Volume 33, Issue 6, June 2006
Index of content:
- Therapy Symposium: Room 224 A
- Stereotactic Body Radiotherapy
33(2006); http://dx.doi.org/10.1118/1.2241474View Description Hide Description
Advances in high precision radiation planning and delivery,image guidance technologies and methods to account for and reduce organ motion have made it possible for cranial stereotactic radiosurgery techniques to be applied to tumors outside of the brain. Stereotactic body radiation therapy(SBRT) refers to the use of a limited number of high dose fractions delivered very conformally to targets with high accuracy, using biologic doses of radiation far higher than those used in standard fractionation.
The rationale for SBRT is that there is a need for improved local therapies for many primary cancers and also in the situation when there are ‘oligo’ (i.e. isolated) metastases, specifically in sites where surgery has been shown previously to be able to cure patients with ‘oligo’ metastases, e.g. colorectal cancer, renal cell cancer and sarcoma.SBRT has the potential to be used in place of surgery in situations when surgery may associated with high risk.
Advancements outside of radiationoncology also provide rationale for SBRT. Functional imaging such as PET allows better patient selection for SBRT. Furthermore, improvements in systemic therapy more likely to control micro‐metastases provide rationale for improving local therapies, such as SBRT, to reduce large foci of tumor burden.
There are radiobiological advantages to SBRT including less opportunity for tumor repopulation and repair. Furthermore, the shorter SBRT treatment times are more convenient for patients and have resource utilization advantages.
With highly potent doses of SBRTdelivered with steep dose gradients, the potential for geometric uncertainties in the setting of SBRT to lead to adverse clinical outcomes (tumor recurrence and/or toxicity) is high. Thus, the need for image guided radiation therapy(IGRT) to improve precision of dosedelivered is heightened. IGRT decreases the heterogeneity in delivereddoses, improving our ability to measure the impact of dosimetric and non‐dosimetric factors on SBRT clinical outcomes.
This lecture will provide an overview of the rapidly increasing clinical experience with SBRT and IGRT in the setting of SBRT. Case examples demonstrating clinical benefits and potential toxicities will be discussed.
1. To understand the clinical rationale for SBRT.
2. To describe the rationale for IGRT in SBRT.
3. To understand the increased risks of SBRT compared to conventional RT and the increased potential for error.
MO‐E‐224A‐02: Stereotactic Body Radiation Therapy: (1) Highlights of the AAPM Task Group Report 101 On SBRT33(2006); http://dx.doi.org/10.1118/1.2241475View Description Hide Description
The approved charges for the AAPM Task Group 101 entitled, “Stereotactic Body Radiation Therapy”, include: Charge (1): To review the literature and identify the range of historical experiences, reported clinical findings and expected outcomes; Charge (2): To review the relevant commercial products and associated clinical findings for an assessment of system capabilities, technology limitations, and patient related expectations and outcomes; Charge (3): Determine required criteria for setting‐up and establishing an ESRT facility, including protocols, equipment, resources, and QA procedures; Charge (4): Develop consistent documentation for prescribing, reporting, and recording ESRT treatment delivery. This part of the presentation will include highlights from the current TG101 report currently under review, including strategies and requirements for patient immobilization and repositioning, respiratory management, treatment planning, and reporting.
33(2006); http://dx.doi.org/10.1118/1.2241476View Description Hide Description
Stereotactic Body Radiotherapy(SBRT) ‐ Clinical Experience from MSKCC SBRT has the potential to maximize the benefit of highly conformal dosedelivery. New imaging capabilities and the improved precision of treatment machines is making possible the delivery of high doses to targets while minimizing dose to normal tissue and sparing nearby critical structures. As a result, new clinical techniques are being established to treat disease in soft tissue, such as metastatic disease in liver,lung, and lymph nodes and also to deliver very high doses to bony targets such as the spine. Both hypo‐fractionated and single fraction strategies are used.
