FMISO-Based Adaptive Radiotherapy in Head and Neck Cancer

Abstract

Concurrent chemoradiotherapy represents one of the most used strategies in the curative treatment of patients with head and neck (HNC) cancer. Locoregional failure is the predominant recurrence pattern. Tumor hypoxia belongs to the main cause of treatment failure. Positron emission tomography (PET) using hypoxia radiotracers has been studied extensively and has proven its feasibility and reproducibility to detect tumor hypoxia. A number of studies confirmed that the uptake of FMISO in the recurrent region is significantly higher than that in the non-recurrent region. The escalation of dose to hypoxic tumors may improve outcomes. The technical feasibility of optimizing radiotherapeutic plans has been well documented. To define the hypoxic tumour volume, there are two main approaches: dose painting by contour (DPBC) or by number (DPBN) based on PET images. Despite amazing technological advances, precision in target coverage, and surrounding tissue sparring, radiation oncology is still not considered a targeted treatment if the “one dose fits all” approach is used. Using FMISO and other hypoxia tracers may be an important step for individualizing radiation treatment and together with future radiomic principles and a possible genome-based adjusting dose, will move radiation oncology into the precise and personalized era.

Adaptive Radiotherapy: Next-Generation Radiotherapy

“…Some recent evidence has emphasized the importance of the tumor microenvironment in the tumor’s response to radiation and underscored the significance of hypoxia in tumor radioresistance [ 72 ]. ART using PET scans with hypoxia-sensitive radiotracers such as fluoromisonidazole (FMISO), fluoroazomycin arabinoside (FAZA), and pentafluorinated etanidazole (EF5) can therefore enhance treatment response [ 73 ]. Recently, a trial protocol was published about the integration of weekly offline MRIs into the CBCT-guided ART of cervical cancer patients with Ethos, allowing additional functional assessment of tissue perfusion, hypoxia, or cellular density [ 14 ].…”

Interdisciplinary Collaboration in Head and Neck Cancer Care: Optimizing Oral Health Management for Patients Undergoing Radiation Therapy

“…Upon defining a subgroup of HPV-positive oropharyngeal cancer patients with a more favorable prognosis, researchers initiated an inquiry into the feasibility of dose deescalation in selected cases [50]. Furthermore, with the FMISO adaptive protocols tracing hypoxia, dose de-escalation has the potential to achieve comparable treatment effectiveness while minimizing treatment-related toxicity [51].…”

Role of 18F-FDG PET/CT in Head and Neck Squamous Cell Carcinoma: Current Evidence and Innovative Applications

“…Tracers like 18 F-fluoromisonidazole ( 18 F-FMISO) and 18 F-fluoroazomycin-arabinofluranoside ( 18 F-FAZA) are under investigation for their ability to provide quantitative evaluations of tissue hypoxia [101]. This topic is separately discussed in this review (see "PET radiopharmaceuticals other than 18 F-FDG").…”

“…Hypoxic volumes measured using 18 F-FMISO and 18 F-FAZA PET/CT at staging are more prone to loco-regional recurrence regardless of primary tumor grading, and also in HPV-positive patients. Non-invasive detection of hypoxia is useful for tumor "dose painting", that is, dose escalation to the PET-depicted hypoxic volumes, without an increased risk of damage to neighboring critical structures [20,101,[126][127][128] and possibly carrying a lower risk of loco-regional recurrence in comparison with standard protocols [20]. Indeed, hypoxic sub-volumes may be unevenly distributed throughout the gross tumor volume visible on a CT or an MRI.…”