Strategy of Using Intratreatment Hypoxia Imaging to Selectively and Safely Guide Radiation Dose De-escalation Concurrent With Chemotherapy for Locoregionally Advanced Human Papillomavirus-Related Oropharyngeal Carcinoma.

Abstract

PURPOSE:

To report a small substudy of an ongoing large, multi-arm study using functional imaging to assess pre-/intratreatment hypoxia for all head and neck cancer, in which we hypothesized that pre- and early-treatment hypoxia assessment using functional positron emission tomography (PET) imaging may help select which human papillomavirus (HPV)-positive (HPV(+)) oropharyngeal cancer (OPC) patients can safely receive radiation de-escalation without jeopardizing treatment outcomes.

METHODS AND MATERIALS:

Patients with HPV(+) oropharyngeal carcinoma were enrolled on an institutional review board-approved prospective study of which de-escalation based on imaging response was done for node(s) only. Pretreatment (18)F-fluorodeoxyglucose and dynamic (18)F-FMISO (fluoromisonidazole) positron emission tomography (PET) scans were performed. For patients with pretreatment hypoxia on(18)F-FMISO PET (defined as a >1.2 tumor to muscle standard uptake value ratio), a repeat scan was done 1 week after chemoradiation. Patients without pretreatment hypoxia or with resolution of hypoxia on repeat scan received a 10-Gy dose reduction to metastatic lymph node(s). The 2-year local, regional, distant metastasis-free, and overall survival rates were estimated using the Kaplan-Meier product-limit method. A subset of patients had biopsy of a hypoxic node done under image guidance.

RESULTS:

Thirty-three HPV(+) OPC patients were enrolled in this pilot study. One hundred percent showed pretreatment hypoxia (at primary site and/or node[s]), and among these, 48% resolved (at primary site and/or node[s]); 30% met criteria and received 10-Gy reduction to the lymph node(s). At the median follow-up of 32 months (range, 21-61 months), the 2-year locoregional control rate was 100%. One patient failed distantly with persistence of hypoxia on (18)F-FMISO PET. The 2-year distant metastasis-free rate was 97%. The 2-year OS rate was 100%. Hypoxia on imaging was confirmed pathologically.

CONCLUSIONS:

Hypoxia is present in HPV(+) tumors but resolves within 1 week of treatment in 48% of cases either at the primary site and/or lymph node(s). Our 100% locoregional control rate suggests that intratreatment functional imaging used to selectively de-escalate node(s) to 60 Gy was confirmed safe using our stringent imaging criteria. Intratreatment functional imaging warrants further study to determine its ultimate role in de-escalation treatment strategies.

• Authors: Nancy Lee, Heiko Schoder, Brad Beattie, Ryan Lanning, Nadeem Riaz, Sean McBride, Nora Katabi, Duan Li, Brett Yarusi, Susie Chan, Lindsey Mitrani, Zhigang Zhang, David G Pfister, Eric Sherman, Shrujal Baxi, Jay Boyle, Luc G T Morris, Ian Ganly, Richard Wong, John Humm
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 96 Issue 1 Pg. 9-17 (09 01 2016) ISSN: 1879-355X [Electronic] United States
• PMID: 27511842 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Radiopharmaceuticals
• fluoromisonidazole
• Misonidazole
• Oxygen

Topics

• Adult
• Aged
• Carcinoma (diagnostic imaging, secondary, therapy)
• Chemoradiotherapy (methods)
• Female
• Humans
• Male
• Middle Aged
• Misonidazole (analogs & derivatives)
• Oropharyngeal Neoplasms (diagnostic imaging, metabolism, therapy)
• Oxygen (metabolism)
• Positron-Emission Tomography (methods)
• Radiation Protection (methods)
• Radiopharmaceuticals
• Radiotherapy Dosage
• Radiotherapy, Image-Guided (methods)
• Treatment Outcome
• Tumor Hypoxia (drug effects)