Hyperfractionated radiotherapy and concomitant cisplatin for locally advanced laryngeal and hypopharyngeal carcinomas: final results of a single institutional program

SUMMARY: ABSTRACT The purpose of this study was to achieve locoregional control of locally advanced laryngeal carcinoma, survival, and organ preservation using split hyperfractionated accelerated radiation therapy and cisplatin concomitantly. This study was a phase II trial of chemoradiotherapy with split hyperfractionated accelerated radiation therapy, 1.6 Gy per fraction given twice per day to a total dose of 64 to 67.2 Gy for a total of 6 weeks with a 2-week gap, and cisplatin 20 mg/m2, days 1 to 5, in continuous perfusion, concomitantly. Seventy-three patients were treated (stage IV, 64%). At a median follow-up of 55 months for living patients, median survival was 44 months, and 5-year overall survival and disease-free survival were 42% and 39%, respectively. Toxicities included mucositis (grade III, 40%; grade IV, 28%), epithelitis (grade III, 28%). Of the 73 patients, 32 (44%) have continued with their larynx free of disease. Split hyperfractionated accelerated radiation therapy and concomitant cisplatin has been demonstrated to be an active treatment for locally advanced laryngeal carcinomas, but more active combinations of chemotherapy and radiotherapy, without increase of toxicity, are necessary to increase the rate of locoregional control, organ preservation, and survival.     

ACR appropriateness criteria® adjuvant therapy for resected squamous cell carcinoma of the head and neck

Locoregional recurrence following surgical resection alone for stage III/IV head and neck cancer is common. Adjuvant radiotherapy has been shown to improve post-operative locoregional control when compared to pre-operative radiotherapy for head and neck cancers. Following surgical resection, adverse pathological features determine the need for adjuvant therapy. High-risk pathologic features include extranodal tumor spread and involved surgical margins. Other adverse pathologic features include T 3-4 tumors, perineural invasion, lymphovascular space invasion, low neck adenopathy, and multiple tumor involved cervical lymph nodes. The standard adjuvant therapies are post-operative radiation therapy or post-operative chemoradiotherapy. Post-operative chemoradiotherapy yields superior locoregional control, progression-free survival, and in some studies, overall survival compared to post-operative radiotherapy for high-risk patients in multiple randomized studies. Pooled analyses of randomized data demonstrate that post-operative concurrent chemoradiotherapy is associated with overall survival benefits for patients with involved surgical margins as well as those with extranodal tumor spread. Post-operative radiotherapy concurrent with cisplatin at 100 mg/m(2) every 21 days is the current standard chemoradiotherapy platform adjuvant head and neck cancer treatment. Post-operative radiotherapy and post-operative chemoradiotherapy radiation treatment volumes are not standardized and should be designed based on the risk of recurrence and clinically occult involvement of head and neck subsites and nodal regions. Evidence supports a post-operative radiotherapy and chemoradiotherapy radiation dose of at least 63 Gy for high-risk patients and at least 57 Gy for low risk patients.     

Concomitant cisplatin significantly improves locoregional control in advanced head and neck cancers treated with hyperfractionated radiotherapy.

PURPOSE: To determine whether the application of two courses of cisplatin simultaneously with hyperfractionated radiotherapy improves the outcome in locally advanced and/or node-positive nonmetastatic carcinomas of the head and neck, compared with hyperfractionated radiotherapy alone. PATIENTS AND METHODS: From July 1994 to July 2000, 224 patients with squamous cell carcinomas of the head and neck (excluding nasopharynx and paranasal sinus) were randomly assigned to hyperfractionated radiotherapy (median dose, 74.4 Gy; 1.2 Gy twice daily) or the same radiotherapy combined with two cycles of concomitant cisplatin (20 mg/m2 on 5 days of weeks 1 and 5). The primary end point was time to any treatment failure; secondary end points were locoregional failure, metastatic relapse, overall survival, and late toxicity. RESULTS: There was no difference in radiotherapy between both treatment arms (74.4 Gy in 44 days). The full cisplatin dose was applied in 93% and 71% of patients during the first and second treatment cycles, respectively. Acute toxicity was similar in both arms. Median time to any treatment failure was not significantly different between treatment arms (19 months for combined treatment and 16 months for radiotherapy only, respectively) and the failure-free rate at 2.5 years was 45% and 33%, respectively. Locoregional control and distant disease-free survival were significantly improved with cisplatin (log-rank test, P = .039 and .011, respectively). The difference in overall survival did not reach significance (log-rank test, P = .147). Late toxicity was comparable in both treatment groups. CONCLUSION: The therapeutic index of hyperfractionated radiotherapy is improved by concomitant cisplatin.     

