T. Lu

Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: an analysis of survival and treatment toxicities.

BACKGROUND AND PURPOSEnTo evaluate the long-term survival outcomes and toxicity of NPC patients treated with intensity-modulated radiotherapy (IMRT).nnnMATERIALS AND METHODSnFrom May 2001 to October 2008, 868 non-metastatic NPC patients treated by IMRT were analyzed retrospectively. The Radiation Therapy Oncology Group (RTOG) criteria were used to assess toxicity.nnnRESULTSnWith a median follow-up of 50 months (range, 5-115 months), the 5-year estimated disease specific survival (DSS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS) and distant metastasis-free survival (DMFS) were 84.7%, 91.8%, 96.4% and 84.6%, respectively. Of the 868 patients, 186 (21.3%) developed failure after treatment. Distant metastasis was the major failure pattern after treatment. The 5-year OS rate in patients with stage I, II, III, and IVa-b were 100.0%, 94.3%, 83.6%, and 70.5%, respectively. The 5-year LRFS rate in patients with stage T1, T2, T3, and T4 disease were 100.0%, 96.0%, 90.4%, and 83.3%, respectively (χ(2) = 26.32, P<0.001). The 5-year DMFS for N0, N1, N2, and N3 patients were 96.1%, 85.6%, 73.7%, and 62.1%, respectively (χ(2) = 65.54, P<0.001). Concurrent chemotherapy failed to improve survival rates for patients with advanced locoregional disease. The most common acute toxicities were mainly in grade 1 or 2. Compared with IMRT alone, IMRT plus concurrent chemotherapy increased the severity of acute toxicities. The incidence of brain radiation damage was relatively high (5.5%, 48/868 cases), and was not observed in patients with stage T1-2.nnnCONCLUSIONnIMRT for NPC yielded excellent survival outcomes, and distant metastasis was the most commonly seen failure pattern after treatment. The role of concurrent chemotherapy for advanced locoregional stage NPC patients needs to be further investigated. Treatment-related toxicities were well tolerable. However, the incidence of brain radiation damage was relatively high, especially for patients with advanced T-stage.

Consensus recommendations for management of head and neck cancer in Asian countries: A review of international guidelines

Head and neck cancer (HNC) is a disease of the upper aerodigestive tract and is one of the most frequently diagnosed cancers worldwide. A high rate of cancers involving the head and neck are reported across the Asian region, with notable variations between countries. Disease prognosis is largely dependent on tumor stage and site. Patients with early stage disease have a 60-95% chance of cure with local therapy. Early diagnosis and appropriate treatment are important to increase the likelihood of cure and survival. However, the majority of patients present with locally advanced disease and require multimodality treatment. This necessitates, a multidisciplinary approach which is essential to make appropriate treatment decisions, particularly with regards to tolerability, costs, available infrastructure and quality of life issues. Unfortunately, majority of the studies that dictate current practice have been developed in the west where diseases biology, patient population and available infrastructure are very different from those in the Asian continent. With this in mind an expert panel of Head and Neck Oncologists was convened in May 2012 to review the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO) clinical practice guidelines and develop practical recommendations on the applicability of these guidelines on the management of head and neck cancer for Asian patients. The objective of this review and consensus meeting was to suggest revisions, to account for potential differences in demographics and resources, to the NCCN and ESMO guidelines, to better reflect current clinical management of head and neck cancer within the Asian region for health care providers. These recommendations, which reflect best clinical practice within Asia, are expected to benefit practitioners when making decisions regarding optimal treatment strategies for their patients.

Comparing treatment outcomes of different chemotherapy sequences during intensity modulated radiotherapy for advanced N-stage nasopharyngeal carcinoma patients

