Alan E. Nahum

Comparison of radiation side-effects of conformal and conventional radiotherapy in prostate cancer: a randomised trial

BACKGROUND Radical radiotherapy is commonly used to treat localised prostate cancer. Late chronic side-effects limit the dose that can be given, and may be linked to the volume of normal tissues irradiated. Conformal radiotherapy allows a smaller amount of rectum and bladder to be treated, by shaping the high-dose volume to the prostate. We assessed the ability of this new technology to lessen the risk of radiation-related effects in a randomised controlled trial of conformal versus conventional radiotherapy. METHODS We recruited men with prostate cancer for treatment with a standard dose of 64 Gy in daily 2 Gy fractions. The men were randomly assigned conformal or conventional radiotherapy treatment. The primary endpoint was the development of late radiation complications (> 3 months after treatment) measured with the Radiation Therapy and Oncology Group (RTOG) score. Indicators of disease (cancer) control were also recorded. FINDINGS In the 225 men treated, significantly fewer men developed radiation-induced proctitis and bleeding in the conformal group than in the conventional group (37 vs 56% > or = RTOG grade 1, p=0.004; 5 vs 15% > or = RTOG grade 2, p=0.01). There were no differences between groups in bladder function after treatment (53 vs 59% > or = grade 1, p=0.34; 20 vs 23% > or = grade 2, p=0.61). After median follow-up of 3.6 years there was no significant difference between groups in local tumour control (conformal 78% [95% CI 66-86], conventional 83% [69-90]). INTERPRETATION Conformal techniques significantly lowered the risk of late radiation-induced proctitis after radiotherapy for prostate cancer. Widespread introduction of these radiotherapy treatment methods is appropriate. Our results are the basis for dose-escalation studies to improve local tumour control.

A model for calculating tumour control probability in radiotherapy including the effects of inhomogeneous distributions of dose and clonogenic cell density

Most calculations of the biological effect of radiation on tumours assume that the clonogenic cell density is uniform even if account is taken of non-uniform dose distribution. In practice tumours will almost certainly have a non-uniform clonogenic cell density. This paper extends one particular model of tumour control probability (TCP) to incorporate a variable clonogenic cell density while at the same time assuming a constant 2 Gy fraction size and a uniform radiosensitivity throughout the treatment. Since there are virtually no in vivo data on the variation of density we consider some model situations. One clear conclusion is that a large reduction in clonogenic cell density at the edges of a tumour would permit only a very modest decrease in dose if the TCP is not to be reduced. In general the effect on TCP is a complicated function of the variation in both dose and clonogenic cell density. We give the equations which enable both to be included.

Converting absorbed dose to medium to absorbed dose to water for Monte Carlo based photon beam dose calculations

Current clinical experience in radiation therapy is based upon dose computations that report the absorbed dose to water, even though the patient is not made of water but of many different types of tissue. While Monte Carlo dose calculation algorithms have the potential for higher dose accuracy, they usually transport particles in and compute the absorbed dose to the patient media such as soft tissue, lung or bone. Therefore, for dose calculation algorithm comparisons, or to report dose to water or tissue contained within a bone matrix for example, a method to convert dose to the medium to dose to water is required. This conversion has been developed here by applying Bragg-Gray cavity theory. The dose ratio for 6 and 18 MV photon beams was determined by computing the average stopping power ratio for the primary electron spectrum in the transport media. For soft tissue, the difference between dose to medium and dose to water is approximately 1.0%, while for cortical bone the dose difference exceeds 10%. The variation in the dose ratio as a function of depth and position in the field indicates that for photon beams a single correction factor can be used for each particular material throughout the field for a given photon beam energy. The only exception to this would be for the clinically non-relevant dose to air. Pre-computed energy spectra for 60Co to 24 MV are used to compute the dose ratios for these photon beams and to determine an effective energy for evaluation of the dose ratio.

Using a Monte Carlo model to predict dosimetric properties of small radiotherapy photon fields

Accurate characterization of small-field dosimetry requires measurements to be made with precisely aligned specialized detectors and is thus time consuming and error prone. This work explores measurement differences between detectors by using a Monte Carlo model matched to large-field data to predict properties of smaller fields. Measurements made with a variety of detectors have been compared with calculated results to assess their validity and explore reasons for differences. Unshielded diodes are expected to produce some of the most useful data, as their small sensitive cross sections give good resolution whilst their energy dependence is shown to vary little with depth in a 15MV linac beam. Their response is shown to be constant with field size over the range 1-10cm, with a correction of 3% needed for a field size of 0.5cm. BEAMnrc has been used to create a 15MV beam model, matched to dosimetric data for square fields larger than 3cm, and producing small-field profiles and percentage depth doses (PDDs) that agree well with unshielded diode data for field sizes down to 0.5cm. For fields sizes of 1.5cm and above, little detector-to-detector variation exists in measured output factors, however for a 0.5cm field a relative spread of 18% is seen between output factors measured with different detectors-values measured with the diamond and pinpoint detectors lying below that of the unshielded diode, with the shielded diode value being higher. Relative to the corrected unshielded diode measurement, the Monte Carlo modeled output factor is 4.5% low, a discrepancy that is probably due to the focal spot fluence profile and source occlusion modeling. The large-field Monte Carlo model can, therefore, currently be used to predict small-field profiles and PDDs measured with an unshielded diode. However, determination of output factors for the smallest fields requires a more detailed model of focal spot fluence and source occlusion.

