Youwang Zhang

RADIATION-INDUCED CRANIAL NERVE PALSY: A CROSS-SECTIONAL STUDY OF NASOPHARYNGEAL CANCER PATIENTS AFTER DEFINITIVE RADIOTHERAPY

PURPOSE To address the characteristics and the causative factors of radiation-induced cranial nerve palsy (CNP) in nasopharyngeal carcinoma (NPC) patients with an extensive period of followed-up. PATIENTS AND METHODS A total of 317 consecutive and nonselected patients treated with definitive external-beam radiotherapy between November 1962 and February 1995 participated in this study. The median doses to the nasopharynx and upper neck were 71 Gy (range, 55-86 Gy) and 61 Gy (range, 34-72 Gy), respectively. Conventional fractionation was used in 287 patients (90.5%). Forty-five patients (14.2%) received chemotherapy. RESULTS The median follow-up was 11.4 years (range, 5.1-38.0 years). Ninety-eight patients (30.9%) developed CNP, with a median latent period of 7.6 years (range, 0.3-34 years). Patients had a higher rate of CNP (81 cases, 25.5%) in lower-group cranial nerves compared with upper group (44 cases, 13.9%) (χ(2) = 34.444, p < 0.001). Fifty-nine cases experienced CNP in more than one cranial nerve. Twenty-two of 27 cases (68.8%) of intragroup CNP and 11 of 32 cases (40.7%) of intergroup CNP occurred synchronously (χ(2) = 4.661, p = 0.031). The cumulative incidences of CNP were 10.4%, 22.4%, 35.5%, and 44.5% at 5, 10, 15, and 20 years, respectively. Multivariate analyses revealed that CNP at diagnosis, chemotherapy, total radiation dose to the nasopharynx, and upper neck fibrosis were independent risk factors for developing radiation-induced CNP. CONCLUSION Radiation-induced fibrosis may play an important role in radiation-induced CNP. The incidence of CNP after definitive radiotherapy for NPC remains high after long-term follow-up and is dose and fractionation dependent.

The risk of second primary tumors in patients with nasopharyngeal carcinoma after definitive radiotherapy.

Second primary tumors (SPTs) have a substantial impact on survival in cancer patients. However, risk factors for SPTs have not been documented well, especially in nasopharyngeal carcinoma (NPC). The objective of this retrospective analysis was to evaluate such risks in patients with NPC after they received definitive radiation treatment.

Neoadjuvant chemotherapy followed by concurrent chemoradiation for locoregionally advanced nasopharyngeal carcinoma: Interim results from 2 prospective phase 2 clinical trials

The authors studied the efficacy of neoadjuvant chemotherapy, consisting of a taxane, cisplatin, and 5‐fluorouracil (5‐FU) (the TPF regimen) followed by concurrent chemoradiation, in 2 separately designed and synchronously executed phase 2 trials for stage III and IVA/IVB nasopharyngeal cancer (NPC).

Treatment for retropharyngeal metastatic undifferentiated squamous cell carcinoma from an unknown primary site: Results of a prospective study with irradiation to nasopharyngeal mucosa plus bilateral neck

Background and Objective To evaluate treatment outcomes for patients with retropharyngeal metastatic undifferentiated squamous cell carcinoma (SCC) from an unknown primary site. Methods From January 2005 to January 2015, patients who presented with enlarged retropharyngeal nodes underwent transoral sonography-guided fine-needle aspiration to confirm histology. Those with metastatic undifferentiated SCC with unknown primary tumors were treated with radical radiotherapy to nasopharyngeal mucosa plus bilateral neck. Chemotherapy was administered for patients staged N2-3. Endpoints included metastatic nodes control, the appearance of primary tumor, overall survival and treatment-related toxicities. Results A total of 49 patients were recruited into this study. Retropharyngeal and cervical nodal disease was controlled in 96% of all patients. The incidence of occult primary cancer appearance was 8%. No primary cancer other than of the nasopharynx was detected during the course of follow-up. Ten patients developed distant metastases. The 5-year overall survival, progression-free survival, regional relapse free survival, distant metastasis free survival were 79.6%, 61.1%, 83.4%, 73.8%, respectively. Common late adverse effects included xerostomia (57%) and hearing impairment (35%). Conclusion Radical radiotherapy to both the nasopharynx and bilateral neck can achieve excellent outcome with mild toxicities for patients with retropharyngeal metastatic undifferentiated squamous cell carcinoma from an unknown primary site.

