Investigating the Tumour Immune Response of Radiotherapy

Study Overview
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Brief Summary
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This study aims to investigate immune changes which occur before and following standard radiotherapy in a range of tumour types. We will collect tissue and blood samples before and after radiation treatment from participants across six cancer types: cervical, rectal, Head and Neck cancer, nodal non-Hodgkin lymphoma, cutaneous lymphoma and cutaneous squamous cell carcinoma/ basal cell carcinoma.

Detailed Description
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The purpose of this prospective, non-CTIMP, translational study is to assess the feasibility of achieving paired biopsies for immune analysis in patients across six different cancer types: cervical, rectal, Head and Neck cancer, nodal non-Hodgkin lymphoma, cutaneous lymphoma and cutaneous squamous cell carcinoma/ basal cell carcinoma. All participants will have a minimum of 1 mandatory biopsy (during/post-radiotherapy [irradiated site]) and the potential to have a pre-treatment biopsy if the archival biopsy does not meet the suitability criteria. Matched blood samples will be collected from participants at baseline, during/post-radiotherapy, and if radiotherapy continues after the on-treatment biopsy is taken, an additional end of treatment blood sample will be collected. We aim to recruit 10-20 participants per study arm, with the option to increase numbers in study arms that are recruiting well - a maximum of 120 patients in total will be recruited to the study.

Official Title
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Investigating the Tumour Immune Response of Radiotherapy

Conditions
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Cancer

Intervention / Treatment
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* Procedure: Biopsy and blood sample collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed cancer, Stage I-IV, in one of the following: Cervical, rectal, nodal Non-Hodgkin lymphoma, cutaneous lymphoma, Head & neck cancer Diagnostic/pre-treatment biopsy confirmed suitable for translational research * Performance status - ECOG 0-2 (Refer to appendix 1), ECOG 3 allowed for arm F (unrelated to underlying cancer) as this group of patients often have ECOG 3 due to age and comorbidities. Age ≥ 18; no upper age limit. Participant considered suitable for radiotherapy Before participant registration, written informed consent must be given according to GCP and national regulations. *Pre-treatment biopsy must be from the gross tumour volume within the planned radiation field and must also: Have been formalin fixed for >12h and <72h Have tumour tissue and morphology confirmed by H&E staining Contain sufficient tumour cells (approximately 100) Exclusion Criteria: Participants deemed unsuitable for a biopsy (during or following radiotherapy) in the opinion of the treating oncologist. Participants who have received chemotherapy within 28 days of starting radiotherapy. Participants with intercurrent or past history of hepatitis B, C or human immunodeficiency virus infection if known. A negative test result for hepatitis B, C and HIV infection is required prior to inclusion in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cervical cancer<br>Cervical cancer patients receiving standard of care radiotherapy | Procedure: Biopsy and blood sample collection<br>* A pre-treatment diagnostic biopsy sample plus 1 mandatory biopsy (during/post-radiotherapy [irradiated site]) will be collected from each participant. Matched blood samples will be collected from participants at baseline, during/post-radiotherapy, and if radiotherapy continues after the on-treatment biopsy is taken, an additional end of treatment blood sample will be collected.<br>|
| Rectal cancer<br>Rectal cancer patients receiving standard of care radiotherapy | Procedure: Biopsy and blood sample collection<br>* A pre-treatment diagnostic biopsy sample plus 1 mandatory biopsy (during/post-radiotherapy [irradiated site]) will be collected from each participant. Matched blood samples will be collected from participants at baseline, during/post-radiotherapy, and if radiotherapy continues after the on-treatment biopsy is taken, an additional end of treatment blood sample will be collected.<br>|
| Head and neck cancer<br>Head and neck cancer patients receiving standard of care radiotherapy | Procedure: Biopsy and blood sample collection<br>* A pre-treatment diagnostic biopsy sample plus 1 mandatory biopsy (during/post-radiotherapy [irradiated site]) will be collected from each participant. Matched blood samples will be collected from participants at baseline, during/post-radiotherapy, and if radiotherapy continues after the on-treatment biopsy is taken, an additional end of treatment blood sample will be collected.<br>|
| nodal non-Hodgkin lymphoma<br>Patients with nodal NHL receiving standard of care radiotherapy | Procedure: Biopsy and blood sample collection<br>* A pre-treatment diagnostic biopsy sample plus 1 mandatory biopsy (during/post-radiotherapy [irradiated site]) will be collected from each participant. Matched blood samples will be collected from participants at baseline, during/post-radiotherapy, and if radiotherapy continues after the on-treatment biopsy is taken, an additional end of treatment blood sample will be collected.<br>|
| cutaneous lymphoma<br>Patients with cutaneous lymphoma receiving standard of care radiotherapy | Procedure: Biopsy and blood sample collection<br>* A pre-treatment diagnostic biopsy sample plus 1 mandatory biopsy (during/post-radiotherapy [irradiated site]) will be collected from each participant. Matched blood samples will be collected from participants at baseline, during/post-radiotherapy, and if radiotherapy continues after the on-treatment biopsy is taken, an additional end of treatment blood sample will be collected.<br>|
| cutaneous squamous cell carcinoma and basal cell carcinoma<br>Patients with cSCC and cBCC receiving standard of care radiotherapy | Procedure: Biopsy and blood sample collection<br>* A pre-treatment diagnostic biopsy sample plus 1 mandatory biopsy (during/post-radiotherapy [irradiated site]) will be collected from each participant. Matched blood samples will be collected from participants at baseline, during/post-radiotherapy, and if radiotherapy continues after the on-treatment biopsy is taken, an additional end of treatment blood sample will be collected.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of obtaining paired biopsy samples | To assess the feasibility of obtaining tumour samples pre-radiotherapy (diagnostic or fresh) and a second biopsy during or immediately after radiotherapy, or a surgical sample, from patients undergoing standard of care RT. | Within 6-7 weeks of starting radiotherapy | 
| Collection of matched blood samples | To obtain additional matched blood samples pre-radiotherapy, during or post-radiotherapy, and at the end of radiotherapy for assessment of immune status of peripheral blood in comparison to the intratumoural microenvironment. | Within 6-7 weeks of starting radiotherapy |