The relationship of vascular endothelial growth factor and osteopontin expression with 3-year progression-free survival of locally advanced nasopharyngeal cancer patients treated with platinum- based chemoradiation

Introduction The incidence of nasopharyngeal cancer (NPC) is high, with new cases accounting for 5.2% of all malignancies in Indonesia. Most cases are detected at an advanced stage, and recurrences are common. Vascular endothelial growth factor (VEGF) and osteopontin (OPN) are important markers in tumorigenesis that serve as prognostic predictors. This study aims to determine the correlation of VEGF and OPN expression with 3-year progression-free survival (PFS). Material and methods This retrospective cohort study analyzed 155 patients with locally advanced NPC. Data were obtained from medical records between 2015 and 2017. The locally advanced sample of this disease that met the inclusion criteria was stained with H&E before being prepared in a paraffin block. Furthermore, the immunohistochemistry staining results for VEGF and OPN were observed with ImageJ 1.50i and calculated semi-quantitatively using the histoscore. Results The 3-year PFS obtained was 39%, with a median of 23 months. Vascular endothelial growth factor expression was detected in 113 of 155 samples (72.9%), while positive OPN expression was discovered in 99 of 155 samples (63.8%). There was a correlation between VEGF (p = 0.747) and OPN expression (p = 0.584) and 3-year PFS. Positive VEGF and OPN expression in the subgroup of patients with stage IVB and N3 tumors was related to improved 3-year PFS (p < 0.05). This was similar to the positive VEGF expression in the subgroup of patients receiving neoadjuvant chemotherapy (p < 0.05). Conclusions Vascular endothelial growth factor and OPN remained potential prognostic predictors in NPC. Patients with positive VEGF and OPN expression in N3, IVB, and neoadjuvant treatment had significantly improved 3-year PFS.

[1]  C. Irawan,et al.  Factors that Influence 2-Year Progression-Free Survival Among Head and Neck Cancer Patients , 2021, Journal of Epidemiology and Global Health.

[2]  N. Al-Rajhi,et al.  Prognostic markers compared to CD3+TIL in locally advanced nasopharyngeal carcinoma , 2021, Medicine.

[3]  Qinxiu Zhang,et al.  Prognostic value of Ki-67 in nasopharyngeal carcinoma: a meta-analysis , 2021, Bioscience reports.

[4]  Liangfang Shen,et al.  The Current Role of Adjuvant Chemotherapy in Locally Advanced Nasopharyngeal Carcinoma , 2021, Frontiers in Oncology.

[5]  Fifi Dwijayanti,et al.  The Five-Year Survival Rate of Patients with Nasopharyngeal Carcinoma Based on Tumor Response after Receiving Neoadjuvant Chemotherapy, Followed by Chemoradiation, in Indonesia: A Retrospective Study , 2020, Oncology.

[6]  Zhimin Ye,et al.  Survival without concurrent chemotherapy for locoregionally advanced nasopharyngeal carcinoma treated with induction chemotherapy plus intensity-modulated radiotherapy , 2019, Medicine.

[7]  E. Mangantig,et al.  Nasopharyngeal Carcinoma (NPC) Risk Factors: A Systematic Review and Meta-Analysis of the Association with Lifestyle, Diets, Socioeconomic and Sociodemographic in Asian Region , 2019, Asian Pacific journal of cancer prevention : APJCP.

[8]  Zhaolong Qiu,et al.  The effectiveness of intensity-modulated radiation therapy versus 2D-RT for the treatment of nasopharyngeal carcinoma: A systematic review and meta-analysis , 2019, PloS one.

[9]  K. Lam,et al.  Management of Nasopharyngeal Carcinoma: Is Adjuvant Therapy Needed? , 2018, Journal of oncology practice.

[10]  A. Jemal,et al.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries , 2018, CA: a cancer journal for clinicians.

[11]  K. Xue,et al.  Clinicopathologic and prognostic significance of VEGF, JAK2 and STAT3 in patients with nasopharyngeal carcinoma , 2018, Cancer Cell International.

[12]  W. Gu,et al.  Evaluation of Detection Methods and Values of Circulating Vascular Endothelial Growth Factor in Lung Cancer , 2018, Journal of Cancer.

[13]  Ying Sun,et al.  Induction Chemotherapy plus Concurrent Chemoradiotherapy in Endemic Nasopharyngeal Carcinoma: Individual Patient Data Pooled Analysis of Four Randomized Trials , 2018, Clinical Cancer Research.

[14]  Yesheng Wei,et al.  Overexpression of osteopontin promotes cell proliferation and migration in human nasopharyngeal carcinoma and is associated with poor prognosis , 2018, European Archives of Oto-Rhino-Laryngology.

