中晚期鼻咽癌新辅助化疗联合放疗前瞻性 临床试验的长期结果

目的：评价新辅助化疗联合放疗在中晚期鼻咽癌治疗的价值。方法：前瞻性临床试验采用化疗方案：Cisplatin20mg/m^2,1-5天,5－FU500mg/m^2,1-5 天,BLM7mg/m^2,第1、5天,化疗2－3个疗程。放射治疗鼻咽剂量：66－74Gy/33-37次,共7－9周;预部淋巴结剂量：60－70Gy/30-35次,共7－8.5周;颈部预防量：48－50Gy。结果：1992－1993年457例鼻咽癌病人进入研究,17例因各种原因退出队列,440例进入分析（化疗＋放疗组219例、单纯放疗组221例）。5年生存率及无瘤生存率实验组及对照组分别为62％vs55％（P＝0.1335)及55％vs48%(P=0.0539)。5年无局部复发生率及无远处转移生存率两组分别为82％vs74%（P＝0.0412)及79％vs75%(P=0.4177)。亚组分析显示新辅助化疗能明显提高T3－4期的局控率;对N2－3病人的远处转移率无影响。结论：新辅助化疗未能提高中晚期鼻咽癌病人的总生存率,亦未能降低远处转移率,有提高无瘤生存率的趋势。新辅助化疗的指征：T3－4期病人。     

Results of a prospective randomized trial comparing neoadjuvant chemotherapy plus radiotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: A prospective randomized trial was performed to evaluate the contribution of neoadjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. PATIENTS AND METHODS: Patients with locoregionally advanced nasopharyngeal carcinoma were treated either with radiotherapy alone (RT group) or neoadjuvant chemotherapy plus radiotherapy (CT/RT group). Neoadjuvant chemotherapy consisting of two to three cycles of cisplatin (100 mg/m(2), day 1), bleomycin (10 mg/m(2), days 1 and 5), and fluorouracil (5-FU; 800 mg/m(2), days 1 through 5, continuous infusion) followed by radiotherapy was given to the CT/RT group. All patients were treated in a uniform fashion by definitive-intent radiation therapy in both groups. RESULTS: Between July 1993 and July 1994, 456 patients were entered onto the study, with 228 patients randomized to each treatment arm, and 449 patients (225 in the RT group and 224 in the CT/RT group) were assessable. All 456 patients were included in survival analysis according to the intent-to-treat principle. The 5-year overall survival (OS) rates were 63% for the CT/RT group and 56% for the RT group (P =.11). The median relapse-free survival (RFS) time was 50 months for the RT group and not reached for the CT/RT group. The 5-year RFS rate was 49% for the RT group versus 59% for the CT/RT group (P =.05). The 5-year freedom from local recurrence rate was 82% for the CT/RT group and 74% for the RT group (P =.04). There was no significant difference in freedom from distant metastasis between the two treatment groups (CT/RT group, 79%; RT group, 75%; P =.40). CONCLUSION: This randomized study failed to demonstrate any significant survival benefit with the addition of neoadjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma. Therefore, neoadjuvant chemotherapy for nasopharyngeal carcinoma should not be used outside of the context of a clinical trial.     

Randomized study of 5 fluorouracil and cis platin as neoadjuvant therapy in head and neck cancer: a preliminary report

A randomized prospective study of 5 fluorouracil (5-FU) and Cis platin preceding definitive local treatment for squamous cell carcinoma of the head and neck region was initiated in September 1986. Seventy-five patients were stratified by site (oral cavity-12, oropharynx-28, larynx-16, hypopharynx-19), and by Stage (Stage II-20, Stage III-43, Stage IV-12) and randomized to receive definitive local treatment (surgery and post-operative radiation or radiation alone) or chemotherapy followed by definitive local treatment. Chemotherapy consisted of three cycles of 120 hr 5-FU infusion 1 g/m2/day plus Cis platin 100 mg/m2 on day 1 on each cycle. Response to chemotherapy was complete in 17 patients (46%) for an overall response rate of 68%. All the patients have completed therapy with a median follow-up of more than 12 months. After local treatment, the complete response rate is 84% for the control group and 86% in the chemotherapy group. Actuarial disease-free survival at 1 year is 61% in the control group and 73% in the chemotherapy group (p = 0.25). These preliminary results show that in spite of initial tumor response, neoadjuvant chemotherapy does not improve long-term control and survival.     

