Induction chemotherapy and radiotherapy in loco-regionally advanced epidermoid carcinoma of the anal canal

Purpose: To evaluate the efficacy of induction chemotherapy in combination with radiotherapy for treatment of loco-regionally advanced epidermoid anal carcinoma.Methods and Materials: Thirty-one patients diagnosed during the period 1989–1994 with loco-regionally advanced cancer of the anal canal (ΦT_max ≥ 4 cm or T4 or N+) were treated with induction chemotherapy consisting of one to three courses of carboplatin (300–375 mg/m² i.v.) and 5-fluorouracil [5,000 mg/(m² × 120 h) i.v.] followed by external beam irradiation ± surgery.Results: The toxicity of the chemotherapy was low. Twenty-nine patients were tumor free after the primary therapy. Kaplan-Meier analyses were made for overall survival, tumor-specific survival, freedom from recurrence, preservation of sphincter, and event-free survival. For these end points the 5-year data were 67, 85, 80, 69, and 51%, respectively.Conclusion: The results are promising but a well-designed randomized trial is needed to further elucidate the role of induction chemotherapy in the treatment of loco-regionally advanced anal carcinoma.     

Improvement of local control of T3 and T4 nasopharyngeal carcinoma by hyperfractionated radiotherapy and concomitant chemotherapy

PURPOSE: When the primary tumor of nasopharyngeal carcinoma (NPC) is treated at the base of skull and intracranium with conventional radiotherapy, the result is generally poor. In this report, we investigated whether hyperfractionated radiotherapy (HFRT) and concomitant chemotherapy (CCT) could achieve better local control and survival in NPC patients with T3 and T4 lesions. PATIENTS AND METHODS: Forty-eight patients (11 T3 and 37 T4 NPC) were treated with HFRT and CCT. HFRT was administered at 1.2 Gy per fraction, two fractions per day, Monday-Friday for 62 fractions for a total dose of 74.4 Gy. Concomitant chemotherapy consisting of cis-diamino-dichloroplatinum (CDDP) alone or CDDP and 5-fluorouracil was delivered simultaneously with radiotherapy during Weeks 1 and 6. Adjuvant chemotherapy consisted of CDDP and 5-fluorouracil for 2 to 3 cycles and was given monthly beginning 1 month after completion of radiation. RESULTS: With a median follow-up of 57 months (range: 28-94 months), the 3-year locoregional control rate was 93%, the disease-free survival rate was 71%, and the overall survival rate was 72%. For T4 patients, the 3-year locoregional control rate was 91%, disease-free survival was 62%, and overall survival was 63%. The major acute toxicity was Grade 3 mucositis in 73% and Grade 2 weight loss in 31% of patients. Fifty percent of patients were tube fed. Most patients tolerated the combined modality treatments relatively well; 88% of patients completed their radiation treatment within 8 weeks. CONCLUSION: HFRT and CCT for T3 and T4 NPC were associated with excellent local control and improved survival. The treatment-related toxicity was acceptable and reversible. We would recommend using HFRT with CCT for advanced T-stage NPC if the three-dimensional conformal radiation planning shows a significant portion of the brainstem to be inside the treatment field.     

Preoperative chemotherapy and radiotherapy in the management of epidermoid carcinoma of the anal canal

Sixteen patients affected by epidermoid carcinoma of the anal canal were treated preoperatively by means of an i.v. infusion of mitomycin C (15 mg/m2) on day 1 and 5-fluorouracil (750 mg/m2) days 1 to 5, followed by radiotherapy (3000 R in 3 weeks). Four to 6 weeks after the end of radiotherapy the response to the preoperative treatment was evaluated by means of biopsy. A reduction of the neoplastic mass was observed in 13 of the 16 patients. An evident correlation exists between the stage of the tumor and 1) the response to preoperative treatment, 2) local recurrence, and 3) long-term survival. In fact: 3/4 T1 patients reached a complete response (CR), and 1/4 T1, 5/5 T2 and 4/7 T3 patients achieved a partial response (PR); only 3/7 T3 patients never responded to preoperative treatment. After the initial surgery, only T2 (3/5) and T3 (4/7) patients underwent a second operation for a recurrence. Overall survival at 42 months was 62.5% (T1, 100%; T2, 80%; T3, 28.5%).     