The clinical procedures used to treat these sites at Memorial Sloan‐Kettering Cancer Center will be described, along with some preliminary outcomes.
- Symposium in Memoriam of C.J. Karzmark: Novel Treatment Modalities
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In the past 15–20 years substantial research and development effort has been put into the optimization of photonbeamradiation therapy, primarily into the development of intensity‐modulation techniques (IMRT). As far as the development of photonIMRT delivery technology is concerned, we may have almost reached a point of diminishing returns. In recent years novel treatment modalities (other than photons) are gaining more attention, which goes hand in hand with the construction of a number of new proton therapy facilities in this country.
The physical advantage of proton therapy is indisputable, even though it is not always used to its full extent in clinical treatments: The blessing of the finite range of protons goes along with some uncertainty in the position of the steep distal dose gradient region in the patient. This is because the position of the distal gradient is affected by setup errors, internal organ motion, metallic implants, and biological effects, among others. Due to these reasons, the distal gradient is not currently used for dose shaping. The full clinical utilization of the physical advantage of proton therapy also requires beam scanning and intensity‐modulated particle therapy (IMPT), which is in clinical use at only two centers.
The clinical benefit of proton therapy has been demonstrated for a relatively limited number of cases, and will be further studied as more proton centers are being brought on line. Of course, the benefit comes at a price. Several investigators now look into novel and potentially cheaper proton acceleration techniques, including laser acceleration, which will be discussed by Dr. Ma, and dielectric wall acceleration.
Outside of the USA the treatment with heavier charged particles, such as carbon ions, has become a topic of great interest, which will be reviewed by Dr. Jäkel. Both the treatment with protons and carbon ions open new avenues for image‐guided radiation therapy: Those particle beams activate positron emitters in the patient, which can be visualized with PET scanners and serve as an in‐vivo dosimeter, as explained by Dr. Parodi.
Last but not least, there has been renewed interest in lighter charged particles, namely electrons. The talks by Drs. Li and Papiez will show that electrons are a particularly attractive treatment option in combination with IMRT.
1. To give a brief update of the state of the art of protonradiation therapy.
2. To link the various presentations of this symposium.
33(2006); http://dx.doi.org/10.1118/1.2241580View Description Hide Description
Given the physical advantages of protons and light ions in target dose conformity and normal tissue sparing over commonly used photon and electron beams, why is proton or ion beam therapy only offered at a few facilities worldwide? The answer is high cost. Conventional proton or ion facilities are either cyclotron‐ or synchrotron‐based. The cost of the accelerator, treatment gantries and the building increases the total capital cost to about $100million for a proton facility and it can cost 2–3 times more for an ion facility. In this presentation we will look at alternative solutions that may provide more cost‐effective proton and light ion beams for radiation therapy. We will review recent developments in compact accelerator designs using superconductors and advances in particle acceleration using laser‐induced plasmas. Take laser‐proton acceleration as an example, theoretical studies show that at a laser intensity of 1021–1022 Wcm−2protons may be accelerated up to 300MeV with a spectrum and angular distribution. Experimental facilities dedicated to laser‐proton acceleration for cancer treatment have recently been established in the US, Japan and France. Because of the small acceleration distance a laser‐proton/ion accelerator is expected to be much more compact than conventional cyclotrons or synchrotrons and once developed may be the best candidate accelerator for particle therapy.