Long-term survival of nasopharyngeal carcinoma following concomitant radiotherapy and chemotherapy

Purpose: The purpose of this study is to demonstrate long-term survival of nasopharyngeal carcinoma treated with concomitant chemotherapy and radiotherapy (CCRT) followed by adjuvant chemotherapy.

Methods and Patients: One hundred and seven patients with Stage III and IV (American Joint Committee on Cancer, AJCC, 1988) nasopharyngeal carcinoma (NPC) were treated with concomitant chemotherapy and radiotherapy (CCRT) followed by adjuvant chemotherapy between April 1990 and December 1997 in Koo Foundation Sun Yat-Sen Cancer Center, Taipei. The dose of radiation was 70 Gray (Gy) given in 35 fractions, 5 fractions per week. Two courses of chemotherapy, consisting of cisplatin and 5-fluorouracil, were delivered simultaneously with radiotherapy in Weeks 1 and 6 and two additional monthly courses were given after radiotherapy. According to the AJCC 1997 staging system, 32 patients had Stage II disease, 44 had Stage III, and 31 had Stage IV disease.

Results: With median follow-up of 44 months, the 5-year overall survival rate in all 107 patients was 84.1%, disease-free survival rate was 74.4%, and locoregional control rate was 89.8%. The 3-year overall survival for Stage II was 100%, for Stage III it was 92.8%, and for Stage IV, 69.4% (p = 0.0002). The 3-year disease-free survival for Stage II was 96.9%, for Stage III it was 87.7%, and for Stage IV it was 51.9% (p = 0.0001).

Conclusion: CCRT and adjuvant chemotherapy is effective in Taiwanese patients with advanced NPC. The prognosis of AJCC 1997 Stage II and III disease is excellent, but, for Stage IV (M0), it is relatively poor. Future strategies of therapy should focus on high-risk AJCC 1997 Stage IV (M0) cohort.     

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.     

A randomized trial comparing radiation therapy versus concomitant radiation therapy and chemotherapy in carcinoma of the thoracic esophagus.

From September 1982 to December 1985, 59 previously untreated patients with Stage II squamous cell carcinoma of the thoracic esophagus were randomly assigned to receive radiation therapy (RT) alone versus the concomitant use of RT and chemotherapy (CT) with 5-fluorouracil (5-FU), mitomycin C, and bleomycin (RT + CT). Thirty-one patients were randomized to the RT regimen and 28 to the RT + CT regimen. The complete local response rate was 58% for the RT group and 75% for the RT + CT group (P = 0.77). The median duration of response was 8 months for both groups. The overall 5-year survival rates were 6% and 16% (P = 0.16) for the RT and RT + CT groups, respectively. Acute toxicities were more pronounced in the RT + CT group. This clinical trial did not detect a difference in outcome with combined-technique therapy. This result must be interpreted with caution because of the small number of patients entered in this trial. Confirmation of the value or lack of value for combined therapy will require additional larger clinical trials.     

Larynx preservation using induction chemotherapy plus radiation therapy as an alternative to laryngectomy in advanced head and neck cancer. A long-term follow-up report.

