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.     

Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial.

PURPOSE: Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy (RT) and chemotherapy. This randomized phase III trial compared concurrent cisplatin-RT (CRT) with RT alone in patients with locoregionally advanced NPC. PATIENTS AND METHODS: Patients with Ho's N2 or N3 stage or N1 stage with nodal size > or = 4 cm were randomized to receive cisplatin 40 mg/m(2) weekly up to 8 weeks concurrently with radical RT (CRT) or RT alone. The primary end point was progression-free survival (PFS). RESULTS: Three hundred fifty eligible patients were randomized. Baseline patient characteristics were comparable in both arms. There were significantly more toxicities, including mucositis, myelosuppression, and weight loss in the CRT arm. There were no treatment-related deaths in the CRT arm, and one patient died during treatment in the RT-alone arm. At a median follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT-alone arm (P =.10) with a hazards ratio of 1.367 (95% confidence interval [CI], 0.93 to 2.00). The treatment effect had a significant covariate interaction with tumor stage, and a subgroup analysis demonstrated a highly significant difference in favor of the CRT arm in Ho's stage T3 (P =.0075) with a hazards ratio of 2.328 (95% CI, 1.26 to 4.28). For T3 stage, the time to first distant failure was statistically significantly different in favor of the CRT arm (P =.016). CONCLUSION: Concurrent CRT is well tolerated in patients with advanced NPC in endemic areas. Although PFS was not significantly different between the concurrent CRT arm and the RT-alone arm in the overall comparison, PFS was significantly prolonged in patients with advanced tumor and node stages.     

Patterns of failure after induction chemotherapy and radiotherapy for locoregionally advanced nasopharyngeal carcinoma: the Queen Mary Hospital experience

Purpose: Our center contributed 183 patients to the Asian–Oceanian Clinical Oncology Association (AOCOA) multicenter randomized trial comparing induction chemotherapy (CT) followed by radiotherapy (RT) vs. RT alone in patients with locoregionally advanced undifferentiated nasopharyngeal carcinoma (NPC). In a preliminary report no difference in terms of overall survival or relapse-free survival was found between the 2 treatment arms. To study the long-term outcome and patterns of failure after CT for NPC, we analyzed our own center data for which a uniform radiation treatment protocol was adopted and a longer follow-up time was available.

Methods and Materials: Between September 1989 and August 1993, a total of 183 patients were recruited into the AOCOA randomized study from our center. Patients with newly diagnosed NPC of Ho’s T3 disease, N2–N3 disease, or with neck node size of at least 3 cm were eligible. Stratification was made according to the nodal size (≤ 3 cm, >3– 6 cm, > 6 cm). Patients were randomized to receive 2–3 cycles of CT with cisplatin 60 mg/m² and epirubicin 110 mg/m² D1 followed by RT or RT alone. Four patients were excluded from the current analysis (2 died before treatment, 2 received treatment elsewhere). The remaining 179 patients were randomized to the two treatment arms, with 92 to the CT arm and 87 to the RT arm. Two patients in the CT arm had RT only, and all patients completed radiation treatment. Overall survival (OAS), relapse-free survival (RFS), local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), and distant metastases-free survival (DMFS) were analyzed using Kaplan–Meier method and significance of survival curve differences calculated using log–rank test. Analysis was performed based on the intent-to-treat.

Results: The median follow-up was 70 months. At the time of analysis, 50% of patients in the CT arm and 61% in the RT arm had relapse, while 32% in the CT arm and 36% in the RT arm had died of the disease. The median RFS was 83 months in the CT arm and 37 months in the RT arm. The median OAS has not yet been reached for both arms. No significant differences were found for the various endpoints, although there was a trend suggesting better nodal control in the CT arm. The 5-year rates for the various endpoints in the CT arm vs. the RT arm were: 53% vs. 42% for RFS (p = 0.13), 70% vs. 67% for OAS (p = 0.68), 80% vs. 77% for LRFS (p = 0.73), 89% vs. 80% for NRFS (p = 0.079), and 70% vs. 68% for DMFS (p = 0.59). There was also no significant difference in the patterns of failure between both arms: in the CT arm, 28% of failures were local only, 13% regional only, 4% locoregional, 44% distant, and 11% mixed locoregional and distant. In the RT arm, 23% of failures were local only, 13% regional only, 11% locoregional, 43% distant, and 9% mixed locoregional and distant.

