- Email: [email protected]
SP-0601: Radiation-related treatment effects across the age spectrum with a focus on prostate cancer
S234
ESTRO 33, 2014
both costs and consequences, such as retreatment. Estimates of the costs of an intervention are clearly dependent on the perspective of the analysis although even just looking at the costs incurred by the provider, significant variability exists in the literature. A useful approach to understanding the resource implications for providers in the technologically complex and diverse area of Radiotherapy is Activity Based Costing in which the contributions of individual cost components, such as image guidance, can be readily identified. As there are inevitably uncertainties in the estimates of both costs and consequences of an economic evaluation it is advisable to perform a sensitivity analysis to understand the degree of reliance that can be placed on any conclusions drawn. In this TEACHING LECTURE all of the topics mentioned above will be explored to provide a context for the Symposium on Radiotherapy Costs which follows.
TEACHING LECTURE SP-0597 Cost-benefit of further optimisation of VMAT and IMRT planning M. Alber1 1 Aarhus University Hospital, Department of Clinical Medicine Department of Oncology, Aarhus C, Denmark This is an intentionally provocative review of the state of affairs in IMRT and VMAT planning. By the standards of modern times, a five-year-old technology like VMAT can hardly be called “innovative”, and a fifteenyear-old one like IMRT can gracefully be called “mature”. Does this imply that the development of treatment planning is complete? In reality, the “user experience” often fails to be a happy one because several aspects of ideal dose optimization are not addressed. Treatment planning is usually a dialogue between a highly trained and experienced individual and specialized software that requires that the interaction follows entirely its rules. This leads not only to economic inefficiency (time spent on training, on working around software quirks) but also to suboptimal treatment plans (optimum is, when the patience, creativity or time is up). One emerging solution is automated treatment planning, which casts the experience of the past decades into an algorithmic form and could remove the arbitrariness and toil of the current interfaces. A separate, but related issue is that of supporting the decision making process to balance risks and benefits of a treatment. A number of possibilities have become available recently (multi-criteria optimization, sensitivity analysis). However, as much as they point a way forward, they also put a spotlight on the most crucial stumbling block of treatment planning: it is one thing to optimize a dose, and another to obtain an applicable treatment plan for it. The two rival approaches: fluence profile sequencing and direct aperture optimization (or combinations thereof) suffer both from the same restrictions. A topquality dose computation is still by orders of magnitude too slow for being called in “the inner loop” of these algorithms, and the delivery constraints of any real-life linac are so convoluted that they render the problem virtually intractable. While it is understood pretty well what makes a dose distribution optimal, there is no method to date that can show that a treatment plan is optimal, other than trial-and-error with an unknown success rate. Yet, optimality of a treatment plan is indispensable for constructing one of the most relevant Pareto fronts in clinical routine: the one that relates plan quality to plan complexity, i.e. delivery time. The fact that the puzzle “How many beams are needed?” has been replaced by the puzzle “How many arcs are needed?” proves the urgency of this problem. It is easy to imagine that with automatic dose constraint generation, efficient decision making support and guaranteed treatment plan optimality, treatment planning would look completely different from today. Any one of these elements would have a sizeable economic impact and improve and homogenize treatment quality on a population scale. Therefore, the question is not if, but how.
TEACHING LECTURE SP-0598 State of the art of radiotherapy under MRI guidance U. Van der Heide1 1 The Netherlands Cancer Institute, Radiotherapy Amsterdam, The Netherlands
Department,
The use of in-room imaging to guide radiotherapy has resulted in a substantial improvement in the targeting accuracy of the treatment. Because of its superior soft-tissue contrast, several initiatives are now being pursued to use MRI rather than cone-beam CT for image guidance
during radiotherapy. In a full integration between a MRI scanner and an irradiation device, fast 3D imaging of the patient becomes feasible during the actual treatment. This opens the door to tracking and gating strategies, using the actual tumor location rather than a surrogate or model. In combination with on-line replanning this provides the means for highly adaptive radiotherapy. To introduce an MRI in the treatment room, several problems need to be resolved: the magnetic field of the MRI scanner will interfere with the acceleration of electrons in the linear accelerator; the radiofrequency waves used in the accelerator are picked up by the MRI scanner and will perturb the imaging; the dose deposition will be distorted as scattered electrons may be deflected by the magnetic field. In this TEACHING LECTURE the technical issues involved in integrating an MRI scanner with radiotherapy treatment equipment will be described. An overview will be given of the various initiatives that are currently developed, the solutions that have been proposed and the potential clinical applications that are investigated.
