Hypopharyngeal squamous cell carcinoma--treatment results in 138 consecutively admitted patients

The aim of this study was to evaluate the results of the initial and salvage treatment for hypopharyngeal carcinoma. The study was conducted in 1963 to 1991and included 138 patients (38 females (28%) and 100 males (73%)). Most of the tumours originated in the piriform sinus (86%). Tumour stage distribution was T1: 20%, T2: 27%, T3: 37% and T4: 17% and nodal stage distribution was N0: 45%, N1: 25%, N2: 10%, and N3: 20%. Primary treatment was delivered with curative intent in 124 out of 138 cases (90%). Treatment failure was noted in 98 patients, with 55% recurrence in T-position, 39% in N-position, and 14% at distant metastases sites. Salvage surgery was successful in 9 out of 32 patients. The overall 5-year locoregional tumour control, cause-specific and overall survival rates were 20%, 25% and 19%, respectively. Univariate actuarial analysis showed that T- and N-stage, clinical stage, tumour size and well-differentiated tumours were significant prognostic parameters. A Cox multivariate analysis showed that only the T- and N-stages were independent prognostic factors. In conclusion, the prognosis for advanced hypopharyngeal carcinoma is extremely poor and the meagre results with conventional radiotherapy alone indicate that other treatment modalities should be introduced in the management of this disease.     

Squamous cell carcinoma of the nasopharynx--an analysis of treatment results in 149 consecutive patients

The purpose of this study was to evaluate the outcome of primary treatment and treatment of recurrences in patients with nasopharyngeal carcinoma. The material included 149 consecutive patients seen at the Aarhus University Hospital from 1963 to 1991 (49 females and 100 males). The stage distribution was: Stage I -9%, II-3%, III-28%, and IV-60%. Primary treatment was delivered with curative intent in 145 patients (97%). Persistent or recurrent disease after primary radical treatment was observed in 82 of the patients; 54% at the T-level, 40% at the N-level, and 33% at the M-level. A curative salvage attempt was carried out in 14 patients only, all with nodal recurrence: surgery in 8 patients (4 controlled) and radiotherapy in 6 patients (2 controlled). The 5-year local tumour control, locoregional tumour control, disease-specific survival rate and the overall survival rate for the patients treated with curative intent were 66%, 53%, 50% and 43%, respectively. Most of the patients (88%) had poorly differentiated tumours and these patients had the best prognosis. A major complication in three patients was radiation-induced myelopathy due to high-dose radiation delivered to the brain stem. Significant positive prognostic factors for treatment outcome in univariate analyses were early T-classification, small clinical stage, poor differentiation and low age. The Cox multivariate analysis showed that early T-categories, low N-categories and poor differentiation were independent, positive prognostic factors. Nasopharyngeal carcinoma is curable with primary radiotherapy; patients with poorly differentiated tumours have the best prognosis. Only a few patients were salvaged after recurrence. The factor most essential for success is primary control of the disease at the T- and N-levels.     

Surgical treatment of locally recurrent rectal cancer.

BACKGROUND: The aim of our study was to analyse data of patients treated by salvage surgery for locally recurrent rectal cancer, with emphasis on the question whether salvage surgery is still worthwhile when adjuvant radiotherapy is no longer a treatment option. METHODS: Forty patients (19 males/21 females) treated by surgery with curative intent for locally recurrent rectal carcinoma were analysed. Local recurrence was defined as cancer recurrence within the lower pelvis. Salvage surgery included abdominoperineal resection, abdominosacral resection, exenteration (posterior or total) and local resection. Clinical and pathological factors were analysed to identify prognostic factors for survival. RESULTS: The median overall survival was 25 months (95% CI: 13-37 months) and 5-year survival was 28% (95% CI: 12-45%). The absence of symptoms at the time of recurrence, central localisation and the absence of microscopic involvement of surgical margins, but not additional radiotherapy, were found to be significant independent prognostic factors for better survival after salvage surgery. CONCLUSION: Salvage surgery, alone or in combination with radiotherapy, can achieve radical resection of locally recurrent rectal cancer and can result in long-term survival.     

