International Journal of
Radiation Oncology biology
physics
www.redjournal.org
Oncology ScandThe Vision of Medical Physics By Eric E. Klein, PhD, Senior Editor, Nesrin Dogan, PhD, Associate Editor, Zhe Chen, PhD, Associate Editor, Claudio Fiorino, PhD, Associate Editor The Physics editorial team for the International Journal of Radiation Oncology, Biology, Physics includes 8 associate editors and 1 senior editor. Physicists from North America and Europe with a variety of expertise constitute the team, which receives the greatest number of manuscripts in relationship to other categories within the journal. This unfortunately leads to a high number of manuscripts being rejected or declined. We recently set up formal decline criteria, which include the following: 1. Weak methods of data collection, absence of statistics 2. Conclusions that mimic the same findings of a higher-quality published work 3. Articles unlikely to be cited 4. Inability to read a manuscript without significant English language editing 5. Low-quality data, such as single-institution experience or treatment planning comparisons 6. A single case study illustrating various situations and general conclusions To this end, we would like to see manuscripts on the following subjects: clinical treatment techniques and strategy, physics- and technology-driven clinical trials, imaging and modeling of tumor and tissue response for adaptive therapy, database mining, and management of treatment uncertainties. We have chosen 3 articles for this month’s Oncology Scan, which we have summarized and on which we comment. One particular article is a part of the 20/20 Vision Series of Medical Physics, which covers subjects in the form of white papers. Schlesinger et al. MR-guided focused ultrasound surgery, present and future. Med Phys 2013. (1) Summary: Magnetic resonance (MR)-guided focused ultrasound surgery (MRgFUS) is an emerging technology with potential for a wide range of applications, including in radiation oncology (2). MRgFUS uses high-intensity focused ultrasound along with MR image guidance and was originally developed for the treatment of bone metastases and uterine fibroids (3). However, it has a potential to be used as an adjuvant therapy to traditional radiation and chemotherapy. This article reviews the aspects of the basic physics and biology of MRgFUS and the challenges that the
Int J Radiation Oncol Biol Phys, Vol. 88, No. 2, pp. 251e253, 2014 0360-3016/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ijrobp.2013.08.022
current technology faces before it can transition into a more widely available clinical tool. For therapeutic applications, the goal of FUS is to minimize the reflection and transfer sufficient thermal energy to the target to create the desired biological effect. The MR guidance is required to identify and localize the target and to determine the absolute temperature changes in the form of MR thermometry. The high-intensity ultrasound has a variety of desirable physical effects (eg, thermal and mechanical effects) and biological effects (eg, local ablation, thrombolysis, radiosensitization) in tissue, which can be used for treatment advantage. Since the first MRgFUS system was cleared in 2004 by the US Food and Drug Administration for the treatment of uterine fibroids, several ultrasound-guided and MR-guided FUS systems have been developed. Current clinical studies on metastatic bone tumors have shown significant reduction in pain and visual acuity scale. Although MRgFUS has much potential, the routine clinical use of this technology is still very limited because of clinical, technical, and regulatory barriers. Furthermore, the MRgFUS need to be expanded to different clinical areas if it is to be widely accepted rather than remaining as a niche treatment for only certain subsets of patients. The authors discuss some of the challenges that MRgFUS overcomes before it can have wideranging uses. The main challenges that have been addressed in this work include enhanced heating caused by the cavitation process; unintended absorption of ultrasound energy by the macroscopic and microscopic calcifications in the tissue; the presence of standing waves, which can cause undesired heating, damaging the unintended tissue; a lack of clear standards for exposure, calibration of dose, and clinical acceptance; long treatment times; additional complications caused by presence of bone and implants; motion of the patient or internal organs; and the long time required to create treatment plans. The authors pointed out that some progress has already been made to solve some of these issues. In addition to the physics and engineering challenges, clinical and financial challenges can be a major barrier for the widespread adoption of this new technology. Gaining clinical acceptance in an already crowded field with many accepted treatment options is another challenge for this new technology, along with proving its safety and effectiveness. There have been some encouraging studies on the use of MRgFUS for the treatment of breast cancer, prostate cancer, hepatic tumors, neuropathic pain, and functional
252
Oncology Scan
disorders, with some early results comparable to or better than those reported for conventional radiation therapy. Comment: MRgFUS is an emerging technology with potential applications in a variety of clinical indications, including benign and malignant tumors, pain management, vascular problems, and many others. As the authors pointed out, the use of ultrasound for therapeutic purposes is not a new idea and has been studied by many researchers. Advances in imaging, computer, and ultrasound technology in the past decade have brought this idea close to reality in the clinic. MRgFUS technology has many technical, practical, and financial challenges that need to be addressed. These challenges are being considered, and it is highly likely that they will be resolved with time. Whether this technique can find widespread adoption will depend on the accumulation of clinical data and cost-effectiveness. It is very possible