Since 1977, we have used induction chemotherapy (CT) plus radiation therapy (RT) with curative intent in 35 advanced head and neck cancer (Ca) patients who otherwise would have required total laryngectomy. Fourteen patients had advanced Ca of the larynx or supraglottic larynx (SGL); 21 patients had Ca of the hypopharynx. In six patients the Ca was Stage III; in 26 patients it was Stage IV. Three patients had Stage II disease--2 with cancer of the pyriform sinus and one patient with Stage II SGL Ca who refused surgery. Chemotherapy consisted of platinum (P) + bleomycin in 18 patients until 1982, then P + fluorouracil in the next 17 patients. Total response rate was 77%--complete (CR) in 26% and partial (PR) in 51%. There were two toxic deaths. Surgery was limited to tracheostomy in 4 patients prior to CT and to radical neck dissection after CT in 4 others. Two patients required salvage laryngectomy at 11 and 31 months, respectively. One patient underwent partial laryngectomy with voice preservation. Thirty-two patients were evaluable for overall response after RT. Final disease-free status was achieved in 20/34. One long-term survivor was lost to follow-up (44 months) and 8 patients remained alive at 13+ to 109+ months. Median failure-free survival for all patients was no less than 24 months. Not counting 4 early deaths free of disease, 2-year local control using only chemotherapy plus radiation was 52% (16:31). Overall, 33 of 35 patients retained their voices. Sixteen patients (46%) have survived 2 years or longer. Survival of patients who achieved CR after induction chemotherapy was 48 months versus 14 months for those with less than a CR (p = 0.001). Patients with a hypopharyngeal primary had only a 33% 2-year local control rate with chemotherapy and radiation and a median survival of only 12 months versus 77% control and a minimum 39-month survival for those whose tumor arose in the larynx (p = 0.009). Induction chemotherapy plus radiation therapy is an effective strategy which can produce a high rate of larynx preservation, local control, and long-term survival in patients with advanced cancer of the larynx. Patients with hypopharyngeal primaries have a lesser rate of long-term survival and local control, despite similar overall response rates.     

Outcome and pattern of failure in pathologic stage I-II papillary serous carcinoma of the endometrium: implications for adjuvant radiation therapy

PURPOSE: To evaluate the outcome and patterns of failure in women with pathologic Stage I-II papillary serous carcinoma of the uterus and to discuss the implications for adjuvant radiation therapy (RT). METHODS: Twenty-three pathologic Stage I-II uterine papillary serous carcinoma patients were treated at our institution between 1980 and 2001. All underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy and assessment of peritoneal cytology. Pelvic and para-aortic lymph node sampling was performed in 12 and 8 patients, respectively. FIGO stages were as follows: IA = 3, IB = 8, IC = 6, IIA = 5, and IIB = 1. Adjuvant therapies included the following: 9 none, 10 RT (6 pelvic, 1 vaginal brachytherapy, 3 both), 4 chemotherapy, and 1 hormonal therapy. No patient received whole abdominal radiation therapy or para-aortic RT. Disease-free survival, pelvic recurrence-free survival, and cause-specific survival were estimated using the method of Kaplan-Meier, and prognostic factors were analyzed by the log-rank test. Median follow-up was 38.7 months (range: 3-109 months). RESULTS: The 5-year actuarial disease-free survival and cause-specific survival for the entire group was 41% and 73.6%, respectively. Nine patients developed recurrent disease. Five failed in the pelvis, of which 4 relapsed in the vagina. No pelvic failures occurred in women treated with adjuvant RT. Patients treated with adjuvant RT had a better 5-year actuarial pelvic recurrence-free survival (100% vs. 57.5%, p = 0.06) than patients treated with surgery alone. Two patients failed in the abdomen. However, neither developed an isolated abdominal recurrence. Six patients failed in distant sites, primarily the lungs and bone. CONCLUSION: Although patients with pathologic Stage I-II uterine papillary serous carcinomas have organ-confined disease, recurrence is common, particularly in the pelvis and distant sites. Our results suggest that adjuvant RT reduces the risk of pelvic failure. Contrary to traditional assumptions, however, abdominal recurrence was uncommon in our patients, despite the lack of whole abdominal radiation therapy. Our results support the use of pelvic RT in these patients. Future studies should investigate the role of adjuvant chemotherapy.     

Adjunctive chemotherapy to radical radiation therapy in the treatment of advanced nasopharyngeal carcinoma