Glottic carcinoma--patterns of failure and salvage treatment after curative radiotherapy in 861 consecutive patients.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate the patterns of failure and the treatment of recurrences, in a series of primary irradiated patients with squamous cell carcinoma of the glottic larynx. MATERIALS AND METHODS: Eight hundred and sixty-one consecutive patients were included in this study from 1963 to 1991, out of which 74 were females and 787 males. The stages were: I 56, II 26, III 15, and IV 3%. In 847 of 861 cases (98%) the primary treatment was delivered with curative intent, and out of these 834 patients received primary radical radiotherapy. RESULTS: With a minimum follow up of 5 years, 274/861(32%) patients had persistent or recurrent disease; in 91% of these the persistent or recurrent disease was in the T-position, 15% in the N-position, and 5% developed distant metastases. Curative salvage attempt was possible in 207 patients, and 145 were subsequently controlled. A total of 718 (83%) patients obtained ultimate tumour control, 584 (68%) without a laryngectomy (134 of the controlled had a laryngectomy, 109 had a total laryngectomy and 25 had a partial laryngectomy). In the patients treated with curative intent, the overall 5-year local tumour control, loco-regional tumour control, disease specific survival rate and overall survival rate was 72, 70, 86 and 66%, respectively. For patients with small tumours the disease specific survival for T1a, T1b and T2 was 95, 93 and 83%, respectively. In the 718 patients cured for their glottic carcinoma, 204 new primary malignant tumours were detected. CONCLUSIONS: The study shows that laryngeal glottic carcinoma can be effectively managed by primary radiotherapy and surgery salvage. The control is obtained with a high proportion of laryngeal preservation (68%). Recurrences treated with surgical salvage have a success rate of 70%. New primaries are a major problem.     

Salvage definitive chemo‐radiotherapy for locally recurrent oesophageal carcinoma after primary surgery: Retrospective review

To determine the overall survival and gastrointestinal toxicity for patients treated with salvage definitive chemo‐radiotherapy after primary surgery for locoregional relapse of oesophageal carcinoma. A retrospective review of 525 patients who had a resection for oesophageal or oesophagogastric carcinoma at Princess Alexandra Hospital identified 14 patients treated with salvage definitive radiotherapy or chemo‐radiotherapy, following localized recurrence of their disease. We analysed the patient and treatment characteristics to determine the median overall survival as the primary end point. Gastrointestinal toxicity was examined to determine if increased toxicity occurred when the stomach was irradiated within the intrathoracic radiotherapy field. The median overall survival for patients treated with curative intent using salvage definitive chemo‐radiotherapy was 16 months and the 2‐year overall survival is 21%. One patient is in clinical remission more than 5 years after therapy. Age <60 years old and nodal recurrence were favourable prognostic factors. Treatment compliance was 93% with only one patient unable to complete the intended schedule. Fourteen per cent of patients experienced grade 3 or 4 gastrointestinal toxicity. Salvage definitive chemo‐radiotherapy should be considered for good performance status patients with oesophageal carcinoma who have a locoregional relapse after primary surgery. The schedule is tolerable with low toxicity and an acceptable median survival.     

