PET-MRI Assessment of Early Tumor Response to Predict Outcomes of HPV-Positive Oropharynx Cancer Patients

Completed

• Conditions: Squamous Cell Carcinoma; Oropharynx Cancer

• Registration Number: NCT03342378
• Lead Sponsor: University of Wisconsin, Madison

Brief Summary

This proposal explores the novel hypothesis that the variability in outcomes within the Intermediate Risk(IR) HPV-positive Oropharynx Squamous Cell Carcinoma(OPSCC) cohort can be exploited to identify a subpopulation that exhibits outcomes similar to Low Risk (LR) HPV-positive Oropharynx Squamous Cell Carcinoma and therefore would be appropriate candidates for radiation dose de-escalation approaches. Current literature using PET, CT, and MRI as single imaging modalities have identified certain criteria within heterogenous patient populations that are associated with clinical outcomes. Here, the investigators will test the hypothesis that multiparametric analysis of simultaneously-acquired MRI and PET quantitative imaging biomarker data from the primary tumor prior to initiating therapy, after 2 weeks of chemoradiation(CRT), and 3 months following completion of chemoradiation in patients with Intermediate Risk HPV-positive Oropharynx Squamous Cell Carcinoma will generate parametric maps that are predictive of clinical outcome.

Furthermore, the investigators will collect blood samples prior to, during, and after radiation therapy to evaluate whether levels of detected circulating tumor cells correlate with response to treatment.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-11-09
• Study First Submitted QC: 2017-11-09
• Study First Posted: 2017-11-17
• Study Start: 2018-05-03
• Primary Completion: 2021-02-19
• Study Completion: 2021-05-15
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-16
• Last Update Posted: 2022-11-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• Histologically- or cytologically-proven diagnosis of squamous cell carcinoma (including papillary squamous cell carcinoma and basaloid squamous cell carcinoma variants) of the oropharynx (tonsil or base of tongue)

• III-IVB (T3N0, T1-3N1, T4aN0-3, T4bN0-3, T1-4N2, T1-4N3) (AJCC 8th edition) based upon the following minimum diagnostic workup:

  • General history and physical examination (including nasolarygopharyngoscopy or indirect mirror exam) by a radiation oncologist or medical oncologist or ENT head and neck surgeon within 8 weeks prior to registration.

  • Diagnostic CT of the neck with IV contrast

  • Chest imaging

    • CXR or CT chest without contrast

• Patient must not have any contraindications to undergoing a 3.0T PET-MRI

• Zubrod Performance Status 0-1 within 2 weeks prior to registration.

• Smoking history defined by pack-years (calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked).

• Negative urine pregnancy test within 2 weeks prior to registration for women of childbearing potential.

• Patient must provide study specific informed consent prior to study entry.

Exclusion Criteria

• Cancers considered to be from an oral cavity, nasopharynx, hypopharynx, or larynx are excluded. Carcinoma of the neck of unknown primary site origin (even if p16 positive) are excluded.
• Distant metastasis
• Gross total excision of the primary tumor with or without nodal dissection.
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years. (For example, carcinoma of the breast, colon or cervix are all permissible if patients are disease free for ≥ 3 years.)
• Prior radiotherapy to the head and neck region that would result in overlap of radiation therapy fields.
• Presence of passive and/or active devices that are not compatible with the 3.0T PET/MR scanner environment. Any person with the following will be excluded: cardiac pacemaker, metal fragments in or around the eye, venous umbrella, permanent eyeliner or permanent artificial eyebrows. Patents with the following potentially non-MRI compatible devices will undergo screening using the standard UWHC MRI screening protocol by trained UWHC personnel: cardiac pacemaker, heart valve replacement, intracranial aneurysm clips, middle ear, eye, joint, or penile implants, joint replacements, implantable hearing aids, neurostimulator devices, insulin pumps, shunts/stents, metal mesh/coil implants; metal plate/pin/screws/wires, or any other metallic implants. Also, patients with anatomical constraints limiting the feasibility of MRI will be excluded.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Radiographic change in the primary tumor of patients with LR and IR HPV-positive OPSCC using MRI/PET imaging	Pre-treatment (baseline) and following 2-weeks of CRT (approximately 2-3 weeks on study)	Patients with LR and IR HPV-positive OPSCC will be segregated into favorable and unfavourable cohorts using radiographic change(MRI/PET) in the primary tumor between pre-treatment and intra-treatment. T-stage, N-stage, and pack-years smoking markers will be used as surrogate markers
Radiographic change in the primary largest pathologic lymph node of patients with LR and IR HPV-positive OPSCC using MRI/PET imaging	Pre-treatment (baseline) and following 2-weeks of CRT (approximately 2-3 weeks on study)	Patients with LR and IR HPV-positive OPSCC will be segregated into favorable and unfavourable cohorts using radiographic change(MRI/PET) in the largest pathologic lymph node between pre-treatment and intra-treatment. T-stage, N-stage, and pack-years smoking markers will be used as surrogate markers

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival	up to 2 years
Absolute volumetric change of the primary tumor	Following 2-weeks of CRT (approximately 2-3 weeks on study)	The primary tumor response in patients with LR HPV-positive OPSCC and HPV-negative OPSCC will be measured in terms of absolute volumetric change in the tumor following 2 weeks of CRT
Absolute metabolic change of the primary tumor	Following 2-weeks of CRT (approximately 2-3 weeks on study)	The primary tumor response in patients with LR HPV-positive OPSCC and HPV-negative OPSCC will be measured in terms of absolute metabolic change in the tumor following 2 weeks of CRT
Absolute physiologic change of the primary tumor	Following 2-weeks of CRT (approximately 2-3 weeks on study)	The primary tumor response in patients with LR HPV-positive OPSCC and HPV-negative OPSCC will be measured in terms of absolute physiologic change in the tumor following 2 weeks of CRT
Absolute volumetric change of involved nodes	Following 2-weeks of CRT (approximately 2-3 weeks on study)	The nodal response in patients with LR HPV-positive OPSCC and HPV-negative OPSCC will be measured in terms of absolute volumetric change of involved nodes following 2 weeks of CRT
Absolute metabolic change of involved nodes	Following 2-weeks of CRT (approximately 2-3 weeks on study)	The nodal response in patients with LR HPV-positive OPSCC and HPV-negative OPSCC will be measured in terms of absolute metabolic change of involved nodes following 2 weeks of CRT
Absolute physiologic change of involved nodes	Following 2-weeks of CRT (approximately 2-3 weeks on study)	The nodal response in patients with LR HPV-positive OPSCC and HPV-negative OPSCC will be measured in terms of absolute physiologic change of involved nodes following 2 weeks of CRT

Trial Locations

Locations (1)

University of Wisconsin Carbone Cancer Center; 🇺🇸 Madison, Wisconsin, United States