C. C. Yau

Concurrent and Adjuvant Chemotherapy for Nasopharyngeal Carcinoma: A Factorial Study

PURPOSE To study the efficacy of concurrent chemoradiotherapy (CRT) and adjuvant chemotherapy (AC) for nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS Patients with Hos stage T3 or N2/N3 NPC or neck node > or = 4 cm were eligible. Patients were randomly assigned to have radiotherapy (RT) or CRT with uracil and tegafur and to have AC or no AC after RT/CRT. AC comprised alternating cisplatin, fluorouracil, vincristine, bleomycin, and methotrexate for six cycles. There were four treatment groups: A, RT; B, CRT; C, RT and AC; D, CRT and AC. For CRT versus RT, groups B and D were compared with groups A and C. For AC versus no AC, groups C and D were compared with groups A and B. RESULTS Three-year failure-free survival (FFS) and overall survival (OS) for CRT versus RT were 69.3% versus 57.8% and 86.5% versus 76.8%, respectively (P =.14 and.06; n = 110 v 109). Distant metastases rate (DMR) was significantly reduced with CRT (14.8% v 29.4%; P =.026). Locoregional failure rates (LRFR) were similar (20% v 27.6%; P =.39). Three-year FFS and OS for AC versus no AC were 62.5% versus 65% and 80.4% versus 83.1%, respectively (P =.83 and.69; n = 111 v 108). DMR and LRFR were not reduced with AC (P =.34 and.15, respectively). Cox model showed CRT to be a favorable prognostic factor for OS (hazard ratio, 0.42; P =.009). CONCLUSION An improvement in OS with CRT was observed but did not achieve statistical significance. The improvement seemed to be associated with a significant reduction in DMR. AC did not improve outcome.

Patterns of failure after induction chemotherapy and radiotherapy for locoregionally advanced nasopharyngeal carcinoma: the Queen Mary Hospital experience

PURPOSE Our center contributed 183 patients to the Asian-Oceanian Clinical Oncology Association (AOCOA) multicenter randomized trial comparing induction chemotherapy (CT) followed by radiotherapy (RT) vs. RT alone in patients with locoregionally advanced undifferentiated nasopharyngeal carcinoma (NPC). In a preliminary report no difference in terms of overall survival or relapse-free survival was found between the 2 treatment arms. To study the long-term outcome and patterns of failure after CT for NPC, we analyzed our own center data for which a uniform radiation treatment protocol was adopted and a longer follow-up time was available. METHODS AND MATERIALS Between September 1989 and August 1993, a total of 183 patients were recruited into the AOCOA randomized study from our center. Patients with newly diagnosed NPC of Hos T3 disease, N2-N3 disease, or with neck node size of at least 3 cm were eligible. Stratification was made according to the nodal size (< or = 3 cm, >3- 6 cm, > 6 cm). Patients were randomized to receive 2-3 cycles of CT with cisplatin 60 mg/m(2) and epirubicin 110 mg/m(2) D1 followed by RT or RT alone. Four patients were excluded from the current analysis (2 died before treatment, 2 received treatment elsewhere). The remaining 179 patients were randomized to the two treatment arms, with 92 to the CT arm and 87 to the RT arm. Two patients in the CT arm had RT only, and all patients completed radiation treatment. Overall survival (OAS), relapse-free survival (RFS), local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), and distant metastases-free survival (DMFS) were analyzed using Kaplan--Meier method and significance of survival curve differences calculated using log--rank test. Analysis was performed based on the intent-to-treat. RESULTS The median follow-up was 70 months. At the time of analysis, 50% of patients in the CT arm and 61% in the RT arm had relapse, while 32% in the CT arm and 36% in the RT arm had died of the disease. The median RFS was 83 months in the CT arm and 37 months in the RT arm. The median OAS has not yet been reached for both arms. No significant differences were found for the various endpoints, although there was a trend suggesting better nodal control in the CT arm. The 5-year rates for the various endpoints in the CT arm vs. the RT arm were: 53% vs. 42% for RFS (p = 0.13), 70% vs. 67% for OAS (p = 0.68), 80% vs. 77% for LRFS (p = 0.73), 89% vs. 80% for NRFS (p = 0.079), and 70% vs. 68% for DMFS (p = 0.59). There was also no significant difference in the patterns of failure between both arms: in the CT arm, 28% of failures were local only, 13% regional only, 4% locoregional, 44% distant, and 11% mixed locoregional and distant. In the RT arm, 23% of failures were local only, 13% regional only, 11% locoregional, 43% distant, and 9% mixed locoregional and distant. CONCLUSION Induction chemotherapy with the regimen used in the current study did not improve the treatment outcome or alter the failure patterns in patients with locoregionally advanced NPC, although there was a trend suggesting better nodal control in the combined modality arm. Alternative strategies of combining chemotherapy and radiotherapy should be tested and employed instead.

