- Email: [email protected]
SP-0441: Treatment planning techniques to handle geometrical and anatomical uncertainties: State of the art
S175
ESTRO 33, 2014 On first entering the clinic, a proof of principle phase maybe useful, particularly when introducing a novel concept from an animal model. For example the observation that AKT pathway inhibition reduces hypoxia in animal models and improves sensitivity needs to be verified in humans with imaging and biomarker analyses to prove the principle of reduced hypoxia in at least a proportion of cases. Such proof of principle studies of drug effect may be performed in a separate cohort or prior to the drug radiation interaction. Phase1 radiotherapy studies may be dose escalation of radiotherapy for instance using SBRT for novel targets, or IMRT to biologically defined boost volumes. Alternatively, they may be evaluating dose escalation of the chemo or novel therapeutic in combination with a standard dose of radiotherapy. The challenge is in balancing having sufficient time to assess late radiation toxicity on normal tissue with the requirement to complete the trial in a reasonable time period. Newer methods of phase 1 assessment including time to event continual reassessment methods (TITE-CRM) can be useful here. These include assessment of later events in earlier cohorts to determine the dose escalation schedule and are based on the principle that the largest proportion of patients should be treated near to the maximum tolerated dose, rather than including many patients at lower doses than the MTD. Increasingly phase 1 trials in radiotherapy are combining novel agents with existing chemoradiotherapy schedules. These are highly challenging studies to undertake. Debate exists as to whether these should always start with a palliative radiotherapy cohort to exclude severe unexpected novel agent radiotherapy interactions, or whether inclusion of low dose novel agent with gradual dose escalation in the radical radiotherapy context is safe and ethical. Examples will be given to illustrate differing approaches to this problem. It is essential to work on such studies in collaboration with an experienced medical oncology team with experience of phase 1 trials to assist with optimal design and running phase 1 trials, with which most radiation oncologists are unfamiliar.
TEACHING LECTURE SP-0441 Treatment planning techniques to handle geometrical and anatomical uncertainties: State of the art M. Söhn1 1 University Hospital Grosshadern – LMU München, Radiation Oncology/Medical Physics, München, Germany Conventional radiotherapy (RT) planning approaches employ a static patient model based on a single CT scan to define the clinical target volume (CTV) and organs at risk (OARs) and to determine the dose distribution. This, however, is only a snapshot of the dynamic processes present in patient treatment. Inevitable geometrical and anatomical uncertainties such as patient setup errors, internal organ motion and tumor shrinkage lead to nontrivial discrepancies between the planning CT scan and the treatment geometries. The widely used approach to account for geometric uncertainties is the extension of the CTV by a margin, and to ensure coverage of the resulting larger planning target volume (PTV) (ICRU reports 50, 62). Similarly, OARs may be expanded to planning organ at risk volumes (PRVs). It is the fundamental conceptional shortcoming of this 'PTV concept' that treatment plan quality is scored using a static dose distribution evaluated based on static surrogate volumes (PTV, OARs/PRVs), which shows nontrivial – and unquantified – deviations from the actually applied (accumulated) doses to the moving and deforming tumor and OARs. In fact, the latter are stochastic quantities at time of treatment planning, which is not explicitly accounted for nor quantitatively accessible in conventional PTV-based planning. The development of methods to overcome the limitations of the PTV concept is crucial for hadron-based RT (TEACHING LECTURE by M. Schwarz on Sunday: "Geometrical uncertainties & proton treatment planning"). For photon-based RT, important improvements in treatment quality were seen in the recent years through technological and methodical developments in imaging and its feedback into the RT process (IGRT, ART), facilitating PTV-margin reduction and/or individualization. This can enable target dose escalation and/or improved OAR sparing, however, even IGRT/ART cannot fundamentally alleviate the stochastic nature of treatment planning and -application due to remaining uncertainties especially of deformative nature, geometrical OAR variability, and intrafractional uncertainties. Thus methods 'beyond the PTV-concept' for treatment planning and evaluation, which inherently make use of multiple imaging information available in IGRT, are desirable. This TEACHING LECTURE will motivate and discuss the need for such problem-tailored approaches to tackle the different categories of geometric and anatomical uncertaities: intra-fx vs. inter-fx, systematic
vs. random vs. quasi-periodic vs. trending. An exemplaric overview of treatment planning approaches 'beyond the PTV concept' including probabilistic planning, '4D-planning' and robust planning will be given, and methods to statistically evaluate and quantify dosimetric uncertainties (virtual treatment course simulations, confidence intervals in DVHs, (joint) outcome probability distributions, worst case estimators) will be discussed.
