Yi Jun Hua

Concurrent Chemoradiotherapy vs Radiotherapy Alone in Stage II Nasopharyngeal Carcinoma: Phase III Randomized Trial

BACKGROUND Concurrent chemoradiotherapy (CCRT) has been shown to improve outcomes for stage III-IV nasopharyngeal carcinoma (NPC) patients compared with radiotherapy (RT) alone, but the effectiveness of the combined therapy for stage II NPC patients is unknown. METHODS Patients with Chinese 1992 stage II NPC were randomly assigned to receive either RT alone (n = 114) or CCRT (n = 116). The CCRT patients were given concurrent cisplatin (30 mg/m(2) on day 1) weekly during RT. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), distant metastasis-free survival, and locoregional relapse-free survival. All patients were analyzed by the intent-to-treat principle. The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) and in multivariable analyses to test the independent statistical significance of treatment intervention. Toxic effects and the response to treatment were analyzed using the χ(2) test. All statistical tests were two-sided. RESULTS With a median follow-up of 60 months, adding chemotherapy statistically significantly improved the 5-year OS rate (94.5% vs 85.8%; HR of death = 0.30, 95% CI = 0.12 to 0.76; P = .007), PFS (87.9% vs 77.8%; HR of progression = 0.45, 95% CI = 0.23 to 0.88; P = .017), and distant metastasis-free survival (94.8% vs 83.9%; HR of distant relapse = 0.27, 95% CI = 0.10 to 0.74; P = .007); however, there was no statistically significant difference in the 5-year locoregional relapse-free survival rate (93.0% vs 91.1%; HR of locoregional relapse = 0.61, 95% CI = 0.25 to 1.51; P = .29). Multivariable analysis showed that the number of chemotherapy cycles was the only independent factor that was associated with OS, PFS, and distant control in stage II NPC. The CCRT arm experienced statistically significantly more acute toxic effects (P = .001), although the rate of late toxic effects did not increase statistically significantly. CONCLUSION Concurrent chemotherapy and radiotherapy is associated with a considerable survival benefit for patients with stage II NPC.

Endoscopic nasopharyngectomy for locally recurrent nasopharyngeal carcinoma.

Nasopharyngectomy is the primary treatment for locally recurrent nasopharyngeal carcinoma (rNPC). However, oncological nasopharyngectomy is difficult to achieve, even using extranasal surgical approaches, with potential risks of severe functional disabilities and serious complications. This report introduces an innovative, minimally invasive, oncological, endoscopic nasopharyngectomy.

Long-term treatment outcome of recurrent nasopharyngeal carcinoma treated with salvage intensity modulated radiotherapy.

PURPOSE To evaluate the long-term treatment outcome in patients with recurrent nasopharyngeal carcinoma (NPC) treated with salvage intensity modulated radiotherapy (IMRT). MATERIALS AND METHODS One hundred and fifty one previously irradiation NPC patients with recurrent disease and re-irradiated by IMRT between 2001 and 2006 had been reviewed. The disease was re-stage I in 7, re-stage II in 21, re-stage III in 50 and re-stage IV in 73. Thirty-seven patients received concurrent chemotherapy, 39 had induction chemotherapy and 75 had radiotherapy alone. RESULTS All patients completed the planned IMRT. The median volume of the recurrent gross target volume of nasopharynx (rGTVnx) was 42.2 cm(3) (range 1.5-146.3 cm(3)). The median mean re-irradiation dose to the rGTVnx was 70.4Gy (range 62.1-77.6Gy). The median follow-up time after re-irradiation was 40.0 months (range 1.9-116.9 month). The 5-year local control rate (LCR) and overall survival rate (OS) for re-stage I, II, III, IV were 80.0%, 85.0%, 80.0%, 78.7% and 71.4%, 62.9%, 35.5%, 30.2%, respectively. Multivariate analysis indicated that rT classification (hazard ratio (HR), 2.02; 95%confidence interval (CI), 1.03-3.97; P=0.04) and the volume of rGTVnx (HR, 2.05; 95%CI, 1.31-3.22; P<0.01) were independent predictors for OS. Patients (39.0%) with re-stage III or IV disease experienced Grade 3 or 4 late toxicities. CONCLUSION Re-irradiation by IMRT for recurrent NPC resulted in encouraging local control. The clinical outcome for patients with early re-stage diseases was satisfactory. Further investigations, focus on optimising radiation dose and establishing effective treatment strategies, are warranted for advanced recurrent disease in order to improve overall survival and minimise late toxicity.

