Abstract
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.
Highlights
The standard treatment of locally advanced rectal cancer (LARC) is neoadjuvant radiotherapy (RT) followed by total mesorectal excision (TME) [1,2]
Since the PD-1/PD-L1 interaction represents one of the major mechanisms of cancer immune escape, which leads to treatment failure, the evaluation of PD-L1 expression in response to RT is important for the establishment of the optimal combination strategy
In patients with locally advanced rectal cancer treated with neoadjuvant radiotherapy, we demonstrated an increase in PD-L1 expression after radiotherapy, but we did not find a differential induction of PD-L1 expression according to fractionation
Summary
The standard treatment of locally advanced rectal cancer (LARC) is neoadjuvant radiotherapy (RT) followed by total mesorectal excision (TME) [1,2]. RT is delivered via either a long-course scheme (i.e., five fractions of 1.8–2 Gy per week for five weeks) or a short-course scheme (i.e., five fractions of 5 Gy in one week (5 × 5 Gy)). Fractionated long-course RT in combination with chemotherapy followed by surgery after 6–8 weeks has been the predominant treatment [3,4], while short-course RT and surgery within the following week has been commonly used in northern. Short-course RT with a delayed surgery has been found to improve tumor regression and to decrease postoperative complications compared to immediate surgery [5]. Preoperative RT can lead to tumor downstaging and to significant reduction of local recurrence, without improving overall survival [3,4,6]. The complete histological response (pCR) rates vary widely among series between 10% and 30% [7]
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