in order to prepare for the radiation treatment. Doctors will use information gathered from these scans to plan the best way to deliver radiation to the tumor.
• The following procedures will be performed either before or during the radiotherapy: Hearing exam; neurocognitive exam; blood tests and cerebral spinal fluid test.
• Not everyone who participates in this study will receive the same amount of proton radiation therapy. The length of time and amount of radiation received will depend upon the condition of the participant's disease. Radiation treatment will be given once a day, 5 days a week (Monday-Friday). The overall treatment course will be approximately 6 weeks.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Massachusetts General Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must have undergone biopsy or attempted surgical resection and must have histologically confirmed medulloblastoma or pineoblastoma.
• Participants may have had a gross total resection, sub-total resection or biopsy only.
• For patients with no prior chemotherapy, treatment must start within 35 days of definitive surgery or as indicated if enrolled on therapeutic study
• Age range between 3 and 25 at the time of enrollment
• Life expectancy of greater than 3 months
• Blood laboratory values as outlined in the protocol
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation

Exclusion Criteria:

• Patients with more than one previous chemotherapy regimen
• Patients with recurrent or progressive disease after one or more regimens of pre-radiation chemotherapy
• Patients with prior radiation therapy
• Any major uncontrolled or poorly controlled intercurrent illness that would limit compliance with study requirements
• Pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: Proton Beam Radiation	Radiation: proton beam radiation; Given once a day, 5 days a week (Monday-Friday)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endocrine Dysfunction	Cumulative incidence (estimated percentage participants) that developed endocrine dysfunction at 3- and 5-years following completion of proton radiation therapy.	3- and 5- years post radiation treatment
Cumulative Incidence of Ototoxicity	Cumulative incidence (estimated percentage participants) who experienced ototoxicity defined as either grade 3 or 4 hearing loss in either ear after the completion of radiation therapy in the overall participant population. Cumulative incidence and 95% confidence intervals are shown at 3- and 5-years post RT (radiation treatment)	3- and 5- years post radiation treatment
Neurocognitive Effects	Difference in Full-Scale Intelligence Quotient (FSIQ) between baseline and latest follow-up neurocognitive test. Tests used include WISC (Wechsler Intelligence Scale for Children) IV, WISC V, WAIS (Wechsler Adult Intelligence Scale) III, WAIS IV. The test measures the FSIQ of children through four indices; the Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), working memory test, and a processing speed test. FSIQ and the four indices are all assessed on a bell curve scale with an average score of 100 and standard deviation of 15. Higher scores represent higher intelligence and lower scores represent reduced intelligence.	Baseline and Follow-up (median of 6 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	3- and 5-year progression free survival rate of pediatric medulloblastoma and pineoblastoma patients treated with proton CSI treatment.	3- and 5-years post radiation treatment
Treatment Efficiency	To modify the speed of treating patients requiring cranial spinal irradiation (CSI) and improve the safety of treating patients under anesthesia	2 years
Percentage of Participants Who Experienced an Acute Toxicity by Grade	All patients shall be assessed for acute toxicity on a weekly basis during craniospinal irradiation (CSI). Percentage of participants who experienced an acute toxicity by grade. Acute toxicities are graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Toxicities are graded on a scale of 1 to 5. A higher grade indicates a worse outcome with 1 being mild, 4 being life-threatening, and 5 being death.	3 months after radiation therapy

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
• Investigators: Principal Investigator: Torunn I Yock, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Vatner RE, Niemierko A, Misra M, Weyman EA, Goebel CP, Ebb DH, Jones RM, Huang MS, Mahajan A, Grosshans DR, Paulino AC, Stanley T, MacDonald SM, Tarbell NJ, Yock TI. Endocrine Deficiency As a Function of Radiation Dose to the Hypothalamus and Pituitary in Pediatric and Young Adult Patients With Brain Tumors. J Clin Oncol. 2018 Oct 1;36(28):2854-2862. doi: 10.1200/JCO.2018.78.1492. Epub 2018 Aug 17.

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2010
• Primary Completion (Actual): November 1, 2021
• Study Completion (Actual): November 1, 2021

Study Registration Dates

• First Submitted: February 3, 2010
• First Submitted That Met QC Criteria: February 3, 2010
• First Posted (Estimated): February 5, 2010

Study Record Updates

• Last Update Posted (Actual): August 13, 2025
• Last Update Submitted That Met QC Criteria: August 11, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: proton beam radiation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Neuroectodermal Tumors, Primitive; Central Nervous System Neoplasms; Brain Neoplasms; Medulloblastoma; Pinealoma
• Other Study ID Numbers: 09-361; P01CA021239 (U.S. NIH Grant/Contract)