鼻咽癌放射治疗失败原因分析

目的：研究鼻咽癌放射治疗失败原因,为制定鼻咽癌治疗策略提供依据。方法：１９９２年８月至１９９３年１２月,６２１例鼻咽癌患者Ｉ～Ⅳ期分别为５．５％,２５．０％,４７．８％及２１．７％,治疗前均行ＣＴ或ＭＲ检查,经鼻咽病理证实的非转移鼻咽癌接受根治术放射治疗。鼻咽腔内残留病灶,给予腔内后装治疗。随诊方法根据症状、体征、病理学及相关部位的影像学检查,生存分析用Ｋａｐｌａｎ－Ｍｅｉｅｒ法,生存指标采用总生     

Patterns of treatment failure following radiotherapy with combination chemotherapy for patients with high-risk stage IIB cervical carcinoma

Background To evaluate the patterns of treatment failure in patients with stage IIB cervical carcinoma with high-risk factors following radiotherapy given concurrently with combination chemotherapy.Methods A retrospective analysis of 349 patients with stage IIB cervical carcinoma with high-risk factors (lesion size 4cm, lymph node metastasis, high-risk cell type) treated by radiotherapy and cisplatin-based chemotherapy was performed. Sites of treatment failure were categorized as pelvic, pelvic plus distant metastases, and distant metastases alone. Pelvic failure included local and pelvic nodal failures.Results Of the 349 patients, treatment failure occurred in 79 patients (22.6%). Forty-six (13.2%) had persistent disease and 33 (9.5%) had recurrent disease. Among these 79 patients, overall pelvic failure was observed in 67%, of whom 72% had local failure; 19%, pelvic nodal failure; and 9%, local with pelvic nodal failure. Incidences of distant metastases alone and pelvic with distant metastases were 24% and 9%. In the 26 patients with distant metastases either alone or combined with pelvic failure, the most frequent metastatic region was the paraaortic lymph node (50%). The distant metastasis rate was 6.5% (19/289) in the pelvic tumor control group and 11.6% (7/60) in the pelvic failure group. Pelvic failure was the most frequent failure in the group with tumor size of 4cm or more, whereas, for the positive-lymph-node group, distant metastasis was most frequent and metastases to paraaortic lymph nodes were common. The incidences of pelvic failure alone and distant metastases were similar in the high-risk cell-type group, and the distant metastasis regions were mostly paraaortic lymph nodes.Conclusion Although systemic chemotherapy was administered concurrently with radiotherapy, the incidence of pelvic failure was highest, followed by paraaortic lymph node metastases, in patients with stage IIB cervical carcinoma with high-risk factors, following radiotherapy with combination chemotherapy.     

局部晚期鼻咽癌诱导化疗后调强放疗同期化疗疗效评价

目的 评价NP方案诱导化疗后调强放疗同期化疗对局部晚期鼻咽癌的疗效和不良反应。
方法 2005-2009年62例经病理、细胞学证实的局部晚期鼻咽癌患者入组,先长春瑞滨(25 mg/m²)和顺铂(25 mg/m²)诱导化疗 2~4周期,然后调强放疗同期化疗。常规分割放疗,鼻咽部 72~76 Gy分 36~38次(有局部残留则γ刀加量5 Gy),颈部淋巴结区预防照射50 Gy (肿大淋巴结则加量至 60~70 Gy)。
结果 随访率为100%。鼻咽原发灶有效率为89%,颈部淋巴结有效率为90%。1、2、3年总生存率,无瘤生存率,无局部区域复发生存率和无远处转移生存率分别为97%、92%、82%,94%、73%、65%,97%、89%、87%和97%、84%、77%。3~4级急性反应发生率白细胞减少为37%、血小板减少为18%、黏膜炎为6%。无 3~4级远期颞颌关节损伤及口干症状。
结论 局部晚期鼻咽癌采用25 mg/m²长春瑞滨、顺铂诱导化疗后调强放疗同期化疗的生存率较高,不良反应可耐受。     

Neoadjuvant chemotherapy and radiation therapy compared with radiation therapy alone in advanced nasopharyngeal carcinoma

