Randomized Evaluation of Machine Learning Assisted Radiation Treatment Planning vs Standard Radiation Treatment Planning

A Randomized Evaluation of Machine Learning Assisted Radiation Treatment Planning Versus Standard Radiation Treatment Planning

The purpose of this study is to determine the magnitude of clinical benefit achieved through machine learning assisted radiation treatment planning (MLAP) on post-treatment clinical outcomes such as acute toxicity and patient reported outcomes.

Study Overview

• Status: Completed
• Conditions: Cancer Head Neck; Cancer Neck; Cancer, Head
• Intervention / Treatment: Radiation: Radiation Therapy Standard of Care (SOC); Radiation: Machine Learning Assisted Radiation (MLAP) RapidPlan

Detailed Description

This is a randomized phase III trial to evaluate the effectiveness of MLAP compared to Standard of Care. Patients will undergo a randomization procedure with a variable allocation ratio where the first third of patients are randomized 3:1 in favor of SOC, the next third randomized 1:1, and the last third randomized 1:3 in favor of MLAP. This is done to give dosimetrists time to optimize the MLAP workflow. Since the treatment team may learn to improve their treatment planning process in the SOC arm through interactions with RapidPlan, as a sensitivity analysis, the primary and secondary goals will be re-analyzed including time of registration as a moderator of the treatment effect.

• Study Type: Interventional
• Enrollment (Actual): 204
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic in Florida
  • Minnesota
    • Albert Lea, Minnesota, United States, 56007
      • Mayo Clinic Health System in Albert Lea
    • Mankato, Minnesota, United States, 56001
      • Mayo Clinic Health Systems-Mankato
  • Wisconsin
    • Eau Claire, Wisconsin, United States, 54701
      • Mayo Clinic Health System-Eau Claire Clinic
    • La Crosse, Wisconsin, United States, 54601
      • Mayo Clinic Health System-Franciscan Healthcare

Participation Criteria

Eligibility Criteria

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

Study Population

The study is open to all eligible patients, regardless of race or ethnic origin.

Description

Inclusion Criteria:

• Age ≥ 18 years at time of registration
• Receiving curative intent intensity modulated radiotherapy for head and neck primary cancer at the discretion of the treating medical doctor (MD)
• Provide written informed consent or allow legally authorized representative to consent on behalf of a participant
• Willing to return to enrolling institution for study follow-up visit

Exclusion Criteria:

• Incarcerated
• Unable to provide informed consent
• Prior Head and Neck (H&N) radiation therapy
• Planned radiation dosing LK<30 Gy or >76 Gy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Arm A: Standard of care (SOC) treatment planning; Patients randomized to the SOC treatment planning arm will receive a treatment planning computed tomography (CT) scan followed by dosimetric planning with a medical dosimetrist; and the plan will be reviewed by a medical physicist and radiation oncologist. This is the current standard practice for all radiation oncology patients.	Radiation: Radiation Therapy Standard of Care (SOC); Radiation therapy simulation, target delineation, dosing, localization, and follow-up will be followed per standard of care practices and/or at the discretion of the treating radiation oncologist. To elaborate, patients will receive a treatment planning CT (computed tomography) scan, followed by normal tissue delineation through the physician and/or medical dosimetry assistant, followed by target delineation by the physician, followed by radiation treatment planning with the dosimetrist and medical physicist, followed by plan change requests and approval by the physician.
Active Comparator: Arm B: Machine Learning Assisted Planning (MLAP); Patients randomized to the MLAP arm will receive a treatment planning scan followed by MLAP through the RapidPlan module produced by Varian. Of note, RapidPlan is an FDA cleared module with treatment planning being the approved usage for the program. The RapidPlan module has site specific treatment packages for different disease sites. These separate disease specific packages have different capabilities. For example, the Head and Neck package currently audits dosimetrist-generated plans for possible improvements. The MLAP arm of the trial will leverage the RapidPlan module's full capabilities upwards to the FDA-approved usage.	Radiation: Machine Learning Assisted Radiation (MLAP) RapidPlan; Radiation therapy simulation, target delineation, dosing, localization, and follow-up will be followed per standard of care practices and/or at the discretion of the treating radiation oncologist. To elaborate, patients will receive a treatment planning CT (computed tomography) scan, followed by normal tissue delineation through the physician and/or medical dosimetry assistant, followed by target delineation by the physician, followed by radiation treatment planning with the dosimetrist and medical physicist. The preliminary plan will be run through the RapidPlan module, which will give a list of possible improvements to the plan. The dosimetrist will then make an amendment to the plan according to RapidPlan suggestions, followed by plan change requests and approval by the physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in swallowing score	Will be assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck module (EORTC QLQ-H&N35). The EORTC QLQ-H&N35 is a 35-item questionnaire used to assess symptoms encountered specifically by patients with head and neck cancer. The H&N35 consists of 7 multiple-item scales (Pain, Swallowing, Senses, Speech, Social eating, Social contact, and Sexuality), in addition to 11 single items (e.g., Opening mouth, Sticky saliva, Dry mouth, etc.). Scores are combined into an overall score ranging from 0=Best to 100=Worst. Swallowing score will be measured at baseline (up to 30 days prior to treatment planning), at the end of Radiation Treatment (+ 14 days), and 3 months post Radiation Treatment (+/-30 days from 3 months post-radiotherapy).	Baseline (up to 30 days prior to treatment planning); up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in physician-reported toxicities	Assessed according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Toxicities will be recorded at baseline (up to 30 days prior to treatment planning), at the end of Radiation Treatment (+14 days), and 3 months post Radiation Treatment (+/-30 days from 3 months post-radiotherapy).	Baseline; up to 6 months
Difference in treatment plan quality metrics (PQMs) across treatment arms	Treatment PQM is a continuous-valued function depending on selected dose-volume histogram statistics for 5 organs-at-risk. Comparisons between treatment arms will be made.	Baseline; up to 6 months
Difference in time to complete treatment planning	Treatment planning time is defined as the time in minutes from the end of physician contouring to the end of physician plan approval.	Baseline; up to 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in quality of life scores	Quality of life scores will be compared between arms, as measured by the 6 remaining subscales and 11 single item scores of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck module (EORTC QLQ-H&N35). EORTC scores will be recorded at baseline (up to 30 days prior to treatment planning), at the end of Radiation Treatment (+14 days), and 3 months post Radiation Treatment (+/-30 days from 3 months post-radiotherapy).	Baseline; up to 6 months
Change in dose-volume histograms (DVHs)	DVH statistics will be compared between treatment arms within cohorts of planned radiation dose (30-54 Gy vs. 54-66 Gy vs. 66-76 Gy) and laterality (bilateral vs. unilateral).	Baseline; up to 6 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Daniel J. Ma, M.D., Mayo Clinic in Rochester

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2023
• Primary Completion (Actual): October 29, 2025
• Study Completion (Actual): October 29, 2025

Study Registration Dates

• First Submitted: July 31, 2023
• First Submitted That Met QC Criteria: July 31, 2023
• First Posted (Actual): August 7, 2023

Study Record Updates

• Last Update Posted (Actual): January 26, 2026
• Last Update Submitted That Met QC Criteria: January 22, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: MLAP (Machine Learning Adaptive Planning); RapidPlan
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Head and Neck Neoplasms
• Other Study ID Numbers: GMROR2371; 23-004732 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No