TEACHING LECTURE SP-0599 Fundamentals of scientific research S Bentzen University of Wisconsin School of Medicine Madison, USA Abstract not received
SYMPOSIUM: CLINICAL FACTORS RADIATION INDUCED TOXICITY
INFLUENCING
SP-0600 Epidemiology of late effects after radiotherapy at childhood and young adult ages F. van Leeuwen The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands Abstract not received SP-0601 Radiation-related treatment effects across the age spectrum with a focus on prostate cancer C. Cozzarini1 1 San Raffaele Scientific Institute, Radiotherapy, Milano, Italy There may be a generic, though possibly not always justified, reluctance to submit elderly patients (pts) to chemotherapy or radiotherapy (CT or RT), alone or combined, deriving from the fear of an excess rate of acute and late side-effects in older subjects. This analysis aims therefore to improve our understanding of the influence of age on the risk of radiation-induced toxicity with the ultimate objective of avoiding any age-based pre-treatment selection. The scenario emerging from a literature review is extremely diversified, with a correlation between toxicity and advanced age emerging clearly for some tumors/districts but not for others. Increasing age, for example, has been clearly identified as an independent risk factor for the onset of radiation-induced lung toxicity (RILT), including radiation pneumonitis and fibrosis in pts treated for lung cancers, with an estimated odds ratio of 1.20-1.30 per decade. Subjects older than 65 years are in fact at higher risk of RILT, and pneumonitis may occur in up to 77% of pts aged 61-70 undergoing RT for lung cancers, while the role of age in increasing the risk of acute Grade ≥2 esophageal injury in those pts is quite controversial. A significantly higher risk of infections, in particular pneumonitis, as well as acute and late esophageal dysfunctions including dysphagia and swallowing disorders leading to nutritional deficits, are on the contrary reported in elderly (>62-65 years) pts receiving chemoradiation for head and neck cancers, while the correlation between age and pharyngo-oesopagheal stricture is more controversial. A subgroup analysis from the German Hodgkin Study Group pertaining to 1204 pts with early-stage Hodgkin’s lymphoma, randomized, after 4 cycles of chemotherapy, to receive 30 Gy with either extended (EF-RT) or involved field (IF-RT) technique, showed that pts ≥60 years at diagnosis treated with EF-RT not only suffered from more acute toxicities but had an even poorer outcome than those receiving IF-RT. With respect to brain tumors, an increased risk of atrophy and white matter lesions was found in adult pts >40 years who received focal or whole brain RT for low-grade gliomas. Likewise, in pts submitted to total
ESTRO 33, 2014 body irradiation (TBI) with autologous bone marrow transplantation for the treatment of hematologic malignancies, those ≥45 years may develop lower average post-transplant values of FEV1 and DLCO than younger pts. Pulmonary complications of TBI can cause long-term morbidity and mortality, and not surprisingly pts ≥50 years may have a posttransplant hazard ratio of death up to 3.5 times higher than their younger counterparts. On the contrary, patient age at the time of irradiation seems not to influence the risk of acute or late toxicity in women receiving postsurgical RT for breast cancer, or submitted to RT, alone or in combination to CT, for gynecologic cancers. Similarly, no clear correlation emerges in pts irradiated for gastrointestinal abdominal cancers, e.g. pancreatic or rectal, with respect to the risk of the most common duodenal or intestinal toxicities. Likewise, in men treated with definitive or post-surgical RT for clinically localized prostate carcinoma (PCa), age does not seem to increase the risk of acute or late rectal or intestinal side-effects. With respect to urinary toxicity, the influence of age on the risk of acute and late urinary complications has been thoroughly investigated in pts undergoing RT with radical intent, with some investigators finding a worse toxicity profile in older pts and others indicating that urinary toxicity was independent of age. In the post-prostatectomy setting, we quite recently found age to be a significant predictor of late Grade 3 urinary sequelae, though with an opposite effect according to the treatment objective: in the salvage cohort age >71 years was in fact a significant predictor of late Grade 3 urinary sequelae, which were more common, on the contrary, in younger (≤62 years) pts in the adjuvant cohort. Finally, a thorough assessment of the impact of age on the risk of radiation-induced erectile dysfunction is made more complex by the physiological decline of erectile function in men aged >65 years, just as those more frequently irradiated for PCa. SP-0602 Age, aging and the age-old question: how does age affect the induction of normal tissue effects? J.P. Williams1, C.J. Johnston2, J.N. Finkelstein3 1 University of Rochester Cancer Center, Environmental Medicine & Radiation Oncology, Rochester NY, USA 2 University of Rochester Cancer Center, Environmental Medicine, Rochester NY, USA 3 University of Rochester Cancer Center, Pediatrics & Neonatology, Rochester NY, USA