Neoadjuvant concurrent chemoradiation with weekly paclitaxel and carboplatin for patients with oesophageal cancer: a phase II study.

This study was performed to assess the efficacy and safety of preoperative chemoradiation consisting of carboplatin and paclitaxel and concurrent radiotherapy for patients with resectable (T2-3N0-1M0) oesophageal cancer. Treatment consisted of paclitaxel 50 mg m(-2) and carboplatin AUC=2 on days 1, 8, 15, 22 and 29 and concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week), followed by oesophagectomy. All 54 entered patients completed the chemoradiation without delay or dose-reduction. Grade 3-4 toxicities were: neutropaenia 15%, thrombocytopaenia 2%, and oesophagitis 7.5%. After completion of the chemoradiotherapy 63% had a major endoscopical response. Fifty-two patients (96%) underwent a resection. The postoperative mortality rate was 7.7%. All patients had an R0-resection. The pathological complete response rate was 25%, and an additional 36.5% had less than 10% vital residual tumour cells. At a median follow-up of 23.2 months, the median survival time has not yet been reached. The probability of disease-free survival after 30 months was 60%. In conclusion, weekly neoadjuvant paclitaxel and carboplatin with concurrent radiotherapy is a very tolerable regimen and can be given on an outpatient basis. It achieves considerable down staging and a subsequent 100% radical resection rate in this series. A phase III trial with this regimen is now ongoing.

[Palliative treatment in patients with oesophagus carcinoma]. / De palliatieve behandeling van patiënten met een oesofaguscarcinoom.

More than 50% of patients with oesophageal carcinoma will undergo palliative treatment because of distant metastases or local tumour ingrowth into surrounding organs. The majority of these patients have symptoms ofdysphagia. If metastases from oesophageal carcinoma are present, the most commonly used treatment modalities for dysphagia in The Netherlands are placement of a self-expanding stent or intraluminal radiotherapy (brachytherapy). If the life expectancy of patients is longer than 3 months, brachytherapy is sometimes combined with external radiotherapy. If patients with metastases are in a good condition, chemotherapy may be considered. If there is local tumour ingrowth but no metastases, chemotherapy in combination with radiation therapy (chemoradiation) is an option. These treatments should preferably make up part of well-designed studies. Quality of life is an important endpoint to consider in the palliative treatment of patients with oesophageal cancer. Well-established standardized and validated questionnaires are available for this purpose.

[Palliative treatment of esophageal cancer with dysphagia: more favourable outcome from single-dose internal brachytherapy than from the placement of a self-expanding stent; a multicenter randomised study]. / Palliatieve behandeling voor slokdarmkanker met passageklachten: gunstiger uitkomsten van eenmalige inwendige brachytherapie dan van plaatsing van een zelfexpanderende stent; multicentrisch, gerandomiseerd onderzoek.

OBJECTIVE: To compare the results of single-dose internal irradiation (brachytherapy) and self-expanding metal stent placement in the palliation of oesophageal obstruction due to cancer of the oesophagus. DESIGN: Randomised trial. METHOD: In the period from December 1999-Jun 2002, 209 patients with dysphagia due to inoperable carcinoma of the oesophagus were randomised to placement of an Ultraflex stent (n = 108) or single-dose (12 Gy) brachytherapy (n = 101). Primary outcome was relief of dysphagia; secondary outcomes were complications, persistent or recurrent dysphagia, health-related quality of life, and costs. Patients were followed up by monthly home visits from a specialised nurse. RESULTS: Dysphagia improved more rapidly after stent placement than after brachytherapy, but long-term relief of dysphagia was better after brachytherapy. Stent placement resulted in more complications than did brachytherapy (36/108 (33%) versus 21/101 (21%); p = 0.02), due mainly to an increased incidence of late haemorrhage in the stent group (14 versus 5; p = 0.05). The groups did not differ with regard to the incidence of persistent or recurrent dysphagia or median survival (p > 0.20). In the long term, quality-of-life scores were higher in the brachytherapy group. Total medical costs were also similar for both treatments: Euro 8,215 for stent placement and Euro 8,135 for brachytherapy. CONCLUSION: Brachytherapy provided better long-term relief of dysphagia than did stent placement and also produced fewer complications. Brachytherapy is therefore recommended as the preferred treatment for the palliation of dysphagia due to oesophageal cancer.

Immediate post-radiotherapy changes in malignant glioma can mimic tumor progression.

