Adjuvant chemotherapy in stage III and IV squamous cell carcinoma of the head and neck

Initial combination drug regimen containing cisplatin in patients with stage III and IV head and neck cancer produced a high percentage of clinical response. This trial was initiated to assess the role of multimodality treatment (chemotherapy plus radiotherapy) versus chemotherapy alone. Ninety-six patients entered into this study; 80 patients were evaluable at time of analysis (Table I). Patients were randomized between chemotherapy and radiotherapy (group I) and chemotherapy alone (group II). The chemotherapy administered consisted of cisplatin, bleomycin and methotrexate and was given in 2 cycles over 35 days. Local radiotherapy followed. In group II 3 cycles of chemotherapy were given without radiotherapy. The overall tumour response after chemotherapy rose up to 75 per cent. After radiotherapy in group II the response rate sank to 59 per cent. In both regimes the remission duration was very short. Patients receiving only two cycles of chemotherapy do not have a statistically shorter survival than patients, who were treated by chemotherapy plus radiotherapy, or by a 3rd cycle of chemotherapy.     

Laryngeal preservation by treatment with induction chemotherapy and radiotherapy protocol for stage III & IV carcinoma larynx--results of a pilot study.

Total laryngectomy for advanced carcinoma of the larynx is effective but functionally disabling. In an effort at laryngeal preservation, 33 patients of stage III/IV carcinoma larynx were treated between 1987 and 1991 with induction chemotherapy followed by definitive radiation. Two chemotherapy protocols were administered. Group I patients received one to three cycles of cisplatin 100 mg/m2 (day 1), bleomycin 15 U/m2 (day 1), and 5-fluorouracil 1000 mg/m2/day (day 2 to 5) at three weekly intervals. This was then followed by radiotherapy. Group II received one to six weekly injections of single agent methotrexate 50 mg/m2 with or without leucocovorin rescue followed by radiotherapy. Any recurrence was salvaged by surgery. Midway through the study, Group II protocol was discontinued as the initial results were not comparable with Group I or standard treatment. The Group I protocol, however, yielded an initial locoregional control rate of 83.3 per cent With the addition of surgical salvage the locoregional control rate was 94.4 per cent and the control rate with laryngeal preservation was 88.8 per cent. The Kaplan-Meier probability of two years and five years disease-free survival was 81.9 per cent and 61.4 per cent respectively. For disease-free survival with laryngeal preservation the corresponding figures for two years and five years were 58.3 per cent and 41.7 per cent. The control group of 51 patients treated with radical surgery followed by radiotherapy yielded survival figures at two years and five years of 64.3 per cent and 57.2 per cent. The difference in the survival of Group I and the control group was not statistically significant (p value = 0.280). These initial results indicate that for stage III and for surgically resectable stage IV laryngeal carcinomas, a protocol of induction combination chemotherapy consisting of cisplatin, bleomycin and 5-fluorouracil followed by radiotherapy and combined with surgical salvage whenever required, can lead to comparable cure rates. In addition, a large proportion of patients are spared the morbidity of a total laryngectomy.     

Second malignancies in early stage laryngeal carcinoma patients treated with radiotherapy

A retrospective review of 240 patients with T1/T2 squamous cell carcinomas of the larynx was performed. Seventy-two per cent had glottic primaries, 27 per cent had supraglottic tumours and one per cent had subglottic disease. Sixty-nine per cent presented with T1 disease and 31 per cent had T2 staged tumours. All patients were treated with definitive radiotherapy between 1973 and 1997. With a median follow-up of 68 months, 68 patients (28 per cent) have developed 72 other cancers. Ten of 68 presented with synchronous primaries (15 per cent). Thirty per cent of glottic patients and 25 per cent of the supraglottic/subglottic patients developed second cancers. The most frequent second malignancy was lung cancer: 28/72 (39 per cent). Fifteen patients developed second head and neck cancers (21 per cent). Other second primary sites included oesophagus (eight), prostate (six), colorectal (five), breast (two) and others (eight). The median time from radiotherapy until the development of a second cancer was 31 months. The Kaplan-Meier survival estimate at five years was significantly less for those patients developing second cancers (55 per cent) compared to those not developing second malignancies (70 per cent), (p<0.05). The median survival from the development of a second cancer was 14 months. More died as a result of a second cancer (41 patients) than their primary laryngeal cancer (40 patients). Second cancers are common and deadly in patients with early stage laryngeal carcinoma.     