Sixty-eight consecutive patients with previously untreated nasopharyngeal carcinoma (NPC) with advanced cervical lymph nodal metastases were studied retrospectively for the effectiveness of combining chemotherapy with radical radiation therapy (RT). In 1981 and 1982, 36 patients were treated with radical radiation therapy alone (arm 1). In 1983, 13 patients were given 2 courses of VBMF prior to RT (arm 2). In 1984, 19 patients were given radical RT sandwiched between 2 courses of PVBMF before and 2 after (arm 3). The three arms were comparable in patient characteristics with similar stages of the disease, sex, age distribution, and rates of completion of the prescribed treatments. There was no significant difference in actuarial or disease-free survival between arm 1 and 3 or arm 2 and 3, but arm 1 compared favorably with arm 2 in actuarial survival (X2 = 9.533, p = 0.002). The distant relapses in arms 2 and 3 occurred at significantly shorter times after diagnosis than those in arm 1 (t = 4.1083, p = 0.0001). Postponement of radiation therapy by chemotherapy might have accounted for the earlier distant relapses in arm 2 and 3. Radiation therapy alone given in radical dose had been demonstrated to achieve significantly more complete responses in cervical nodal metastases than either forms of chemotherapy (VBMF or PVBMF) given just two courses prior to radiation therapy (p less than 0.00003). More controlled clinical trials must be completed before acceptance of chemotherapy as part of a standard radical treatment for advanced nasopharyngeal carcinoma with advanced cervical lymph nodal metastases. In all future trials, closer integration in time sequence between the two treatment modalities is indicated. Meanwhile cervical nodal status (CR vs, PR plus NR) at the end of any treatment was shown to be of paramount prognostic significance.     

Another way to estimate outcome of advanced nasopharyngeal carcinoma--is concurrent chemoradiotherapy adequate?

PURPOSE: To evaluate a simple risk grouping system and determine whether concurrent chemoradiotherapy (CCRT) is adequate for patients with advanced nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: A total of 284 patients with 1992 American Joint Committee on Cancer (AJCC) Stage III to IV (M0) NPC were analyzed retrospectively. They were treated by either radiotherapy (RT) alone or CCRT. We divided patients into high-risk and low-risk subgroups according to our experience. High-risk patients met at least one of the following criteria: (1) nodal size >6 cm, (2) supraclavicular node metastases, (3) 1992 AJCC stage T4N2, (4) multiple neck node metastases with 1 node >4 cm. The disease extent of each patient was stratified by our risk grouping system, AJCC 1992 and 1997 staging systems. Survival analyses-including nasopharynx disease free (TS), neck disease free (NS), distant metastasis disease free (MS), overall survival (OS), and progression-free (PFS) survival curves-were compared between these three different classifications. RESULTS: According to the 1992 AJCC staging system, 80.3% (228/284) of NPC patients are Stage IV, whereas only 19.7% are Stage III. Most patients are downstaged by the 1997 AJCC staging system with 28.5% (81/284) Stage IV and 71.5% (203/284) Stage III/II. Our risk criteria stratify more even patient distribution, because 119 patients (41.9%) are assigned to the high-risk group and 165 patients (58.1%) to the low-risk group. Log-rank test of Kaplan-Meier survival curves, multivariate comparison of the Cox proportional hazards model, and 3 goodness-of-fit indices validated that our risk grouping system seemed to be at least as efficacious as, or slightly superior to, the 1992 and 1997 AJCC systems. The 5-year TS (95.1% vs. 76.8%, p = 0.0012), NS (100% vs. 95.7%, p = 0.0974), MS (90.5% vs. 78.1%, p = 0.0282), OS (83.2% vs. 59.7%, p = 0.0041), and PFS (87.3% vs. 61.5%, p = 0.0003) were significantly better in patients receiving CCRT than RT alone for the low-risk group. However, the corresponding survival rates between CCRT and RT for high-risk patients were 74.9% vs. 67.6% (p = 0.2545) for TS, 92.1% vs. 86.8% (p = 0.4744) for NS, 59.7% vs. 60.0% (p = 0.5537) for MS, 55.8% vs. 46.3% (p = 0.1761) for OS, and 44.5% vs. 43.1% (p = 0.3911) for PFS, respectively. CONCLUSIONS: Concurrent chemoradiotherapy is superior to RT alone for low-risk patients but inadequate for high-risk patients. Adding neoadjuvant and/or adjuvant chemotherapy would be a reasonable approach for high-risk patients. Our risk grouping criteria are a simple and useful guide that will have important implications in the design of future therapeutic trials.     