Conclusion: Induction chemotherapy with the regimen used in the current study did not improve the treatment outcome or alter the failure patterns in patients with locoregionally advanced NPC, although there was a trend suggesting better nodal control in the combined modality arm. Alternative strategies of combining chemotherapy and radiotherapy should be tested and employed instead.     

Efficacy and feasibility of cisplatin-based concurrent chemoradiotherapy for nasopharyngeal carcinoma

OBJECTIVE: To investigate the efficacy and feasibility of a cisplatin-based concurrent chemoradiotherapy (CRT) protocol based on Intergroup Study 0099 for nasopharyngeal carcinoma (NPC). METHODS: Sixteen patients with stage II-IVB NPC were treated with a protocol of cisplatin-based concurrent CRT and adjuvant chemotherapy from 1998 to 2002. Three courses of cisplatin (80 mg/m2) were scheduled during 70 Gy of radiotherapy (RT), and two agents of adjuvant chemotherapy (FP regimen: cisplatin 80 mg/m2 and 5-fluorouracil 800 mg/m2/day by 4-day continuous infusion) were challenged. Overall survival (OS) and relapse-free survival (RFS) rates were calculated by the Kaplan-Meier method. RESULTS: Median follow-up duration was 45 months. Both 3-year OS and RFS rates were 81%. Proportions of patients who tolerated each scheduled treatment were 94% for RT, 63% for concurrent chemotherapy and 38% for adjuvant chemotherapy. CONCLUSIONS: Our protocol of the cisplatin-based concurrent CRT followed by adjuvant chemotherapy consisting of FP regimen was effective for Japanese patients with NPC. However, the doses and numbers of cycle of chemotherapy need to be modified because of the low compliance rate. Larger numbers of data accumulation and/or multi-institutional trials may be warranted to confirm the efficacy of this protocol.     

A phase III study of adjuvant chemotherapy in advanced nasopharyngeal carcinoma patients

To evaluate the role of adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma (NPC) patients, we conducted a randomized Phase III trial comparing radiotherapy (RT) followed by adjuvant chemotherapy to RT alone in patients with advanced NPC.

Between November 1994 and March 1999, 157 patients with Stage IV, M₀ (UICC/AJCC, 1992) advanced NPC disease were randomized to receive standard radiotherapy, as follows: 35–40 fractions, 1.8–2.0 Gy/fraction/day, 5 days/week, to a total dose 70–72 Gy with or without 9 weekly cycles of 24-h infusional chemotherapy (20 mg/m² cisplatin, 2,200 mg/m² 5-fluorouracil, and 120 mg/m² leucovorin) after RT. Of 157 patients enrolled, 154 (77 radiotherapy, 77 combined therapy) were evaluable for survival and toxicity analysis.

With a median follow-up of 49.5 months, the 5-year overall survival and relapse-free survival rates were 60.5% vs. 54.5% (p = 0.5) and 49.5% vs. 54.4% (p = 0.38) for the radiotherapy-alone group and the combined radiotherapy and adjuvant chemotherapy group, respectively. The Cox regression showed that the hazard rates ratio of combined treatment to RT alone was 0.673 (p VALUE = 0.232); the 95% confidence interval was 0.352 and 1.288, respectively. Patients who received combined treatment had a lower systemic relapse rate than radiotherapy-alone patients, according to relapse pattern analysis. The incidence of leukopenia (≥ Grade 3) occurred in 17 out of 819 (2.1%) cycles of weekly chemotherapy. No patient developed moderate to severe mucositis (≥ Grade 3).

We conclude that adjuvant chemotherapy after RT for patients with advanced NPC has no benefit for overall survival or relapse-free survival.     

放化疗中不同化疗方式对N3期鼻咽癌预后影响

目的 评价放化疗中不同方式化疗对N3期鼻咽癌患者预后的影响.方法 回顾分析114例N3期鼻咽癌患者资料.9例接受单纯放疗;105例接受以铂类为基础化疗联合放疗,其中同期放化疗37例,诱导化疗+同期放化疗53例,同期放化疗+辅助化疗15例.鼻咽原发灶采用60Co γ线、6 MV X线常规分割照射70 Gy,颈部根治量60～68 Gy,颈部预防量54～60 Gy.结果 中位随访时间54个月,共51例患者死亡.全组5年总生存率为59.1%.单纯放疗、同期放化疗、诱导化疗+同期放化疗、同期放化疗+辅助化疗的5年总生存率分别为17%、51%、68%、71%(X2=15.44,P=0.001),无复发生存率分别为83%、77%、88%、93%(X2=2.34,P:0.505),无转移生存率分别为17%、54%、72%、80%(X2=19.28,P=0.000).结论 诱导化疗+同期放化疗及同期放化疗+辅助化疗方式对N3期鼻咽癌患者比单纯同期放化疗更具优势,最有效治疗方式有待随机研究证实.

