Is less more? Revisiting elective nodal irradiation in head and neck cancer

Radiotherapy is an important pillar of treatment for patients with locally advanced head and neck squamous cell carcinoma (HNSCC) in both adjuvant and definitive treatment. However, radiotherapy in the head and neck region is associated with relevant acute and late side effects. With the advent of modern radiotherapy and imaging techniques, numerous studies are underway to personalize radiotherapy with the aim of reducing toxicity while maintaining good control rates. Since the side effects of radiotherapy are often directly related to the irradiated volume, an important approach to individualizing radiotherapy is the reduction of elective nodal irradiation (ENI). Our aim was to provide an overview of published and ongoing studies investigating the de-escalation of radiotherapy in the elective lymphatic drainage areas of head and neck tumors.

The literature search in MEDLINE, Web of Science, and clinicaltrials.gov was conducted using the following search terms in various combinations: head and neck cancer, elective nodal irradiation, de-escalation, and radiotherapy. Studies that included nasopharyngeal cancer or carcinomas with non-squamous histology were excluded.

Various approaches to deintensifying ENI have been investigated, ranging from ENI dose reduction, general dose reduction, and volume reduction to complete omission of ENI, with some studies using response-adjusted dose and/or volume reduction after induction chemotherapy or dose reduction depending on hypoxia measured by FMISO-PET scan or sentinel lymph nodes measured by SPECT-CT after 99mTc-nanocolloid injection around the primary tumor. All these phase II trials indicate that the recurrence rate outside the radiation field is low (up to 4%). Most recurrences occur in high-risk regions of the clinical target volume (CTV) and in distant regions. However, results of phase III trials are still pending.

Reducing or even omitting ENI in patients with HNSCC seems to be a promising approach to de-escalation, but results of phase III trials are still pending.