Partially hyperfractionated accelerated radiotherapy and concurrent chemotherapy for advanced nasopharyngeal carcinoma

A newly designed concomitant chemoradiotherapy was undertaken to assess the feasibility and efficacy for advanced nasopharyngeal carcinoma (NPC).

Sixty-three patients with biopsy-proven NPC were entered in this Phase II trial from March 1992 to November 1993. Most patients present with Stage IV disease (93.4%) and poorly differentiated epidermoid carcinoma or undifferentiated carcinoma were the major pathologic type. Radiotherapy was delivered using a telecobalt unit and 10 MV x-rays and by altered fractionation (72–74 Gy/45 fractions/6 weeks). Chemotherapy with cisplatin 75 mg/mm², 2 h infusion at day 1, followed by 5-FU 400 mg/m²/day, continuosly infused for 4 days was given concurrently during the first and fifth weeks of radiotheraphy.

The major toxicity was mucositis (61% belong to Grade 3, 31% to Grade 2). Weight loss, leucopenia, and skin reaction were frequently encountered. Three patients withdrew from treatment at 15, 25, and 55.5 Gy, three patients interrupted the radiotherapy for 1–4.5 weeks, and two patients refused the second cycle of concomitant chemotherapy due to toxicities. The initial tumor response showed 100% overall response rate, with 90.5% complete response. After a median follow-up tiem of 38 months, five patients failed at the primary and/or neck (four recurrent and one persistent), and 14 patients developed distant metastases alone. The 3-year primary disease-free, regional disease-free, distant disease-free, and overall survival rates are 89.1, 92.8, 74.3, and 73.6%, respectively. The late complication rate is acceptable so far.

Our data indicates that concurrent chemoradiotherapy for advanced NPC is both feasible and effective, with acceptable toxicities. Distant metastases are the major site of treatment failure. Postradition adjuvant chemotherapy to eradicate subclinical distant metastasis should be further studied.     

Combined radiotherapy and chemotherapy in stage T3 and T4 nasopharyngeal carcinoma in children

Twelve children younger than 16 years affected by undifferentiated nasopharyngeal carcinoma (NPC) with advanced primary tumor (T3, T4) were treated with chemotherapy consisting of Adriamycin (ADM [doxorubicin; Adria Laboratories, Columbus, OH]), vincristine (VCR), and cyclophosphamide (CYC), and radiotherapy. Preradiation chemotherapy produced partial responses in eight of ten evaluable patients. Eleven of 12 patients achieved a complete response following radiotherapy. The actuarial 3-year continuous relapse-free survival (CRFS) was 75%. This represents a significant improvement when compared with the 8% rate obtained in a previous series of patients treated with radiotherapy either with or without adjuvant CYC.     

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.     

后程加速超分割放疗联合同步化疗治疗晚期鼻咽癌

 目的　探讨后程加速超分割放疗联合同步化疗治疗Ⅲ期、ⅣA期鼻咽癌的疗效。方法　将116例Ⅲ期、ⅣA期鼻咽癌确诊患者随机分为单放组（38例）、同步放化疗组（39例）和后程加速放化疗组（39例）。单放组给予60Coγ线和深部X线常规外照射，面颈联合野剂量达36～38 Gy后，改双侧耳前野，鼻咽部照射总量70～75 Gy，颈部转移灶预防照射量为50 Gy，总剂量达70～80 Gy；同步放化疗组同时给予5-氟尿嘧啶（5-Fu）＋顺铂（DDP）的FP方案化疗，共2周期；后程加速同步放化疗组在鼻咽部剂量达36～38 Gy后，改双侧耳前野加速超分割放疗，1.3 Gy／次，2次／d，间隔6 h以上，鼻咽部总剂量69.8～75 Gy，化疗方案同同步放化疗组。结果　后程加速放化疗、同步放化疗、单纯放疗三组有效率分别为94.9 %、89.7 %、76.3 %，其中单纯放疗组原发肿瘤消退率明显高于后程加速放化疗组，差异具有统计学意义（P < 0.05）。三组1、2、3年局控率分别为100 ％、97.4 ％、89.5 ％，94.9 ％、84.6 ％、68.4 ％和89.7 ％、74.4 ％、57.9 ％；1、2、3年生存率分别为100 ％、92.3 ％、84.2 ％，89.7 ％、84.6 ％、71.0 ％和79.5 ％、76.9 ％、57.9 ％。局控率和生存率后程加速放化疗组均明显高于单放组（P < 0.05），但后程加速放化疗组与同步放化疗组、同步放化疗组与单放组之间差异无统计学意义。结论　后程加速超分割联合同步化疗治疗晚期鼻咽癌能进一步提高肿瘤的近期疗效，提高肿瘤的局控率和患者的生存率，值得临床推广和进一步研究。     