Favorable long-term survival following induction chemotherapy with cisplatin, fluorouracil, and leucovorin and concomitant chemoradiotherapy for locally advanced head and neck cancer.

BACKGROUND: The majority of patients with head and neck cancer die of locoregional recurrence of disease following surgery and/or radiotherapy. PURPOSE: Our purpose was to administer induction chemotherapy, perform surgery, and administer concomitant chemoradiotherapy in rapid sequence and to evaluate their impact on locoregional and distant tumor control. METHODS: Sixty-four patients with previously untreated, locoregionally advanced head and neck cancer received two cycles of cisplatin, bleomycin, and methotrexate (PBM) (33 patients) or cisplatin, fluorouracil (5-FU), and leucovorin (PFL) (31 patients). PFL was given to patients who were unable to receive bleomycin. Local therapy consisted of surgery and/or concomitant chemoradiotherapy with 5-FU, hydroxyurea, leucovorin, and radiotherapy (FHX-L), all administered every other week. RESULTS: Complete and overall induction response rates were 21% and 79%, respectively, for PBM and 29% and 81%, respectively, for PFL. At completion of local therapy, 81% of the patients were disease-free. With a median follow-up of 35 months, the median survival and time to progression are 22 and 17 months, respectively, for PBM and have not been reached for PFL. Locoregional recurrence of disease is 30% for PBM and 26% for PFL. Distant disease progression is 24% for PBM and only 3% for PFL. CONCLUSIONS: The sequencing of induction chemotherapy and concomitant chemoradiotherapy is feasible and results in a high local control rate and in an encouraging survival rate with PFL. The high distant failure (i.e., outside the head and neck area) rate of PBM suggests insufficient systemic activity for that regimen. IMPLICATIONS: Concomitant FHX-L chemoradiotherapy may improve regional control rates of advanced head and neck cancer. Effective systemic therapy may be needed to control systemic micrometastases. PFL, but not PBM, appears to be suitable to accomplish that goal.     

A phase III randomized trial comparing adjuvant concomitant chemoradiotherapy versus standard adjuvant chemotherapy followed by radiotherapy in operable node-positive breast cancer: final results

PURPOSE: To compare concomitant and sequential adjuvant chemoradiotherapy regimens in node-positive, operable breast cancer patients. METHODS AND MATERIALS: This was a randomized, French, multicenter, phase III trial enrolling 638 eligible women with prior breast surgery and positive axillary dissection. Patients in Arm A received 500 mg/m2 5-fluorouracil, 12 mg/m2 mitoxantrone, and 500 mg/m2 cyclophosphamide, with concomitant radiotherapy (50 Gy +/- 10-20-Gy boost). Patients in Arm B received 500 mg/m2 5-fluorouracil, 60 mg/m2 epirubicin, and 500 mg/m2 cyclophosphamide, with subsequent radiotherapy. Chemotherapy was administered on Day 1 every 21 days for 4 cycles. RESULTS: Median treatment durations were 64 and 126 days (Arms A and B, respectively), with no significant difference in overall or disease-free survival. Five-year locoregional relapse-free survival favored patients with conservative surgery (two thirds of the population), with less local and/or regional recurrence in Arm A than in Arm B (3% vs. 9%; p = 0.01). Multivariate analysis in this subgroup showed a 2.8-fold increased risk of locoregional recurrence with sequential chemoradiotherapy, independent of other prognostic factors (p = 0.027). Febrile neutropenia and Grade 3-4 leukopenia were significantly more frequent in Arm A. Subclinical left ventricular ejection fraction events at 1 year were more frequent with concomitant radiotherapy (p = 0.02). CONCLUSIONS: Concomitant radiotherapy with adjuvant fluorouracil, mitoxantrone, and cyclophosphamide has significantly better locoregional control in node-positive breast cancer after conservative surgery and 50% shorter treatment, albeit with slightly more acute toxicity. With mitoxantrone no longer available for adjuvant breast cancer treatment, alternative concomitant chemoradiotherapy studies are needed.     