BackgroundN-stage is related to distant metastasis of nasopharyngeal carcinoma (NPC) patients. We performed this study to compare the efficacy of different chemotherapy sequences in advanced N-stage (N2 and N3) NPC patients treated with intensity modulated radiotherapy (IMRT).MethodsFrom 2001 to 2008, 198 advanced N-stage NPC patients were retrospectively analyzed. Thirty-three patients received IMRT alone. Concurrent chemoradiotherapy (CCRT) was delivered to 72 patients, neoadjuvant chemotherapy (NACT)u2009+u2009CCRT to 82 patients and CCRTu2009+u2009adjuvant chemotherapy (AC) to 11 patients.ResultsThe 5-year overall survival rate, recurrence-free survival rate, distant metastasis-free survival rate and progress-free survival rate were 47.7% and 73.1%(p<0.001), 74.5% and 91.3% (pu2009=u20090.004), 49.2% and 68.5% (pu2009=u20090.018), 37.5% and 63.8% (p<0.001) in IMRT alone and chemoradiotherapy group. Subgroup analyses indicated that there were no significant differences among the survival curves of CCRT, NACTu2009+u2009CCRT and CCRTu2009+u2009AC groups. The survival benefit mainly came from CCRT. However, there was only an improvement attendency in distant metastasis-free survival rate of CCRT group (pu2009=u20090.107) when compared with RT alone group, and NACTu2009+u2009CCRT could significantly improve distant metastasis-free survival (pu2009=u20090.017).ConclusionsFor advanced N-stage NPC patients, NACTu2009+u2009CCRT might be a reasonable treatment strategy.

Intensity-modulated radiotherapy for stage IVA/IVB nasopharyngeal carcinoma: clinical outcomes and patterns of failure in an endemic area in China.

PurposeThe purpose of this study was to analyze the mode of relapse patterns and survival of 209 patients with stage IVA and IVB nasopharyngeal carcinoma (NPC).Patients and materialsA total of 209 patients who underwent magnetic resonance imaging (MRI) and were subsequently histologically diagnosed with nondisseminated stage IV NPC received intensity-modulated radiotherapy (IMRT) as their primary treatment and were included in this retrospective study.ResultsMedian follow-up time was 65 months (range, 3–108 months). The 5-year overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates for patients with stage IVA and stage IVB NPC were 72.7 vs. 60.0u2009% (pu2009=u20090.319), 62.9 vs. 51.3u2009% (pu2009=u20090.070), 82.9 vs. 93.1u2009% (pu2009=u20090.070), 82.9 vs. 82.9u2009% (pu2009=u20090.897), 76.4 vs. 58.5u2009% (pu2009=u20090.003), respectively. Age older than 44 years was found to be a statistically significant adverse independent prognostic factor for OS. Patients with advanced N status had worse OS, DFS, and DMFS rates. Patients with a primary gross tumor volume (GTV-P) ≥u200955.11u2009ml had worse OS, DFS, and LRRFS rates.ConclusionThe results of treating stage IVA NPC with IMRT were excellent. Distant metastasis remains the most difficult treatment challenge for patients with stage IVA and IVB NPC, and more effective systemic chemotherapy should be explored.ZusammenfassungZielZiel dieser Studie war die Analyse der Rezidivmuster und des Überlebens von 209xa0Patienten mit nasopharyngealem Karzinom (NPC) im Stadiumxa0IVA und IVB.Patienten und MethodenInsgesamt 209xa0Patienten, die mittels MRT und anschließender histologischer Untersuchung mit nichtdisseminiertem NPC im Stadiumxa0IV diagnostiziert worden waren, erhielten eine intensitätsmodulierte Strahlentherapie (IMRT) als Primärbehandlung und wurden in diese retrospektive Studie aufgenommen.ErgebnisseDie mediane Follow-up-Dauer betrug 65xa0Monate (Bereich 3–108xa0Monate). Das 5-Jahres-Gesamtüberleben (OS), das krankheitsfreie (DFS), lokal rezidivfreie (LRFS), lokal-regionär rezidivfreie (LRRFS) und fernmetastasenfreie Überleben (DMFS) bei Patienten im Stadiumxa0IVA und IVB betrugen jeweils 72,7 vs. 60,0u2009% (pu2009=u20090,319), 62,9 vs. 51,3u2009% (pu2009=u20090,070), 82,9 vs. 93,1u2009% (pu2009=u20090,070), 82,9 vs. 82,9u2009% (pu2009=u20090,897), 76,4 vs. 58,5u2009% (pu2009=u20090,003) bzw. Ein Alter über 44xa0Jahre erwies sich als statistisch signifikanter, ungünstiger, unabhängiger prognostischer Faktor für OS. Patienten im fortgeschrittenen N-Stadium wiesen ein schlechteres OS, DFS und DMFS auf. Patienten mit einem primären makroskopischen Tumorvolumen (GTV-P) von mehr als 55.11xa0ml hatten ein schlechteres OS, DFS und LRRFS.SchlussfolgerungDie Ergebnisse der Behandlung von Patienten mit NPC im Stadiumxa0IVA mit IMRT waren ausgezeichnet. Fernmetastasen bleiben die schwierigste Herausforderung bei der Behandlung von Patienten mit NPC im Stadiumxa0IVA und IVB und es müssen wirksamere systemische Chemotherapien erforscht werden.