[15]  W. Cho,et al.  Cancer and Aging - the Inflammatory Connection , 2017, Aging and disease.

[16]  Supriyati,et al.  The role of Indonesian patients’ health behaviors in delaying the diagnosis of nasopharyngeal carcinoma , 2017, BMC Public Health.

[17]  Ying Sun,et al.  Tumor response to neoadjuvant chemotherapy predicts long‐term survival outcomes in patients with locoregionally advanced nasopharyngeal carcinoma: A secondary analysis of a randomized phase 3 clinical trial , 2017, Cancer.

[18]  Ying Sun,et al.  Advanced-Stage Nasopharyngeal Carcinoma: Restaging System after Neoadjuvant Chemotherapy on the Basis of MR Imaging Determines Survival. , 2017, Radiology.

[19]  Likun Chen,et al.  Osteopontin is a useful predictor of bone metastasis and survival in patients with locally advanced nasopharyngeal carcinoma , 2015, International journal of cancer.

[20]  S. Liang,et al.  Potential surrogate endpoints for overall survival in locoregionally advanced nasopharyngeal carcinoma: an analysis of a phase III randomized trial , 2015, Scientific Reports.

[21]  Ying Sun,et al.  Efficacy of the Additional Neoadjuvant Chemotherapy to Concurrent Chemoradiotherapy for Patients with Locoregionally Advanced Nasopharyngeal Carcinoma: a Bayesian Network Meta-analysis of Randomized Controlled Trials , 2015, Journal of Cancer.

[22]  Suwartono Dasar-Dasar Metodologi Penelitian , 2014 .

[23]  R. Samant,et al.  Role of osteopontin in the pathophysiology of cancer. , 2014, Matrix biology : journal of the International Society for Matrix Biology.

[24]  Hodgkin Lymphoma NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines , 2014 .

[25]  Jianji Pan,et al.  Prognostic significance of expression of cyclooxygenase‐2, vascular endothelial growth factor, and epidermal growth factor receptor in nasopharyngeal carcinoma , 2013, Head & neck.

[26]  Jaap M Middeldorp,et al.  Chinese a Nti鄄 Cancer a Ssociation , 2022 .

[27]  C. Kang,et al.  Prognostic significance of expression of vegf and cox‐2 in nasopharyngeal carcinoma and its association with expression of C‐erbB2 and EGFR , 2011, Journal of surgical oncology.

[28]  G. Leitão,et al.  Plasma osteopontin levels in patients with head and neck cancer undergoing chemoradiotherapy. , 2009, Archives of otolaryngology--head & neck surgery.

[29]  S. Haryana,et al.  Elevation of vascular endothelial growth factor in Indonesian advanced stage nasopharyngeal carcinoma. , 2009, The Kobe journal of medical sciences.

[30]  P. Balaram,et al.  Expression of VEGF as prognosticator in primary nasopharyngeal cancer and its relation to EBV status. , 2006, Virus research.

[31]  T. Mok,et al.  Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. , 2005, Journal of the National Cancer Institute.

[32]  S. Leung,et al.  Treatment results for nasopharyngeal carcinoma in the modern era: the Hong Kong experience. , 2005, International journal of radiation oncology, biology, physics.

[33]  Jun Ma,et al.  Long-term survival after cisplatin-based induction chemotherapy and radiotherapy for nasopharyngeal carcinoma: A pooled data analysis of two phase III trials. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  Xiang Guo,et al.  [Clinical value of vascular endothelial growth factor detection in forecasting distant metastasis risk of nasopharyngeal carcinoma]. , 2004, Ai zheng = Aizheng = Chinese journal of cancer.

[35]  C. J. Chen,et al.  Occupational exposure to wood, formaldehyde, and solvents and risk of nasopharyngeal carcinoma. , 2001, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[36]  Y. Xiang,et al.  Non‐dietary risk factors for nasopharyngeal carcinoma in Shanghai, China , 2000, International journal of cancer.

[37]  B. McKnight,et al.  Descriptive epidemiology and survival analysis of nasopharyngeal carcinoma in the united states , 1992, International journal of cancer.

[38]  D M Parkin,et al.  Cancer Incidence in Five Continents. Comparability and quality of data. , 1992, IARC scientific publications.

[39]  R. Prentice Surrogate endpoints in clinical trials: definition and operational criteria. , 1989, Statistics in medicine.

[40]  Y. Zong,et al.  Histopathologic types and incidence of malignant nasopharyngeal tumors in Zhongshan County. , 1983, Chinese medical journal.