It is increasingly well recognized that the mechanisms that underlie the progression towards radiation-induced normal tissue effects are a complex interaction of altered physiological systems and regulatory pathways: these include localized and/or systemic immune dysfunction, stem cell deficits, barrier breakdown, and parenchymal-inflammatory cell crosstalk. Adding further complexity is that, given the range of endpoints that have been identified as treatment (radiation)-related, it is likely that the degree of influence asserted by each of the involved elements will vary according to biological and physical factors. Interestingly, one biological factor that has seen little to no research is age, despite the significant role that this may play in late effect development. Some of the differences that are seen between pediatric and adult normal tissue late effects may be considered a reflection of the differential complexities and varying developmental rates in tissue organization seen between the three stages of development: pediatric, adult and geriatric. Furthermore, the physics of radiation treatment will be affected by the physical size of the patient and their respective anatomy, which obviously can vary considerably across the age spectrum. Accompanying treatment modalities may also affect the normal tissue response; for example, chemotherapy is more widely used in the pediatric population and its interaction with fractionated radiation protocols is not widely assessed in terms of age. These and other confounding factors that may influence the role of age in normal tissue late effect development will be discussed.
SYMPOSIUM: DOSE ESCALATION SP-0603 The use of normal tissue-to-tumour alpha/beta ratios evaluate and optimise radiotherapy treatments H.A. Gay1, J.Y. Jin2, A.J. Chang3, R.K. Ten Haken4 1 Washington University in Saint Louis, Radiation Oncology, Saint Louis, USA 2 Georgia Regents University Cancer Center, Radiation Oncology, Augusta, USA
S235 3 University of California San Francisco, Radiation Oncology, San Francisco, USA 4 University of Michigan, Radiation Oncology, Ann Arbor, USA
Purpose: To achieve a better understanding of the effect of the number of fractions on normal tissue sparing for equivalent tumor control in radiation therapy plans by using equivalent biologically effective dose (BED) isoeffect calculations. Methods and materials:The simple linear quadratic (LQ) model was assumed to be valid up to 10 Gy per fraction. Using the model, we formulated a well-known mathematical equality for the tumor prescription dose and probed and solved a second mathematical problem for normal tissue isoeffect. That is, for a given arbitrary relative isodose distribution (treatment plan in percentages), 2 isoeffective tumor treatment regimens (N fractions of the dose D and n fractions of the dose d) were denoted, which resulted in the same BED (corresponding to 100% prescription isodose). Given these situations, the LQ model was further exploited to mathematically establish a unique relative isodose level, z (%), for the same arbitrary treatment plan, where the BED to normal tissues was also isoeffective for both fractionation regimens. Results: For the previously stated problem, the relative isodose level z (%), where the BEDs to the normal tissue were also equal, was defined by the normal tissue α/β ratio divided by the tumor α/β times 100%. Fewer fractions offers a therapeutic advantage for those portions of the normal tissue located outside the isodose surface, z, whereas more fractions offer a therapeutic advantage for those portions of the normal tissue within the isodose surface, z. Conclusions: Relative isodose-based treatment plan evaluations may be useful for comparing isoeffective tumor regimens in terms of normal tissue effects. Regions of tissues that would benefit from hypofractionation or standard fractionation can be identified. SP-0604 Clinical data demonstrating dose response in breast / cervix / prostate / head and neck E. Van Limbergen1 1 University Hospital Gasthuisberg, Radiation Oncology, Leuven, Belgium Brachytherapy is a well established radiation modality for dose escalation in many tumor sites, usually implemented as a boost but in some cases also as monotherapy. In breast cancer there is strong evidence that increasing the doses above 50 Gy with 15 Gy reduces local failure rates with a factor 2, as well after breast conservative surgery with negative or positive margins, as after radical radiotherapy alone (Van Limbergen 1987, 1990). This dose escalation concept has been confirmed in several randomized trials. Data from several retrospective and randomized studies suggest that the higher integral dose delivered by brachytherapy improves local control, although most studies are underpowered to prove that the observed gain is significantly different from external beam modalities. Further research on larger sample sizes is needed. For cervix cancer, increased local control rates have been related to higher doses to point A, leading to higher prescription doses for larger tumors. However Point A dose is a rather poor surrogate for target dose. With the implementation of IGABT, full 3 D data have become available. A recent analysis of retrospective multicenter