Concomitant adjuvant chemoradiotherapy with weekly low-dose cisplatin for high-risk squamous cell carcinoma of the head and neck: a phase II prospective trial

Aims

Several randomised trials have tested adjuvant regimens using concomitant high-dose cisplatin and radiotherapy to improve outcome in high-risk locally advanced squamous cell head and neck cancer (HNSCC), showing a substantial increase in locoregional control and disease-free survival, despite a higher and eventually detrimental toxicity profile. The aim of the present phase II single-stage prospective study was to investigate whether a weekly cisplatin-based chemoradiotherapy regimen might be able to improve patients’ compliance compared with standard-dose cisplatin with similar outcome results.

Materials and methods

Between January 2004 and November 2008, 54 patients with high-risk locally advanced HNSCC were enrolled on to this phase II trial. Patient characteristics were: median age 59.7 years, Eastern Cooperative Oncology Group performance status 1 in 72% of patients and stage IV disease in 82%, extracapsular nodal spread in 67% and positive/close surgical margins in 37%. Patients received cisplatin (30 mg/m²) once a week for 7-8 weeks concurrent with external beam radiotherapy delivered with a median dose of 66.6 Gy (1.8 Gy each day; five fractions/week) on the primary site and 50 Gy (2 Gy each day) for the lower neck.

Results

Major acute toxicity of the combined treatment, defined as grade 3-4 mucositis, was observed in 35.2% of patients. No fatal complications occurred, with 81.5% of patients completing the planned regimen. Late reactions were mild (total 16% with a grade 3 dysphagia rate of 12%). The locoregional control rate was 82%; 5 year overall and disease-free survival were 63 and 62%, respectively.

Conclusions

Concomitant adjuvant chemoradiotherapy with weekly cisplatin seems to be a feasible and well-tolerated therapeutic approach in ‘unfit’ patients. Clinical results seem to be at least comparable with those previously reported. However, to draw any definitive conclusion, large confirmatory phase III randomised trials are demanded.     

Ⅲ、Ⅳa期鼻咽癌患者放疗同期化疗加辅助化疗的疗效

背景与目的:较多研究认为放疗前诱导化疗未能提高中晚期鼻咽癌的生存率,对放疗后的辅助化疗能否提高中晚期鼻咽癌的生存率有争议.有作者报道同期放化疗能提高中晚期鼻咽癌患者的疗效.本研究着重探讨放疗同期化疗加辅助化疗治疗Ⅲ、Ⅳa期鼻咽癌的疗效.方法:将80例Ⅲ、Ⅳa期鼻咽癌患者随机分为放疗同期化疗加辅助化疗组(研究组)及单纯放疗组(对照组),每组各40例.研究组于放疗第一周开始使用同期化疗,顺铂25 mg/m2静脉滴注,每周一次,连用6周.辅助化疗于放疗结束后一个月开始,顺铂25 mg/m2,静脉滴注,第1～3天;氟尿嘧啶1000 mg/m2,静脉滴注,第1～3天.每月一次,连用3次.放疗使用常规分割放疗,鼻咽部总剂量70Gy.对照组放疗方法与放疗加化疗组相同,不使用化疗.生存率采用Kaplan-Meier法,生存期的差别比较用log-rank检验,计数资料组间差异用卡方检验.结果:治疗后,研究组和对照组分别有34例和32例鼻咽肿瘤达到CR者(x2=0.35,P＞0.05);颈部淋巴结达到CR者分别为37例和30例(x2=4.50,P＜0.05).研究组1、3、5年生存率分别为92.7%、78.6%、64.2%,对照组1、3、5年生存率分别为81.2%、52.7%、42.3%,两组比较差异有显著性(P＜0.01).研究组1、3、5年无瘤生存率分别为91.2%、76.7%、63.5%,对照组1、3、5年无瘤生存率分别为78.2%、51.9%、40.3%,两组比较差异有显著性(P＜0.01).5年累积远处转移发生率研究组为15.0%,对照组为35.0%,两组比较差异有显著性(x2=4.27,P＜0.05).Ⅲ度口腔粘膜炎发生率研究组为75.0%,对照组为25.0%(x2=20.00,P＜0.01).结论:同期加辅助化疗联合放疗较单纯放疗提高了Ⅲ、Ⅳa期鼻咽癌的颈部淋巴结完全缓解率以及1、3、5年生存率和无瘤生存率,显著降低了远处转移的发生率,但增加了Ⅲ度口腔粘膜炎的发生率.     

