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

Lee VH, Lo AW, Leung CY, Shek WH, Kwong DL, Lam KO, Tong CC, Sze CK, Leung TW - PLoS ONE (2016)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong.

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.

No MeSH data available.


Related in: MedlinePlus

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.
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pone.0157969.g003: 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.

Mentions: Seventy-eight patients (75.0%) had no membrane staining with PD-L1 for their tumor cells. Four (3.8%) and 22 (21.2%) patients had IHC 1+ and IHC 2+ for their tumor cells respectively (Fig 2). The baseline clinical demographics between these 2 groups of patients were shown, without any statistically significant differences noted (Table 2). This observation suggested that PD-L1 expression might not be common in NPC tumor cells. However, once the gene was induced, expression level can be prominent and in significant proportion of the tumor. Therefore we grouped IHC 0 or 1+ as one group against IHC 2+ in our subsequent univariable and multivariable analyses as we believed that tumour cells with IHC 1+ (minimal to moderate membrane staining) behaved similarly as those with IHC 0. Interestingly, although there were many TILs associated with the tumor cells, PD-L1 was only expressed in these tumor-associated lymphoid cells in a scattered manner. None of the tumors had more than 10% of intimately associated lymphocytes with discernible PD-L1 staining and thus all TILs scored 0 for their PD-L1 expression (Fig 3).


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

Lee VH, Lo AW, Leung CY, Shek WH, Kwong DL, Lam KO, Tong CC, Sze CK, Leung TW - PLoS ONE (2016)

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.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4920427&req=5

pone.0157969.g003: 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.
Mentions: Seventy-eight patients (75.0%) had no membrane staining with PD-L1 for their tumor cells. Four (3.8%) and 22 (21.2%) patients had IHC 1+ and IHC 2+ for their tumor cells respectively (Fig 2). The baseline clinical demographics between these 2 groups of patients were shown, without any statistically significant differences noted (Table 2). This observation suggested that PD-L1 expression might not be common in NPC tumor cells. However, once the gene was induced, expression level can be prominent and in significant proportion of the tumor. Therefore we grouped IHC 0 or 1+ as one group against IHC 2+ in our subsequent univariable and multivariable analyses as we believed that tumour cells with IHC 1+ (minimal to moderate membrane staining) behaved similarly as those with IHC 0. Interestingly, although there were many TILs associated with the tumor cells, PD-L1 was only expressed in these tumor-associated lymphoid cells in a scattered manner. None of the tumors had more than 10% of intimately associated lymphocytes with discernible PD-L1 staining and thus all TILs scored 0 for their PD-L1 expression (Fig 3).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong.

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.

No MeSH data available.


Related in: MedlinePlus