Exploratory Study of Clonal Evolution in Cancer for Patients Undergoing Transoral Robotic Surgery for Radiation Exposed Residual/reCurrent Tumours of the Upper Aerodigestive Tract

Official title

RECUT PLUS: Exploratory Study of Clonal Evolution in Cancer for Patients Undergoing Transoral Robotic Surgery for Radiation Exposed Residual/reCurrent Tumours of the Upper Aerodigestive Tract

Overview

Radical radiotherapy for head and neck squamous cell cancer (HNSCC) can be administered to primary disease with curative intent. Residual disease, recurrence or further tumours may subsequently occur in this irradiated field. It is unknown whether these cancers reflect primary resistance or represent the evolution of resistance on treatment. Understanding this could allow stratification of patients to more effective primary treatments, such as transoral robotic surgery, or help tailor systemic therapies for these cancers in previously irradiated fields. RECUT+ is an exploratory molecular analysis study to assess the selective impact of radiation therapy on HNSCC. Participants will be recruited from the Royal Marsden Hospital (RMH), Chelsea, a tertiary referral H\&N cancer unit in London, UK, specialising in transoral robotic surgery. Retrospective participants will be identified from previous Head and neck MDT lists at RMH. Prospective participants will be screened for by the RECUT+ team during the weekly H\&N MDT meetings at the Royal Marsden Hospital (RMH). Blood/saliva samples will be collected pre operatively (prospective participants) and post operatively (retrospective and prospective participants) for germline and circulating tumour DNA analysis. Biopsy samples from the original cancer and resected specimens from the post radiotherapy residual/recurrent/new primary disease will undergo molecular analysis to assess for any selective impact of radiotherapy on these further tumours.

Interventions

• Other DNA Analysis
  Molecular analysis includes DNA analysis on the blood/saliva and on the cancer specimens from the biopsies \& subsequent resections

Primary outcome measures

• Identification of resistant sub clones in post radiotherapy tumour samples [Time frame: Within 1 year of surgery & receipt of blood/saliva and tissue samples]

Secondary outcome measures (4)

• Identification of differences in sub clonal architecture of H&N SCC before and after radiotherapy. [Time frame: Within 1 year of surgery & receipt of blood/saliva and tissue samples]
• Identification of differences in mutational signatures between the primary disease and resistant sub clones. [Time frame: Within 1 year of surgery & receipt of blood/saliva and tissue samples]
• Identification of loss of heterozygosity at the HLA loci in resistant sub clones [Time frame: Within 1 year of surgery & receipt of blood/saliva and tissue samples]
• Disease-specific and overall survival at 5 years related to identified molecular characteristics. [Time frame: 5 years following the date of surgery of the final participant recruited.]

Eligibility criteria

Inclusion criteria

• Aged over 18
• Previous H\&N cancer treated with radiotherapy.
• Undergoing TORS as part of their management for residual, recurrent or new primary H\&N cancer.

Exclusion criteria

• Where TORS is used in a diagnostic setting only
• Nasopharyngeal and thyroid head and neck cancers
• Where no tissue specimens are available from the recurrent/residual/secondary tumour for the retrospective cohort

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United Kingdom · 1 center

• The Royal Marsden Hospital — London

Identifiers

NCT: NCT04671940 · CCR 5263

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