Shaojun Lin

NASOPHARYNGEAL CARCINOMA TREATED WITH REDUCED-VOLUME INTENSITY-MODULATED RADIATION THERAPY: REPORT ON THE 3-YEAR OUTCOME OF A PROSPECTIVE SERIES

PURPOSEnTo evaluate the efficacy of intensity-modulated radiotherapy (IMRT) using reduced clinical target volumes (CTV) in the treatment of nasopharyngeal carcinoma (NPC).nnnMETHODS AND MATERIALSnBetween August 2003 and December 2006, 323 patients with NPC were treated with IMRT according to this institutional protocol. Presenting stages were Stage II in 63, Stage III in 166, and Stage IVA/B in 94 patients. High-risk CTV encompassed gross tumor volume and entire nasopharyngeal mucosa with a margin. A reduced CTV was delineated for the remaining subclinical regions adjacent to the primary disease. Uninvolved neck nodes were delineated according to the Radiation Therapy Oncology Group (RTOG)/European Organisation for Research and Treatment of Cancer (EORTC) consensus excluding the deep jugular (i.e., lymph nodes in retrostyloid space above C1 vertebra) and submental nodes. Patients with locoregionally advanced diseases also received cisplatin-based chemotherapy.nnnRESULTSnWith a median follow-up of 30 months (range, 4-53 months), 12, 6, and 26 patients had developed local, regional, and distant failures, respectively. The 3-year estimated local control, regional control, metastasis-free survival, disease-free survival and overall survival were 95%, 98%, 90%, 85%, and 90%, respectively. Multivariate analyses revealed that T-classification had no predictive value for outcome, whereas N-classification was significant for predicting metastasis-free (p = 0.005) and overall survival (p =0.006). Ten patients (7.8%) experienced Grade II xerostomia at 24 months after treatment. No Grade III or IV late-toxicities were observed. Two patients died of treatment-induced complications.nnnCONCLUSIONnThe IMRT approach using a reduced target volume provided favorable outcome for NPC with acceptable toxicity. This strategy needs to be optimized and then tested in a prospective setting to learn whether further improvement can be achieved.

Sequential chemotherapy and intensity-modulated radiation therapy in the management of locoregionally advanced nasopharyngeal carcinoma: Experience of 370 consecutive cases

IntroductionTo investigate the outcome of locoregionally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT) after induction chemotherapy, with or without concomitant chemotherapy.MethodsBetween August 2003 and March 2007, 370 patients with locoregionally advanced NPC were treated with IMRT. Presenting stages were stage IIB in 62, stage III in 197, and stage IVA/B in 111 patients. All patients except for 36 patients with cervical lymphadenopathy of 4 cm or less in diameter received 2 cycles of cisplatin-based neoadjuvant chemotherapy. Forty-eight patients received cisplatin-based concurrent chemotherapy as well.ResultsWith a median follow-up time of 31 months (range 5 to 61 months), the 3-year local control, regional control, metastasis-free survival (MFS), disease-free survival (DFS) and overall survival (OS) rates were 95%, 97%, 86%, 81% and 89%, respectively. Multivariate analyses revealed that both age (≤ 60 vs. >60) and N-classification are significant prognosticators for OS (P = 0.001, hazard ratio [HR] 2.395, 95% confidence interval [CI] 1.432-4.003; P = 0.012, hazard ratio [HR] 2.614, 95% confidence interval [CI] 1.235-5.533); And N-classification is the only significant predicative factor for MFS (P = 0.002, [HR] 1.99, 95% CI 1.279-3.098). T-classification and concurrent chemotherapy were not significant prognostic factors for local/regional control, MFS, DFS, or OS. Subgroup analysis revealed that concurrent chemotherapy provided no significant benefit to IMRT in locoregionally advanced NPC, but was responsible for higher rates of grade 3 or 4 acute toxicities (50% vs. 29.8%, P < 0.005). No grade 3 or 4 late toxicity including xerostomia was observed. However, two patients treated with IMRT and neoadjuvant but without concurrent and adjuvant chemotherapy died of treatment related complications.ConclusionIMRT following neoadjuvant chemotherapy produced a superb outcome in terms of local control, regional control, MFS, DFS, and OS rates in patients with stage IIB to IVB NPC. Effective treatment strategy is urgently needed for distant control in patients diagnosed with locoregionally advanced NPC.

Intensity-modulated radiation therapy in the salvage of locally recurrent nasopharyngeal carcinoma.