study (Retro Embrace) on 600 patients showed a clear dose response with > 95% local control when the D90 to the High Risk CTV exceeds 86 Gy EQD2. Also for prostate cancer control a dose response has been demonstrated both with external beam and LDR prostate brachytherapy treatments. The use of post-implant D90 (the minimum dose received by 90% of the prostate) and V100 (the percentage of the prostate that receives at least 100% of the prescription dose) as quality measures in LDR prostate brachytherapy is standard practice but clinical and dosimetric uncertainty factors can have a significant impact on these metrics. Evidence is emerging in prostate brachytherapy of the predictive role of these metrics with clinical outcomes of HDR brachytherapy. For Head and Neck retrospective data showed improved local control with increased dose and dose rates. However since the oral and oropharyngeal mucosa (OAR) are part of the CTV this improved local control is accompagnied by higher complication rates, which makes the choice of an optimal dose / dose rate more difficult than in situations where the OAR can be spared by improving dose distributions with the help of 3D imaging and Stepping Source optimization possibilities of a Stepping Source afterloader.
ESTRO 33, 2014
both costs and consequences, such as retreatment. Estimates of the costs of an intervention are clearly dependent on the perspective of the analysis although even just looking at the costs incurred by the provider, significant variability exists in the literature. A useful approach to understanding the resource implications for providers in the technologically complex and diverse area of Radiotherapy is Activity Based Costing in which the contributions of individual cost components, such as image guidance, can be readily identified. As there are inevitably uncertainties in the estimates of both costs and consequences of an economic evaluation it is advisable to perform a sensitivity analysis to understand the degree of reliance that can be placed on any conclusions drawn. In this TEACHING LECTURE all of the topics mentioned above will be explored to provide a context for the Symposium on Radiotherapy Costs which follows.
TEACHING LECTURE SP-0597 Cost-benefit of further optimisation of VMAT and IMRT planning M. Alber1 1 Aarhus University Hospital, Department of Clinical Medicine Department of Oncology, Aarhus C, Denmark This is an intentionally provocative review of the state of affairs in IMRT and VMAT planning. By the standards of modern times, a five-year-old technology like VMAT can hardly be called “innovative”, and a fifteenyear-old one like IMRT can gracefully be called “mature”. Does this imply that the development of treatment planning is complete? In reality, the “user experience” often fails to be a happy one because several aspects of ideal dose optimization are not addressed. Treatment planning is usually a dialogue between a highly trained and experienced individual and specialized software that requires that the interaction follows entirely its rules. This leads not only to economic inefficiency (time spent on training, on working around software quirks) but also to suboptimal treatment plans (optimum is, when the patience, creativity or time is up). One emerging solution is automated treatment planning, which casts the experience of the past decades into an algorithmic form and could remove the arbitrariness and toil of the current interfaces. A separate, but related issue is that of supporting the decision making process to balance risks and benefits of a treatment. A number of possibilities have become available recently (multi-criteria optimization, sensitivity analysis). However, as much as they point a way forward, they also put a spotlight on the most crucial stumbling block of treatment planning: it is one thing to optimize a dose, and another to obtain an applicable treatment plan for it. The two rival approaches: fluence profile sequencing and direct aperture optimization (or combinations thereof) suffer both from the same restrictions. A topquality dose computation is still by orders of magnitude too slow for being called in “the inner loop” of these algorithms, and the delivery constraints of any real-life linac are so convoluted that they render the problem virtually intractable. While it is understood pretty well what makes a dose distribution optimal, there is no method to date that can show that a treatment plan is optimal, other than trial-and-error with an unknown success rate. Yet, optimality of a treatment plan is indispensable for constructing one of the most relevant Pareto fronts in clinical routine: the one that relates plan quality to plan complexity, i.e. delivery time. The fact that the puzzle “How many beams are needed?” has been replaced by the puzzle “How many arcs are needed?” proves the urgency of this problem. It is easy to imagine that with automatic dose constraint generation, efficient decision making support and guaranteed treatment plan optimality, treatment planning would look completely different from today. Any one of these elements would have a sizeable economic impact and improve and homogenize treatment quality on a population scale. Therefore, the question is not if, but how.
