Mid-treatment Fluorodeoxyglucose Positron Emission Tomography in Human Papillomavirus-related Oropharyngeal Squamous Cell Carcinoma Treated with Primary Radiotherapy: Nodal Metabolic Response Rate can Predict Treatment Outcomes

P Lin; M Min; K Lai; M Lee; L Holloway; W Xuan; V Bray; A Fowler; C S Lee; J Yong

doi:10.1016/j.clon.2021.07.011

Mid-treatment Fluorodeoxyglucose Positron Emission Tomography in Human Papillomavirus-related Oropharyngeal Squamous Cell Carcinoma Treated with Primary Radiotherapy: Nodal Metabolic Response Rate can Predict Treatment Outcomes

Clin Oncol (R Coll Radiol). 2021 Dec;33(12):e586-e598. doi: 10.1016/j.clon.2021.07.011. Epub 2021 Aug 7.

Authors

P Lin¹, M Min², K Lai³, M Lee⁴, L Holloway⁵, W Xuan⁶, V Bray⁷, A Fowler⁷, C S Lee⁸, J Yong⁹

Affiliations

¹ Department of Nuclear Medicine and PET, Liverpool Hospital, Liverpool, New South Wales, Australia; South Western Sydney Clinical School, University of New South Wales, New South Wales, Australia; School of Medicine, Western Sydney University, New South Wales, Australia. Electronic address: peter.lin1@health.nsw.gov.au.
² Department of Radiation Oncology, Sunshine Coast University Hospital, Queensland, Australia; Faculty of Science, Health, Education and Engineering, University of Sunshine Coast, Queensland, Australia; Cancer Therapy Centre, Liverpool Hospital, Liverpool, New South Wales, Australia.
³ Department of Nuclear Medicine and PET, Liverpool Hospital, Liverpool, New South Wales, Australia; School of Medicine, Western Sydney University, New South Wales, Australia.
⁴ South Western Sydney Clinical School, University of New South Wales, New South Wales, Australia; Cancer Therapy Centre, Liverpool Hospital, Liverpool, New South Wales, Australia.
⁵ South Western Sydney Clinical School, University of New South Wales, New South Wales, Australia; School of Medicine, Western Sydney University, New South Wales, Australia; Cancer Therapy Centre, Liverpool Hospital, Liverpool, New South Wales, Australia; Ingham Institute of Applied Medical Research, Liverpool, New South Wales, Australia.
⁶ South Western Sydney Clinical School, University of New South Wales, New South Wales, Australia; Ingham Institute of Applied Medical Research, Liverpool, New South Wales, Australia.
⁷ Cancer Therapy Centre, Liverpool Hospital, Liverpool, New South Wales, Australia.
⁸ South Western Sydney Clinical School, University of New South Wales, New South Wales, Australia; School of Medicine, Western Sydney University, New South Wales, Australia; Ingham Institute of Applied Medical Research, Liverpool, New South Wales, Australia; Department of Anatomical Pathology, Liverpool Hospital, Liverpool, New South Wales, Australia; Central Clinical School, University of Sydney, New South Wales, Australia.
⁹ Department of Anatomical Pathology, Liverpool Hospital, Liverpool, New South Wales, Australia.

PMID: 34373179
DOI: 10.1016/j.clon.2021.07.011

Abstract

Aims: To evaluate whether biomarkers derived from fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) performed prior to (prePET) and during the third week (interim PET; iPET) of radiotherapy can predict treatment outcomes in human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPC).

Materials and methods: This retrospective analysis included 46 patients with newly diagnosed OPC treated with definitive (chemo)radiation and all patients had confirmed positive HPV status (HPV+OPC) based on p16 immunohistochemistry. The maximum standardised uptake value (SUV_max), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) of primary, index node (node with the highest TLG) and total lymph nodes and their median percentage (≥50%) reductions in iPET were analysed, and correlated with 5-year Kaplan-Meier and multivariable analyses (smoking, T4, N2b-3 and AJCC stage IV), including local failure-free survival, regional failure-free survival, locoregional failure-free survival (LRFFS), distant metastatic failure-free survival (DMFFS), disease-free survival (DFS) and overall survival.

Results: There was no association of outcomes with prePET parameters observed on multivariate analysis. A complete metabolic response of primary tumour was seen in 13 patients; the negative predictive value for local failure was 100%. More than a 50% reduction in total nodal MTV provided the best predictor of outcomes, including LRFFS (88% versus 47.1%, P = 0.006, hazard ratio = 0.153) and DFS (78.2% versus 41.2%, P = 0.01, hazard ratio = 0.234). More than a 50% reduction in index node TLG was inversely related to DMFFS: a better nodal response was associated with a higher incidence of distant metastatic failure (66.7% versus 100%, P = 0.009, hazard ratio = 3.0).

Conclusion: The reduction (≥50%) of volumetric nodal metabolic burden can potentially identify a subgroup of HPV+OPC patients at low risk of locoregional failure but inversely at higher risk of distant metastatic failure and may have a role in individualised adaptive radiotherapy and systemic therapy.

Keywords: FDG PET-CT; human papillomavirus; oropharyngeal squamous cell carcinoma; prognostic and predictive imaging biomarkers; radiotherapy.

MeSH terms

Alphapapillomavirus*
Fluorodeoxyglucose F18
Head and Neck Neoplasms*
Humans
Positron Emission Tomography Computed Tomography
Positron-Emission Tomography
Prognosis
Radiopharmaceuticals
Retrospective Studies
Squamous Cell Carcinoma of Head and Neck
Treatment Outcome

Substances

Radiopharmaceuticals
Fluorodeoxyglucose F18