Combined chemotherapy and preoperative irradiation for locally advanced noninflammatory breast cancer: updated results in a series of 120 patients

PURPOSE: To evaluate our updated data concerning survival and locoregional control in a prospective study of locally advanced noninflammatory breast cancer (LABC) after primary chemotherapy (CT) followed by external preoperative irradiation (RT). METHODS AND MATERIALS: Between 1982 and 1998, 120 patients (75 Stage IIIA, 41 Stage IIIB, and 4 Stage IIIC according to AJCC staging system 2002) were treated by four courses of induction CT with anthracycline-containing combinations followed by preoperative RT (45 Gy to the breast and nodal areas) and a fifth course of CT. Three different locoregional approaches were proposed depending on tumor characteristics and tumor response. After completion of local therapy, all patients received a sixth course of CT and a maintenance adjuvant CT regimen without anthracycline. The median follow-up from the beginning of treatment was 140 months. RESULTS: Mastectomy and axillary dissection were performed in 49 patients (with residual tumor larger than 3 cm in diameter or located behind the nipple or with bifocal tumor), and conservative treatment in 71 patients (39 achieved clinical complete response or partial response >90% and received additional radiation boost to initial tumor bed; 32 had residual mass < or =3 cm in diameter and were treated by wide excision and axillary dissection followed by a boost to the excision site). Ten-year actuarial local failure rate was 13% after RT alone, 23% after wide excision and RT, and 4% after mastectomy (p = 0.1). After multivariate analysis, possibility of breast-conserving therapy was related to initial tumor size (<6 cm vs. > or =6 cm in diameter, p = 0.002). Ten-year overall metastatic disease-free survival rate was 61%. After multivariate analysis, metastatic disease-free survival rates were significantly influenced by clinical stage (Stage IIIA-B vs. IIIC, p = 0.0003), N-stage (N0 vs. N1-2a, and 3c, p = 0.017), initial tumor size (<6 cm vs. > or =6 cm in diameter, p = 0.008), and tumor response after induction CT and preoperative RT (clinically complete response + partial response vs. nonresponder, p = 0.0015). In the nonconservative breast treatment group, of the 32 patients with no change in clinical tumor size after induction CT, the 10-year metastatic disease-free survival rate was 59% with only one local relapse. Arm lymphedema was noted in 17% (14 of 81) after axillary dissection and in 2.5% (1 of 39) without axillary dissection. Cosmetic results were satisfactory in 70% of patients treated by RT alone and in 51.5% of patients after wide excision and RT. CONCLUSION: Despite the poor prognosis of patients with LABC resistant to primary anthracycline-based regimen, aggressive locoregional management using preoperative RT and mastectomy with axillary dissection offers a possibility of long-term survival with low local failure rate for patients without extensive nodal disease. On the other hand, the rate of local failure seems to be high in patients with clinical partial tumor response after induction CT and breast-conserving treatment combining preoperative RT and large wide excision.     

Impact of adjuvant therapy on survival of patients with early-stage uterine papillary serous carcinoma

PURPOSE: To determine the efficacy of adjuvant therapy in patients with early-stage uterine papillary serous carcinoma. METHODS AND MATERIALS: Data were collected on all surgically staged Stage I-II uterine papillary serous carcinoma patients. Statistical analyses were performed using the Kaplan-Meier and Cox proportional hazards regression methods. RESULTS: Of 68 patients, 50 had Stage I and 18 had Stage II disease; 35 underwent adjuvant treatment, including radiotherapy in 26, chemotherapy in 7, and combined RT and chemotherapy in 2. The remaining 33 were treated expectantly. The median follow-up was 56 months (range 1-173). The 5-year overall survival rate was 69%. Of 19 patients with disease limited to the endometrium, 10 received no additional therapy, 3 of whom developed recurrence. However, all 9 women who underwent adjuvant treatment remained free of disease. Patients receiving adjuvant therapy with chemotherapy or radiotherapy had a prolonged 5-year overall and disease-free survival compared with those who were treated expectantly (85% vs. 54%, p = 0.002 for overall survival and 85% vs. 49%, p = 0.01 for disease-free survival). In multivariate analysis, adjuvant therapy (p = 0.035) and the absence of lymphovascular space invasion (p = 0.001) remained as independent prognostic factors for improved survival. CONCLUSION: Adjuvant therapy with chemotherapy or radiotherapy improves the survival of women with early-stage uterine papillary serous carcinoma.     

