Marnix Witte - Academia.edu (original) (raw)

Papers by Marnix Witte

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, Jan 30, 2015

We evaluated dose distributions in the anorectum and its relation to acute gastrointestinal toxic... more We evaluated dose distributions in the anorectum and its relation to acute gastrointestinal toxicities using dose surface maps in an image-guided (IG) IMRT and 3D-conformal radiotherapy (3D-CRT) population. For patients treated to 78Gy with IG-IMRT (n=260) or 3D-CRT (n=215), for whom acute toxicity data were available, three types of surface maps were calculated: (1) total anorectum using regular intervals along a central axis with perpendicular slices, (2) the rectum next to the prostate, and (3) the anal canal (horizontal slicing). For each toxicity, an average dose map was calculated for patients with and without the toxicity and subsequently dose difference maps were constructed, 3D-CRT and IG-IMRT separately. P-values were based on permutation tests. Dose distributions in patients with grade ⩾2 acute proctitis were significantly different from dose distributions in patients without toxicity, for IG-IMRT and 3D-CRT. At the cranial and posterior rectal site, in areas receiving mo...

International journal of radiation oncology, biology, physics, Jan 15, 2015

Image-guided intensity modulated radiation therapy (IG-IMRT) allows significant dose reductions t... more Image-guided intensity modulated radiation therapy (IG-IMRT) allows significant dose reductions to organs at risk in prostate cancer patients. However, clinical data identifying the benefits of IG-IMRT in daily practice are scarce. The purpose of this study was to compare dose distributions to organs at risk and acute gastrointestinal (GI) and genitourinary (GU) toxicity levels of patients treated to 78 Gy with either IG-IMRT or 3D-CRT. Patients treated with 3D-CRT (n=215) and IG-IMRT (n=260) receiving 78 Gy in 39 fractions within 2 randomized trials were selected. Dose surface histograms of anorectum, anal canal, and bladder were calculated. Identical toxicity questionnaires were distributed at baseline, prior to fraction 20 and 30 and at 90 days after treatment. Radiation Therapy Oncology Group (RTOG) grade ≥1, ≥2, and ≥3 endpoints were derived directly from questionnaires. Univariate and multivariate binary logistic regression analyses were applied. The median volumes receiving 5...

Radiation oncology (London, England), 2013

Comparing incidental dose distributions (i.e. images) of patients with different outcomes is a st... more Comparing incidental dose distributions (i.e. images) of patients with different outcomes is a straightforward way to explore dose-response hypotheses in radiotherapy. In this paper, we introduced a permutation test that compares images, such as dose distributions from radiotherapy, while tackling the multiple comparisons problem. A test statistic T max was proposed that summarizes the differences between the images into a single value and a permutation procedure was employed to compute the adjusted p-value. We demonstrated the method in two retrospective studies: a prostate study that relates 3D dose distributions to failure, and an esophagus study that relates 2D surface dose distributions of the esophagus to acute esophagus toxicity. As a result, we were able to identify suspicious regions that are significantly associated with failure (prostate study) or toxicity (esophagus study). Permutation testing allows direct comparison of images from different patient categories and is a useful tool for data mining in radiotherapy.

Radiotherapy and Oncology, 2011

Dose painting by numbers lacks the conventional margin approach for geometric uncertainties. More... more Dose painting by numbers lacks the conventional margin approach for geometric uncertainties. Moreover, the DVH is unable to assess the geometric accuracy of a non-uniform dose distribution because spatial information is lost. In this work we present tools for planning and evaluation of non-uniform treatment dose which take geometric uncertainties into account. The IMRT optimization functions in the Pinnacle treatment planning software were extended to allow non-uniform prescription dose distributions, e.g., derived from a PET image set. Also, explicit handling of systematic and random geometric uncertainties was incorporated in the functions, enabling confidence level based probabilistic treatment planning. For plan evaluation the concept of ΔVH was introduced, which is the volume histogram of the difference between planned and prescribed doses. Probability distributions for ΔVH points were estimated using Monte Carlo methods. As a demonstration of these methods, two examples are presented; one plan for a lung cancer patient and one for a tumor in the head-and-neck region. Dose distributions were obtained using the PET SUV, while allowing for geometric uncertainties. Optimization was performed such that the ΔVH evaluation indicated a 90% confidence of having under-dosage less than 5% of prescription dose maximum in 99% of the tumor volume. This corresponds to the clinical target constraint for margin based planning with uniform dose prescription. Clinical treatment planning tools were extended to allow non-uniform prescription. For planning we introduced confidence level based probabilistic optimization with non-uniform target dose, while confidence levels of ΔVH points summarize the probability of proper target coverage.