Prognostic efficacy of combining tumor volume with Epstein-Barr virus DNA in patients treated with intensity-modulated radiotherapy for nasopharyngeal carcinoma

OBJECTIVESnTo evaluate the prognostic effect of combining tumor volume with pre-treatment plasma Epstein-Barr virus DNA (EBV DNA) in patients treated with intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC).nnnMATERIALS AND METHODSnA total of 180 consecutive NPC patients enrolled in this observational, prospective study and underwent IMRT. Tumor volume was delineated with IMRT planning system and plasma EBV DNA level was quantified by polymerized chain-reaction assay. The effects of tumor volume and EBV DNA level, either alone or in combination, on 5-year overall survival (OS) were cross-compared.nnnRESULTSnThe 5-year OS in patients with gross tumor volume of nasopharynx (GTVnx)⩽20cc and >20cc was significantly different (P=0.001). The 5-year OS in patients with EBV DNA <6800copies/mL and ⩾6800copies/mL was also significantly different (P<0.001). Based on the combination of GTVnx with EBV DNA, the 5-year OS in different subgroups was: low-risk (100%), intermediate-risk (87.8%, 95% CI: 70.6-95.2%) and high-risk (61.3%, 95% CI: 47.9-72.2%). Patients with small tumor volume and high EBV DNA level had a worse prognosis than those with large tumor and low EBV DNA level. Patients with low EBV DNA levels, and either small or large tumor volumes, had favorable prognosis. According to small or large tumor volume, patients with high EBV DNA level were divided into intermediaterisk and high-risk subgroups.nnnCONCLUSIONnCombining tumor volume with pre-treatment plasma EBV DNA level altered survival-risk definition for subgroups of NPC patients and this combination, more than individual factors alone, improved the accuracy of prognostic evaluation.

Prognostic significance of tumor volume in locally recurrent nasopharyngeal carcinoma treated with salvage intensity-modulated radiotherapy.

Introduction To evaluate the prognostic value of gross tumor volume (TV) in patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma. Methods Between 2001 and 2012, 291 consecutive patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma underwent salvage IMRT were retrospectively reviewed. The correlations between TV and recurrent T classification were analyzed. Survival analyses were performed. Receiver operating characteristic (ROC) curves were calculated to identify cut-off point of TV. The Akaike information criterion and Harrell’s concordance index (c-index) were utilized to test the prognostic value. Results The median TV significantly increased with advancing recurrent T classification (P<0.001). The 5-year overall survival rate was 33.2% for the entire cohort. On multivariate analysis, TV was an independent negative prognostic factor for distant metastasis-free survival (hazard ratio =1.013, P =0.003), overall survival (hazard ratio = 1.015, P<0.001) and toxicity-related death (hazard ratio = 1.014, P<0.001). The 5-year overall survival rates were 63.1% and 20.8% for patients with a TV < 22 cm3 and TV ≥22 cm3, respectively (P < 0.001). In patient with TV <22 cm3, locoregional failure is the leading cause of death. In patients with TV≥22 cm3, distant metastasis rate is higher and occurred within short term after local recurrence; meanwhile, radiation-induced injuries became more common and led to half of deaths in this group. The Akaike information criterion and c-index analyses indicated that the predictive ability of recurrent T classification improved when combined with TV. Conclusions Our data suggests TV is a significant prognostic factor for predicting the distant metastasis, overall survival and toxicity-related death of patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma after salvage IMRT. TV should be considered when designing personalized salvage treatments for these patients. For patients with bulky local recurrent tumor, radiation may need to be de-emphasized in favor of systemic treatment or best supportive care.