Abstract：

Objective Nasopharyngeal carcinoma patients with stage N3 disease are prone to develop distant metastasis even treated with standard concurrent chemoradiotherapy(CRT).The aim of this study is to compare the ettlcacy of difierent chemotherapy sequences in these patients.Methotis All patients with histologically proven,carcinoma of the nasopharynx treated between July 1999 and November 2003 were restaged according to the AJCC 2002 stage classification system.A total of 114 patients had AJCC N3 diseases were analyzed retrospectively.Patients were treated by conventional RT technique using 6 MV photons or 60 Coγ-ray with 1.8-2.0 Gy per fraction,5 fractions a week,to a planned dose of 70 Gy.The prophylactic irradiation dose of the neck wss 54-60 Gy.Any positive lymph node was boosted to a total dose of 60-68 Gy.All patients received cisplatin-based chemotherapy of difierent sequences but 9 patients RT alone.CRT regimen was delivered in 37 patients,neoadjuvant chemotherapy(NACT)+CRT regimen in 53 patients and CRT+adjuvant chemotherapy(AC)regimen in 15 patients.Results The prophylactic irradiation dose of the neck wss 54-60 Gy.Any positive lymph node was boosted to a total dose of 60-68 Gy.All patients received cisplatin-based chemotherapy of difierent sequences but 9 patients received RT alone.CRT regimen was delivered in 37 patients,neoadjuvant chemotherapy(NACT)+CRT regimen in 53 patients and CRT+adjuvant chemotherapy(AC)regimen in 15 patients.Results The median follow up time was 54 months(3-117months).The 5-year overall survival rate was 59.1%in whole groups,and with 17%,51%,68%and 71%in RT,CRT,NACT+CRT and CRT+AC group,respectively(X2=15.44,P=0.001).The 5-year relapse-free survival rates were 83%,77%,88%and 93%in RT,CRT,NACT+CRT and CRT+AC group,respectively(X2=2.34,P=0.505).The 5-year metastasis-free survival rates were 17%,54%,72%and 80%in RT,CRT,NACT+CRT and CRT+AC group,respectively(X2=19.28,P=0.000).Conclusions The NACT+CRT and CRT+AC regimens were more effective than CRT alone for N3 disease in the current study.Large prospective,randomized clinieal studies are warranted.     

Radiation therapy with or without chemotherapy for cervical cancer with periaortic lymph node metastasis

The purpose of this article is to evaluate the efficacy of chemoradiation therapy (CRT) and radiation therapy (RT) alone for cervical cancer with periaortic nodal metastasis (PANM). Twenty-one patients with cervical cancer with PANM were identified. Eleven patients received concomitant CRT with cisplatin-based chemotherapy and 10 received RT alone. The median age was 44 years. Ten, 5, and 6 patients had International Federation of Gynecology and Obstetrics stages IB, IIB, and IIIB disease. The RT doses to point A and the periaortic region were 80 to 85 Gy (low dose rate equivalent) and 45 Gy. The median follow-up was 26 months (range 3 to 141 months). The 1- and 3-year disease-specific survival were 81.8% and 81.8%, and 70% and 30%, respectively, for the CRT and RT groups, (P = 0.11). The 1- and 3-year pelvic and periaortic control rates (PPC) were 100% and 100% (CRT), and 56.3% and 42.2% (RT) (P = 0.03). The 1- and 3-year free-from-distant metastasis (DM) rates were 81.8% and 81.8% (CRT), and 78.7% and 49.2% (RT) (P = 0.54). All patients who developed DM died of their disease. CRT is a feasible treatment option to improve the PPC for these patients. Because of the high rate of distant metastasis despite PPC, more effective systemic therapy should be explored.     