1. Review existing accelerator designs and alternative compact accelerator designs.
2. Review recent advances in laser technology and laser‐ion acceleration.
3. Discuss potential applications of laser‐accelerated protons for radiation therapy.
33(2006); http://dx.doi.org/10.1118/1.2241581View Description Hide Description
In 2004 hadron therapy celebrated its 50th anniversary and between 1954 and 2004 nearly 40'000 patients were treated with protons and about 4500 with heavier particles (mainly helium, carbon and neon). Especially within the last decade, hadron therapy has gained increasing interest. In mid 2004, 22 proton facilities were operational and about half of all patients treated with protons received their treatment within the last 5 years. There are currently 3 facilities treating patients with carbonions, two of them in Japan within a clinical setting. In Germany, a research therapy facility is in operation at the German heavy ion research Laboratory GSI (Darmstadt) since 1997. Currently, the construction of a new hospital based facility at the Heidelberg University hospital is ongoing and the facility is scheduled to start clinical operation in late 2007. Furthermore, an Italian facility is under construction and Austrian and French projects have been approved recently.
The Heidelberg facility will be the first one worldwide that will be equipped with an isocentric scanning gantry. The facility will offer proton and carbonions beams and thus will enable a direct comparison of treatment outcome applying both modalities using the same beam delivery system. The Heidelberg facility is designed to produce also beams of other ions like Helium or Oxygen and thus offers a large research potential to investigate which ion is best suited for which application.
An outline of the current potential of ion radiotherapy will be given and some open questions will be addressed. This includes a description of passive and active beam shaping systems, as well as their implications for treatment planning and dosimetry. The potential of ions will be compared against IMRT and radiotherapy with protonbeams on the basis of their physical and radiobiological properties. A short comparison of patient treatment plans for the various modalities will also be presented. The current clinical results gained with ions in Japan and Germany will be reviewed and an outlook on the clinical program in Heidelberg will be given.
33(2006); http://dx.doi.org/10.1118/1.2241582View Description Hide Description
Positron emission tomography(PET) is increasingly considered a promising technique for in‐vivo, non invasive verification of the actual treatment delivery in ion therapy. Positron‐emitting isotopes such as 11C (half‐life T1/2=20.4 min) and 15O (T1/2=2 min) are produced in tissue along the ion beam penetration as a by‐product of irradiation and can be potentially visualised by PET as a spatial marker of radiationdose deposition. PETimage guidance can contribute to a better clinical exploitation of the physical advantages of ion beams. It may improve confidence in the planning and delivery of more conformal treatments or allow for adaptive strategies in case of detected disagreements between the intended and actually delivered fields during fractionated radiotherapy.
As opposed to heavier ions like carbon, the positron activation induced by proton beams is limited to target (no projectile) fragments of the irradiatedtissue. This results in a weak spatial correlation between PETimages and dose. Nevertheless, previous phantom studies of several groups indicated feasibility and usefulness of the method for proton therapy. Information on the dosedelivery and the beam range in the patient can be gained by comparing the measured activity with a model prediction, as already clinically implemented for therapy with stable carbon ion beams elsewhere in Germany.
Issues related to the possible on‐line (i.e. during treatment) or off‐line (i.e. after treatment) imaging strategies will be briefly addressed. The presentation will focus on the first clinical pilot study recently concluded at Massachusetts General Hospital, Boston. Nine patients with a variety of tumour types and anatomical sites were imaged at a commercial, LSO‐based PET/CT scanner for 30 min starting within 20 min after single or multi‐field protonirradiation. Measured PET/CT images are compared to predictions based on Monte Carlo techniques combined with functional information taken from the literature and from the measured activity decay curves. The same Monte Carlo methods were also used to calculate the pattern of dose deposition for an additional direct comparison with the treatment plan, to enforce the clinical value of the comparison between measured and calculated PETimages. First conclusions on clinical feasibility, potential and limitations of off‐line PET/CT imaging of proton therapy will be discussed.
This lecture will provide an overview on the physical principles and issues of the unconventional application of PET to treatment verification in ion therapy, with a more detailed insight on the role of PET/CT image guidance after proton treatment.
1. Understand the physical principles of positron activation induced by therapeutic ion irradiation.
2. Understand the issues related to ion treatment verification by means of PETimaging, including the strategies for data acquisition and analysis.
