Practical Radiation Oncology (2012) 2, 314–318
www.practicalradonc.org
Teaching Case
Spot scanning proton therapy for craniopharyngioma Mark J. Amsbaugh BS, X. Ronald Zhu PhD, Matthew Palmer CMD, MBA, Falk Poenisch PhD, Mary F. McAleer MD, PhD, Anita Mahajan MD, David R. Grosshans MD, PhD ⁎ Division of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas Received 16 August 2011; revised 19 December 2011; accepted 2 January 2012
Introduction Craniopharyngiomas are histologically benign tumors that represent the third most common pediatric brain tumor. Despite their benign appearance, craniopharyngiomas are locally invasive with a propensity for recurrence. Historically craniopharyngiomas were treated with surgery alone. However, aggressive surgical resection is frequently associated with significant sequealae including endocrinopathies. As early as 1961, groups began to report the benefits of employing more limited surgical resection followed with adjuvant radiation therapy. 1,2 Radiation therapy now holds a more prominent role in the treatment of craniopharyngiomas when coupled with limited surgical resection. 1,3-6 Understandably, fears persist over the long-term complications of irradiation in the developing brain, including cognitive dysfunction, vascular disease, and secondary malignancies. However, in counseling patients and parents the practitioner must also consider the implications of tumor recurrence and additional surgical interventions. 6,7 Advancements in radiation therapy have increased the ability to spare normal tissues. Intensity modulated radiation therapy (IMRT) has shown promise in the treatment of pediatric tumors. 8 Particle therapy is also particularly attractive for young patients because exposure of normal tissues to low-dose bath radiation is miniConflicts of interest: None. ⁎ Corresponding author. Division of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, 1840 Old Spanish Trail #1150, Houston, TX 77054. E-mail address: [email protected] (D.R. Grosshans).
mized. 9,10 The preliminary efficacy of particle therapy for the treatment of craniopharyngiomas has been published by Luu et al, who presented 16 pediatric and adult patients who underwent proton therapy. 11 Despite its promise, proton therapy is technically challenging given the location of these tumors and their propensity to enlarge during the course of treatment. 12 Here we present a case of a young female treated with spot scanning (pencil beam) proton therapy.
Teaching case An otherwise healthy prepubertal girl presented to her primary care doctor with a 6-month history of headaches occurring mainly in the morning and waking her from sleep. A computed tomographic (CT) scan demonstrated a partially calicified mass in the suprasellar area (Fig 1A). Magnetic resonance (MR) imaging confirmed the presence of a cystic lesion filling the suprasellar cistern with obstruction of the third ventricle and foramen of Monro, resulting in hypdrocephalus (Fig 1B). Imaging was consistent with a craniopharyngioma. Neurosurgery performed a right frontotemporal craniotomy with microscopic dissection. The cystic components were noted to contain the characteristic liquid “crankcase oil,” high in lipid and cholesterol content. Deeper, the lesion contained solid, calicified components and was found to be adherent near the hypothalamic area. In order to avoid hypothalamic or pituitary stalk damage a subtotal resection was performed. Final pathology revealed adamantinomatous craniopharyngioma, a histologic variant common in children. On postoperative
1879-8500/$ – see front matter. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. http://dx.doi.org/10.1016/j.prro.2012.01.001
Practical Radiation Oncology: October-December 2012
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315
Figure 1 Sagittal imaging. (A) Computed tomographic imaging revealed a suprasellar lesion with areas of calcification and dilated ventricles. (B) The cystic nature of the lesion was better defined on magnetic resonance imaging (MRI). (C) The postoperative MRI documented cyst decompression with residual disease.