Breast cancer patients with 10 or more involved axillary lymph nodes treated by multimodality therapy: influence of clinical presentation on outcome

PURPOSE: To analyze tumor control and survival for breast cancer patients with 10 or more positive lymph nodes without systemic disease, treated by adjuvant radiation alone or combined-modality therapy. METHODS AND MATERIALS: We reviewed the records of 309 consecutive patients with these characteristics who received locoregional radiotherapy (RT) at our institution. The majority of patients had clinical Stage II or IIIA-B disease (43% and 48%, respectively). The median number of positive axillary lymph nodes was 15 (range, 10-78). Adjuvant therapy consisted of RT alone, with or without chemotherapy, tamoxifen, and/or ovarian castration. RESULTS: The overall 5-year and 10-year disease-free survival (DFS) rates were 20% and 7%, respectively. Median DFS was higher for patients with Stage I-II compared with those with Stage IIIABC (28 vs. 19 months; p = 0.006). Median DFS for patients aged 相似文献   

Combined chemoradiation versus radiation therapy alone in locally advanced nasopharyngeal carcinoma: results of a meta-analysis of 1,528 patients from six randomized trials

It is currently unclear whether the addition of chemotherapy to standard radiation therapy improves clinical outcome in patients with locoregionally advanced nasopharyngeal cancer. A meta-analysis was performed to evaluate the impact of integrating chemotherapy with external beam radiation therapy in this clinical setting. Using previously described methods, a protocol was developed outlining a meta-analysis examining the influence of chemoradiation versus radiation alone (control arm) in locoregionally advanced nasopharyngeal carcinoma. The outcomes of interest were disease-free/progression-free and overall survival. Literature search techniques, study inclusion criteria, and statistical procedures were prospectively defined. Data from all available randomized controlled trials was pooled using a fixed effects model (Peto). Results were expressed as summary relative risks. Statistical tests for heterogeneity were performed. If statistical heterogeneity was demonstrated, sensitivity analyses were performed to evaluate possible sources of heterogeneity across the included studies. The literature search identified six randomized controlled trials enrolling more than 1,500 patients. All trials compared standard radical external beam radiation therapy (control arm) with radiation plus chemotherapy delivered either adjuvantly, neoadjuvantly, or concurrently with radiation. Pooling all six studies using disease-free/progression-free survival as the endpoint demonstrated that the addition of chemotherapy to radiation therapy increased disease-free/progression-free survival by 37% at 2 years, 40% at 3 years, and 34% at 4 years after treatment. Likewise, the summary relative risk for overall survival at 2 years after treatment with the addition of chemotherapy to the treatment regimen was 0.80 (0.63-1.02), reflecting a 20% increase in 2-year survival. This finding was marginally non-statistically significant. Three- and 4-year survival was increased by 19% and 21%, respectively, with the data for 4-year survival being statistically significant. The addition of chemotherapy to standard radical radiation therapy for locoregionally advanced nasopharyngeal cancer increases both disease-free/progression-free and overall survival by 19 to 40% at 2 to 4 years after treatment, depending on the endpoint of interest. Future trials are needed to confirm these results and determine the most effective regimen for integrating chemotherapy with radiation therapy in this setting.     

A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage IIIB cervical carcinoma.

To clarify the role of thermoradiotherapy for FIGO Stage IIIB cervical carcinomas, both the clinical response and survival of patients treated with radio- or thermoradiotherapy were investigated. Forty patients with Stage IIIB uterine cervix carcinoma were treated with external beam irradiation to the pelvis, combined with iridium 192 high-dose-rate intracavitary brachytherapy. All patients were divided randomly into the following two groups: the radiotherapy (RT) group of 20 patients, who underwent radiotherapy alone; and the thermoradiotherapy (TRT) group of 20 patients, who underwent three sessions of hyperthermia in addition to radiotherapy. The primary endpoint of this study was local complete response and survival. A complete response was achieved in 50% (10 of 20) in the RT group versus 80% (16 of 20) in the TRT group (p = 0.048). The 3-year overall survival and disease-free survival of the patients who were treated with TRT (58.2 and 63.6%) were better than those of the patients treated with RT (48.1 and 45%), but these differences were not significant. The 3-year local relapse-free survival of the patients who were treated with TRT (79.7%) was significantly better than that of the patients treated with RT (48.5%) (p = 0.048). TRT, as delivered in this trial, was well tolerated and did not significantly add to either the relevant clinical acute or long-term toxicity over radiation alone. TRT resulted in a better treatment response and 3-year local relapse-free survival rate than RT for patients with FIGO Stage IIIB cervical carcinoma.     