Radiotherapy and Oncology, 2013

Objective: High-risk prostate cancer patients are at risk for subclinical disease and micro-metas... more Objective: High-risk prostate cancer patients are at risk for subclinical disease and micro-metastasis at the time of treatment. Nowadays, tight margins reduce dose to periprostatic areas compared to earlier techniques. We investigated whether rectangular fields were associated with fewer failures compared to conformal fields (with lower extraprostatic dose). Methods: We selected 164 high-risk patients from the trial population of 266 T1-T4N0M0 patients, randomized between rectangular (n = 79) and conformal fields (n = 85). Prescribed dose was 66 Gy to the prostate and seminal vesicles plus 15 mm margin. We compared clinical failure rates (in-and excluding local failures), between both arms. Dose differences around the prostate were calculated based on an inter-patient mapping method. Results: Median follow-up was 34 months. There were 9 clinical failures in the rectangular arm versus 24 in the conformal arm (p = 0.012). Number of failures outside the prostate was 7 and 19, respectively (p = 0.025). We observed average dose differences of 5-35 Gy between the arms in the regions around the prostate. Conclusions: We found a significantly lower risk of early tumor progression for patients treated with rectangular fields. Treatment failure can probably in part be prevented by irradiation of areas suspected of subclinical disease in high-risk prostate cancer.

Physics in Medicine and Biology, 2013

We present a method to implement probabilistic treatment planning of intensity-modulated radiatio... more We present a method to implement probabilistic treatment planning of intensity-modulated radiation therapy using custom software plugins in a commercial treatment planning system. Our method avoids the definition of safety-margins by directly including the effect of geometrical uncertainties during optimization when objective functions are evaluated. Because the shape of the resulting dose distribution implicitly defines the robustness of the plan, the optimizer has much more flexibility than with a margin-based approach. We expect that this added flexibility helps to automatically strike a better balance between target coverage and dose reduction for surrounding healthy tissue, especially for cases where the planning target volume overlaps organs at risk. Prostate cancer treatment planning was chosen to develop our method, including a novel technique to include rotational uncertainties. Based on population statistics, translations and rotations are simulated independently following a marker-based IGRT correction strategy. The effects of random and systematic errors are incorporated by first blurring and then shifting the dose distribution with respect to the clinical target volume. For simplicity and efficiency, dose-shift invariance and a rigid-body approximation are assumed. Three prostate cases were replanned using our probabilistic objective functions. To compare clinical and probabilistic plans, an evaluation tool was used that explicitly incorporates geometric uncertainties using Monte-Carlo methods. The new plans achieved similar or better dose distributions than the original clinical plans in terms of expected target coverage and rectum wall sparing. Plan optimization times were only about a factor of two higher than in the original clinical system. In conclusion, we have developed a practical planning tool that enables margin-less probability-based treatment planning with acceptable planning times, achieving the first system that is feasible for clinical implementation.

Medical Physics, 2004

The minimum margins required to compensate for random geometric uncertainties in the delivery of ... more The minimum margins required to compensate for random geometric uncertainties in the delivery of radiotherapy treatment were determined for a spherical Clinical Target Volume, using an analytic model for the cumulative dose. Margins were calculated such that the minimum dose in the target would be no less than 95% of the prescribed dose for 90% of the patients. The dose distribution model incorporated two Gaussians, and could accurately represent realistic dose profiles for various target sizes in lung and water. It was found that variations in target size and tissue density lead to significant changes in the minimum margin required for random errors. The random error margin increased with tissue density, and decreased with target size. The required margins were similar for dose distributions of spherical and cylindrical symmetry. Significant dose outside the spherical high dose region, as could result from multiple incident beams, lead to an increased margin for the larger targets. We could confirm that the previously proposed margin of 0.7 times the standard deviation of the random errors is safe for standard deviations up to 5 mm, except for very small targets in dense material.