Neoadjuvant docetaxel and cisplatin chemotherapy followed by local irradiation is highly active on locoregionally advanced squamous cell carcinoma of the head and neck

The purpose of this study was to determine the treatment outcome of neoadjuvant docetaxel and cisplatin chemotherapy followed by local radiotherapy for chemotherapy-na?ve patients with locoregionally advanced squamous cell carcinoma of the head and neck. Thirty-seven patients with stage III or IV squamous cell carcinoma of the head and neck who received docetaxel and cisplatin regimen for a maximum of three cycles followed by radiation therapy were enrolled in this study. The overall response rate to the regimen was 91.9 per cent (34 of 37) (the complete remission rate was 48.6 per cent). The median time to treatment failure was 38 months (95 per cent confidence interval, 15-61 months). The four year estimated overall survival rates were 85.1 per cent. The most frequent moderate-to-severe toxicity was grade 3-4 neutropenia. The most common acute non-haematologic toxicities included anorexia, nausea and asthenia. Neoadjuvant docetaxel and cisplatin chemotherapy followed by radiotherapy is a feasible treatment strategy for patients with locoregionally advanced squamous cell carcinoma of the head and neck.     

Laryngeal carcinoma: five-year survival and patterns of failure in 202 consecutive patients treated with primary or post-operative radiotherapy in Hong Kong

OBJECTIVES: We aimed to conduct a retrospective analysis of patients treated with radiotherapy for laryngeal carcinoma at a single institution. METHODS: We analysed data from 202 consecutive patients treated with primary or post-operative radiotherapy for laryngeal carcinoma over a 10-year period. RESULTS: Sixty-nine patients had a T1, 65 a T2, 39 a T3 and 29 a T4 lesion. Forty-one patients were node-positive. The clinical stage was I in 67 patients, II in 53, III in 36 and IV in 46. Primary radiotherapy was given to 152 patients. The median follow up was 60 months. The five-year overall local control rate was 86 per cent, the ultimate local control rate was 93 per cent, the five-year regional control rate was 96 per cent, the five-year relapse-free survival rate was 82 per cent and the five-year overall survival rate was 69 per cent. CONCLUSIONS: Patients with laryngeal carcinoma treated with primary or post-operative radiotherapy had a five-year overall survival rate of 69 per cent.     

Squamous cell carcinoma of the nasal vestibule.

We reviewed 30 patients with squamous cell carcinoma of the nasal vestibule to present our experience of their management and to evaluate the prognostic factors that may influence their outcome. For T1 lesions radiotherapy remains the treatment of choice, because of the superior cosmetic result. Fifteen (68 per cent) out of 22 patients with T2 lesions were treated with primary radiotherapy. Surgery however, was eventually required in 16 (72 per cent) out of 22 patients, either as a primary treatment (seven patients) or as salvage surgery (nine patients). For the larger T3 lesions the treatment of choice is surgery followed by post-operative radiotherapy where appropriate. Regional nodal metastases at the time of presentation were a significant indicator of local and regional recurrence and of prognosis. The cause specific five-year survival for patients with an uninvolved neck (22 patients) was 100 per cent compared with 38 per cent for patients with nodal metastases at presentation (eight patients). Elective treatment for uninvolved regional nodes is not considered necessary.     

Pre-treatment anaemia alters outcome in early squamous cell carcinoma of the larynx treated by radical radiotherapy

The purpose of this study was to examine the effect of pre-treatment anaemia on tumour recurrence and survival in patients treated with primary radiotherapy for early squamous cell carcinoma of the larynx. A retrospective analysis of 117 patients with previously untreated T1N0M0 and T2N0M0 squamous cell carcinoma of the larynx was carried out. Patients were considered anaemic if their pre-treatment haemoglobin levels were below 13 g/dl in males and 11.5 g/dl in females. The influence of pre-treatment haemoglobin levels on local control and survival were evaluated using Cox proportional hazards regression models. Two- and five-year local-regional control estimates for anaemic patients were 58 per cent and 53 per cent respectively while patients with normal haemoglobin levels had two and five-year local-regional control rates of 90 per cent and 81 per cent respectively (p = 0.002). Multivariate Cox regression analysis showed pre-treatment haemoglobin significantly influencing recurrence-free survival (p = 0.0094). Patients with a low haemoglobin level prior to radiation therapy suffered higher levels of local-regional failure.     