Long-term survival of nasopharyngeal carcinoma patients treated with adjuvant chemotherapy subsequent to conventional radical radiotherapy

PURPOSE: To assess the long-term survival of patients with nasopharyngeal carcinoma (NPC) who were treated with conventional radical radiotherapy (RT) followed by adjuvant chemotherapy. METHODS AND MATERIALS: Ninety-one newly diagnosed patients with Stage III and IV (American Joint Committee on Cancer, 1988) NPC, seen at the University of Malaya Medical Center, Kuala Lumpur, Malaysia between January 1992 and May 1997, were treated with RT followed by adjuvant chemotherapy. The tumor dose was 70 Gy delivered in 35 fractions, 5 fractions weekly. Three cycles of chemotherapy, each consisting of 5-fluorouracil, 1 g/m(2)/d on Days 1-4 and cisplatin 100 mg/m(2) on Day 1, were administered 3 weeks after RT completion. Thirty-six patients had Stage II, 10 had Stage III, and 45 had Stage IV disease (AJCC 1997 staging system). RESULTS: After a median follow-up of 61 months, the 5-year overall survival rate for all 91 patients was 80.1%, the disease-free survival rate was 76%, and the locoregional control rate was 85%. The 3-year overall survival rate for Stage II was 94.3%; it was 80% for Stage III and 79.8% for Stage IV (p = 0.0108). The 3-year DFS rate for Stage II was 90%; it was 80% for Stage II and 65% for Stage IV. The rate of distant failure for Stage IV was 8.9%. CONCLUSION: Radical RT followed by adjuvant chemotherapy was effective in our patients with locoregionally advanced NPC. The long-term results appear encouraging, even for patients with Stage IV disease. This single institution experience deserves further investigation in prospective trials.     

Patterns of failure in patients with locally advanced head and neck cancer treated postoperatively with irradiation or concomitant irradiation with Mitomycin C and Bleomycin

PURPOSE: The long term results and patterns of failure in patients with squamous cell head and neck carcinoma (SCHNC) treated in a prospective randomized trial in which concomitant postoperative radiochemotherapy with Mitomycin C and Bleomycin (CRT) was compared with radiotherapy only (RT), were analyzed. PATIENTS AND METHODS: Between March 1997 and December 2001, 114 eligible patients with Stage III or IV SCHNC were randomized. Primary surgical treatment was performed with curative intent in all patients. Patients in both groups were postoperatively irradiated to the total dose of 56-70 Gy. Chemotherapy included Mitomycin C 15 mg/m2 after 10 Gy and 5 mg of Bleomycin twice weekly during irradiation. Median follow-up was 76 months (48-103 months). RESULTS: At 5 years in the RT and CRT arms, the locoregional control was 65% and 88% (p = 0.026), disease-free survival 33% and 53% (p = 0.035), and overall survival 37% and 55% (p = 0.091) respectively. Patients who benefited from chemotherapy were those with high-risk factors. The probability of distant metastases was 22% in RT and 20% in CRT arm (p = 0.913), of grade III or higher late toxicity 19% in RT and 26% in CRT arm (p = 0.52) and of thyroid dysfunction 36% in RT and 56% in CRT arm (p = 0.24). The probability to develop a second primary malignancy (SPM) was 34% in the RT and 8% in the CRT arm (p = 0.023). One third of deaths were due to infection, but there was no difference between the 2 groups. CONCLUSION: With concomitant radiochemotherapy, locoregional control and disease free survival were significantly improved. Second primary malignancies in the CRT arm compared to RT arm were significantly less frequent. The high probability of post treatment hypothyroidism in both arms warrants regular laboratory evaluation.     

Outcome for children with group III rhabdomyosarcoma treated with or without radiotherapy

PURPOSE: To analyze the sites of relapse, relapse-free survival, and overall survival in children with Group III rhabdomyosarcoma treated with or without radiotherapy (RT). METHODS AND MATERIALS: The outcomes of 48 children with Group III rhabdomyosarcoma treated between 1980 and 1997 were evaluated. The median overall survival follow-up was 7.3 years. Of the 48 patients, 65% had embryonal histology. Local treatment after induction chemotherapy included complete surgical resection (CSR) alone in 9 (19%), CSR plus RT in 13 (27%), partial resection or rebiopsy plus RT in 10 (21%), and RT alone in 15 patients (31%). One child developed distant disease before completing local therapy. RESULTS: Of the 48 patients, 12 developed relapse at local (n = 3), regional (n = 4), or distant (n = 5) sites. All 9 patients treated with CSR after induction chemotherapy had embryonal/botryoid histology. Only 1 of these 9 patients developed relapse. No statistically significant difference was found in overall survival (p = 0.95) or relapse-free survival (p = 0.67) between patients treated with or without RT. The Kaplan-Meier estimate of 5-year overall survival and relapse-free survival was 76% +/- 7% and 74% +/- 7%, respectively. Significant predictors of relapse-free survival on univariate analysis included CSR (p = 0.03), nodal positivity (p = 0.001), and embryonal histology (p = 0.0003). On multivariate analysis, embryonal histology was the most significant predictor of relapse-free (p = 0.001) and overall (p = 0.01) survival. CONCLUSION: The overall survival for children with Group III rhabdomyosarcoma in this series was favorable. Embryonal/botryoid histology was the most significant predictor of both overall and relapse-free survival. We found that for a selected subgroup of children with embryonal histology, induction chemotherapy followed by complete surgical resection alone may be adequate local therapy.     