Medical Physics, 2007

The purpose of this work was the development of a probabilistic planning method with biological c... more The purpose of this work was the development of a probabilistic planning method with biological cost functions that does not require the definition of margins. Geometrical uncertainties were integrated in tumor control probability (TCP) and normal tissue complication probability (NTCP) objective functions for inverse planning. For efficiency reasons random errors were included by blurring the dose distribution and systematic errors by shifting structures with respect to the dose. Treatment plans were made for 19 prostate patients following four inverse strategies: Conformal with homogeneous dose to the planning target volume (PTV), a simultaneous integrated boost using a second PTV, optimization using TCP and NTCP functions together with a PTV, and probabilistic TCP and NTCP optimization for the clinical target volume without PTV. The resulting plans were evaluated by independent Monte Carlo simulation of many possible treatment histories including geometrical uncertainties. The results showed that the probabilistic optimization technique reduced the rectal wall volume receiving high dose, while at the same time increasing the dose to the clinical target volume. Without sacrificing the expected local control rate, the expected rectum toxicity could be reduced by 50% relative to the boost technique. The improvement over the conformal technique was larger yet. The margin based biological technique led to toxicity in between the boost and probabilistic techniques, but its control rates were very variable and relatively low. During evaluations, the sensitivity of the local control probability to variations in biological parameters appeared similar for all four strategies. The sensitivity to variations of the geometrical error distributions was strongest for the probabilistic technique. It is concluded that probabilistic optimization based on tumor control probability and normal tissue complication probability is feasible. It results in robust prostate treatment plans with an improved balance between local control and rectum toxicity, compared to conventional techniques.

$Research paper thumbnail of Biologic and physical fractionation effects of random geometric errors$

International Journal of Radiation Oncology*Biology*Physics, 2003

We are developing a system to model the effect of random and systematic geometric errors on radio... more We are developing a system to model the effect of random and systematic geometric errors on radiotherapy delivery. The purpose of this study was to investigate biologic and physical fractionation effects of random geometric errors and respiration motion and compare the resulting dose distributions with Gaussian blurring of the planned dose. A hypothetical dose distribution with Gaussian penumbra was used. Random errors drawn from a normal distribution, optionally combined with simulated respiration motion (in the cranio-caudal direction), were used to displace the dose distribution for N simulated fractions. To simulate biologic effects of fractionation, the physical dose was converted to a biologically effective dose using the linear-quadratic model (including repopulation), then summed and converted back to physical dose for comparison. Differences between dose distributions were quantified in terms of the distance between selected isodose levels. A limited number of fractions led to an uncertainty in the position of isodose levels in the total dose with as standard deviation (SD) the SD of the random error divided by radical N. Due to biologic fractionation effects, the total dose distribution became slightly wider: 0.4 mm for alpha/beta = 1 Gy and a random error SD of 3 mm. The widening increased with random error and reduced with increasing alpha/beta but does not depend on the number of fractions or on repopulation. Respiration motion caused an asymmetric deviation in the shape of the total dose distribution, but no additional dose widening was seen from the biologic effect of fractionation. With a random error SD of 3 mm and respiration amplitude, A, of 1 cm or less (SD &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.36 cm), the asymmetry was negligible. For larger respiration amplitudes (combined with the same random error), the shift of the 95% isodose level was about 0.25*A caudally, and 0.45*A cranially. Gaussian blurring with a combined SD of organ motion, setup error, and respiration motion is a valid approximation for the effect of purely random errors in fractionated radiotherapy. For respiration motion in excess of 1 cm in amplitude, isodose lines shift in a distinctly asymmetric fashion and asymmetric margins need to be used.