PURPOSE: To analyze the impact of neoadjuvant chemotherapy on the treatment of locoregionally advanced nasopharyngeal carcinoma and to assess the outcomes of patients receiving such treatment. METHODS AND MATERIALS: We analyzed 137 previously untreated and histologically confirmed advanced stage nasopharyngeal carcinoma patients treated with either radiation therapy only or combined radiation therapy and chemotherapy at the Seoul National University Hospital between 1984 and 1996. The stage distribution was as follows: AJCC Stage III-21, Stage IV-61 in the radiation therapy group (RT group); AJCC Stage III-1, Stage IV-54 in neoadjuvant chemotherapy and radiation therapy group (CT/RT group). The median follow-up for surviving patients was 48 months. RESULTS: The 5-year overall survival (OS) rates were 71% for the CT/RT group and 59% for the RT group (p = 0.04). The 5-year actuarial disease-free survival (DFS) rates were 63% for the CT/RT group and 52% for the RT group (p = 0.04). Distant metastasis (DM) incidence was significantly lower in the CT/RT group. The 5-year freedom from distant metastasis rates were 84% for the CT/RT group and 66% for the RT group (p = 0.01). The incidence of locoregional failures was also lower in the CT/RT group, although this difference did not reach statistical significance (69% vs. 56%, p = 0.09) CONCLUSION: While not providing conclusive evidence, historical evidence from this institution suggests that neoadjuvant chemotherapy significantly improves both overall and the disease-free survival of patients with advanced stage nasopharyngeal carcinoma.     

Platinum-based chemotherapy with or without thoracic radiation therapy in patients with unresectable thymic carcinoma

BACKGROUND: Thymic carcinoma is a rare mediastinal neoplasm with poor prognosis. Although the clinical benefit of chemotherapy for thymic carcinoma is controversial, cisplatin-based chemotherapy with or without radiation therapy is ordinarily adopted in advanced cases. We evaluated the clinical outcome of platinum-based chemotherapy with or without radiation therapy in unresectable thymic carcinoma patients. METHODS: Ten patients with unresectable thymic carcinoma were treated with platinum-based chemotherapy with or without radiation therapy in the National Cancer Center Hospital between 1989 and 1998. We reviewed the histological type, treatment, response and survival of these patients. RESULTS: Four of the 10 patients responded to chemotherapy and both the median progression-free survival period and the median response duration were 6.0 months. The median survival time was 11.0 months. There was no relationship between histological classification and prognosis. CONCLUSIONS: Platinum-based chemotherapy with or without thoracic radiation is, regardless of tumor histology, marginally effective in advanced thymic carcinoma patients, giving only a modest tumor response rate and short response duration and survival.     

Salvage ifosfamide-doxorubicin chemotherapy in patients with recurrent nasopharyngeal carcinoma pretreated with cisplatin-based chemotherapy

This study evaluated the efficacy and toxicity of ifosfamide and doxorubicin chemotherapy regimen in Turkish patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) previously treated with platinum-based chemotherapy. Twenty-one patients with recurrent or metastatic NPC previously treated with platinum-based chemotherapy as adjuvant or palliative treatments who received ifosfamide 2500 mg/m² d 1–3, mesna 2500 mg/m² d 1–3, doxorubicin 60 mg/m² d 1, repeated every 21 d was retrospectively analyzed. Patients received a median number of three cycles of ifosfamide-doxorubicin (range: 1–6). Seven patients (33.3%) achieved partial response and no patient achieved complete response. Six (28.5%) had stable disease, whereas three (18.75%) had progressive disease. The median time to progression was 7.0 mo. Ifosfamide-doxorubicin regimen is an effective salvage regimen in patients with recurrent and metastatic NPC.     

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.     

