Prognostic significance of the total dose of cisplatin administered during concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: Concurrent chemoradiotherapy (CRT) confers survival benefit over radiotherapy (RT) alone in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). This study explored the prognostic significance of the total dose of cisplatin delivered during CRT. MATERIALS AND METHODS: A retrospective analysis was performed in patients with stage II to IVB NPC (AJCC 6th edition) who participated in 3 prospective studies. All patients received cisplatin at a fixed dose of 40 mg/m(2)/week during a 6-7-weeks course of CRT. Chi-square test was used in the univariate analysis. Relationship between prognostic factors, the total dose of cisplatin administered and time-to-event endpoints were analyzed with the Cox Hazards model. RESULTS: Two hundred and forty-one patients were identified with the following stage distribution: Stage II=13.7%, III=45.2%, IV=41.1%. The median total number of cycles of cisplatin administered per patient was 5 cycles (range 1-8 cycles). At a median follow-up of 56.5 months (range 4.2-200.2 months), 93 patients (38.6%) had relapsed and 85 patients (35.2%) died. For all patients, the total number of cycles of cisplatin delivered was significantly associated with survival in the univariate but not the multivariate analysis. In a sub-group analysis of 142 patients with stage II and III NPC, patients who received more than 5 cycles of cisplatin had significantly better overall survival than those who did not (hazard ratio 0.44; 95% confidence interval, 0.23-0.85; p=0.02). CONCLUSION: Number of cycles of cisplatin delivered is an independent prognostic factor in patients with stage II-III NPC undergoing CRT with weekly cisplatin.

Surgical salvage nasopharyngectomy for recurrent nasopharyngeal carcinoma: a multivariate analysis of prognostic factors.

BACKGROUND: The purpose of this study was to identify independent prognostic factors that influenced local relapse-free survival (LRFS) and overall survival (OS) of patients who underwent salvage surgery for residual or recurrent nasopharyngeal carcinoma (NPC). METHODS: Ninety-seven patients who had been treated with radiotherapy or chemoradiotherapy for NPC underwent a nasopharyngectomy for a residual or recurrent local tumor between November 1987 and June 2007. The subsequent minimum follow-up was 2 years. Univariate and multivariate analyses were performed to identify prognostic factors for LRFS and OS. RESULTS: The 5-year LRFS and OS was 46.7% and 51.9%, respectively. On multivariate analysis for LRFS and OS, respectively, recurrent regional disease (hazard ratio [HR], 3.245; p = .008) and (HR, 4.990; p = .001), and positive surgical margins (HR, 5.963; p = .000), and (HR, 4.912; p = .000) were independent prognostic factors. CONCLUSION: In patients undergoing surgical salvage nasopharyngectomy for residual or recurrent NPC, positive surgical margins have an independent negative influence on LRFS and OS.

Plasma osteopontin, hypoxia, and response to radiotherapy in nasopharyngeal cancer.

PURPOSE: Recent studies have suggested that osteopontin is induced by hypoxia in head and neck cancer cell lines and its plasma level may serve as a surrogate marker for tumor hypoxia and treatment outcome in head and neck cancer. We investigated the response of osteopontin to in vitro hypoxia in nasopharyngeal carcinoma cell lines, and determined plasma osteopontin levels in nasopharyngeal carcinoma patients, nonnasopharyngeal carcinoma head and neck cancer patients, and healthy controls. We explored the relationship of plasma osteopontin and response to radiotherapy in nasopharyngeal carcinoma. EXPERIMENTAL DESIGN: Nasopharyngeal carcinoma cell lines HK1, HONE-1, C666-1, and CNE-2 were treated with 0 to 48 hours of hypoxia or normoxia, +/- reoxygenation. Osteopontin secretion in the supernatant was measured by ELISA assay. Cellular osteopontin protein and mRNA were detected by Western blotting and reverse transcription-PCR, respectively. Plasma osteopontin levels in patients (n=66; 44 nasopharyngeal carcinoma, 22 head and neck cancer) and controls (n=29) were measured by ELISA. RESULTS: Hypoxia has no effect on osteopontin protein and mRNA level in nasopharyngeal carcinoma cells. Only CNE-2 secreted osteopontin, and there was no significant induction by hypoxia. Plasma osteopontin levels in patients of metastatic nasopharyngeal carcinoma and head and neck cancer, but not in locoregional nasopharyngeal carcinoma, were significantly higher than in controls. In patients with locoregional nasopharyngeal carcinoma receiving curative radiotherapy (n=31), a high (>median) pretreatment plasma osteopontin level was a significant predictor of poor response to radiotherapy (complete response rate, 40% versus 88%; P=0.009), which remained significant in multivariate analysis. CONCLUSION: Our results suggested that the pretreatment plasma osteopontin level may be a useful biomarker of response to radiotherapy in nasopharyngeal carcinoma.

Nasopharyngectomy: does the approach to the nasopharynx influence survival?

OBJECTIVE: To investigate whether the approach used to the nasopharynx to perform a salvage nasopharyngectomy for recurrent or residual nasopharyngeal carcinoma influences survival. STUDY DESIGN: A retrospective case series. SUBJECTS AND METHODS: Eighty patients underwent a nasopharyngectomy via a transpalatal, maxillary swing, or midfacial degloving approach. Local progression-free, locoregional progression-free, and overall survival rates were calculated for each approach. RESULTS: For the whole group (N = 80), there were no significant differences in the survival rates between the three approaches. For the subgroup of patients with recurrent T1 and T2 tumors (n = 68), the local progression-free and locoregional progression-free survival rates were significantly better when a maxillary swing approach was used than when a midfacial degloving approach was used. CONCLUSION: The maxillary swing approach is associated with significantly better survival rates than the midfacial degloving approach when used to perform a salvage nasopharyngectomy for residual or recurrent T1 and T2 nasopharyngeal carcinoma.