TPF方案诱导化疗加同期调强放化疗治疗晚期鼻咽癌的临床观察

目的:探讨TPF方案诱导化疗结合同期调强放化疗治疗局部区域晚期鼻咽癌的有效剂量及近期疗效.方法:Docetaxel与DDP剂量60 mg/m2,静脉滴入;5-FU初始剂量450 mg/(m2·d),持续120 h静脉灌注,按50 mg/(m2·d)剂量递增,根据剂量递增法则确定其最大耐受剂量(MTD),观察终点为出现剂量限制性毒性(DLT).每位患者行3个周期诱导化疗,每个周期化疗间隔3周,第3个周期化疗后3周给予调强放疗(IMRT)加上同期DDP 80 mg/m2化疗.结果:12例患者共完成了450～550 mg/(m2·d)3个剂量水平共34个周期诱导化疗.在550 mg/(m2·d)剂量水平,1例患者出现3度黏膜反应及4度腹泻的DLT,按既定方案再以此剂量依次治疗3例患者,未再发生DLT,该剂量水平即为MTD.除1例DLT患者停止诱导化疗外,余11例患者均行3个周期诱导化疗,3个周期诱导化疗后总反应率(OR)100%,完全缓解率(CR)64%(7/11).12例患者均完成同期放化疗,诱导化疗未加重同期放化疗的毒副反应.结论:TPF方案在Docetaxel 60 mg/m2、DDP 60 mg/m2剂量前提下治疗局部区域晚期鼻咽癌,5-FU的 MTD为550 mg/(m2·d),该方案具有较高近期反应率.     

超分割放射同期化疗治疗Ⅲ和Ⅳ期鼻咽癌前瞻性研究

目的；比较超分割加同期化疗与单纯超分割放射治疗Ⅲ-Ⅳ期鼻咽癌的生存率和局部控制率。方法：150例鼻咽癌患者随机分人超分割加同期化疗组（研究组）和单纯超分割放射治疗组（对照组）。放射治疗方式2个组相同，1．2Gy／次， 2次／d。研究组在放射治疗前、中加用化疗，放射、化疗同期进行。结果：5年总生存率为57．3％，5年无瘤生存率无远地转移生存率均为55．9％。研究组和对照组5年生存率分别为64．0％和50．7％,(x^2＝4．26，P＝0．037）。研究组有1例鼻咽部复发而对照组有5例鼻咽部复发，5年局部控制率分别为98．7％和93．4％。研究组的急性黏膜反应高于对照组，但能耐受，无严重并发症发生。结论：超分割放射同期化疗治疗Ⅲ-Ⅳ期鼻咽癌生存率和局部控制率有所提高，且能耐受。化疗对Ⅳ期的生存率影响更大。     

Accelerated concomitant boost radiotherapy and chemotherapy for advanced nasopharyngeal carcinoma.

