Phase III randomised trial
Prevalence and peak incidence of acute and late normal tissue morbidity in the DAHANCA 6&7 randomised trial with accelerated radiotherapy for head and neck cancer

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Abstract

Background and purpose

The aim of this report was to describe the incidence and prevalence of acute and late morbidity in the DAHANCA 6&7 multicentre randomised trial with accelerated radiotherapy for squamous cell carcinoma of the head and neck.

Materials and methods

The DAHANCA 6&7 study included 1476 patients eligible for primary radiotherapy alone. Patients were randomised between five or six weekly fractions of conventional radiotherapy. The prescribed dose was 66–68 Gy in 33–34 fractions. All patients were seen weekly during treatment and at regular intervals after completion where detailed morbidity recording was done. Reports from 1468 patients were available for analysis of treatment related morbidity.

Results

Accelerated radiotherapy caused a significant (p < 0.05) increase in the peak incidence of: use of analgesics (53% vs. 65%), dysphagia (35% vs. 45%), mucosal oedema (52% vs. 59%), and mucositis (33% vs. 53%). All acute reactions were reversible and healed within three months after radiotherapy. Loss of taste, xerostomia, and acute skin reaction was not different between the two groups. For all late endpoints except fibrosis and atrophy a decline in prevalence was observed in the years after radiotherapy, there was no significant difference between randomisation arms in any of the late endpoints.

Conclusions

Six fractions per week, resulting in a one-week reduction in overall treatment time relative to conventional radiotherapy increased acute but not late morbidity. Since acceleration improves loco-regional tumour control, the schedule represents a significant improvement of the therapeutic ratio for head and neck radiotherapy and might be close to the maximal gain possible with accelerated fractionation alone.

Section snippets

Materials and methods

The study set-up has been described in detail previously [5]. In brief, the DAHANCA 6&7 multicentre trial randomised patients to receive either five or six weekly fractions of conventional radiotherapy. A total of 1485 patients with stage I–IV squamous cell carcinoma of the oral cavity, pharynx and larynx were randomised between January 1992 and December 1999, 1476 of these were eligible. DAHANCA 6 included 690 patients with tumours of the glottic larynx. DAHANCA 7 included 786 patients with

Results

Of the 1476 patients evaluable in the DAHANCA 6&7 trial 1229 (83%) were men and 247 (17%) were women. The medium age at randomisation was 62 years (range 20–88). The most frequent tumour localisation was glottic larynx (47%) followed by pharynx (29%). Tumour stages were 29%, 25%, 21% and 25% for stage I, II, III, IV, respectively. The distribution of patient and tumour characteristics was similar in the two groups at baseline and the adherence to radiotherapy was the same in the two groups, with

Discussion

The aim of this study was to analyse acute and late toxicity in the DAHANCA 6&7 study. The primary findings of the DAHANCA 6&7 study was that a moderate, one-week shortening of the overall treatment time applied to squamous cell carcinoma of the head and neck yielded better loco-regional control than conventional radiotherapy with same total dose and fraction size [5]. These findings have recently been confirmed in a similar trial sponsored by the International Atomic Energy Agency (IAEA) [6].

Conclusions

The moderate shortening of the overall treatment time with one week increased acute toxicity but all reactions were reversible. For all late endpoints except fibrosis and atrophy a decline in prevalence was observed in the years after radiotherapy, and there was no significant difference between randomisation arms in any of the late endpoints. Six fractions per week, resulting in a one-week reduction in overall treatment time relative to conventional radiotherapy represents a significant

Acknowledgments

Supported by the Danish Cancer Society, CIRRO – The Lundbeck Foundation Center for Interventional Research in Radiation Oncology, Dansk Kræftforskningsfond, and The Danish Council for Strategic Research.

References (35)

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On behalf of the DAHANCA group.

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