No abstract

Patients with anaplastic thyroid carcinoma can rarely be cured, but every effort should be made to prevent death due to suffocation. Between 1984 and 1999, 55 consecutive patients with anaplastic thyroid carcinoma were prospectively treated according to a combined regimen consisting of hyperfractionated radiotherapy, doxorubicin, and when feasible surgery. Radiotherapy was carried out for 5 days a week. The daily fraction until 1988 was 1.0 Gy×2 (A) and 1989–92 1.3 Gy×2 (B) . Thereafter 1.6 Gy×2 (C) was administered. Radiotherapy was administered to a total target dose of 46 Gy; of which 30 Gy was administered preoperatively in the first two protocols (A and B), while the whole dose was given preoperatively in the third protocol (C). The therapy was otherwise identical. Twenty mg doxorubicin was administered intravenously weekly. Surgery was possible in 40 patients. No patient failed to complete the protocol due to toxicity. In only 13 cases (24%) was death attributed to local failure. Five patients (9%) ‘had a survival’ exceeding 2 years. No signs of local recurrence were seen in 33 patients (60%); 5 out of 16 patients in Protocol A, 11 out of 17 patients in Protocol B, 17 out of 22 patients in Protocol C ( P =0.017). In the 40 patients undergoing additional surgery, no signs of local recurrence were seen in 5 out of 9 patients, 11 out of 14 patients and 17 out of 17 patients, respectively ( P =0.005). British Journal of Cancer (2002) 86 , 1848–1853. doi: 10.1038/sj.bjc.6600361 www.bjcancer.com © 2002 Cancer Research UK

Trismus, a well-known sequelae after treatment of head and neck cancer, decreases a patient's oral function and quality of life. The main objectives of this study were to: 1) investigate the long-term prevalence of radiation-induced trismus in patients treated for head and neck cancer according to two different fractionation schedules; and 2) model a dose-response relationship for trismus. Material and methods. Patients were recruited from the Swedish ARTSCAN trial, a prospective randomised multicentre study comparing conventional and accelerated fractionation. A total of 124 patients agreed to a clinical ENT examination 21-127 months (median 66 months) after beginning radiation therapy. Trismus-related scores were assessed using the EORTC H&N35 Quality of Life questionnaire. The TheraBite ® range of motion scale was used to measure maximal interincisal distance. The dose-response relationship for structures important for mastication and the temporomandibular joints was investigated by normal tissue complication probability modelling. results. No significant differences in patient-reported trismus or maximal interincisal distance were found between the two trial arms. Patient-reported moderate to high scores regarding trismus increased from 3% at the start of radiation therapy to 25% at the long-term follow-up. Maximal interincisal distance correlated significantly with patient-reported scores of trismus. The best dose-response fit to the endpoint data was found for the dose to the ipsilateral masseter. conclusions. Trismus is a persistent complication after radiotherapy with 3D-conformal radiation therapy. We found no difference between the severity and prevalence of trismus between conventional and accelerated fractionation, but a significant correlation between the absorbed dose to the mastication structures and opening of the mouth. Further prospective studies may determine whether a reduced dose to structures important for mastication using intensitymodulated radiation therapy will reduce problems with trismus.

Summary Survival in squamous cell carcinoma of the head and neck (HNSCC) was compared with overexpression and mutation of the p53 gene. Archival tissue from 77 tumours was analysed for protein expression using immunohistochemistry (IHC) with the monoclonal antibody Do-7, and for the presence of mutation in exons 5-8 using single-stranded conformation polymorphism (SSCP), followed (4/19) or low protein expression (4/33). Fifty-eight patients were eligible for survival analysis. There was a strong correlation between p53 mutation and cause-specific survival; median survival among mutated cases was 12.5 months compared with >160 months among non-mutated patients (P < 0.005). There was no correlation between p53 overexpression and survival. The results suggest that p53 mutation status is an important prognostic factor in HNSCC, and that IHC analysis of protein overexpression is an inadequate measure of gene mutation in these tumours.

Background. Anaplastic carcinoma of the thyroid (ACT) rarely can be cured, but every effort should be made to improve prognosis and, above all, prevent death due to suffocation or large local tumor ulceration. Methods. From 1984 to 1992, 33 consecutive patients with ACT were treated prospectively according to a combined treatment program consisting of hyperfractionated radiotherapy, doxorubicin, and debulking surgery. Preoperative radiotherapy was administered to a target dose of 30 Gy and postoperatively to a total dose of 46 Gy. Radiotherapy was performed 5 days a week. The daily fraction was 1.0 Gy × 2 until 1988, after which it was 1.3 Gy × 2. Otherwise, the therapy remained unchanged. Twenty milligrams of doxorubicin were administered intravenously per week. Debulking surgery was possible in 23 patients (70%). Results. No patient failed to complete the protocol because of toxicity. There were no signs of local recurrence in 16 patients (48%). In only eight patients (24%) was death attributed to local failure. In four patients, survival with no evidence of disease exceeded 2 years. Improvement in local tumor control was marginally significant (P = 0.08) in the 17 patients treated in the latter part of the study, with no sign of local disease in 11 patients and deaths due to local failure in only 2 patients. The improved local control could not be attributed to any differences between the two series. Conclusion. Combination modality treatment of ACT is feasible and effective despite the patients' advanced age and locally advanced disease. There was a tendency for local control to be improved after accelerated radiotherapy.