[18F]-Fluoromisonidazole positron emission tomography/computed tomography visualization of tumor hypoxia in patients with chordoma of the mobile and sacrococcygeal spine

Abstract

Purpose: To investigate [18F]-fluoromisonidazole positron emission tomography/computed tomography (FMISO-PET/CT) detection of targetable hypoxic subvolumes (HSVs) in chordoma of the mobile or sacrococcygeal spine.

Methods and materials: A prospective, pilot study of 20 patients with primary or locally recurrent chordoma of the mobile or sacrococcygeal spine treated with proton or combined proton/photon radiation therapy (RT) with or without surgery was completed. The FMISO-PET/CT was performed before RT and after 19.8-34.2 GyRBE (relative biologic effectiveness). Gross tumor volumes were delineated and HSVs defined including voxels with standardized uptake values ≥1.4 times the muscle mean. Clinical characteristics and treatments received were compared between patients with and without HSVs.

Results: The FMISO-PET/CT detected HSVs in 12 of 20 patients (60%). Baseline and interval HSV spatial concordance varied (0%-94%). Eight HSVs were sufficiently large (≥5 cm(3)) to potentially allow an intensity modulated proton therapy boost. Patients with HSVs had significantly larger gross tumor volumes (median 410.0 cm(3) vs 63.4 cm(3); P=.02) and were significantly more likely to have stage T2 tumors (5 of 12 vs 0 of 8; P=.04). After a median follow-up of 1.8 years (range, 0.2-4.4 years), a local recurrence has yet to be observed. Three patients developed metastatic disease, 2 with HSVs.

Conclusions: Detection of targetable HSVs by FMISO-PET/CT within patients undergoing RT with or without surgery for treatment of chordoma of the mobile and sacrococcygeal spine is feasible. The study's inability to attribute interval HSV changes to treatment, rapidly changing hypoxic physiology, or imaging inconsistencies is a limitation. Further study of double-baseline FMISO-PET/CT and hypoxia-directed RT dose escalation, particularly in patients at high risk for local recurrence, is warranted.

Figure 1

[¹⁸F] fluoromisonidazole positron emission tomography/computed tomography (FMISO-PET/CT) visualization of hypoxic chordoma sub-volumes (HSV) and theoretical use for dose-escalated intensity modulated proton therapy (IMPT). (A) Pre-treatment T2-weighted MRI demonstrating a 22.8 cm sacral chordoma. (B) Pre-treatment FMISO-PET/CT fused with radiation planning CT showing contoured HSV, gross tumor volume (GTV), clinical target volume (CTV), bladder, and rectum. (C) FMISO-PET/CT fused with radiation planning CT after 25.2 GyRBE (relative biologic effectiveness) with additionally contoured interval HSV and 3 mm expansion of combined HSVs. (D) Actual delivered proton/photon treatment plan to 73.8 GyRBE to the GTV. (E) Theoretical IMPT plan to 77.4 GyRBE to the GTV with integrated boost to the combined pre-treatment and interval HSVs to 84.9 GyRBE.