Practical Radiation Oncology (2011) 1, 47–51
www.practicalradonc.org
Teaching Case
First use of electromagnetic setup and real-time tracking in a pediatric patient with vaginal rhabdomyosarcoma Randall J. Kimple MD, PhD a,⁎, Katharine E. Wallen MD b , Talisha Person RTT a , Raina N. Erwin CMD a , Michael A. Helmrath MD c,d , Stuart Gold MD b,d , David E. Morris MD a,d a
Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina c Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina d Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina b
Received 20 August 2010; accepted 23 August 2010
Abstract We report the first use of the Calypso system (Calypso Medical, Seattle, WA) in a pediatric patient with group III vaginal rhabdomyosarcoma. The Calypso system was used to improve patient setup, to limit anesthesia, to provide for real-time tracking of target location, and to minimize the need for daily portal imaging studies and their associated extraneous radiation dose. © 2011 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
Introduction Accurate localization of target tissues is a cornerstone of modern conformal radiation therapy (RT). The Calypso system (Calypso Medical, Seattle, WA) allows for localization and real-time tracking of target tissue to improve the accuracy of RT delivery. Electromagnetic markers (ie, Beacon transponders) implanted within target tissue are powered by a nonionizing oscillating electromagnetic field generated by an electromagnetic array that is Sources of support: RJK has been designated a B. Leonard Holman Pathway Fellow by the American Board of Radiology and is supported by a Resident/Fellows in Radiation Oncology Seed Grant from the American Society for Radiation Oncology. Conflicts of interest: None. ⁎Corresponding author. Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. E-mail address: [email protected] (R.J. Kimple).
placed anterior to the supine patient, as shown in Fig 1A.1-3 The location of the “activated” transponders, and hence the target, is determined by triangulating their position relative to the array. Approved for use in the treatment of prostate cancer, the Calypso system is being investigated for the treatment of breast tumors and other tumors. In this report, we describe the first use of the Calypso system in a pediatric patient undergoing definitive radiotherapy. The decision to use the Calypso system was made for the following reasons: 1) to overcome the potential inaccuracy of softtissue and bony anatomy landmark identification for treatment setup; 2) to provide rapid patient setup, thus limiting the anesthesia time needed to safely deliver therapy; 3) to provide for real-time tracking of target location throughout delivery of radiation, thus allowing the use of smaller planning target volume margins; and 4) to minimize the need for daily portal imaging studies and their associated extraneous radiation dose.
1879-8500/$ – see front matter © 2011 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.prro.2010.08.001
48
R.J. Kimple et al
Practical Radiation Oncology: January-March 2011
Figure 1 A. Position of patient, Calypso array, and gantry prior to treatment. B. Digitally reconstructed radiograph showing the position of the left and right ovary, the 3 Calypso markers, and the gross tumor volume. C. Cross-sectional image at the level of the femoral heads reveals 2 Calypso markers, the gross tumor volume (innermost contour line), clinical target volume (middle contour line), and planning target volume (outer contour line). D. Dose-volume histograms of the clinical target volume (upper left), gross tumor volume (upper right), and bilateral femoral heads (lower left and lower right).
Practical Radiation Oncology: January-March 2011
Case report A 2-year-old African American female was diagnosed with botryoid vaginal rhabdomyosarcoma (RMS) from excisional biopsy after presenting with a vaginal mass seen while bathing. After initial vincristine, dactinomycin, and cyclophosphamide chemotherapy per children's oncology group ARST 0331, second-look surgery at week 12 revealed multiple areas of gross residual tumor consistent with clinical group III and not amenable to surgical resection. After discussion with the pediatric oncologist, the pediatric surgeon, and the treating radiation oncologist, a recommendation for locally directed RT was made. The plan was discussed with the patient's mother, and the potential value of using Calypso transponders rather than gold seeds was made. The patient's mother signed consent for the radiation, including implantation of Calypso Beacon transponders during anesthesia at the time of second-look surgery and use of de-identified setup pictures for educational purposes. The fiducial markers were placed while under anesthesia in the operating room prior to transposition of the ovaries in preparation for locally directed therapy with RT. Using the manufacturer-supplied kit, 3 Beacon transponders were implanted by the radiation oncologist into the vaginal wall in the 2, 7, and 10 o'clock positions. Hemostasis was achieved, and the surgeon completed the ovarian transposition. One week later, the patient presented for computed tomography simulation with anesthesia assistance. To ensure reproducible positioning, a VacLok immobilization device (Civco Worldwide, Kalona, Iowa) was used, the legs were placed in the frog-leg position, and initial isocenter marks were placed on the Vac-Lok. A computed tomographic scan from the upper abdomen through the knees was obtained using 3-mm thin slices as recommended by the manufacturer. The standard prostate protocol was adapted for a pediatric patient to minimize radiation exposure.