Sequential treatment for recurrent localized prostate cancer

To compare toxicity and efficacy of both salvage prostatectomy and salvage radiotherapy for prostate cancer a retrospective analysis was conducted. Thirty-two and 41 patients were treated with external beam radiotherapy or prostatectomy for cT1c-T2 prostate cancer later requiring salvage surgery or radiotherapy. Salvage surgery was performed when a local recurrence was biopsy confirmed and life-expectancy was more than 10 years. Salvage external beam radiotherapy was performed when PSA rose over 0.1 ng/ml in the absence of systemic disease. Ten-year PSA-recurrence free survival after primary treatment in the salvage surgery group and salvage radiotherapy groups was 55% and 44% (P > 0.05) respectively whereas prostate cancer specific survival was 93% and 89%, respectively (P > 0.05). Both, biopsy Gleason score prior to primary treatment and PSADT prior to salvage treatment were predictive of PSA-recurrence free survival. Patients after salvage radiotherapy (13%) were less likely to wear pads for urinary incontinence compared to patients after salvage surgery (56%). Erectile dysfunction was more frequent after salvage surgery (81%) compared to salvage radiotherapy (61%). Salvage surgery and salvage prostatectomy after primary cT1-2 prostate cancer provide comparable PSA-recurrence free survival after primary treatment. Genitourinary functions were better preserved in the salvage radiotherapy group compared to the salvage prostatectomy group.     

196例鼻咽癌患者疗效分析

目的:回顾性分析鼻咽癌治疗疗效,并分析影响预后的因素。方法:对在我科接受根治性放射治疗的196例鼻咽癌患者进行随访,所有患者均接受6MV-X线照射,剂量范围64～80Gy。其中37例患者配合化疗,化疗方案均采用5-FU DDP,化疗周期2～4周期。结果:全组患者5年和10年的总生存率分别为53.10%和39.90%。单因素分析发现,性别、临床分期、T分期、N分期、原发灶剂量和下颈淋巴引流区剂量是影响预后的因素。多因素分析仅提示临床分期明显影响预后。结论:鼻咽癌放射治疗的疗效确切,临床分期、T分期、N分期是影响预后最主要的因素,提高早期患者的检出率是提高治疗鼻咽癌疗效的关键。     

Expression of Cox-2 protein in radioresistant laryngeal cancer.

BACKGROUND: Radiotherapy is the principal modality used to treat early stage laryngeal cancer. Unfortunately treatment failures occur in 10-25% of patients. Subsequent salvage surgery is technically more difficult, with increased complication and failure rates. The ability to predict or prevent radioresistance would improve the poor survival associated with this disease. Cox-2 is an inducible enzyme involved with prostaglandin synthesis. We investigated a potential role for Cox-2 in predicting radioresistance in laryngeal cancer. PATIENTS AND METHODS: Using immunohistochemical techniques we examined the expression of Cox-2 protein in 122 pre-treatment laryngeal biopsies. All tumours were treated with single modality radiotherapy (curative intent). The group comprised of 61 radioresistant and 61 radiosensitive tumours matched for T stage, laryngeal subsite, gender and smoking history. RESULTS: Cox-2 expression was detected in 41 of 61 (67%) biopsy samples from patients with radioresistant tumours and 25 of 61 (41%) radiosensitive tumours. Overexpression was significantly associated with radioresistant tumours (P = 0.004). Cox-2 has a 67% accuracy in predicting radiotherapy failure. CONCLUSION: Cox-2 may have prognostic value in predicting response to radiotherapy. Cox-2 inhibitors such as NS-398 have been shown to enhance the effects of radiotherapy. We suggest that their use may be beneficial in patients who are destined to fail radiotherapy.     

Salvage radiotherapy in recurrent Hodgkin's disease.

Forty-four patients with Hodgkin's disease (HD) which relapsed after chemotherapy were treated with salvage radiotherapy (S-RT) with curative intent. Patients were aged 7 to 80 years (median 32 years) at the time of S-RT and the median follow-up from S-RT was 5 years (1-15). Nine patients had recurrent HD following first-line chemotherapy and thirty five patients had refractory HD. Salvage therapy consisted of radiotherapy alone in 25 and combined chemotherapy and radiotherapy in 19 patients. The overall CR rate of salvage therapy was 66%. The overall median survival of 44 patients was 4.6 years from S-RT with 46% 5 year and 40% 10 year survivals. Age (greater than 40 years) and progression free interval (less than or equal to 1 year) were adverse independent prognostic factors for survival on multivariate analysis. The 5 and 10 year progression free survivals were 38% and 23% respectively. Adverse independent prognostic factors for progression-free survival were extranodal site of recurrence and short progression free interval (less than or equal to 1 year). We conclude that radiotherapy with or without chemotherapy has a role in the salvage of patients failing chemotherapy, particularly in those with nodal disease and progression-free interval greater than 1 year.     