Carcinoma of the maxillary antrum treated by pre-operative radiotherapy or radical radiotherapy alone.

The results of pre-operative radical radiotherapy and subsequent maxillary resection are reported in 54 consecutive patients with carcinoma of the maxillary antrum treated at The Royal London Hospital from 1965 to 1989. The actuarial two and five year survivals were 50.3 per cent and 38.5 per cent respectively. Patients with adenocarcinomas fared better when compared with squamous and undifferentiated carcinomas (log rank p = < 0.01). Undifferentiated carcinoma and involved regional lymph nodes were both very poor prognostic factors. In those patients who were either unfit for or refused maxillary resection, radical radiotherapy alone was still an effective treatment, with only a slight disadvantage in terms of local control and survival.     

Adult head and neck soft-tissue sarcomas

Adult soft tissue sarcomas of the head and neck are so rare that an accurate diagnosis and appropriate therapy are frequently delayed. A retrospective study of such patients seen at the University of Illinois over the last 15 years has helped to better characterize this disease entity. Patients with sarcoma of the neck, the most common anatomic location (37 per cent), had the highest 5-year disease-free survival rate (67 per cent). Fibrosarcoma was the most common histologic type (25 per cent). Aggressive fibromatosis patients experienced the longest mean survival time (93 months). The disease-free 2-year, 5-year, and 10-year survival rates were found to be 68, 54, and 28 per cent, respectively. Wide excision was the treatment of choice, with adjuvant radiotherapy or chemotherapy, or both, used in selected patients. The sarcomas of all long-term survivors were either well-differentiated or 5.0 cm or less in diameter. It is evident that aggressive therapy of adult head and neck sarcomas can provide good long-term results.     

A preliminary report on the combination of initial chemotherapy and radiotherapy for advanced head and neck cancer

A RETROSPECTIVE review of 45 patients with advanced squamous cell carcinoma of the head and neck treated by a combination of initial chemotherpy (Price and Hill Schedule A) followed by radiotherapy is presented. The regime produced excellent immediate palliation with a tumour control of 50 per cent, and a disease-free survival of 33 per cent at one year and 27 per cent at two years. Treatment morbidity was minimal in an aged patient group.     

Laryngeal preservation in cases of advanced laryngeal cancer treated with platinum based induction chemotherapy before local treatment.

In this study we analyse our preliminary results after treating 28 patients with locally advanced laryngeal cancer with platinum based induction chemotherapy followed by radiation therapy or surgery. The median age of our patients was 60 (46-75) years and median performance status was 80 (60-100). In 18 of the 28 patients locoregional treatment was radiation therapy with an overall response of 94.4 per cent. After a median follow-up of 26 (15-40) months 39.3 per cent of the whole group of patients are alive and disease-free and six (21.4 per cent) patients are alive and disease-free preserving their larynx. We conclude that although more extensive studies with large groups of patients and longer follow-up is needed to reach definite conclusions, it seems that platinum based induction chemotherapy can be used successfully in locally advanced laryngeal cancer followed by radiotherapy. In those cases who respond well, the patient's larynx is preserved without compromizing the overall survival.     

Non-Hodgkin's lymphoma of the tonsil. Experience of treatment over a 27-year period

Over the 27-year period from 1954-1981, 51 patients with non-Hodgkin's lymphoma arising in the tonsil were treated at the Regional Radiotherapy Centre, Mount Vernon Hospital. The original biopsy material was reviewed in each case and reclassified using the British National Lymphoma Investigation criteria. Grade 2 non-Hodgkin's lymphoma was reported in 80 per cent of cases. Ninety per cent of patients presented in stages IE or IIE and were treated with radical local radiotherapy. A 5-year survival of 51 per cent was achieved and a 5-year relapse-free survival of 35 per cent. Stage IE patients had a statistically significant survival advantage compared to stage IIE. Sixty-one per cent of patients relapsed, of whom 74 per cent died from active lymphoma. The abdomen was the most frequent site for relapse with involvement of both nodal and extranodal sites.     