Calypso in pediatric vaginal rhabdomyosarcoma
49
growth plates (b1000 cGy), rectum, and bladder. Final dose-volume histograms are shown in Fig 1D.
Description of daily treatment Each day, anesthesia provides sedation and the patient is transferred to the treatment machine. Setup is performed using the localization function of the Calypso system and treatment proceeds with real-time tracking of target movement. The 3 Calypso beacons define a point in space termed the centroid. This point approximates the location of the tumor and is monitored at a frequency of 10 Hz throughout treatment. Representative localization graphs showing movements of the centroid in the X, Y, and Z directions are shown in Fig 2. Average daily setup takes less than 1 minute (Fig 2A). During daily setup, if rotation of the transponders was noted, the patient was repositioned in the Vac-Lok. Translation was performed to position the patient appropriately using standard table movements in the X, Y, and Z directions. To confirm that the transponders did not migrate, weekly port films were
Treatment planning The gross tumor volume was identified based on the imaging and physical examination findings. The Beacon transponders were identified, verified to be in the vicinity of the target volume, and used to aid in delineation of the proximal and distal extent of the tumor. The 3 Calypso markers (crosses) approximate the position of the gross tumor volume (contoured volume) as seen on digitally reconstructed radiograph (Fig 1B). The clinical target volume (middle contour line) included the entire gross tumor volume and appropriate proximal and distal margins with extension to the pelvic sidewall and exclusion of normal musculature (Fig 1C). The planning target volume (outer contour line) was defined as the clinical target volume with a 3-mm margin (Fig 1C). A 7-field intensity modulated RT plan was generated to deliver 5040 cGy to the target volumes and minimize dose to the femoral
Figure 2 A. Representative localization graph showing movement of the centroid in the X, Y, and Z directions from the time the array is in place until the patient is correctly set up. B. Representative real-time tracking of the Calypso centroid (Calypso Medical, Seattle, WA) during a daily treatment. Time zero represents beam-on time and the graph continues for the duration of treatment.
50
R.J. Kimple et al
taken. In addition, no change in the relative localization of the transponders was noted throughout treatment. The system alerts the therapist if the centroid moves in any direction by more than 3 mm and sounds an audible alert if this movement persists for more than 5 seconds, allowing the therapist to interrupt treatment and reposition the patient. Nearly 6000 data points are analyzed instantaneously during treatment each day. A representative daily treatment is shown in Fig 2B. This allows us to ensure that even a simple cough be monitored, and, if necessary, treatment interrupted and the patient repositioned prior to completing the daily radiation treatment. Overall mean daily treatment time was 10.3 minutes (range, 7.9-23.3), with significantly longer times corresponding to days on which port films were taken or during which anesthesia required additional time.