PURPOSEnLocal recurrences of nasopharyngeal carcinoma (NPC) may be salvaged by reirradiation with conventional techniques, but with significant morbidity. Intensity-modulated radiation therapy (IMRT) may improve the therapeutic ratio by reducing doses to normal tissue. The aim of this study was to address the efficacy and toxicity profile of IMRT for a cohort of patients with locally recurrent NPC.nnnMETHODS AND MATERIALSnBetween August 2003 and June 2009, 70 patients with radiologic or pathologically proven locally recurrent NPC were treated with IMRT. The median time to recurrence was 30 months after the completion of conventional radiation to definitive dose. Fifty-seven percent of the tumors were classified asrT3-4. The minimum planned doses were 59.4 to 60 Gy in 1.8- to 2-Gy fractions per day to the gross disease with margins, with or without chemotherapy.nnnRESULTSnThe median dose to the recurrent tumor was 70 Gy (range, 50-77.4 Gy). Sixty-five patients received the planned radiation therapy; 5 patients received between 50 and 60 Gy because of acute side effects. With a median follow-up time of 25 months, the rates of 2-year locoregional recurrence-free survival, disease-free survival, and overall survival were 65.8%, 65.8%, and 67.4%, respectively. Moderate to severe late toxicities were noted in 25 patients (35.7%). Eleven patients (15.7%) had posterior nasal space ulceration, 17 (24.3%) experienced cranial nerve palsies, 12 (17.1%) had trismus, and 12 (17.1%) experienced deafness. Extended disease-free interval (relative risk 2.049) and advanced T classification (relative risk 3.895) at presentation were adverse prognostic factors.nnnCONCLUSIONnReirradiation with IMRT provides reasonable long-term control in patients with locally recurrent NPC.

A Comparison Between the Chinese 2008 and the 7th Edition Ajcc Staging Systems for Nasopharyngeal Carcinoma

Objectives:The Chinese 1992 staging system for nasopharyngeal carcinoma (NPC) was revised in 2008 and was renamed as the Chinese 2008 staging system. The seventh edition of the American Joint Committee on Cancer (AJCC) staging manual also defined new rules for classifying NPC in 2010. The purpose of the current study is to compare the 2 in terms of patient distribution and efficacy in predicting prognosis. Methods:A total of 816 patients with untreated nondisseminated NPC who underwent magnetic resonance imaging scan of the nasopharynx and neck were studied retrospectively. All magnetic resonance imaging scans were reevaluated independently by 2 radiologists specialized in head and neck cancers. All patients were restaged according to the Chinese 2008 staging system and the AJCC staging system of NPC. Results:Using the 2 staging systems, the consistency for patient distributions in T, N, and overall stages was found to be moderate, with the &kgr; value of 0.65, 0.54, and 0.46, respectively. According to the Chinese 2008 and the AJCC staging systems, the proportion of patients in stages I, II, III, and IV accounted for 2.3% versus 2.3%, 11.0% versus 23.7%, 39.4% versus 49.1%, and 47.3% versus 24.9%, respectively. The AJCC T classification was better in predicting the 5-year local relapse-free survival, whereas the Chinese 2008 N classification was superior in predicting the 5-year distant metastasis-free survival. However, survival curves for the 5-year overall survival were comparable in both systems. Conclusions:We revealed a slightly better patient distribution of overall stage with AJCC comparing with the Chinese 2008 staging system. The prognostic value of AJCC T classification was considered to be better, whereas that of Chinese 2008 N classification was superior.

Intensity-Modulated Radiation Therapy Without Concurrent Chemotherapy for Stage IIB Nasopharyngeal Cancer

Objectives:To evaluate the treatment outcome of patients with stage IIB nasopharyngeal carcinoma (NPC) after definitive intensity-modulated radiotherapy (IMRT) without concurrent chemotherapy. Methods:Between August 2003 and December 2006, 107 patients with T1N1M0 (8%), T2N0M0 (13%), or T2N1M0 (79%) NPC were definitively treated with IMRT. Sixty-one received IMRT only, and 46 patients had various strategies of systemic treatment, consisting of abbreviated neoadjuvant (38 patients), concurrent (8 patients), or adjuvant (16 patients) chemotherapy. Radiation doses prescribed to the planning tumor volume of the gross disease, high-risk clinical tumor volume, and low-risk clinical tumor volume were 66 to 70 Gy, 54 to 60 Gy, and 50–54 Gy, respectively. Results:With a median follow-up of 39 months (range, 7–77 months), 6 patients had locoregional relapse: 1 local only, 1 locoregional, and 4 regional only. Five patients had distant failure. Five of 6 total deaths were cancer related. The 3-year estimated local control, regional control, metastasis-free survival, disease-free survival, and overall survival were 96.5%, 98%, 94.8%, 90.7%, and 95.8%, respectively. No significant difference in treatment outcome was demonstrated in patients treated with or without chemotherapy of any schedule. Conclusions:IMRT without concurrent chemotherapy provides good outcome for patients with stage IIB NPC with acceptable toxicity. Neoadjuvant chemotherapy did not appear to provide significant additional benefit for this patient subgroup. Further investigation in the prospective setting is warranted to explore the role of systemic agents in the treatment of NPC with limited primary disease and cervical lymphadenopathy when IMRT is used.