A randomized trial of neoadjuvant vs concomitant chemotherapy vs radiotherapy alone in the treatment of stage IV head and neck squamous cell carcinoma

Summary Treatment results of irradiation as a single treatment for advanced stage IV unresectable head and neck cancer remains uniformly poor and apparently has not changed with the most recent improvements in oncological care. Despite several negative results of randomized studies, neoadjuvant or concomitant chemotherapy and radiotherapy seems to improve the number of complete responses and also the duration of disease-free survival. The present study was designed to determine the feasibility, potential risks and benefits of the two methods of combined treatment and radiotherapy alone on the management of advanced unresectable squamous cell carcinoma of the upper respiratory and digestive system. From 1983 to 1986, 90 patients entered the trial. Thirty patients were randomized to each study group: radiotherapy alone (70 Gy); neoadjuvant chemotherapy (vinblastine, mitomycin, cisplatin, and bleomycin) and radiotherapy; concomitant chemotherapy (cisplatin and bleomycin) and radiotherapy. An increased frequency of complete responses (33%) was seen in patients treated with the two different combinations of chemotherapy and irradiation compared to irradiation alone (10%). However, toxicity was more common in patients treated with the two modalities of combined treatment and there were no differences in overall survival rates (P = 0.706).     

Vertical partial laryngectomy: our results after treating 81 cases of T2 and T3 laryngeal carcinomas.

From 1976 to 1989, 81 patients with T2 and T3 laryngeal carcinomas were treated with vertical patrial laryngectomy at the University ENT Department of Thessaloniki, Greece. All patients were male with a median age of 56 years (33-71 years). Four patients had N1 lymph nodes. Ten patients received post-operative radiotherapy. Seventeen patients developed local recurrences or distant metastases. Mean follow-up was more than seven years. Absolute three-year survival was 94.6 per cent for 74 patients and absolute five-year survival was 89.6 per cent for 58 patients. Actuarial five-year survival of the whole group of 81 patients was 91 per cent calculated with the Kaplan-Meier method. Recurrence rate and survival of stage II and III patients are also discussed and compared using the log-rank test. We conclude that vertical partial laryngectomy is a very successful treatment selection for T2 glottic and false vocal cord carcinomas and for some selected T3 glottic lesions.     

Radiotherapy for T1 glottic carcinoma: impact of anterior commissure involvement

The clinical notes of all new patients with T(1) squamous cell carcinoma of the glottis seen in one head and neck cancer unit between 1989 and 1996 were reviewed. Fifty-three patients were treated with radical radiotherapy and of these 42 (79.2 per cent) had no loco-regional recurrence, after a median follow-up of seven years. Eleven (20.8 per cent) developed local recurrence and were treated with salvage surgery. Fourteen of the 53 (26.4 per cent) tumours involved the anterior commissure and eight of these 14 (57.1 per cent) developed recurrence, whereas only three of the 19 (15.8 per cent) tumours arising from the anterior half of the fold but not involving the anterior commissure had recurrence. None of the remaining tumours recurred. This difference is statistically significant (p<0.001). Anterior commissure involvement is a predictor of poor response to radiotherapy. This may be the result of understaging as none of the cases had computed tomography (CT) scans performed. Technical radiotherapy factors may also be important, although in all cases of anterior commissure involvement steps were taken to ensure adequate radiation dose to this region.     

Pharyngo-laryngo-oesophagectomy and gastric pull-up for post-cricoid and cervical oesophageal squamous cell carcinoma

Pharyngo-laryngo-oesophagectomy and gastric pull-up (PLOGP) is a complex and relatively uncommon procedure. The aim of this study is to analyse the results of PLOGP in patients with post-cricoid and cervical oesophageal squamous cell carcinomas. This study was a retrospective review of 26 patients (11 males + 15 females, mean age 63.5 years) who underwent PLOGP from 1988 to 1997. Eighteen (69 per cent) patients were staged as T(3) and eight (31 per cent) T(4). Eighteen (69 per cent) patients had N(0), seven (27 per cent) N(1) and one (four per cent) N(2) disease. Multiple primary tumours were recorded in three (11.5 per cent) patients. Four (15 per cent) patients had pre-operative radiotherapy with poor response and two (eight per cent) required emergency tracheotomy prior to surgery. Feeding jejunostomy was performed on 19 (73 per cent) and neck lymph node dissection in eight (31 per cent) patients. The mean duration of surgery was five hours (range 3.5 to 7.5) with a mean blood loss of 840 ml (range 160 to 1800), a mean stay in ICU of 4.2 days and hospital stay ranged from nine to 84 days (mean 34). Three (11.5 per cent) patients died (pneumonia - one, congestive heart failure - one, pulmonary embolus - one) in the early post-operative period. Eight (31 per cent) patients remain alive from 30 to 136 months (mean 58 months). Two (eight per cent) patients died with no evidence of disease. Thirteen (50 per cent) patients died of their disease between two to 51 months (mean 17.3 months) post-operatively. Kaplan-Meier survival estimates for one year was 65 per cent, for three years 35 per cent and for five years 26 per cent (see Figure 1). Median survival in the whole series was 18 months. Post-operative speech was with an electrolarynx in 16 (62 per cent). One patient (four per cent) used gastric speech and one patient (four per cent) used a Blom-Singer valve effectively. Five (19 per cent) patients had no speech post-operatively. All patients maintained oral feeding. Gastric transposition constitutes a safe and reliable method of restoring the continuity of the upper digestive tract following pharyngo-laryngo-oesophagectomy.     