3. Understand the issues related to clinical application of PET/CT imaging after proton therapy.
33(2006); http://dx.doi.org/10.1118/1.2241583View Description Hide Description
Purpose: To review and highlight the current status of the investigation and implementation of advanced mixed beam radiation therapy (MBRT) using energy‐ and intensity‐modulated electron radiotherapy (MERT) and intensity‐modulated photonradiotherapy(IMRT).Methods and Material: Disease sites such as post‐mastectomy chest wall, breast and head and neck etc. are better suited for MERT or MBRT. Feasibility studies on this topic have been performed. Monte Carlodose calculations, optimization methods and beam delivery systems using prototype electron MLCs or existing photonMLCs have been investigated. Smaller SSDs (60–70cm) are recommended when existing photonMLCs are used for beam delivery on Simens or Varian accelerators. Surface dose and beam properties are studied using the Monte Carlo method and compared with measurements. Treatment plans for head and neck and breast are generated with advanced MBRT using IMRT and MERT. MBRT beam delivery accuracy and efficiency are evaluated with phantom measurements. Results: Results show that the Monte Carlo method can provide accurate (2% or 2mm) dose distributions for MBRT. MBRT plans show advantageous dose distributions because IMRT provides superior lateral dose conformity while MERT added extra conformity in the depth direction. The combination of IMRT and MERT provides excellent dose conformity for treatments involving shallow target volumes such as breast and head and neck. Our results of MBRT for 78 breast patients showed that the acute skin complications were significantly reduced in a hypofractionated breast trial. Conclusion: MBRT can provide much improved target dose conformity and uniformity, adequate skin coverage/avoidance and significant reduction in the dose to the adjacent normal organs and critical structures for shallow tumor treatment. Preliminary results have shown great potential of this technique for treating breast, chest wall and head and neck cancers.
33(2006); http://dx.doi.org/10.1118/1.2241584View Description Hide Description
Purpose: To evaluate the feasibility of very high‐energy electron beams (VHEE, 150 – 300 MeV) for radiotherapy. The specific goal is to exploit fast scanning capabilities of pencil VHEE beams for better targeting of moving tumor tissue and moving sensitive organs in 4D image guided intensity modulated radiation therapy (IGIMRT). Method and Materials: VHEE have dosimetriccharacteristics comparable, and for some applications superior, to photonbeams. The dosimetry of the VHEE treatments can be verified by means of Monte Carlo simulations. The dosimetry of the VHEE treatments for moving tissues requires the knowledge of body geometries in subsequent phases of cyclical motions of regions of patient body that undergo treatment. The mutual interaction of dosesdelivered at different phases allows for optimal treatment in 4D radiation therapy. Therefore, optimization of 4D radiation therapy involves calculating jointly the set of all intensities at all phases of the cyclical tissue motion. This in turn means that optimal 4D IGIMRT plans require delivery of intensity maps that appropriately distribute given fractions of intensity maps over particular phases of moving tissues. Existing delivery systems for IMRT therapy (step and shoot IMRT and/or DMLC IMRT) are not capable of efficient delivery of predetermined by 4D IGIMRT planning “intensity map rates”. In contrast, fast scanning beam of VHEE electrons provides ideal tool for 4D IGIMRT delivery.Results: A sequence of dose calculations for representative VHEE beams are presented and compared with traditional photonbeam irradiations. Examples illustrating VHEE intensity rate maps for delivery of optimal 4D IGIMRT are presented and their delivery discussed in the context of MLC and electromagnetic pencil beam scanning capabilities of radiation devices. Conclusion: VHEE devices, capable to provide fast, electromagnetic scanning of pencil beams, are capable to efficiently deliver “intensity rate maps” of truly optimized 4D IGIMRT treatments.