The efficacy and safety of Endostar combined with chemoradiotherapy for patients with advanced, locally recurrent nasopharyngeal carcinoma

Purpose To evaluate the short-term efficacy and safety of recombinant human endostatin (Endostar) combined with chemoradiotherapy for the treatment of advanced, locally recurrent nasopharyngeal carcinoma (NPC). Materials and Methods Between March 2010 and October 2013, a total of 22 patients with stage rIII-IVb locally recurrent NPC underwent salvage radiotherapy with Endostar in Sun Yat-Sen University Cancer Center. Intensity-modulated radiotherapy (IMRT) was delivered. Platinum-based chemotherapy was used in a neoadjuvant protocol. Endostar was continuously administered intravenously (105 mg/m2) for 14 days (Days 1–14) from the first day of treatment during a 21-day cycle. Tumor response and treatment toxicities were observed. Results Until January 2014, the median follow-up time was 13 months (range, 4–41 months). All patients completed the planned radiotherapy. A complete response was achieved in 20 patients, and a partial response was achieved in 2 patients. The incidence of grade 3–5 late radiation injury in this study was 50% (11/22) and that of nasopharyngeal mucosal necrosis was 31.8% (7/22). Conclusions Endostar combined with chemoradiotherapy may be effective in decreasing both the incidence of nasopharyngeal mucosal necrosis. Studies with a larger sample size and longer follow-up are warranted.

Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in nasopharyngeal carcinoma patients with cervical nodal necrosis

The effectiveness of neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiotherapy (CCRT) compared with CCRT alone in nasopharyngeal carcinoma (NPC) patients who presented with cervical nodal necrosis (CNN) is unknown. A total of 792 patients with stage T1-4N1-3M0 NPC and presented with CNN based on magnetic resonance imaging were retrospectively reviewed. Propensity score matching method was used to balance treatment arms for baseline characteristics. Eventually, 508 patients were propensity-matched on a 1:1 basis to create two groups (NACTu2009+u2009CCRT and CCRT groups). Survival rates were calculated by Kaplan–Meier method and differences were compared by using the log-rank test. The 5-year disease specific survival, disease-free survival and distant metastasis-free survival were significantly higher in NACTu2009+u2009CCRT group relative to the matched CCRT group (82.1% vs. 72.5%, Pu2009=u20090.021; 70.3% vs. 54.1%, Pu2009<u20090.001; 81.9% vs. 67.3%, Pu2009<u20090.001, respectively). Although the rates of grade 3–4 leucopenia and mucositis were higher in NACTu2009+u2009CCRT group than CCRT group, compliance with the combined treatment was good and no significant difference was observed between two groups. NACT followed by CCRT was relatively safe and could achieve better survival than CCRT alone in NPC patients with CNN by reducing the risk of death, tumor progression and distant metastasis.

Oligometastases in AJCC stage IVc nasopharyngeal carcinoma: A subset with better overall survival.

The purpose of this study was to analyze the patterns of metastasis and therapeutic approaches in American Joint Committee on Cancer (AJCC) stage IVc nasopharyngeal carcinoma (NPC).

Elevated plasma fibrinogen level shows superior prognostic value than Epstein–Barr virus DNA load for stage IVA/B nasopharyngeal carcinoma patients in the intensity-modulated radiotherapy era

Purpose Effective prognostic factors for patients with stage IVA/B nasopharyngeal carcinoma (NPC) who are susceptible to distant metastases are limited. We aim to investigate the prognostic value of pretreatment plasma fibrinogen (FIB) level and Epstein–Barr virus DNA (EBV-DNA) load in these patients in the era of intensity-modulated radiotherapy (IMRT). Results The 5-year DSS, DFS and DMFS rates of the entire cohort were 72.7%, 66.8%, 80.0%, respectively. High FIB level was identified as a negative prognostic factor for survival: the 5-year DSS, DFS and DMFS rates for patients with high FIB (> 4.0 g/L) and normal FIB (≤ 4.0 g/L) were 60.3% vs. 76.0%, 56.0% vs. 69.9%, and 59.4% vs. 85.5%, respectively (all P < 0.001). Subgroup analysis demonstrated that DSS, DFS and DMFS decreased as FIB gradually increased, even within the normal range. The risk of distant metastasis in patients with high FIB was over 3-fold than patients with normal FIB. EBV-DNA was not an independent prognostic factor for any survival outcomes in multivariate analysis. Conclusion High pretreatment FIB level shows superior prognostic value than EBV-DNA load for stage IVA/B NPC patients in the era of IMRT. Materials and Methods A total of 755 patients with newly-diagnosed stage IVA/B NPC treated with definitive IMRT between January 2007 and December 2011 were enrolled. Plasma FIB and EBV-DNA were measured before treatment. Disease-specific survival (DSS), disease-free survival (DFS) and distant metastasis-free survival (DMFS) were calculated using the Kaplan-Meier method; differences were compared using the log-rank test.