To determine the frequency of progressive MRI lesions shortly after radiotherapy for glioma with spontaneous improvement or stabilization, the authors studied a cohort of patients treated within two prospective phase III trials with radiotherapy only. In 9 out of 32 patients, the first post-radiotherapy MRI showed progressive enhancement. In 3 of these 9 the MRI improved or stabilized for 6 months without additional treatment. The authors conclude that patients with progressive lesions within 3 months after radiotherapy should not be eligible for phase II trials on recurrent glioma.

Salivary gland carcinoma: independent prognostic factors for locoregional control, distant metastases, and overall survival: results of the Dutch head and neck oncology cooperative group.

BACKGROUND: We analyzed the records of patients with malignant salivary gland tumors, as diagnosed in centers of the Dutch Head and Neck Oncology Cooperative Group, in search of independent prognostic factors for locoregional control, distant metastases, and overall survival. METHODS: In 565 patients, we analyzed general results and looked for the potential prognostic variables of age, sex, delay, clinical and pathologic T and N stage, site (332 parotid, 76 submandibular, 129 oral cavity, 28 pharynx/larynx), pain, facial weakness, clinical and pathologic skin involvement, histologic type (WHO 1972 classification), treatment, resection margins, spill, perineural and vascular invasion, number of neck nodes, and extranodal disease. The median follow-up period was 74 months; it was 99 months for patients who were alive on the last follow-up. RESULTS: The rates of local control, regional control, distant metastasis-free and overall survival after 10 years were, respectively, 78%, 87%, 67%, and 50%. In multivariable analysis, local control was predicted by clinical T-stage, bone invasion, site, resection margin, and treatment. Regional control depended on N stage, facial nerve paralysis, and treatment. The relative risk with surgery alone, compared to surgery plus postoperative radiotherapy, was 9.7 for local recurrence and 2.3 for regional recurrence. Distant metastases were independently correlated with T and N stage, sex, perineural invasion, histologic type, and clinical skin involvement. Overall survival depended on age, sex, T and pN stage, site, skin and bone invasion. CONCLUSIONS: Several prognostic factors for locoregional control, distant metastases, and overall survival were found. Postoperative radiotherapy was found to improve locoregional control.

The effect of retrobulbar irradiation on exophthalmos, ductions and soft tissue signs in Graves' ophthalmopathy: a retrospective analysis of 90 cases.

PURPOSE: Retrospective analysis of the effect of retrobulbar irradiation on exophthalmos, ductions and soft tissue signs in patients with Graves' ophthalmopathy. METHODS: We analysed the charts of 111 consecutive patients who were treated with retrobulbar irradiation according to standardised intake criteria between 1992 and 1997. After exclusion of patients who underwent other treatment (with steroids or orbital decompression) shortly before or within 6 months after irradiation, and on whom insufficient data were available, 90 patients were included. For these 90 patients, we analysed the exophthalmometry, ductions, soft tissue signs and visual acuity shortly before irradiation and after 3 and 6 months, respectively. RESULTS: In the whole group, the Hertel value was on average 22 mm (SD 2.9) both before irradiation and after 3 and 6 months of follow-up. Separate analysis of data on 25 patients with bilateral exophthalmos of more than 24 mm also revealed no change in exophthalmos at follow-up. In the whole group, both abduction and elevation had improved by about 1 degree (SD 6.6 degrees; p = 0.05) after 3 months. This improvement has little clinical significance. In a subgroup of 14 patients who showed more than 10 degrees of restricted eye motility in one or more directions, both abduction and elevation had increased by about 4 degrees (SD 10 degrees; p = 0.02) at 3 and 6 months follow-up. Soft tissue signs had improved at 6 months after irradiation. We found no change in visual acuity after irradiation. CONCLUSION: Retrobulbar irradiation in Graves' ophthalmopathy does not seem to reduce exophthalmos. It probably improves eye motility in patients with severe restrictions. The late improvement in soft tissue signs may either be a late effect of irradiation or be related to the natural history of the disease.

Identification of prognostic factors in patients with brain metastases: a review of 1292 patients.