- Symposium in Memoriam of Peter Wootton: Secondary Cancer Risk for Emerging Radiation Treatments
33(2006); http://dx.doi.org/10.1118/1.2241733View Description Hide Description
Peter Wootton was a legendary figure in the field of medical physics. He is known for early work on the foundations of dosimetry, for pioneering neutron therapy, for establishing regional medical physics services in the Pacific Northwest, and for many years leading the medical physics training program at the University of Washington. The American Association of Physicists in Medicine (AAPM) was incorporated in 1965, with Peter as a member of the initial Board of Directors, and signer of the organization's articles of incorporation. He also served a term as AAPM President in 1978. Under his leadership, in the early 1980's the University of Washington acquired, installed and operated what was then the most sophisticated neutron therapy facility in the entire world. This facility, still in service over 20 years later, continues to be state of the art. Peter was a superb teacher, and left a legacy of many M.S., Ph.D. and postdoctoral trainees, of which the author is one. His kind and wise spirit is greatly missed and remembered with awe and appreciation.
1. Understand the role of Peter Wootton in the development of the field of medical physics.
33(2006); http://dx.doi.org/10.1118/1.2241734View Description Hide Description
The increasing numbers of radiation treated patient surviving for long periods forces an assessment of their risk of radiation associated cancer. Dose response relationships for cancer induction in the laboratory mice varies with strain, gender, tissue/organ of concern, observation period, dose fractionation and LET. For most experiments, risk increased with dose in an orderly manner. However, in some large experiments on mice and one on Macaca mullata, there was no evident increase risk of cancer at 1–2.Gy single dose WBI. These studies were life span and autopsy examinations.
Risk of death due radiation induced solid cancer among 86,611 survivors of the atom bomb explosions in 1945 [entered the study in 1950] increased throughout the observation period of 52 years. There have been 10,127 deaths due to solid cancer and of these, 479 [4.7%] have been attributed to the radiation exposure. The time distribution of these cancer deaths have been: 18%, 19.1%, 27.1% and 35.4 % for the periods 1950–67, 1968–77, 1978–87 and 1988–97. Namely, 35% of these radiation cancer deaths occurred at 42–52 years post irradiation.
Data from 14 large and long follow‐up series of irradiated human patients demonstrate increased risk with dose for cancers of the stomach and pancreas; over the dose range 1–45 Gy. In contrast there was no evident increased risk of bladder or rectal cancer after doses of 1–60 Gy. For the studies on murine, canine, sub‐human and human subjects there is not a constant relative risk for the different organs,viz probability of a radiation cancer for a specified dose varies with the organ.
Consideration will be given to the differential risk between photon [conformal and IMXT], proton [broad beam energy modulated and pencil beam scattered] and 12C ion beams.
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The National Cancer Institute funds numerous clinical trials that employ radiation therapy either as the primary question in the trial or as standard of care adjuvant therapy that is only secondary to the primary agent. In any case it has been shown that the validity of the trial is strongly dependant upon the quality and reproducibility of the radiation administered. In all cases it is of paramount concern that the risks of the treatments be as quantified as possible so that the study design is valid and there can be a true informed consent. Toward those ends the NCI also funds efforts to ensure the correctness of the physical dosimetry (ie. Radiological Physics Center) and the comparability of advanced technical methods (ie. The Advanced Technology Consortium). This presentation will explain these cooperative agreements and highlight some of their accomplishments that impact upon the risks of using advanced radiotherapy methods in clinical trials.
