DMH-Based Plan Evaluation and Inverse Optimization in Radiotherapy

• Sponsor: University of Miami (Other)
• Overall Status: Completed
• CT.gov ID: NCT02663817
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 52
• Location: 1
• Arm: 1
• Actual Duration (Months): 45.5
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

The hypotheses of the study are as follows:

• Mass-based inverse optimization in radiotherapy treatment planning will result in a reduction of normal tissue and organs at risk (OAR) doses for desired prescription therapeutic doses to the targets.

• Dose-mass histograms (DMHs) may be more relevant to radiotherapy treatment planning and treatment plan assessment than the standard of care, realized through dose-volume histograms (DVHs)

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer; Lung Cancer; Prostate Cancer	Device: CT Scan	N/A

Detailed Description

Cancer patients continue to represent a challenging disease population, which faces rather poor prognosis with current treatment planning and delivery practices. Venues for a potential dose escalation and/or increased healthy tissue sparing, through innovative therapeutic approaches for those patients, are clearly needed. Current state of the art radiotherapy treatment planning relies on the dose-volume-histogram (DVH) paradigm, where doses to fractional (most often) or absolute volumes of anatomical structures are employed in both optimization and plan evaluation process. It has been argued however, that the effects of delivered dose seem to be more closely related to healthy tissue toxicity (and thereby to clinical outcomes) when dose-mass-histograms (DMHs) are considered in treatment plan evaluation.

The investigators propose the incorporation of mass and density information explicitly into the cost functions of the inverse optimization process, thereby shifting from DVH to DMH treatment planning paradigm. This novel DMH-based intensity modulated radiotherapy (IMRT) optimization aims in minimization of radiation doses to a certain mass, rather than a volume, of healthy tissue. The investigators' working hypothesis is that DMH- optimization will reduce doses to healthy tissue substantially. In certain cases, with extensive, difficult to treat disease, lower doses to healthy tissue can be used for isotoxic dose escalation, which may result in an increase in estimated loco-regional tumor control probability.

To test the study hypothesis, the investigators will pursue the following specific aims:

• (1) Develop the theoretical and computational framework of the DMH-based IMRT optimization. This framework will incorporate 3D and 4D IMRT as well as 3D volumetric modulated arc (VMAT) planning for different anatomical sites.

• (2) Investigate different parametric forms for DMH-optimization functions. The ultimate goal would be the simultaneous minimization of healthy tissue doses and/or escalation of therapeutic doses, without violating the established dosimetric tolerances for healthy anatomical structures.

• (3) Practical implementation and application of this novel optimization paradigm, where virtual clinical trials for cohorts of lung, head-and-neck, and prostate cancer cases will be performed.

Statistical significance of the DMH-optimization dosimetric improvements over standard of care DVH-optimization will be quantified. Prospective 3D and 4D CT data collection will be used to study the interactions between tumor time-trending changes and DMH-based optimization results. 4D CT data will also be used to investigate and quantify the correlation between DMH-based end points and the loss of pulmonary function during and after radiotherapy treatment. The deliverability (with the existing radiotherapy treatment equipment) of the investigators' 3D VMAT and 3D/4D IMRT plans will be experimentally verified, thereby paving the road for initiation of clinical trials.

Study Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Health Services Research
• Official Title: DMH-Based Plan Evaluation and Inverse Optimization in Radiotherapy
• Actual Study Start Date: Jun 19, 2015
• Actual Primary Completion Date: Apr 4, 2019
• Actual Study Completion Date: Apr 4, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: IMRT Study participants being treated according to the standard of care with intensity modulated radiotherapy (IMRT). Several CT scans will be performed for each enrolled subject: one before the radiotherapy course for patient treatment planning purposes (as part of the standard of care), one during the radiotherapy treatment course (between fraction 10 and 20), and one at follow up visit or at least 6 weeks post-radiotherapy treatment (whichever comes first).

Device: CT Scan; Other Names: Computed Tomography Imaging Scan

Outcome Measures

Primary Outcome Measures

1. Percent Change in Radiation Dose to Healthy Human Tissue. [Baseline, up to three years.]

   The study is computational in nature. A new treatment planning paradigm is proposed, where from the newly proposed treatment plans, and the treatment plans generated with the standard of care, radiation doses to different organs and tissues would be derived. Radiotherapy toxicity (to healthy human tissue) is proportional to radiation dose - more radiation dose results in higher toxicity. Thereby, if radiation dose is decreased, the toxicity would also be decreased. The dosimetric differences which the investigators observe between the standard of care and their novel optimization approach are reported as percent change with respect to the standard of care.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have histologically confirmed head-and-neck, lung, or prostate tumors.

• Patients who will be treated with radiation therapy or concurrent chemoradiation therapy.

• Gross Tumor Volume (GTV) or resection cavity must be visible on CT such that it can be delineated as a target for radiotherapy.

• Patients who are able to understand the investigational nature of this study and agree to sign a written informed consent document.