TEACHING LECTURE SP-0442 Dosimetry of small fields: Present status and future guidelines by IAEA H. Palmans1 1 National Physical Laboratory, Acoustics and Ionising Radiation, Teddington, United Kingdom The increased use of small photon fields in stereotactic and intensity modulated radiotherapy has raised the need for standardizing the dosimetry of such fields using procedures consistent with those for conventional radiotherapy. An international working group, established by the IAEA in collaboration with AAPM and IPEM, is finalising a Code of Practice for the dosimetry of small static photon fields. While many problems of small field dosimetry have been raised, e.g. in IPEM Report 103, a vast amount of literature has addressed most of those and solutions have been proposed (often for specific situations though). The reported problems include the definition of field size, the field size dependent response of detectors, volume averaging, fluence perturbation corrections, reference conditions and beam quality in nonconventional reference fields. One area of importance for establishing a code of practice is the availability of data and this happens to be a dynamic area in which many papers have been published recently with new data or insights that enhance our understanding of small field dosimetry substantially. The code of practice will formalise and will make recommendations on the practical implementation of those solutions. It will consist of six chapters; an introduction, physics and technology of small field dosimetry, concepts and formalism, detectors and equipment, practical implementation of machine-specific reference dosimetry and practical implementation of relative dosimetry. It will also contain appendices on data, uncertainties, Monte Carlo simulation of correction factors and worksheets. This lecture will review the present understanding and solutions proposed in the literature for small field dosimetry, give an overview of the formalism and procedures that have been developed in the code of practice providing practical recommendations based on those solutions and present compilations of available data from the literature.
TEACHING LECTURE SP-0443 Current status of palliative radiation therapy J. Leer1 1 Radboud University Nijmegen Medical Centre, Radiotherapy, Nijmegen, The Netherlands Although palliative treatment with radiotherapy is about half of our workload, most clinical studies try to improve curative treatments. Until the end of the last decade, the used treatment schedules e.g. for brain or bone metastases were non evidence based. In the last 20 years however, several studies changed this. It is proven now that a single fraction for bone metastases is as effective as multiple fractions. This is also true for reirradiation as recently presented, based on the data of an international study. Radiotherapy used to be the standard for an imminent cord compression. Due to better surgical techniques, the role of surgery is being reinvestigated. For patients with favorable prognostic factors, life expectancy is an important basis to decide on a more aggressive or less aggressive treatment. More tailor made approaches are therefore proposed in function of the expected life expectancy of patients. To use this approach we need better methods to improve our estimation of life expectancy. Several recent studies have tried to categorize patients according to their life expectancy. In the last years a special group of patients is indentified, being the patients with a long life expectancy and oligometastases. More radical treatments with stereotactic radiotherapy are proposed and tested for these patients. In this presentation we will discuss all these more recent developments.
ESTRO 33, 2014 On first entering the clinic, a proof of principle phase maybe useful, particularly when introducing a novel concept from an animal model. For example the observation that AKT pathway inhibition reduces hypoxia in animal models and improves sensitivity needs to be verified in humans with imaging and biomarker analyses to prove the principle of reduced hypoxia in at least a proportion of cases. Such proof of principle studies of drug effect may be performed in a separate cohort or prior to the drug radiation interaction. Phase1 radiotherapy studies may be dose escalation of radiotherapy for instance using SBRT for novel targets, or IMRT to biologically defined boost volumes. Alternatively, they may be evaluating dose escalation of the chemo or novel therapeutic in combination with a standard dose of radiotherapy. The challenge is in balancing having sufficient time to assess late radiation toxicity on normal tissue with the requirement to complete the trial in a reasonable time period. Newer methods of phase 1 assessment including time to event continual reassessment methods (TITE-CRM) can be useful here. These include assessment of later events in earlier cohorts to determine the dose escalation schedule and are based on the principle that the largest proportion of patients should be treated near to the maximum tolerated dose, rather than including many patients at lower doses than the MTD. Increasingly phase 1 trials in radiotherapy are combining novel agents with existing chemoradiotherapy schedules. These are highly challenging studies to undertake. Debate exists as to whether these should always start with a palliative radiotherapy cohort to exclude severe unexpected novel agent radiotherapy interactions, or whether inclusion of low dose novel agent with gradual dose escalation in the radical radiotherapy context is safe and ethical. Examples will be given to illustrate differing approaches to this problem. It is essential to work on such studies in collaboration with an experienced medical oncology team with experience of phase 1 trials to assist with optimal design and running phase 1 trials, with which most radiation oncologists are unfamiliar.
