Locally advanced nasopharyngeal carcinoma in adolescents treated with tomotherapy: Experience at King Faisal Specialist Hospital and Research Centre.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a rare disease worldwide; To the best of our knowledge, there is no established standard of care specifically tailored for the adolescent population. The majority of existing research relies on retrospective data analysis. OBJECTIVE: Evaluate clinical features, treatment results, prognostic factors and late toxicities of locally advanced NPC patients treated with tomotherapy. DESIGN: Retrospective. SETTINGS: Tertiary care hospital. PATIENTS AND METHODS: Between January 2007 and January 2020, we treated patients with NPC, aged between 14 and 21 years, with concomitant chemoradiotherapy using tomotherapy at our institution. We prospectively collected details of clinical characteristics, treatment modalities, outcomes and prognostic factors of these patients and then analysed them retrospectively. MAIN OUTCOME MEASURES: 3-5 years overall survival (OS), 3-5 years locoregional control rate, 3-5 years disease-free survival (DFS), prognostic factors. SAMPLE SIZE: 51 patients. RESULTS: There were 26 male and 25 female patients included in our study. The mean age was 16.5 years, 5 (9.8%) patients with stage III, and 46 (90.2%) with stage IVa according to the American Joint Committee on Cancer, 8th edition staging system. Most patients (98%) received two or more cycles of induction chemotherapy. All patients received concomitant chemoradiotherapy. The median total dose of radiotherapy delivered was 6600 cGy (range 4800-7000). With a median follow-up of 73 months (range 9-168 months), a 5-year locoregional control rate, 5-year OS and 5-year DFS rates were 100%, 86.8% and 71.7%, respectively. Five years later, disease control was 71.7%. Ten (19.6%) patients had disease recurrence in the form of distant metastases during the follow up. CONCLUSIONS: Helical tomotherapy has an excellent late toxicity profile without compromising clinical outcome for patients with NPC. Radiotherapy remains the mainstay of treatment of nasopharyngeal carcinoma to achieve remarkable local control rates. LIMITATIONS: Single institution experience, small number of patients, and retrospective design.

Prognostic markers compared to CD3+TIL in locally advanced nasopharyngeal carcinoma.

ABSTRACT: Locally advanced nasopharyngeal carcinoma (LA-NPC) is more prevalent in some geographic regions, including Saudi Arabia. Typically, Tumor-Node-Metastasis (TNM) staging is used in NPC. However, it is inadequate to assess the prognosis of LA-NPC.Therefore, we analyzed and compared several previously reported prognostic factors in LA-NPC patients, retrospectively, including CD3+tumor-infiltrating lymphocytes (TIL) and peripheral blood hemoglobin, EBV DNA copy number, ratios of albumin-to-alkaline phosphatase ratio (AAPR), neutrophils, or platelets-to-lymphocytes (NLR, PLR). The studied cohort was 83 LA-NPC patients previously recruited for a randomized phase II trial with a different aim.Univariate cox regression analysis showed no significant correlation between any of the tested variables with disease-free survival (DFS) or overall survival (OS) with the exception of low CD3+ TIL infiltration, which correlated significantly with DFS (HR = 6.7, P = <.001) and OS (HR = 9.1, P = .043). Similarly, in a validated multivariate cox regression analysis, only low CD3+ TIL correlated significantly with DFS (HR = 7.0, P < .001 for TIL) and OS (HR = 9.4, P = .040).Among tested parameters, CD3+ TIL was the only independent prognostic marker for DFS and OS in LA-NPC patients treated with CCRT. This study supports the use of CD3+TIL, over other factors, as an independent prognostic factor in LA-NPC.

Low-dose fractionated radiation with induction docetaxel and cisplatin followed by concurrent cisplatin and radiation therapy in locally advanced nasopharyngeal cancer: A randomized phase II-III trial.

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.

CD3+T-lymphocyte infiltration is an independent prognostic factor for advanced nasopharyngeal carcinoma.

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.

Retraction Note: SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers.

The authors are retracting this article [1] because the data have already been published in [2] making this a redundant publication. Ghazi Alsbeih, Najla Al-Harbi, Khaled Al-Hadyan, Mohamed Shoukri and Nasser Al-Rajhi agree with this retraction. Medhat El-Sebaie did not respond to our correspondence.

Antibiotic protocol for the prevention of osteoradionecrosis following dental extractions in irradiated head and neck cancer patients: A 10 years prospective study.

