Adaptive radiotherapy for head and neck cancer

Abstract

Background: Although there have been dramatic improvements in radiotherapy for head and neck squamous cell carcinoma (HNSCC), including robust intensity modulation and daily image guidance, these advances are not able to account for inherent structural and spatial changes that may occur during treatment. Many sources have reported volume reductions in the primary target, nodal volumes, and parotid glands over treatment, which may result in unintended dosimetric changes affecting the side effect profile and even efficacy of the treatment. Adaptive radiotherapy (ART) is an exciting treatment paradigm that has been developed to directly adjust for these changes.

Main body: Adaptive radiotherapy may be divided into two categories: anatomy-adapted (A-ART) and response-adapted ART (R-ART). Anatomy-adapted ART is the process of re-planning patients based on structural and spatial changes occurring over treatment, with the intent of reducing overdosage of sensitive structures such as the parotids, improving dose homogeneity, and preserving coverage of the target. In contrast, response-adapted ART is the process of re-planning patients based on response to treatment, such that the target and/or dose changes as a function of interim imaging during treatment, with the intent of dose escalating persistent disease and/or de-escalating surrounding normal tissue. The impact of R-ART on local control and toxicity outcomes is actively being investigated in several currently accruing trials.

Conclusions: Anatomy-adapted ART is a promising modality to improve rates of xerostomia and coverage in individuals who experience significant volumetric changes during radiation, while R-ART is currently being studied to assess its utility in either dose escalation of radioresistant disease, or de-intensification of surrounding normal tissue following treatment response. In this paper, we will review the existing literature and recent advances regarding A-ART and R-ART.

Keywords: Adaptive radiotherapy; Head and neck squamous cell carcinoma; IMRT; MRI-guided radiotherapy; PET-guided radiotherapy.

Fig. 1

Primary tumor, nodal, and parotid volumes decrease over the course of radiation. This patient is a 54 year-old man with p16-positive cT4N1M0 squamous cell carcinoma of the left tonsil who required adaptive radiotherapy over the course of radiation secondary to significant tumor response and weight loss during treatment noted on review of daily CBCTs. The primary tumor decreased by 25.0% from baseline (A1) to week 5 (A2). The grossly involved nodes decreased by 48.6% from baseline (B1) to week 5 (B2). The left parotid decreased by 37.2% (cyan) and the right parotid (blue) decreased by 41.9% from baseline (C1) to week 5 (C2). Note contraction of the lateral border of the bilateral parotids at time of re-simulation (C2)

Fig. 2

Adaptive re-planning reduces unplanned dose inhomogeneity and parotid gland overdose. These images are from the same case as presented in Fig. 1. At time of initial simulation (a), anticipated coverage of the high dose planned target volume (PTV) was 98.5% receiving 70Gy and the mean dose of the left and right superficial parotids were 25.0 and 24.5 Gy, respectively. However, by week 5 (b), there was wide variation in dose within the high dose PTV with cold spots down to 88.0% and hot spots up to 113.4% of the prescription. In addition, the mean left and right superficial parotids doses increased to 32.2 Gy and 36.7 Gy, respectively. With adaptive re-planning (c), dose homogeneity was improved with cold spots only being 94.8% and hot spots only being 104.4% inside of the high dose PTV, with reduction of the mean right and left superficial parotid dose back to 24.9 Gy and 24.6 Gy, respectively. The main benefit of A-ART in this case was sparing of the parotids, given there was an unplanned overdose of an additional 7.2 Gy to the left and 12.2 Gy to the right parotids which was mitigated with adaptive re-planning