imaging, cystic components were reduced in size with the majority of the solid component remaining and continued abnormalities visualized along the walls of the third ventricle (Fig 1C). Following surgery she was referred for adjuvant radiation therapy. The patient was enrolled in a prospective observational study of proton therapy for pediatric malignancies. She underwent CT simulation with a bite block and thermoplastic mask fabricated for immobilization. Postoperative MR imaging was fused to the planning CT. The gross tumor volume (GTV) included the remaining tumor as well as the hypothalamic area where invasion had been noted intraoperatively. The clinical target volume (CTV) consisted of a 5-mm expansion of the GTV. The choice for CTV expansion varies among practitioners. Investigators from St. Jude Children's Research Hospital have published on the use of a 1-cm CTV expansion and currently utilize a 5-mm expansion for additional normal tissue sparing. 5 Researchers at The University of Heidelberg have utilized a smaller expansion from the GTV with fractionated,
stereotactic radiotherapy treatments. 13 In addition to target delineation, avoidance structures, including the optic chiasm and hippocampus, were contoured. 14 For most proton treatments delivered to date, passive scattering proton therapy has been used. Scattering devices are introduced to expand a pencil beam laterally and range modulation devices are used to create a spread-out Bragg peak (SOBP). Patient-specific brass apertures and Lucite compensators shape the lateral and distal aspects of the beam, respectively. With passive scattering technology there is little control of the proximal edge of the beam and conformality is often less than with IMRT. 15 Uniform scanning is a hybrid approach of delivering proton beam treatment, in which scanning magnets spread a large pencil beam laterally, a range modulation device expands the beam in depth direction to create the SOBP and patientspecific apertures and compensators shape individual fields. 16 In contrast to other techniques, with spot scanning beam proton therapy a pencil beam (spot) can be magnetically scanned in both directions lateral to the
Figure 2 Beam angles. Axial (A) and coronal (B) images obtained during simulation depict beam angles selected for treatment planning. The gross target volume is highlighted in red and the hippocampal formations in blue. Gantry and couch angles used included left vertex 70 degrees/340 degrees; right vertex 290 degrees/20 degrees; posterior vertex 195 degrees/90 degrees.
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beam direction to create a large field without introducing scattering elements into the beam path. Monoenergetic pencil beams of different energies from a synchrotron can be used to create the desired dose distribution in the depth direction, including greater control over the proximal edge of the target. Cyclotrons may also be used for scanning
Practical Radiation Oncology: October-December 2012
beam proton therapy. However, cyclotrons produce a beam of fixed energy and a mechanical device is normally used to degrade the energy. The advantages and disadvantages using synchrotrons and cyclotrons has been described elsewhere. 17 Some have raised concerns that the presence of devices within the proton beam may
Figure 3 Generated treatment plans. (A) Intensity modulated radiation or photon therapy (IMRT or IMPT) plan demonstrating excellent target coverage (gross target volume [GTV] in red, clinical target volume [CTV] in dark blue) and conformality but with spread of low-dose radiation and exposure of the hippocampi contoured in light blue. (B) Passive scattering proton plan. (C) Scanning beam proton plan generated using single-field optimization (SFO). Improved conformality of high doses, similar to that of IMRT, is noted in comparison with passive scattering. (D) For this relatively uniformly shaped lesion, multifield optimization (multiple field optimization [MFO] or IMPT) showed little benefit in comparison with the SFO plan.
Practical Radiation Oncology: October-December 2012
lead to unnecessary neutron contamination. 18 In comparison to other proton delivery modalities, spot scanning may limit the production of secondary neutrons given the absence of additional components within the beam. 19 Thus, spot scanning beam proton therapy offers the physical benefits of proton therapy, with the theoretical benefit of reduced neutron exposure and practical benefit of improved conformality. 15 In contrast to photon-based therapy, proton treatment typically utilizes fewer beams. Given this and the potential for a higher relative biologic effectiveness at the distal edge of the beam, great care must be taken in selecting beam angles. 20 In general it is advisable to avoid beam arrangements where the distal edge of the beam is in proximity to a critical structure. Shorter beam path lengths and avoidance of air cells or metallic devices may also help to reduce uncertainties. For this patient 3 fields were utilized: right and left anterior superior obliques, and a posterior, superior oblique. Anterior oblique beams provided an angle, which spared the hippocampus from entrance dose. The addition of a vertex beam, designed to stop superiorly to the brainstem, improved dose homogeneity and temporal lobe sparing (Fig 2). IMRT, passive scattering proton, and spot scanning proton plans were generated for comparison (Fig 3). Seven beams were utilized for IMRT planning and 3 for proton therapy. For both proton and IMRT planning the hippocampus was assigned the same optimization constraints. In contrast to the passive scattering plan, visual inspection revealed that the pencil beam plan displayed higher conformality with additional sparing of the hippocampi. Craniopharyngiomas are known to undergo cystic changes during radiotherapy. 5,12 Consequently, the patient underwent serial CT imaging during the course of radiotherapy. Verification scans were performed following the first week of treatment and every 2 weeks thereafter. 12,21 No change in the lesion was identified. The patient tolerated the treatment without significant acute side effects and is now being seen in regular follow-up intervals without evidence of disease progression.
