Concurrent chemoradiotherapy in locoregionally recurrent nasopharyngeal carcinoma

PURPOSE: To analyze the results of concurrent chemoradiotherapy in patients with locoregional recurrent nasopharyngeal carcinoma. METHODS AND MATERIALS: We performed a retrospective analysis of 35 patients with locoregional recurrent nasopharyngeal carcinoma referred to our department between March 1994 and November 2002. Most patients were male (77%), Chinese (97%), and had undifferentiated carcinoma (89%). Most had extensive locally recurrent Stage rT3-T4 disease (66%) with a median age at recurrence of 49 years (range, 35-69 years). A repeat course of radiotherapy was given concurrently with cisplatin, with cisplatin/5-fluorouracil as consolidation treatment. Significant morbidities were present, including cranial nerve palsies due to extensive recurrent local disease before treatment of the recurrence. RESULTS: The response rate to concurrent chemoradiotherapy was 58% (29% complete response and 29% partial response). The 5-year progression-free and overall survival rate, calculated using the Kaplan-Meier method, was 15% and 26%, respectively. Only 3 patients developed systemic metastases. Grade 3-4 acute toxicities included emesis (9%) and neutropenia (14%), and Grade 3-4 late toxicities consisted of temporal lobe necrosis (3%), cranial neuropathy (6%), and endocrine abnormalities (14%). CONCLUSION: Concurrent chemoradiotherapy is feasible in a selected group of patients with locoregional recurrent NPC, but the risk of major late toxicities is significant.     

Preliminary results of a phase I/II study of simultaneous modulated accelerated radiotherapy for nondisseminated nasopharyngeal carcinoma

PURPOSE: To present preliminary results of intensity-modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiotherapy (SMART) boost technique in patients with nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Twenty patients who underwent IMRT for nondisseminated NPC at the Asan Medical Center between September 2001 and December 2003 were prospectively evaluated. Intensity-modulated radiotherapy was delivered with the "step and shoot" SMART technique at prescribed doses of 72 Gy (2.4 Gy/day) to the gross tumor volume, 60 Gy (2 Gy/day) to the clinical target volume and metastatic nodal station, and 46 Gy (2 Gy/day) to the clinically negative neck region. Eighteen patients also received cisplatin once per week. RESULTS: The median follow-up period was 27 months. Nineteen patients completed the treatment without interruption; the remaining patient interrupted treatment for 2 weeks owing to severe pharyngitis and malnutrition. Five patients (25%) had Radiation Therapy Oncology Group Grade 3 mucositis, whereas 9 (45%) had Grade 3 pharyngitis. Seven patients (35%) lost more than 10% of their pretreatment weight, whereas 11 (55%) required intravenous fluids and/or tube feeding. There was no Grade 3 or 4 xerostomia. All patients showed complete response. Two patients had distant metastases and locoregional recurrence, respectively. CONCLUSION: Intensity-modulated radiotherapy with the SMART boost technique allows parotid sparing, as shown clinically and by dosimetry, and might also be more effective biologically. A larger population of patients and a longer follow-up period are needed to evaluate ultimate tumor control and late toxicity.     

Treatment outcomes after reduction of the target volume of intensity-modulated radiotherapy following induction chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: A prospective,multi-center,randomized clinical trial

Purpose

To investigate whether reducing the target volume of intensity-modulated radiotherapy (IMRT) after induction chemotherapy (IC) improves the quality of life (QOL) in locoregionally advanced nasopharyngeal carcinoma (NPC) without decreasing the local control and survival rate.