PURPOSE: Prognostic factors in 1292 patients with brain metastases, treated in a single institution were identified in order to determine subgroups of patients suitable for selection in future trials. MATERIALS AND METHODS: From January 1981 through December 1990, 1292 patients with CT-diagnosed brain metastases were referred to the Department of Radiation Oncology, Daniel den Hoed Cancer Center, Rotterdam. The majority of patients were treated with whole brain radiotherapy (84%), the remainder were treated with steroids only or surgery and radiotherapy. Information on potential prognostic factors (age, sex, performance status, number and distribution of brain metastases, site of primary tumor, histology, interval between primary tumor and brain metastases, systemic tumor activity, serum lactate dehydrogenase, response to steroid treatment, and treatment modality) was collected. Univariate and multivariate analyses were performed to determine significant prognostic factors. Results were compared with literature findings using a review of prognostic factors in 18 published reports. RESULTS: Overall median survival was 3.4 months, with 6-month, 1-year, and 2-year survival percentages of 36%, 12%, and 4% respectively. Survival was statistically significantly different between treatment modalities, with median survival of 1.3 months in patients treated with steroids only, 3.6 months in patients treated with radiotherapy, and 8.9 months in patients treated with neurosurgery followed by radiotherapy (p < 0.0001). Multivariate analysis confirmed literature findings of the major prognostic value of treatment modality on survival of patients with brain metastases. Performance status, response to steroid treatment, systemic tumor activity, and serum lactate dehydrogenase were independent prognostic factors with the strongest impact on survival, second only to treatment modality. Site of primary tumor, age, and number of brain metastases were also identified as prognostic factors in our material, although with lesser importance. In patients with lung primaries, sex was found to have significant impact on survival. In patients with breast primaries, interval between primary tumor and development of brain metastases appeared to be a statistically significant prognostic factor. Histology in patients with lung primaries and distribution of brain metastases were not found to be statistically significant in multivariate analysis. CONCLUSIONS: In this large database, the value of established prognostic factors was confirmed and, furthermore, some less well-recognized parameters such as response to steroid treatment, serum lactate dehydrogenase, age, sex in lung primaries, and site of primary tumor were established. From the three strongest prognostic factors--performance status, response to steroids, and evidence of systemic disease--simple identification of favorable and unfavorable subgroups of patients with brain metastases can be constructed.

Fractionated high-dose-rate brachytherapy in primary carcinoma of the nasopharynx.

PURPOSE: A growing body of data suggests that local control in nasopharyngeal cancer (NPC) is related to the radiation dose administered. We conducted a single-institution study of high-dose radiotherapy (RT), which incorporated high-dose-rate (HDR) brachytherapy (BT). These results were analyzed together with data obtained from controls who did not receive BT. PATIENTS AND METHODS: The BT group comprised 42 consecutive patients of whom 29 patients were staged according to the tumor, node, metastasis system as T1 through 3, 13 patients were T4, and 34 patients were N+ disease. BT was administered on an outpatient basis by means of a specially designed flexible nasopharyngeal applicator, and the dose distributions were optimized. Treatment for T1 through 3 tumors comprised 60 Gy of external-beam radiotherapy (ERT) followed by six fractions of 3 Gy BT (two fractions per day). Patients with parapharyngeal tumor extension and/or T4 tumors received 70 Gy ERT and four fractions of 3 Gy BT. The no-BT group consisted of all patients treated from 1965 to 1991 (n = 109), of whom 82 patients had stages T1 through 3, 27 patients had T4, and 80 patients had N+ disease. Multivariate Cox proportional hazards analyses were performed by using the end points time to local failure (TTLF), time to distant failure (TTDF), disease-free survival (DFS), cause-specific survival (CSS), and the prognostic factors age, tumor stage, node stage, and grade. Because the overall treatment time varied substantially in the no-BT group, the dependence of local failure (LF) on the physical dose as well as the biologic effective dose (BED) corrected for the overall treatment time (OTT) (BEDcor10) was studied. RESULTS: The BT group had a superior 3-year local relapse-free rate (86% v 60%; univariate analysis, P = .004). Multivariate analysis showed hazards ratios for BT versus no-BT of 0.24 for TTLF (P = .003), 0.35 for TTDF (P = .038), 0.31 for DFS (P < .001), and 0.44 for CSS (P = .01). The best prognostic group consisted of patients with T1 through 3, N0 through 2b tumors treated with BT who attained a 5-year TTLF of 94% and CSS of 91%. In contrast, the worst prognostic group, i.e., 5-year TTLF of 47% and CSS of 24%, was composed of patients with T4 and/or N2c through 3 tumors who did not receive BT. CONCLUSION: High doses of radiation (73 to 95 Gy) can be administered to patients with NPC with minimal morbidity by means of optimized HDR-BT. The use of a BT boost proved to be of significant benefit, particularly in patients with T1 through 3, N0 through 2b disease. The steep dose-effect relationship seen for the physical dose and the BEDcor10 indicates that the results are dose related. The analysis has identified a poor prognostic group in whom treatment intensification with chemotherapy (CHT) is indicated.

