Hans Svensson

Dose response and latency for radiation-induced fibrosis, edema, and neuropathy in breast cancer patients.

PURPOSE To study the incidence of various forms of late normal tissue injuries to determine the latency and dose-response relationships. METHODS We retrospectively analyzed the clinical records of 150 breast cancer patients treated with radiotherapy after mastectomy in the mid to late 1960s. None of the patients had received chemotherapy as a part of their primary treatment. Radiotherapy was delivered to the parasternal, axillary, and supraclavicular lymph node regions. Almost all the patients continued to be checked at regular 3-month to 1-year intervals at our Oncology Department. Detailed records were available for the entire 34 years of the follow-up period. The patients were divided into 3 groups. The prescribed dose was either 11 x 4 Gy (treated with 60Co photons) or 11 x 4 Gy or 14-15 x 3 Gy (treated with both 60Co photons and electrons). The dose recalculation at the brachial plexus where the axillary and supraclavicular beams overlapped was performed in the early 1970s and expressed in cumulative radiation effect (CRE) units. It varied widely among the individual patients. The received dose has now been converted to biologic effective dose(3) units, and from that into the equivalent dose in 2-Gy fractions to plot the dose-response relationships. RESULTS We present a comparison of the latency and frequency of fibrosis, edema, brachial plexus neuropathy, and paralysis in the three different subgroups and the total group. Dose-response relationships are shown at 5, 10, and 30 years after irradiation. CONCLUSION The use of large daily fractions, combined with hotspots from overlapping fields, was the cause of the complications. Clear dose-response curves were seen for late radiation injuries. The incidence seen at 5 years did not represent the full spectrum of injuries. Doses that seem safe at 5 years can lead to serious complications later.

Timescale of evolution of late radiation injury after postoperative radiotherapy of breast cancer patients

PURPOSE To evaluate the incidence and prevalence of various signs of late morbidity, their time of appearance and pattern of progression during an observation period up to 34 years in breast cancer patients treated with postoperative radiation therapy after radical mastectomy. METHODS AND MATERIALS A group of 71 breast cancer patients received in 1963-1965 aggressive postoperative telecobalt therapy to the parasternal, axillary, and supraclavicular lymph node regions after total mastectomy and axillary clearance. None of the patients received chemotherapy either prior to, or after the irradiation as part of their primary treatment. The prescribed dose to the three lymph node regions was 44 Gy in 11 fractions. Only two of the three fields were treated per day. This total dose was given in 16-17 fractions over 3-4 weeks. Because of the overlap of the supraclavicular and axillary fields, the dose received by the brachial plexus was not the dose that was prescribed. A retrospective dose calculation showed that the total dose to the brachial plexus was 57 Gy, delivered as a complex combination of 1.8 Gy, 3.4 Gy, and 5.2 Gy fractions. This cohort of patients has now been followed to 34 years and the late side effects of the treatment evaluated and scored. RESULTS This series is unique in the literature. There is no comparable report of a detailed long-term follow-up in a homogeneously treated group of patients with such a high survival, especially among the younger women, where it is almost 50% at 30 years. This is the reason that they were able to develop some of the very slowly evolving injuries. There was progression of many of the late effects in the period between 5 and 34 years. The more serious morbidities have increased progressively over the whole 34-year follow-up period. Ninety-two percent of the long-term survivors have paralysis of their arm. Other neurological findings included unilateral vocal cord paralysis among 5% of the patients, who developed the disease after a median time of 19 years. All of them were left-sided, indicating a mediastinal involvement of the recurrent nerve. Local recurrence or the appearance of a new primary tumor infiltrating or causing pressure on the recurrent nerve were vigorously investigated and excluded as possible causes of these symptoms. CONCLUSION The greatest risk for all cancer patients is the inadequate treatment of their disease, because this is inevitably lethal. The aggressiveness of the therapy and the acceptable risk of complications must therefore be balanced against the risk of recurrence. The neuropathy seems to be closely linked to the development of fibrosis around the nerve trunks. The use of large daily fractions, combined with hot spots from overlapping fields contributed to the severity of the complications.