TEACHING LECTURE SP-0598 State of the art of radiotherapy under MRI guidance U. Van der Heide1 1 The Netherlands Cancer Institute, Radiotherapy Amsterdam, The Netherlands
Department,
The use of in-room imaging to guide radiotherapy has resulted in a substantial improvement in the targeting accuracy of the treatment. Because of its superior soft-tissue contrast, several initiatives are now being pursued to use MRI rather than cone-beam CT for image guidance
during radiotherapy. In a full integration between a MRI scanner and an irradiation device, fast 3D imaging of the patient becomes feasible during the actual treatment. This opens the door to tracking and gating strategies, using the actual tumor location rather than a surrogate or model. In combination with on-line replanning this provides the means for highly adaptive radiotherapy. To introduce an MRI in the treatment room, several problems need to be resolved: the magnetic field of the MRI scanner will interfere with the acceleration of electrons in the linear accelerator; the radiofrequency waves used in the accelerator are picked up by the MRI scanner and will perturb the imaging; the dose deposition will be distorted as scattered electrons may be deflected by the magnetic field. In this TEACHING LECTURE the technical issues involved in integrating an MRI scanner with radiotherapy treatment equipment will be described. An overview will be given of the various initiatives that are currently developed, the solutions that have been proposed and the potential clinical applications that are investigated.
TEACHING LECTURE SP-0599 Fundamentals of scientific research S Bentzen University of Wisconsin School of Medicine Madison, USA Abstract not received
SYMPOSIUM: CLINICAL FACTORS RADIATION INDUCED TOXICITY
INFLUENCING
SP-0600 Epidemiology of late effects after radiotherapy at childhood and young adult ages F. van Leeuwen The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands Abstract not received SP-0601 Radiation-related treatment effects across the age spectrum with a focus on prostate cancer C. Cozzarini1 1 San Raffaele Scientific Institute, Radiotherapy, Milano, Italy There may be a generic, though possibly not always justified, reluctance to submit elderly patients (pts) to chemotherapy or radiotherapy (CT or RT), alone or combined, deriving from the fear of an excess rate of acute and late side-effects in older subjects. This analysis aims therefore to improve our understanding of the influence of age on the risk of radiation-induced toxicity with the ultimate objective of avoiding any age-based pre-treatment selection. The scenario emerging from a literature review is extremely diversified, with a correlation between toxicity and advanced age emerging clearly for some tumors/districts but not for others. Increasing age, for example, has been clearly identified as an independent risk factor for the onset of radiation-induced lung toxicity (RILT), including radiation pneumonitis and fibrosis in pts treated for lung cancers, with an estimated odds ratio of 1.20-1.30 per decade. Subjects older than 65 years are in fact at higher risk of RILT, and pneumonitis may occur in up to 77% of pts aged 61-70 undergoing RT for lung cancers, while the role of age in increasing the risk of acute Grade ≥2 esophageal injury in those pts is quite controversial. A significantly higher risk of infections, in particular pneumonitis, as well as acute and late esophageal dysfunctions including dysphagia and swallowing disorders leading to nutritional deficits, are on the contrary reported in elderly (>62-65 years) pts receiving chemoradiation for head and neck cancers, while the correlation between age and pharyngo-oesopagheal stricture is more controversial. A subgroup analysis from the German Hodgkin Study Group pertaining to 1204 pts with early-stage Hodgkin’s lymphoma, randomized, after 4 cycles of chemotherapy, to receive 30 Gy with either extended (EF-RT) or involved field (IF-RT) technique, showed that pts ≥60 years at diagnosis treated with EF-RT not only suffered from more acute toxicities but had an even poorer outcome than those receiving IF-RT. With respect to brain tumors, an increased risk of atrophy and white matter lesions was found in adult pts >40 years who received focal or whole brain RT for low-grade gliomas. Likewise, in pts submitted to total