Fractionated high-dose-rate and pulsed-dose-rate brachytherapy: first clinical experience in squamous cell carcinoma of the tonsillar fossa and soft palate.

PURPOSE: Fractionated high-dose-rate (fr.HDR) and pulsed-dose-rate (PDR) brachytherapy (BT) regimens, which simulate classical continuous low-dose-rate (LDR) interstitial radiation therapy (IRT) schedules, have been developed for clinical use. This article reports the initial results using these novel schedules in squamous cell carcinoma (SCC) of the tonsillar fossa (TF) and/or soft palate (SP). METHODS AND MATERIALS: Between 1990 and 1994, 38 patients with TF and SP tumors (5 T1, 22 T2, 10 T3, and 1 T4) were treated by fr.HDR or PDR brachytherapy, either alone or in combination with external irradiation (ERT). Half of the patients were treated with fr.HDR, which entailed twice-daily fractions of > or = 3 Gy. The other 19 patients were administered PDR, which consisted of pulses of < or = 2 Gy delivered 4-8 times/day. The median cumulative dose of IRT +/- ERT series was 66 Gy (range 55-73). The results in these patients treated by brachytherapy were compared to 72 patients with similar tumors treated in our institute with curative intent, using ERT alone. The median cumulative dose of ERT-only series was 70 Gy (range 40-77). RESULTS: Excellent locoregional control was achieved with the use of IRT +/- ERT, with only 13% (5 of 38) developing local failure, and salvage surgery being possible in three of the latter (60%). Neither BT scheme (fr.HDR vs. PDR) nor tumor site (TF vs. SP) significantly influenced local control rates. The type and severity of the side effects observed are comparable to those reported in the literature for LDR-IRT. These results contrast sharply with our ERT-only series, in which 39% of patients (28 of 72) developed local failure, with surgical salvage being possible only in three patients (11%). Taking the data set of 110 patients, in a univariate analysis IRT, T stage, N stage, overall treatment time (OTT), and BEDcor10 (biological effective dose with a correction for the OTT) were significant prognostic factors for local relapse-free survival (LRFS) and overall survival (OS) at 3 years. Using Cox proportional hazard analysis, only T stage and BEDcor10 remained significant for LRFS (p < 0.001 and 0.008, respectively), as well as for OS (p < 0.001 and 0.003, respectively). With regard to the current (IRT) and historical (ERT) series, for the LRFS at 3 years, dose-response relationships were established, significant, however, only for the BEDcor10 (p = 0.03). CONCLUSION: The 3-year LRFS of approximately 90% for TF and SP tumors reported here is comparable with the best results in the literature, particularly given the fact that 30% of the patients (11 of 38) presented with T3/4 tumors. When compared with our historical (ERT-only) controls, the patients treated with IRT had superior local control. A dose-response relationship was established for the BEDcor10.

Local tumor control in radiation therapy of cancers in the head and neck.

BACKGROUND: A retrospective study of 1,493 head and neck cancer patients was designed to test current radiobiological thinking, postulating the detrimental effect of protracted overall treatment times (OTT) and/or split course (SC) regimes in radiation therapy on local tumor control. METHODS: Primary squamous cell carcinomas of the oral cavity (OC), oropharynx (OP), hypopharynx (HP), nasopharynx (NP), and larynx radiated with a dose of at least 50 Gy were analyzed. Those patients treated by brachytherapy and/or primary surgery were excluded. A detailed analysis of the 997 cancers of the larynx was recently published. This paper focuses on the relationship between local tumor control and treatment characteristics for the 496 tumors originating from the OC, OP, HP, and NP. Total doses of radiation ranged from 50 to 79 Gy, with a mean of 64 Gy. RESULTS: A local failure (LF) was observed for 278 patients. Using Cox regression analysis, T stage and site were strongly related to LF. Corrected for T stage and with reference to OP, tumors in the NP, HP, and OC had a relative LF rate of 0.5, 1.6, and 1.8, respectively. Patients treated with continuous course (CC) and higher doses of radiation therapy fared best. No association was found with OTT and the use of chemotherapy. CONCLUSIONS: The results observed for the OC, OP, HP, and NP are in line with the findings for the larynx. Analyzing all 1,493 patients, for SC regimes lower local control rates were observed as opposed to the CC treatment series. Moreover, for the normalized total doses, a dose-effect relationship could be established. This study corroborates that disruption of the treatment per se and/or the use of suboptimal total doses of RT are detrimental; it is argued that these observations could be of relevance when designing combined modality protocols.