Nasopharyngectomy and surgical margin status: a survival analysis.

OBJECTIVE: To explore whether the margin status at surgical salvage nasopharyngectomy for local residual or recurrent nasopharyngeal carcinoma affects patient survival. DESIGN: Retrospective case series review. SETTING: Academic tertiary referral center. PATIENTS: Seventy-nine consecutive patients with operable local residual or recurrent nasopharyngeal carcinoma after failure of primary treatment with radiotherapy with or without chemotherapy underwent surgical salvage nasopharyngectomy with curative intent between November 28, 1987, and November 17, 2003. Sixty-one patients were men and 18 were women. Their mean age was 48 years (age range, 26-70 years). INTERVENTION: Surgical salvage nasopharyngectomy. MAIN OUTCOME MEASURES: The status of the closest margin at surgery was assessed as clear, close, or positive. Survival time was measured from the date of surgery to the date of the last follow-up, to the date of an event occurrence, or to the date of death. The Kaplan-Meier method was used to estimate the probability of local progression-free survival and overall survival at 5 years. Differences in survival rates between surgical margin statuses were assessed using the log-rank test. RESULTS: Five-year overall survival for patients with clear margins was 77%, for patients with close margins was 46% (P = .05), and for patients with positive margins was 23% (P < .001). CONCLUSION: Clear surgical margins at the time of surgical salvage nasopharyngectomy for residual or recurrent nasopharyngeal carcinoma positively affect patient survival.

Prospective randomized study of intensity-modulated radiotherapy on salivary gland function in early-stage nasopharyngeal carcinoma patients.

PURPOSE: This randomized trial compared the rates of delayed xerostomia between two-dimensional radiation therapy (2DRT) and intensity-modulated radiation therapy (IMRT) in the treatment of early-stage nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Between November 2001 and December 2003, 60 patients with T1-2bN0-1M0 NPC were randomly assigned to receive either IMRT or 2DRT. Primary end point was incidence of observer-rated severe xerostomia at 1 year after treatment based on Radiotherapy Oncology Group /European Organisation for the Research and Treatment of Cancer late radiation morbidity scoring criteria. Parallel assessment with patient-reported outcome, stimulated parotid flow rate (SPFR), and stimulated whole saliva flow rate (SWSFR) were also made. RESULTS: At 1 year after treatment, patients in IMRT arm had lower incidence of observer-rated severe xerostomia than patients in the 2DRT arm (39.3% v 82.1%; P = .001), parallel with a higher fractional SPFR (0.90 v 0.05; P < .0001), and higher fractional SWSFR (0.41 v 0.20; P = .001). As for patient's subjective feeling, although a trend of improvement in patient-reported outcome was observed after IMRT, recovery was incomplete and there was no significant difference in patient-reported outcome between the two arms. CONCLUSION: IMRT is superior to 2DRT in preserving parotid function and results in less severe delayed xerostomia in the treatment of early-stage NPC. Incomplete improvement in patient's subjective xerostomia with parotid-sparing IMRT reflects the need to enhance protection of other salivary glands.

Laryngeal carcinoma: five-year survival and patterns of failure in 202 consecutive patients treated with primary or post-operative radiotherapy in Hong Kong.

OBJECTIVES: We aimed to conduct a retrospective analysis of patients treated with radiotherapy for laryngeal carcinoma at a single institution. METHODS: We analysed data from 202 consecutive patients treated with primary or post-operative radiotherapy for laryngeal carcinoma over a 10-year period. RESULTS: Sixty-nine patients had a T1, 65 a T2, 39 a T3 and 29 a T4 lesion. Forty-one patients were node-positive. The clinical stage was I in 67 patients, II in 53, III in 36 and IV in 46. Primary radiotherapy was given to 152 patients. The median follow up was 60 months. The five-year overall local control rate was 86 per cent, the ultimate local control rate was 93 per cent, the five-year regional control rate was 96 per cent, the five-year relapse-free survival rate was 82 per cent and the five-year overall survival rate was 69 per cent. CONCLUSIONS: Patients with laryngeal carcinoma treated with primary or post-operative radiotherapy had a five-year overall survival rate of 69 per cent.

Nasopharyngeal granulomatous inflammation and tuberculosis complicating undifferentiated carcinoma.

OBJECTIVE: Four cases of nasopharyngeal granulomatous inflammation after radiotherapy for undifferentiated carcinoma were analyzed for tuberculosis, and the histologic features were compared. STUDY DESIGN AND SETTING: We conducted a retrospective study with analysis of tuberculosis by Ziehl Neelsen staining and polymerase chain reaction analysis for Mycobacterium tuberculosis DNA on histologic materials. RESULTS: Three patients had previous nasopharyngeal undifferentiated carcinoma, one had previous metastatic undifferentiated carcinoma to cervical lymph nodes, and all patients received similar radiotherapy regimen. The light microscopic features were similar with epithelioid histiocytes and granulomas with Langhan's giant cells. In 3 cases, acid-fast bacilli were identified by Ziehl Neelsen stain, and 1 was negative. The results of 2 cases were confirmed by polymerase chain reaction analysis for Myocbacterium tuberculosis DNA. CONCLUSION: Granulomatous reaction after radiotherapy of nasopharyngeal undifferentiated carcinoma can be caused by tuberculosis. SIGNIFICANCE: Diligent search for organisms in postirradiation granulomatous inflammation is warranted to avoid missing an occult tuberculosis infection.