Concurrent chemoradiotherapy with or without adjuvant chemotherapy in intermediate and locoregionally advanced nasopharyngeal carcinoma

Concurrent chemoradiotherapy (CCRT) showed a significant improvement in disease control and clinical outcome in patients with intermediate and locoregionally advanced nasopharyngeal carcinoma (NPC) (stage II, III and IVA+B). However, there has been debate about the contribution and application of additional adjuvant chemotherapy (AC) to a CCRT regime. This study aims to evaluate the additional value of AC in the treatment of intermediate and locally advanced NPC with regard to toxicity and clinical outcomes. A total of 189 patients with American Joint Committee on Cancer (AJCC) stage II to stage IVB NPC were retrospectively identified. Patient characteristics, toxicity, compliance with treatment and clinical outcomes, including response to treatment, overall survival (OS), progression-free survival (PFS), relapse-free survival (RFS), freedom from local recurrence (FLR) and freedom from distant metastasis (FDM), were analyzed. The overall response rate of CCRT and CCRT/AC groups was 97.92 % and 97.83 %, respectively (P?=?0.643). The 5-year OS rate was 68.2 % in the CCRT group and 75.9 % in the CCRT/AC group (P?=?0.53). The 5-year PFS rate was 66.7 % and 71.4 % in CCRT and CCRT/AC groups, respectively (P?=?0.96). This study showed no evidence of an additional value of AC in CCRT treatment in disease control and clinical outcomes in patients with locally advanced NPC in endemic regions. Moreover, three additional cycles of AC after CCRT appeared to be poorly tolerated in patients. Therefore, AC should not be routinely used for treatment, although clinical trials may be justified.     

鼻咽癌IMRT后局部与区域失败模式研究

目的 分析鼻咽癌患者IMRT后局部与区域失败的剂量学模式,为进一步提高鼻咽癌疗效提供临床依据。方法 分析2007—2012年我院收治的364例初治无远处转移鼻咽癌患者的局部与区域失败模式,失败模式定义为V_95%(95%等剂量曲线包括的复发灶体积)≥95%定义为野内复发,20%≤V_95%<95%为野边缘复发,V_95%<20%为野外复发。生存率计算采用Kaplan-Meier法。     

Factors associated with overall survival in 1706 patients with nasopharyngeal carcinoma: Significance of intensive neoadjuvant chemotherapy and radiation break

Background and purpose

To exam factors associated with overall survival (OS) in patients with nasopharyngeal carcinoma (NPC).

Materials and methods

This study is a retrospective study of a total of 1706 consecutive NPC patients from a single institution between January 1995 and December 1998. One thousand eighty-one patients were treated with radiotherapy (RT) alone and 625 with an intensive course of neoadjuvant chemotherapy followed by RT. Patient, tumor and treatment factors were analyzed for their significance on 5-year overall survival (OS).

Results

Younger age, female gender, absence of anemia pre-RT, early tumor stage, interruption of RT, and neoadjuvant chemotherapy were significantly associated with survival under multivariate analysis (all P < 0.05). The 5-year OS rates were 100%, 75.9% (95%CI 71.6-80.2%), 66.5% (95%CI 62.8-70.2%), and 49.3% (95%CI 45.0-53.6%) for stage I, II, III, and IV (P < 0.05); 68.9% (95%CI 66.2-71.5%) and 63.7% (95%CI 61.5-65.8%), for patients treated with or without neoadjuvant chemotherapy (P = 0.0051), and 51.7% (95%CI 45.0-58.4%) and 69.5% (95%CI 67.2-71.7%) for patients with or without treatment break (P < 0.0001), respectively.

Conclusion

Intensive neoadjuvant chemotherapy and absence of radiation break seem to be favorable factors associated with long-term survival in patients with NPC.     

Symptomatic hypothalamic-pituitary dysfunction in nasopharyngeal carcinoma patients following radiation therapy: a retrospective study