that MRgFUS will be used in conjunction with radiation therapy in the future. O¨de´n et al. Dosimetric comparison between intra-cavitary breast brachytherapy techniques for accelerated partial breast irradiation and a novel stereotactic radiotherapy device for breast cancer: GammaPod. Phys Med Biol 2013. (4) Summary: This article describes the results of a dosimetric study aimed at comparing the dose-shaping capabilities of a new dedicated stereotactic radiation therapy device for breast cancer, known as GammaPod, with those of commonly used and relatively well-developed intracavitary brachytherapy techniques for accelerated partial breast irradiation (APBI) with an 192Ir remote afterloader (5). The GammaPod device consists of a hemispherical source carrier containing 36 60Co sources and a complete patient support and dose delivery system. Dose distributions achievable by GammaPod, for spherical target volumes with diameters of 2, 4, 5.6, and 6.5 cm and different proximities to critical structures, were determined by use of the integrated treatment planning system of GammaPod based on the computed tomography (CT) images of 1 test patient. The test patient was CT-scanned in the prone GammaPod treatment position with the target breast resting in a specially designed breast cup under negative pressure. For comparison, dose distributions of 3 APBI brachytherapy techniques (single-lumen balloon with 1 central dwell position, multilumen balloon with multiple dwell positions in up to 5 catheters, and multicatheter applicators using 1 central and 6 to 10 evenly distributed peripheral catheters) were generated for balloon diameters of 4, 4.5, and 5 cm and for various applicator-to-skin distances, respectively. The 3-dimensional (3D) dose distribution for each case was optimized to meet the same dose coverage constraints of the National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-39 guidelines. Comparative analysis of the dose distributions was performed with respect to dose coverage for the target volume, dose fall-off characteristics outside the target, and dose to critical organs such as skin. The key findings of this article are these: 1. Both GammaPod and brachytherapy techniques could produce dose distributions that meet the dosimetric goals of the NSABP B-39 protocol for all target sizes investigated, and GammaPod produced more homogeneous dose distributions within the target volume than did the brachytherapy techniques. The mean
International Journal of Radiation Oncology Biology Physics values of V95 for the brachytherapy techniques and GammaPod were 95% and 96% of the target volume, respectively. 2. The dose falloff outside the target was generally steeper with the brachytherapy techniques at small distances from the target edge (up to approximately 1 cm). At larger distances (more than about 1 cm), however, the dose fall-off produced by GammaPod was steeper. 3. For targets close to the skin, the relative skin doses were considerably lower for GammaPod than for any of the brachytherapy techniques because of the dose optimization ability of GammaPod. The authors conclude that GammaPod allows adequate and more uniform dose coverage to centrally and peripherally located targets, with acceptable dose falloff and lower relative skin dose than the brachytherapy techniques considered. Comment: Accelerated partial breast irradiation using intracavitary brachytherapy techniques or 3D conformal radiation therapy (3DCRT) has become an established modality for selected women with early-stage breast cancer. Over the past decade, technical improvements for APBI dose delivery have involved mainly the development of multilumen balloon and multicatheter applicators, whereas the techniques using 3DCRT and intensity modulated radiation therapy (IMRT) have remained relatively unchanged. The introduction of the GammaPod as a dedicated stereotactic radiation therapy device for breast cancer is potentially a major development in 3DCRT techniques for APBI. Whether this novel modality can enhance breast cancer radiation therapy depends on its dose-shaping capability and its ease of use for patient treatment. Given that the GammaPod system is progressing toward clinical implementation, dosimetric comparisons with the existing treatment modalities are necessary. Although a few preliminary comparisons of GammaPod with 3DCRT/IMRT have been reported (6), the dosimetric comparison reported in this article with respect to conventional brachytherapy techniques provides additional information on the dosimetric capabilities of this new dose delivery system. In this regard, this article is timely and potentially interesting to medical physicists and physicians alike. A couple of points about this article are worth noting. First, the dose distributions used in this comparison were calculated with different algorithms: Monte Carlo algorithm with tissue heterogeneity correction for GammaPod and the American Association of Physicists in Medicine Task Group 43 formalism without tissue heterogeneity correction for the brachytherapy techniques. The latter generally overestimates skin dose, an effect that was discussed in the article but was not quantitatively included in the comparison of skin doses with GammaPod. Second, for the purpose of comparison with balloon-based brachytherapy, the irradiated volume for GammaPod was artificially large (eg, a spherical volume with a 6.5-cm diameter was used to compare with brachytherapy using a 4.5-cm diameter balloon). Although this is understandable for the purpose of this study, and could be true if a 4.5-cm tissue expander is to be used for GammaPod, one might expect that an advantage of using GammaPod is to treat the (smaller) collapsed lumpectomy cavity, as in the case of 3DCRT, without the need of surgical insertion of an expander. If this is the case, a comparison of a GammaPod plan for a positively identified clinical target volume (CTV) in the collapsed state with the plan of a balloon-based brachytherapy for the same CTV (after expansion by a balloon) would be more relevant.