Sequential induction chemotherapy and concomitant chemoradiotherapy in the management of locoregionally advanced laryngeal cancer

Purpose:To determine overall survival, progression-free survival,rate of voice preservation, and patterns of failure in locoregionally advancedlaryngeal cancer treated with induction chemotherapy with or without surgeryfollowed by concomitant chemoradiation. Background:Locoregionally advanced laryngeal cancer has beenconventionally treated with either surgery and adjuvant radiotherapy orradiotherapy alone, and clinical and functional outcomes have been poor.Chemoradiotherapy has been demonstrated to improve functional outcome anddisease control over conventional treatment in recent randomized head and necktrials. Patients and methods:Advanced head and neck cancer patients wereenrolled onto two consecutive phase II studies. Induction treatment consistedof three cycles of cisplatin, 5-fluorouracil (5-FU), leucovorin, andinterferon-2b (PFL-IFN) followed by surgery for residual disease.Surgical intent was to spare the larynx when possible. All patients thenproceeded to concomitant chemoradiation consisting of seven or eight cyclesof 5-FU, hydroxyurea, and a planned total radiotherapy dose of 7000 cGy(FHX). Results:A subset of thirty-two laryngeal cancer patients withpredominantly stage IV disease comprises the study group for this report.Clinical CR was observed in 59% of patients following inductiontherapy. The median follow-up was 63.0 months for surviving patients and 44.5months for all patients. At five years, overall survival is 47%,progression-free survival is 78%, and locoregional control is78%. No distant failures were observed. Voice preservation with diseasecontrol was 75% at five years. Only two total laryngectomies wereperformed during the course of treatment and follow-up. Treatment-relatedtoxicity accounted for two deaths. Conclusions:The addition of concomitant chemoradiotherapy toinduction chemotherapy for locoregionally advanced laryngeal cancer appearsto increase locoregional control and survival rates. PFL-IFN–FHXresulted in high rates of disease cure and voice preservation in a group ofpatients that has traditionally fared poorly in both clinical and functionaloutcome.     

Cisplatin, fluorouracil, and leucovorin induction chemotherapy followed by concurrent cisplatin chemoradiotherapy for organ preservation and cure in patients with advanced head and neck cancer: long-term follow-up.

PURPOSE: The poor functional outcome in patients with advanced head and neck squamous cell carcinoma (HNSCC) with surgery and radiation has led to alternative approaches to advanced disease. We conducted a phase II study of induction chemotherapy followed by concurrent chemoradiotherapy for organ preservation in patients with advanced resectable and unresectable (nasopharyngeal) tumors. PATIENTS AND METHODS: Forty-two patients with stage III to IV resectable HNSCC and nasopharyngeal tumors received induction chemotherapy with two courses of cisplatin (20 mg/m2/d continuous infusion [CI]), fluorouracil (800 mg/m2/d CI), and leucovorin (500 mg/m2/d CI; PFL) for 4 days followed by concurrent therapy with cisplatin (100 mg/m2/d on days 1 and 22) and approximately 70 Gy of external-beam radiotherapy. RESULTS: Response to induction chemotherapy included partial response rate of 52% and complete response rate of 24%. The most common grade 3 or 4 toxicity was neutropenia (59%). After cisplatin chemoradiotherapy the complete response rate was 67%. Toxicities of cisplatin chemoradiotherapy consisted of grade 3 or 4 mucositis (79%) and neutropenia (51%). At a median follow-up of 71.5 months, 43% of the patients are still alive and disease-free. The 5-year progression-free survival (PFS) rate was 60%, and the 2- and 5-year overall survival (OS) rates were 67% and 52%, respectively. Three patients died of second primaries. Late complications of treatment included xerostomia and hoarseness. One patient had persistent dysphagia and required laser epiglotectomy 108 months after treatment. CONCLUSION: Induction chemotherapy with PFL followed by concurrent cisplatin chemoradiotherapy is well tolerated and results in a good likelihood of organ preservation and excellent PFS and OS.     

Induction chemotherapy for head and neck cancer: recent data

The addition of chemotherapy to radiotherapy in the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN) patients improves survival. Meta-analyses of randomized trials have indicated that the benefit of this approach is associated with the timing of chemotherapy administration. It has been demonstrated that the greatest survival benefit over locoregional treatment alone is seen with the concurrent administration of chemotherapy and radiotherapy. However, sequential chemotherapy administration, in the form of induction chemotherapy followed by radiotherapy or concurrent chemoradiotherapy, has been successful as a strategy for organ function preservation in patients with potentially resectable SCCHN. In addition, a meta-analysis of trials using platinum and 5-fluorouracil (PF)-containing induction regimens demonstrated a significant survival benefit for this approach over locoregional treatment alone in locally advanced disease. In recent years, the introduction of the taxanes into induction chemotherapy has provided physicians with more active regimens. The triplet combination induction regimen of docetaxel, cisplatin, and 5-fluorouracil has been shown to be more effective in prolonging survival than the doublet PF. Current trials are testing whether the addition of induction chemotherapy to standard concomitant chemoradiotherapy is superior to concomitant chemoradiotherapy alone.     