Discussion Proton therapy has unique physical characteristics allowing one to deliver the prescribed dose while limiting exposure of normal tissues. Despite their physical advantages, particle therapy such as proton therapy is technically challenging and uncertainties remain. Spot scanning proton therapy is not yet widely available. However, many new proton facilities will incorporate scanning beam technology. The scanning nozzle delivers the spot scanning treatment both “spotby-spot” and “layer-by-layer.” 22,23 Spot scanning beam raises the option of intensity modulated proton therapy (IMPT). With IMPT (also known as multiple field
Spot scanning proton therapy for craniopharyngioma
317
optimization or MFO), spots from all fields are optimized simultaneously. 24,25 As such, an individual beam intentionally covers only part of the target in order to spare additional normal tissues. When all beams are summed, in theory, the target receives a homogeneous dose. As with any new technology there are inherent uncertainties. These uncertainties are heightened in particle therapy. With particle therapy, the exact position of the rapid distal falloff of the beam depends on the radiological path length. Changes in patient position may introduce increased or decreased tissue density along the path of the beam. Such changes may alter the radiological path length thereby compromising target coverage or exposing distal tissues to unnecessary dose. This feature of proton beams contrasts with photons where changes in the radiological path length have minimal effects since photon beams attenuate exponentially. Additional concerns arise for particle beam therapy of craniopharyngiomas, due to the fact that cystic changes may occur within the target during the several-week course of fractionated radiotherapy. As a result of these uncertainties, recent work has cautioned against the use of IMPT without adaptive planning. 26 Beltran et al 26 compared IMRT, passive scattering proton therapy (PSPT), and IMPT plans in 14 children with craniopharyngioma. Although the IMPT spared more normal brain tissue, target coverage was 60% more sensitive to changes in volume than IMRT or PSPT. Linear regression techniques suggested that a 5% change in the primary target volume may require altering the IMPT plan. They concluded that when using conformal techniques, patients should be closely monitored and adaptive planning may be necessary. When using spot scanning proton therapy, there are important differences in planning; primarily, the choice of single-field optimization (SFO) or multifield optimization (MFO or IMPT). With SFO, each field is individually optimized to deliver the entire prescribed dose, covering the entire target volume. 27 SFO is most commonly used to produce a uniform dose over the target volume by each field, which is known as single field uniform dose (SFUD). 27,28 For the patient case reported here, the scanning beam treatment plan was optimized using SFO and an Eclipse treatment planning system (version 8.9; Varian Medical Systems, Palo Alto, CA) with 2 different dose levels, 50.4 Gy(RBE) to the CTV and 54 Gy(RBE) to the GTV. The SFO technique creates highly conformal plans yet is less sensitive to proton range uncertainties than IMPT. 24,25 As such, spot scanning with an SFO technique was chosen for treatment. Craniopharyngiomas represent a unique challenge for the practicing radiation oncologist. The location offers an opportunity to maximize the benefits of advanced treatment methods that spare normal brain structures. However, the cystic changes frequently seen during radiation therapy mandate the utilization of surveillance imaging and possible adaptive treatment to ensure
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adequate primary target volume coverage. Prospective follow-up after treatment of these patients with advanced modalities is warranted.
Practical Radiation Oncology: October-December 2012
14. 15.