Volume 88 Number 2 2014 Nijkamp et al. Relating acute esophagitis to radiotherapy dose using FDG-PET in concurrent chemo-radiotherapy for locally advanced non-small cell lung cancer. Radiother Oncol 2013. (7) Summary: The study by Nijkamp et al (7) dealt with the development of a model for acute esophagitis (AE) after moderately hypofractionated (24 2.75 Gy) radiation therapy (RT) delivered with concurrent chemotherapy. The study cohort included 82 patients treated in a single institute; a post-RT positron emission tomography/computed tomography (PET-CT) (PET-post) scan acquired within 3 months from the end of the therapy was available for each patient. The authors used the PET-post information in terms of standardized uptake value (SUV)mean encompassed by the 50% SUV contour within the esophagus (SUV50%) to correlate the early response measured by PET with the occurrence and the severity of AE. After propagation of the planning CT esophagus contours on the PET-CT scan through elastic registration, the local dose to the esophagus wall was correlated to the local SUV values and modeled by a power-law fit; then the risk of 2 grade AE was modeled by the normal tissue complication probability Lyman-Kutcher-Burman equivalent uniform dose (NTCP LKB_EUD model) (using EUD to reduce the doseevolume histogram [DVH]) and a modified LKB_EUD model assuming the parameter, n, to be the same relating the local dose and the local SUV value by the power-law fit. The results show that both esophagus SUV50% and DVH are correlated with the risk of 2 grade AE. The local SUV within the esophagus is also clearly correlated with the local dose. The NTCP LKB_EUD model fit the data quite well (TD50 Z 51.5 Gy, n Z 0.117, m Z 0.24); when fixing n Z 0.130, as resulting from the power-law fit between local dose and local SUV, the modified NTCP model incorporating the functional PET information translated into much lower confidence intervals of the best-fit parameters (TD50 Z 50.4 Gy, n Z 0.130, m Z 0.25): for instance, the 95% confidence intervals for TD50 were 20.6 to 70.0 Gy and 37.5 to 55.4 Gy for the original and the PET-modified NTCP model, respectively. The PET-modified model was shown to have the best predictive value also, compared with other dose– volume predictors previously reported in the literature. Comment: The field of advanced predictive modeling of radiation-induced toxicities has receiving increasing attention during recent years (8). This work well stays in this rapidly growing wave and represents an elegant example of how the classic “DVH-based” NTCP approach to modeling doseevolume effects may find new life from the largely increasing availability of individual information including, as in this case, data recovered by functional imaging. The original approach developed by
Oncology Scan
253
Nijkamp et al (7) tried to combine the doseevolume information summarized by the DVH/EUD with the functional information relating the local SUV value to the local dose, implicitly assuming that the SUV is a surrogate of the local (acute) radiation-induced damage. The (reasonable) hypothesis is that the inflammation process quantitatively captured by the PET signal is a direct measure of the damage and that the occurrence of clinical symptoms depends on the amount of organ with high SUV signal: the classic power-law curve was chosen to reasonably represent this local effect relationship. The integration of individual 3D dose-volume information with clinical, imaging, functional, and possibly genetic information is a very promising field of research wherein the integration of medical physics with many other disciplines promises to help us in developing more and more reliable predictive models of radiationinduced toxicities and more in general of the outcome of modern radiation therapy (9).