Prospective Study of Tailoring Whole-Body Dual-Modality [18F]Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography With Plasma Epstein-Barr Virus DNA for Detecting Distant Metastasis in Endemic Nasopharyngeal Carcinoma at Initial Staging

PURPOSE To evaluate which patients with nasopharyngeal carcinoma (NPC) obtained the greatest benefits from the detection of distant metastasis with [(18)F]fluorodeoxyglucose positron emission tomography and computed tomography (PET/CT) combined with plasma Epstein-Barr virus (EBV) DNA levels. PATIENTS AND METHODS Consecutive patients with NPC were prospectively enrolled. PET/CT, conventional work-up (CWU), and quantification of plasma EBV DNA were performed before treatment. The accuracy of these strategies for distant metastases was assessed. The costs of the diagnostic strategies were compared. RESULTS Eighty-six (14.8%) of the 583 eligible patients were found to have distant metastases; 71 patients (82.6%) by PET/CT and 31 patients (36.0%) by CWU. In the multivariable analysis, advanced N stage (odds ratio, 2.689; 95% CI, 1.894 to 3.818) and pretreatment EBV DNA level (odds ratio, 3.344; 95% CI, 1.825 to 6.126) were significant risk factors for distant metastases. PET/CT was not superior to CWU for detecting distant metastases in very low-risk patients (N0-1 with EBV DNA < 4,000 copies/mL; P = .062), but was superior for the low-risk patients (N0-1 with EBV DNA ≥ 4,000 copies/mL and N2-3 with EBV DNA < 4,000 copies/mL; P = .039) and intermediate-risk patients (N2-3 disease with EBV DNA ≥ 4,000 copies/mL; P < .001). The corresponding patient management changes based on PET/CT were 2.9%, 6.3%, and 16.5%, respectively. The costs per true-positive case detected by PET/CT among these groups were ¥324,138 (≈

Intensity-modulated radiotherapy prolongs the survival of patients with nasopharyngeal carcinoma compared with conventional two-dimensional radiotherapy: A 10-year experience with a large cohort and long follow-up

47,458), ¥96,907 (≈

A randomized trial of induction chemotherapy plus concurrent chemoradiotherapy versus induction chemotherapy plus radiotherapy for locoregionally advanced nasopharyngeal carcinoma

14,188), and ¥34,182 (≈

Establishment and Validation of Prognostic Nomograms for Endemic Nasopharyngeal Carcinoma

5,005), respectively. CONCLUSION PET/CT detects more distant metastases than conventional staging in patients with NPC. The largest benefit in terms of cost and patient management was observed in the subgroup with N2-3 disease and EBV DNA ≥ 4,000 copies/mL.

Postradiation nasopharyngeal necrosis in the patients with nasopharyngeal carcinoma

BACKGROUND To evaluate the survival benefit of intensity-modulated radiotherapy (IMRT) compared with conventional two-dimensional radiotherapy (2D-CRT) in nasopharyngeal carcinoma (NPC) using a large cohort with long follow-up. METHODS We retrospectively analysed 7081 non-metastatic NPC patients who received curative IMRT or 2D-CRT from February 2002 to December 2011. RESULTS Of the 7081 patients, 2245 (31.7%) were administered IMRT, while 4836 (68.3%) were administered 2D-CRT. At 5 years, the patients administered IMRT had significantly higher local relapse-free survival (LRFS), loco-regional relapse-free survival (LRRFS), progression-free survival (PFS) and overall survival (OS) (95.6%, 92.5%, 82.1% and 87.4%, respectively) than those administered 2D-CRT (90.8%, 88.5%, 76.7% and 84.5%, respectively; p<0.001). The distant metastasis-free survival (DMFS) was higher for IMRT than 2D-CRT, with borderline significance (87.6% and 85.7%, respectively; p=0.056). However, no difference was observed between IMRT and 2D-CRT in nodal relapse-free survival (NRFS; 96.3% and 97.4%, respectively; p=0.217). Multivariate analyses showed that IMRT was an independent protective prognostic factor for LRFS, LRRFS and PFS, but not NRFS, DMFS or OS. CONCLUSIONS IMRT provided an improved LRFS, LRRFS and PFS in both the early and advanced T classifications and overall stage for non-disseminated NPC compared with 2D-CRT. However, no significant advantage was observed in NRFS, DMFS or OS when IMRT was used.