AIMS OF STUDY: The aim of the study was to establish the long term efficacy of a perioperative antibiotic protocol combined with antibacterial mouthwashes in preventing osteoradionecrosis (ORN). MATERIALS AND METHODS: Irradiated head and neck cancer patients reporting for dental extractions were prospectively enrolled to the study between January 2002 and December 2009. Selection criteria for the patients included the presence of nonrestorable tooth/teeth in the field of radiation, latency period of 6 months since completion of radiotherapy, radiation dosages >60 Gy, and availability for follow-up. Starting from 10 days preextraction, the patients were prescribed 8th hourly oral amoxicillin 500 mg along with 12th hourly mouthwashes using 10 ml of undiluted chlorhexidine gluconate 0.2% solution. The same prescription was continued for 7 days postextraction. All patients were followed-up at regular intervals until December 2013. RESULTS: A total of 89 patients (55 male and 34 female) underwent extractions of teeth which were present in the radiation field. Mean age of the patients was 41.8 years (range 36-54 years) and extractions were done between 12 and 33 months (mean - 15 months) postradiation therapy. Altogether, 232 teeth were extracted (maxilla - 78/mandible - 154) at an average of 2.6 teeth per patients. After a mean follow-up period of 63 months (range 48-123 months) there were no reported cases of ORN. CONCLUSION: Based on the results of this study, perioperative oral antibiotics in combination with antibacterial mouthwashes are effective in preventing ORN following dental extractions in irradiated patients.

Among 45 variants in 11 genes, HDM2 promoter polymorphisms emerge as new candidate biomarker associated with radiation toxicity.

Due to individual variations in radiosensitivity, biomarkers are needed to tailor radiation treatment to cancer patients. Since single nucleotide polymorphisms (SNPs) are frequent in human, we hypothesized that SNPs in genes that mitigate the radiation response are associated with radiotoxicity, in particular late complications to radiotherapy and could be used as genetic biomarkers for radiation sensitivity. A total of 155 patients with nasopharyngeal cancer were included in the study. Normal tissue fibrosis was scored using RTOG/EORTC grading system. Eleven candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were selected for their presumed influence on radiosensitivity. Forty-five SNPs (12 primary and 33 neighboring) were genotyped by direct sequencing of genomic DNA. Patients with severe fibrosis (cases, G3-4, n = 48) were compared to controls (G0-2, n = 107). Results showed statistically significant (P < 0.05) association with radiation complications for six SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). We conclude that these six SNPs are candidate genetic biomarkers for radiosensitivity in our patients that have cumulative effects as patients with severe fibrosis harbored significantly higher number of risk alleles than the controls (P < 0.001). Larger cohort, independent replication of these findings and genome-wide association studies are required to confirm these results in order for SNPs to be used as biomarkers to individualize radiotherapy on genetic basis.

SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers.

BACKGROUND: 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. METHODS: A cohort of 155 patients was included. Normal tissue fibrosis was scored using RTOG/EORTC grading system. A total of 45 SNPs in 11 candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were genotyped by direct genomic DNA sequencing. Patients with severe fibrosis (cases, G3-4, n = 48) were compared to controls (G0-2, n = 107). RESULTS: Univariate analysis showed significant association (P < 0.05) with radiation complications for 6 SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). In addition, Kaplan-Meier analyses have also highlighted significant association between genotypes and length of patients' follow-up after radiotherapy. Multivariate logistic regression has further sustained these results suggesting predictive and prognostic roles of SNPs. CONCLUSIONS: Univariate and multivariate analysis suggest that radiation toxicity in radiotherapy patients are associated with certain SNPs, in genes including HDM2 promoter studied for the 1st time. These results support the use of SNPs as genetic predictive markers for clinical radiosensitivity and evoke a prognostic role for length of patients' follow-up after radiotherapy.

Involvement of mitochondrial DNA sequence variations and respiratory activity in late complications following radiotherapy.