Radiation therapy for cancer of the piriform sinus. A failure analysis.

This paper analyzes the results of 109 piriform sinus (PS) cancers treated between 1973 and 1984 by surgery and/or external beam radiation therapy (EBRT) in a large comprehensive cancer center, and in particular tries to redefine the role of EBRT in the management of these tumors. At the time the policy was to start with EBRT to a dose of 40 Gy. A good response to a first series was to be continued by EBRT (RT-1); in case of poor responding tumors, the primary and neck were to be operated upon (RT-S). Poor responders unfit for S or those refusing S were also carried to a full course of EBRT (RT-2). The RT-S, RT-1, and RT-2 actuarial 5-year locoregional relapse-free survival (LR-RFS) and overall survival (OS) were 60%, 40%, and 20% and 40%, 30%, and 20%, respectively. In a multivariate Cox regression analysis the most important prognostic factor appeared to be N-stage, with hazard ratios of 1.16 (N1), 2.2 (N2), and 3.3 (N3). The RT-S treatment group fared best (hazard ratio 0.5). The risk of relapse for T3,4 was 1.3 times as high as opposed to T1,2. For stage I/II (19/21 treated by EBRT only), a LR-RFS and OS at 5 years of 60% and 40%, respectively, was observed. This analysis supports data for stage III/IV PS cancers to be treated by surgery combined with EBRT; in stage I/II there might be a role for EBRT alone. It is speculated that with further sophistication in RT-techniques, the locoregional control rates by EBRT alone could improve.

Radiation-induced fibrosarcoma of the tongue.

Three patients with a radiation-induced fibrosarcoma of the tongue are presented. All three patients had interstitial radiotherapy and tumour-induction by irradiation seems to be the most likely explanation for the tumour in these patients.

No demonstrated effect of pre-enucleation irradiation on survival of patients with uveal melanoma.

PURPOSE: To evaluate the hypothetical effect of pre-enucleation irradiation on survival of patients with uveal melanoma. METHODS: In a prospective study between 1978 and 1990, 145 patients with uveal melanoma were treated by irradiation in two fractions of 4 Gy before enucleation. A historical control group of 89 patients with uveal melanoma treated by enucleation alone was operated on between 1971 and 1990. Patients were followed up until December 1992 or until death. The mean follow-up period was 65 months in the irradiated group and 88 months in the control group. RESULTS: The preoperatively irradiated group of patients showed no significant improvement of the survival rate after 7 1/2 years (75.9%) compared with the control group (72.1%). Preoperative irradiation was not associated with survival (P = .93), as assessed by Cox proportional hazard analysis, adjusted for age, gender, tumor location, tumor size, cell type, and year of enucleation. Women in both the irradiated and control groups had a better prognosis than men (P = .002). CONCLUSION: Preoperative irradiation in this nonrandomized study had no effect on survival of patients with uveal melanoma.

[Reconstruction of the digestive tract using a free small intestine interpositional graft following total larynx-pharynx extirpation. Follow-up results]. / Reconstructie van de tractus digestivus met een vrij dunne-darminterponaat na totale larynx-farynxextirpatie, en follow-up-resultaten.