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As new treatment modalities in RadiationOncology such as Intensity Modulated Radiation Therapy(IMRT) and Proton Therapy (PT) become more widely used, improved target coverage and lower doses to surrounding normal tissues are achieved at the expense of higher out‐of‐field doses to distant normal tissues. These higher out‐of‐field normal tissuedoses are the result of increased X ray leakage radiation from longer beam‐on times associated with IMRT and neutron leakage radiation associated with high energy X ray beams (>10 MV) and protons.IMRT beam‐on times can be 4–6 times that of conventional 3D treatments and neutrons produced by the high‐energy X rays and protons striking a patient have a high relative biological effectiveness (RBE). Measurement of the increased X ray and neutron leakage radiation is crucial if one is to assess any additional risks to the patient that might result from the higher out‐of‐field radiationdoses from these new treatment modalities. A variety of dosimeters, large volume ion chambers, diodes, survey meters, small volume ion chambers and thermoluminescent dosimeters(TLD), have been used to measure the X ray leakage in the treatment room and in the patient plane. TLD, because of its spatial resolution and ability to precisely measure low doses associated with leakage radiation, appears to be the preferable dosimeter.Neutrons are measured with bubble detectors, neutron meters utilizing a BF3 proportional counter, 197Au foil based activation either with a Bonner Sphere system/moderator or LiI dosimeters in Bonner Spheres. The gold activation technique has a calibration directly traceable to NIST and is the detector of choice for X ray produced neutrons. Due to the limited amount of neutron leakage measurement data around proton machines the ideal dosimeter has yet to be determined for this type of measurement. The measured dose‐equivalent values in an anthropomorphic phantom for X ray leakage from an X ray accelerator decrease with increased distance from central axis (CAX) in the patient plane by a factor of 3 to 10, depending on the delivery mode and accelerator type. IMRTtreatments on a Siemens machine results in higher dose‐equivalents than the same energies on a Varian machine. Neutron measurements in the patient plane were approximately the same despite the distance from the CAX. Overall, the total dose‐equivalent, X ray and neutrondose, decrease with distance from CAX with the Varian IMRT having the greatest decrease. Measured neutrondose‐equivalents from proton therapy strongly depend on the delivery apparatus and decrease with distance from the nozzle. This lecture will provide an overview of the measurement techniques for X ray and neutron leakage radiation from both X ray and proton therapy machines and the resulting measured dose‐equivalent values from which the risk of secondary cancers can be estimated.
1. Understand the various techniques used to accurately measure X ray and neutron leakage radiation in the patient plane.
2. Understand the magnitude of the dose‐equivalent in the patient plane from the various X ray accelerators and from proton therapy.
33(2006); http://dx.doi.org/10.1118/1.2241737View Description Hide Description
The risk for a patient to develop secondary cancers from non‐target exposures can be assessed from the equivalent doses to various radiosensitive organs. To determine organdoses, a computational model or physical phantom that represents the whole patient anatomy must be used. Physical phantoms (such as the RANDO and ATOM phantoms) have tiny cavities on each of the tissue‐equivalent slices for inserting TL and MOSFET dosimeters. When beam is delivered according to a patient's treatment plan, the dosimeters are processed to provide organdose information. The experimental procedures can be time‐consuming and expensive, especially when various patients and treatment plans are studies. Virtual patient models, on the other hand, can be combined with a Monte Carlo code to simulate the transport of radiation in the body. These models cover the entire body and typically contain a large number of defined organs. Coupled with a model of the accelerator, one can calculate detailed information about secondary dose distributions in the patient body. Whole‐body models are classified into three types: 1) Stylized models that are based on surface equations, 2) Tomographic models that are derived from medical images, and 3) Hybrid equation‐voxel models that describe organ boundaries using advanced primitives such as the NURBS for realtime deformation (4D simulations). To date, more than 20 tomographic models have been developed for radiation protection and nuclear medicine applications. An international consortium on computational human models (www.virtualphantoms.org) has been recently formed to promote research in this area. A team of researchers from Rensselaer, Vanderbilt, University of Florida, Massachusetts General Hospital and Johns Hopkins University is working on a project to standardize a library of age‐ and gender‐specific models.
This lecture presents the current status of patient modeling and the application of various tools to study secondary doses from radiation treatment involving both photons and protons. Detailed information on the VIP‐Man model developed from the Visible Human Project is presented. Segmentation of more than 80 organs, including the red bone marrow, and the implementation of the VIP‐Man model into EGS, MCNP/X and GEANT4 are discussed. Finally, organdoses and effective doses for protontreatment plans using various adult and pediatric patient models are presented.