Neoadjuvant Chemotherapy Plus Conventional Radiotherapy or Accelerated Hyperfractionation in Stage III and IV Nasopharyngeal Carcinoma - A Phase II Study

A prospective phase II trial was initiated in previously untreated patients with locally advanced nasopharyngeal carcinoma (NPC). The goal was to achieve improvement in locoregional control, disease-free interval and overall survival using induction chemotherapy and to compare conventional fractionation (CF) with an accelerated hyperfractionation (AHF) regimen. Fifty patients were treated (5 AJCC Stage III, 45 Stage IV) with induction chemotherapy consisting of two cycles of cisplatin and 5-fluorouracil. Patients were then randomized between CF and AHF therapy. A clinical response to induction chemotherapy was reported in 86% of patients prior to radiotherapy (44% complete response, 42% partial response). Patients with complete or major partial responses to induction chemotherapy had a significantly better 5-year overall survival (60%) and disease-free interval (59%) than those with no response or minor partial response (15% and 18%, p = 0.009 and 0.0009). Acute radiation reactions were more pronounced in the AHF group (p = 0.0002), and the incidence of late normal tissue injury was more frequent (p = 0.08). At 5 years, the locoregional control rate was higher in the AHF arm (76%) than in the CF group (54%), but the difference was not significant (HR, 0.52; 95% CI, 0.15?2.83; p = 0.186). With a median follow-up period of 55 months (range 4?120), the 5-year disease-free interval and overall survival rates were more favorable in the AHF group than in the CF group, but the differences were not significant (59% and 54% vs. 34% and 36%, respectively, HR for disease-free interval=0.71; 95% CI, 0.27?1.88; p = 0.198 and HR for overall survival = 0.81; 95% CI, 0.37?1.78; p = 0.433). The overall treatment failure rate was 48%. Locoregional failures occurred in 12 patients (24%) and the incidence of distant metastases reached 30%. Response to induction chemotherapy is strongly predictive for locoregional control, disease-free interval and overall survival. Accelerated hyperfractionation was associated with high incidence of acute and late toxicity without significant improvement in locoregional control rate. The optimal chemotherapy dose and sequencing with radiotherapy needs to be investigated in future studies. Distant metastases remain the main cause of treatment failure in NPC.     

Hyperfractionated radiation therapy for locoregionally advanced nasopharyngeal cancer

OBJECTIVE: The purpose of this study is to clarify the efficacy and toxicity of hyperfractionated radiation therapy (RT) for patients with nasopharyngeal cancer (NPC). METHODS: Twenty-two patients with NPC treated at our hospital between April 1994 and December 2002 were the subjects of this study. They received hyperfractionated RT with a fraction size of 1.2 Gy, with a median tumor dose of 72 Gy (range 64.8-80.4). During this study period, our institutional strategy for locoregionally advanced NPC included neoadjuvant or concurrent chemotherapy combined with hyperfractionated RT, and 17 patients received some forms of cisplatin-containing chemotherapy. RESULTS: With a median follow-up of 59 months, the estimated 5-year disease-free survival rate and overall survival rate were 72.7 and 85.2%, respectively. Acute hematological toxicities were acceptable and manageable. However, >50% of patients required nutritional support, and experienced severe pharyngitis, skin reaction and body weight loss. With regard to late sequelae, one patient developed grade 3 osteomyelitis, and one patient each developed grade 4 passage disturbance and laryngeal edema. No patients experienced any grades of optic nerve injury or temporal lobe necrosis. CONCLUSIONS: Hyperfractionated RT using 1.2 Gy per fraction, for a total dose of 72 Gy, produces a comparable treatment outcome. Although deleterious neurological sequelae were not observed in this study, caution should be exercised regarding other late sequelae, such as osteomyelitis and passage disturbance.     

Does induction chemotherapy have a role in the management of nasopharyngeal carcinoma? Results of treatment in the era of computerized tomography

To assess the outcomes of patients with nasopharyngeal carcinoma (NPC) whose treatment was determined by computerized tomography (CT) and/or magnetic resonance imaging staging and to analyze the impact of induction chemotherapy and accelerated fractionated radiotherapy.

