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.

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.

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.