References 1. DiPatri Jr AJ, Prabhu V. A history of the treatment of craniopharyngiomas. Childs Nerv Syst. 2005;21:606-621. 2. Kramer S, McKissock W, Concannon JP. Craniopharyngiomas. Treatment by combined surgery and radiation therapy. J Neurosurg. 1961;18:217-226. 3. Kiehna EN, Merchant TE. Radiation therapy for pediatric craniopharyngioma. Neurosurg Focus. 2010;28:E10. 4. Lin LL, El Naqa I, Leonard JR, et al. Long-term outcome in children treated for craniopharyngioma with and without radiotherapy. J Neurosurg Pediatr. 2008;1:126-130. 5. Merchant TE, Kiehna EN, Kun LE, et al. Phase II trial of conformal radiation therapy for pediatric patients with craniopharyngioma and correlation of surgical factors and radiation dosimetry with change in cognitive function. J Neurosurg. 2006;104(Suppl 2):94-102. 6. Puget S, Garnett M, Wray A, et al. Pediatric craniopharyngiomas: classification and treatment according to the degree of hypothalamic involvement. J Neurosurg. 2007;106(Suppl 1):3-12. 7. Merchant TE, Kiehna EN, Sanford RA, et al. Craniopharyngioma: the St. Jude Children's Research Hospital experience 1984-2001. Int J Radiat Oncol Biol Phys. 2002;53:533-542. 8. Huang E, Teh BS, Strother DR, et al. Intensity-modulated radiation therapy for pediatric medulloblastoma: early report on the reduction of ototoxicity. Int J Radiat Oncol Biol Phys. 2002;52:599-605. 9. Merchant TE. Proton beam therapy in pediatric oncology. Cancer J. 2009;15:298-305. 10. Merchant TE, Hua CH, Shukla H, et al. Proton versus photon radiotherapy for common pediatric brain tumors: Comparison of models of dose characteristics and their relationship to cognitive function. Pediatr Blood Cancer. 2008;51:110-117. 11. Luu QT, Loredo LN, Archambeau JO, et al. Fractionated proton radiation treatment for pediatric craniopharyngioma: preliminary report. Cancer J. 2006;12:155-159. 12. Winkfield KM, Linsenmeier C, Yock TI, et al. Surveillance of craniopharyngioma cyst growth in children treated with proton radiotherapy. Int J Radiat Oncol Biol Phys. 2009;73:716-721. 13. Combs SE, Thilmann C, Huber PE, et al. Achievement of long-term local control in patients with craniopharyngiomas
16.
17. 18. 19. 20.
21.
22. 23.
24.
25.
26.
27.
28.
using high precision stereotactic radiotherapy. Cancer. 2007;109: 2308-2314. Chera BS, Amdur RJ, Patel P, et al. A radiation oncologist's guide to contouring the hippocampus. Am J Clin Oncol. 2009;32:20-22. Boehling NS, Grosshans DR, Bluett JB, et al. Dosimetric comparison of three-dimensional conformal proton radiotherapy, intensity-modulated proton therapy, and intensity-modulated radiotherapy for treatment of pediatric craniopharyngiomas. Int J Radiat Oncol Biol Phys. 2011;27:27. Farr JB, Mascia AE, Hsi WC, et al. Clinical characterization of a proton beam continuous uniform scanning system with dose layer stacking. Med Phys. 2008;35:4945-4954. DeLaney TF, Kooy HM. Proton and Charged Particle Radiotherapy. Philadelphia, PA: Lippincott Williams & Wilkins; 2008. Hall EJ. Intensity-modulated radiation therapy, protons, and the risk of second cancers. Int J Radiat Oncol Biol Phys. 2006;65:1-7. Flanz J, Smith A. Technology for proton therapy. Cancer J. 2009; 15:292-297. Robertson JB, Williams JR, Schmidt RA, et al. Radiobiological studies of a high-energy modulated proton beam utilizing cultured mammalian cells. Cancer. 