Treatment and survival of locally recurrent rectal cancer: A cross-sectional population study 15 years after the Dutch TME trial

IntroductionOptimized treatment of primary rectal cancer might have influenced treatment characteristics and outcome of locally recurrent rectal cancer (LRRC). Subgroup analysis of the Dutch TME trial showed that preoperative radiotherapy (PRT) for the primary tumour was an independent poor prognostic factor after diagnosis of LRRC. This cross-sectional population study aimed to evaluate treatment and overall survival (OS) of LRRC patients, stratified for prior preoperative radiotherapy (PRT) and intention of treatment of LRRC.MethodsAll patients developing LRRC were selected from a collaborative Snapshot study on 2095 surgically treated rectal cancer patients from 71 Dutch hospitals in the year 2011. Cox proportional hazard analysis was performed to determine predictors for OS.ResultsA total of 107 LRRC patients (5.1%) were included, of whom 88 (82%) underwent PRT for their primary tumour. LRRC was treated with initial curative intent in 31 patients (29%), with eventual resection in 20 patients (19%). Median OS was 22 and 8 months after curative and palliative intent treatment, respectively (p < 0.001). Initial CRM positivity and palliative intent treatment were associated with worse OS after LRRC, while prior PRT was not.ConclusionsThis cross-sectional study revealed that rectal cancer patients, who underwent curative resection in the Netherlands in 2011 and subsequently developed local recurrence, were amenable for again curative intent treatment in 29%, with a corresponding median survival of 22 months. Prior PRT was not significantly associated with survival after diagnosis of LRRC.     

The treatment of early (T1) glottic and supra-glottic carcinoma: does partial laryngectomy have a place?

A series of 900 patients with laryngeal carcinoma is described. Patients with glottic T1N0 tumours were treated by radiotherapy with a 5-year survival of 92%. Seven per cent of patients suffered recurrence and most were salvaged by surgery: vertical hemilaryngectomy was occasionally useful as a salvage procedure. Patients with supra-glottic T1N0 tumours were treated for the first 7 years by supra-glottic laryngectomy and prophylactic neck dissection and thereafter by radiotherapy. The results were equally good in both series: a 5-year survival of 75-80%. Salvage surgery for failed radiotherapy or surgery for supra-glottic carcinoma gave poor results.     

Role of radiotherapy in the treatment of cervical lymph node metastases from an unknown primary site: retrospective analysis of 113 patients

PURPOSE: The management of patients with cervical lymph-node metastases from unknown primary site (UPS) remains a matter of discussion. This study aimed to analyze the results and prognostic factors in a series of patients treated with radiotherapy. METHODS AND MATERIALS: Data from 113 patients who presented with cervical lymph nodes metastases from UPS treated from 1980 to 2004 were reviewed. Eighty-seven patients (77.0%) were squamous cell carcinoma (SCC). Ninety-one patients were treated with curative and 22 with palliative intent. Fifty-nine of 113 patients (52.2%) received surgery followed by radiotherapy and 54 of 113 (47.8%) received radiotherapy alone. Radiotherapy was delivered to the neck and pharyngeal mucosa in 67 patients and to the ipsilateral or bilateral neck in 45 patients. Twenty-one patients (18.5%) also received chemotherapy. RESULTS: The 5-year overall survival rates were 40.7% for the entire group and 46.6% for the SCC subgroup. The occurrence of the occult primary was observed in 23 of 113 patients (20.3%), 19 (82.6%) within the head and neck region. At multivariate analysis, treatment with curative intent and extensive irradiation of bilateral neck and pharyngeal mucosa were favorable prognostic factors for the whole series, and treatment with curative intent, extensive irradiation of bilateral neck and pharyngeal mucosa, and absence of extracapsular spread were favorable prognostic factors for the SCC subgroup. CONCLUSIONS: Patients with cervical lymph node metastases from UPS have a similar prognosis to those affected by other head and neck malignancies. Curative treatment strategies including neck dissection and extensive irradiation by three-dimensional conformal radiation therapy resulted in significantly better outcomes.     

