PD-RAD sample analysis
Research type
Research Study
Full title
PD-RAD sample analysis: A translational study investigating immune changes in tumour and blood after radiotherapy in non-small cell lung cancer (NSCLC) using samples from the PD-RAD trial
IRAS ID
297993
Contact name
Tim Illidge
Contact email
Sponsor organisation
The University of Manchester
Duration of Study in the UK
2 years, 0 months, 0 days
Research summary
Radiotherapy (RT) has been shown to have both positive and negative immune effects on the tumour microenvironment. Whilst immune checkpoint inhibition has been shown to enhance the efficacy of RT in some murine models, it is hypothesised that those tumours with low numbers of infiltrating T-cells or large numbers of immunosuppressive myeloid cells might benefit from combining different immuno-oncology (IO) agents with RT. Thus it is important to determine what effects RT has on the tumour immune microenvironment and identify immune biomarkers which might predict which IO agent to combine with RT.
Furthermore, investigating systemic immune changes in peripheral blood and comparing them to those seen in the tumour may help in the identification of non-invasive biomarkers which are reflective of changes in the tumour.
The PD-RAD study was a translational study looking at upregulation of PD-L1 after radiotherapy in patients with NSCLC. Patients consented to donate a diagnostic biopsy and an additional biopsy during the second week of radiotherapy, along with regular blood samples. Tumour biopsies were formalin fixed and embedded in paraffin, PBMC and plasma were isolated from peripheral blood and tempus tubes were stored for future isolation of RNA from blood. During the study RNA was extracted from tumour biopsies and stored for future research.
We wish to continue analysis of these samples to look for RT induced changes and potential biomarkers of RT induced changes or response. The results from this study will increase our understanding of the immune response to radiotherapy, and guide future research studies.Lay Summary of Results
The PD-RAD study was set up to investigate immune changes in the tumour and blood of non small cell lung cancer patients receiving radiotherapy. The study closed early secondary to the COVID-19 pandemic. Paired lung tissue taken from tumour pre-treatment and in the second week of radiotherapy was collected from only three patients. Blood samples taken at baseline, week 2 of radiotherapy and end of radiotherapy was collected from only four patients. Analysis of tumour tissue showed that the expression of PD-L1 (an immune checkpoint ligand involved in regulating immune responses) increased in the tumour tissue in the patient who responded well to treatment, particularly on macrophages (an immune cell). The levels of circulating classical monocytes in the blood also appeared to increase during treatment and were highest in the patient who responded well to treatment. Due to the small number of patients recruited to the study it is difficult to draw definitive conclusions. However, results suggest PD-L1+ macrophages in the tumour and circulating classical monocytes are worthy of further exploration as possible biomarkers of response to radiotherapy in non small cell lung cancer.
Has the registry been updated to include summary results?: No
If yes - please enter the URL to summary results:
If no – why not?: The study is not on a registry. That is because this study was to perform further translational analysis on samples collected in the PD-RAD study. That study was originally approved under IRAS 180593 and was registered on a USCRN and clinicaltrials.gov database (NCT03258788), the PD-RAD study has ended and no further results from these samples will uploaded onto those sites.
Did you follow your dissemination plan submitted in the IRAS application form (Q A51)?: Yes
If yes, describe or provide URLs to disseminated materials: The results from the translational analysis of the PD-RAD study have been accepted for publication in the journal Oncology Research
https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fwww.techscience.com%252For%252Fonline%252Fdetail%252F25660%2FNBTI%2FpiLDAQ%2FAQ%2F3ae5d91c-4e27-4ce1-a78e-8b471ad80236%2F1%2FYP7ZUURFjY&data=05%7C02%7Cleedswest.rec%40hra.nhs.uk%7C3562d62fe3f447f287ae08de6274f4ca%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639056451626213141%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=jjq2u1DOM02nN2Cjtyt5LFVfqibyovcg%2BqWsdQBD3PE%3D&reserved=0They were also published in the PhD thesis of Dr Shuhui Cheng (University of Manchester)
https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fpure.manchester.ac.uk%252Fws%252Fportalfiles%252Fportal%252F270979819%252FFULL_TEXT.PDF%2FNBTI%2FpiLDAQ%2FAQ%2F3ae5d91c-4e27-4ce1-a78e-8b471ad80236%2F2%2FtDJT1V41yP&data=05%7C02%7Cleedswest.rec%40hra.nhs.uk%7C3562d62fe3f447f287ae08de6274f4ca%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639056451626249891%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=fCR4pK23vIFi9LYcMm0DpFE%2BGzpcpes0nUUHy4ZbIeU%3D&reserved=0
If pending, date when dissemination is expected:
If no, explain why you didn't follow it:
Have participants been informed of the results of the study?: No
If yes, describe and/or provide URLs to materials shared and how they were shared:
If pending, date when feedback is expected:
If no, explain why they haven't: The original IRAS application (180593) stated that the participants would not be informed of the results:
The expected survival rate of this patient group is poor, therefore patients may not survive long term in order to receive
the results of the study. However, patients who survive, or other patients with the same or similar conditions will have
access to the results of the study through their oncologist, once the results have been published in a scientific journal
and presented at relevant conferences.
Have you enabled sharing of study data with others?: No
If yes, describe or provide URLs to how it has been shared:
If no, explain why sharing hasn't been enabled: Patients did not consent for their data to be shared with others. However, we are happy to share anonymised data with others where appropriate. As this study was translational analysis of tissue from a clinical study there is no specific place where data can be automatically shared that is of relevance to the study/results obtained (e.g. not gene data). We are open to sharing results as appropriate though if requested. However, as there were only 4 patient samples which were analysed as part of the study the data is unlikely to be of significant interest to others.
Have you enabled sharing of tissue samples and associated data with others?: No
If yes, describe or provide a URL:
If no, explain why: The pre-treatment tissue samples were returned to the original hospitals at the end of the PD-RAD study. The on-treatment tissue samples are of less value without the pre-treatment counterparts. Additionally, there is very limited tissue remaining and tissue is available only from three patients. Patients only consented for tissue to be available for future research by University of Manchester staff.
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Yorkshire & The Humber - Leeds West Research Ethics Committee
REC reference
21/YH/0289
Date of REC Opinion
22 Nov 2021
REC opinion
Favourable Opinion