1975;35:1664-1677. Kornguth D, Mahajan A, Frija E, et al. Shape variability of craniopharyngioma as measured on CT-on-rails during radiatiotherapy treatment. Int J Radiat Oncol Biol Phys. 2006:S259-S260. Smith A, Gillin M, Bues M, et al. The M. D. Anderson proton therapy system. Med Phys. 2009;36:4068-4083. Gillin MT, Sahoo N, Bues M, et al. Commissioning of the discrete spot scanning proton beam delivery system at The University of Texas M. D. Anderson Cancer Center, Proton Therapy Center, Houston. Med Phys. 2010;37:154-163. Lomax AJ. Intensity modulated proton therapy and its sensitivity to treatment uncertainties 1: The potential effects of calculational uncertainties. Phys Med Biol. 2008;53:1027-1042. Lomax AJ. Intensity modulated proton therapy and its sensitivity to treatment uncertainties 2: the potential effects of inter-fraction and inter-field motions. Phys Med Biol. 2008;53:1043-1056. Beltran C, Roca M, Merchant TE. On the benefits and risks of proton therapy in pediatric craniopharyngioma. Int J Radiat Oncol Biol Phys. 2011;11:11. Zhu XR, Sahoo N, Zhang X, et al. Intensity modulated proton therapy treatment planning using single-field optimization: the impact of monitor unit constraints on plan quality. Med Phys. 2010;37:1210-1219. Lomax A. Intensity modulation methods for proton radiotherapy. Phys Med Biol. 1999;44:185-205.
www.practicalradonc.org
Teaching Case
Spot scanning proton therapy for craniopharyngioma Mark J. Amsbaugh BS, X. Ronald Zhu PhD, Matthew Palmer CMD, MBA, Falk Poenisch PhD, Mary F. McAleer MD, PhD, Anita Mahajan MD, David R. Grosshans MD, PhD ⁎ Division of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas Received 16 August 2011; revised 19 December 2011; accepted 2 January 2012
Introduction Craniopharyngiomas are histologically benign tumors that represent the third most common pediatric brain tumor. Despite their benign appearance, craniopharyngiomas are locally invasive with a propensity for recurrence. Historically craniopharyngiomas were treated with surgery alone. However, aggressive surgical resection is frequently associated with significant sequealae including endocrinopathies. As early as 1961, groups began to report the benefits of employing more limited surgical resection followed with adjuvant radiation therapy. 1,2 Radiation therapy now holds a more prominent role in the treatment of craniopharyngiomas when coupled with limited surgical resection. 1,3-6 Understandably, fears persist over the long-term complications of irradiation in the developing brain, including cognitive dysfunction, vascular disease, and secondary malignancies. However, in counseling patients and parents the practitioner must also consider the implications of tumor recurrence and additional surgical interventions. 6,7 Advancements in radiation therapy have increased the ability to spare normal tissues. Intensity modulated radiation therapy (IMRT) has shown promise in the treatment of pediatric tumors. 8 Particle therapy is also particularly attractive for young patients because exposure of normal tissues to low-dose bath radiation is miniConflicts of interest: None. ⁎ Corresponding author. Division of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, 1840 Old Spanish Trail #1150, Houston, TX 77054. E-mail address: [email protected] (D.R. Grosshans).
mized. 9,10 The preliminary efficacy of particle therapy for the treatment of craniopharyngiomas has been published by Luu et al, who presented 16 pediatric and adult patients who underwent proton therapy. 11 Despite its promise, proton therapy is technically challenging given the location of these tumors and their propensity to enlarge during the course of treatment. 12 Here we present a case of a young female treated with spot scanning (pencil beam) proton therapy.