Patterns of recurrence and outcome for patients with clinical stage II non-small-cell lung cancer

Forty-six patients with pathologic clinical stage II non-small-cell lung carcinoma underwent resection with or without adjuvant radiotherapy from 1989 through 1994. These patients were analyzed to determine patterns of recurrence and survival. Surgery consisted of pneumonectomy for 11 patients, bilobectomy for two patients, lobectomy for 29 patients, and wedge or segmental resection for four patients. Adjuvant radiotherapy was delivered to 29 patients, and the median total dose was 54 Gy (range, 44-60 Gy). Median follow-up time was 23 months for all patients and 25 months for surviving patients. Twenty-six of 46 patients have had recurrence. The site of first recurrence was locoregional for 9 of 46 patients (20%) and distant for 17 of 46 patients (37%). The median time to locoregional recurrence was 18 months for patients treated with radiotherapy and 13 months for patients treated without radiotherapy. An isolated locoregional recurrence (with no simultaneous distant recurrence) was seen in 2 of 28 evaluable patients (7%) treated with radiotherapy compared with 3 of 17 patients (18%) not treated with radiotherapy. For all patients, the 3-year disease-free survival rate was 52%, and the overall survival rate was 52%. Among patients treated with radiotherapy, the 3-year disease-free survival and overall survival rates were 56% and 56%, respectively, compared with 46% and 43%, respectively, for patients who did not receive radiotherapy (p values were not significant). The locoregional recurrence rate was 33% for patients with adenocarcinoma and 15% for those with squamous cell carcinoma. The distant recurrence rates by histologic characteristic were 56% and 20%, respectively. For patients with clinical stage II non-small-cell lung cancer, postoperative radiotherapy appears to improve locoregional control. However, the preponderance of recurrences remains distant. Further study is warranted with special emphasis on control of systemic disease.     

Preliminary results of radiation dose escalation for locally advanced nasopharyngeal carcinoma

PURPOSE: To study the safety and efficacy of dose escalation in tumor for locally advanced nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: From September 2000 to June 2004, 50 patients with T3-T4 NPC were treated with intensity-modulated radiotherapy (IMRT). Fourteen patients had Stage III and 36 patients had Stage IVA-IVB disease. The prescribed dose was 76 Gy to gross tumor volume (GTV), 70 Gy to planning target volume (PTV), and 72 Gy to enlarged neck nodes (GTVn). All doses were given in 35 fractions over 7 weeks. Thirty-four patients also had concurrent cisplatin and induction or adjuvant PF (cisplatin and 5-fluorouracil). RESULTS: The average mean dose achieved in GTV, GTVn, and PTV were 79.5 Gy, 75.3 Gy, and 74.6 Gy, respectively. The median follow-up was 25 months, with 4 recurrences: 2 locoregional and 2 distant failures. All patients with recurrence had IMRT alone without chemotherapy. The 2-year locoregional control rate, distant metastases-free and disease-free survivals were 95.7%, 94.2%, and 93.1%, respectively. One treatment-related death caused by adjuvant chemotherapy occurred. The 2-year overall survival was 92.1%. CONCLUSIONS: Dose escalation to 76 Gy in tumor is feasible with T3-T4 NPC and can be combined with chemotherapy. Initial results showed good local control and survival.     