The ESTRO-QUALity assurance network (EQUAL)

BACKGROUND AND PURPOSE ESTRO has set up a Quality Assurance network (EQUAL) to check the dose delivered on axis in reference and non-reference conditions for external radiotherapy. The external audits covered by the network are based on measurements made with mailed thermoluminescent dosimeters (TLD). MATERIAL AND METHODS The TLD consist of LiF powder type DTL 937 read with a PCL 3 automatic TLD reader. The participating centres are instructed to deliver to the TLDs absorbed doses of 2 Gy calculated with the Treatment Planning System used in clinical routine. A maximum of three photon energies by participating centre have been checked with 10 on-axis points per beam. The quantities checked include the reference beam output, beam output variation with collimator opening, depth dose data and wedge transmission factor. RESULTS During the 1998 EQUAL programme 102 centres have been checked corresponding to 235 beams (28 (60)Co beams and 207 X-ray beams). About 3% of the outputs in reference conditions show deviations outside tolerance level (>+/-5%). A similar rate of deviation is noted for the percentage depth doses. A rate of deviation (6%) has been observed for the beam output variation (open and wedged beams) and the wedge transmission factor. The analysis of the results shows that for 24 out of the 102 centres, a deviation outside tolerance level is observed at least in one point, mainly for the large and rectangular field sizes and for the wedged beams. CONCLUSIONS The results for the EQUAL programme show the importance of a quality assurance network in Radiotherapy especially for the non reference points even if they are only located on the beam axis (In order to participate in this network, please contact EQUAL secretariat or download the attached application form ESTRO web site: Dr I.H. Ferreira or Mrs Aline Mechet, EQUAL-ESTRO, Physics Department, Institut Gustave-Roussy 39 Rue Camille Desmoulins, F-94805 Villejuif Cedex, France. e-mail:equal@igr.fr or http://www.estro.be/).

Brachial plexopathy after postoperative radiotherapy of breast cancer patients--a long-term follow-up.

In 1963-1965 a group of 71 patients operated on for breast cancer with total mastectomy and axillary clearance were given aggressive postoperative telecobalt therapy to the axillary, supraclavicular and parasternal lymph node regions. The prescribed dose to these lymph node regions was 44 Gy in 11 fractions. Only two of the three fields were treated per day. Retrospective dose calculations showed that the total dose in the brachial plexus from the axillary and supraclavicular fields was c. 57 Gy in 16-17 fractions over 3-4 weeks. After a few years, symptoms and signs of brachial plexus injury appeared in many patients, which was reported in some early papers. The cohort has now been followed-up to 34 years. As expected, there was progression of both prevalence and severity of the late effects between 5 and 34 years and 11 of 12 patients who are still alive have paralysis of their arms. The neuropathy seems to be closely linked to fibrosis around the nerve trunks. The use of large daily fractions, in some cases combined with hot spots from overlapping fields, was certainly the cause of the complication.

Photon beam characteristics on the MM50 racetrack microtron and a new approach for beam quality determination

The photon beams of the MM50 racetrack microtron have special characteristics which make them more suitable than conventional photon beams for precision radiation therapy with good dosimetric control. The beam flattening is obtained by the scanning of an elementary beam instead of using a flattening filter. This will give a number of advantages such as the possibility to optimize field flattening to individual field forms and field sizes. The radiation quality is the same across the whole beam, which gives smaller changes in dose profiles with depth and also makes it easier to perform careful dose planning. Beam collimation is mainly performed by a multileaf collimator and the special design of the treatment head gives nearly ideal characteristics for dose determination in an arbitrary point in the treatment fields. The output factor has been shown to depend almost solely on scattering within the treatment field. The conventional methods for beam quality characterization have been found less suitable at high energies and a new method based on HVL measurements in water is proposed.