References 1. Schlesinger D, Benedict S, Diederich C, et al. MR-guided focused ultrasound surgery, present and future. Med Phys 2013; 40: 080901. 2. Cline HE, Schenck JF, Hynynen K, et al. MR-guided focused ultrasound surgery. J Comput Assist Tomogr 1992;16:956-965. 3. Taran FA, Tempany CM, Regan L, et al. Magnetic resonance-guided focused ultrasound (MRgFUS) compared with abdominal hysterectomy for treatment of uterine leiomyomas. Ultrasound Obstet Gynecol 2009;34:572-578. ¨ de´n J, Toma-Dasu I, Yu CX, et al. Dosimetric comparison between 4. O intra-cavitary breast brachytherapy techniques for accelerated partial breast irradiation and a novel stereotactic radiotherapy device for breast cancer: GammaPod. Phys Med Biol 2013;58:4409-4421. 5. Njeh CF, Saunders MW, Langton CM. Accelerated partial breast irradiation (APBI): A review of available techniques. Radiat Oncol 2010;5:90. 6. Mutaf YD, Zhang J, Yu CX, et al. Dosimetric and geometric evaluation of a novel stereotactic radiotherapy device for breast cancer: The GammaPodTM. Med Phys 2013;40: 041722. 7. Nijkamp J, Rossi M, Lebesque J, et al. Relating acute esophagitis to radiotherapy dose using FDG-PET in concurrent chemo-radiotherapy for locally advanced non-small cell lung cancer. Radiother Oncol 2013;106:118-123. 8. Bentzen SM, Constine LS, Deasy JO, et al. Quantitative analyses of normal tissue effects in the clinic (QUANTEC): An introduction to the scientific issues. Int J Radiat Oncol Biol Phys 2010;76(3 Suppl): S3-S9. 9. Lambin P, van Stiphout RG, Starmans MH, et al. Predicting outcomes in radiation oncology: Multifactorial decision support systems. Nat Rev Clin Oncol 2013;10:27-40.
Radiation Oncology biology
physics
www.redjournal.org
Oncology ScandThe Vision of Medical Physics By Eric E. Klein, PhD, Senior Editor, Nesrin Dogan, PhD, Associate Editor, Zhe Chen, PhD, Associate Editor, Claudio Fiorino, PhD, Associate Editor The Physics editorial team for the International Journal of Radiation Oncology, Biology, Physics includes 8 associate editors and 1 senior editor. Physicists from North America and Europe with a variety of expertise constitute the team, which receives the greatest number of manuscripts in relationship to other categories within the journal. This unfortunately leads to a high number of manuscripts being rejected or declined. We recently set up formal decline criteria, which include the following: 1. Weak methods of data collection, absence of statistics 2. Conclusions that mimic the same findings of a higher-quality published work 3. Articles unlikely to be cited 4. Inability to read a manuscript without significant English language editing 5. Low-quality data, such as single-institution experience or treatment planning comparisons 6. A single case study illustrating various situations and general conclusions To this end, we would like to see manuscripts on the following subjects: clinical treatment techniques and strategy, physics- and technology-driven clinical trials, imaging and modeling of tumor and tissue response for adaptive therapy, database mining, and management of treatment uncertainties. We have chosen 3 articles for this month’s Oncology Scan, which we have summarized and on which we comment. One particular article is a part of the 20/20 Vision Series of Medical Physics, which covers subjects in the form of white papers. Schlesinger et al. MR-guided focused ultrasound surgery, present and future. Med Phys 2013. (1) Summary: Magnetic resonance (MR)-guided focused ultrasound surgery (MRgFUS) is an emerging technology with potential for a wide range of applications, including in radiation oncology (2). MRgFUS uses high-intensity focused ultrasound along with MR image guidance and was originally developed for the treatment of bone metastases and uterine fibroids (3). However, it has a potential to be used as an adjuvant therapy to traditional radiation and chemotherapy. This article reviews the aspects of the basic physics and biology of MRgFUS and the challenges that the
Int J Radiation Oncol Biol Phys, Vol. 88, No. 2, pp. 251e253, 2014 0360-3016/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ijrobp.2013.08.022