Preliminary results of a prospective randomized trial comparing concurrent chemoradiotherapy plus adjuvant chemotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma in endemic regions of china

PURPOSE: A prospective randomized trial was performed to evaluate the efficacy of concurrent chemotherapy and adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) in endemic regions of China. METHODS AND MATERIALS: Between July 2002 and September 2005, 316 eligible patients were randomly assigned to receive either radiotherapy alone (RT) or chemoradiotherapy concurrent with adjuvant chemotherapy (CRT). All patients received 70 Gy in 7 weeks using standard RT portals and techniques. The CRT patients were given concurrent cisplatin (40 mg/m(2) on Day 1) weekly during RT, followed by cisplatin (80 mg/m(2) on Day 1) and fluorouracil (800 mg/m(2) on Days 1-5) every 4 weeks (Weeks 5, 9, and 13) for three cycles after completion of RT. All patients were analyzed by intent-to-treat analysis. RESULTS: The two groups were well-balanced in all prognostic factors and RT parameters. The CRT group experienced significantly more acute toxicity (62.6% vs. 32%, p = 0.000). A total of 107 patients (68%) and 97 patients (61%) completed all cycles of concurrent chemotherapy and adjuvant chemotherapy, with a median follow-up time of 29 months. The 2-year overall survival rate, failure-free survival rate, distant failure-free survival rate, and locoregional failure-free survival rate for the CRT and RT groups were 89.8% vs. 79.7% (p = 0.003), 84.6% vs. 72.5% (p = 0.001), 86.5% vs. 78.7% (p = 0.024), and 98.0% vs. 91.9% (p = 0.007), respectively. CONCLUSIONS: This trial demonstrated the significant survival benefits of concurrent chemotherapy plus adjuvant chemotherapy in patients with locoregionally advanced NPC in endemic regions of China.     

鼻咽癌同步推量同步放化疗与常规分割后缩野同步放化疗的疗效及毒性反应对比分析

目的 对比分析鼻咽癌同步推量同步放化疗与常规分割后缩野同步放化疗的疗效及毒性反应。方法 回顾性分析自2007年1月—2008年12月于我院接受同步放化疗后的90例鼻咽癌患者,其中同步推量组45例,常规分割后缩野组45例。对比分析两组患者的5年总生存率(Overall survival,OS)、无进展生存率(Progression free survival,PFS)、无局部区域复发生存率(Loco-regional recurrence-free survival,LRFS)以及毒性反应。结果 同步推量组5年OS、PFS、LRFS分别为84.4%、75.6%、88.9%,常规分割后缩野组5年OS、PFS、LRFS分别为82.2%、71.1%、86.7%,两组OS、PFS、LRFS差异无统计学意义。常规分割后缩野组脑干、脊髓、腮腺放疗反应要轻于同步推量组。结论 在调强放疗时代,应用同步推量同步放化疗和常规分割后缩野同步放化疗两种方式在预后方面无统计学差异,而常规分割后缩野组放疗毒性较轻。     

Concurrent chemoradiotherapy followed by adjuvant chemotherapy compared with concurrent chemoradiotherapy alone for the treatment of locally advanced nasopharyngeal carcinoma: a retrospective controlled study

Objective

We evaluated the survival benefit of providing concurrent chemoradiotherapy (ccrt) plus adjuvant chemotherapy compared with ccrt alone to patients with locally advanced nasopharyngeal carcinoma.

Methods

This retrospective study included 130 patients with nasopharyngeal carcinoma treated with ccrt plus adjuvant chemotherapy from June 2005 to December 2010. Another 130 patients treated with ccrt alone during the same period were matched on age, sex, World Health Organization histology, T stage, N stage, and technology used for radiotherapy. The endpoints included overall survival, locoregional failure-free survival, distant metastasis failure-free survival, and failure-free survival.

Results

At a mean follow-up of 42.1 months (range: 8–85 months), the observed hazard ratios for the group receiving ccrt plus adjuvant chemotherapy compared with the group receiving ccrt alone were: for overall survival, 0.77 [95% confidence interval (ci): 0.37 to 1.57]; for locoregional failure-free survival, 1.00 (95% ci: 0.37 to 2.71); for distant metastasis failure-free survival, 1.15 (95% ci: 0.56 to 2.37); and for failure-free survival, 1.26 (95% ci: 0.69 to 2.28). There were no significant differences in survival between the groups. After stratification by disease stage, ccrt plus adjuvant chemotherapy provided a borderline significant benefit for patients with N2–3 disease (hazard ratio: 0.35; 95% ci: 0.11 to 1.06; p = 0.052). Multivariate analyses indicated that only tumour stage was a prognostic factor for overall survival.