Discussion Rhabdomyosarcoma is the third most common extracranial solid tumor of childhood, and is believed to arise from immature mesenchymal cells.4 The botryoid variant, a subset of embryonal RMS, is almost exclusively found in younger children and develops from the bladder or vagina. The successful treatment of RMS requires a multidisciplinary approach of surgical removal, radiation therapy, and systemic chemotherapy.3 The radiation therapy continues to prove an integral part of primary disease treatment and prevention of recurrence. Preliminary data from ARST 0331 demonstrated a high local failure rate with disease recurrence in patients with primary embryonal vaginal RMS when local RT was delayed or avoided altogether (ARST0331, clinical protocol version date August 19, 2009, unpublished work).5 Data from prior RMS studies also support the conclusion that without timely initiation of local control measures, prognosis may be compromised.6,7 Recent analysis of the Intergroup Rhabdomyosarcoma Study I-III data demonstrates that even patients with complete resection had improved outcome when RT was used in conjunction with intensified systemic chemotherapy.8 Side effects of RT, particularly in children, are numerous, and efforts to perfect delivery mechanisms of RT and minimize morbidity are ongoing. Although most commonly used in the treatment of prostate cancer, the Calypso system provides an opportunity to improve treatment delivery of radiation for many patients. Consisting of small, implantable markers, this nonionizing system was successfully used for the daily setup and real-time monitoring of treatment delivery in a pediatric patient with vaginal RMS. Although the use of Calypso in vaginal RMS may be infrequent, the technology to continuously monitor a patient's tumor throughout treatment will continue to evolve. Although the case reported herein is not likely to
Practical Radiation Oncology: January-March 2011
be a common encounter in most radiation oncologist's office, it can be used to illustrate how to adapt current technology to new areas. We continue to consider the use of Calypso in additional disease, similar to work being done at Emory University where they are studying cervical motion during therapy using the Calypso system (ClinicalTrials.gov ID: NCT00907634). The ability to rapidly position the patient for treatment minimizes the time the patient spends under anesthesia and the associated risks and costs that accompany prolonged and repeated anesthesia.9 Use of the real-time tracking component of the system, which alerts the therapist if the patient moves outside of pre-defined parameters, allows the radiation oncologist to use smaller margins to expand a clinical target volume into a planning target volume. Precise and accurate delivery of radiation enables more conformal dose delivery and improves our ability to spare critical normal structures, such as the femoral head, bladder, and rectum. Finally, because the Calypso system uses electromagnetic fields, rather than ionizing radiation to localize and track patient positioning, it decreases the total body radiation dose. Alternative methods for daily localization include orthogonal portal imaging or cone-beam computed tomography, both of which take significantly longer to perform and check, and both of which use additional ionizing radiation. Although proportional to the therapeutic dose of radiation delivered in this case, the additional radiation from daily imaging may represent only a 1%-2% increase in a 2-year-old patient with a curable disease, and reasonable attempts to decrease total body radiation should be taken.
Conclusion We report here the first use of the Calypso system for treatment of a pediatric patient. This approach has allowed us to deliver more conformal radiation while better sparing normal tissues and minimizing treatment setup and delivery time. This technology may be easily adapted for use in treatment of appropriate pediatric patients to improve treatment and minimize potential long- and short-term effects associated with RT.
References 1. Balter JM, Wright JN, Newell LJ, et al. Accuracy of a wireless localization system for radiotherapy. Int J Radiat Oncol Biol Phys. 2005;61:933-937. 2. Willoughby TR, Kupelian PA, Pouliot J, et al. Target localization and real-time tracking using the Calypso 4D localization system in patients with localized prostate cancer. Int J Radiat Oncol Biol Phys. 2006;65:528-534. 3. Seiler PG, Blattmann H, Kirsch S, Muench RK, Shilling C. A novel tracking technique for the continuous precise measurement of tumour
Practical Radiation Oncology: January-March 2011 positions in conformal radiotherapy. Phys Med Biol. 2000; N103-N110. 4. Halperin E, Constine L, Tarbell N, Kun L. Pediatric Radiation Oncology. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2005. 5. Stevens MC, Rey A, Bouvet N, et al. Treatment of nonmetastatic rhabdomyosarcoma in childhood and adolescence: third study of the International Society of Paediatric Oncology – SIOP Malignant Mesenchymal Tumor 89. J Clin Oncol. 2005;23:2618-2628. 6. Donaldson SS, Anderson JR. Rhabdomyosarcoma: many similarities, a few philosophical differences. J Clin Oncol. 2005;23:2586-2587.
Calypso in pediatric vaginal rhabdomyosarcoma
51
7. Puri DR, Wexler LH, Meyers PA, La Quaglia MP, Healey JH, Wolden SL. The challenging role of radiation therapy for very young children with rhabdomyosarcoma. Int J Radiat Oncol Biol Phys. 2006;65: 1177-1184. 8. Wolden SL, Anderson JR, Crist WM, et al. Indications for radiotherapy and chemotherapy after complete resection in rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Studies I to III. J Clin Oncol. 1999;17:3468-3475. 9. Cravero JP. Risk and safety of pediatric sedation/anesthesia for procedures outside the operating room. Curr Opin Anaesthesiol. 2009;22:509-513.