Endocrine assessment was performed in 32 relapse-free southern Chinese patients (21 males and 11 females, aged 27-50 years at the time of assessment) 5-17 years following radiation therapy (RT) alone for early nasopharyngeal carcinoma (NPC). Initial screening was done using questionnaires emphasizing on impaired sexual function and menstrual disturbance plus measurement of serum levels of thyroxine, free thyroxine index, thyrotropic hormone, prolactin, and additionally testosterone for males only. Those showing abnormalities were subjected to detailed pituitary function tests. Hypothalamic-pituitary dysfunction was found in 7 female patients and only 1 male patient. A delayed TSH response to thyrotropin releasing hormone suggesting a hypothalamic disorder was seen in 6 of the affected female patients, and hyperprolactinaemia in also 6. None of the patients had evidence of diabetes insipidus. Hypopituitarism became symptomatic 2-5 years after RT with a mean latent interval of 3.8 years. A practical protocol for regular endocrine assessment for NPC patients after RT has been proposed. Multiple linear regression analysis of the radiotherapeutic data from the 11 female patients indicates that the likelihood of late occurrence of symptomatic hypothalamic-pituitary dysfunction following RT is dependent on the TDF of the target dose to the nasopharyngeal region and the height of the upper margin of the opposed lateral facial fields above the diaphragma sellae (coefficient of multiple correlation = 0.9025). Except when the sphenoid sinus or the middle cranial fossa is involved, it is advisable to set the height of the upper margin of the lateral facial field at a level no higher than the diaphragma sellae. The hypothalamus and possibly the pituitary stalk as well may sustain permanent damage by doses of radiation within the conventional radiotherapeutic range for carcinomas.     

鼻咽癌放射性脑病147例MR表现特点分析

目的:探讨鼻咽癌放射性脑病(REP)147例的MR表现特征。方法:回顾性分析147例鼻咽癌REP患者MR常规加增强扫描的影像学特点。结果:147例鼻咽癌REP中颞叶损伤122例(83.0%),脑干损伤13例(8.8%),颞叶+脑干混合损伤12例(8.2%),共检出224侧颞叶及25例脑干REP病灶。颞叶型REP:形态多样,水肿(96.9%)及强化(94.7%)常见,30.8%有占位效应。脑干型REP:多数为单发(22/25),体积较小(≤2.0 cm),多均匀强化,水肿及占位效应较轻,动态观察可见病灶消失(7/25),明显缩小(4/25)。结论:鼻咽癌REP的MR表现具有特征性及动态变化的特点。颞叶仅1侧病灶消失;脑干REP经治后部分病灶可缩小或消失,并伴有脑干萎缩。     

Comparative therapeutic trial of radiation with or without chemotherapy in pancreatic carcinoma

Two hundred and twenty eight patients with carcinoma of the pancreas conrmed to the pancreas and peripancreatic area were randomly allocated to receive either radiation therapy alone to a dose of 6000 rad or radiation therapy delivered in conjunction with 5-Fuorouracil (FU). Fluorouracil was administered concomitant with the rust three days of 2000 rad increments of the radiation therapy and continued weekly indefinitely. The median survival of patients receiving radiation alone was 17.8 weeks compared to 35 weeks for patients receiving chemotherapy in conjunction with radiation (p<0.001). Within the group receiving concomitant chemotherapy, two dose levels of radiation were evaluated by random assignment: 4000 vs. 6000 rad. The superiority of 6000 rad plus 5-FU over 4000 rad plus 5-FU was established by median survival analysis, 39 weeks compared to 31 weeks and by time to progression, 31 weeks vs. 22 weeks (p < 0.09). The survival curves of the 4000 and the 6000 rad arm intercepted by approximately week 60 such that there was essentially no difference in the fraction of patients surviving beyond one year. Thus, the addition of chemotherapy to radiation for pancreatic cancer potentiates the therapeutic effect and promotes longer survival. The importance of radiation dose to the therapeutic benefit can be detected in median survival but is not sustained beyond one year.     