Conclusions

Patients with locally advanced nasopharyngeal carcinoma received no significant survival benefit from the addition of adjuvant chemotherapy to ccrt. However, patients with N2–3 disease might benefit from the addition of adjuvant chemotherapy to ccrt.     

Treatment of Stage IV(A-B) nasopharyngeal carcinoma by induction-concurrent chemoradiotherapy and accelerated fractionation: impact of chemotherapy schemes

PURPOSE: The aim of this study was to evaluate the impact of different chemotherapy regimens in patients with advanced nasopharyngeal carcinoma (NPC) treated by induction-concurrent chemoradiotherapy. METHODS AND MATERIALS: Between 1998 and 2003, 75 Stage IV(A-B) NPC patients were treated with 3 cycles of induction chemotherapy with cisplatin plus 5-fluorouracil (PF) (n = 41) or cisplatin plus gemcitabine (PG) (n = 34), followed by accelerated radiotherapy in concurrence with 2 cycles of cisplatin. In 18 (24%) patients, cisplatin was completely replaced by carboplatin in both concurrent cycles, mainly because of borderline renal functions. RESULTS: The median follow-up was 3.6 years. The 3-year locoregional failure-free survival, progression-free survival, and overall survival of the whole group were 80%, 68%, and 80% respectively. No significant difference was found between patients treated with either induction regimens. However, patients with only carboplatin in the 2 concurrent cycles had significantly inferior 3-year locoregional failure-free survival (56% vs. 86%, p = 0.014), progression-free survival (39% vs. 72%, p = 0.001), and overall survival (61% vs. 87%, p = 0.046) when compared with the rest of the group. In multivariate analysis, the complete replacement of cisplatin by carboplatin during concurrent chemoradiotherapy was still an independent adverse factor in locoregional failure-free survival (hazard ratio, 3.662; 95% CI, 1.145-11.765; p = 0.029) and progression-free survival (hazard ratio, 3.390; 95% CI, 1.443-7.937; p = 0.005). CONCLUSIONS: The more convenient PG regimen is as effective as the PF regimen as induction chemotherapy for patients with advanced NPC. Replacing cisplatin with carboplatin in the concurrent phase carries a poor prognosis.     

Serum C-reactive protein predicts poor prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy

Background

We aimed to evaluate the association of serum C-reactive protein (crp) with prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.

Methods

We retrospectively reviewed 79 patients with locoregionally advanced nasopharyngeal carcinoma (cT3–4N0–3M0) treated with chemoradiotherapy. Chemoradiotherapy consisted of external-beam radiotherapy to the nasopharynx (70–80 Gy), the lymph node–positive area (60–70 Gy), and the lymph node–negative area (50–60 Gy) combined with 3 cycles of various platinum-based regimens delivered at 3-week intervals. Elevated crp was defined as more than 8 mg/L. The survival rate was calculated using the Kaplan–Meier method, and univariate and multivariate analyses (Cox proportional hazards model) were used to identify factors significantly associated with prognosis.

Results

During the median follow-up of 3.9 years (range: 1–5.5 years), 23 patients died from nasopharyngeal cancer. The 5-year cancer-specific survival (css) rate was 62.90%. Before chemoradiotherapy, 18 patients had high serum crp; the css rate in that subgroup was significantly worse than the rate in the remaining patients (p = 0.0002). Multivariate analysis showed that crp was an independent prognostic indicator of css, with a hazard ratio of 3.04 (95% confidence interval: 1.22 to 7.55; p = 0.017). Among the 18 patients with elevated serum crp, 9 achieved normal serum crp after chemoradiotherapy, of whom 5 remained living with no evidence of recurrence or metastasis during follow-up. By contrast, the remaining 9 patients in whom serum crp did not normalize after chemoradiotherapy died within 4.2 years.

Conclusions

Elevated serum crp before treatment predicts poor prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.     