www.practicalradonc.org
Teaching Case
First use of electromagnetic setup and real-time tracking in a pediatric patient with vaginal rhabdomyosarcoma Randall J. Kimple MD, PhD a,⁎, Katharine E. Wallen MD b , Talisha Person RTT a , Raina N. Erwin CMD a , Michael A. Helmrath MD c,d , Stuart Gold MD b,d , David E. Morris MD a,d a
Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina c Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina d Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina b
Received 20 August 2010; accepted 23 August 2010
Abstract We report the first use of the Calypso system (Calypso Medical, Seattle, WA) in a pediatric patient with group III vaginal rhabdomyosarcoma. The Calypso system was used to improve patient setup, to limit anesthesia, to provide for real-time tracking of target location, and to minimize the need for daily portal imaging studies and their associated extraneous radiation dose. © 2011 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
Introduction Accurate localization of target tissues is a cornerstone of modern conformal radiation therapy (RT). The Calypso system (Calypso Medical, Seattle, WA) allows for localization and real-time tracking of target tissue to improve the accuracy of RT delivery. Electromagnetic markers (ie, Beacon transponders) implanted within target tissue are powered by a nonionizing oscillating electromagnetic field generated by an electromagnetic array that is Sources of support: RJK has been designated a B. Leonard Holman Pathway Fellow by the American Board of Radiology and is supported by a Resident/Fellows in Radiation Oncology Seed Grant from the American Society for Radiation Oncology. Conflicts of interest: None. ⁎Corresponding author. Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. E-mail address: [email protected] (R.J. Kimple).
placed anterior to the supine patient, as shown in Fig 1A.1-3 The location of the “activated” transponders, and hence the target, is determined by triangulating their position relative to the array. Approved for use in the treatment of prostate cancer, the Calypso system is being investigated for the treatment of breast tumors and other tumors. In this report, we describe the first use of the Calypso system in a pediatric patient undergoing definitive radiotherapy. The decision to use the Calypso system was made for the following reasons: 1) to overcome the potential inaccuracy of softtissue and bony anatomy landmark identification for treatment setup; 2) to provide rapid patient setup, thus limiting the anesthesia time needed to safely deliver therapy; 3) to provide for real-time tracking of target location throughout delivery of radiation, thus allowing the use of smaller planning target volume margins; and 4) to minimize the need for daily portal imaging studies and their associated extraneous radiation dose.
1879-8500/$ – see front matter © 2011 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.prro.2010.08.001
48
R.J. Kimple et al
Practical Radiation Oncology: January-March 2011
Figure 1 A. Position of patient, Calypso array, and gantry prior to treatment. B. Digitally reconstructed radiograph showing the position of the left and right ovary, the 3 Calypso markers, and the gross tumor volume. C. Cross-sectional image at the level of the femoral heads reveals 2 Calypso markers, the gross tumor volume (innermost contour line), clinical target volume (middle contour line), and planning target volume (outer contour line). D. Dose-volume histograms of the clinical target volume (upper left), gross tumor volume (upper right), and bilateral femoral heads (lower left and lower right).
Practical Radiation Oncology: January-March 2011
Case report A 2-year-old African American female was diagnosed with botryoid vaginal rhabdomyosarcoma (RMS) from excisional biopsy after presenting with a vaginal mass seen while bathing. After initial vincristine, dactinomycin, and cyclophosphamide chemotherapy per children's oncology group ARST 0331, second-look surgery at week 12 revealed multiple areas of gross residual tumor consistent with clinical group III and not amenable to surgical resection. After discussion with the pediatric oncologist, the pediatric surgeon, and the treating radiation oncologist, a recommendation for locally directed RT was made. The plan was discussed with the patient's mother, and the potential value of using Calypso transponders rather than gold seeds was made. The patient's mother signed consent for the radiation, including implantation of Calypso Beacon transponders during anesthesia at the time of second-look surgery and use of de-identified setup pictures for educational purposes. The fiducial markers were placed while under anesthesia in the operating room prior to transposition of the ovaries in preparation for locally directed therapy with RT. Using the manufacturer-supplied kit, 3 Beacon transponders were implanted by the radiation oncologist into the vaginal wall in the 2, 7, and 10 o'clock positions. Hemostasis was achieved, and the surgeon completed the ovarian transposition. One week later, the patient presented for computed tomography simulation with anesthesia assistance. To ensure reproducible positioning, a VacLok immobilization device (Civco Worldwide, Kalona, Iowa) was used, the legs were placed in the frog-leg position, and initial isocenter marks were placed on the Vac-Lok. A computed tomographic scan from the upper abdomen through the knees was obtained using 3-mm thin slices as recommended by the manufacturer. The standard prostate protocol was adapted for a pediatric patient to minimize radiation exposure.