PURPOSE: Mitochondria and ionizing radiation overlap in a number of features; for instance, both generate harmful reactive oxygen species, and that radiation can induce cell death through the intermediary of mitochondria. Because a number of genetic variations in nuclear genes are frequently associated with response to cancer treatment, the aim of this case-control study was to test the hypothesis that mitochondrial DNA (mtDNA) genetic variations can contribute to patient-to-patient variability in normal tissue response to radiotherapy. EXPERIMENTAL DESIGN: Thirty-two nasopharyngeal carcinomas patients treated with definitive radiotherapy were included. The grade (G) of s.c. and deep tissue fibrosis was scored according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer grading system. Coding and RNA mtDNA (between 611 and 15,978 bp) were sequenced, and genetic variations were scored. Mitochondrial respiratory activity was measured by resazurin reduction assay. RESULTS: Data showed a significantly (P = 0.003) higher number of nonsynonymous genetic variations in the radiosensitive (G(2)-G(3); 16 patients) as compared with the control (G(0)-G(1); 16 patients) groups. The nonsynonymous A10398G variation in the ND3 gene was significantly associated with fibrotic reaction (P = 0.01). The radiosensitive patients had a 7-fold (95% confidence interval, 1.16-51.65) higher risk of developing moderate to severe fibrosis (G(2)-G(3)) following radiotherapy. This was significantly correlated with lower mitochondrial respiratory activity (P = 0.001). CONCLUSION: Mitochondria contribute to radiation sensitivity, and genetic variations can be associated with late reactions to radiotherapy. Predictive markers of radiosensitivity should take into account mtDNA genetic variations in addition to variations in nuclear genes.

The Role of 18-FDG Positron Emission Tomography (FDG-PET) in Detecting Post- Radiotherapy Loco Regional Relapse/Residual Disease in Nasopharyngeal Cancer.

BACKGROUND: Post-radiotherapy nasopharyngeal changes represent a diagnostic dilemma. Early detection of persistent or recurrent disease may be translated to better cure rate if salvage therapy is implemented. Neither clinical exam nor current radiological anatomical studies (CT/MRI) can differentiate between benign post therapy changes and recurrence. PET scan is a functional study capable of identifying viable tumors as areas of increased radiotracer uptake. METHODS: Fifty-five patients underwent 18-FDG PET scans post radiation therapy for nasopharyngeal carcinoma at King Faisal Specialist Hospital and Research Centre. We compared the 18-FDG PET scan with the clinical, radiological and pathological findings. RESULTS: Clinical examination and CT of the head and neck showed post-treatment abnormality in the nasopharynx in 40 patients. Among these, 28 patients had asymmetry in the CT scan. Three out of the 28 patients had positive PET scan. Out of the 12 patients with positive primary disease in the CT scan, 3 had negative PET scan which was also confirmed by biopsy in 2 patients. Eleven patients had positive PET scan in the primary site; this was pathologically confirmed to be recurrent disease in 5 patients. In 2 patients repeat PET scan was converted to negative. The remaining 4 patients did not have biopsy due to the presence of concurrent distant disease. None of the patients with negative PET scan in the neck exhibit recurrence or persistent neck disease to the day of reporting the study. PET scan showed persistent higher sensitivity, specificity, positive and negative predictive values at both the primary site and the neck region than the CT did. CONCLUSION: PET scan is a useful tool in differentiating between post radiotherapy fibrosis and recurrent nasopharyngeal cancer. KEY WORDS: Nasopharyngeal cancer - FDG/PET - Post therapy changes.

Association between XRCC1 G399A Polymorphism and Late Complications to Radiotherapy in Saudi Head and Neck Cancer Patients.

BACKGROUND: It has been hypothesized that patient to patient variation in normal tissue reactions to radiotherapy is associated with the presence of polymorphic variations in genes involved in DNA repair. PURPOSE: To test for a possible association between two single-nucleotide polymorphisms (SNPs), XRCC1 399 G>A Arg/Gln and XRCC3 241 C>T Thr/Met and late reactions to radiotherapy. PATIENTS AND METHODS: In this case control study, 50 Head and Neck cancer patients were retrospectively recruited. The grade (G) of fibrosis, a late complication to radiotherapy, was scored using the RTOG/EORTC grading system. Radiosensitive patients with moderate to severe subcutaneous and deep tissue fibrosis (cases, G2-3, n=25) where matched with patients with minimal fibrotic reactions (control, G0-1, n=25). The two nonsynonymous SNPs were genotyped by direct sequencing of DNA extracted from blood or cultured fibroblasts. RESULTS: Allelic frequency showed significant association with grade of fibrosis for XRCC1 399 G/A (p=0.05), but not for XRCC3 241 C>T (p=0.10). CONCLUSIONS: This pilot study corroborates the association between XRCC1 399 G>A and risk of late normal tissue complications following radiotherapy in our patients. Large studies are required to unravel more SNPs that can influence radiosensitivity and ascertain the associations with reactions to radiotherapy in order to be used as genetic predictive biomarkers of individual radiosensitivity. KEY WORDS: Single nucleotide polymorphism - Radiosensitivity - Late reactions to radiotherapy - XRCC1 - XRCC3.

