Quantification of late complications after radiation therapy
Introduction
At the Department of Radiotherapy of the University of Hamburg, a subgroup of patients with rectal carcinoma was subjected to an unconventional treatment schedule from 1986 to 1990. High total doses were applied pre- and postoperatively to large volumes using high doses/fraction, and short time intervals between fractions. A considerable proportion of these patients developed severe late complications. This led to litigation, which has not yet been finally resolved. The authors of this study were not involved in the radiation treatments, but evaluated the data for scientific purposes [39]. The high rate of late morbidity observed in this group of patients made it possible to analyze in detail the time course of the incidence of late complications occurring after irradiation. For comparison, a large number of data sets was collected from the literature and analyzed in the same way.
Section snippets
Treatment
Treatment of rectal carcinoma consisted of preoperative irradiation, radical surgery of tumor, and postoperative irradiation using photons (16 MV) or electrons (42 MeV). Preoperative treatment was given by an opposed AP and PA pair of fields in four sessions of 5 Gy each. Most patients received two fractions of 5 Gy/day on 2 successive days. The median irradiated volume was 5.8 l (range, 4–14 l). Most patients underwent surgery the day after the last preoperative irradiation. Twenty-five
Complications after sandwich therapy for rectal cancer
Fig. 1 shows complications following sandwich therapy for rectal cancer. The percentage of patients without late complications in the corresponding organ is plotted in a semilogarithmic scale as a function of time after the start of radiation therapy. The data were taken from the actuarial incidence curves published previously (Fig. 1 in Ref. [39]). The straight lines drawn were calculated by fitting the data to Eq. (1); each point was weighed in inverse proportion to its standard error
Data from the literature
Due to the far-reaching conclusions that might be drawn from our results, numerous data sets from the literature were reanalyzed to address the question of whether the exponential kinetics reported here might be a peculiarity of the unconventional sandwich treatment applied. In particular, papers reporting on relatively large numbers of late effects were analyzed, since time kinetics may not be derived with sufficient accuracy, when late morbidity occurred in very few of the patients treated.
The annual incidence rate pa
The main innovation of the present paper appears to be the introduction of the parameter pa describing what percentage of the patients at risk in a given year after radiotherapy develop a late effect of a given grade in a specific organ or organ group. In this respect, pa is an objective measure for describing the occurrence of late morbidity in quantitative terms and — equally important — in a comprehensible way. Since pa contains information about frequency and time of occurrence of late
Conclusions
Three different types of kinetics for the occurrence of late morbidity following radiotherapy were identified. For each type of kinetics, provided that the dose distribution is not too heterogeneous, the incidence of late effects, even after many years, occurs at exponential or approximately exponential kinetics that may be quantified by pa, the percentage of patients at risk of developing late morbidity/year. That means that the annual rate of the incidence of complications/patient at risk
Acknowledgements
The authors thank the Erich and Gertrud Roggenbuck Foundation, Hamburg, for funding the present study.
References (44)
- et al.
Fractionation sensitivity and latency of telangiectasia after postmastectomy radiotherapy: a graded-response analysis
Radiother Oncol
(1990) - et al.
Repair halftimes estimated from observations of treatment-related morbidity after CHART or conventional radiotherapy in head and neck cancer
Radiother Oncol
(1999) - et al.
Estimation of the incidence of late bladder and rectum complications after high-dose (70–78 Gy) conformal radiotherapy for prostate cancer, using dose–volume histograms
Int J Radiat Oncol Biol Phys
(1998) - et al.
Comparison of radiation side-effects of conformal and conventional radiotherapy in prostate cancer: a randomised trial
Lancet
(1999) - et al.
Do acute mucosal reactions lead to consequential late reactions in patients with head and neck cancer?
Radiother Oncol
(1999) - et al.
A randomised multicentre trial of CHART versus conventional radiotherapy in head and neck cancer
Radiother Oncol
(1997) - et al.
An analysis of the radiation related morbidity observed in a randomized trial of neutron therapy for bladder cancer
Int J Radiat Oncol Biol Phys
(1986) - et al.
Time course and incidence of late complications in patients treated with radiation therapy for FIGO stage IB carcinoma of the uterine cervix
Int J Radiat Oncol Biol Phys
(1995) - et al.
Tolerance of normal tissue to therapeutic irradiation
Int J Radiat Oncol Biol Phys
(1991) - et al.
Radiation late effects in children treated for orbital rhabdomyosarcoma
Radiother Oncol
(1999)
Late effects of hyperfractionated radiotherapy for advanced head and neck cancer: long-term follow-up results of RTOG 83-13
Int J Radiat Oncol Biol Phys
Rectal complications associated with transperineal interstitial brachytherapy for prostate cancer
Int J Radiat Oncol Biol Phys
Long-term cardiac morbidity and mortality in a randomized trial of pre- and postoperative radiation therapy versus surgery alone in primary breast cancer
Radiother Oncol
Analysis of complications in a prospective randomized trial comparing two brachytherapy low dose rates in cervical carcinoma
Int J Radiat Oncol Biol Phys
A ten year follow-up of 682 patients treated for prostate cancer with radiation therapy in the United States
Int J Radiat Oncol Biol Phys
Myelopathy following radiotherapy of bronchial carcinoma with large single fractions: a retrospective study
Int J Radiat Oncol Biol Phys
Diabetes mellitus: a predictor for late radiation morbidity
Int J Radiat Oncol Biol Phys
Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma: final analysis of a randomized trial of the EORTC cooperative group of radiotherapy
Radiother Oncol
Accelerated fractionation (AF) compared to conventional fractionation (CF) improves loco-regional control in the radiotherapy of advanced head and neck cancers: results of the EORTC 22851 randomized trial
Radiother Oncol
Late complications after postoperative radiotherapy in endometrial cancer: analysis of 317 consecutive cases with application of linear–quadratic model
Int J Radiat Oncol Biol Phys
Timescale of evolution of late radiation injury after postoperative radiotherapy of breast cancer patients
Int J Radiat Oncol Biol Phys
Effect of time, dose, and fractionation on temporal lobe necrosis following radiotherapy for nasopharyngeal carcinoma
Int J Radiat Oncol Biol Phys
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Former affiliation: Department of Radiotherapy, Department of Clinical Oncology, St. Mary's Hospital, Portsmouth Oncology Centre, Portsmouth, UK.