Calypso in pediatric vaginal rhabdomyosarcoma
49
growth plates (b1000 cGy), rectum, and bladder. Final dose-volume histograms are shown in Fig 1D.
Description of daily treatment Each day, anesthesia provides sedation and the patient is transferred to the treatment machine. Setup is performed using the localization function of the Calypso system and treatment proceeds with real-time tracking of target movement. The 3 Calypso beacons define a point in space termed the centroid. This point approximates the location of the tumor and is monitored at a frequency of 10 Hz throughout treatment. Representative localization graphs showing movements of the centroid in the X, Y, and Z directions are shown in Fig 2. Average daily setup takes less than 1 minute (Fig 2A). During daily setup, if rotation of the transponders was noted, the patient was repositioned in the Vac-Lok. Translation was performed to position the patient appropriately using standard table movements in the X, Y, and Z directions. To confirm that the transponders did not migrate, weekly port films were
Treatment planning The gross tumor volume was identified based on the imaging and physical examination findings. The Beacon transponders were identified, verified to be in the vicinity of the target volume, and used to aid in delineation of the proximal and distal extent of the tumor. The 3 Calypso markers (crosses) approximate the position of the gross tumor volume (contoured volume) as seen on digitally reconstructed radiograph (Fig 1B). The clinical target volume (middle contour line) included the entire gross tumor volume and appropriate proximal and distal margins with extension to the pelvic sidewall and exclusion of normal musculature (Fig 1C). The planning target volume (outer contour line) was defined as the clinical target volume with a 3-mm margin (Fig 1C). A 7-field intensity modulated RT plan was generated to deliver 5040 cGy to the target volumes and minimize dose to the femoral
Figure 2 A. Representative localization graph showing movement of the centroid in the X, Y, and Z directions from the time the array is in place until the patient is correctly set up. B. Representative real-time tracking of the Calypso centroid (Calypso Medical, Seattle, WA) during a daily treatment. Time zero represents beam-on time and the graph continues for the duration of treatment.
50
R.J. Kimple et al
taken. In addition, no change in the relative localization of the transponders was noted throughout treatment. The system alerts the therapist if the centroid moves in any direction by more than 3 mm and sounds an audible alert if this movement persists for more than 5 seconds, allowing the therapist to interrupt treatment and reposition the patient. Nearly 6000 data points are analyzed instantaneously during treatment each day. A representative daily treatment is shown in Fig 2B. This allows us to ensure that even a simple cough be monitored, and, if necessary, treatment interrupted and the patient repositioned prior to completing the daily radiation treatment. Overall mean daily treatment time was 10.3 minutes (range, 7.9-23.3), with significantly longer times corresponding to days on which port films were taken or during which anesthesia required additional time.