Analysis of 1379 patients with nasopharyngeal carcinoma treated by radiation

One thousand three hundred seventy-nine nasopharyngeal carcinoma (NPC) patients were treated from March 1958 to December 1978. Twenty-two percent had stage I or II and 78% Stage III or IV had lesions. Two hundred twenty-Kv radiographs were used before 1960; and telecobalt was used from 1961 to 1978. Factors influencing the 5-year survival rate favorably are youth of patient, being female, pathologic condition (poorly differentiated carcinoma, 45.1% versus adenocarcinoma, 13%), stage (Stage I, 86%, Stage II, 59.5%; Stage III, 45.8%; Stage IV, 29.2%), decade admitted for treatment in the past (31% in the 1950s, 48.6% in the 1970s), total dose delivered to the nasopharynx (40 to 49 Gy, 46%; 70 to 79 Gy, 54.1%; 90 Gy or more, 64%) and prophylactic radiation to the neck regions (with prophylactic irradiation, 53.8%, without prophylactic irradiation, 23%). This implies that prophylactic radiation of the neck is crucial even without positive clinical metastasis. For those who have a residual tumor in the primary site when 70 Gy has been delivered, the total dose may be boosted to more than 90 Gy with the cone-down technique or on basis of adding 20 Gy to the dose at which the primary lesion disappeared grossly. The common postirradiation complications are: radiation myelitis, trismus, and otitis media. Because disease recurred in some patients after the fifth year, NPC patients should be followed for at least 10 years.     

鼻咽癌放射治疗的失败模式

目的分析鼻咽癌患者治疗失败模式及其与治疗前相关因素的关系,探求更好的治疗方案。方法自1990年1月1日至1999年5月30日收治首程治疗的患者905例。分析放射治疗后失败的模式及其影响因素。组间差别用χ2检验。结果254例首次治疗后出现失败,失败率为28.1%。5、10年局部控制率分别为81.7%、76.7%。首次治疗失败中局部失败104例,占失败患者的40.9%;远地转移124例,占失败患者的48.8%。79.5%的局部失败和88.6%远地转移出现在治疗后3年内。骨转移是最常见的部位,其次是肝和肺。1992年福州T、N分期和临床分期对局部失败的影响无显著性差异(P>0.05),对远地转移的影响有极显著性差异(P<0.01)。结论远地转移已成为鼻咽癌放射治疗失败的主要原因之一,如何降低T4、N3期患者的远地转移是当前面临的课题。     

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.     

鼻咽癌急性放射性皮炎的研究进展

急性放射性皮炎是鼻咽癌放疗患者最常见的不良反应之一,主要表现为红斑、脱屑和溃疡等,严重影响患者的生活质量,目前无公认的标准防治方法。本文主要就鼻咽癌急性放射性皮炎的防治方法进行文献回顾,并提出问题及展望,为临床和科研提供一定参考。     

M-VCA方案治疗晚期鼻咽癌35例疗效分析

目的 探讨Ｍ－ＶＣＡ方案治疗晚期鼻咽癌的疗效及毒副反应,方法：对３５例晚期鼻咽癌患者（初治诱导化疗者１１例,复发或转移者２４例）采用ＭＴＸ＋ＶＣＲ＋ＤＤＰ＋ＡＤＭ联合化疗方案治疗。结果 评定其化疗２疗程后的客观疗效,总有效率为７５．５１％,无ＣＲ病例,其中初治肿瘤有效率达１００％,复发者为６６．６７％,远处转移总有效率为７０．０％,肺转移疗效最好（８８．８９％）,主要毒副反应是脱发,轻到中度的骨髓     

202例老年鼻咽癌放化疗疗效分析

目的 回顾分析初诊老年鼻咽癌的放、化疗结果、不良反应和预后因素。方法 2004—2007年共202例60岁以上的初诊老年鼻咽癌患者在本院接受根治性放疗或化疗,男165例、女37例,中位年龄65岁。AJCC第六版分期标准Ⅰ期1例、Ⅱ期25例、Ⅲ期120例、Ⅳ a或Ⅳ b期56例。所有患者放疗剂量≥66 Gy,72、3%(146例)局部进展期患者联合化疗。Cox 法多因素预后分析。结果 随访率为100%。5年局部控制率、区域淋巴结控制率、无远处转移生存率、无瘤生存率及总生存率分别为93%、94%、82%、74%及和67%。经多因素分析发现肿瘤T、N分期及年龄是影响总生存及无远处转移生存的预后因素(P=0、006、0、002、0、008及0、020、0、002、0、022)。严重的急性不良反应包括4级放射性皮炎1例(0、5%)、放射性黏膜炎2例(1、0%)、骨髓抑制5例(2、5%)。结论 老年鼻咽癌患者放化疗耐受性可,针对分期较晚及一般状态较好的60~74岁患者应采取积极的综合治疗。