Imaging and blood biomarkers: towards personalized medicine in head and neck cancer

Abstract

© 2020 Sweet Ping NgHead and neck cancer is the 6th most common malignancy, accounting for approximately 4% of malignancies, and 1 – 2% of cancer-related deaths. Radiation therapy utilises high energy radiation to kill cancer cells. In head and neck cancer, radiotherapy is one of the main treatment modalities, particularly in curative-intent treatments. Despite advancements in imaging and radiation treatment planning and delivery, the prescribed dose and radiation treatment workflow remained unchanged and is largely ‘one size fits all’. Similarly, the survivorship program for patients with head and neck cancer is ‘one size fits all’, often one standard institutional follow up schedule for all patients treated for head and neck cancer, regardless of expected risk of treatment-related late toxicities, patients’ subsequent risk of recurrence and second malignancy. This thesis focuses on the value and efficacy of imaging and blood biomarkers in improving treatment personalisation in patients with head and neck cancer. In chapters 1 and 2, I explored the use of imaging and blood markers in the pre-, during, and post-radiotherapy settings to further improve risk stratification. In chapter 1, I investigated the potential use of readily available and ‘cheap’ blood biomarkers (neutrophil and lymphocyte counts) as predictors of subsequent outcomes in a large cohort of patients with oropharyngeal cancer. In chapter 2, I designed and conducted a prospective observational study to systematically characterize the kinetics of gross tumour volume and apparent diffusion coefficient (ADC) changes observed in magnetic resonance imaging (MRI) and circulating tumour cells (CTCs) counts during radiotherapy in patients with head and neck squamous cell cancer. In the survivorship period (Chapter 3), I evaluated the effectiveness of current surveillance program and investigated the potential use of PET imaging and alternative imaging frequencies to improve the cost-effectiveness of the survivorship program. In this chapter, I found that 70% of disease recurrence occur within 2 years and the probability of a surveillance imaging detecting a recurrence in an asymptomatic patient with no adverse clinical finding is very low. Furthermore, in patients with human papillomavirus (HPV)-related oropharyngeal cancer, achieving a complete response on post-treatment PET imaging has a negative predictive value of any subsequent recurrence of 92%, so the yield of surveillance imaging is very low in this group. Using a partially observed Markov decision model, a potentially effective surveillance program with less frequent imaging was propositioned in this chapter. Finally, in chapter 4, I assessed the potential use of re-irradiation in the era of modern imaging and new radiation treatment techniques including intensity-modulated radiotherapy (IMRT), proton therapy and stereotactic body radiotherapy (SBRT). I showed the value of different imaging modality (dual energy CT and MRI) in target delineation in patients who had previous radiation. In addition, I demonstrated that the local control rate for each treatment technique is similar. Although wide field radiotherapy (IMRT and proton therapy) had improve disease-specific survival, treatment with these techniques are longer (typically 6 to 7 weeks) and had higher toxicity rates than SBRT (delivered over 5 treatments)