current technology faces before it can transition into a more widely available clinical tool. For therapeutic applications, the goal of FUS is to minimize the reflection and transfer sufficient thermal energy to the target to create the desired biological effect. The MR guidance is required to identify and localize the target and to determine the absolute temperature changes in the form of MR thermometry. The high-intensity ultrasound has a variety of desirable physical effects (eg, thermal and mechanical effects) and biological effects (eg, local ablation, thrombolysis, radiosensitization) in tissue, which can be used for treatment advantage. Since the first MRgFUS system was cleared in 2004 by the US Food and Drug Administration for the treatment of uterine fibroids, several ultrasound-guided and MR-guided FUS systems have been developed. Current clinical studies on metastatic bone tumors have shown significant reduction in pain and visual acuity scale. Although MRgFUS has much potential, the routine clinical use of this technology is still very limited because of clinical, technical, and regulatory barriers. Furthermore, the MRgFUS need to be expanded to different clinical areas if it is to be widely accepted rather than remaining as a niche treatment for only certain subsets of patients. The authors discuss some of the challenges that MRgFUS overcomes before it can have wideranging uses. The main challenges that have been addressed in this work include enhanced heating caused by the cavitation process; unintended absorption of ultrasound energy by the macroscopic and microscopic calcifications in the tissue; the presence of standing waves, which can cause undesired heating, damaging the unintended tissue; a lack of clear standards for exposure, calibration of dose, and clinical acceptance; long treatment times; additional complications caused by presence of bone and implants; motion of the patient or internal organs; and the long time required to create treatment plans. The authors pointed out that some progress has already been made to solve some of these issues. In addition to the physics and engineering challenges, clinical and financial challenges can be a major barrier for the widespread adoption of this new technology. Gaining clinical acceptance in an already crowded field with many accepted treatment options is another challenge for this new technology, along with proving its safety and effectiveness. There have been some encouraging studies on the use of MRgFUS for the treatment of breast cancer, prostate cancer, hepatic tumors, neuropathic pain, and functional
252
Oncology Scan
disorders, with some early results comparable to or better than those reported for conventional radiation therapy. Comment: MRgFUS is an emerging technology with potential applications in a variety of clinical indications, including benign and malignant tumors, pain management, vascular problems, and many others. As the authors pointed out, the use of ultrasound for therapeutic purposes is not a new idea and has been studied by many researchers. Advances in imaging, computer, and ultrasound technology in the past decade have brought this idea close to reality in the clinic. MRgFUS technology has many technical, practical, and financial challenges that need to be addressed. These challenges are being considered, and it is highly likely that they will be resolved with time. Whether this technique can find widespread adoption will depend on the accumulation of clinical data and cost-effectiveness. It is very possible that MRgFUS will be used in conjunction with radiation therapy in the future. O¨de´n et al. Dosimetric comparison between intra-cavitary breast brachytherapy techniques for accelerated partial breast irradiation and a novel stereotactic radiotherapy device for breast cancer: GammaPod. Phys Med Biol 2013. (4) Summary: This article describes the results of a dosimetric study aimed at comparing the dose-shaping capabilities of a new dedicated stereotactic radiation therapy device for breast cancer, known as GammaPod, with those of commonly used and relatively well-developed intracavitary brachytherapy techniques for accelerated partial breast irradiation (APBI) with an 192Ir remote afterloader (5). The GammaPod device consists of a hemispherical source carrier containing 36 60Co sources and a complete patient support and dose delivery system. Dose distributions achievable by GammaPod, for spherical target volumes with diameters of 2, 4, 5.6, and 6.5 cm and different proximities to critical structures, were determined by use of the integrated treatment planning system of GammaPod based on the computed tomography (CT) images of 1 test patient. The test patient was CT-scanned in the prone GammaPod treatment position with the target breast resting in a specially designed breast cup under negative pressure. For comparison, dose distributions of 3 APBI brachytherapy techniques (single-lumen balloon with 1 central dwell position, multilumen balloon with multiple dwell positions