Correlation of endoscopic and histologic findings before and after treatment for nasopharyngeal carcinoma

Background The endoscopic and histologic findings before and after radiotherapy (RT) for nasopharyngeal carcinoma (NPC) were correlated to study the sensitivity and specificity of endoscopic findings in predicting histologic results. The efficiacy of endoscopic examination and post-RT multiple site biopsies in detecting persistent disease was also evaluated. Methods Seven hundred forty-six patients were evaluated. Pre-RT, biopsies were taken from both sides of the nasopharynx to assess the extent of tumor. Four to 16 weeks after RT, routine six-site biopsy specimens were taken from both roofs, lateral, and posterior walls of the nasopharynx and repeated 2 weeks later. Endoscopic findings of exophytic growth, nodule, ulcer, and submucosal bulge were considered “residual tumor,” others were considered “no residual tumor.” Persistent disease was defined as positive histologic findings 12 weeks after RT. Results Before RT, sensitivity of endoscopic findings and biopsy specimens in detecting malignancy were 99.7% and 94.2%, respectively. After RT, sensitivity and specificity of endoscopic findings in predicting positive histologic findings were 29% and 85.8%, respectively, with a positive predictive value of 34.9% and a negative predictive value of 82.2%. Of positive histologic findings, 27.7% were missed in the first session of biopsies; 33.5% of those with positive histologic findings turned out to have persistent disease. For prediction of persistent disease, the sensitivity and specificity of endoscopic findings were 40.4% and 84.4%, with a positive predictive value of 16.3% and a negative predictive value of 95%, and that of histologic findings in the first session of biopsies were 59.6% and 88.3%, respectively, with a positive predictive value of 27.7% and a negative predictive value of 96.7%. Conclusions Endoscopic findings alone have low sensitivity in predicting persistent disease, multiple sites biopsy specimens are indicated. Because only 1.9% of patients with endoscopic findings of “no residual tumor” and negative histologic findings in first session of biopsies had persistent disease, this group can be spared second biopsies. Repeat biopsies are indicated for those with endoscopic findings of “residual tumor” or positive histologic findings in first session of biopsies to improve detection of persistent disease.

MicroRNA profiling study reveals miR-150 in association with metastasis in nasopharyngeal carcinoma

MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in pathogenesis of human cancers. Several miRNAs have been shown to involve in nasopharyngeal carcinoma (NPC) pathogenesis through alteration of gene networks. A global view of the miRNA expression profile of clinical specimens would be the best way to screen out the possible miRNA candidates that may be involved in disease pathogenesis. In this study, we investigated the expression profiles of miRNA in formalin-fixed paraffin-embedded tissues from patients with undifferentiated NPC versus non-NPC controls using a miRNA real-time PCR platform, which covered a total of 95 cancer-related miRNAs. Hierarchical cluster analysis revealed that NPC and non-NPC controls were clearly segregated. Promisingly, 10 miRNA candidates were differentially expressed. Among them, 9 miRNAs were significantly up-regulated of which miR-205 and miR-196a showed the most up-regulated in NPC with the highest incidence percentage of 94.1% and 88.2%, respectively, while the unique down-regulated miR-150 was further validated in patient sera. Finally, the in vitro gain-of-function and loss-of-function assays revealed that miR-150 can modulate the epithelial-mesenchymal-transition property in NPC/HK-1 cells and led to the cell motility and invasion. miR-150 may be a potential biomarker for NPC and plays a critical role in NPC tumourigenesis.