International Journal of Radiation Oncology*Biology*Physics, 2010

39 Chapter 4: Urinary obstruction in prostate cancer patients from the Dutch trial (68 Gy vs. 78 ... more 39 Chapter 4: Urinary obstruction in prostate cancer patients from the Dutch trial (68 Gy vs. 78 Gy): relationships with local dose, acute effects and baseline characteristics. Heemsbergen WD, Al-Mamgani A, Witte MG, van Herk M, Pos FL, Lebesque JV Int J Radiat Oncol Biol Phys 2010 (Epub ahead of print) 55 Chapter 5: Dose-escalation and quality-of-life in patients with localized prostate cancer treated with radiotherapy: long-term results of the Dutch randomized dose-escalation trial (CKTO 96-10 trial) Al-Mamgani A, van Puttem WLJ, van der Wielen GJ, Levendag PC, Incrocci L Int J Radiat Oncol Biol Phys 2010 (Epub ahead of print) 71 Chapter 6: Subgroup analysis of patients with localized prostate cancer treated within the Dutch randomized dose-escalation trial Al-Mamgani A, Heemsbergen WD, Levendag PC, Lebeque JV Radiother Oncol 2010;96:13-18.

International Journal of Radiation Oncology*Biology*Physics, 2008

International Journal of Radiation Oncology*Biology*Physics, 2011

International Journal of Radiation Oncology*Biology*Physics, 2007

To apply target probabilistic planning (TPP) approach to intensity modulated radiotherapy (IMRT) ... more To apply target probabilistic planning (TPP) approach to intensity modulated radiotherapy (IMRT) plans for head and neck cancer (HNC) patients. Twenty plans of HNC patients were re-planned replacing the simultaneous integrated boost IMRT optimization objectives for minimum dose on the boost target and the elective volumes with research probabilistic objectives: the latter allow for explicit handling of systematic and random geometric uncertainties, enabling confidence level based probabilistic treatment planning. Monte-Carlo evaluations of geometrical errors were performed, with endpoints D98%, D2% and Dmean, calculated at a confidence level of 90%. The dose distribution was expanded outside the patient to prevent large bilateral elective treatment volumes ending up in air for probabilistic shifts. TPP resulted in more regular isodoses and in reduced dose, on average, to organs at risk (OAR), up to more than 6Gy, while maintaining target coverage and keeping the maximum dose to limiting structures within requirements. In particular, when the surrounding OARs overlap with the planning target volume (PTV) but not with the clinical target volume (CTV), better results were achieved. The TPP approach was evaluated in HNC patients, and proven to be an efficient tool for managing uncertainties.

Practical Radiation Oncology, 2015

Non-small cell lung cancer is typically irradiated with 60-66 Gy in 2-Gy fractions. Local control... more Non-small cell lung cancer is typically irradiated with 60-66 Gy in 2-Gy fractions. Local control could be improved by increasing dose to the more radiation-resistant areas (eg, based on the standardized uptake values of a pretreatment [(18)F]fluoro-deoxyglucose positron emission tomography scan). Such dose painting approaches, however, are poorly suited for a conventional planning target volume margin expansion; therefore, typically no margins are used. This study investigates dose deterioration of a dose painting by numbers (DPBN) approach resulting from geometrical uncertainties. For 9 DPBN plans of stage II/III non-small cell lung cancer patients, the boost dose was escalated up to 130 Gy (in 33 fractions) or until a dose-limiting constraint was reached. Then, using Monte Carlo methods, a probabilistic evaluation of dose endpoints for 99%, 98%, and 2% of gross tumor volume at a 90% confidence level was performed considering 8 different combinations of systematic (∑) and random (σ) geometric error distributions. Important underdosages, because of geometric uncertainties, of up to 38 Gy with minimal image guidance occur, reducing to 8 Gy with the highest level of image guidance, for a patient where a maximum dose of 119 Gy could be achieved. The evaluation showed that systematic errors had the largest influence. The effects of the uncertainties are most evident where the dose or its gradient is high. Probabilistic evaluation showed that the geometric uncertainties have a large effect and should be evaluated before approving DPBN plans.