Management of locally advanced anal canal carcinoma with intensity-modulated radiotherapy and concurrent chemotherapy

The best curative option for locally advanced (stages II–III) squamous-cell carcinomas of the anal canal (SCCAC) is concurrent chemo-radiotherapy delivering 36–45 Gy to the prophylactic planning target volume with an additional boost of 14–20 Gy to the gross tumor volume with or without a gap-period between these two sequences. Although 3-dimensional conformal radiotherapy led to suboptimal tumor coverage because of field junctions, this modality remains a standard of care. Recently, intensity-modulated radiotherapy (IMRT) techniques improved tumor coverage while decreasing doses delivered to organs at risk. Sparing healthy tissues results in fewer severe acute toxicities. Consequently, IMRT could potentially avoid a gap-period that may increase the risk of local failure. Furthermore, these modalities reduce severe late toxicities of the gastrointestinal tract as well as better functional conservation of anorectal sphincter. This report aims to critically review contemporary trends in the management of locally advanced SCCAC using IMRT and concurrent chemotherapy.     

中晚期鼻咽癌放化疗综合治疗的临床研究

目的：探讨患者对联合应用诱导化疗和放疗同期口服卡莫氟治疗中晚期鼻咽癌疗效和毒副反应。方法：将66例局部中晚期鼻咽癌患者,随机分为诱导化疗随后放疗组33例（对照组）和诱导化疗随后放疗同期卡莫氟治疗组33例（治疗组）。两组放疗方法相同,鼻咽部剂量70Gy/（35次.7周）,颈部淋巴结根治量为（60-70Gy）/[（30-35次）.（6-7）周]。治疗组在放疗期间同时口服卡莫氟,200mg/次,3次/d。结果：诱导化疗效率高,平均有效率高达87.0%,其中平均CR8.7%,PR78.4%。治疗组白细胞下降Ⅲ-Ⅳ级（18.2%）高于对照组（13.1%）,χ^2=.6,P=0.010。治疗组口腔黏膜炎Ⅲ-Ⅳ级发生率（63.6%）高于对照组（30.3%）,χ^2=.360,P=0.007。治疗组恶心发生率（87.9%）高于对照组（39.4%）,χ^2=6.762,P=0.0001,经对症处理大部分患者能按计划完成治疗。结论：初步研究结果提示放疗同期口服卡莫氟治疗局部中晚期鼻咽癌有潜在性的增益,其远期疗效有待于进一步观察。     

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。     

局部晚期食管癌体外放射联合腔内放疗同期化疗的随机研究

目的　分析体外放射联合腔内放疗加同期化疗治疗局部晚期食管癌的疗效。方法　 1995年 12月至 1997年 12月 ,88例局部晚期食管癌随机分为两组 :44例用60 Co γ射线或 6MV X射线外放射DT=5 5 2 0～ 6 0 0 0CG/4 6～ 5 0次 /2 3～ 2 5天 ;平均 3天后用192 Ir源HDR腔内放疗DT=5 0 0～ 10 0 0CGY/2～ 4次。DF方案化疗于放疗前一周开始 ,共化疗两周期 (综合组 ) ;对照组 44例单用放疗。结果　综合组 1、2、3年生存率分别为 79.2 %、33 .4%、15 .6 % ,对照组 77.3 %、36 .4%、12 .5 %。两组局部未控、复发和转移率相似 (P >0 .0 5 ) ,非癌死亡率综合组明显高于对照组 (P <0 .0 5 )。结论　体外放射联合腔内放疗加同期化疗不能进一步提高局部晚期食管癌 3年生存率。     

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.     

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.     

放疗同期卡莫氟化疗治疗局部中晚期鼻咽癌疗效评价

探讨联合应用诱导化疗和放疗同期口服卡莫氟治疗局部中晚期鼻咽癌的疗效及不良反应。将收治的70例局部中晚期鼻咽癌患者随机分为诱导化疗后放疗组（对照组）和诱导化疗后放疗同期卡莫氟治疗组（治疗组）两组,两组均为35例,两组患者放疗前均接受2个疗程诱导化疗,治疗组在放疗期间同时口服卡莫氟。鼻咽肿瘤及颈部淋巴结完全消退率治疗组明显高于对照组,P〈0.05。3和5年内局部复发率治疗组明显低于对照组,分别是11.4%、22.9%和34.3%、48.6%,差异有统计学意义,P〈0.05。3年生存率治疗组和对照组分别是77.1%和51.4%,P〈0.05。初步研究结果提示,放疗同期口服卡莫氟治疗局部中晚期鼻咽癌,降低了鼻咽和颈部肿瘤完全消退的照射剂量,提高了鼻咽和颈部肿瘤的完全缓解率,抑制或延缓肿瘤复发和远处转移,尽管患者的不良反应加重,但可以耐受。其远期疗效有待于进一步证实。     

