Prognostic Biomarkers for Patients With Human Papillomavirus (HPV) Positive Oropharyngeal Squamous Cell Carcinoma (OPSCC)
Full Exchange Pharmacokinetic Model Analysis of Dynamic Contrast-Enhanced MRI Data for Identification of Vascular Habitats and Evaluation of Treatment Response in Human Papillomavirus Positive Oropharyngeal Squamous Cell Carcinomas
The purpose of this research study is to investigate the relationship between vascular habitats and treatment response AND to investigate the potential utility of dynamic contrast enhanced (DCE)-MRI derived parameters in predicting treatment response.
This data can be used to assist in the development of a clinical decision support (CDS) tool for risk categorization and individualized decision-making. While "low-risk" patients could benefit from de-escalated radiation therapy, "high-risk" patients could receive early initiation of targeted therapies, or immunotherapies.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The current standard of care treatment for inoperable human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) patients includes concurrent cisplatin and radiation therapy with a total dose of 70Gy over a period of 7 weeks. As reported by our group and others, the full dose of CRT regimen is associated with a considerable acute and chronic toxicity profile, negatively impacting the quality of life of OPSCC patients. Moreover, treatment related morbidities result in adverse social and economic consequences. Given that HPV-positive OPSCCs are more chemo-radiosensitive in patients who are typically younger and have a high likelihood of surviving their disease, there is great interest across the world in the development of de-escalated therapeutic strategies. The de-escalation approaches include omitting, replacing, or reducing cytotoxic chemotherapy; reducing dose or field of radiation therapy; and incorporation of less-invasive surgical procedures. The goal of these treatment de-intensification strategies is to maintain good cure rates while preserving normal functional outcomes and minimizing long-term morbidity.
Despite promising outcome measures with de-escalated radiation therapy in HPV-positive OPSCC patients, clinical trials have also reported considerable variability in response among individual patients receiving low-dose radiation therapy. Between 5-25% of these patients develop disease recurrence (at loco-regional or distant sites) within 2 years post-treatment. Recently, two large phase-III trials, RTOG 1016 and De-ESCALaTE, demonstrated inferior outcomes [hazard of locoregional failure in de-escalated treatment arm was more than twice that of standard of care treatment arm (HR=2.05, 95%CI=1.35-3.10; p=0.0005)] in HPV-positive OPSCC patients. Taken together, these findings advocate for applying a cautious approach while selecting HPV-positive OPSCC patients for de-escalation therapies. In clinical practice, less advanced tumor (T0-T3) or nodal (N0-N2) stage, and non-significant smoking history (less than or equal to 10 pack years as threshold) are generally used for selecting patients for de-escalation therapies. However, there is a lack of consensus on the utility of these highly subjective factors which are not sufficiently appropriate to identify suitable candidates for participating in de-escalation trials. Additionally, response to induction therapy, determined by greater than or equal to 50% reduction in tumor size, relative to baseline, has been used to select patients. However, measurement of tumor volume using anatomical images alone is not a good predictor of treatment response. Assessment of pre- and early post-treatment hypoxia from the primary tumor and metastatic nodes using F-FMISO (fluoromisonidazole)-positron emission tomography (PET) has also been used to select patients for receiving de-escalated radiation therapy. However, nonspecific and overlapping findings have been reported with F-FMISO-PET in HNSCCs, raising concerns about its utility as a reliable imaging biomarker. Moreover, F-FMISO radiotracer is not readily available for clinical applications around the world.
Therefore, there is a pressing need for the development of reliable, objective, and quantifiable MRI biomarkers for risk stratification and individualized decision making for HPV-positive OPSCC patients.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Lisa Desiderio
- Phone Number: 610-721-3365
- Email: lisa.desiderio@pennmedicine.upenn.edu
Study Contact Backup
- Name: Marisa Sanchez, Bachelor of Science
- Phone Number: 215-901-9994
- Email: marisa.sanchez@pennmedicine.upenn.edu
Study Locations
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Hospital of the University of Pennsylvania
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Adult population (≥18 years) of both genders
- Biopsy confirmed diagnosis of OPSCC
- Known HPV status as determined by p16 immunohistochemistry (p16 positivity defined as >70% of carcinoma cells showing nuclear reactivity) or polymerase chain reaction (PCR) sequencing
- Prior to any treatment except for incisional or excisional biopsies
- T0 to T4, N1 to N3, M0 (American Joint Committee on Cancer, 8th edition)
- A willingness to undergo multiple phlebotomy (blood withdrawal) during standard CRT for liquid biopsy analyses.
Exclusion Criteria:
- HPV- negative OPSCC
- Presence of distant metastatic (M1) disease
- Pregnancy
- Existence of significant co-morbidities at baseline which would prevent standard CRT treatment
- Implanted cardiac pacemaker or defibrillator, programmable shunts, deep brain stimulator, other implanted electronic devices which may be contraindicated for 3T MRI
- Presence of significant hemorrhage in and around the tumor bed that may potentially degrade the image quality
- Significant claustrophobia.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Other: HPV Positive Oropharyngeal Squamous Cell Carcinoma
You are being asked to complete two research MRI scans with and without contrast because you have been newly diagnosed HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and plan to receive chemoradiation therapy (CRT). MRI contrast agents act like a dye to make MRI pictures brighter and easier to read. During each MRI scan, you will have an intravenous line (IV line) placed. The IV line allows the contrast agent to be injected into your vein. |
Magnetic Resonance Imaging (MRI) is a type of scan that uses radio waves to take detailed pictures of the body.
You will be asked to lie on an MRI table where the technologist will place a receiver on the part of your body to be studied.
You will be provided a blanket for comfort and earplugs since the MRI makes noises while it is scanning.
You will still be able to hear some sound to ensure you can communicate with the technologist and can follow any direction given throughout the MRI scan.
The technologist will slowly slide you into the MRI magnet where radio waves will be transmitted into you.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Time to Progression
Time Frame: 1 Year
|
Determination of the clinical utility of pretreatment Diffusion Weighted Imaging (DWI) and Dynamic Contrast Enhanced-MRI (DCE-MRI) derived parameters in predicting response to standard Chemo-radiotherapy (CRT) in patients with HPV-positive Oropharyngeal Squamous Cell Carcinomas (OPSCC).
|
1 Year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Secondary Outcome
Time Frame: 1 year
|
Development of a Bayesian Network-based prediction model in identifying good responders to standard Chemo-Radiotherapy (CRT).
|
1 year
|
Collaborators and Investigators
Investigators
- Principal Investigator: Sanjeev Chawla, University of Pennsylvania
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 26-0210
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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