Non-randomized clinical study comparing chemotherapy plus radiotherapy with radiotherapy alone in neoadjuvant therapy for oral cancer

Neoadjuvant therapy plays an important role for organ preservation and survival rate in the treatment of oral cancer. We clinically compared the effect of neoadjuvant radiotherapy and chemoradiotherapy in patients with oral cancer. We retrospectively examined 47 patients diagnosed with oral squamous cell carcinoma who underwent neoadjuvant therapy followed by curative surgery in the oral and maxillofacial surgery department of Ehime University Hospital. We divided them into two groups: radiotherapy alone (24 cases) and chemoradiotherapy (23 cases). The patients in the radiotherapy group underwent irradiation of 32.6 +/- 5.0 Gy (mean +/- SD). The patients in the chemoradiotherapy group received a low-dose fraction of cisplatin (8 mg/mm2/day, 5 days a week; total dose: 139.4 +/- 67.1 mg) and 5-fluorouracil (300 mg/mm2/day, 5 days a week; total dose: 5,900 +/- 1,839.8 mg) combined with simultaneous irradiation of 31.0 +/- 3.2 Gy. None of the 24 patients had a complete response to radiotherapy alone and 12 (50%) had a partial response. Six (26%) of the 23 patients had a complete response to chemoradiotherapy and 12 (52%) had a partial response. The primary control rate (82.6%) to chemoradiotherapy was higher than that (67.5%) to radiotherapy alone although no significant difference was found. The 5-year survival rate was 64.3% in the radiotherapy group and 62.8% in the chemoradiotherapy group. The findings of the present study suggest that while the combination of radiation and cisplatin/5-fluorouracil in neoadjuvant therapy for oral cancer may not bring a significant benefit to improve survival rate, the primary local control rate is improved in comparison with radiotherapy alone.     

Synchronous radiotherapy and chemotherapy with cisplatin in the management of locally advanced or recurrent head and neck cancer.

A synergism between cisplatin and radiotherapy has been demonstrated in in vitro and in vivo studies. To improve the locoregional control of disease and the survival rate in patients affected by locally advanced or recurrent squamous cell carcinoma of the head and neck, we planned a Phase II study of concurrent radiotherapy, 2 Gy for 5 days every week for a total dose of 60-70 Gy with cisplatin 80 mg/m2 every 21 days for 2 or 3 doses (on days 1, 21, 42). Fifty-one patients were entered in the study; 48 were evaluable for response and toxicity; 18 (37.5%) had untreated Stage III disease; 25 (52%) had Stage IV disease; 5 (10.5%) had recurrent disease. The complete response rate in Stage III-IV patients was 63% (27 of 43) with 95% confidence limits from 48 to 77% (+/- 14.5%). In the group of five patients with recurrent disease, only one (20%) achieved a complete response. In patients with Stage III-IV disease, a significantly higher complete response rate was observed for those younger than 58.5 years (p = 0.05). The overall estimated 1- and 2-year survival was 59% and 37%, respectively, and a significantly better survival was observed in complete responders compared to partial responses or patients with stable disease (p = 0.037). Disease-free survival was 46% and 36% at 1 and 2 years, respectively. Distant failure occurred only in 12.5% of the patients. Overall, the treatment was well tolerated, and only three patients refused to complete the planned therapy. Gastrointestinal and hematological toxicity were the most common side effects. Data from present trial were compared with that of 50 patients with comparable characteristics treated with radiotherapy alone from 1985 to 1987 as a historical control. The complete response rate, the disease-free survival, and the overall survival appear to be better in the patients treated with chemoradiotherapy. It was concluded that the combination of chemoradiotherapy in patients with Stage III-IV head and neck squamous cell carcinoma is an effective and safe treatment with an apparent better locoregional control than radiotherapy alone. Survival results need to be evaluated in a Phase III randomized trial.     

Surgery and adjuvant radiotherapy vs concurrent chemoradiotherapy in stage III/IV nonmetastatic squamous cell head and neck cancer: a randomised comparison

We compared concurrent combination chemotherapy and radiotherapy with surgery and adjuvant radiotherapy in patients with stage III/IV nonmetastatic squamous cell head and neck cancer. Patients with non-nasopharyngeal and nonsalivary resectable squamous cell head and neck cancer were randomised to receive either surgery followed by adjuvant radiotherapy (60 Gy over 30 fractions) or concurrent combination chemotherapy and radiotherapy (66 Gy in 33 fractions). Combination chemotherapy comprised two cycles of i.v. cisplatin 20 mg m(-2) day(-1) and i.v. 5-fluorouracil 1000 mg m(-2) day(-1), both to run over 96 h given on days 1 and 28 of the radiotherapy. A total of 119 patients were randomised. At a median follow-up of 6 years, there was no significant difference in the 3-year disease-free survival rate between the surgery and concurrent chemoradiotherapy (50 vs 40% respectively). The overall organ preservation rate or avoidance of surgery to primary site was 45%. Those with laryngeal/hypopharyngeal disease subsite had a higher organ-preservation rate than the rest (68 vs 30%). Combination chemotherapy and concurrent irradiation with salvage surgery was not superior to conventional surgery and postoperative radiotherapy for resectable advanced squamous cell head and neck cancer. However, this form of treatment schedule with a view to organ-preservation can be attempted especially for those with laryngeal/hypopharyngeal and possibly oropharyngeal disease subsites.     

