Background: Locally advanced nasopharyngeal carcinoma (LA-NPC) is a relatively rare disease in the west but more common in East Asia and areas of the Middle East like Saudi Arabia. Despite the advances in radiation therapy techniques, some patients relapse after treatment. In the coming era of cancer immunotherapy, prognostic factors for LA-NPC need to be further defined using immune-relevant markers. Several markers are available; however, the most robust and accessible/affordable marker is not well-defined. Methods: Retrospectively, tumor-infiltrating lymphocytes (TIL), their subsets as well as tumoral PD-L1 expression were analyzed in tumor tissues from 63 LA-NPC patients treated with platinum-based concurrent chemo-radiotherapy (CCRT) in addition to 20 cases with metastatic (MET) disease. Immunostaining was done using a validated and fully automated system. Scoring was done by two independent pathologists and results were compared. Results: There was no statistical difference between LA-NPC and MET disease in terms of CD3+, CD8+ TIL infiltration, or tumoral PD-L1 expression. In LA-NPC, low CD3+ TIL infiltration highly correlated with shorter disease-free survival (DFS, HR = 8.5, p = < 0.001) and overall survival (OS, HR = 13, p = 0.015) with substantial agreement between scoring pathologists. A similar correlation was found between low CD8+ TIL and survival. Correlation of total TIL was significant with DFS (HR = 4.0, p = 0.008), borderline with OS and the correlation was dependent on the scoring pathologist. Having histological WHO type I&II correlated significantly with shorter DFS (HR 4.03, p = 0.008) and low CD3+ TIL (p = 0.009). Subgroup analysis of LA-NPC that included undifferentiated type (WHO type III) cases only (n = 58), showed a strong correlation between low CD3+ TIL and shorter DFS (HR = 7.2, p = < 0.001) and OS (HR = 17.3, p = 0.008). PD-L1 was expressed in 72% of type III LA-NPC cases while lacking PD-L1 expression correlated with shorter OS (HR = 6.1, p = 0.031). Patients with a combination of low CD3+ TIL and lack of PD-L1 expression had the worst OS (p < 0.001). Conclusions: CD3+ TIL is promising as a robust and independent prognostic marker for DFS and OS of LA-NPC patients treated with platinum-based CCRT. We would suggest the use of CD3 + TIL as a stratifying factor for LA-NPC, which warrants further validation in prospective trials.

Biomarkers are needed to individualize cancer radiation treatment. Therefore, we have investigated the association between various risk factors, including single nucleotide polymorphisms (SNPs) in candidate genes and late complications to radiotherapy in our nasopharyngeal cancer patients.

Objective/Background: To evaluate the efficacy and outcome of adding low-dose fractionated radiotherapy (LDFRT) to induction chemotherapy plus concurrent chemoradiation in locally advanced nasopharyngeal carcinoma (LANPC). Methods: A single-institute, phase II–III, prospectively controlled randomized clinical trial was performed at King Faisal Specialist Hospital and Research Centre. Patients aged 18–70 years with WHO type II and III, stage III–IVB nasopharyngeal carcinoma, Eastern Cooperative Oncology Group performance score of 0–2, with adequate hematological, renal, and hepatic function were eligible. In total, 108 patients were enrolled in this trial. All patients received two cycles of induction docetaxel and cisplatin (75 mg/m² each) chemotherapy on Days 1 and 22, followed by concurrent chemoradiation therapy. Radiation therapy consisted of 70 Gy in 33 fractions, with concurrent cisplatin 25 mg/m² for 4 days on Days 43 and 64. Patients were randomly assigned to either adding LDFRT (0.5 Gy twice daily 6 hours apart for 2 days) to induction chemotherapy in the experimental arm (54 patients) or induction chemotherapy alone in the control arm (54 patients). Results: There was no significant difference in the post-induction response rates (RRs) or in toxicity between the two treatment arms. The 3-year overall survival (OS), locoregional control (LRC), and distant metastases-free survival (DMFS) rates for experimental arm and control arm were 94% versus 93% (p = .8), 84.8% versus 87.5% (p = .58), and 84.1% versus 91.6% (p = .25), respectively. Conclusion: The results showed no benefit from adding LDFRT to induction chemotherapy in terms of RR, OS, LRC, and DMFS.

OBJECTIVE: To evaluate the outcome of radical treatment for patients with stage IV squamous cell carcinoma of the oral cavity. METHODS: Using head and neck tumor database, 57 patients with stage IV non-metastatic invasive squamous cell carcinoma of the oral cavity treated with curative intent at King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia, between July 1992 and June 1998, were identified and retrospectively reviewed. RESULTS: Our cohort of patients consisted of 33 males and 24 females, with a median age of 65 years. The primary sites were alveolus (26), tongue (22), buccal mucosa (6), floor of mouth (2) and retromolar trigone (one). Definitive radiotherapy was used in 7 patients, surgery in 17 and combined modality in 33. With a median follow-up for surviving patients of 53-months, the actuarial 5-year overall survival and relapse free survival was 20% and 14%. Tumors arising from the alveolus showed a better outcome as compared to the rest of oral cavity sites with an overall survival and relapse free survival of 32% and 26% compared to 8% and 4% (p value=0.0057 and 0.0038). CONCLUSION: Advanced oral cavity tumors are aggressive neoplasms with a poor outcome to conventional treatment modalities. New approaches like neoadjuvant or concurrent chemoradiotherapy with or without surgery need to be considered and evaluated in prospective studies.