Teaching case An otherwise healthy prepubertal girl presented to her primary care doctor with a 6-month history of headaches occurring mainly in the morning and waking her from sleep. A computed tomographic (CT) scan demonstrated a partially calicified mass in the suprasellar area (Fig 1A). Magnetic resonance (MR) imaging confirmed the presence of a cystic lesion filling the suprasellar cistern with obstruction of the third ventricle and foramen of Monro, resulting in hypdrocephalus (Fig 1B). Imaging was consistent with a craniopharyngioma. Neurosurgery performed a right frontotemporal craniotomy with microscopic dissection. The cystic components were noted to contain the characteristic liquid “crankcase oil,” high in lipid and cholesterol content. Deeper, the lesion contained solid, calicified components and was found to be adherent near the hypothalamic area. In order to avoid hypothalamic or pituitary stalk damage a subtotal resection was performed. Final pathology revealed adamantinomatous craniopharyngioma, a histologic variant common in children. On postoperative
1879-8500/$ – see front matter. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. http://dx.doi.org/10.1016/j.prro.2012.01.001
Practical Radiation Oncology: October-December 2012
Spot scanning proton therapy for craniopharyngioma
315
Figure 1 Sagittal imaging. (A) Computed tomographic imaging revealed a suprasellar lesion with areas of calcification and dilated ventricles. (B) The cystic nature of the lesion was better defined on magnetic resonance imaging (MRI). (C) The postoperative MRI documented cyst decompression with residual disease.
imaging, cystic components were reduced in size with the majority of the solid component remaining and continued abnormalities visualized along the walls of the third ventricle (Fig 1C). Following surgery she was referred for adjuvant radiation therapy. The patient was enrolled in a prospective observational study of proton therapy for pediatric malignancies. She underwent CT simulation with a bite block and thermoplastic mask fabricated for immobilization. Postoperative MR imaging was fused to the planning CT. The gross tumor volume (GTV) included the remaining tumor as well as the hypothalamic area where invasion had been noted intraoperatively. The clinical target volume (CTV) consisted of a 5-mm expansion of the GTV. The choice for CTV expansion varies among practitioners. Investigators from St. Jude Children's Research Hospital have published on the use of a 1-cm CTV expansion and currently utilize a 5-mm expansion for additional normal tissue sparing. 5 Researchers at The University of Heidelberg have utilized a smaller expansion from the GTV with fractionated,
stereotactic radiotherapy treatments. 13 In addition to target delineation, avoidance structures, including the optic chiasm and hippocampus, were contoured. 14 For most proton treatments delivered to date, passive scattering proton therapy has been used. Scattering devices are introduced to expand a pencil beam laterally and range modulation devices are used to create a spread-out Bragg peak (SOBP). Patient-specific brass apertures and Lucite compensators shape the lateral and distal aspects of the beam, respectively. With passive scattering technology there is little control of the proximal edge of the beam and conformality is often less than with IMRT. 15 Uniform scanning is a hybrid approach of delivering proton beam treatment, in which scanning magnets spread a large pencil beam laterally, a range modulation device expands the beam in depth direction to create the SOBP and patientspecific apertures and compensators shape individual fields. 16 In contrast to other techniques, with spot scanning beam proton therapy a pencil beam (spot) can be magnetically scanned in both directions lateral to the
Figure 2 Beam angles. Axial (A) and coronal (B) images obtained during simulation depict beam angles selected for treatment planning. The gross target volume is highlighted in red and the hippocampal formations in blue. Gantry and couch angles used included left vertex 70 degrees/340 degrees; right vertex 290 degrees/20 degrees; posterior vertex 195 degrees/90 degrees.
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beam direction to create a large field without introducing scattering elements into the beam path. Monoenergetic pencil beams of different energies from a synchrotron can be used to create the desired dose distribution in the depth direction, including greater control over the proximal edge of the target. Cyclotrons may also be used for scanning
Practical Radiation Oncology: October-December 2012
beam proton therapy. However, cyclotrons produce a beam of fixed energy and a mechanical device is normally used to degrade the energy. The advantages and disadvantages using synchrotrons and cyclotrons has been described elsewhere. 17 Some have raised concerns that the presence of devices within the proton beam may
Figure 3 Generated treatment plans. (A) Intensity modulated radiation or photon therapy (IMRT or IMPT) plan demonstrating excellent target coverage (gross target volume [GTV] in red, clinical target volume [CTV] in dark blue) and conformality but with spread of low-dose radiation and exposure of the hippocampi contoured in light blue. (B) Passive scattering proton plan. (C) Scanning beam proton plan generated using single-field optimization (SFO). Improved conformality of high doses, similar to that of IMRT, is noted in comparison with passive scattering. (D) For this relatively uniformly shaped lesion, multifield optimization (multiple field optimization [MFO] or IMPT) showed little benefit in comparison with the SFO plan.