Educational Objectives of this symposium are:
1. Understanding new tools of Monte Carlo‐based patient and accelerator modeling for secondary dose studies.
2. Understanding the effective dose data for various modalities.
- The Role of External Beam in Brachytherapy
WE‐E‐224A‐01: The Best of Both Worlds: Taking Advantage of Brachytherapy and External Beam Radiotherapy33(2006); http://dx.doi.org/10.1118/1.2241817View Description Hide Description
Introduction. Brachytherapy and external beam radiation represent opposite ends of the inverse square dose fall off spectrum. Brachytherapy is well suited for the delivery of conformal localized high doseradiation. While external beam radiation is well suited for conformal local and regional treatment, it is able to treat larger volumes in comparison to brachytherapy. This paradigm fits well with the natural history of many malignancies to provide maximal tumor control probability while minimizing normal tissue complications.
Methods and Materials. Two examples of combining brachytherapy and external beam radiation which illustrate the brachytherapy/external beam radiation therapy paradigm will be presented: The combination of high dose rate (HDR) brachytherapy and intensity modulated radiation(IMRT) for the definitive management of localized prostate cancer, and the use of a Yttrium 90 dural plaque in conjunction with image guided IMRT for vertebral body chordomas with significant epidural disease.
Results: HDR prostate brachytherapy and IMRT provides a very high level of disease control with only minor toxicity for patients with localized prostate cancer. This is likely due to careful treatment planning to minimize dose to critical structures such as the rectum and urethra while delivering a very high biologic effective dose to tumor bearing tissue. Similarly, Yttrium 90 dural plaques are able to deliver a very high dose of radiation to the dural surface, while underlying spinal cord will receive less than 5% of the prescribed dose. This will allow for a extremely high dose of radiation to be given to the planning target volume and increase the tumor control probability. Conclusions: Both brachytherapy and IMRT have inherent physical advantages that can be utilized to improve the therapeutic ratio of radiation therapy. Particularly in the management of tumors where a dose‐control relationship exits situated near dose sensitive structures, this paradigm is especially important.
33(2006); http://dx.doi.org/10.1118/1.2241818View Description Hide Description
Combination of permanent low dose‐rate interstitial implantation (LDR‐BRT) and external beam radiotherapy(EBRT) has been used in the treatment of clinically localized prostate cancer. Patients treated with this regimen initially receive an I‐125 implant prescribed to 110 Gy followed, two months later, by 50.4 Gy in 28 fractions using intensity modulated external beam radiotherapy. While a high radiationdose is delivered to the prostate in this setting, the actual biologic dose equivalence compared to monotherapy is not commonly invoked. I shall describe methodology for obtaining the fused dosimetry of this combined treatment and assigning a dose equivalence which in turn can be used to develop desired normal tissue and target constraints for biologic‐based treatment planning. Furthermore, I shall argue that LDR‐EBRT treatments, when properly designed, may confer significant advantages in terms of: a) escalating the dose without normal tissue penalties, b) avoid the question of organ motion, and c) decrease significantly the size of the PTV.
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For most tumors, increasing the number of fractions / lowering the dose rate, results in an improved therapeutic ratio between tumorcontrol and late sequelae. Why might this not be true for prostate cancer?
1. The basis for the difference in fractionation response of tumors and normal tissues is generally related to the fact that there is a larger proportion of cycling cells in tumors.
2. Back in 1999, various authors reasoned that prostate tumors might not respond to changes in fractionation in the same way as other cancers, as they contain smaller fractions of cycling cells — rather that they might respond like a late‐responding normal tissue. If so, much of the rationale for using many fractions, or using LDR, would disappear.
3. A first estimate of α/β for prostate cancer was made in 1999, by comparing results from external beam RT (EBRT) with those from brachytherapy. The estimate was 1.5 Gy [0.8–2.2 Gy], similar to α/β values for late‐responding normal tissues (∼3 Gy).
