Anders Montelius

Acute lumbosacral plexopathy during and after preoperative radiotherapy of rectal adenocarcinoma

The benefit of preoperative radiotherapy of adenocarcinoma of the rectum with respect to a reduced local recurrence rate and an improved survival should be weighed against adverse effects. For 14 years a three-beam, isocentric technique was employed at our hospital to deliver five fractions (5.0 or 5.1 Gy), over 5 or 7 days preoperatively, to patients with rectal cancer which was considered primarily resectable. The adverse effects of the radiotherapy were few, but acute pain and subacute neurological symptoms and signs did occur. An apparent increase in the frequency of these symptoms/signs was noted during 1993. The pain and neurological symptoms are described in case reports and the individual treatments are reviewed. The three-beam technique was analyzed in detail with individual, CT-based, three-dimensional dose-planning and dose distributions in the vicinity of the lumbar nerve plexus are presented. The major result of this analysis showed that technical errors could be excluded, that human errors were unlikely, and that the culprit probably was an unexpected sensitivity to marginal changes in the daily dose and unknown or unexpected radiosensitizing effects of concurrent diseases or medication.

Potential advantages of protons over conventional radiation beams for paraspinal tumours

BACKGROUND AND PURPOSE Conformal treatment planning with megavoltage X-rays and protons was studied in an attempt to determine if there are advantage of boost therapy with protons instead of X-rays for a patient with a tumour growing around the cervical spinal cord. MATERIALS AND METHODS A patient with a Ewing sarcoma was selected for the model study. The proton boost plan was realised with a six beam patched technique. Several X-ray boost techniques were planned, some not yet practically realisable. The techniques giving the best dose distributions and the best tumour control probabilities in the absence of significant late toxicity were looked for. The boost techniques were added to two large lateral X-ray beams covering the planning target volume (PTV) and the main risk organ, the spinal cord. The evaluation was made with two biological models, i.e. the tumour control probability (TCP) model, proposed by Webb and Nahum (Webb, S. and Nahum, A.E. A model for calculating tumour control probability in radiotherapy including the effect of inhomogeneous distributions of dose and clonogenic cell density. Phys. Med. Biol. 38: 653-666, 1993), and the normal tissue complication probability (NTCP) model, first derived by Lyman (Lyman, J.T. Complication probability as assessed from dose-volume histograms. Radiat. Res. 104: s13-s19, 1985). RESULTS The comparison showed small but clear advantages of protons for the boost. At 1% NTCP in the spinal cord, the calculated TCP was on average 5% higher. However, depending on the values of the parameters chosen in the biological models, the gain for protons varied from 0-10%. The smallest gains were seen in radiosensitive tumours for which the TCP was close to 100% with any of the techniques and in radioresistant tumours for which neither technique resulted in any appreciable probability of local cure. CONCLUSION Protons appear to have therapeutic advantages over conventional radiotherapy in tumours with relatively high radiosensitivity situated close to the spinal cord.

Implementation of pencil kernel and depth penetration algorithms for treatment planning of proton beams

The implementation of two algorithms for calculating dose distributions for radiation therapy treatment planning of intermediate energy proton beams is described. A pencil kernel algorithm and a depth penetration algorithm have been incorporated into a commercial three dimensional treatment planning system (Helax-TMS, Helax AB, Sweden) to allow conformal planning techniques using irregularly shaped fields, proton range modulation, range modification and dose calculation for non-coplanar beams. The pencil kernel algorithm is developed from the Fermi Eyges formalism and Molière multiple-scattering theory with range straggling corrections applied. The depth penetration algorithm is based on the energy loss in the continuous slowing down approximation with simple correction factors applied to the beam penumbra region and has been implemented for fast, interactive treatment planning. Modelling of the effects of air gaps and range modifying device thickness and position are implicit to both algorithms. Measured and calculated dose values are compared for a therapeutic proton beam in both homogeneous and heterogeneous phantoms of varying complexity. Both algorithms model the beam penumbra as a function of depth in a homogeneous phantom with acceptable accuracy. Results show that the pencil kernel algorithm is required for modelling the dose perturbation effects from scattering in heterogeneous media.