Improvement of survival after addition of induction chemotherapy to radiotherapy in patients with early-stage nasopharyngeal carcinoma: Subgroup analysis of two Phase III trials

PURPOSE: Induction chemotherapy has not been shown to improve survival in nasopharyngeal carcinoma (NPC) in Phase III trials. To evaluate the effect of induction chemotherapy in NPC further, we performed subgroup analysis of two Phase III trials according to the T and N stage. METHODS AND MATERIALS: Data from two phase III trials comparing cisplatin/epirubicin or cisplatin/bleomycin/5-fluorouracil followed by radiotherapy (RT) vs. RT alone in NPC were pooled together for analysis. Patients were stratified into four subgroups according to the 1997 American Joint Committee on Cancer T and N stage: T1-T2N0-N1, Group 1 (early-stage disease); T1-T2N2-N3, Group 2 (advanced N disease); T3-T4N0-N1, Group 3 (advanced T stage); and T3-T4N2-N3, Group 4 (advanced T and N disease). Group 1 consisted entirely of patients with Stage IIB disease. A total of 784 patients were included for analysis on an intent-to-treat basis. The median follow-up for the surviving patients was 67 months. RESULTS: No significant differences in overall survival, locoregional failure-free, or distant metastasis-free rates were observed between the combined and RT arms in Groups 2 to 4. Significant differences in the overall survival and distant metastasis-free rates were observed only in Group 1, favoring the combined chemotherapy and RT arm. The 5-year overall survival rate was 79% in the combined arm and 67% in the RT-alone arm (p = 0.048). The corresponding 5-year distant metastasis-free rates were 86% and 74% (p = 0.0053). CONCLUSIONS: Our results have shown that patients in Group 1, with early-stage NPC treated by RT alone, had relatively poor survival because of distant metastases. The observation of improved outcomes in this subgroup after the addition of induction chemotherapy has not been previously reported and warrants additional investigation.     

Adjuvant chemotherapy with vincristine, cyclophosphamide, and doxorubicin after radiotherapy in local-regional nasopharyngeal cancer: results of a 4-year multicenter randomized study

To evaluate the effect of adjuvant chemotherapy in patients with local-regional nasopharyngeal carcinoma (NPC) (squamous or undifferentiated) in complete remission at the end of curative radiotherapy (RT) 229 patients were randomized from 1979 to 1983 in a multicenter study to no further therapy (116 patients) or a combination of vincristine, cyclophosphamide, and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) (VCA) for six monthly cycles (113 patients). The RT and RT + VCA groups were well balanced for median age (50 v 49 years), histology (undifferentiated carcinoma, 73% v 70%), tumor extent (tumor limited to nasopharynx, 57% v 57%), and nodal extent (negative nodes 26% v 24%, nodes in the lower cervical levels, 17% v 16%). RT was delivered to the nasopharynx, the base of the skull, and bilateral cervical nodes using a split course technique over 10 weeks up to the dose of 60 to 70 Gy in involved sites and 50 Gy to negative nodes. Response to RT was evaluated within 65 days post-RT treatment. Analysis at 48 months did not show significant difference between the two treatment groups in terms of relapse-free survival (RT, 55.8%, RT + VCA, 57.7%, P = .45) and overall survival (RT, 67.3%, RT + VCA, 58.5%, P = .13). The pattern of relapse was similar in the two treatment arms. Distant metastases were the cause of treatment failure in about 50% of relapsing patients. Although the results of the present study did not show any benefit from VCA administered after curative RT, combined systemic chemotherapy should be further explored due to the high incidence of local and distant failure after intensive RT.     

