Long - Term Efficacy And Failure Modes Of Nasopharyngeal Carcinoma With Intensity Modulated Radiation Therapy

Objective:To study and report the patterns of failure after intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC).Methods:From January 2007 to December 2011,527 patients with biopsy-proven, nonmetastatic NPC treated by IMRT were analyzed retrospectively.Results:The Median follow-up time were 45.5 months (range,4 to 97 months). Overall disease failure (at any site) developed in 23.0% patients (121/527 cases). Among these, distant metastasis was the major failure pattern after treatment (69 cases,57.0%). The secondary pattern of failure was local recurrence (26 cases,21.5%). In addition,9 patients (7.5%) had distant metastasis and local recurrence,7 patients (5.8%) had regional recurrence,7 patients (5.8%) had distant metastasis and regional recurrence,2 patients (1.7%) had local and regional recurrence. Only 1 patient (0.8%) had distant metastasis, local and regional recurrence.38 patients have developed local recurrence (37 cases valid), surrounding structures were involved as following:nasopharynx 29 cases, skull base 21 cases, paranasalsinus 11 cases, parapharyngeal space 10 cases, intracranial cavity 9 cases, nasalcavity 7 cases, masticatory muscles 3 cases, Infratemporal fossa 1 case, Orbital apex 1 case, laryngopharynx 1 case, oropharynx 1 case. The incidence of invasion to nasopharynx and parapharyngeal space by the primary tumors was 100%and 86.5%, respectively, but 78.4% and 27.0% at recurrence, respectively (P=0.008 and P<0.001).17 patients have developed regional recurrence (17 cases valid), the invasion site were level Ⅰ 4 cases, level Ⅱ 11 cases, level Ⅲ 4 cases, level Ⅴ 5 cases. The incidence of invasion to level Ⅱ and level Ⅲ by the primary tumors was 100% and 58.8%, respectively, but 64.7% and 23.5% at recurrence, respectively (P=0.031 and P=0.031). The distant metastasis were bone 37 cases, lung 36 cases, liver 27 cases, mediastinal lymph nodes 15 cases, Abdominal lymph nodes 10 cases, Axillary lymph node 2 cases, Brain 5 cases, Pancreas 1 case, Kidney 1 case, Pericardium 1 case, respectively.Conclusions:Distant metastasis was the most commonly seen failure pattern after treatment. Local recurrent of nasopharyngeal carcinoma mainly located in nasopharynx and skull base. Regional recurrence of nasopharyngeal carcinoma mainly occurred in level II. Distant metastasis of nasopharyngeal carcinoma mainly located in Bone, lung and liver.Objective:To study and report the second primary tumor (SPT) after intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). To assess the risks of SPT in NPC patients following IMRT.Methods:Between January 2007 to December 2011,527 patients with biopsy-proven, non-metastatic NPC treated by IMRT were analyzed retrospectively. Cumulative risk of all SPTs from the date of finishing radiotherapy was estimated by the Kaplan-Meier method. Differences in cumulative risk between groups were based on the log-rank test.Results:Median follow-up was 3.8 years (range,0.3 to 8.1 years), average follow-up was 4.1 years ±1.5 years. Of the 527 patients,12 cases (2.3%) developed SPTs after treatment. Among them 9 were males,3 were females,6 were located within the radiation field,7 were upper aerodigestive tract (UADT), 6 were head/neck,3 were lung,2 were tongue,2 were neck,2 were kidney,1 was brain,1 was oral,1 was stomach. The cumulative incidence of SPTs was 0.4% at 1 year,2.3% at 3 years and 5.8% at 5 years. The cumulative incidence of in-field SPTs was 0.4% at 1 year,0.8% at 3 years and 1.5% at 5 years. Univariate analysis revealed that sex (male had an 3.3% 5-year cumulative incidence of SPTs compared with 2.8% in female, P=0.886), age (Patients age >44 years at diagnosis NPC had an 4.0% 5-year cumulative incidence of SPTs compared with 2.9% in younger patients, P=0.142), Clinical stages(I-II stage had an 0.8% 5-year cumulative incidence of SPTs compared with 4.1% in Ⅲ-Ⅳa_b stage, P=0.122), Chemotherapy (Chemotherapy had an 3.3% 5-year cumulative incidence of SPTs compared with 1.8% in non-Chemotherapy, P=0.664), overall IMRT time (overall IMRT time>44 days had an 4.0% 5-year cumulative incidence of SPTs compared with 2.9% in overall IMRT time ≤44 days, P=0.970), had no influence on the risk of SPTs.Conclusions:The anatomic location of second primary tumor does not appear to be random. The SPTs of UADT was the most commonly seen disease site after IMRT for NPC patients. As it to SPTs, lung was the most commonly seen disease organ after IMRT for NPC patients.Objective:To evaluate the long-term survival outcomes and prognostic factor of nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT).Methods:From January 2007 to December 2011,527 patients with biopsy-proven, non-metastatic NPC treated by IMRT were analyzed retrospectively. The stage distribution (by American Joint Committee on Cancer and International Union Against Cancer staging system,2010) was 3.4% Stage Ⅰ, 21.1% Stage Ⅱ,46.5% Stage Ⅲ, and 29% Stage IVa-b. The Kaplan-Meier method was used to calculate overall survival rate (OS), local recurrence-free survival rate (LRFS), regional recurrence-free survival rate (RRFS), distant metastasis-free survival rate (DMFS), progress-free survival rate (PFS). Log-rank test was conducted to determine significance. The Cox proportional hazards regression model was used to confirm the significance of prognostic factors.Results:The median follow-up time were 45.5 months (range,4 to 97 months). Of the 527 patients,23.0%(121/527 cases) developed failure after treatment and 2.3%(12/527 cases) developed second primary tumors after treatment. The distant metastasis was 71.1% (69/121 cases). The local recurrence was 31.4% (26/121 cases). The regional recurrence was 14.0% (69/121 cases). The 5-year actuarial OS, LRFS, RRFS, DMFS and PFS were 80.9%,91.7%,96.2%,83.0% and 75.6%, respectively. The 5-year LRFS in patients with stage T1, T2, T3 and T4 disease were 100%,93.1%,92.0% and 85.8%, respectively (x2=14.250,P=0.003). Group comparison analysis revealed that LRFS were significantly different among groups of patients with different T stages except groups of patients with T1 and T2 stage (x2=3.540,P=0.060), T2 and T3 stage (x2=0.684,P=0.408), T3 and T4 stage (x2=3.264,P=0.071). The 5-year DMFS for No, N1, N2, and N3 patients were 95.0%,86.1%,79.5% and 67.2%, respectively (x2=16.088,P=0.001). Group comparison analysis revealed that DMFS were significantly different among groups of patients with different N stages except groups of patients with No and Ni stage (x2=2.878,P=0.090), N2 and N3 stage (x2=2.059,P=0.151). Multivariate analysis by Cox proportional-hazards model showed that the age and T stage were the independent prognostic predictors of OS. T stage was only independent prognostic predictors of LRFS. Age and N stage were independent prognostic predictors of DMFS and PFS.Conclusions:IMRT for NPC yielded excellent survival outcomes. And a greater improvement of treatment results with IMRT than with 2D-CRT was demonstrated primarily by achieving a higher local tumor control rate and overall survival rate in NPC patients. Distant metastasis was the most commonly seen failure pattern after treatment.