The analysis is based on 122 of 143 previously untreated patients with NPC treated with radiation therapy at The University of Texas M. D. Anderson Cancer Center between 1983 and 1992. Excluded were 4 patients treated with palliative intent, 4 children, 12 patients not staged with CT, and 1 patients who died of a cerebrovascular accident prior to completion of treatment. The stage distribution was as follows: AJCC Stage I---2; Stage II---7, Stage III---12, Stage IV---101; T1---15; T2---33, T3---22; T4---52; N0---32; N1---10; N2---47, N3---32, Nx---1. Fifty-nine (48%) patients has sqamous cell carcinoma; 63 (52%) had lymphoepitheliomas, undifferentiated NPC or poorly differentiated carcinoma, NOS (UNPC). Sicty-seven patients (65 with Stage IV disease) received induction chemotherapy. Fifty-eight patients (24 of whom had induction chemotherapy) were treated with the concomitant boost fractionation schedule. The median follow-up for surviving patients was 57 months.

The overall actuarial 2- and 5-year survival rates were 78 and 68%, respectively. Forty-nine patients (40%) has disease recurrence. Thirty-three (27%) had local regional failures; 19 at the primary site only, 8 in the neck and 6 in both. Local failure occurred in 31% of patients staged T4 compared to 13% of T1–T3 (p = 0.007). Sixteen patients failed at distant sites alone. Among Stage IV patients the 5-year actuarial rates for patients who did and did not receive induction chemotherapy were as follows: overall survival: 68 vs. 56% p = 0.02), freedom from relapse; 64 vs. 37% (p = 0.01), and local control: 86 vs. 56% (p = 0.009). The actuarial 5-year distant failure rate in patients with UNPC who were treated with induction chemotherapy and controlled in the primary and neck was 13%. In patients who did not receive chemotherapy, the acturial 5-year local control rates for patients treated with concomitant boost or conventional fractionation were 66 and 67%, respectively.

While not providing conclusive evidence, this single institution experience suggests that neoadjuvant chemotherapy for Stage IV NPC patients improves both survival and disease control. Recurrence within the irradiated volume was the most prevalent mode of failure and future studies will evaluate regimens to enhance local regional control.     

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.     

Postoperative radiotherapy increases locoregional control of patients with stage IIIA non-small-cell lung cancer treated with induction chemotherapy followed by surgery

PURPOSE: To determine the effectiveness of postoperative radiotherapy (RT) in patients with Stage IIB and Stage IIIA non-small-cell lung cancer (NSCLC) treated with induction chemotherapy followed by surgery. METHODS AND MATERIALS: We retrospectively reviewed the treatment records of 98 patients (58 men and 40 women; median age 61 years, range 31-91) with Stage IIB and Stage IIIA NSCLC who were treated with induction chemotherapy followed by surgery at our institution between January 1990 and December 2000. Patients were grouped by treatment (chemotherapy/surgery alone vs. chemotherapy/surgery/RT), by disease stage and nodal classification. The rates of local control (LC), disease-specific survival, disease-free survival, and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: Of the 98 patients, 40 had Stage IIB and 58 had Stage IIIA. The clinical disease stage and N stage were significantly greater in those patients who underwent RT than in those who did not; however, no statistically significant differences were identified in the additional characteristics between those receiving and not receiving RT within each stage or nodal group. The overall 5-year actuarial LC rate was 81% in the RT group and 54% in the chemotherapy/surgery-alone group (p = 0.07). Postoperative RT significantly improved the 5-year LC rate in patients with Stage IIIA disease (from 35% to 82%, p = 0.01). Postoperative RT did not significantly improve the 5-year OS rate (30% with RT vs. 49% without) for all patients or for patients with Stage IIIA disease. The disease-specific survival and disease-free survival rates did not differ between the treatment groups. Patients who responded to induction chemotherapy had a significantly greater 5-year OS rate (49%) than did those with stable or progressive disease (22%, p = 0.003). CONCLUSION: Postoperative RT in patients with Stage IIIA NSCLC treated with induction chemotherapy followed by surgery significantly improved LC without improving OS. Significantly improved survival was observed in all patients who responded to induction chemotherapy compared with those with stable or progressive disease.