Node-positive left-sided breast cancer patients after breast-conserving surgery : potential outcomes of radiotherapy modalities and techniques

PURPOSE To determine how much proton and intensity modulated photon radiotherapy (IMRT) can improve treatment results of node-positive left-sided breast cancer compared to conventional radiation qualities (X-rays and electrons) after breast-conserving surgery in terms of lower complication risks for cardiac mortality and radiation pneumonitis. METHODS AND MATERIAL For each of 11 patient studies, one proton plan, one IMRT, and two conventional (tangential and patched) plans were calculated using a three-dimensional treatment-planning system, Helax-TMS(). The evaluation of the different treatment plans was made by applying the normal tissue complication probability model (NTCP) proposed by Källman (also denoted the relative seriality model) on the dose distributions in terms of dose-volume histograms. The organs at risk are the spinal cord, the left lung, the heart, and the non-critical normal tissues (including the right breast). RESULTS The comparison demonstrated that the proton treatment plans provide significantly lower NTCP values for the heart and lung when compared to conventional radiation qualities including IMRT for all 11 patients. At a prescribed dose of 50 Gy in the PTV, the calculated mean NTCP value for the patients decreased, on the average, from 14.7 to 0.6% for the lung (radiation pneumonitis) for the proton plans compared with the best plan using conventional radiation qualities. The corresponding figures for the heart (cardiac mortality) were from 2.1 to 0.5%. The figures for cardiac mortality for IMRT, tangential technique and the patched technique were 2.2, 6.7, and 2.1%, respectively. CONCLUSIONS Protons appear to have major advantages in terms of lower complication risks when compared with treatments using conventional radiation qualities for treating node-positive left-sided breast cancer after breast-conserving surgery.

Comparative treatment planning between proton and X-ray therapy in esophageal cancer

PURPOSE Conformal treatment planning with megavoltage x-rays and protons for five patients with esophageal cancer has been studied in an attempt to determine if there are advantages of using protons instead of x-rays. METHODS AND MATERIALS For each of the five patients, two different proton plans, one x-ray plan, and one mixed plan with x-rays and protons were made. A three-dimensional treatment planning system, TMS, was used. The evaluation of the different plans was made by applying the tumor control probability (TCP) model proposed by Nahum and Webb and the normal tissue complication (NTCP) model proposed by Lyman on the dose distributions in terms of dose-volume histograms (DVHs). RESULTS The comparison shows advantages of using protons instead of x-rays for all five patients. The dose-limiting organs at risk are the spinal cord, the lungs, and the heart, but the proton plans also spare the kidneys better than the x-ray plan does. At 5% NTCP in any risk organ, the calculated mean TCP value for the five patients is increased by an average of 20%-units (from 2 to 23%-units) with the best proton plan compared with x-rays only. However, if we assume maximally a 1% risk in the spinal cord and a total NTCP for the two lungs of 100%, the mean TCP value for the five patients is increased from 6 to 49% with the best proton plan compared with x-rays only. The corresponding figure for the mixed plan is 27%. These gains are relatively insensitive to variations within reasonable limits in the biological parameters. CONCLUSIONS Protons appear to have clear therapeutic advantages over conventional external radiotherapy when treating esophageal carcinoma.

Dose calculations in proton beams: range straggling corrections and energy scaling

Three-dimensional dose planning systems employing accurate proton transport algorithms are essential for calculating absorbed dose distributions in proton therapy. In this paper, a pencil beam algorithm for the transport of protons in materials of interest for radiation therapy is developed. The Fermi-Eyges multiple-scattering theory is used to derive transport equations for calculating proton fluence and absorbed dose distributions. The multiple-scattering theory of Molière is used to predict mean square scattering angles and to develop an expression for calculating the root mean square (RMS) radial spread of a proton pencil beam, as a function of depth, in an arbitrary scattering material. A correction factor is suggested to account for the decrease in the radial spread at the end of the range due to range straggling. The effects of neglecting large-angle scattering events and the possibility of incorporating such events into the pencil beam algorithm are discussed. An energy scaling technique for determining the water-equivalent surface energy at a given depth in a heterogeneous scattering medium is developed. The water-equivalent energy, giving the same Molière scattering parameter B in water, is determined and the 1/e angle in water is scaled to the appropriate width in the scattering material. By using stored analytically or Monte Carlo calculated pencil beam distributions in water, the large-angle single-scattering events may be incorporated by approximating the scattering in an arbitrary material by the scattering in water for protons of the appropriate water-equivalent surface energy.