Handbook of Radiotherapy Physics: Theory and Practice

This article reviews Handbook of Radiotherapy Physics: Theory and Practice by P. Mayles, A. Nahum, J. C. Rosenwald , Boca Raton, FL, 2007. Hardcover 1470 pp. Price:

The use and QA of biologically related models for treatment planning: short report of the TG-166 of the therapy physics committee of the AAPM.

269.95. ISBN: 9780750308601.

Correlations between dose-surface histograms and the incidence of long-term rectal bleeding following conformal or conventional radiotherapy treatment of prostate cancer.

Treatment planning tools that use biologically related models for plan optimization and/or evaluation are being introduced for clinical use. A variety of dose-response models and quantities along with a series of organ-specific model parameters are included in these tools. However, due to various limitations, such as the limitations of models and available model parameters, the incomplete understanding of dose responses, and the inadequate clinical data, the use of biologically based treatment planning system (BBTPS) represents a paradigm shift and can be potentially dangerous. There will be a steep learning curve for most planners. The purpose of this task group is to address some of these relevant issues before the use of BBTPS becomes widely spread. In this report, the authors (1) discuss strategies, limitations, conditions, and cautions for using biologically based models and parameters in clinical treatment planning; (2) demonstrate the practical use of the three most commonly used commercially available BBTPS and potential dosimetric differences between biologically model based and dose-volume based treatment plan optimization and evaluation; (3) identify the desirable features and future directions in developing BBTPS; and (4) provide general guidelines and methodology for the acceptance testing, commissioning, and routine quality assurance (QA) of BBTPS.

The quality dependence of LiF TLD in megavoltage photon beams: Monte Carlo simulation and experiments

BACKGROUND AND PURPOSE In a randomized trial, the incidence of rectal bleeding among patients treated for prostate cancer using conformal radiotherapy was significantly lower (p = 0.002) than that among those treated conventionally. Here the relationship between rectal dose distributions and incidences of bleeding is assessed. METHODS AND MATERIALS Rectal dose-surface histograms (DSHs) have been calculated for 79 trial patients. The relationship between the DSHs and incidences of Grade 1-3 bleeding has been explored using both semiempiric and biologic (parallel) model-based approaches. RESULTS Semiempiric analysis of the trial data suggests that it is more useful to work with DSH fractional surface areas multiplied by outlined rectal lengths than with either raw DSH fractional areas or fractional areas multiplied by absolute total outlined rectal surface area. Fitting the parallel model to length-multiplied rectal DSHs and complication data reveals the existence of a significant volume effect, the rate of Grade 1-3 bleeding falling by 1.1% (95% confidence interval [0.04, 2.2]%) for each 1% decrease in the fraction of rectal wall (outlined over an 11-cm length) receiving a dose of more than 57 Gy. CONCLUSION The existence of this volume effect suggests that dose escalation can be achieved using conformal techniques, although the extent to which doses may be safely escalated cannot be reliably estimated from the trial data.

A comparison of techniques for stereotactic radiotherapy by linear accelerator based on 3-dimensional dose distributions

The quality dependence of LiF TLD in megavoltage photon beams with qualities from 60Co gamma-rays to 25 MV x-rays has been studied experimentally against ion chamber measurements and theoretically by Monte Carlo simulation using the EGS4 Monte Carlo code system. The experimental findings are that the energy dependence of 1 mm thick TLD-100 (micro-rods and chips) on average decreases slowly from 1.0 for 60Co gamma-rays to 0.989 +/- 1.3% for 6 MV x-rays (TPR20/10 = 0.685) and to 0.974 +/- 1.3% for 25 MV x-rays (TPR20/10 = 0.800) relative to 60Co gamma-rays. The Monte Carlo results vary from 0.991 +/- 0.9% for 6 MV x-rays to 0.978 +/- 0.8% for 25 MV x-rays. Differences between chips and micro-rods were negligible and there was no difference in the energy dependence between TLDs irradiated in water or Perspex (PMMA). The Monte Carlo simulation shows that the contribution to the total absorbed dose from photon interactions in the 1 mm diameter and 6 mm long TLD material varies from 50% for 60Co gamma-rays to 10% for 25 MV x-rays. When the diameter of the TLD micro-rod was increased from 1 mm to 5 mm there was no significant change in response computed by Monte Carlo even though the dose contribution to the total dose scored in the TLD material from photon interactions in the cavity increased to 85% for 60Co gamma-rays and 30% for 25 MV x-rays.

An empirical method to build up a model of proton dose distribution for a radiotherapy treatment-planning package

In order to establish the appropriate beam arrangement for use in stereotactic radiotherapy using a linear accelerator, dose volume distributions were calculated for a number of spherical targets in a head phantom and assessment was made by dose sparing of normal tissue outside the target volume. Using a single isocentre, fixed beam arrangements were compared with single and multiple non-coplanar isocentric arc rotations at target sizes from 10 to 55 mm diameter on a 6 MV Philips linear accelerator. From the dose-volume histograms produced, an arrangement of 3 or 4 arcs of rotation proved most suitable, in terms of sparing of normal tissue outside the target volume to high dose irradiation, across the range of target sizes studied. There was little further benefit with increasing the number of arcs beyond this. At target sizes greater than 20 mm diameter an arrangement of 6 static non-coplanar beams achieved sparing equivalent to multiple arc rotations and may have considerable advantages in the treatment of irregular volumes where customised beam shaping could be employed.