Salvage surgery following irradiation with different fractionation regimes in the treatment of carcinoma of the laryngo pharynx: experience gained from a British Institute of Radiology study.

The 10-year follow-up of patients in a clinical trial involving the comparison of treatment by three fractions per week versus five fractions per week in radiotherapy of squamous carcinoma of the larynx and hypopharynx has now been completed. The trial involved an intake of 734 patients between 1966 and 1975. No statistically significant differences have been found between the two trial arms in terms of overall survival, age corrected survival, local recurrence, laryngectomy-free rates or effects on the normal tissues. Local recurrence was found in 320 of the 713 evaluable patients (45 per cent). Salvage laryngectomy was performed in 151 of the 320 patients with recurrence (47 per cent). Survival at 10 years for all node negative patients was 50 per cent in those patients without primary recurrence, compared with 40 per cent in those undergoing salvage laryngectomy.     

Radiotherapy in carcinoma of the middle ear and auditory canal.

In the decade 1961 to 1970, 89 patients with epidermoid carcinoma of the middle ear or auditory canal were seen. Seventy-eight were treated with 5-year survival figures of 22 per cent for middle ear, 42 per cent for auditory canal and 31 per cent for the total group. The majority of failures occurred within 18 months of diagnosis. The author suggests that radiotherapy and surgery must be combined to improve results. Eleven patients in the series developed second primary tumours.     

Analysis of 2167 head and neck cancer patients' management, treatment compliance and outcomes from a regional cancer centre, Delhi, India

Head and neck cancer care was analysed in 2167 unselected patients for management compliance and outcome. Median age was 55 years, with a male to female ratio of 5.5ratio1. Major sites were oropharynx (32.4 per cent), larynx (19.8 per cent), oral (16.6 per cent) and hypopharynx (12.9 per cent). Stage-wise distribution was I-II=8.9 per cent, III=20.6 per cent and IV=60.3 per cent and unstaged=10.2 per cent. Squamous cell carcinoma was the dominant histology for 90.9 per cent. Clinic-based cancer-directed treatment decisions were made for 1905 patients: curative intent in 53 per cent, palliative in 35 per cent and for the remaining 262 (12 per cent) supportive care. Overall, 1209 (56 per cent) patients complied with the prescribed treatments; 62 per cent, 54 per cent, and 35 per cent of curative, palliative and supportive care intent groups, respectively. Modalities were radiotherapy alone (64.6 per cent), combined surgery with irradiation (17.6 per cent), and chemoradiotherapy (11.2 per cent). Median follow-up periods were 17.5 and three months in curative and palliative groups respectively. Overall, 712 (33 per cent) cases received curative therapy, with three-year disease-specific survival of 49 per cent. Patient compliance was a major obstacle. The comparison of this series with the USA, Canada and Norway showed wide disparities in stage of presentation and survival.     

Squamous cell carcinoma of the maxillary sinus: A retrospective analysis of 36 cases.

36 patients with advanced squamous cell carcinomas of the maxillary sinuses formed the basis of this review. There were 16 T3 and 20 T4. Treatment consisted of radiotherapy alone in 21 cases and radiotherapy followed by systemic chemotherapy in 15 cases. The median survival for all analysed patients was 19 months and the 3-year and 5-year estimated survivals were 30% and 17%. The respective 3-and 5-year survival probabilities were 19% and 9% for patients treated with radiotherapy alone and 40% and 27% for patients treated with radiotherapy and chemotherapy (p= 0.01). Our findings seem to suggest that the addititon of systemic chemotherapy to radiotherapy may imporve overall survival in advanced squamous cell carcinomas of the maxillary sinuses.