Chemoradiotherapy regimens for locoregionally advanced nasopharyngeal carcinoma: A Bayesian network meta-analysis

BackgroundConcurrent chemoradiotherapy followed by adjuvant chemotherapy (CRT-A) is often the regimen of choice in locoregionally advanced nasopharyngeal carcinoma (NPC). Many alternative regimens have been reported in the literature, however, it is unknown how effective these regimens are compared to each other due to the lack of direct comparisons. Our objective was to perform a network meta-analysis (NMA) to determine the relative survival benefits of these treatments for locoregionally advanced NPC.MethodsWe performed a systematic review following the Cochrane methodology, using MEDLINE, EMBASE and CENTRAL to identify all randomised controlled trials (RCTs) that compared different chemoradiotherapy regimens for locoregionally advanced NPC. Overall survival (OS) was the primary outcome of interest, and hazard ratios (HRs) were extracted using the Parmar method. Bayesian NMAs with random effects were conducted using WinBUGS.ResultsTwenty-five RCTs (5576 patients) were included in this review. All together, these trials compared seven different regimens: radiotherapy (RT), concurrent chemoradiotherapy (CRT), neoadjuvant followed by CRT (N-CRT), CRT-A, RT-A, N-RT and N-RT-A. All regimens that contained CRT performed significantly better than RT. CRT-A did not improve survival compared to CRT alone (0.98; 95% credible regions: 0.71–1.34). For N-CRT versus CRT, the HR was 1.03 (0.69–1.47). When CRT-A was compared against N-CRT, the resulting HR was 0.96 (0.64–1.48).ConclusionsAdjuvant chemotherapy does not appear to improve survival following CRT. The efficacies of CRT, CRT-A and N-CRT all appeared to be similar. Further studies are warranted to determine the value of additional chemotherapy phases in specific patient subgroups.     

454例鼻咽癌IMRT±化疗远期疗效及影响因素分析

目的 对454例鼻咽癌IMRT±化疗的远期疗效及影响因素分析。方法 回顾分析本中心2007—2012年采用IMRT±化疗的454例无远处转移鼻咽癌患者资料。放疗处方剂量:鼻咽大体肿瘤69.96~73.92 Gy分33次, 颈部转移淋巴结69.96 Gy分33次, 高危引流区60.06 Gy分33次, 低危引流区50.96 Gy分28次。诱导化疗438例, 同期化疗420例, 辅助化疗216例, 顺铂、紫杉醇为主。Kaplan-Meier法计算生存并Logrank 法检验和单因素预后分析, Cox法多因素预后分析。结果 3年样本数为210例, 3年OS、LRFS、NRFS、PFS、DMFS分别为88.1%、91.0%、90.7%、80.5%、85.1%。影响OS因素有年龄(P=0.011)、T分期(P=0.005)、N分期(P=0.033);T、N分期对DPFS (P=0.017、 0.005)、DMFS (P=0.012、0.019)均有影响。≥3级急性及晚期不良反应主要为血液学、口腔黏膜反应, 口干、吞咽困难和脑损伤。结论 IMRT提高了鼻咽癌患者长期生存, 远处转移是主要失败原因, IMRT联合化疗不良反应能耐受。     

Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee on Cancer/International Union against cancer stage III and IV nasopharyngeal cancer of the endemic variety.

PURPOSE: The Intergroup 00-99 Trial for nasopharyngeal cancer (NPC) showed a benefit of adding chemotherapy to radiotherapy. However, there were controversies regarding the applicability of the results to patients in endemic regions. This study aims to confirm the findings of the 00-99 Trial and its applicability to patients with endemic NPC. PATIENTS AND METHODS: Between September 1997 and May 2003, 221 patients were randomly assigned to receive radiotherapy (RT) alone (n = 110) or chemoradiotherapy (CRT; n = 111). Patients in both arms received 70 Gy in 7 weeks using standard RT portals and techniques. Patients on CRT received concurrent cisplatin (25 mg/m2 on days 1 to 4) on weeks 1, 4, and 7 of RT and adjuvant cisplatin (20 mg/m2 on days 1 to 4) and fluorouracil (1,000 mg/m2 on days 1 to 4) every 4 weeks (weeks 11, 15, and 19) for three cycles after completion of RT. All patients were analyzed by intent-to-treat analysis. The median follow-up time was 3.2 years. RESULTS: Distant metastasis occurred in 38 patients on RT alone and 18 patients on CRT. The difference in 2-year cumulative incidence was 17% (95% CI, 14% to 20%; P = .0029). The hazard ratio (HR) for disease-free survival was 0.57 (95% CI, 0.38 to 0.87; P = .0093). The 2- and 3-year overall survival (OS) rates were 78% and 85% and 65% and 80% for RT alone and CRT, respectively. The HR for OS was 0.51 (95% CI, 0.31 to 0.81; P = .0061). CONCLUSION: This report confirms the findings of the Intergroup 00-99 Trial and demonstrates its applicability to endemic NPC. This study also confirms that chemotherapy improves the distant metastasis control rate in NPC.     