PURPOSE: To evaluate the feasibility and efficacy of concomitant boost radiotherapy (RT) plus cisplatin-based chemotherapy compared with standard fractionation RT for patients with advanced nasopharyngeal cancer. PATIENTS AND METHODS: From 1988 through 1999, 50 patients with American Joint Committee on Cancer stage II-IVb nasopharyngeal carcinoma were treated with 70-Gy concomitant boost RT (1.8 Gy/d, weeks 1 through 6; 1.6 Gy second daily fraction, weeks 5 through 6) and two cycles of concurrent cisplatin 100 mg/m(2) days 1 and 22. Thirty-seven patients also received three cycles of cisplatin-based adjuvant chemotherapy. These 50 patients were compared with a nonrandomized cohort of 51 patients with nasopharyngeal cancer treated with 70-Gy standard fractionation RT (1.8 Gy/d) without chemotherapy from 1988 through 1995. The groups were well matched for prognostic factors except stage, for which the concomitant boost RT/chemotherapy group was more advanced (54%, T3-4; 54%, N2-3; 44%, stage IV) compared with the standard RT group (31%, T3-4, P =.03; 22%, N2-3, P <.001; 20%, stage IV, P <.01). RESULTS: With a median follow-up of 42 months (range, 12 to 129 months), the 3-year actuarial local control, progression-free survival, and survival rates were 89% v 74% (P <.01), 66% v 54% (P =.01), and 84% v 71% (P =.04) for the concomitant boost RT/chemotherapy group and the standard RT patients, respectively. Acute grade 3 mucositis was more prevalent with combined therapy, 84% v 43% (P <.001), resulting in a higher rate of temporary gastrostomy tube placement, 46% v 20% (P <.01). CONCLUSION: Concomitant boost RT with cisplatin-based chemotherapy is feasible and improves local-regional control as well as survival for patients with advanced nasopharyngeal cancer compared with standard RT alone.     

Preoperative concomitant radiotherapy and chemotherapy in ultrasound-staged T3 and T4 rectal cancer

BACKGROUND: To analyze early results of a single institution's experience using neo-adjuvant chemoradiotherapy in locally advanced, ultrasound-staged rectal cancer. PATIENTS AND METHODS: Since 1998, 67 consecutive patients (36 males and 31 females; mean age, 59.5) have received preoperative combined treatment for T3 or T4 rectal cancer. All patients were staged by endorectal ultrasound and computed tomography, and all had a pathology-demonstrated invasive adenocarcinoma of the rectum. Patients were treated preoperatively with concomitant radiochemotherapy: pelvic irradiation (50 Gy in 25 fractions) and protracted-venous-infusion 5-fluorouracil (225 mg/m2/d, 7 days per week). Patients were restaged within 4 weeks, then submitted to surgery within 6-7 weeks after the end of therapy. Adjuvant postoperative chemotherapy with 5-fluorouracil plus folinic acid--the "de Gramont" schedule--for 24 weeks was purposed to all patients. RESULTS: Radiotherapy was completed in all cases; only one patient required suspension of the treatment for grade 4 toxicity (diarrhea). Instead, chemotherapy was interrupted in 3 cases (2 for central venous catheter thrombosis and 1 for grade IV diarrhea). Sixty-six patients underwent surgical resection (1 patient died before surgical treatment). Radical surgery was performed in 94%, and 46% of the 26 patients with distal rectal cancer had a conservative sphincter-sparing surgery. A complete pathologic response (defined as no evidence of viable tumor cells) was obtained in 22%. At a median follow-up of 17 months, distant metastases have been observed in 10 patients, and 3 of them developed a local recurrence. The actuarial estimations of 4-year overall survival, disease-free survival, local and distant control are 79%, 61%, 94% and 61%, respectively. CONCLUSIONS: Preoperative chemoradiotherapy seems to be an effective and well-tolerated treatment with a low complication rate. The high percentage of down-staging and sphincter sparing, also in distal rectal cancer, shows the efficacy of the treatment, which could significantly influence the incidence of relapses and quality of life.     

Ⅲ期、Ⅳa期鼻咽癌后程加速超分割放疗联合化疗的临床研究

 目的 研究后程加速超分割放疗联合化疗治疗Ⅲ、Ⅳa期鼻咽癌的疗效。方法 将100例Ⅲ期、Ⅳa期鼻咽癌随机分为后程加速超分割放疗联合化疗组（LCAF+CT）及常规分割放疗联合化疗组（CF+CT）。LCAF+CT于放疗前先行诱导化疗二次，化疗后先行常规分割放疗至鼻咽部剂量40 Gy，缩野后行后程加速超分割放疗至鼻咽部总剂量70 Gy。于放疗结束后行辅助化疗2次。CF+CT化疗方法与LCAF+CT相同。放疗采用常规分割，鼻咽部总剂量70 Gy。结果 LCAF+CT 3，5年实际生存率分别是70 %，62 %；CF+CT 3，5年实际生存率分别是58 %，46 %（P＜0.05）。3，5年无瘤生存率LCAF+CT分别是66 %、58 %，CF+CT分别是52 %，42 %（P＜0.05）。3，5年局部区域无复发生存率LCAF+CT及CF+CT分别为76 %，74 %及62 %，56 %（P＜0.05）。5年累积远处转移发生率LCAF+CT及CF+CT分别为18 %及22 %（P＞0.05）。LCAF+CT有2例出现放射性后组脑神经损伤，CF+CT无严重后期并发症。结论 LCAF+CT较CF+CT提高了Ⅲ、Ⅳa期鼻咽癌的3，5年实际生存率、局部区域无复发生存率及3，5年无瘤生存率，但增加了晚期并发症的发生。     