Combined high-dose radiation therapy and systemic chemotherapy improves survival in patients with newly diagnosed metastatic nasopharyngeal cancer.

ObjectivesTo investigate the efficacy of high-dose radiation therapy (RT) to the primary and regional disease in combination with systemic chemotherapy and local treatment to metastatic foci in patients with newly diagnosed metastatic nasopharyngeal carcinoma (NPC). MethodsOne hundred and five consecutive patients with pathologically confirmed NPC with distant metastasis at diagnosis seen between 1995 and 2002 were reviewed. All were offered cisplatin-based chemotherapy, high-dose RT (>30 Gy) to the head and neck region, and active treatment to the metastatic foci. ResultsPatients’ median age was 46 years, and all had a Karnofsky Performance Score of ≥70. Eighty-nine patients (85%) had metastases confined to 1 organ. Ninety-six patients (91%) received at least 1 cycle of chemotherapy and 71 (68%) received greater than 65 Gy of radiation to the head and neck region. With a median follow-up time of 22 months (range: 2 to 142 mo), 90 patients had deceased, and the median survival time of the entire group was 25 months. The 2 and 5-year estimated overall survival rates were 50% and 17%, respectively. Radiation dose of greater than 65 Gy to the primary region (P = 0.05) and number of organs with metastases (single vs. multiple) (P = 0.002) were independent predictive factors for overall survival on log-rank tests. Only moderately severe acute toxicities, such as Radiation Therapy Oncology Group grade 3 mucositis, skin desquamation, and leukocytopenia were observed. No patient experienced grade 4 acute toxicities. ConclusionsHigh-dose RT is indicated for local disease control in patients with metastatic NPC, and may improve survival when actively used with systemic chemotherapy and local treatment for metastatic foci. Patients with single-organ metastases have a better prognosis as compared with those with more widespread metastases.

Analysis of rare periparotid recurrence after parotid gland-sparing intensity-modulated radiotherapy for nasopharyngeal carcinoma

PURPOSEnPeriparotid recurrence is an uncommon phenomenon after intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma. This study aimed to discuss the clinical characteristics, reasonable causes and feasible therapeutic modalities of patients with nasopharyngeal carcinoma and periparotid recurrence.nnnPATIENTS AND METHODSnThe medical records of 1852 patients with non-metastatic nasopharyngeal carcinoma treated with initial IMRT between January 2008 and December 2012 were retrospectively reviewed, and nine patients were finally found to have developed periparotid recurrence after IMRT. After periparotid failure, four received radiotherapy and chemotherapy, two had surgery, two had surgery and adjuvant radiotherapy or chemotherapy, and one received radiotherapy alone.nnnRESULTnThe incidence rate of periparotid recurrence was 4.9‰. According to pretreatment magnetic resonance imaging (MRI) scans, all patients had both ipsilateral retropharyngeal lymph nodes metastasis with 66.7% of extracapsular spread and level II lymphadenopathy with all extracapsular spread. The median time interval to periparotid failure was 14.8 months, and six patients were found to have a relapse in the primary sites of unsuspicious parotid nodules. After a median follow-up of 46.4 months, five patients developed distant metastasis, three of them developed local failure. In addition, one developed regional failure, one developed locoregional recurrence, and only one was alive without evidence of disease at the last follow-up.nnnCONCLUSIONnPeriparotid recurrences are rare after definitive IMRT for nasopharyngeal carcinoma. However, patients with ipsilateral retropharyngeal lymph nodes or level II nodal extracapsular spread on pretreatment MRI could be suspicious of metastatic periparotid nodules. Distant metastases were the main treatment failure despite a combination of several salvage treatment of periparotid recurrence. More effective chemotherapy should be explored.