For patients with locally advanced non-small cell lung cancer (NSCLC), the standard treatment protocol involves chemoradiotherapy (CRT), followed by anti-PD-L1 therapy. However, a growing body of preclinical and clinical research has shown that chemotherapy and radiotherapy might further increase the expression of PD-L1, potentially impacting the effectiveness of subsequent immunotherapy. Currently, multiple clinical studies are investigating if combining PD-L1 therapy with chemoradiotherapy in patients with NSCLC improves the overall treatment efficacy.
Putting PET to work
Assessing PD-L1 expression dynamics during treatment is difficult. Traditional methods involve longitudinal biopsies, which are invasive, challenging, and often don’t capture the full picture of tumor PD-L1 expression.
To overcome these limitations, researchers from Imaging and Biomarkers at Cancer Center Amsterdam employed the Philips Vereos en Philips Ingenuity whole body PET-scanners to visualize early changes in PD-L1 expression across all tumor sites and relevant non-malignant tissues. This groundbreaking approach allowed for a non-invasive and comprehensive assessment of PD-L1 dynamics before and during chemoradiotherapy in patients with NSCLC.
PET imaging provides unexpected answers
The team hypothesized that PD-L1 expression would initially rise as a defense mechanism during the early phases of chemoradiotherapy before declining due to cancer cell demise.
However, the results did not support this expectation.
“While there was a visible enhancement in the tumor tracer signal in the early treatment phase in the 2 mg cohort, the 22.5 mg cohort either stayed stable on-treatment or even decreased,” says Hanneke Pouw, a Technical Physician and PhD candidate. The researchers speculated the results could potentially be saturation effects obscuring small differences, or limitations in the study's design.
They also noted changes in healthy tissue uptake of the PD-L1 tracer. “We found it interesting that most patients had decreased uptake in the spleen, while there was a trend for increase in the bone marrow,” says Idris Bahce, Associate Professor in the Multidisciplinary Thoracic Oncology Research Group.
This observation hints that PD-L1 positive immune cells are shifting in response to chemoradiotherapy. “The observed combination of decreased tracer uptake in the spleen and increased uptake in the bone marrow might reflect leukocyte death, followed by hematopoiesis and lymphocyte migration” adds Idris.
From first baseline to future
These preliminary findings, albeit from a small sample size of 11 patients, warrant further investigation with larger trials and potentially utilizing PET tracers with faster kinetics to further investigate PD-L1 dynamics during chemoradiotherapy.
For more information, contact Idris Bahce, or read the scientific publication:
Pouw, J.E.E., et al. (2024) First exploration of the ontreatment changes in tumor and organ uptake of a radiolabeled anti PD-L1 antibody during chemoradiotherapy in patients with non-small cell lung cancer using whole body PET. Journal for ImmunoTherapy of Cancer;12:e007659. https://jitc.bmj.com/content/12/2/e007659
Funding
Funding for this clinical study was provided by AstraZeneca, which also provided in-kind support. JEEP is collaborator of the Immune-Image project, which has received funding from the EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking.
Researchers involved at Cancer Center Amsterdam
Hanneke Pouw
Sayed Hashemi
Marc Huisman
Jessica Wijngaarden
Maarten Slebe
Daniela Oprea-Lager
Gerben Zwezerijnen
Danielle Vugts
Ezgi Ulas
Tanja de Gruijl
Teodora Radonic
Suresh Senan
Willemien Menke-van der Houven van Oordt
Idris Bahce
Follow the Lung Cancer Patient Research Group Amsterdam UMC on LinkedIn, or check out clinical trial information at Amsterdam UMC regarding lung oncology here.
Text by Laura Roy
This article was created for Cancer Center Amsterdam.
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