Discussion Rhabdomyosarcoma is the third most common extracranial solid tumor of childhood, and is believed to arise from immature mesenchymal cells.4 The botryoid variant, a subset of embryonal RMS, is almost exclusively found in younger children and develops from the bladder or vagina. The successful treatment of RMS requires a multidisciplinary approach of surgical removal, radiation therapy, and systemic chemotherapy.3 The radiation therapy continues to prove an integral part of primary disease treatment and prevention of recurrence. Preliminary data from ARST 0331 demonstrated a high local failure rate with disease recurrence in patients with primary embryonal vaginal RMS when local RT was delayed or avoided altogether (ARST0331, clinical protocol version date August 19, 2009, unpublished work).5 Data from prior RMS studies also support the conclusion that without timely initiation of local control measures, prognosis may be compromised.6,7 Recent analysis of the Intergroup Rhabdomyosarcoma Study I-III data demonstrates that even patients with complete resection had improved outcome when RT was used in conjunction with intensified systemic chemotherapy.8 Side effects of RT, particularly in children, are numerous, and efforts to perfect delivery mechanisms of RT and minimize morbidity are ongoing. Although most commonly used in the treatment of prostate cancer, the Calypso system provides an opportunity to improve treatment delivery of radiation for many patients. Consisting of small, implantable markers, this nonionizing system was successfully used for the daily setup and real-time monitoring of treatment delivery in a pediatric patient with vaginal RMS. Although the use of Calypso in vaginal RMS may be infrequent, the technology to continuously monitor a patient's tumor throughout treatment will continue to evolve. Although the case reported herein is not likely to
Practical Radiation Oncology: January-March 2011
be a common encounter in most radiation oncologist's office, it can be used to illustrate how to adapt current technology to new areas. We continue to consider the use of Calypso in additional disease, similar to work being done at Emory University where they are studying cervical motion during therapy using the Calypso system (ClinicalTrials.gov ID: NCT00907634). The ability to rapidly position the patient for treatment minimizes the time the patient spends under anesthesia and the associated risks and costs that accompany prolonged and repeated anesthesia.9 Use of the real-time tracking component of the system, which alerts the therapist if the patient moves outside of pre-defined parameters, allows the radiation oncologist to use smaller margins to expand a clinical target volume into a planning target volume. Precise and accurate delivery of radiation enables more conformal dose delivery and improves our ability to spare critical normal structures, such as the femoral head, bladder, and rectum. Finally, because the Calypso system uses electromagnetic fields, rather than ionizing radiation to localize and track patient positioning, it decreases the total body radiation dose. Alternative methods for daily localization include orthogonal portal imaging or cone-beam computed tomography, both of which take significantly longer to perform and check, and both of which use additional ionizing radiation. Although proportional to the therapeutic dose of radiation delivered in this case, the additional radiation from daily imaging may represent only a 1%-2% increase in a 2-year-old patient with a curable disease, and reasonable attempts to decrease total body radiation should be taken.
Conclusion We report here the first use of the Calypso system for treatment of a pediatric patient. This approach has allowed us to deliver more conformal radiation while better sparing normal tissues and minimizing treatment setup and delivery time. This technology may be easily adapted for use in treatment of appropriate pediatric patients to improve treatment and minimize potential long- and short-term effects associated with RT.
References 1. Balter JM, Wright JN, Newell LJ, et al. Accuracy of a wireless localization system for radiotherapy. Int J Radiat Oncol Biol Phys. 2005;61:933-937. 2. Willoughby TR, Kupelian PA, Pouliot J, et al. Target localization and real-time tracking using the Calypso 4D localization system in patients with localized prostate cancer. Int J Radiat Oncol Biol Phys. 2006;65:528-534. 3. Seiler PG, Blattmann H, Kirsch S, Muench RK, Shilling C. A novel tracking technique for the continuous precise measurement of tumour
Practical Radiation Oncology: January-March 2011 positions in conformal radiotherapy. Phys Med Biol. 2000; N103-N110. 4. Halperin E, Constine L, Tarbell N, Kun L. Pediatric Radiation Oncology. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2005. 5. Stevens MC, Rey A, Bouvet N, et al. Treatment of nonmetastatic rhabdomyosarcoma in childhood and adolescence: third study of the International Society of Paediatric Oncology – SIOP Malignant Mesenchymal Tumor 89. J Clin Oncol. 2005;23:2618-2628. 6. Donaldson SS, Anderson JR. Rhabdomyosarcoma: many similarities, a few philosophical differences. J Clin Oncol. 2005;23:2586-2587.
Calypso in pediatric vaginal rhabdomyosarcoma
51
7. Puri DR, Wexler LH, Meyers PA, La Quaglia MP, Healey JH, Wolden SL. The challenging role of radiation therapy for very young children with rhabdomyosarcoma. Int J Radiat Oncol Biol Phys. 2006;65: 1177-1184. 8. Wolden SL, Anderson JR, Crist WM, et al. Indications for radiotherapy and chemotherapy after complete resection in rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Studies I to III. J Clin Oncol. 1999;17:3468-3475. 9. Cravero JP. Risk and safety of pediatric sedation/anesthesia for procedures outside the operating room. Curr Opin Anaesthesiol. 2009;22:509-513.
