Impact of PD-L1 Scores and Changes on Clinical Outcome in Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy

Huemer, Florian; Klieser, E.; Neureiter, Daniel; Schlintl, Verena; Rinnerthaler, Gabriel; Pagès, Franck; Kirilovsky, Amos; Sissy, Carine El; Iglseder, W.; Singhartinger, Franz; Jäger, Tarkan; Dinnewitzer, Adam; Zaborsky, Nadja; Steiner, Markus J.; Greil, Richard; Weiß, Lukas

doi:10.3390/jcm9092775

Cited by 10 publications

(13 citation statements)

References 42 publications

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“…The role of CPS predicting the efficiency of immunotherapy for the locally advanced rectal cancer should be elucidated in the future. In the study including 72 patients with rectal cancer after neoCRT, low PD-L1 TPS prior to neoCRT was associated with inferior survival (HR 0.29, 95% CI: 0.11-0.76, p = 0.01) [13], which was similar to our study. Colorectal cancers with microsatellite instability-high have favorable response to the anti-PD-1 immunotherapy [20].…”

Section: Discussionsupporting

confidence: 89%

“…Firstly, high surgical volume is associated with clinical outcomes for rectal cancer [ 32 ]. The inclusion period of locally advanced rectal cancer patients in our study was 6 years (2012–2018), which was comparable to other studies [ 12 , 13 ]. Secondly, all the included LARC patients were treated at a single center and no patients were treated by PD-1/PD-L1 antibodies, leaving the prediction value of PD-L1 scores uncertain at this moment.…”

Section: Discussionsupporting

confidence: 86%

“…Combined positive score (CPS) determined by PD-L1 staining has been identified for predicting anti-PD1 efficacy in head and neck squamous cell carcinoma and gastric cancer [ 10 , 11 ]. To date, the data of PD-L1 scores including tumor proportion score (TPS), combined positive score (CPS), and immune cell score (IC) for LARC is limited [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Programmed death-ligand 1 and mammalian target of rapamycin signaling pathway in locally advanced rectal cancer

et al. 2022

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Purpose To evaluate the role of programmed death-ligand 1 (PD-L1) and mammalian target of rapamycin (mTOR) signaling pathway in locally advanced rectal cancer (LARC). Methods Between February 2012 and February 2018, 103 patients with LARC treated by neoadjuvant chemoradiotherapy (neoCRT) and total mesorectal excision (TME) were included. PD-L1, mTOR and p-mTOR of pair-matched pre-neoCRT biopsies and post-neoCRT surgical tissue were evaluated by immunohistochemistry. Results The mean combined positive score (CPS), tumor proportion score (TPS) and immune cell score (IC) of pre-neoCRT were 2.24 (0–70), 1.87 (0–70) and 0.67 (0–10), respectively. The mean CPS, TPS and IC of post-neoCRT were 2.19 (0–80), 1.38 (0–80) and 1.60 (0–20), respectively. Significant difference was observed in terms of IC between pre-neoCRT and post-neoCRT (p = 0.010). The 5-year disease-free survival (DFS) rate of the whole group was 62.4%. Multivariate analysis by Cox model indicated that pre-neoCRT TPS [hazard ratio (HR) 1.052, 95% confidence interval (CI) 1.020–1.086, p = 0.001] and post-neoCRT CPS (HR 0.733, 95% CI 0.555–0.967, p = 0.028) were associated with DFS. In the 89 patients without pathological complete response, p-mTOR and IC were upregulated after neoCRT. Conclusions For patients with LARC treated by neoCRT and TME, p-mTOR and IC were upregulated after neoCRT. Pre-neoCRT TPS and post-neoCRT CPS were independent prognostic predictors of DFS.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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Programmed death-ligand 1 and mammalian target of rapamycin signaling pathway in locally advanced rectal cancer

et al. 2022

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“…H&E sections were also reviewed for the presence of tumors. Each section was evaluated by 2 experienced pathologists according to the CPS (PD-L1-stained tumor cells and immune cells/total number of viable tumor cells × 100) in rectal biopsy specimens prior to neoadjuvant chemoradiotherapy [ 9 ].…”