ESTRO 33, 2014 body irradiation (TBI) with autologous bone marrow transplantation for the treatment of hematologic malignancies, those ≥45 years may develop lower average post-transplant values of FEV1 and DLCO than younger pts. Pulmonary complications of TBI can cause long-term morbidity and mortality, and not surprisingly pts ≥50 years may have a posttransplant hazard ratio of death up to 3.5 times higher than their younger counterparts. On the contrary, patient age at the time of irradiation seems not to influence the risk of acute or late toxicity in women receiving postsurgical RT for breast cancer, or submitted to RT, alone or in combination to CT, for gynecologic cancers. Similarly, no clear correlation emerges in pts irradiated for gastrointestinal abdominal cancers, e.g. pancreatic or rectal, with respect to the risk of the most common duodenal or intestinal toxicities. Likewise, in men treated with definitive or post-surgical RT for clinically localized prostate carcinoma (PCa), age does not seem to increase the risk of acute or late rectal or intestinal side-effects. With respect to urinary toxicity, the influence of age on the risk of acute and late urinary complications has been thoroughly investigated in pts undergoing RT with radical intent, with some investigators finding a worse toxicity profile in older pts and others indicating that urinary toxicity was independent of age. In the post-prostatectomy setting, we quite recently found age to be a significant predictor of late Grade 3 urinary sequelae, though with an opposite effect according to the treatment objective: in the salvage cohort age >71 years was in fact a significant predictor of late Grade 3 urinary sequelae, which were more common, on the contrary, in younger (≤62 years) pts in the adjuvant cohort. Finally, a thorough assessment of the impact of age on the risk of radiation-induced erectile dysfunction is made more complex by the physiological decline of erectile function in men aged >65 years, just as those more frequently irradiated for PCa. SP-0602 Age, aging and the age-old question: how does age affect the induction of normal tissue effects? J.P. Williams1, C.J. Johnston2, J.N. Finkelstein3 1 University of Rochester Cancer Center, Environmental Medicine & Radiation Oncology, Rochester NY, USA 2 University of Rochester Cancer Center, Environmental Medicine, Rochester NY, USA 3 University of Rochester Cancer Center, Pediatrics & Neonatology, Rochester NY, USA It is increasingly well recognized that the mechanisms that underlie the progression towards radiation-induced normal tissue effects are a complex interaction of altered physiological systems and regulatory pathways: these include localized and/or systemic immune dysfunction, stem cell deficits, barrier breakdown, and parenchymal-inflammatory cell crosstalk. Adding further complexity is that, given the range of endpoints that have been identified as treatment (radiation)-related, it is likely that the degree of influence asserted by each of the involved elements will vary according to biological and physical factors. Interestingly, one biological factor that has seen little to no research is age, despite the significant role that this may play in late effect development. Some of the differences that are seen between pediatric and adult normal tissue late effects may be considered a reflection of the differential complexities and varying developmental rates in tissue organization seen between the three stages of development: pediatric, adult and geriatric. Furthermore, the physics of radiation treatment will be affected by the physical size of the patient and their respective anatomy, which obviously can vary considerably across the age spectrum. Accompanying treatment modalities may also affect the normal tissue response; for example, chemotherapy is more widely used in the pediatric population and its interaction with fractionated radiation protocols is not widely assessed in terms of age. These and other confounding factors that may influence the role of age in normal tissue late effect development will be discussed.