Induction chemotherapy forlocoregionally advanced nasopharyngeal carcinoma

The value of adding induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) for the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC) remains unclear. In our recent article entitled “Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial” published in theLancet Oncology, we reported the results of a phase III, multicenter, randomized controlled trial comparing cisplatin, 5?lfuo?rouracil, and docetaxel (TPF) IC plus CCRT versus CCRT alone in patients with T3?4N1/TxN2?3M0 NPC (ClinicalTrials.gov registration number NCT01245959). The IC?plus?CCRT group showed signiifcantly higher 3?year failure?free survival, overall survival, and distant failure?free survival rates than the CCRT?alone group, with an acceptable toxicity proifle. Our study suggests that adding TPF IC to CCRT could increase survival rates and reduce distant failure in patients with locoregionally advanced NPC. However, long?term follow?up is required to assess the eventual effcacy and toxicity of this strategy, and a more accurate method to determine prognosis is needed to enable better tailoring of treatment strategy for individual patients.     

消癌平联合同步放化疗治疗局部晚期鼻咽癌的临床观察

目的：观察消癌平注射液联合同步放化疗治疗晚期鼻咽癌的临床疗效。方法：选取２００７年７月１日～２００７年１０月３１日经病理学证实为局部晚期鼻咽癌６９例患者（按９２年福州分期Ⅲ、ⅣＡ期的低分化鳞状细胞癌）,随机分成两组：消癌平组（同步放化疗联合消癌平）３９例和对照组（同步放化疗）３０例。两组同步放化疗均采用常规放疗技术照射和ＴＰ方案化疗（多西他赛７５ｍｇ／ｍ２ｄ１,顺铂１００ｍｇ／ｍ２ｄ２,２８天重复）。消癌平组中消癌平注射液４０ｍｌ＋５％葡萄糖注射液２５０ｍｌ,ｄ１～ｄ７。治疗期间每周观察口咽反应、皮肤反应、骨髓抑制等副反应。同步放化疗结束后２周观察患者机能状态及免疫功能。放疗后３个月、１２个月评价有效率（ＣＲ＋ＰＲ）。结果：消癌平组患者的体力状况评分（ＫＰＳ评分）较对照组优。口咽反应、皮肤反应、骨髓抑制等不良反应在消癌平组均较对照组轻（Ｐ＜０.０５）。消癌平组有效率高于对照组（８９.７４％ ｖｓ．７３.３３％）,差别有统计学意义（Ｐ＝０.０３７５）。结论：消癌平注射液联合放化疗治疗局部晚期鼻咽癌能减轻放化疗的副反应,提高肿瘤患者的生存质量,并能提高有效率,值得进一步研究证实。     

Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: A phase III multicentre randomised controlled trial

BackgroundThe role of neoadjuvant chemotherapy (NACT) for locoregionally advanced nasopharyngeal carcinoma (NPC) is unclear. We aimed to evaluate the feasibility and efficacy of NACT followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in locoregionally advanced NPC.MethodsPatients with stage III–IVB (excluding T3N0-1) NPC were randomly assigned to receive NACT followed by CCRT (investigational arm) or CCRT alone (control arm). Both arms were treated with 80 mg/m² cisplatin every 3 weeks concurrently with radiotherapy. The investigational arm received cisplatin (80 mg/m² d1) and fluorouracil (800 mg/m² civ d1–5) every 3 weeks for two cycles before CCRT. The primary end-point was disease-free survival (DFS) and distant metastasis-free survival (DMFS). Secondary end-point was overall survival (OS). Survival curves for the time-to-event endpoints were analyzed by the Kaplan–Meier method and compared using the log-rank test. The P value was calculated using the 5-year endpoints.ResultsFour hundred seventy six patients were randomly assigned to the investigational (n = 238) and control arms (n = 238). The investigational arm achieved higher 3-year DFS rate (82.0%, 95% CI = 0.77–0.87) than the control arm (74.1%, 95% CI = 0.68–0.80, P = 0.028). The 3-year DMFS rate was 86.0% for the investigational arm versus 82.0% for the control arm, with marginal statistical significance (P = 0.056). However, there were no statistically significant differences in OS or locoregional relapse-free survival (LRRFS) rates between two arms (OS: 88.2% versus 88.5%, P = 0.815; LRRFS: 94.3% versus 90.8%, P = 0.430). The most common grade 3–4 toxicity during NACT was neutropenia (16.0%). During CCRT, the investigational arm experienced statistically significantly more grade 3–4 toxicities (P < 0.001).ConclusionNACT improved tumour control compared with CCRT alone in locoregionally advanced NPC, particularly at distant sites. However, there was no early gain in OS. Longer follow-up is needed to determine the eventual therapeutic efficacy.     