in up to 5 catheters, and multicatheter applicators using 1 central and 6 to 10 evenly distributed peripheral catheters) were generated for balloon diameters of 4, 4.5, and 5 cm and for various applicator-to-skin distances, respectively. The 3-dimensional (3D) dose distribution for each case was optimized to meet the same dose coverage constraints of the National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-39 guidelines. Comparative analysis of the dose distributions was performed with respect to dose coverage for the target volume, dose fall-off characteristics outside the target, and dose to critical organs such as skin. The key findings of this article are these: 1. Both GammaPod and brachytherapy techniques could produce dose distributions that meet the dosimetric goals of the NSABP B-39 protocol for all target sizes investigated, and GammaPod produced more homogeneous dose distributions within the target volume than did the brachytherapy techniques. The mean
International Journal of Radiation Oncology Biology Physics values of V95 for the brachytherapy techniques and GammaPod were 95% and 96% of the target volume, respectively. 2. The dose falloff outside the target was generally steeper with the brachytherapy techniques at small distances from the target edge (up to approximately 1 cm). At larger distances (more than about 1 cm), however, the dose fall-off produced by GammaPod was steeper. 3. For targets close to the skin, the relative skin doses were considerably lower for GammaPod than for any of the brachytherapy techniques because of the dose optimization ability of GammaPod. The authors conclude that GammaPod allows adequate and more uniform dose coverage to centrally and peripherally located targets, with acceptable dose falloff and lower relative skin dose than the brachytherapy techniques considered. Comment: Accelerated partial breast irradiation using intracavitary brachytherapy techniques or 3D conformal radiation therapy (3DCRT) has become an established modality for selected women with early-stage breast cancer. Over the past decade, technical improvements for APBI dose delivery have involved mainly the development of multilumen balloon and multicatheter applicators, whereas the techniques using 3DCRT and intensity modulated radiation therapy (IMRT) have remained relatively unchanged. The introduction of the GammaPod as a dedicated stereotactic radiation therapy device for breast cancer is potentially a major development in 3DCRT techniques for APBI. Whether this novel modality can enhance breast cancer radiation therapy depends on its dose-shaping capability and its ease of use for patient treatment. Given that the GammaPod system is progressing toward clinical implementation, dosimetric comparisons with the existing treatment modalities are necessary. Although a few preliminary comparisons of GammaPod with 3DCRT/IMRT have been reported (6), the dosimetric comparison reported in this article with respect to conventional brachytherapy techniques provides additional information on the dosimetric capabilities of this new dose delivery system. In this regard, this article is timely and potentially interesting to medical physicists and physicians alike. A couple of points about this article are worth noting. First, the dose distributions used in this comparison were calculated with different algorithms: Monte Carlo algorithm with tissue heterogeneity correction for GammaPod and the American Association of Physicists in Medicine Task Group 43 formalism without tissue heterogeneity correction for the brachytherapy techniques. The latter generally overestimates skin dose, an effect that was discussed in the article but was not quantitatively included in the comparison of skin doses with GammaPod. Second, for the purpose of comparison with balloon-based brachytherapy, the irradiated volume for GammaPod was artificially large (eg, a spherical volume with a 6.5-cm diameter was used to compare with brachytherapy using a 4.5-cm diameter balloon). Although this is understandable for the purpose of this study, and could be true if a 4.5-cm tissue expander is to be used for GammaPod, one might expect that an advantage of using GammaPod is to treat the (smaller) collapsed lumpectomy cavity, as in the case of 3DCRT, without the need of surgical insertion of an expander. If this is the case, a comparison of a GammaPod plan for a positively identified clinical target volume (CTV) in the collapsed state with the plan of a balloon-based brachytherapy for the same CTV (after expansion by a balloon) would be more relevant.