SYMPOSIUM: DOSE ESCALATION SP-0603 The use of normal tissue-to-tumour alpha/beta ratios evaluate and optimise radiotherapy treatments H.A. Gay1, J.Y. Jin2, A.J. Chang3, R.K. Ten Haken4 1 Washington University in Saint Louis, Radiation Oncology, Saint Louis, USA 2 Georgia Regents University Cancer Center, Radiation Oncology, Augusta, USA
S235 3 University of California San Francisco, Radiation Oncology, San Francisco, USA 4 University of Michigan, Radiation Oncology, Ann Arbor, USA
Purpose: To achieve a better understanding of the effect of the number of fractions on normal tissue sparing for equivalent tumor control in radiation therapy plans by using equivalent biologically effective dose (BED) isoeffect calculations. Methods and materials:The simple linear quadratic (LQ) model was assumed to be valid up to 10 Gy per fraction. Using the model, we formulated a well-known mathematical equality for the tumor prescription dose and probed and solved a second mathematical problem for normal tissue isoeffect. That is, for a given arbitrary relative isodose distribution (treatment plan in percentages), 2 isoeffective tumor treatment regimens (N fractions of the dose D and n fractions of the dose d) were denoted, which resulted in the same BED (corresponding to 100% prescription isodose). Given these situations, the LQ model was further exploited to mathematically establish a unique relative isodose level, z (%), for the same arbitrary treatment plan, where the BED to normal tissues was also isoeffective for both fractionation regimens. Results: For the previously stated problem, the relative isodose level z (%), where the BEDs to the normal tissue were also equal, was defined by the normal tissue α/β ratio divided by the tumor α/β times 100%. Fewer fractions offers a therapeutic advantage for those portions of the normal tissue located outside the isodose surface, z, whereas more fractions offer a therapeutic advantage for those portions of the normal tissue within the isodose surface, z. Conclusions: Relative isodose-based treatment plan evaluations may be useful for comparing isoeffective tumor regimens in terms of normal tissue effects. Regions of tissues that would benefit from hypofractionation or standard fractionation can be identified. SP-0604 Clinical data demonstrating dose response in breast / cervix / prostate / head and neck E. Van Limbergen1 1 University Hospital Gasthuisberg, Radiation Oncology, Leuven, Belgium Brachytherapy is a well established radiation modality for dose escalation in many tumor sites, usually implemented as a boost but in some cases also as monotherapy. In breast cancer there is strong evidence that increasing the doses above 50 Gy with 15 Gy reduces local failure rates with a factor 2, as well after breast conservative surgery with negative or positive margins, as after radical radiotherapy alone (Van Limbergen 1987, 1990). This dose escalation concept has been confirmed in several randomized trials. Data from several retrospective and randomized studies suggest that the higher integral dose delivered by brachytherapy improves local control, although most studies are underpowered to prove that the observed gain is significantly different from external beam modalities. Further research on larger sample sizes is needed. For cervix cancer, increased local control rates have been related to higher doses to point A, leading to higher prescription doses for larger tumors. However Point A dose is a rather poor surrogate for target dose. With the implementation of IGABT, full 3 D data have become available. A recent analysis of retrospective multicenter study (Retro Embrace) on 600 patients showed a clear dose response with > 95% local control when the D90 to the High Risk CTV exceeds 86 Gy EQD2. Also for prostate cancer control a dose response has been demonstrated both with external beam and LDR prostate brachytherapy treatments. The use of post-implant D90 (the minimum dose received by 90% of the prostate) and V100 (the percentage of the prostate that receives at least 100% of the prescription dose) as quality measures in LDR prostate brachytherapy is standard practice but clinical and dosimetric uncertainty factors can have a significant impact on these metrics. Evidence is emerging in prostate brachytherapy of the predictive role of these metrics with clinical outcomes of HDR brachytherapy. For Head and Neck retrospective data showed improved local control with increased dose and dose rates. However since the oral and oropharyngeal mucosa (OAR) are part of the CTV this improved local control is accompagnied by higher complication rates, which makes the choice of an optimal dose / dose rate more difficult than in situations where the OAR can be spared by improving dose distributions with the help of 3D imaging and Stepping Source optimization possibilities of a Stepping Source afterloader.