4. If the α/β value for prostate cancer is indeed similar to that for the surrounding late‐responding normal tissue, one could use many fewer fractions, or HDR, and yet, by choosing the right dose, have
• Comparable tumorcontrol and late sequelae to conventional fractionation
• Reduced early urinary sequelae
• Patient convenience
• Financial / resource advantages
• Potential for biologically‐based individualized treatments
5. Various other groups used the same approach (comparing EBRT with brachytherapy) for estimating the α/β ratio, and got similar results. However the weakness inherent in this comparative approach (different dose distributions, different treatment times, different dose rates, different RBEs, etc) has led to much controversy.
6. Subsequently an analysis was performed which avoided many of these pitfalls, in which EBRT + a 2‐fraction HDR boost was compared with EBRT + a 3‐fraction boost, all done with the same technique at the same institution. The result was 1.2 Gy [0.03–4.1 Gy], again comparable with α/β values for late‐responding normal tissues (∼3 Gy), and confirming that hypo‐fractionation or HDR are promising subjects for clinical trials of prostate cancer RT.
7. The arguments presented above really relate to the α/β value for prostate cancerin relation to that for the relevant late‐responding normal tissue. Just what is the appropriate α/β value for late rectal complications? Evidence from animal studies is that α/β>4 Gy for late rectal sequelae. This high value for late rectal damage is now supported by clinical results, which also suggest that much late rectal injury is actually consequential of early effects, and thus a high α/β value is not unreasonable.
8. If, then, the α/β value for prostate cancer is actually less than that for the surrounding late‐responding normal tissue, now hypofractionation or LDR, at the appropriate dose, would yield
• increased tumorcontrol for a given level of late complications, or
• decreased late complications for a given level of tumorcontrol.
9. The 2005 bottom line is that the long‐term clinical results to date for prostate hypofractionation do not give any indication of increased late sequelae compared with conventional fractionation — despite the fact that most of these results come from the pre‐IMRT era.
There is a great deal of controversy in the literature about the most appropriate value of the α/β ratio for prostate cancer. Hopefully the audience will leave with a better understanding of 1) why this is, and the 2) what is its significance in terms of optimizing prostate cancerradiotherapy?
33(2006); http://dx.doi.org/10.1118/1.2241820View Description Hide Description
Combinations of external‐beam radiation therapy (EB) and brachytherapy (BT) and have been used for many years. Conventionally, the EB and BT components are planned independently and limited to combinations of doses and dose‐time‐fractionation patterns that have been directly validated by clinical outcome studies. Ongoing research in radiobiological modeling, deformable image registration, and quantification of dose delivery uncertainties has the potential to provide the scientific foundation for truly integrated EB‐BT planning that could significantly improve clinical outcomes. First, the complementary strengths and weaknesses of BT and highly conformal EB methods, such as intensity‐modulated radiation therapy(IMRT), will be reviewed. Both IMRT and BT can support high dose conformality. IMRT can treat large surgically inaccessible target volumes with relatively homogeneous dose distributions. Where BT can be surgically realized, large dose fractions can be delivered with much higher geometric precision than with current IMRT delivery techniques. Next, clinical settings where integrated BT‐IMRT can have benefit will be reviewed. One example is definitive treatment of cervical cancer in which IMRT is used to compensate for primary tumor underdosing or normal tissue overdosing by the intracavitary BT insertions as well as for conformal treatment of the pelvic lymph nodes. Finally, the scientific and clinical challenges to integrated BT‐IMRT will be reviewed. For example, in high dose‐rate (HDR) interstitial BT of the prostate combined with IMRT whole pelvic irradiation for intermediate risk disease, a major source of dose‐delivery uncertainty is the conversion from physical‐to‐isoeffective dose needed to account for differences in fractionation.