Correlation of PD-L1 Expression of Tumor Cells with Survival Outcomes after Radical Intensity-Modulated Radiation Therapy for Non-Metastatic Nasopharyngeal Carcinoma

Abstract

Purpose: We investigated if programmed death-ligand 1 (PD-L1) expression levels were prognostic of survival outcomes after intensity-modulated radiation therapy (IMRT) for non-metastatic nasopharyngeal carcinoma (NPC).

Methods and materials: 104 patients with non-metastatic NPC treated with radical IMRT were investigated for their PD-L1 expression by immunohistochemistry (IHC) which were correlated with survival endpoints including locoregional failure-free survival (LRFFS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and overall survival (OS).

Results: After a median follow-up of 7.6 years, 21 (20.2%), 19 (18.3%) and 31 (29.8%) patients suffered from locoregional failure, distant metastases and overall disease progression, respectively, and 31 (29.8%) patients died. Patients whose tumors had PD-L1 IHC 2+ (moderate to strong membrane staining in ≥ 25% of tumor cells) enjoyed longer LRFFS (5-year 100% vs. 74.4%, Hazard ratio [HR], 0.159, 95% confidence interval [CI], 0.021-0.988; P = 0.042) and marginally longer PFS (5-year 95.0% vs. 65.2%, HR, 0.351, 95% CI, 0.08-0.999, P = 0.067) compared to those whose tumors had PD-L1 IHC 0 (minimal membrane staining with PD-L1 in < 5% tumor cells or no staining with PD-L1) or 1+ (minimal to moderate membrane staining with PD-L1 in between 5-24% tumor cells). PD-L1 IHC 2+ was independently prognostic of both LRFFS (P = 0.014) and PFS (P = 0.045) in multivariable analyses. Only induction chemotherapy followed by concurrent chemoradiation was prognostic of DMFS (P = 0.003) and no prognostic factor for OS was identified.

Conclusion: PD-L1 expression levels correlated with LRRFS and PFS in non-metastatic NPC treated with radical IMRT. It may play a role in radiosensitivity for NPC, which should be further confirmed in prospective studies using immunotherapy together with IMRT.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Computed tomography image showing the beam orientation and isodose distribution of a 9-field intensity-modulated radiation therapy (IMRT) plan for a patient with non-metastatic nasopharyngeal carcinoma.

Fig 2. Immunohistochemical staining for PD-L1 in patients with non-metastastic nasopharyngeal carcinoma.

(A) A patient whose tumor was scored 1+ (weak to moderate membrane in about 5% of tumor cells) on immunohistochemical staining with PD-L1. (B) Another patient whose tumor was scored 2+ (moderate to strong membrane staining in more than 25% tumor cells) on immunohistochemical staining with PD-L1.

Fig 3. Micrograph showing the absence of immunohistochemical staining for PD-L1 in tumor-infiltrating lymphocytes.

(A) Low-power field. (B) High-power field despite strong immune-positivity to PD-L1 in the adjacent tumor cells.

Fig 4. Kaplan-Meier curves stratified by the patterns of immunohistochemical staining for PD-L1 (2+ vs 0 or 1+).

(A) Loco-regional failure-free survival. (B) Progression-free survival. (C) Distant metastasis failure-free survival. (D) Overall survival.

Fig 5. Receiver operating characteristics curve showing the performance of PD-L1 IHC 2+ as cut-off for locoregional progression of patients with non-metastatic NPC treated with radical intensity-modulated radiation with or without adjunct chemotherapy.

Fig 6. Receiver operating characteristics curve showing the performance of PD-L1 IHC 2+ as cut-off for overall progression of patients with non-metastatic NPC treated with radical intensity-modulated radiation with or without adjunct chemotherapy.