Exclusion Criteria:

• Pregnant or nursing women will not participate. Women of reproductive potential must be offered a pre-treatment pregnancy test and informed of the need to practice an effective contraceptive method during the therapy.

• Patients younger than 18 years.

• Patients whose size and weight would not allow CT scanning.

• No vulnerable populations (fetuses, pregnant women, children, prisoners) will be included in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami	Miami	Florida	United States	33136

Sponsors and Collaborators

• University of Miami
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ivaylo Mihaylov, PhD, University of Miami

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 6, 2017

More Information

Publications

None provided.

• Responsible Party: Ivaylo Mihaylov, PhD, DABR, Associate Professor, University of Miami
• ClinicalTrials.gov Identifier: NCT02663817
• Other Study ID Numbers: 20130751; R01CA163370
• First Posted: Jan 26, 2016
• Last Update Posted: Feb 5, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Additional relevant MeSH terms: Head and Neck Neoplasms

Study Results

Participant Flow

Arm/Group Title	IMRT
Arm/Group Description	Study participants being treated according to the standard of care with intensity modulated radiotherapy (IMRT). Several CT scans will be performed for each enrolled subject: one before the radiotherapy course for patient treatment planning purposes (as part of the standard of care), one during the radiotherapy treatment course (between fraction 10 and 20), and one at follow up visit or at least 6 weeks post-radiotherapy treatment (whichever comes first).
Period Title: Overall Study
STARTED	52
COMPLETED	50
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	IMRT
Arm/Group Description	Study participants being treated according to the standard of care with intensity modulated radiotherapy (IMRT). Several CT scans will be performed for each enrolled subject: one before the radiotherapy course for patient treatment planning purposes (as part of the standard of care), one during the radiotherapy treatment course (between fraction 10 and 20), and one at follow up visit or at least 6 weeks post-radiotherapy treatment (whichever comes first).
Overall Participants	52
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	25 48.1%
>=65 years	27 51.9%
Sex: Female, Male (Count of Participants)
Female	16 30.8%
Male	36 69.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	29 55.8%
Not Hispanic or Latino	23 44.2%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	9 17.3%
White	39 75%
More than one race	2 3.8%
Unknown or Not Reported	2 3.8%
Disease site (Count of Participants)
Head and neck	27 51.9%
Prostate	9 17.3%
Lung	16 30.8%

Outcome Measures

1. Primary Outcome

Title	Percent Change in Radiation Dose to Healthy Human Tissue.
Description	The study is computational in nature. A new treatment planning paradigm is proposed, where from the newly proposed treatment plans, and the treatment plans generated with the standard of care, radiation doses to different organs and tissues would be derived. Radiotherapy toxicity (to healthy human tissue) is proportional to radiation dose - more radiation dose results in higher toxicity. Thereby, if radiation dose is decreased, the toxicity would also be decreased. The dosimetric differences which the investigators observe between the standard of care and their novel optimization approach are reported as percent change with respect to the standard of care.
Time Frame	Baseline, up to three years.

Outcome Measure Data

Analysis Population Description

Two participants with prostate cancer were screen failures.

Arm/Group Title	IMRT Lung	IMRT Prostate	IMRT Head and Neck
Arm/Group Description	Study participants being treated according to the standard of care with intensity modulated radiotherapy (IMRT) for Lung cancer.	Study participants being treated according to the standard of care with intensity modulated radiotherapy (IMRT) for Prostate cancer.	Study participants being treated according to the standard of care with intensity modulated radiotherapy (IMRT) for Head-and-Neck cancer.
Measure Participants	16	7	27
Dmh - Heart	3.0
Dmh - Spinal Cord	31.0
Dmh - Esophagus	25.0
Dmh - Lungs	2.0
Energy - Heart	11.0
Energy - Spinal Cord	24.0	7.0
Energy - Esophagus	16.0
Energy - Lungs	10.0
Energy for HN - Brainstem	11.0
Energy for HN - Larynx	9.0
Energy for HN - Lt Parotid	14.0
Energy for HN - Rt Parotid	13.0
Energy Prostate - Bladder D15	2.0
Energy Prostate - Bladder D25	6.5
Energy Prostate - Rectum D15	1.7
Energy Prostate - Rectum D25	5.0
Energy Prostate - Rt Femur D10	32.5
Energy Prostate - Lt Femur D10	32.7

Adverse Events

Adverse Event Reporting Description	No adverse events were collected in this protocol
Arm/Group Title	IMRT
Arm/Group Description	Study participants being treated according to the standard of care with intensity modulated radiotherapy (IMRT). Several CT scans will be performed for each enrolled subject: one before the radiotherapy course for patient treatment planning purposes (as part of the standard of care), one during the radiotherapy treatment course (between fraction 10 and 20), and one at follow up visit or at least 6 weeks post-radiotherapy treatment (whichever comes first).
All Cause Mortality
	IMRT
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Serious Adverse Events
	IMRT
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	IMRT
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.