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

• Published in: PloS one 2016-06, Vol.11 (6), p.e0157969-e0157969
• Main Authors: Lee, Victor H F, Lo, Anthony W I, Leung, Chun-Yin, Shek, Wai-Hung, Kwong, Dora L W, Lam, Ka-On, Tong, Chi-Chung, Sze, Chun-Kin, Leung, To-Wai
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Analysis of Variance; Antigens; Apoptosis; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Cancer metastasis; Cancer therapies; Carcinoma - diagnosis; Carcinoma - metabolism; Carcinoma - mortality; Carcinoma - radiotherapy; Cell survival; Chemoradiotherapy; Chemotherapy; Combined Modality Therapy; Confidence intervals; Correlation; Development and progression; Drug therapy; Fatalities; Female; Gene Expression; Head & neck cancer; Hospitals; Humans; Immunohistochemistry; Immunotherapy; Kaplan-Meier Estimate; Ligands; Lung cancer; Lymphocytes; Male; Medical prognosis; Medicine; Medicine and Health Sciences; Metastases; Metastasis; Middle Aged; Nasopharyngeal cancer; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms - diagnosis; Nasopharyngeal Neoplasms - metabolism; Nasopharyngeal Neoplasms - mortality; Nasopharyngeal Neoplasms - radiotherapy; Neoplasm Staging; Oncology; Patients; PD-L1 protein; Prognosis; Radiation; Radiation therapy; Radiosensitivity; Radiotherapy, Intensity-Modulated; Research and Analysis Methods; Review boards; ROC Curve; Staining; Survival; Throat cancer; Tomography, X-Ray Computed; Treatment Outcome; Tumor cells; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0157969

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). 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). 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. 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.