OBJECTIVE: To evaluate the results of pharyngo-oesophageal reconstruction after pharyngolaryngectomy using a free jejunal interposition graft. DESIGN: Retrospective study. SETTING: University Hospital Dijkzigt, Rotterdam. PATIENTS AND METHODS: Between 1982 and 1992, 59 selected patients (median age 63 years) undergoing laryngopharyngectomy for cancer had the continuity of the upper gastrointestinal tract restored by use of a free jejunal autograft. Twenty-three (36%) had had no previous treatment and received post-operative radiotherapy. Eight patients had laryngeal tumour recurrence after irradiation and in 28 (48%) patients pre-operative radiotherapy had been administered. RESULTS: Follow-up ranged from 1-127 months (mean 37 months). Graft necrosis secondary to vascular problems initially occurred in 5 patients. In four cases the jejunum was successfully replaced by another segment and in one patient a gastric transposition was performed. Fistulas occurred in eight patients of whom four required surgery. The mortality rate was 8.5%. After discharge 6 patients were reoperated on for dysphagia due to stricture formation. In four cases the distal or proximal anastomosis was revised and in the other two patients the graft was replaced, by another segment and by a colonic autograft, respectively. One year after operation 85% of the patients reported an adequate swallowing function and a normal oral intake. The overall 5-year survival rate of this selected group of patients was 42%, for those without primary lymph node involvement 66%. All patients with primary locoregional metastasis died within a period of 34 months after operation. CONCLUSION: Reconstruction of the upper alimentary tract after a laryngopharyngectomy with a free jejunal autograft appears to be a relatively safe procedure with an acceptable mortality and morbidity and, in patients without local lymph node involvement, good long-term results.

The influence of the extent of surgery on the neurological function and survival in malignant glioma. A retrospective analysis in 243 patients.

A retrospective analysis was performed on 66 patients with anaplastic astrocytoma (AA) and 177 patients with glioblastoma multiforme (GM). The prognostic importance of age, performance status, tumour location, extent of surgery and radiation treatment was studied. Radiation therapy gave a significant improvement in survival in both AA (p less than 0.003) and GM (p less than 0.002), but was given only to patients in a good neurological condition. Both younger age (p less than 0.003), and good preoperative performance status (p less than 0.002) were associated with a longer survival in AA, but not in GM. Extensive surgery was correlated with a better immediate postoperative performance, a lower one-month mortality rate and a longer survival, in both AA and GM. There was no relationship between preoperative neurological function status and the extent of surgery. Because of the retrospective nature of this study, the conclusion is that performing extensive surgery instead of limited surgery does not lead to more deterioration in postoperative neurological function.

Cancer of the supraglottic larynx with neck node metastasis treated by radiation therapy only. The revised 1987 UICC classification system as prognostic indicator.

In 1987, a thoroughly renewed TNM classification was published; the revision was a conjunct effort of the International Union Against Cancer (UICC) and American Joint Committee on Cancer (AJCC). With respect to the former UICC classification, a major change was introduced regarding the regional lymph node subcategories in head and neck cancer; that is compared to the 1978 edition the subjective subcategory of fixation was eliminated and size of the lymph node has become of paramount importance. To see whether the 1987 UICC classification system is indeed more predictive and discriminatory than the 1978 edition, we have analysed patients with supraglottic cancer with clinically detectable lymph node metastasis (T1-4, N+). All patients treated between 1965 and 1980 by radiation therapy only were staged according to both editions of the UICC classification system. From these data we conclude that the prognosis of patients with lymph nodal involvement indeed worsens from N1 to N3 when classified according to the 1987 edition; in contrast, no difference is seen between the N1, N2 or N3 subcategories when staged according to the 1978 classification rules.

Evaluation of treatment results of squamous cell carcinoma of the buccal mucosa.

Of the 49 patients with squamous cell carcinoma of the buccal mucosa referred to the Rotterdam Radio-Therapeutic Institute (RRTI) and Universital Hospital Dijkzigt Rotterdam (AZD) during 1970-1984, 31 patients had an advanced stage of disease, 21 patients had clinical evidence of lymph node metastasis. Forty patients were treated with curative intention. Treatment modalities were: radiation therapy, preoperative radiation followed by surgery, and primary surgery. Eighteen of the 40 patients (45%) developed a local tumor recurrence; nearly all recurrences occurred within 2 years. The incidence was equal in all treatment groups. Of the 22 patients with initial clinically negative neck, regional relapse occurred in 3 of the 14 patients, of whom the neck was not treated electively by radiation therapy; all three in combination with a local recurrence. None of the 8 patients with electively irradiated necks developed a regional relapse. Eight of the 18 patients with initial clinically enlarged lymph nodes treated either by radiotherapy or surgery, developed a regional relapse, 5 in combination with a local recurrence. Treatment of the clinically positive neck by neck dissection was superior to radiotherapy. Local recurrence carried a poor prognosis. Almost 70% died of their disease. The overall and corrected 5-year survival was 38% and 52% respectively.