Radiosensitivity of human fibroblasts is associated with amino acid substitution variants in susceptible genes and correlates with the number of risk alleles.

PURPOSE: Genetic predictive markers of radiosensitivity are being sought for stratifying radiotherapy for cancer patients and risk assessment of radiation exposure. We hypothesized that single nucleotide polymorphisms in susceptible genes are associated with, and the number of risk alleles has incremental effect on, individual radiosensitivity. METHODS AND MATERIALS: Six amino acid substitution variants (ATM 1853 Asp/Asn G>A, p53 72 Arg/Pro G>C, p21 31 Ser/Arg C>A, XRCC1 399 Arg/Gln G>A, XRCC3 241 Thr/Met C>T, and TGFbeta1 10 Leu/Pro T>C) were genotyped by direct sequencing in 54 fibroblast strains of different radiosensitivity. RESULTS: The clonogenic survival fraction at 2 Gy range was 0.15-0.50 (mean, 0.34, standard deviation, 0.08). The mean survival fraction at 2 Gy divided the cell strains into radiosensitive (26 cases) and normal (28 controls). A significant association was observed between the survival fraction at 2 Gy and ATM 1853 Asn, XRCC3 241 Met, and TGFbeta1 10 Leu alleles (p = 0.05, p = 0.02, and p = 0.02, respectively). The p53 72 Arg allele showed a borderline association (p = 0.07). The number of risk alleles increased with increasing radiosensitivity, and the group comparison showed a statistically significant difference between the radiosensitive and control groups (p < or = 0.001). CONCLUSION: The results of our study have shown that single nucleotide polymorphisms in susceptible genes influence cellular radiation response and that the number of risk alleles has a combined effect on radiosensitivity. Individuals with multiple risk alleles could be more susceptible to radiation effects than those with fewer risk alleles. These results may have implications in predicting normal tissue reactions to radiotherapy and risk assessment of radiation exposure.

Neoadjuvant chemotherapy followed by concurrent chemo-radiation therapy in locally advanced nasopharyngeal carcinoma.

PURPOSE: To evaluate the efficacy and outcomes of neoadjuvant cisplatinum and epirubicin chemotherapy followed by concurrent cisplatinum chemotherapy with radiotherapy in patients with locally advanced nasopharyngeal carcinoma. METHODS AND MATERIALS: One hundred ten patients (80 male, 30 female) with locally advanced nasopharyngeal carcinoma, staged according to the 1997 International Union Against Cancer/American Joint Committee on Cancer classification system as IIB (n = 9), III (n = 20), IVA (n = 32), and IVB (n = 49), World Health Organization types II (n = 25) and III (n = 85), were included in this protocol between January 1998 and July 2000 at King Faisal Specialist Hospital and Research Centre. Patients underwent two cycles of induction chemotherapy with cisplatinum 100 mg/m(2) and epirubicin 70 mg/m(2) on Days 1 and 21, followed by a radical course of radiotherapy (6,600 cGy in 6.5 weeks, 200 cGy/fraction) starting on Day 42, with three cycles of concurrent cisplatinum 25 mg/m(2) for 4 days on Days 42, 63, and 84. RESULTS: Of 110 patients included in this study, intracranial extension was present in 32 (29%), and nodal stage was N3 in 49 (45%). Complete remission and partial remission were achieved in 87 patients (79%) and 23 patients (21%), respectively. At a median follow-up for surviving patients of 37 months (22-55 months), 49 of 110 patients (44%) had failed treatment: 12 with local, 9 with regional nodes, 4 locoregional, 5 locoregional plus distant areas, and 19 with distant metastases. At the time of writing, 34 patients had died; all deaths were related to the patients' cancer except for 1 patient with treatment-related toxicity. Three-year actuarial overall survival, relapse-free survival, locoregional control, and distant metastasis-free survival rates were 89%, 78%, 88%, and 89% for patients with stage IIB; 71%, 70%, 89%, and 74% for stage III; 68%, 49%, 61%, and 77% for stage IVA; and 70%, 45%, 60%, and 69% for stage IVB, respectively. One patient received only one induction cycle; all others received two cycles; however, 9 of them required 20% reduction in the second cycle dose. Ninety patients (82%) completed two or more concurrent cycles of cisplatinum. Rates of Grade 3 and 4 reactions after induction chemotherapy were as follows: anemia 1% and 0%, leukopenia 8% and 4%, nausea 27% and 0%, vomiting 25% and 0%, and infection 4% and 4%, respectively. Acute Grade 3 and 4 reactions were also observed during chemoradiotherapy: anemia 1% and 0%, leukopenia 31% and 4%, nausea 35% and 0%, vomiting 26% and 2%, infection in 4% and 2%, mucositis in 49% and 0%, and skin reaction in 39% and 0%, respectively. CONCLUSIONS: Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy is a safe and effective method of treatment for locally advanced nasopharyngeal carcinoma. Further investigations in prospective studies are required to evaluate this regimen.

