Radiotherapy Scheme Effect on PD-L1 Expression for Locally Advanced Rectal Cancer.
Jihane BoustaniValentin DerangèreAurélie BertautOlivier AdoteviVéronique MorgandCéline Charon-BarraFrançois GhiringhelliCéline MirjoletPublished in: Cells (2020)
In locally advanced rectal cancer, radiotherapy (RT) followed by surgery have improved locoregional control, but distant recurrences remain frequent. Although checkpoint inhibitors have demonstrated objective response in several cancers, the clinical benefit of PD-1/PD-L1 blockade remains uncertain in rectal cancer. We collected data from biopsies and surgical specimens in 74 patients. The main objective was to evaluate the impact of neoadjuvant RT and fractionation on PD-L1 expression. Secondary objectives were to study the relation between PD-L1 expression and tumor regression grade (TRG), progression-free survival (PFS), overall survival (OS), and CD8 TILs infiltration. Median rates of cells expressing PD-L1 pre- and post-RT were 0.15 (range, 0-17) and 0.5 (range, 0-27.5), respectively (p = 0.0005). There was no effect of RT fractionation on PD-L1+ cell rates. We found no relation between CD8+ TILs infiltration and PD-L1 expression and no difference between high-PD-L1 or low-PD-L1 expression and TRG. High-to-high PD-L1 expression profile had none significant higher OS and PFS compared to all other groups (p = 0.06). Median OS and PFS were higher in biopsies with >0.08 PD-L1+ cells. High-to-high PD-L1 profile and ypT0-2 were significantly associated with higher OS and PFS. This study did not show the differential induction of PD-L1 expression according to fractionation.
Keyphrases
- locally advanced
- rectal cancer
- neoadjuvant chemotherapy
- squamous cell carcinoma
- free survival
- phase ii study
- radiation therapy
- induced apoptosis
- early stage
- minimally invasive
- lymph node
- end stage renal disease
- dna damage
- chronic kidney disease
- newly diagnosed
- coronary artery disease
- prognostic factors
- atrial fibrillation
- ejection fraction
- acute coronary syndrome
- signaling pathway
- big data
- open label
- study protocol
- patient reported
- pi k akt
- percutaneous coronary intervention