Equivalent outcome of patients with clinical Stage IIIA non-small-cell lung cancer treated with concurrent chemoradiation compared with induction chemotherapy followed by surgical resection

PURPOSE: To compare the outcome of induction chemotherapy followed by surgery (C/S) and concurrent chemoradiotherapy (CRT) for clinical Stage IIIA non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Between 1990 and 2000, 107 patients underwent either induction C/S (n = 55) or concurrent CRT (n = 52) for clinical Stage IIIA NSCLC at The University of Texas M. D. Anderson Cancer Center. Patient and tumor characteristics were balanced in the two treatment groups with respect to T and N stage, race, median age, performance status, weight loss, and histologic findings. In the C/S group, induction chemotherapy included two to four cycles of cisplatin-based chemotherapy followed by lobectomy and mediastinal lymph node dissection. Postoperative RT was delivered in 35 patients, with referral for RT made at the discretion of the treating physician. CRT consisted of three cycles of cisplatin-based chemotherapy given every 3 weeks concurrent with RT to 60-63 Gy in 30-35 fractions in 27 patients and 69.6 Gy in 58 fractions (b.i.d.) in 25 patients. Local control, overall disease-free survival, and distant metastasis-free survival rates were calculated using the Kaplan-Meier method. The median follow-up duration was 20 months in all patients and 32 months in surviving patients. RESULTS: No statistically significant differences were found in the end points measured in the two treatment groups. Specifically, the median survival time was 31 and 27 months and the 5-year overall survival rate was 33% and 30% in the C/S and CRT groups, respectively. Likewise, the 5-year local control (58% vs. 61%), disease-free (24% vs. 23%), and distant metastasis-free (44% vs. 36%) survival rates in the two groups were not significantly different. In the C/S group, postoperative RT significantly improved the 5-year local control rate from 33.8% to 81.5% (p = 0.007) but did not significantly improve overall survival. Additionally, patients in the C/S group whose disease responded to induction chemotherapy had a significantly improved 5-year overall survival rate (50%) compared with those who had stable or progressive disease (16%, p = 0001). CONCLUSION: Treatment of Stage IIIA NSCLC using either induction C/S or CRT resulted in similar outcomes in terms of local control and median overall, 5-year overall, distant metastasis-free, and disease-free survival. However, patients undergoing induction C/S often needed postoperative RT to achieve local control equivalent to that achieved with concurrent CRT. Advances in radiation-based treatment as reflected in this study have resulted in similar outcomes compared with modern induction C/S. To improve survival, however, newer systemic agents that reduce and control distant metastasis are required.     

Patterns of failure following radiation with and without chemotherapy in patients with nasopharyngeal carcinoma

PURPOSE: Aim of this study was to retrospectively evaluate patterns of failure, results, and prognostic factors for patients with nasopharyngeal cancer (NPC) following radiotherapy (RT) with and without concurrent chemotherapy (RCT). PATIENTS AND METHODS: Between 1978 and 1999, a total of 101 patients with NPC were treated in our hospital, of whom 53 received external megavoltage RT alone with a median total dose of 76 Gy (1978-1988), and 48 patients had RCT (1989-1999). For RCT a combination of 5-FU and cisplatin was used together with a median total dose of 72 Gy. Patterns of relapse, survival rates and toxicity as well as prognostic factors were evaluated retrospectively. RESULTS: RCT was associated with a marked reduction in distant metastases: 6/48 (13%) vs. 17/53 (32%) after RT alone. Locoregional tumor persistence was only marginally lower with RCT: 10/48 (21%) vs. 17/53 (32%) following RT. Patients with RCT demonstrated a survival advantage compared to those with RT alone (5-year overall survival (OS): 64% vs. 44%, p = 0.1). OS, disease-specific survival and locoregional control rates were 53, 57, and 78% at 5 years and 47, 51 and 78% at 10 years, respectively. OS was significantly affected by histology (p = 0.007), the patients' age (p = 0.009) and gender (p = 0.01). CONCLUSION: This retrospective study provides further evidence that both reduction of distant metastasis and enhanced local tumor control by combined radiochemotherapy may be associated with improved survival rates in NPC compared to radiation alone. Concurrent RCT is therefore considered the preferable treatment option, however, confirmation in randomized trials is still warranted.     