食管癌术后同步放化疗的临床研究

目的：探讨术后辅助放化疗对食管癌患者生存期的影响,并分析其预后因素。方法：２００２年４月～２００４年６月,选择经根治术后病理学检查确诊的食管鳞癌患者９０例,分成３组,每组３０例,治疗组采用放化疗同步治疗,另设单纯放疗组和单纯化疗组作为对照组进行研究。单纯放疗组于术后３～６周内开始用１５ＭＶ-Ｘ线照射,ＤＴ５０Ｇｙ／２５ｆ,３０天完成。单纯化疗组于术后３～４周内开始用ＦＰ方案化疗,治疗组放化疗的剂量同对照组。结果：全部患者的１年、３年、５年生存率及中位生存期分别为９０.０％、４３.３％和３７.２５％及３２个月,３组比较生存时间无明显差异。单因素分析提示临床分期、有无淋巴结转移及病变局部有无溃疡是影响生存的主要因素,多因素分析提示有无淋巴结转移及病变局部有无溃疡是其预后的独立因素。结论：食管癌术后应用单纯放疗、化疗或同步放化疗作为辅助治疗手段疗效上似无明显差异,有无淋巴结转移和病变局部有无溃疡为其独立预后因素。     

Prospective randomised study of split-course radiotherapy versus cisplatin plus split-course radiotherapy in inoperable squamous cell carcinoma of the oesophagus

Between 1983 and 1989, 211 patients with inoperable squamous cell carcinoma of the oesophagus were randomised in a study comparing split-course irradiation (two courses of 20 Gy in five fractions of 4 Gy, separated by a rest of 2 weeks) (arm A) and the same split-course irradiation in combination with cisplatin (CDDP) (3-4 days before each of the two courses of radiotherapy, repeated every 3-4 weeks, for a total of six cycles) (arm B). The Cox's regression model with retrospective stratification was used to compare the two arms to correct for the imbalance at randomisation of the T classification. The median overall survival was 7.9 (95% confidence interval (CI) 7.3-9.4) months in arm A and 9.6 (95% CI 8-13.5) months in arm B. The difference in overall survival was only borderline significant (P=0.048) with a reduction of the instantaneous rate of death of 24%. The 1 and 2 year overall survival rate were respectively 29% (95% CI 21-37%) and 15% (95% CI 8-22%) in arm A and 45% (95% CI 36-54%) and 20% (95% CI 13-27%) in arm B; thereafter, the survival curves became similar. The median progression free survival (PFS) was 5.0 (95% CI 4.6-5.7) versus 6.9 (95% CI 5.3-8.7) months (P=0.028) and the median time to local progression was 6.2 (95% CI 5.1-7.6) months versus 10.9 (95% CI 8.1-15.5) months (P=0.018), respectively, in arms A and B. Haematological toxicities were slightly more commonly observed in the combined group (1% versus 6%). This study shows that split-course irradiation in combination with CDDP is very well tolerated and should be preferred to radiotherapy alone.     

Effect of surgical modality and hypofractionated split-course radiotherapy on local control and survival from sinonasal mucosal melanoma

Aims

To assess the efficacy of surgery and high-dose split-course radiotherapy in sinonasal head and neck mucosal melanoma (SHNMM).

Material and methods

Between 1991 and 2006, 23 patients (median age 73 years, male:female ratio 0.4) with non-metastatic SHNMM underwent surgery and postoperative radiotherapy, two had exclusive radiotherapy. Radiotherapy consisted of three series of 18 Gy (3 × 6 Gy every other day for 1 week) with 3 week planned treatment breaks. Chi-squared tests, Kaplan–Meyer method and Log-rank test were used to assess prognostic factors for survival and local control.

Results

There were 20 nasal cavity tumours; 12 of these involved more than one sinonasal site. One patient (4%) had lymphadenopathies at diagnosis. Six SHNMMs (24%) were amelanotic. The median follow-up was 39 months. Fourteen patients had en bloc surgery, 16 underwent radiation (14 postoperative, two exclusive). Eleven patients had local relapse, three had regional relapse and three had bone or liver metastases. Five year local control was 49 ± 12%. Five year overall and SHNMM-specific survival was 38 ± 12% and 62 ± 12%, respectively. Five patients were alive without disease after 5 years and three after 10 years. En bloc excision (tumour removed in one piece) was prognostic for survival.

Conclusions

En bloc surgery was a prognostic factor on outcomes for local control and survival in this series. Data from the literature have shown that postoperative radiation therapy improves local control. Most series were carried out with conventional fractionation. The effect of planned breaks (split-course radiotherapy) may be deleterious, as suggested in this series. Therefore, split-course radiotherapy cannot be recommended for SHNMM.     