Salvage endoscopic nasopharyngectomy is superior to intensity-modulated radiation therapy for local recurrence of selected T1–T3 nasopharyngeal carcinoma – A case-matched comparison

The aim of this randomized study was to compare the efficacy of induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) versus induction chemotherapy plus radiotherapy (IC+RT) for patients with locoregionally advanced nasopharyngeal carcinoma. From August 2002 to April 2005, 408 patients were randomly divided into two groups: an IC+CCRT group and an IC+RT group. Patients in both groups received the same induction chemotherapy: two cycles of floxuridine (FuDR)+carboplatin (FuDR, 750 mg/m(2), d1-5; carboplatin, area under the curve [AUC]=6). The patients received radiotherapy 1 week after they finished the induction chemotherapy. The patients in the IC+CCRT group also received carboplatin (AUC=6) on days 7, 28, and 49 of radiotherapy. Eight patients did not meet the inclusion criteria, and the remaining 400 cases were analyzed. Grade III or IV toxicity was found in 28.4% of the patients in the IC+CCRT group and 13.1% of those in the IC+RT group (P<.001). Five-year overall survival rates were 70.3% and 71.7% (P=0.734) in the IC+CCRT and IC+RT groups, respectively. No significant differences in failure-free survival, locoregional control, and distant control were found between the two groups. Compared with the IC+RT program, the IC+CCRT program used in the present study did not improve the overall survival and failure-free survival in patients with locoregionally advanced nasopharyngeal carcinoma. Using carboplatin in the concurrent chemoradiotherapy was not suitable for nasopharyngeal carcinoma.

High expression of XPA confers poor prognosis for nasopharyngeal carcinoma patients treated with platinum-based chemoradiotherapy

BACKGROUND This study aimed to establish an effective prognostic nomogram with or without plasma Epstein-Barr virus DNA (EBV DNA) for nondisseminated nasopharyngeal carcinoma (NPC). METHODS The nomogram was based on a retrospective study of 4630 patients who underwent radiotherapy with or without chemotherapy at Sun Yat-sen University Cancer Center from 2007 to 2009. The predictive accuracy and discriminative ability of the nomogram were determined by a concordance index (C-index) and calibration curve and were compared with EBV DNA and the current staging system. The results were validated using bootstrap resampling and a prospective cohort study on 1819 patients consecutively enrolled from 2011 to 2012 at the same institution. All statistical tests were two-sided. RESULTS Independent factors derived from multivariable analysis of the primary cohort to predict recurrence were age, sex, body mass index (BMI), T stage, N stage, plasma EBV DNA, pretreatment high sensitivity C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), and hemoglobin level (HGB), which were all assembled into the nomogram with (nomogram B) or without EBV DNA (nomogram A). The calibration curve for the probability of recurrence showed that the nomogram-based predictions were in good agreement with actual observations. The C-index of nomogram B for predicting recurrence was 0.728 (P < .001), which was statistically higher than the C-index values for nomogram A (0.690), EBV DNA (0.680), and the current staging system (0.609). The C-index of nomogram B (0.730) and nomogram A (0.681) remained higher for predicting recurrence among patients treated with intensity-modulated radiotherapy (P < .001). The results were confirmed in the validation cohort. CONCLUSIONS The proposed nomogram with or without plasma EBV DNA resulted in more accurate prognostic prediction for NPC patients.