Preliminary results of a randomized study (NPC-9902 Trial) on therapeutic gain by concurrent chemotherapy and/or accelerated fractionation for locally advanced nasopharyngeal carcinoma

PURPOSE: To compare the benefit achieved by concurrent chemoradiotherapy (CRT) and/or accelerated fractionation (AF) vs. radiotherapy (RT) alone with conventional fractionation (CF) for patients with T3-4N0-1M0 nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: All patients were irradiated with the same RT technique to > or =66 Gy at 2 Gy per fraction, conventional five fractions/week in the CF and CF+C (chemotherapy) arms, and accelerated six fractions/week in the AF and AF+C arms. The CF+C and AF+C patients were given the Intergroup 0099 regimen (concurrent cisplatin plus adjuvant cisplatin and 5-fluorouracil). RESULTS: Between 1999 and April 2004, 189 patients were randomly assigned; the trial was terminated early because of slow accrual. The median follow-up was 2.9 years. When compared with the CF arm, significant improvement in failure-free survival (FFS) was achieved by the AF+C arm (94% vs. 70% at 3 years, p = 0.008), but both the AF arm and the CF+C arm were insignificant (p > or = 0.38). Multivariate analyses showed that CRT was a significant factor: hazard ratio (HR) = 0.52 (0.28-0.97), AF per se was insignificant: HR = 0.68 (0.37-1.25); the interaction of CRT by AF was strongly significant (p = 0.006). Both CRT arms had significant increase in acute toxicities (p < 0.005), and the AF+C arm also incurred borderline increase in late toxicities (34% vs. 14% at 3 years, p = 0.05). CONCLUSIONS: Preliminary results suggest that concurrent chemoradiotherapy with accelerated fractionation could significantly improve tumor control when compared with conventional RT alone; further confirmation of therapeutic ratio is warranted.     

Induction chemotherapy with cisplatin and epirubicin followed by radiotherapy and concurrent cisplatin in locally advanced nasopharyngeal carcinoma observed in a non-endemic population

Background and purpose

Chemoradiotherapy (CRT) represents the main therapy choice in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). The aim of this study was the clinical evaluation of neoadjuvant chemotherapy (NACT) followed by CRT in a non-endemic population affected by advanced NPC.

Materials and methods

Patients with locoregionally advanced NPC were treated with three cycles of induction chemotherapy (CHT) with cisplatin (100 mg/m²) plus epirubicin (90 mg/m²), followed by cisplatin (100 mg/m²) and concomitant radiotherapy (70 Gy).

Results

In 40 patients treated with such protocol, after the completion of induction CHT and CRT we observed the objective response rates of 90% and 100%, respectively. Treatment tolerability and toxicity were easily controllable. With a median follow-up time of 54 months, 3- and 5-year disease-free survival was 75% and 65% and 3- and 5-year overall survival was 84% and 77%.Three- and 5-year locoregional control was 82% and 70%, and 5-year distant metastases free survival was 75%.

Conclusions

NACT with cisplatin and epirubicin followed by concomitant CRT represents a feasible, efficient treatment for patients with advanced NPC. This regimen ensures an excellent locoregional disease control and overall survival with a low incidence of distant metastases.     

局部晚期鼻咽癌同期放化疗的疗效分析

目的评估同期放化疗方案对局部晚期鼻咽癌患者的疗效、急性毒性反应、依从性和晚期损伤情况。方法74例Ⅲ、Ⅳ期中国人种局部晚期鼻咽癌患者,按照北美Intergroup0099方案接受了同期放疗加辅助化疗的治疗,其急性与晚期毒性反应采用美国放射治疗协作组织（RTOG）的标准进行评价。结果74例患者的5年生存率和无瘤生存率分别为71．3％和43．5％。无5级毒性反应发生,3,4级急性毒性反应主要为造血系统25例,占33．8％;咽部黏膜19例,占25．7％;放疗区皮肤损伤6例,占8．1％。完成放疗、同期放化疗和全部化疗者分别为100．0％、75．7％和47．3％;3—4级晚期并发症主要为唾液腺损伤（17例）、听力损伤（13例）、皮肤及皮下组织损伤（7例）,晚期损伤的5年累积发生率为44．3％。结论与常规放射治疗相比,同期放化疗方案有助于中国人种局部晚期鼻咽癌患者疗效的提高,其急性毒性反应有所增加,晚期损伤基本相同。