Stereotactic radiosurgical boost following radiotherapy in primary nasopharyngeal carcinoma: impact on local control

PURPOSE: Treatment of patients with nasopharyngeal carcinoma using external beam radiation therapy (EBRT) alone results in significant local recurrence. Although intracavitary brachytherapy can be used as a component of management, it may be inadequate if there is extension of disease to the skull base. To improve local control, stereotactic radiosurgery was used to boost the primary tumor site following fractionated radiotherapy in patients with nasopharyngeal carcinoma. METHODS AND MATERIALS: Twenty-three consecutive patients were treated with radiosurgery following radiotherapy for nasopharyngeal carcinoma from 10/92 to 5/98. All patients had biopsy confirmation of disease prior to radiation therapy; Stage III disease (1 patient), Stage IV disease (22 patients). Fifteen patients received cisplatinum-based chemotherapy in addition to radiotherapy. Radiosurgery was delivered using a frame-based LINAC as a boost (range 7 to 15 Gy, median 12 Gy) following fractionated radiation therapy (range 64.8 to 70 Gy, median 66 Gy). RESULTS: All 23 patients (100%) receiving radiosurgery as a boost following fractionated radiation therapy are locally controlled at a mean follow-up of 21 months (range 2 to 64 months). There have been no complications of treatment caused by radiosurgery. However, eight patients (35%) have subsequently developed regional or distant metastases. CONCLUSIONS: Stereotactic radiosurgical boost following fractionated EBRT provides excellent local control in advanced stage nasopharynx cancer and should be considered for all patients with this disease. The treatment is safe and effective and may be combined with cisplatinum-based chemotherapy.     

Conformal therapy improves the therapeutic index of patients with anal canal cancer treated with combined chemotherapy and external beam radiotherapy

PURPOSE: To evaluate the clinical outcomes of three-dimensional conformal radiotherapy (3D-CRT) in patients with anal canal cancer, in terms of local control (LC), freedom from relapse (FFR), and overall survival (OS) rates, and to estimate long-term toxicity data. METHODS AND MATERIALS: Sixty historical patients, treated with conventional radiation techniques (C-RT), were used as controls, and 62 consecutive patients were treated with 3D-CRT. Patients treated with 3D-CRT received 54 Gy in 30 fractions delivered continuously, compared with 45-58.9 Gy (median dose, 54 Gy) in a split course in patients treated with C-RT. Chemotherapy consisted of 5-fluorouracil with either mitomycin-C or cis-platinum given concurrently with radiation. Survival curves were performed using the Kaplan-Meier model, and the Cox proportional hazards model was used for multivariate analysis of risk factors. RESULTS: No differences in stage and age distribution were observed between the two groups. Patients treated with 3D-CRT and C-RT had an actuarial 5-year LC rate of 85.1% and 61.1%, respectively (p = 0.0056); the FFR rate was 70.2% and 46.1% (p = 0.0166), and the OS rate was 80.7% and 53.9% (p = 0.0171). In multivariate analysis, factors of significance for LC were nodal (N) status (p < 0.001); for OS, 3D-CRT (p = 0.038), N status (p = 0.011), and T status (p = 0.012); and for FFR, 3D-CRT (p = 0.024) and N status (p < 0.001). CONCLUSION: The use of 3D-CRT allows patients with anal canal cancer to complete radiation and chemotherapy without interruption for toxicity, with significant improvements in LC, FFR, and OS.     

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.     