TPF方案诱导化疗联合替吉奥同步放疗治疗局部晚期鼻咽癌的临床观察

目的 探讨TPF方案诱导化疗联合替吉奥（S-1）同步调强适形放疗（IMRT）治疗局部晚期鼻咽癌的临床疗效及安全性。方法采用诱导化疗联合S-1同步IMRT治疗38例局部晚期鼻咽癌患者,诱导化疗采用TPF方案：紫杉醇（PTX）135 mg/m2,静滴,d1;顺铂（DDP）80 mg/m2静滴,d1;氟尿嘧啶（5 FU）750 mg/（m2&#8226;d）,持续静脉泵入,d1～d5（120 h）。21天为1个周期,共行2个周期。同步化疗采用替吉奥（S-1）单药,40 mg/m2,口服,2次/日,d1～d14。21天为1个周期,共行2～3个周期。同步放疗PGTVnx（69.96～73.92）Gy/33 f,PGTVnd 69.96 Gy/33 f,PTV1 60.06 Gy/33 f,PTV2 50.96 Gy/28 f,PTVnd 50.96 Gy/28 f,1次/日,5次/周。结果 38例患者均完成2个周期诱导化疗和2～3个周期同步放化疗。所有患者治疗结束评价即刻疗效,获CR 29例,PR 8例,SD 1例,有效率（RR）为974%。治疗结束3个月评价近期疗效,获CR 33例,PR 5例,RR为100%。诱导化疗的主要毒副反应为恶心、白细胞减少、血红蛋白减少。同步放化疗的主要毒副反应为口腔黏膜炎、放射野内皮炎、吞咽痛。其中3级口腔黏膜炎、放射野内皮炎、吞咽痛的发生率分别为7.9%、2.6%、2.6%,均无4、5级毒副反应。结论TPF方案诱导化疗同步替吉奥化疗联合IMRT治疗鼻咽癌,近期疗效好,且毒副反应较小,患者耐受性好。     

局部晚期鼻咽癌不同化疗方案配合IMRT多中心前瞻性随机对照研究

目的 评价局部晚期鼻咽癌奈达铂联合多西他赛诱导化疗+奈达铂同期IMRT与顺铂的疗效及不良反应。方法 2011—2012年间5个治疗中心共 223例经病理确诊的初治局部晚期鼻咽癌患者被随机分为两组,试验组 113例采用多西他赛(65 mg/m²第1天)+奈达铂(80 mg/m²第1天)诱导化疗2周期,奈达铂(40 mg/m²第1天)每周方案同期IMRT;对照组 110例采用相同方案诱导化疗2周期,IMRT顺铂(40 mg/m²第1天)每周方案同期IMRT。Kaplan-Meier计算生存率并Logrank检验两组差异,不良反应行z检验。结果 随访率为99.1%。治疗结束后3个月两组有效率均为100%,试验和对照组 2年LRFS、RRFS、DMFS、OS分别为94.0%和93.4%、94.2%和94.1%、88.2%和86.7%、90.3%和87.3%(P=0.757、0.478、0.509、0.413);试验组白细胞、中性粒细胞、血小板减少发生率及严重程度较对照组高(P=0.027、0.028、0.035),血红蛋白减少发生率及严重程度低于对照组(P=0.000);试验组恶心、呕吐发生率及程度低于对照组(P=0.023),两组口腔黏膜炎、口干发生率相近(P=0.483、0.781)。结论 局部晚期鼻咽癌奈达铂联合多西他赛诱导化疗+奈达铂同期IMRT的近期疗效与顺铂的相似,胃肠道反应轻患者可耐受,但其骨髓抑制较重使用时应密切监测。     