喉癌单纯放疗后原发灶复发的救援治疗

目的：探讨对喉癌单纯放疗后原发灶复发进行挽救治疗的疗效。方法：回顾52例1990年-1995年于中山大学肿瘤防治中心进行单纯放疗的喉癌患者，其中17例治疗后原发灶复发的患者进行总结。5例患者进行姑息性化疗，另外12例患者行手术挽救，6例行喉部分切除术，6例行喉全切除术。应用SPSS10．0统计软件进行分析。结果：单纯放射治疗后原发灶复发经再次挽救治疗后总体三年和五年累计生存率分别为56．3％和37．5％。其中进行姑息化疗的患者经挽救后的生存时间介于8～26个月，进行手术挽救的患者三年和五年累计生存率分别为75％和50％，Kaplan—Meier分析表明两者之间存在显著差异(Log Rank=8．14，P=0．0043)。另外，进行手术挽救的患者中，喉部分切除术和喉全切除术挽救患者的五年累计生存率均为50％，Kaplan-Meier分析显示两者间无显著差异(Log Rank=0．08，P=0．7782)。12例进行手术挽救的患者中5例(41．7％)出现术后并发症，主要是术后感染(25％)和咽瘘(25％)。结论：喉癌单纯放疗后原发灶复发患者进行手术挽救可以获得较好的疗效。原发灶早期(T1和T2)患者复发后可选择进行喉部分切除术挽救。手术挽救后的并发症主要是术后感染和咽瘘。     

Carcinoma of the hard palate treated with radiotherapy: a retrospective review of 31 cases.

There are few studies reporting the results of radical radiotherapy for carcinoma of the hard palate. We have examined our results of patients treated within a single institution, and assessed survival, local control and morbidity. A retrospective analysis was made on 31 patients with hard palate carcinoma treated with external beam radiotherapy at the Christie Hospital between 1990 and 1997. Twenty-six patients received radiotherapy alone and five were treated for post-operative positive surgical margins. The 5-year actuarial survival rate was 55%. The actuarial 5-year local control rate was 53%, rising up to 69% after salvage surgery. Survival was 48% for squamous cell carcinomas and 63% for salivary gland carcinomas, the difference was not significant. The only significant predictor of local control was T-stage, with 80% 5-year local control of T1-2 lesions and 24% control of T3-4 lesions. N-stage was the only significant factor predicting for survival. Radiation necrosis occurred in one patient. Radical radiotherapy for carcinoma of the hard palate is safe and well tolerated. It is an effective treatment for both squamous cell carcinoma and salivary gland carcinoma.     

Epidermoid anal cancer: a review of a population-based series of 308 consecutive patients treated according to prospective protocols

PURPOSE: The primary therapy in epidermoid anal cancer is radiotherapy, generally with chemotherapy. The use of neoadjuvant chemotherapy has been infrequently reported in the literature. This study presents results from a large population-based series and provides comparisons between different treatments. METHODS AND MATERIALS: Between 1985 and 2000, 308 patients with invasive epidermoid anal cancer were diagnosed in the Stockholm Health Care Region. Treatment was given according to defined protocols. External beam radiotherapy alone or with concomitant bleomycin and neoadjuvant chemotherapy followed by radiotherapy alone were the primary treatments. Radical surgery was reserved for poor responders or recurrences. Data were reviewed with regard to treatment, outcome, and prognostic factors. RESULTS: Among the 276 patients (90%) treated with curative intent, 264 (96%) received treatment in accordance with the protocols. The overall 5-year survival rate was 68%. Among the 142 patients with locally advanced tumors (T > or =4 cm or N+), patients treated with neoadjuvant platinum-based chemotherapy (n = 91) had significantly better complete response rates compared with patients treated with radiotherapy with or without bleomycin (n = 51) (92% vs. 76%, p < 0.01). A significantly increased overall 5-year survival rate was also found among patients receiving neoadjuvant therapy (63% vs. 44%, p < 0.05). CONCLUSION: Structured treatment protocols result in favorable outcome on a population level. The results further suggest a significant therapeutic gain from including neoadjuvant chemotherapy in the treatment of locally advanced anal cancer.     