Effects of induction docetaxel, platinum, and fluorouracil chemotherapy in patients with stage III or IVA/B nasopharyngeal cancer treated with concurrent chemoradiation therapy: Final results of 2 parallel phase 2 clinical trials

The effects of docetaxel, platinum, and fluorouracil (TPF) induction chemotherapy plus concurrent chemoradiotherapy (CCRT) on locoregionally advanced nasopharyngeal cancer (NPC) are unclear. This study examined the long‐term outcomes of the addition of this regimen to CCRT for stage III and IVA/B NPC.

Management of indeterminate pulmonary nodules (<1 cm) newly detected during the follow-up of nasopharyngeal carcinoma patients

To investigate the management for the indeterminate pulmonary nodules newly detected during the follow‐up for nasopharyngeal carcinoma (NPC) patients.

Effects of induction taxotere, platinum, and fluorouracil (TPF) chemotherapy in patients with stage III and IVA/B nasopharyngeal cancer treated with concurrent chemoradiation therapy: final results of two parallel phase 2 clinical trials

BACKGROUND Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced nasopharyngeal cancer. The effect of induction chemotherapy plus CCRT in patients with this stage of disease is unclear. We therefore examined the long-term outcomes of the addition of induction chemotherapy (consisting of docetaxel, cisplatin, and fluorouracil [TPF]) to CCRT in patients with stage III and IVA/B nasopharyngeal cancer. METHODS Between January, 2007, and July, 2011, we synchronously undertook two parallel phase 2 single-arm trials to evaluate the efficacy and toxicity of TPF-based induction chemotherapy. One trial was for patients with stage III nasopharyngeal cancer, and the other was for patients with stage IVA/B disease. Treatment regimens used in both trials were identical. The induction chemotherapy consisted of three cycles of docetaxel 75 mg/m2 (day 1), cisplatin 75 mg/m2 (day 1), and a continuous fluorouracil infusion at 500 mg/m2 per day (days 1-5) every 4 weeks. Radiotherapy was given mainly with intensity-modulated technique (IMRT) at 2·0 Gy per fraction with five daily fractions per week to a total dose of 70 Gy to the primary tumour and neck adenopathy, and 54-60 Gy to the uninvolved neck region. The concurrent chemotherapy consisted of weekly cisplatin at 40 mg/m2. Our primary endpoint for both trials was 5-year overall survival, based on intention-to-treat analysis. Both studies were designed to detect a 20% improvement in 5-year overall survival from historical controls. Comparison of results between the two trials was planned. The protocol was conducted with approval from the institutional review board of the Shanghai Proton and Heavy Ion Center. The trials are registered with ClinicalTrials.gov, numbers NCT00816855 and NCT00816816. FINDINGS 52 eligible patients with stage III nasopharyngeal cancer and 64 eligible patients with non-metastatic stage IV disease were accrued to the two trials. With a median follow-up of 66·8 months (range 15·9-105·4), 5-year overall survival was 91·6% (95% CI 83·6-99·6) for stage III patients and 83·1% (72·9-93·3) for stage IVA/B patients (p=0·059), which approximated to a 20% improvement compared with historical controls. 5-year progression-free survival was 80·1% (95% CI 69·1-91·1) versus 66·8% (54·1-79·5; p=0·072), distant metastasis free survival was 93·0% (85·4-100·0) versus 93·1% (86·6-99·6; p=0·387), and local progression-free survival was 92·0% (84·6-99·4) versus 87·2% (77·6-96·8; p=0·276), for patients with stage III versus stage IVA/IVB nasopharyngeal cancer. Multivariate analyses indicated that T-classification (T1/2 vs T3/4) and N-classification (N3 vs N0-2) were the only two significant prognosticators for overall survival (hazard ratio [HR] 2·52, 95% CI 1·178-5·394, p=0·017; HR 1·808, 95% CI 1·002-3·264, p=0·045, respectively), whereas age, gender, number of induction chemotherapy cycles (two vs three), number of concurrent chemotherapy cycles (four or more vs five or less), RT technique, and the presence of residual primary or neck disease were not significant in predicting overall survival. INTERPRETATION TPF-based induction chemotherapy significantly improved overall and progression-free survival when given before CCRT in locoregionally advanced nasopharyngeal cancer. T-classification and N-classification were the only two significant prognostic factors in predicting overall survival. A phase 3 trial is ongoing to confirm such benefit. FUNDING None.