Sequential chemoradiotherapy with gemcitabine and cisplatin for locoregionally advanced nasopharyngeal carcinoma

We investigated a new chemoradiotherapy (CRT) regimen for locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 240 patients were randomly assigned to three different CRT regimens: sequential CRT [1 cycle chemotherapy + Phase I radiotherapy (RT) + 1 cycle chemotherapy + Phase II RT + 2 cycles chemotherapy] with a cisplatin–gemcitabine (GC) regimen (800 mg/m² gemcitabine on Days 1 and 8 and 20 mg/m² cisplatin on Days 1–5, every 4 weeks) (sGC‐RT); sequential chemoradiotherapy with a cisplatin–fluorouracil (PF) regimen (20 mg/m² DDP and 500 mg/m² 5‐FU on Days 1–5, every 4 weeks) (sPF‐RT) and cisplatin‐based concurrent chemoradiotherapy plus adjuvant PF chemotherapy (Con‐RT + PF). The complete response rate was higher in the sGC + RT group than in the other two groups (98.75% vs. 92.50%, p < 0.01). The 3‐year overall survival (OS), disease‐free survival (DFS) and distant metastasis‐free survival (DMFS) rates in the sGC‐RT group were significantly higher than those observed in the Con‐RT group (OS, 95.0% vs. 76.3%, p < 0.001; DFS, 89.9% vs. 67.5%, p < 0.001; DMFS, 92.5% vs. 76.0%, p = 0.004) and in the sPF + RT group (OS, 95.0% vs. 73.6%, p < 0.001; DFS, 89.9% vs. 63.3%, p < 0.001; DMFS, 92.5% vs. 74.7%, p = 0.002). There were no significant differences in 3‐year OS, DFS and MFS rates between the Con‐RT and the sPF‐RT groups. The GC‐RT group experienced more hematologic toxicity, constipation and rash; however, there were no differences in late RT toxicity between the groups. These results demonstrate that a sGC‐RT regimen is effective and well tolerated in patients with locoregionally advanced NPC.     

Concurrent chemoradiotherapy with/without induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: Long-term results of phase 3 randomized controlled trial

To report long-term results of a randomized controlled trial that compared cisplatin/fluorouracil/docetaxel (TPF) induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma (NPC). Patients with stage III–IVB (except T3–4 N0) NPC were randomly assigned to receive IC plus CCRT (n = 241) or CCRT alone (n = 239). IC included three cycles of docetaxel (60 mg/m² d1), cisplatin (60 mg/m² d1), and fluorouracil (600 mg/m²/d civ d1–5) every 3 weeks. Patients from both groups received intensity-modulated radiotherapy concurrently with three cycles of 100 mg/m² cisplatin every 3 weeks. After a median follow-up of 71.5 months, the IC plus CCRT group showed significantly better 5-year failure-free survival (FFS, 77.4% vs. 66.4%, p = 0.019), overall survival (OS, 85.6% vs. 77.7%, p = 0.042), distant failure-free survival (88% vs. 79.8%, p = 0.030), and locoregional failure-free survival (90.7% vs. 83.8%, p = 0.044) compared to the CCRT alone group. Post hoc subgroup analyses revealed that beneficial effects on FFS were primarily observed in patients with N1, stage IVA, pretreatment lactate dehydrogenase ≥170 U/l, or pretreatment plasma Epstein–Barr virus DNA ≥6000 copies/mL. Two nomograms were further developed to predict the potential FFS and OS benefit of TPF IC. The incidence of grade 3 or 4 late toxicities was 8.8% (21/239) in the IC plus CCRT group and 9.2% (22/238) in the CCRT alone group. Long-term follow-up confirmed that TPF IC plus CCRT significantly improved survival in locoregionally advanced NPC with no marked increase in late toxicities and could be an option of treatment for these patients.     