Electron beam characteristics of the 50-MeV racetrack microtron

Electron beams in the MM50 racetrack microtron are generated by computer controlled scanning of a well-focused electron pencil beam. The treatment head is optimized to give a minimum of scatter between the source position and the collimator plane by a general minimization of all scattering material in the beam and by replacement of the air in the treatment head by helium, which has a much lower linear scattering power than air. A double-focused multileaf collimator with a 31-cm collimator to patient distance is used both for electron and photon collimation. In general, no extra electron collimation is needed for the standard SSD of 100 cm. To make irregular field collimation at a distance this far from the patient possible, a number of requirements have to be fulfilled regarding the virtual source position and the spatial and angular distribution of the initial electron beam. The virtual source position has been found to be at a fixed position for different irradiation parameters. This is important for the use of the light field in electron beam treatment but also for achieving a high degree of accuracy in the dosimetry. Scatter from the multileaf collimator has not been found to give any significant contribution to the radiation field or to the monitor output factor of the MM50. Experimental dose distribution data on the MM50 have been compared to data both from other types of treatment units and to Monte Carlo simulations.

Specification of electron beam quality from the central‐axis depth absorbed‐dose distribution

The distribution of absorbed dose in a medium irradiated by broad electron beam has been analyzed from physical and therapeutic points of view. A number of parameters which describe the beam quality and the shape of the absorbed-dose distribution along the central axis are defined. Several comparisons are made of the values of these parameters obtained from measurements made on different therapy accelerators and from theoretically calculated dose distributions for monoenergetic and monodirectional beams. It is found that the major part of the observed differences between experimental and theoretical results can be attributed to the energy distribution of the accelerator beam and to processes in the scattering material, such as energy straggling and the production of secondary electrons and photons. A simple expression is derived relating the slower falloff in dose found for most accelerator beams to the large energy spread found in these beams. Further, a semiempirical relationship is found which makes it possible to obtain the mean electron energy at the phantom surface from the depth where the absorbed dose has decreased to 50% of its maximum value along the central axis.

Quality assurance in radiotherapy: the importance of medical physics staffing levels. Recommendations from an ESTRO/EFOMP joint task group

The safe application of ionising radiation for diagnosis and therapy requires a high level of knowledge of the underlying processes and of quality assurance. Sophisticated modern equipment can be used effectively for complicated diagnostic and therapeutic techniques only with adequate physics support. In the light of recent analyses and recommendations by national and international societies a joint working group of representatives from ESTRO (European Society for Therapeutic Radiology and Oncology) and from EFOMP (European Federation of Organisations for Medical Physics) was set up to assess the necessary staffing levels for physics support to radiotherapy. The method used to assess the staffing levels, the resulting recommendations and examples of their practical application are described.

Recent Advances in Electron and Photon Dosimetry

The possibilities to improve radiation therapy have increased during recent years, not only because of the use of new or improved tools such as computed tomography and dose planning, and high-quality electron and photon beams from therapy accelerators, but also because of increased knowledge in fields like clinical radiation biology about dose fractionation and dose-response relations. These new developments increase the demand for accurate dosimetry as illustrated by the following examples.

Quality assurance in radiation therapy: physical aspects.

The present status of the quality assurance work regarding the physical aspects in radiation treatments is discussed. In particular, the situation in Europe is surveyed. An analysis of the errors in the delivered absorbed dose to a specified point in the irradiated patient shows that the uncertainty, to approximately the same degree, depends on the dose distribution determination, the dose planning and the patient irradiation. Following the procedure generally in use, the overall uncertainty will be about 8%. The random uncertainties are estimated as one standard deviation and non-random uncertainties to corresponding degree of uncertainty. It is argued that this level must be improved. Furthermore, dose intercomparisons show that in reality much larger errors occur in clinical practice. Different means to improve this situation are discussed.