Long-term results of conventional radiotherapy versus accelerated hyperfractionated radiotherapy versus concomitant radiotherapy and chemotherapy in locoregionally advanced carcinoma of the oropharynx

AIMS AND BACKGROUND: To compare conventional fractionation (CF) radiation therapy (RT), arm A, versus a split-course accelerated hyperfractionated schedule (S-AHF), arm B, versus CFRT plus concomitant chemotherapy (CT), arm C, in terms of five-year survival and toxicity for squamous cell tumors of the oropharynx. METHODS AND STUDY DESIGN: Between January 1993 and June 1998, 192 previously untreated patients with stage III and IV oropharyngeal carcinoma (excluding T1N1 and T2N1) were enrolled in a multicenter randomized phase III trial (ORO 93-01). In arms A and C, 66 to 70 Gy in 33 to 35 fractions was administered five days a week for six and a half to seven weeks. In arm B, the dose delivered was 64 to 67.2 Gy in two fractions of 1.6 Gy every day, five days a week, with a planned two-week split at 38.4 Gy. In arm C the CT regimen consisted of three cycles of carboplatin and 5-fluorouracil (CBDCA 75 mg/m2 on days 1 to 4 and 5-FU 1000 mg/m2 i.v. on days 1 to 4 every 28 days). RESULTS: No statistically significant difference was found in five-year overall survival (P = 0.39): 21% for arm A, 21% for arm B, and 40% for arm C. Similarly, there was no statistically significant difference in terms of five-year relapse-free survival: 15% for arm A, 17% for arm B, and 36% for arm C. There was a slight trend towards better five-year locoregional control (P = 0.07) for the combined arm: patients without locoregional relapse were 48% in arm C, 21% in arm A and 18% in arm B. Locoregional control was significantly better when arm C was compared with arms A and B combined (P = 0.02; arm A+B 20%; arm C 48%). Distant metastases were fairly balanced in the three arms (A: 14; B: 9; C: 11), with a tendency towards more frequent isolated distant metastasis development in arm C (8 of 11 [72%] versus 7 of 23 [30%] in arms A+B). Five-year second-tumor-free survival was 85%. The 13 second tumors were equally distributed and were mainly correlated with tobacco and alcohol consumption (five lung, two esophagus, two oral cavity, one larynx, one pancreas, one hepatocarcinoma, one myeloma). Arm C showed slightly more G3+ late side effects involving subcutaneous tissues and mucosa, although significant late sequelae were relatively uncommon and the mucosal side effects were mostly transient. The occurrence of persistent G3 xerostomia was comparable in the three treatment arms. CONCLUSIONS: The results obtained with the combination of CT and RT compared with RT alone did not reach statistical significance, but combined treatment almost doubled the five-year overall survival, relapse-free survival and locoregional control rate. Patients with advanced squamous cell carcinomas of the oropharynx who are medically suitable for the combined approach should be treated with a combination of radiotherapy and chemotherapy. The occurrence of second tumors is relatively common in these patients and may contribute substantially to the causes of death.     