A general solution to charged particle beam flattening using an optimized dual-scattering-foil technique, with application to proton therapy beams

This paper describes a dual-scattering-foil technique for flattening of radiotherapeutic charged particle beams. A theory for optimization of shapes and thicknesses of the scattering foils is presented. The result is a universal optimal secondary-scatterer profile, which can be adapted to any charged particle beam by a simple scaling procedure. The calculation of the mean square scattering angle of the beam after passing through the scattering foils is done using the generalized Fermi-Eyges model for charged particle transport. It is shown that the fluence profile in the plane of interest can be made flat to better than 1% inside a predefined beam radius provided the shaped secondary scatterer has the universal radial thickness profile. The thicknesses of the two foils are optimized to minimize the total energy loss. The theory has been tested experimentally in an 180 MeV clinical proton beam. The measured distributions agree well with the calculations.

Comparative treatment planning between proton and X-ray therapy in locally advanced rectal cancer.

BACKGROUND AND PURPOSE Conformal treatment planning with megavoltage X-rays and protons for medically inoperable patients with a large rectal cancer has been studied in an attempt to determine if there are advantages of using protons instead of X-rays. MATERIAL AND METHODS Three dose plans were made for each of the six patients: one proton plan, including three beams covering the primary tumour and adjacent lymph nodes and three boost beams covering the primary tumour: one X-ray plan, eight beams including a boost with four beams and one mixed plan with four X-ray beams and a boost with three proton beams. A three dimensional treatment-planning systems, TMS, was used. The evaluation of the different plans was made by applying the biological models TCP and NTCP on the dose distributions in terms of dose-volume histograms. RESULTS The comparison shows advantages of using protons instead of X-rays for all six patients, but in three of them, the advantage is only marginal. The dose-limiting organ at risk is the small bowel, but the proton plan and the mixed plan also spare the bladder and the femoral heads better. At 5% NTCP in any risk organ, the calculated mean TCP value for the six patients is increased by 14%-units with the proton plan and 8%-units with the mixed plan compared to X-rays only. CONCLUSIONS Proton beam therapy has potential advantages when treating medically inoperable patients with a large rectal cancer over conventional X-ray therapy. Since the benefits are comparatively small, although clinically worthwhile, large randomised studies are needed.

Radiotherapy of breast cancer after breast-conserving surgery: an improved technique using mixed electron–photon beams with a multileaf collimator

BACKGROUND AND PURPOSE Loco-regional radiotherapy after breast cancer surgery significantly reduces the risk of recurrences. An increase of cardiac deaths for irradiated breast cancer patients has been reported in some studies, especially for women with tumours in the left breast. The aim of this study was to compare retrospectively the conventionally used technique using two opposed tangential photon beams with a modified technique using a combination of photon and electron beams to find an optimal technique with respect to dose homogeneity in the breast and surrounding regional lymph nodes and a minimal dose in the organs at risk. MATERIALS AND METHODS Thirty patients with stage II breast cancer who received different types of adjuvant systemic therapy were included in the investigation. Comparative dose planning of two techniques was performed, i.e. an isocentric technique with two photon beams with coplanar medial beam edges and a technique with one electron and three photon beams with a common isocentre for all beams aided by a multileaf collimator. RESULTS The mixed technique was selected for eight of 12 patients with left-sided breast cancers because of significantly lower doses to the heart. However, the decision-making was influenced by many factors such as dose coverage of the target volume combined with minimizing of the doses to the organs at risk and the contralateral breast. CONCLUSION The use of the mixed technique will optimize the loco-regional radiotherapy after breast-conserving surgery for many left-sided breast cancers.

The IMRT information process—mastering the degrees of freedom in external beam therapy

The techniques and procedures for intensity-modulated radiation therapy (IMRT) are reviewed in the context of the information process central to treatment planning and delivery of IMRT. A presentation is given of the evolution of the information based radiotherapy workflow and dose delivery techniques, as well as the volume and planning concepts for relating the dose information to image based patient representations. The formulation of the dose shaping process as an optimization problem is described. The different steps in the calculation flow for determination of machine parameters for dose delivery are described starting from the formulation of optimization objectives over dose calculation to optimization procedures. Finally, the main elements of the quality assurance procedure necessary for implementing IMRT clinically are reviewed.