Treatment of locally recurrent rectal cancer, results and prognostic factors.

PURPOSE: Assessment of the results and prognostic factors in patients with locally recurrent rectal cancer treated with curative intent. PATIENTS AND METHODS: Forty patients with an isolated pelvic recurrence of rectal cancer were studied retrospectively. The treatment consisted of radiotherapy alone or combined with chemotherapy and/or surgery performed between January 1992 and July 2001. Radiotherapy was given with a 3-4 fields technique (6-15 MV), five times a week. The median radiation dose was 50 Gy (range 25-66.6 Gy). Twenty-five patients underwent salvage surgery. Five patients were treated with concomitant chemotherapy (5-fluoro-uracil/leucovorin) (5FU/LV) during the 1st and 5th week of radiotherapy. RESULTS: Twenty-two of the 40 patients were male. The local recurrence free survival after 3 and 5 years, respectively, was 49 and 39%. Male gender was the only independent factor associated with failure of local control. The 3 and 5-year overall survival of the total group was 36 and 19%, respectively, with a median survival of 26 months. CONCLUSION: In a selection of patients in the treatment of locally recurrent rectal cancer valuable local palliation if not cure, can be reached. A multimodality approach seems to offer the best chances in this threatening situation.     

Cancer of the larynx--treatment results after primary radiotherapy with salvage surgery in a series of 1005 patients

The aim of this study is to present and discuss the results of initial radiotherapy with salvage surgery and to compare them with those from centres where primary surgery is the prevailing principle. The series comprised 1005 consecutive patients treated during the period 1965-1998. Salvage surgery was performed if patients had residual tumour or developed recurrence. Disease-specific survival (DSS) and crude survival (CS) after 5 years, among 643 patients with glottic carcinomas treated with curative radiotherapy was 88.6% (SE =1.3) and 65.3% (SE =2.0), respectively. Among T1 glottic carcinomas the locoregional control was 88%, i.e. 88% of patients were cured after radiotherapy alone, and the DSS was 99%, both evaluated after 5 years, i.e. the salvage surgery added approximately 11% to the survival of T1 glottic patients. Only 4% (12/312) of T1 glottic patients had laryngectomies. Locoregional control among T2 glottic cases was 67% and the DSS 88%, but, 18% (41/233) of patients lost their larynx. The corresponding results among T3 glottic cases were 30% and 59%, i.e. the organ preservation was close to 50%. Among patients with supraglottic carcinomas, the two estimates were 44% and 63%, respectively. Compared with our results, recent results published in the literature after initial laser surgery of T1 glottic carcinomas indicate that there are only minor differences in DSS and organ preservation, but it is generally agreed, but not proven, that voice quality after radiotherapy is better. T2 glottic carcinomas treated by initial supracricoid partial laryngectomy in a selected series have yielded very high DSS rates with better organ preservation than was observed in the present series. As to T3 glottic carcinomas, initial surgery does not produce better survival rates than those produced in the present series but our organ preservation is higher. The treatment of patients with supraglottic carcinoma has benefited from optimization of radiotherapy during recent decades. The role of initial laser surgery is as yet undecided.     