The impact of gap duration on local control in anal canal carcinoma treated by split-course radiotherapy and concomitant chemotherapy

PURPOSE: To investigate the potential benefit of reducing the intersequence gap in patients with anal cancer treated with split-course chemoradiotherapy. METHODS: The study group consisted of 90 patients with anal squamous carcinoma treated between 1981 and 1998, using concomitant chemotherapy (CT) and radiation (RT). Median age was 65 years (range 41-87). RT was delivered in a split course, with a median gap of 37.5 days (range 4-97) between sequences. First (pelvic) sequence delivered a median dose of 40 Gy (range 36-50.4), using AP/PA megavoltage photon beams. Boost treatment (median dose 20 Gy, range 13-26) consisted of either Iridium-192 implantation (49 patients) or external beam RT (41 patients). CT consisted of 1-2 cycles of a 5-day continuous infusion of 5-fluorouracil and bolus mitomycin C, usually administered during the first week of each RT course. Median follow-up was 76.2 months. Univariate and multivariate analyses were performed to determine the factors associated with locoregional control (LRC). RESULTS: Five-year actuarial LRC was 72.5%. Factors associated with poorer LRC (univariate) were: age < or = 65, male gender, and gap > 37.5 days. Number of CT cycles (1 vs. 2 or more), boost technique (brachytherapy vs. external), and T-stage were not significantly associated with LRC. In multivariate analysis, only age (p = 0.01), and gap (p = 0.02) retained their significance. In patients older than 65 years, LRC was 92.3% and 75% for shorter and longer gaps, respectively. In younger patients, the corresponding values for LRC were 73.7% and 50%. CONCLUSION: In anal cancers, split-course RT with > 50 Gy dose delivery is difficult to avoid because of acute toxicity. The present analysis suggests that shortening the gap contributes to optimizing LRC. Gaps longer than 5 weeks correlated with poorer LRC, with especially unsatisfactory results observed in younger patients.     

Tumor volume and local control in primary radiotherapy of nasopharyngeal carcinoma

An investigation of the effect of tumor volume and total dose on local control following primary radiotherapy for nasopharyngeal carcinoma was carried out in order to estimate the radiation dose necessary to control a specific tumor volume. Between 1983 and 1996 a total of 104 patients underwent radiation therapy for nasopharyngeal carcinoma at the Department of Radiation Oncology of the University of Wuerzburg. Total doses of between 8 and 80 Gy (5 fractions per week) were administered. Complete CT-data on primary tumor size, total tumor dose (calculated by 3D- or quasi 3D-CT-based radiation planning computer) and on local control status in the follow-up period were available for 63 patients. Lymph node metastases were present in 38 of these patients and they were also entered into the study. Thus this study is based on a total of 101 tumor regions. A Poisson probability-based model was used for calculating the dose-response relationship. Assuming a correlation between tumor volume and the total dose necessary to obtain local control, the individual tumor volumes were rescaled to a 1 ml volume by introducing a volume-dependent modification factor for the applied dose, in order to eliminate the influence of different individual tumor volumes. All dose values given are based on a fractionation scheme of 2 Gy single dose, 5 fractions per week. Nineteen tumors and 11 lymph nodes were considered locally uncontrolled or recurrent. Without dose-volume modification, a weak dose-response correlation was found and a typical shallow dose-response curve was calculated with a 50% response dose (RD50) of 60.2 Gy and a normalized dose-response gradient (gamma50) of 3.2+/-0.62. After dose-volume modification and rescaling to a 1 ml tumor volume, a steep dose-response curve with an RD50 of 40.9 Gy and gamma50 of 8.2. was found. Tumor volume is a very important factor influencing local control in nasopharyngeal carcinoma. The rescaling procedure to a reference volume of 1 ml used in this study revealed a very steep dose-response relationship. This result suggests that the clinically observed smooth dose-response relationships may be explained by interindividual tumor volume heterogeneity. The additional dose necessary to control a tumor of the double volume is close to 5 Gy. With a total dose of 72 Gy (5x2 Gy/week), tumor volumes larger than 64 ml are unlikely to be controlled.     