局部晚期鼻咽癌放疗与化疗综合治疗的生存分析

目的探讨局部晚期鼻咽癌放化综合治疗疗效和毒副反应。方法回顾性分析77例经病理证实鼻咽癌患者。年龄17～74岁,男:女=3.8:1。1992年福州分期T1、12、T3、T4期分别为11、33、22、11例,N0、N1、N2、N3期分别为7、15、44、11例。临床分期Ⅲ期56例,ⅣA期21例。所有患者放疗前接受诱导化疗1～3个疗程:顺铂20 mg/m~2,氟尿嘧啶500 mg/m~2,其中62例应用甲酰四氢叶酸钙100 mg/m~2,均为第1～3天,2周后重复。化疗结束后2周内放疗:鼻咽原发病灶均采用~(60)Co照射1.8～2.0 Gy/次,总剂量64～78 Gy;57例采用面颈联合野 耳前野 鼻前野治疗,20例采用耳前野 鼻前野照射,9例采用耳后野加量6～8 Gy分3～4次,13例给予颅底小野补量4～8 Gy分2～4次;颈部放射源用~(60)Co、180 kV X线和9 MeV电子束,N0期患者仅照射上颈部,有颈部转移者照射全颈,预防剂量50～55 Gy,根治剂量60～68 Gy;1例外照射结束后因鼻咽腔内肿瘤残留,给予后装治疗2次,间隔1周,10 Gy/次)。放疗结束后3周给予辅助化疗:顺铂20 mg/m~2,氟尿嘧啶500 mg/m~2,甲酰四氢叶酸钙100 mg/m~2,均为第1～3天,3周后重复,共2～4疗程。结果中位随访60个月,5年总生存率、无瘤生存率、无复发生存率、无远处转移生存率分别为68%、58%、81、75%。≥4个化疗周期与≤3个化疗周期生存曲线比较差异无统计学意义(X~2=0.05,P=0.831)。主要急性反应有血液学毒性:1级11例,2级7例,3级2例;黏膜炎:2级33例,3级20例,4级1例;消化道反应:1级21例,2级11例,3级1例;皮肤反应:2级30例,3级4例。晚期损伤:1例发生放射性脑损伤,无其他颅神经损伤发生;张口困难轻度4例,中度1例;听力减退轻度31例,中度7例,严重1例。化疗周期≥4个与≤3个的听力损伤差异有统计学意义(z=2.06,P=0.039)。绝大多数放疗结束后都有程度不等的口干,随访中都明显好转,至末次随访时轻度口干13例,中度3例。结论以顺铂和氟尿嘧啶为基础的诱导化疗 放疗 辅助化疗局部晚期鼻咽癌的疗效较单纯放疗无明显提高,但可能加重患者听力的晚期损伤。     

Examining prognostic factors and patterns of failure in nasopharyngeal carcinoma following concomitant radiotherapy and chemotherapy: impact on future clinical trials

PURPOSE: Concomitant chemotherapy and radiotherapy (CCRT), followed by adjuvant chemotherapy, has improved the outcome of nasopharyngeal carcinoma (NPC). However, the prognosis and patterns of failure after this combined-modality treatment are not yet clear. In this report, the prognostic factors and failure patterns we observed with CCRT may shed new light in the design of future trials. METHODS AND PATIENTS: One hundred forty-nine (149) patients with newly diagnosed and histologically proven NPC were prospectively treated with CCRT followed by adjuvant chemotherapy between April 1990 and December 1997. One hundred and thirty-three (89.3%) patients had MRI of head and neck for primary evaluation before treatment. Radiotherapy was delivered either at 2 Gy per fraction per day up to 70 Gy or 1.2 Gy per fraction, 2 fractions per day, up to 74.4 Gy. Chemotherapy consisted of cisplatin and 5-fluorouracil. According to the AJCC 1997 staging system, 32 patients were in Stage II, 53 in Stage III, and 64 in Stage IV (M0). RESULTS: Univariate analysis revealed that WHO (World Health Organization) Type II histology, T4 classification, and parapharyngeal extension were poor prognostic factors for locoregional control. Multivariate analysis revealed that T4 disease was the most important adverse factor that affects locoregional control, the risk ratio being 5.965 (p = 0.02). Univariate analysis for distant metastasis revealed that T4 and N3 classifications, serum LDH level > 410 U/L (normal range, 180-460), parapharyngeal extension, and infiltration of the clivus were significantly associated with poor prognosis. Multivariate analysis, however, revealed that T4 classification and N3 category were the only two factors that predicted distant metastasis; the risk ratios were 3.994 (p = 0.02) and 3.390 (p = 0.01), respectively. Therefore, based on the risk factor analysis, we were able to identify low-, intermediate-, and high-risk patients. Low-risk patients were those without the risk factors mentioned above. They consisted of Stage II patients with T2aN0, T1N1, and T2aN1 categories and of Stage III patients with T1N2 and T2aN2 categories. Their risk of recurrence is low (4%). Intermediate-risk patients were those with at least one univariate risk factor. They are Stage II patients with T2bN0 and T2bN1 categories and Stage III patients with T2bN2 and T3N0-2 categories. The risk of recurrence is modest (18%). High-risk patients have risk factors by multivariate analysis. They are stage T4 or N3 patients. Their risk of recurrence is high (36%). CONCLUSION: Low-risk patients have an excellent outcome. Future trials should focus on reducing treatment-associated toxicities and complications and reevaluate the benefit of sequential adjuvant chemotherapy. The recurrence in treatment of intermediate-risk patients is modest; CCRT and adjuvant chemotherapy may be the best standard for them. Patients with T4 and N3 disease have poorer prognosis. Hyperfractionated radiotherapy may be considered for the T4 patients. Future study in these high-risk patients should also address the problem of distant spread of the disease.