Practical Radiation Oncology: October-December 2012
lead to unnecessary neutron contamination. 18 In comparison to other proton delivery modalities, spot scanning may limit the production of secondary neutrons given the absence of additional components within the beam. 19 Thus, spot scanning beam proton therapy offers the physical benefits of proton therapy, with the theoretical benefit of reduced neutron exposure and practical benefit of improved conformality. 15 In contrast to photon-based therapy, proton treatment typically utilizes fewer beams. Given this and the potential for a higher relative biologic effectiveness at the distal edge of the beam, great care must be taken in selecting beam angles. 20 In general it is advisable to avoid beam arrangements where the distal edge of the beam is in proximity to a critical structure. Shorter beam path lengths and avoidance of air cells or metallic devices may also help to reduce uncertainties. For this patient 3 fields were utilized: right and left anterior superior obliques, and a posterior, superior oblique. Anterior oblique beams provided an angle, which spared the hippocampus from entrance dose. The addition of a vertex beam, designed to stop superiorly to the brainstem, improved dose homogeneity and temporal lobe sparing (Fig 2). IMRT, passive scattering proton, and spot scanning proton plans were generated for comparison (Fig 3). Seven beams were utilized for IMRT planning and 3 for proton therapy. For both proton and IMRT planning the hippocampus was assigned the same optimization constraints. In contrast to the passive scattering plan, visual inspection revealed that the pencil beam plan displayed higher conformality with additional sparing of the hippocampi. Craniopharyngiomas are known to undergo cystic changes during radiotherapy. 5,12 Consequently, the patient underwent serial CT imaging during the course of radiotherapy. Verification scans were performed following the first week of treatment and every 2 weeks thereafter. 12,21 No change in the lesion was identified. The patient tolerated the treatment without significant acute side effects and is now being seen in regular follow-up intervals without evidence of disease progression.
Discussion Proton therapy has unique physical characteristics allowing one to deliver the prescribed dose while limiting exposure of normal tissues. Despite their physical advantages, particle therapy such as proton therapy is technically challenging and uncertainties remain. Spot scanning proton therapy is not yet widely available. However, many new proton facilities will incorporate scanning beam technology. The scanning nozzle delivers the spot scanning treatment both “spotby-spot” and “layer-by-layer.” 22,23 Spot scanning beam raises the option of intensity modulated proton therapy (IMPT). With IMPT (also known as multiple field
Spot scanning proton therapy for craniopharyngioma
317
optimization or MFO), spots from all fields are optimized simultaneously. 24,25 As such, an individual beam intentionally covers only part of the target in order to spare additional normal tissues. When all beams are summed, in theory, the target receives a homogeneous dose. As with any new technology there are inherent uncertainties. These uncertainties are heightened in particle therapy. With particle therapy, the exact position of the rapid distal falloff of the beam depends on the radiological path length. Changes in patient position may introduce increased or decreased tissue density along the path of the beam. Such changes may alter the radiological path length thereby compromising target coverage or exposing distal tissues to unnecessary dose. This feature of proton beams contrasts with photons where changes in the radiological path length have minimal effects since photon beams attenuate exponentially. Additional concerns arise for particle beam therapy of craniopharyngiomas, due to the fact that cystic changes may occur within the target during the several-week course of fractionated radiotherapy. As a result of these uncertainties, recent work has cautioned against the use of IMPT without adaptive planning. 