Volume 88 Number 2 2014 Nijkamp et al. Relating acute esophagitis to radiotherapy dose using FDG-PET in concurrent chemo-radiotherapy for locally advanced non-small cell lung cancer. Radiother Oncol 2013. (7) Summary: The study by Nijkamp et al (7) dealt with the development of a model for acute esophagitis (AE) after moderately hypofractionated (24 2.75 Gy) radiation therapy (RT) delivered with concurrent chemotherapy. The study cohort included 82 patients treated in a single institute; a post-RT positron emission tomography/computed tomography (PET-CT) (PET-post) scan acquired within 3 months from the end of the therapy was available for each patient. The authors used the PET-post information in terms of standardized uptake value (SUV)mean encompassed by the 50% SUV contour within the esophagus (SUV50%) to correlate the early response measured by PET with the occurrence and the severity of AE. After propagation of the planning CT esophagus contours on the PET-CT scan through elastic registration, the local dose to the esophagus wall was correlated to the local SUV values and modeled by a power-law fit; then the risk of 2 grade AE was modeled by the normal tissue complication probability Lyman-Kutcher-Burman equivalent uniform dose (NTCP LKB_EUD model) (using EUD to reduce the doseevolume histogram [DVH]) and a modified LKB_EUD model assuming the parameter, n, to be the same relating the local dose and the local SUV value by the power-law fit. The results show that both esophagus SUV50% and DVH are correlated with the risk of 2 grade AE. The local SUV within the esophagus is also clearly correlated with the local dose. The NTCP LKB_EUD model fit the data quite well (TD50 Z 51.5 Gy, n Z 0.117, m Z 0.24); when fixing n Z 0.130, as resulting from the power-law fit between local dose and local SUV, the modified NTCP model incorporating the functional PET information translated into much lower confidence intervals of the best-fit parameters (TD50 Z 50.4 Gy, n Z 0.130, m Z 0.25): for instance, the 95% confidence intervals for TD50 were 20.6 to 70.0 Gy and 37.5 to 55.4 Gy for the original and the PET-modified NTCP model, respectively. The PET-modified model was shown to have the best predictive value also, compared with other dose– volume predictors previously reported in the literature. Comment: The field of advanced predictive modeling of radiation-induced toxicities has receiving increasing attention during recent years (8). This work well stays in this rapidly growing wave and represents an elegant example of how the classic “DVH-based” NTCP approach to modeling doseevolume effects may find new life from the largely increasing availability of individual information including, as in this case, data recovered by functional imaging. The original approach developed by
Oncology Scan
253
Nijkamp et al (7) tried to combine the doseevolume information summarized by the DVH/EUD with the functional information relating the local SUV value to the local dose, implicitly assuming that the SUV is a surrogate of the local (acute) radiation-induced damage. The (reasonable) hypothesis is that the inflammation process quantitatively captured by the PET signal is a direct measure of the damage and that the occurrence of clinical symptoms depends on the amount of organ with high SUV signal: the classic power-law curve was chosen to reasonably represent this local effect relationship. The integration of individual 3D dose-volume information with clinical, imaging, functional, and possibly genetic information is a very promising field of research wherein the integration of medical physics with many other disciplines promises to help us in developing more and more reliable predictive models of radiationinduced toxicities and more in general of the outcome of modern radiation therapy (9).
References 1. Schlesinger D, Benedict S, Diederich C, et al. MR-guided focused ultrasound surgery, present and future. Med Phys 2013; 40: 080901. 2. Cline HE, Schenck JF, Hynynen K, et al. MR-guided focused ultrasound surgery. J Comput Assist Tomogr 1992;16:956-965. 3. Taran FA, Tempany CM, Regan L, et al. Magnetic resonance-guided focused ultrasound (MRgFUS) compared with abdominal hysterectomy for treatment of uterine leiomyomas. Ultrasound Obstet Gynecol 2009;34:572-578. ¨ de´n J, Toma-Dasu I, Yu CX, et al. Dosimetric comparison between 4. O intra-cavitary breast brachytherapy techniques for accelerated partial breast irradiation and a novel stereotactic radiotherapy device for breast cancer: GammaPod. Phys Med Biol 2013;58:4409-4421. 5. Njeh CF, Saunders MW, Langton CM. Accelerated partial breast irradiation (APBI): A review of available techniques. Radiat Oncol 2010;5:90. 6. Mutaf YD, Zhang J, Yu CX, et al. Dosimetric and geometric evaluation of a novel stereotactic radiotherapy device for breast cancer: The GammaPodTM. Med Phys 2013;40: 041722. 7. Nijkamp J, Rossi M, Lebesque J, et al. Relating acute esophagitis to radiotherapy dose using FDG-PET in concurrent chemo-radiotherapy for locally advanced non-small cell lung cancer. Radiother Oncol 2013;106:118-123. 8. Bentzen SM, Constine LS, Deasy JO, et al. Quantitative analyses of normal tissue effects in the clinic (QUANTEC): An introduction to the scientific issues. Int J Radiat Oncol Biol Phys 2010;76(3 Suppl): S3-S9. 9. Lambin P, van Stiphout RG, Starmans MH, et al. Predicting outcomes in radiation oncology: Multifactorial decision support systems. Nat Rev Clin Oncol 2013;10:27-40.