Maxillary sinus carcinoma. Natural history and outcome.

OBJECTIVE: To assess natural history, treatment outcome and pattern of relapse in patients with maxillary sinus carcinoma. METHODS: A review was conducted of the medical records of all adult patients with maxillary sinus carcinoma, who were treated at King Faisal Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia, between January 1990 and December 1999. A total of 60 patients were identified for analysis, 36 men and 24 women; the median age was 58-years (range 23-95). Major presenting symptoms were facial swelling 55%, facial pain 50%, and nasal obstruction 43.4%, with a median duration of 5-months (range 1-24). Histology was squamous cell carcinoma in 71.7% and adenoid cystic in 16.7%. They were restaged according to American Joint Committee on Cancer classification 1997 as II, III and IV in 1, 10 and 49. Thirty patients received treatment with curative intent (surgery in 4 patients, radiotherapy in 2, and combined modality in 24), 6 patients refused treatment and 24 were treated palliatively. RESULTS: With a median follow up of 50-months (range 2-128) in surviving patients treated with a curative intent, 12/30 failed locally, 4/30 in the regional neck nodes and 2/30 had systemic relapse. The actuarial 5-year overall survival (OS), relapse free survival (RFS) and local control rate (LC) were 55%, 39% and 51%. Treatment modality was the only significant prognostic factor for outcome, with 5 year OS, RFS and LC of 72%, 49% and 61%, for combined modality using surgery followed by radiotherapy compared to 0% for single approach (p=0.0003, p=0.0052 and p=0.0098) CONCLUSION: This study indicates that the majority of our patients presented with advanced disease, resulting in poor outcome to conventional treatment modalities. Efforts should be directed to minimize the delay in diagnosis at the primary care level. Combined modality treatment should be offered to all patients with locally advanced disease. New approaches such as neoadjuvant or concurrent chemoradiotherapy with or without surgery need to be considered and evaluated in prospective studies.

A study comparing different approaches in managing neck nodes in early carcinoma of the tongue.

OBJECTIVE: To evaluate elective neck treatment in patients with early stage (T1-2 negative neck node [N0]) squamous cell carcinoma of the oral tongue. METHODS: The medical records of all patients with early stage (T1-2 N0) of oral tongue cancer at the King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia, between January 1980 and December 1997, were identified and retrospectively reviewed. RESULTS: Our cohort consisted of 93 patients: 45 males and 48 females, with a median age of 60 years. All patients received treatment with curative intent. Partial glossectomy was carried out, except for 8 patients who underwent tongue brachytherapy. The neck was observed in 29 patients, 36 were treated by modified neck dissection, and 28 by elective neck irradiation. With a median follow-up of 62 months, 29 patients had documented neck node recurrence. Ninety six percent (28/29) of recurrences occurred within 22 months from treatment completion. The 5 year actuarial event free survival with regard to nodal relapse in observed was 59%, dissected was 79% and irradiated neck was 63%. Our results showed a trend toward better neck node control in patients managed by elective neck dissection compared to those observed (p=0.07) or receiving elective neck irradiation (p=0.18). Tumor thickness of more than 10 mm was associated with increased risk of nodal relapse (p=0.0004). Neck node recurrence has a poor prognosis with a 5 year disease specific survival of 16%. CONCLUSION: A trend for higher neck control was observed after neck dissection in patients with T1-2 N0 squamous cell carcinoma of the oral tongue. Elective neck dissection should be considered particularly for patients with tumor thickness of more than 10 mm.

Stage IV oral cavity carcinoma. Is conventional radical treatment an option?

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.