Section: Methodsmentioning

confidence: 99%

Glasgow prognostic score and combined positive score for locally advanced rectal cancer

et al. 2022

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Purpose This study was performed to investigate the association of Glasgow prognostic score (GPS), combined positive score (CPS), and clinicopathological characteristics of locally advanced rectal cancer. Methods Between February 2012 and February 2018, 103 patients with locally advanced rectal cancer treated by neoadjuvant chemoradiotherapy and total mesorectal excision (TME) were retrospectively evaluated. Results According to the classification of the GPS, 85 (82.5%), 13 (12.6%), and 5 patients (4.9%) were classified as a score of 0, 1, and 2, respectively. Patients were classified into the GPS-low group (GPS of 0, n = 85) and GPS-high group (GPS of 1 or 2, n = 18) with an area under the curve of 0.582 for overall survival (OS). The mean programmed death-ligand 1 (PD-L1) CPS of the whole group was 2.24 (range, 0–70). The PD-L1 CPS of the GPS-high group was higher than the GPS-low group (P < 0.001). Multivariate analysis by Cox proportional hazards model indicated that GPS was associated with OS and disease-free survival (DFS). Furthermore, PD-L1 CPS was associated with DFS (hazard ratio, 1.050; 95% confidence interval, 1.017–1.083; P = 0.003). Conclusion Elevated GPS was related to the PD-L1 CPS. GPS and PD-L1 CPS were associated with the prognosis of locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by TME.

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“…Furthermore, understanding the tumor microenvironment formed by interactions among tumor cells, immune system, endothelial cells and cytokines is essential to determine possible therapeutic strategies and prognostic evaluation [ 26 ]. The expression of programmed cell death ligand-1 (PD-L1) in rectal cancer is still poorly studied, but some authors have shown that radiotherapy can stimulate its expression, although its prognostic/predictive impact is still unknown [ 27 , 28 , 29 , 30 ]. The transforming growth factor-β (TGF-β) is one of the numerous cytokines found in the tumor microenvironment and plays an important role in the tumor progression, increased angiogenesis and suppression of the immune response [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular and Dynamic Evaluation of Proteins Related to Resistance to Neoadjuvant Treatment with Chemoradiotherapy in Circulating Tumor Cells of Patients with Locally Advanced Rectal Cancer

Silva

Abdallah

Flores

et al. 2021

Cells

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The heterogeneity of response to neoadjuvant chemoradiotherapy (NCRT) is still a challenge in locally advanced rectal cancer (LARC). The evaluation of thymidylate synthase (TYMS) and RAD23 homolog B (RAD23B) expression in circulating tumor cells (CTCs) provides complementary clinical information. CTCs were prospectively evaluated in 166 blood samples (63 patients) with LARC undergoing NCRT. The primary objective was to verify if the absence of RAD23B/TYMS in CTCs would correlate with pathological complete response (pCR). Secondary objectives were to correlate CTC kinetics before (C1)/after NCRT (C2), in addition to the expression of transforming growth factor-β receptor I (TGF-βRI) with survival rates. CTCs were isolated by ISET and evaluated by immunocytochemistry (protein expression). At C1, RAD23B was detected in 54.1% of patients with no pCR and its absence in 91.7% of patients with pCR (p = 0.014); TYMS− was observed in 90% of patients with pCR and TYMS+ in 51.7% without pCR (p = 0.057). Patients with CTC2 > CTC1 had worse disease-free survival (DFS) (p = 0.00025) and overall survival (OS) (p = 0.0036) compared with those with CTC2 ≤ CTC1. TGF-βRI expression in any time correlated with worse DFS (p = 0.059). To conclude, RAD23B/TYMS and CTC kinetics may facilitate the personalized treatment of LARC.

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Impact of PD-L1 Scores and Changes on Clinical Outcome in Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy

Cited by 10 publications

References 42 publications

Programmed death-ligand 1 and mammalian target of rapamycin signaling pathway in locally advanced rectal cancer

Programmed death-ligand 1 and mammalian target of rapamycin signaling pathway in locally advanced rectal cancer

Glasgow prognostic score and combined positive score for locally advanced rectal cancer

Molecular and Dynamic Evaluation of Proteins Related to Resistance to Neoadjuvant Treatment with Chemoradiotherapy in Circulating Tumor Cells of Patients with Locally Advanced Rectal Cancer

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