Clinical trial NCT03342378: PET-MRI Assessment of Early Tumor Response to Predict Outcomes of HPV-Positive Oropharynx Cancer Patients
Official title: PET-MRI Assessment of Early Tumor Response to Predict Outcomes of HPV-Positive Oropharynx Cancer Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Squamous Cell Carcinoma
Oropharynx Cancer
Keywords: HPV
HPV-positive
Oropharynx Cancer
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: National Institute of Dental and Craniofacial Research (NIDCR)
First posted: 2017-11-17
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants with OPSCC will be enrolled on an institutional review board approved clinical trial and treated with comprehensive head and neck RT to 70 Gy in 33 fractions, some with concurrent weekly cisplatin at 40 mg/m2 and at the University of Wisconsin.

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Radiographic change in the primary tumor of patients with LR and IR HPV-positive OPSCC using MRI/PET imaging
timeFrame: Pre-treatment (baseline) and following 2-weeks of CRT (approximately 2-3 weeks on study)
measure: Radiographic change in the primary largest pathologic lymph node of patients with LR and IR HPV-positive OPSCC using MRI/PET imaging
timeFrame: Pre-treatment (baseline) and following 2-weeks of CRT (approximately 2-3 weeks on study)
Secondary outcomes:
measure: Progression Free Survival
timeFrame: up to 2 years
measure: Absolute volumetric change of the primary tumor
timeFrame: Following 2-weeks of CRT (approximately 2-3 weeks on study)
measure: Absolute metabolic change of the primary tumor
timeFrame: Following 2-weeks of CRT (approximately 2-3 weeks on study)
measure: Absolute physiologic change of the primary tumor
timeFrame: Following 2-weeks of CRT (approximately 2-3 weeks on study)
measure: Absolute volumetric change of involved nodes
timeFrame: Following 2-weeks of CRT (approximately 2-3 weeks on study)
measure: Absolute metabolic change of involved nodes
timeFrame: Following 2-weeks of CRT (approximately 2-3 weeks on study)
measure: Absolute physiologic change of involved nodes
timeFrame: Following 2-weeks of CRT (approximately 2-3 weeks on study)
Other outcomes:
measure: Number of Circulating Tumor Cells
timeFrame: Pre-treatment (baseline) and following 2-weeks of CRT (approx. 2-3 weeks on study), 3-months post-treatment (approx. 19-23 weeks on study)
measure: Change in Number of Circulating Tumor Cells Between Time Points
timeFrame: Pre-treatment (baseline) and following 2-weeks of CRT (approx. 2-3 weeks on study), 3-months post-treatment (approx. 19-23 weeks on study)
Locations:
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Randy Kimple, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Witek ME, Kimple RJ, Avey GD, Burr AR, Chandereng T, Yu M, Hu R, Wieland AM, Labby ZE, Bruce JY, Brower JV, Hartig GK, Harari PM. Prospective Study of PET/MRI Tumor Response During Chemoradiotherapy for Patients With Low-risk and Intermediate-risk p16-positive Oropharynx Cancer. Am J Clin Oncol. 2022 May 1;45(5):202-207. doi: 10.1097/COC.0000000000000910. Epub 2022 Apr 12.