Two-year results from a Swedish study on conventional versus accelerated radiotherapy in head and neck squamous cell carcinoma--the ARTSCAN study.

BACKGROUND AND PURPOSE: Studies on accelerated fractionation (AF) in head and neck cancer have shown increased local control and survival compared with conventional fractionation (CF), while others have been non-conclusive. In 1998 a national Swedish group decided to perform a randomised controlled clinical study of AF. MATERIALS AND METHODS: Patients with verified squamous cell carcinoma of the oral cavity, oropharynx, larynx (except glottic T1-T2, N0) and hypopharynx were included. Patients with prior chemotherapy or surgery were excluded. Patients were randomised to either CF (2Gy/day, 5days/week for 7 weeks, total dose 68Gy) or to AF (1.1Gy+2.0Gy/day, 5days/week for 4.5weeks, total dose 68Gy). An extensive quality assurance protocol was followed throughout the study. The primary end point was loco-regional tumour control (LRC) at two years after treatment. RESULTS: The study was closed in 2006 when 750 patients had been randomised. Eighty-three percent of the patients had stages III-IV disease. Forty eight percent had oropharyngeal, 21% laryngeal, 17% hypopharyngeal and 14% oral cancers. There were no significant differences regarding overall survival (OS) or LRC between the two regimens. The OS at two years was 68% for AF and 67% for CF. The corresponding figures for LRC were 71% and 67%, respectively. There was a trend towards improved LRC for oral cancers treated (p=0.07) and for large tumours (T3-T4) (p=0.07) treated with AF. The AF group had significantly worse acute reactions, while there was no significant increase in late effects. CONCLUSION: Overall the AF regimen did not prove to be more efficacious than CF. However, the trend towards improved results in AF for oral cancers needs to be further investigated.

Statistical methods for clinical verification of dose-response parameters related to esophageal stricture and AVM obliteration from radiotherapy.

The purpose of this work is to provide some statistical methods for evaluating the predictive strength of radiobiological models and the validity of dose-response parameters for tumour control and normal tissue complications. This is accomplished by associating the expected complication rates, which are calculated using different models, with the clinical follow-up records. These methods are applied to 77 patients who received radiation treatment for head and neck cancer and 85 patients who were treated for arteriovenous malformation (AVM). The three-dimensional dose distribution delivered to esophagus and AVM nidus and the clinical follow-up results were available for each patient. Dose-response parameters derived by a maximum likelihood fitting were used as a reference to evaluate their compatibility with the examined treatment methodologies. The impact of the parameter uncertainties on the dose-response curves is demonstrated. The clinical utilization of the radiobiological parameters is illustrated. The radiobiological models (relative seriality and linear Poisson) and the reference parameters are validated to prove their suitability in reproducing the treatment outcome pattern of the patient material studied (through the probability of finding a worse fit, area under the ROC curve and chi2 test). The analysis was carried out for the upper 5 cm of the esophagus (proximal esophagus) where all the strictures are formed, and the total volume of AVM. The estimated confidence intervals of the dose-response curves appear to have a significant supporting role on their clinical implementation and use.

Stricture of the proximal esophagus in head and neck carcinoma patients after radiotherapy.

BACKGROUND: It is well recognized that many patients with head and neck carcinoma have problems with food intake and malnutrition. The objective of the current study was to determine the clinical pattern of patients with nonneoplastic stricture of the upper esophagus after radiotherapy for head and neck carcinoma. METHODS: A retrospective chart study of 22 patients with stricture of the proximal esophagus diagnosed between 1993 and 1999 at Karolinska Hospital was performed. The dose volume histograms of the first 2 cm and 5 cm, respectively, of the proximal esophagus were calculated. RESULTS: Five of the patients (23%) had total obliteration. The first 2 cm of the esophagus received at least 60 grays (Gy) in > 80% of the volume. Radiation injury was not reported to occur at doses < 60 Gy. There was a correlation found between dysphagia during radiotherapy and the development of proximal esophageal stricture. Stricture was diagnosed 1-60 months (median, 6 months) after radiotherapy. In 18 patients, the stricture was treated with single or repeated endoscopic dilation. These treatments allowed a nearly normal diet in 78% of the patients. CONCLUSIONS: Stricture of the upper esophagus is one deglutition disorder that is reported to occur after radiotherapy for head and neck carcinoma. In the current study, the authors emphasize the importance of knowing the tolerance of the normal esophagus to irradiation as well as early diagnosis of stricture of the proximal esophagus because this condition may lead to physical and emotional distress.

Determination and clinical verification of dose-response parameters for esophageal stricture from head and neck radiotherapy.

The purpose of this work is to determine the parameters and evaluate the predictive strength of the relative seriality model. This is accomplished by associating the calculated complication rates with the clinical follow-up records. The study is based on 82 patients who received radiation treatment for head and neck cancer. For each patient the 3D dose distribution delivered to the esophagus and the clinical treatment outcome were available. Clinical symptoms and radiological findings were used to assess the manifestation of radiation-induced esophageal strictures. These data were introduced into a maximum likelihood fitting to calculate the best estimates of the parameters used by the relative seriality model (D50 = 68.4 Gy, gamma = 6.55, s = 0.22). The uncertainties of these parameters were also calculated and their individual influence on the dose-response curve was demonstrated. The best estimate of the parameters was applied to 58 patients of the study material and their esophageal stricture induction probabilities were calculated to illustrate the clinical utilization of the calculated parameters. The calculation of the biological effective dose (BED) appeared to be significantly sensitive to the applied fractionation correction for complex treatment plans. The relative seriality model was proved suitable in reproducing the treatment outcome pattern of the patient material studied (probability of finding a worse fit = 61.0%, the area under the ROC curve = 0.84 and chi2 test = 0.95). The analysis was carried out for the upper 5 cm of the esophagus (proximal esophagus) where all the strictures are formed. Radiation-induced strictures were found to have a strong volume dependence (low relative seriality). The uncertainties of the parameters appear to have a significant supporting role on the estimated dose-response curve.