TEACHING LECTURE SP-0441 Treatment planning techniques to handle geometrical and anatomical uncertainties: State of the art M. Söhn1 1 University Hospital Grosshadern – LMU München, Radiation Oncology/Medical Physics, München, Germany Conventional radiotherapy (RT) planning approaches employ a static patient model based on a single CT scan to define the clinical target volume (CTV) and organs at risk (OARs) and to determine the dose distribution. This, however, is only a snapshot of the dynamic processes present in patient treatment. Inevitable geometrical and anatomical uncertainties such as patient setup errors, internal organ motion and tumor shrinkage lead to nontrivial discrepancies between the planning CT scan and the treatment geometries. The widely used approach to account for geometric uncertainties is the extension of the CTV by a margin, and to ensure coverage of the resulting larger planning target volume (PTV) (ICRU reports 50, 62). Similarly, OARs may be expanded to planning organ at risk volumes (PRVs). It is the fundamental conceptional shortcoming of this 'PTV concept' that treatment plan quality is scored using a static dose distribution evaluated based on static surrogate volumes (PTV, OARs/PRVs), which shows nontrivial – and unquantified – deviations from the actually applied (accumulated) doses to the moving and deforming tumor and OARs. In fact, the latter are stochastic quantities at time of treatment planning, which is not explicitly accounted for nor quantitatively accessible in conventional PTV-based planning. The development of methods to overcome the limitations of the PTV concept is crucial for hadron-based RT (TEACHING LECTURE by M. Schwarz on Sunday: "Geometrical uncertainties & proton treatment planning"). For photon-based RT, important improvements in treatment quality were seen in the recent years through technological and methodical developments in imaging and its feedback into the RT process (IGRT, ART), facilitating PTV-margin reduction and/or individualization. This can enable target dose escalation and/or improved OAR sparing, however, even IGRT/ART cannot fundamentally alleviate the stochastic nature of treatment planning and -application due to remaining uncertainties especially of deformative nature, geometrical OAR variability, and intrafractional uncertainties. Thus methods 'beyond the PTV-concept' for treatment planning and evaluation, which inherently make use of multiple imaging information available in IGRT, are desirable. This TEACHING LECTURE will motivate and discuss the need for such problem-tailored approaches to tackle the different categories of geometric and anatomical uncertaities: intra-fx vs. inter-fx, systematic
vs. random vs. quasi-periodic vs. trending. An exemplaric overview of treatment planning approaches 'beyond the PTV concept' including probabilistic planning, '4D-planning' and robust planning will be given, and methods to statistically evaluate and quantify dosimetric uncertainties (virtual treatment course simulations, confidence intervals in DVHs, (joint) outcome probability distributions, worst case estimators) will be discussed.
TEACHING LECTURE SP-0442 Dosimetry of small fields: Present status and future guidelines by IAEA H. Palmans1 1 National Physical Laboratory, Acoustics and Ionising Radiation, Teddington, United Kingdom The increased use of small photon fields in stereotactic and intensity modulated radiotherapy has raised the need for standardizing the dosimetry of such fields using procedures consistent with those for conventional radiotherapy. An international working group, established by the IAEA in collaboration with AAPM and IPEM, is finalising a Code of Practice for the dosimetry of small static photon fields. While many problems of small field dosimetry have been raised, e.g. in IPEM Report 103, a vast amount of literature has addressed most of those and solutions have been proposed (often for specific situations though). The reported problems include the definition of field size, the field size dependent response of detectors, volume averaging, fluence perturbation corrections, reference conditions and beam quality in nonconventional reference fields. One area of importance for establishing a code of practice is the availability of data and this happens to be a dynamic area in which many papers have been published recently with new data or insights that enhance our understanding of small field dosimetry substantially. The code of practice will formalise and will make recommendations on the practical implementation of those solutions. It will consist of six chapters; an introduction, physics and technology of small field dosimetry, concepts and formalism, detectors and equipment, practical implementation of machine-specific reference dosimetry and practical implementation of relative dosimetry. It will also contain appendices on data, uncertainties, Monte Carlo simulation of correction factors and worksheets. This lecture will review the present understanding and solutions proposed in the literature for small field dosimetry, give an overview of the formalism and procedures that have been developed in the code of practice providing practical recommendations based on those solutions and present compilations of available data from the literature.
TEACHING LECTURE SP-0443 Current status of palliative radiation therapy J. Leer1 1 Radboud University Nijmegen Medical Centre, Radiotherapy, Nijmegen, The Netherlands Although palliative treatment with radiotherapy is about half of our workload, most clinical studies try to improve curative treatments. Until the end of the last decade, the used treatment schedules e.g. for brain or bone metastases were non evidence based. In the last 20 years however, several studies changed this. It is proven now that a single fraction for bone metastases is as effective as multiple fractions. This is also true for reirradiation as recently presented, based on the data of an international study. Radiotherapy used to be the standard for an imminent cord compression. Due to better surgical techniques, the role of surgery is being reinvestigated. For patients with favorable prognostic factors, life expectancy is an important basis to decide on a more aggressive or less aggressive treatment. More tailor made approaches are therefore proposed in function of the expected life expectancy of patients. To use this approach we need better methods to improve our estimation of life expectancy. Several recent studies have tried to categorize patients according to their life expectancy. In the last years a special group of patients is indentified, being the patients with a long life expectancy and oligometastases. More radical treatments with stereotactic radiotherapy are proposed and tested for these patients. In this presentation we will discuss all these more recent developments.