Intensity-modulated radiotherapy for nasopharyngeal carcinoma: clinical correlation of dose to the pharyngo-esophageal axis and dysphagia

PURPOSE: The aim of this study was to quantify the dose delivered to the pharyngo-esophageal axis using different intensity-modulated radiation therapy (IMRT) techniques for treatment of nasopharyngeal carcinoma and to correlate this with acute swallowing toxicity. METHODS AND MATERIALS: The study population consisted of 28 patients treated with IMRT between February 2002 and August 2005: 20 with whole field IMRT (WF-IMRT) and 8 with IMRT fields junctioned with an anterior neck field with central shielding (j-IMRT). Dose to the pharyngo-esophageal axis was measured using dose-volume histograms. Acute swallowing toxicity was assessed by review of dysphagia grade during treatment and enteral feeding requirements. RESULTS: The mean pharyngo-esophageal dose was 55.2 Gy in the WF-IMRT group and 27.2 Gy in the j-IMRT group, p < 0.001. Ninety-five percent (19/20) of the WF-IMRT group developed Grade 3 dysphagia compared with 62.5% (5/8) of the j-IMRT group, p = 0.06. Feeding tube duration was a median of 38 days for the WF-IMRT group compared with 6 days for the j-IMRT group, p = 0.04. CONCLUSIONS: Clinical vigilance must be maintained when introducing new technology to ensure that unanticipated adverse effects do not result. Although newer planning systems can reduce the dose to the pharyngo-esophageal axis with WF-IMRT, the j-IMRT technique is preferred at least in patients with no gross disease in the lower neck.     

Timing of chemoradiotherapy and patient selection for locally advanced nasopharyngeal carcinoma

Aims: Predictors of outcome after radiotherapy alone for nasopharyngeal carcinoma (NPC) are now available from several retrospective studies. On the basis of these, it is theoretically possible to separate patients at risk of local failure from patients at risk of distant metastases (DM). According to classical principles of chemoradiotherapy timing, patients at risk of local failure would benefit mostly from concomitant chemoradiotherapy, whereas patients at risk distantly would benefit from sequential combinations.Materials and methods: We reviewed the literature on combined chemoradiotherapy treatment for nasopharyngeal carcinoma to assess whether timing of combined treatment matches pattern of failure.Results: Available data show a significant overlap of activity, sequential treatments reducing local failure and concomitant treatments reducing DM. Therefore, in the individual patient, the strict adoption of traditional risk profiles in therapeutic decision-making may not fully exploit all the potential therapeutic effects derived from the maximal association of both sequential and concomitant therapies.Conclusion: Whether such combination is clinically worthwhile in every patient with locoregionally advanced nasopharyngeal carcinoma needs prospective validation, because of the high toxicity of this modality.     

初治鼻咽癌调强放疗的前瞻性多中心临床研究

目的 观察调强放疗(IMRT)初治鼻咽癌的临床疗效及不良反应,并分析影响预后的因素。方法 2006—2008年,6个治疗中心共 300例经病理活检确诊为鼻咽癌的初治患者接受全程IMRT。UICC/AJCC 2002分期Ⅰ、Ⅱ、Ⅲ、Ⅳ_a+b期分别为6、45、141、108例。放疗处方剂量鼻咽原发灶计划把体积为 70~74 Gy,颈部转移淋巴结计划把体积为 68~70 Gy,计划靶体积 -1为 60~64 Gy,计划靶体积 -2为 50~54 Gy,均分30次6周完成。Ⅲ~Ⅳ_a+b期患者接受了以铂类为基础化疗。Cox法多因素预后分析。结果 随访率为99.7%。4年局部控制率、区域控制率、无远处转移率、无瘤生存率及总生存率分别为94.0%、95.5%、87.4%、80.8%及86.1%。急性1、2、3级放射性黏膜炎分别占18.0%、48.7%、33.3%,晚期 0、1、2级口干分别占12.0%、 75.7%、12.3%。18、15、42例出现局部﹑颈部淋巴结复发、远处转移。多因素分析显示N分期影响总生存率(χ²=5.17,P=0.023)、无远处转移率(χ²=6.91,P=0.009)、无瘤生存率(χ²=8.15,P=0.004)。结论 IMRT可提高初治鼻咽癌患者临床疗效,不良反应可耐受,治疗失败最主要原因为远处转移,N分期是影响预后的主要因素。