26 Beltran et al 26 compared IMRT, passive scattering proton therapy (PSPT), and IMPT plans in 14 children with craniopharyngioma. Although the IMPT spared more normal brain tissue, target coverage was 60% more sensitive to changes in volume than IMRT or PSPT. Linear regression techniques suggested that a 5% change in the primary target volume may require altering the IMPT plan. They concluded that when using conformal techniques, patients should be closely monitored and adaptive planning may be necessary. When using spot scanning proton therapy, there are important differences in planning; primarily, the choice of single-field optimization (SFO) or multifield optimization (MFO or IMPT). With SFO, each field is individually optimized to deliver the entire prescribed dose, covering the entire target volume. 27 SFO is most commonly used to produce a uniform dose over the target volume by each field, which is known as single field uniform dose (SFUD). 27,28 For the patient case reported here, the scanning beam treatment plan was optimized using SFO and an Eclipse treatment planning system (version 8.9; Varian Medical Systems, Palo Alto, CA) with 2 different dose levels, 50.4 Gy(RBE) to the CTV and 54 Gy(RBE) to the GTV. The SFO technique creates highly conformal plans yet is less sensitive to proton range uncertainties than IMPT. 24,25 As such, spot scanning with an SFO technique was chosen for treatment. Craniopharyngiomas represent a unique challenge for the practicing radiation oncologist. The location offers an opportunity to maximize the benefits of advanced treatment methods that spare normal brain structures. However, the cystic changes frequently seen during radiation therapy mandate the utilization of surveillance imaging and possible adaptive treatment to ensure
318
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adequate primary target volume coverage. Prospective follow-up after treatment of these patients with advanced modalities is warranted.
Practical Radiation Oncology: October-December 2012
14. 15.
References 1. DiPatri Jr AJ, Prabhu V. A history of the treatment of craniopharyngiomas. Childs Nerv Syst. 2005;21:606-621. 2. Kramer S, McKissock W, Concannon JP. Craniopharyngiomas. Treatment by combined surgery and radiation therapy. J Neurosurg. 1961;18:217-226. 3. Kiehna EN, Merchant TE. Radiation therapy for pediatric craniopharyngioma. Neurosurg Focus. 2010;28:E10. 4. Lin LL, El Naqa I, Leonard JR, et al. Long-term outcome in children treated for craniopharyngioma with and without radiotherapy. J Neurosurg Pediatr. 2008;1:126-130. 5. Merchant TE, Kiehna EN, Kun LE, et al. Phase II trial of conformal radiation therapy for pediatric patients with craniopharyngioma and correlation of surgical factors and radiation dosimetry with change in cognitive function. J Neurosurg. 2006;104(Suppl 2):94-102. 6. Puget S, Garnett M, Wray A, et al. Pediatric craniopharyngiomas: classification and treatment according to the degree of hypothalamic involvement. J Neurosurg. 2007;106(Suppl 1):3-12. 7. Merchant TE, Kiehna EN, Sanford RA, et al. Craniopharyngioma: the St. Jude Children's Research Hospital experience 1984-2001. Int J Radiat Oncol Biol Phys. 2002;53:533-542. 8. Huang E, Teh BS, Strother DR, et al. Intensity-modulated radiation therapy for pediatric medulloblastoma: early report on the reduction of ototoxicity. Int J Radiat Oncol Biol Phys. 2002;52:599-605. 9. Merchant TE. Proton beam therapy in pediatric oncology. Cancer J. 2009;15:298-305. 10. Merchant TE, Hua CH, Shukla H, et al. Proton versus photon radiotherapy for common pediatric brain tumors: Comparison of models of dose characteristics and their relationship to cognitive function. Pediatr Blood Cancer. 2008;51:110-117. 11. Luu QT, Loredo LN, Archambeau JO, et al. Fractionated proton radiation treatment for pediatric craniopharyngioma: preliminary report. Cancer J. 2006;12:155-159. 12. Winkfield KM, Linsenmeier C, Yock TI, et al. Surveillance of craniopharyngioma cyst growth in children treated with proton radiotherapy. Int J Radiat Oncol Biol Phys. 2009;73:716-721. 13. Combs SE, Thilmann C, Huber PE, et al. Achievement of long-term local control in patients with craniopharyngiomas
16.
17. 18. 19. 20.
21.
22. 23.
24.
25.
26.
27.
28.
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