International Journal of Radiation Oncology*Biology*Physics
Clinical investigation: head and neckCompliance to the prescribed dose and overall treatment time in five randomized clinical trials of altered fractionation in radiotherapy for head-and-neck carcinomas
Introduction
A substantial proportion of all patients treated by radiotherapy experience an unplanned protraction of overall treatment time 1, 2, 3, even in the case of controlled randomized clinical trials (4). The reasons for treatment protraction are varied but typically include the following: national holidays; machine breaks down; severe normal tissue reactions; intercurrent disease. For head-and-neck squamous cell carcinoma (HNSCC), protraction of overall treatment time leads to a reduction in the local control probability. This probably reflects accelerated tumor repopulation occurring during the extra treatment days (5). An extra radiation dose of approximately 0.6 Gy for each additional day of treatment (when using 2 Gy daily fractions) is required to keep the level of local control constant (6). The evidence for the detrimental effect of treatment protraction on tumor control comes from the analysis of both split-course treatment (7) and conventional treatment with unplanned gaps where the actual treatment duration and the prescribed duration were known (8). Detailed analysis of data collected from Manchester, Glasgow, Edinburgh, and Toronto have also shown similar values for the time factor for the planned prolonged continuous treatment times as for gap times (9). Recently, the Danish Head and Neck Cancer Study (DAHANCA) 6 and 7 trials, where overall treatment time was reduced by a week through increasing the weekly number of fractions from 5 to 6 while keeping the total dose fixed, resulted in an increased local tumor control and disease-free survival (10).
The fractionation IMPACT study is an intergroup analysis of individual patients’ data from five randomized trials on radiotherapy fractionation in HNSCC, which were performed over the period 1980–1995. One aim of the analysis is to advise on new improved fractionation schedules for specific subgroups of patients. The IMPACT project involves a series of detailed studies to estimate various radiobiologic parameters that characterize the response of head-and-neck carcinoma to treatment. One of these parameters is the overall treatment time. In the present study, the compliance to the prescribed overall treatment time in the IMPACT database is thoroughly examined.
Section snippets
IMPACT database
The trials included in IMPACT are the European Organization for Research and Treatment of Cancer (EORTC) 22791 (11), EORTC 22811 (12), EORTC 22851 (13), the trial from Princess Margaret Hospital (PMH) in Toronto (14), as well as a continuous hyperfractionated accelerated radiotherapy (CHART) head-and-neck trial from the UK (15).
EORTC 22791 compared a conventional fractionation arm (daily fractionation of 70 Gy in 35 fractions) with pure hyperfractionation of 80.5 Gy in 70 fractions over 7 weeks.
Results
Nine randomized cases failed to receive any radiotherapy but were included in the analysis, as they clearly contribute to the overall noncompliance in an intention-to-treat analysis. The time in excess of ideal was calculated for all the 2555 cases, with information on the overall treatment time. It ranged from −45 to 97 days, with an average of 3.9 days and a median of 2 days. Figure 1 shows the distribution of the time in excess of ideal. Only in 767 patients (30%) was there an agreement
Discussion
The current analysis showed that the compliance to the overall treatment time in five major randomized clinical trials of radiotherapy fractionation was less than satisfactory. More than 1 in 4 patients finished their radiotherapy in overall treatment times exceeding the ideal by more than 5 days.
Harari et al. (2) previously used the difference between ideal and actual treatment time to evaluate the compliance to the prescribed overall treatment time in both arms of the EORTC 22791. Similar
References (29)
- et al.
Evaluation of unplanned interruptions in radiotherapy treatment schedules
Int J Radiat Oncol Biol Phys
(1988) - et al.
Idealised versus realised overall treatment times
Int J Radiat Oncol Biol Phys
(1994) - et al.
Actual versus ideal treatment time in radiotherapy for head and neck cancerCatching up with the gaps
Int J Radiat Oncol Biol Phys
(1995) - et al.
The effect of overall treatment time on the outcome of definitive radiotherapy for localized prostate carcinomaThe Radiation Therapy Oncology Group 75-06 and 77-06 experience
Int J Radiat Oncol Biol Phys
(1991) - et al.
A modelled comparison of the effects of using different ways to compensate for missed treatment days in radiotherapy
Clin Oncol (R Coll Radiol)
(1996) - et al.
Local control of T3 carcinomas after accelerated fractionationA look at the gap
Int J Radiat Oncol Biol Phys
(1996) - et al.
Planned and unplanned gaps in radiotherapyThe importance of gap position and gap duration
Radiother Oncol
(1994) - et al.
Similar decreases in local tumor control are calculated for treatment protraction and for interruptions in the radiotherapy of carcinoma of the larynx in four centers
Int J Radiat Oncol Biol Phys
(1998) - et al.
Hyperfractionated versus conventional fractionation in oropharyngeal carcinomaFinal analysis of a randomized trial of the EORTC cooperative group of radiotherapy
Radiother Oncol
(1992) - et al.
The EORTC randomized trial on three fractions per day and misonidazole (trial 22811) in advanced head and neck cancerLong term results and side effects
Radiother Oncol
(1995)
Accelerated fractionation (AF) compared to conventional fractionation (CF) improves loco-regional control in the radiotherapy of advanced head and neck cancersResults of the EORTC 22851 randomized trial
Radiother Oncol
A randomised multicentre trial of CHART versus conventional radiotherapy in head and neck cancer
Radiother Oncol
Avoidance of treatment interruptionAn unrecognized benefit of accelerated radiotherapy in oropharyngeal carcinoma?
Int J Radiat Oncol Biol Phys
The effect of treatment duration in the local control of cervix cancer
Radiother Oncol
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