Primary intramedullary ependymomas: retrospective study of 16 cases]

PURPOSE: To review the radiotherapy department experience in treating primary spinal cord ependymomas (PSCE), analyse prognostic factors and provide treatment recommendations regarding literature review. MATERIALS AND METHODS: Sixteen patients with PSCE received postoperative radiotherapy between 1972 and 1997. There were 10 male and 6 female patients with a mean age of 34 years (range 2-63). Surgery was gross total resection in 2 cases, subtotal resection in 9, biopsy in 4 and of unknown type in one patient. All patients were treated with radiotherapy to the craniospinal axis (4 cases), spinal cord (1 case) and to the site of primary tumour in 11 cases. RESULTS: Five year-survival rate was 73%. Two patients had recurrent tumours within the primary site. Gender, extent of surgery and treatment field extent were not prognostic factors. Histologic type was the only variable predictive of outcome. Patients with myxopapillary type had a 5-year survival rate of 100% compared with 47% for those with other histology types. CONCLUSION: We conclude that aggressive surgery is not necessary in the management of PSCE, localised field radiotherapy is associated with favourable outcome, and tumour grade is an important prognostic factor.     

Prognostic factors for survival and tumor control in cervical lymph node metastases from head and neck cancer. A multivariate study of 492 cases.

A multivariate analysis was carried out in 492 patients with metastatic neck disease from squamous cell carcinoma to determine the influence of clinical and therapeutic factors on survival, local and regional control, and distant metastases. After radiation treatment with radical intent, recurrence at the primary site was the most frequent site of treatment failure (20% of cases), followed by distant metastases (14% of the cases), whereas isolated neck recurrences occurred in only 7% of the patients. The most significant factors influencing survival were primary tumor site, node fixation, N-stage, T-stage, and number of lymphatic chains. The most significant factors influencing local control were primary site, T-stage, and node fixation. Significant factors influencing regional control were radiation therapy volume, primary tumor site, node fixation, and node location (upper and lower neck). Significant factors influencing distant control were N-stage, number of nodes, and number of involved lymphatic chains.     

Radiotherapy with or without mitomycin c in the treatment of locally advanced head and neck cancer: results of the IAEA multicentre randomised trial.

BACKGROUND AND PURPOSE: Single agent mitomycin c (MMC) has been shown to improve the outcome of radiotherapy in single institution trials. In order to confirm these findings in a broader worldwide setting, the International Atomic Energy Agency (IAEA) initiated a multicentre trial randomising between radiotherapy alone versus radiotherapy plus MMC. MATERIAL AND METHODS: Patients with advanced head and neck cancer were treated with primary curative radiotherapy (66 Gy in 33 fractions with five fractions per week) +/-a single injection (15 mg/m(2)) of MMC at the end of the first week of radiotherapy. Stratification parameters were tumour localization, T-stage, N-stage, and institution. A total of 558 patients were recruited in the trial from February 1996 to December 1999. Insufficient accrual and reporting led to the exclusion of three centres. The final study population consisted of 478 patients from seven centres. Patients had stage III (n=223) or stage IV (n=255) squamous cell carcinoma of the oral cavity (n=230), oropharynx (n=140), hypopharynx (n=65) or larynx (n=43). Prognostic factors like age, gender, site, size, differentiation and stage were well balanced between the two arms. RESULTS: The haematological side effects of MMC were very modest (<5% grade 3-4) and did not require any specific interventions. Furthermore, MMC did not enhance the incidence or severity of acute and late radiation side effects. Confluent mucositis and dry skin desquamation was common, occurring in 56% and 62% of patients, respectively. The overall 3-year primary locoregional tumour control, disease-specific and overall survival rates were 19, 36 and 30%, respectively. Gender, haemoglobin drop, tumour site, tumour and nodal stage were significant parameters for loco-regional tumour control. There was no significant effect of MMC on locoregional control or survival, except for the 161 N0 patients, where MMC resulted in a better loco-regional control (3-year estimate 16% vs. 29%, P=0.01). CONCLUSIONS: The study did not show any major influence of MMC on loco-regional tumour control, survival or morbidity after primary radiotherapy in stage III-IV head and neck cancer except in N0 patients where loco-regional control was significantly improved.