紫杉醇加顺铂同步放化疗治疗局部晚期食管癌的临床研究

目的:探讨紫杉醇加顺铂(TP)同步放化疗治疗局部晚期食管癌的疗效及毒副反应。方法:48例局部晚期食管癌患者,随机分成两组,每组24例,A组为单纯放疗组,B组为每周紫杉醇加顺铂同步放化疗组。两组均采用6MV或者18MVX射线放射治疗,食管癌原发灶剂量60～68Gy,区域淋巴结剂量50～60Gy。B组放疗同时给予紫杉醇40mg/m2 DDP20mg/m2,均于d1、d8、d15、d22、d29、d36静滴。结果:单纯放疗组和紫杉醇加顺铂组的有效率(CR PR)分别为75%和88%,差异有显著性意义(P<0.05)。两组的1、3、5年局部无进展生存率分别为60.7%、21.0%和9.5%,71.2%、49.3%和19.2%,两组局部无进展生存率差异有显著性意义(P=0.034);两组的1、3、5年生存率分别为66.7%、25.0%和12.5%,79.2%、58.3%和29.2%,总生存率差异有显著性意义(P=0.041)。同步放化疗组的Ⅲ、Ⅳ级毒副反应高于单纯放疗组。结论:同步放化疗可提高局部晚期食管癌的无进展生存率和总生存率,但毒副反应有增加的趋势。     

局部晚期鼻咽癌同期调强放化疗联合辅助化疗的临床疗效

目的观察同期调强放射治疗联合辅助化疗对局部晚期鼻咽癌的临床疗效和不良反应。方法初治局部晚期鼻咽癌患者49例,按92福州分期Ⅲ期30例,ⅣA期19例。鼻咽和上颈部靶体积采用IMRT技术照射,下颈部和锁骨上靶体积采用下颈前切野常规照射。调强放疗设鼻咽大体肿瘤为GTVnx、颈部阳性淋巴结GTVnd、高危临床靶体积CTV1和低危临床靶体积CTV2。处方剂量分别为GTVnx 73.9Gy/33次、GTVnd及CTV166Gy/33次、CTV2(504~594)Gy/(28~33)次。按EORTC或RTOG标准评价急性反应。全组患者均给与同期化疗,放疗结束予3周期辅助化疗。结果中位随访28月,1、2年局部控制率100％,97．96％,1、2年总生存率(OS) 均为97．96％,1、2年无远处转移生存率95.92％、93.89％。结论局部晚期鼻咽癌同期调强放化疗联合辅助化疗可获得较理想的局部区域控率和总生存率。3~4级急性黏膜炎和3～4级血液系统不良反应是化疗的剂量限制性因素。     

Accelerated postoperative radiotherapy with weekly concomitant boost in patients with locally advanced head and neck cancer.

BACKGROUND AND PURPOSE: To assess the feasibility and efficacy of accelerated 66-Gy postoperative radiotherapy (PORT) using a single-fraction regimen from Mondays to Thursdays and a concomitant boost on Friday afternoon sessions in patients with locally advanced head and neck cancer (LAHNC). PATIENTS AND METHODS: Between December 1997 and June 2002, 89 consecutive patients with pT1-pT4 and/or pN0-pN3 LAHNC were included. PORT was indicated in patients with positive surgical margins, T4 tumors, or extracapsular nodal infiltration. RT consisted of 66 Gy (2 Gy/fr) in 5 weeks and 3 days. Median follow-up was 21 months (range 2-59). RESULTS: Acute morbidity was acceptable: grade 3 mucositis in 20 (22%) patients, grade 3 dysphagia in 22 (25%) patients, and grade 3 skin erythema in 18 (20%) patients. Median weight loss was 2 kg (range 0-14.5). No grade 4 toxicity was observed. Late effects included grade 3 xerostomia in 6 (7%) patients, and grade 3 edema in 2 (2%) patients. Median time to locoregional relapse was 10 months (range 2-21). Two-year overall, cause-specific, and disease-free survival rates were 70% (95% confidence interval (CI) 59-81), 75% (95% CI 64-86), and 63% (95% CI 52-74), respectively. The 2-year actuarial locoregional control rate was 80% (95% CI 70-90). Distant metastasis probability at 4 years was 38% (95% CI 20-56). Multivariate analysis revealed that pT-classification (pT1-2 vs. pT3-4) and extranodal extension (0, 1 vs. 2 or more) were the two factors independently influencing the outcome. CONCLUSIONS: We conclude that reducing the overall treatment time using an accelerated PORT schedule including a once-weekly concomitant boost (six fractions per week) is easily feasible with excellent local control. Acute and late RT-related morbidity is acceptable. Given the disease progression pattern (distant metastases), adjuvant chemotherapy should be considered.     