局部复发鼻咽癌超分割加立体定向适形放疗的临床研究

目的:初步评价超分割外照射加立体定 向适形放射剂量治疗局部复发鼻咽癌的临床疗 效及毒副反应。方法:对1999～2002年收治的 14例复发鼻咽癌进行超分割外照射(1.3Gy/次, 2次/d,总剂量42～60Gy)加立体定向适形放射 推量(4Gy/次,隔日照射,共10次,总量20Gy) 的临床研究。结果:总有效率(CR+PR)85.7% (12/14),其中完全消退(CR)64.3%(9/14),部分 消退(PR)21.4%,肿瘤稳定14.3%,2年总生存 率57.1%(8/14),无瘤生存率42.8%(6/14),靶 区肿瘤控制率为78.6%(11/14)。结论:超分割 外照射加立体定向适形放射剂量治疗局部复发 鼻咽癌在临床上是可行及有效的。     

局部复发鼻咽癌超分割加立体定向适形放疗的临床研究

目的：初步评价超分割外照射加立体定向适形放射剂量治疗局部复发鼻咽癌的临床疗效及毒副反应。方法：对1999～2002年收治的14例复发鼻咽癌进行超分割外照射（1．3Gy／次，2次／d，总剂量42～60Gy）加立体定向适形放射推量（4Gy／次，隔日照射，共10次，总量20Gy）的临床研究。结果：总有效率（CR＋PR）85．7％（12／14），其中完全消退（CR）64．3％（9／14），部分消退（PR）21．4％，肿瘤稳定14．3％，2年总生存率57．1％（8／14），无瘤生存率42．8％（6／14），靶区肿瘤控制率为78．6％（11／14）。结论：超分割外照射加立体定向适形放射剂量治疗局部复发鼻咽癌在临床上是可行及有效的。     

鼻咽癌腔内近距离超分割推量照射的研究

目的 分析鼻咽癌腔内近距离超分割放射治疗的临床及效及适应证的选择。方法 体外照射＋腔内后装超分割推量放射治疗鼻咽癌128例，体外常规放射治疗50－66Gy后进行腔内近距离放射治疗，1996年6月以后由于经颌下鼻咽旁区插植术的开展，腔内后装的适应证的选择严格按肿瘤侵犯深度在鼻咽部粘膜下≤10mm。施源管技术采用个体化模块将施源管固定在鼻咽腔内，并将软腭推开，剂量分割采用超分割法2．5－3．0Gy／次，2次／d，间隔6h，总剂量12－24Gy，中位剂量18Gy。体外照射剂量分为3个组，即：56Gy组44例（其中37例为56Gy），60Gy组54例，66Gy组30例。结果 全组3、4年无瘤生存率分别为84．2％、74．9％，3、4年局部无复发生存率分别为97．1％、92．7％。体外照射56、60和66Gy组的3年无瘤生存率分别为83．6、88．4％和84．6％（X^6=0.92,P=0.63),3年局部无复发生存率分别为100％、90．9％、93．3％（X^2=0.25,P=0.88)，差异均无统计学意义。结论 腔内近距离治疗前应该进行CT或MRI影像评价并进行严格的适应证选择及后装技术的选择，腔内近距离治疗的适应证为病变厚度≤10mm的病例为好。在此基础上T1、T2期鼻咽癌计划外照射的剂量可以降低至56Gy。腔内近距离治疗超分割方法的晚期放射性反应少，患者可以耐受，具有可行性。     

局部晚期鼻咽癌同时放、化疗疗效观察

目的：观察同期放、化疗治疗局部晚期鼻咽癌的近期疗效、生存率、局部控制率、远处转移率和毒副反应。方法：60例局部晚期鼻咽癌为综合治疗组，分别在放疗第1，5周及放疗后1周给予DDP30mg／m^2 1天～3天，5-Fu500mg／m^2 1天～5天化疗共4～5个周期，另配对选取60例单纯放疗者为对照组，两组放疗方法相同。结果：综合组与单放组鼻咽肿瘤完全消退率分别为93％和84．2％（P〉0．05），颈部淋巴结完全消退率分别为87．2％和59．8％（P〈0．05），3年生存率分别为75．2％和48．3％（P〈0．05），3年局控率分别为87．2％和70．3％（P〈0．05），3年远处转移率分别为17．2％和38．8％（P〈0．05）。综合组白细胞减少症、胃肠道反应和口腔粘膜反应较单放组多且明显（P〈0．05），但可接受。结论：同期放、化疗与辅助化疗有助于提高局部控制率和生存率，减少远处转移率。     

Late course accelerated hyperfractionated radiotherapy of nasopharyngeal carcinoma (LCAF).

