Survival and functional outcomes following salvage surgery for RESidual or reCurrent sqUamous cEll carcinoma of the head and neck (RESCUE)

Research summary

Head and neck squamous cell carcinoma (H&N SCC) incorporate tumours of varying areas of the upper aerodigestive tract,including the larynx,hypopharynx,nasopharynx,and oropharynx. H&N cancer is increasingly common in the UK,with rates increasing by 34% since the early 1990s. The rising prevalence of H&N cancer has been attributed to a rising rate in women,and the prevalence of the Human papilloma virus (HPV) in oropharyngeal cancer,which can account for up to 70% of cases. The survival in H&N cancer is highly variable,ranging from over 80% at 5 years in HPV positive oropharyngeal cancer,to as low as 25–35% for hypopharyngeal cancer. However,many patients may experience residual (within 12 months),recurrent (beyond 12 months),or new primary cancer following radiotherapy treatment,with H&N SCC being 11 times more likely to experience long term recurrent or new primary disease than other cancers. The treatment of relapsed and recurrent H&N SCC is predominantly surgical,as radiotherapy-treated tissue is often extensively fixed,fibrosed,and devascularised,meaning re-irradiation is not possible without causing significant morbidity and dysfunction to the patient. Irradiated tissue also presents a significant surgical challenge,as extensive scarring and poor blood supply can impede effective dissection and wound healing. In order to reduce post-operative morbidity,minimally invasive techniques including transoral robotic surgery (TORS) are increasingly employed to resect recurrent H&N cancers. The recently published international RECUT study,conducted through the Royal Marsden Hospital,has shown that use of TORS can achieve excellent 2 and 5-year overall survival of 71.8% and 49.8% in selected H&N recurrence patients. Unfortunately,a number of patients are not amenable to TORS,due to recurrent tumour stage,size,or location. As such,patients may require extensive surgery either via the neck (lingual release or transvervical/ pharyngotomy) or mandible (mandibulotomy),which may include complete or partial removal of the tongue (glossectomy) or voice box (laryngectomy) to achieve oncological control. Little data exists on the surgical outcomes of these often extensive,disfiguring,and debilitating surgeries. A limited number of retrospective series have demonstrated only modest short-term survival and swallowing results,with many patients remaining dependant on gastrostomy and tracheostomy many months post-operatively. We therefore have insufficient clinical data to help identify suitable surgical candidates pre-operatively,and can offer prospective patients limited counselling on the expected outcomes of their surgery. This study thus aims to both prospectively and retrospectively study the 2-5-year survival,quality of life,and functional outcomes in patients undergoing salvage surgeries for recurrent H&N cancer,and thus help provide better patient and clinician informed decision making. In addition to unanswered questions on post-operative survival and functional outcomes,it is not known if recurrent H&N SCC after curative radiotherapy reflects an innate radio-resistance of the primary tumour or tumour evolution of resistance throughout treatment. Understanding this could open new avenues for improving the efficacy of radical radiotherapy and tailor the surgical and systemic treatments to create individualised treatment regimens for patients with tumour relapse. Recent analysis of head and neck cancer specimens has suggested higher levels of intra-tumoural genetic heterogeneity may be associated with worse survival outcomes. In addition,several small studies have demonstrated the influence of clonal evolution in the both the carcinogenesis and progression of various H&N SCC tumours. However,the impact of molecular characteristics on treatment with radiotherapy and the subsequent disease recurrence has not been studied extensively at a molecular level. Although primary radiotherapy is associated with excellent oncological outcomes in all areas of the head and neck,we do not understand why certain patients are more likely to develop recurrent,residual and new primary following radiation treatment. There has been an explosion in genomics research in many cancers,but this remains an understudied area in head and neck cancer,particularly in the recurrent disease population. There are currently no genomic based treatments available to patients with head and neck cancer that may complement and improve survival following surgical salvage. This study begins to address the unmet need of patients who are failed by radical treatment and provides a starting point for more detailed investigations into the relationships between cancer genomics,recurrence,and patient outcomes.

Principal Investigator

Mr Stuart Winter

Contact us

Email: crndirectdeliveryteam@ouh.nhs.uk

IRAS number

319983