291例局部进展期直肠癌术前新辅助放化疗的临床意义分析

目的 评价局部进展期直肠癌(LARC)术前新辅助放化疗的疗效及安全性。方法 2003—2012年间291例LARC接受了术前新辅助放化疗+手术±术后辅助化疗。放疗为2DRT、3DRT,45~50 Gy分23~25次。化疗方案包括FOLFOX6、XELOX及单药希罗达等,术前化疗2~4周期。放疗结束后3~8周手术,遵循全直肠系膜切除术原则。134例患者术后接受了辅助化疗。Kaplan-Meier法计算OS、DFS、RFS和DMFS等,Logrank法检验和单因素预后分析,Cox模型多因素预后分析。结果 全组均完成术前新辅助放化疗及手术。R0切除率为98.9%,保肛率为53.6%。T降期73.1%,N降期83.6%,临床分期降期79.4%。pCR率为26.8%,3级血液系统反应为7.9%,3级腹泻为7.2%,3级放射性皮炎为2.7%。术后会阴部疼痛占12.3%,伤口延迟愈合占8.2%。随访率94.5%,5年样本量为95例。5年OS、DFS、RFS和DMFS分别为76.6%、72.1%、88.8%和79.7%,5年LR率为7.5%,远处转移率为15.8%。术后病理分期是预后影响因素。结论 术前新辅助放化疗提高了LARC的R0切除率及保肛率,并使肿瘤显著降期,不良反应较轻且未增加手术并发症,LR率低且远期生存率得到改善。术前新辅助放化疗作为LARC标准治疗策略宜推广应用。     

Induction chemotherapy followed by concomitant chemoradiotherapy in the treatment of locoregionally advanced nasopharyngeal cancer.

BACKGROUND: Since 1990, we have treated patients with advanced nasopharyngeal cancer with induction chemotherapy and concomitant chemoradiotherapy. We herein report the results of our experience. PATIENTS AND METHODS: From 1990 to 1999, 27 patients with locoregionally advanced nasopharyngeal cancer were treated with induction chemotherapy followed by concomitant chemoradiotherapy. Using the American Joint Committee on Cancer's 1992 stage classification, all patients were stage III (11%) or IV (89%). By histology, 63% were poorly differentiated carcinoma and 37% squamous cell carcinoma. The median age was 42 years. Three cycles of induction chemotherapy consisting of cisplatin, 5-fluorouracil, leucovorin and interferon-alpha2b were administered, followed by concomitant chemoradiotherapy consisting of seven cycles of 5-fluorouracil, hydroxyurea and once-daily radiotherapy (FHX) on a week-on week-off schedule. The median radiotherapy dose was 70 Gy. RESULTS: Clinical response to induction chemotherapy was 100%, 54.2% complete response (CR) and 45.8% partial response. Clinical and/or pathological (37% of all patients had post-treatment biopsy with or without neck dissection) CR after FHX was 100%. At a median follow-up of 52 months, three failures were observed. Two patients have died of disease, one of local failure and one of distant metastases. One patient is alive with an isolated rib metastasis. At 5 years, actuarial locoregional control is 93% and actuarial distant control 92%. The overall survival at 3 and 5 years is 88% and 77%, respectively. Four patients died of unrelated illnesses and had no evidence of disease with respect to their nasopharyngeal cancer. The progression-free survival at 3 and 5 years is 92% and 86%, respectively. Thirty-three per cent of patients required a reduction in the chemotherapy dose due to acute toxicity. Chronic toxicity was not observed, with all patients able to eat orally without dietary restrictions. CONCLUSIONS: Treatment of locoregionally advanced nasopharyngeal cancer with induction chemotherapy followed by concomitant chemoradiotherapy resulted in excellent overall survival with acceptable toxicity. These results are encouraging and warrant further investigation of intensified approaches.