BACKGROUND AND PURPOSE: To study the efficacy of late course accelerated fractionated (LCAF) radiotherapy in the treatment of nasopharyngeal carcinoma (NPC). The end-points were local control, radiation-induced complications, and factors influencing survival. PATIENTS AND METHODS: Between December 1995 and April 1998, 178 consecutive NPC patients were admitted for radiation treatment. The radiation beam used was (60)Co gamma or 6 MV X rays. For the first two-thirds of the treatment, two daily fractions of 1.2 Gy were given to the primary lesion, with an interval of > or =6h, 5 days per week to a total dose of 48 Gy/40 fractions, over a period of 4 weeks. For the last third of the treatment, i.e., beginning the 5th week of treatment, an accelerated hyperfractionated schedule was carried out. The dose per fraction was increased to 1.5 Gy, 2 fractions per day with an interval of > or =6h, the total dose for this part of the protocol was 30 Gy/20 fractions over 2 weeks. Thus the total dose was 78 Gy in 60 fractions in 6 weeks. RESULTS: All patients completed the treatment. Acute mucositis: none in 2 cases, Grade 1 in 43 cases, Grade 2 in 78 cases, Grade 3 in 52 cases, and Grade 4 in 3 cases. Local control rate: the 5 year nasopharyngeal local control rate was 87.7%, and the cervical lymph nodes local control rate was 85.7%. The 5-year distant metastasis rate was 26.1%, and 5 year survivals were 67.9%, 16 (9%) patients had radiation-induced cranial nerve palsy, 7(4%) patients had temporal lobe or brainstem damage. CONCLUSIONS: With this treatment schedule, patients' tolerance was good, local control and 5 year survivals were better than conventional fractionation schedules, and radiation-related late complications did not increase, as 5-year survival rates of conventional fractionation radiotherapy were only 58%. Randomized clinical trials are being carried out to further confirm the efficacy of LCAF for nasopharyngeal carcinoma.     

Enhancement of local control in locally advanced node-positive nasopharyngeal carcinoma by adjunctive chemotherapy

PURPOSE: To determine the efficacy of chemotherapy adjunctive to radical radiotherapy (neoadjuvant +/- adjuvant) in patients with node-positive nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: All the node-positive patients given adjunctive chemotherapy between 1984-1989 (n = 209, CHEMO) were compared with all the node-positive patients treated by radical radiotherapy alone during the same period (n = 409, NCHEMO). The CHEMO group had significantly more bulky nodes, lower cervical/supraclavicular nodes, and more advanced overall stages than the NCHEMO group because nodal size (> or =24 cm) was used as a selection criterion for chemotherapy (1984-1988 departmental protocol and 1988-1989 prospective randomized trial). The chemotherapy consisted of two courses of neoadjuvant cisplatin (100 mg/m2 D1) and 5-fluorouracil (5-FU) (1 gm/m2 D1-D3) in 191 patients. In addition to the two courses of neoadjuvant, four courses of adjuvant chemotherapy, of the same combination, were given after radical radiotherapy in a further 18 patients. Radical radiotherapy delivered a nasopharyngeal dose of 60-62.5 Gy. In addition, parapharyngeal booster external radiotherapy (20 Gy) was given in the presence of parapharyngeal involvement, and intracavitary brachytherapy (24 Gy) was used to treat any local residual tumor diagnosed at 4-6 weeks after external radiotherapy. Both crude and actuarial rates were compared (survival, distant metastases, and local failures) between CHEMO and NCHEMO for all patients, for individual Ho's overall stage, for patients with nodes of different sizes (< or =3 cm, >3-< or =6 cm, >6 cm), for individual T-stage and individual N-stage, and for patients belonging to different gender and different age groups (<40 years, > or =40 years). Multivariate analyses using the Cox Regression Model were performed to identify significant prognostic factors. RESULTS: With a median follow-up of 5.5 years (range 0.7 to 10 years), CHEMO had significantly less local failures overall than NCHEMO; this was especially true for patients with advanced stages (III + IV). Additionally, in all nodal-size subgroups, in all node-positive T3, and in node-positive T3-Stage IV, there was a significant reduction in local failures after chemotherapy. There was a trend toward fewer local failures in favor of chemotherapy in Stage III, Stage IV, and T3-Stage III (0.05相似文献