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Tech Savvy
Susan Doyle-Lindrud, DNP, AOCNP®, DCC—Associate Editor
Proton Beam Therapy for Pediatric Malignancies Susan Doyle-Lindrud, DNP, AOCNP®, DCC
Although major advances have been made in radiation techniques, concerns still exist about the treatment-related acute and long-term side effects. This issue is most notable in the pediatric population because of developing organs and tissues combined with longer life expectancies. Proton beam therapy has the advantage of a reduced dose of radiation with less scatter to normal tissue, which may lead to fewer adverse side effects. At a Glance • Many pediatric patients with cancer receive radiation therapy. • Radiation treatments can cause significant acute and long-term side effects. • Proton beam therapy reduces radiation scatter to normal tissues and may decrease acute and late toxicities. Susan Doyle-Lindrud, DNP, AOCNP®, DCC, is an assistant dean of Academic Affairs and a director of the Doctor of Nursing Practice Program and Oncology Program in the School of Nursing at Columbia University in New York, NY. The author takes full responsibility for the content of the article. The author did not receive honoraria for this work. No financial relationships relevant to the content of this article have been disclosed by the author or editorial staff. Doyle-Lindrud can be reached at [email protected], with copy to editor at [email protected]. Key words: radiation; survivorship; technology Digital Object Identifier: 10.1188/15.CJON.521-523
P
roton beam therapy is one of the latest advancements in radiation therapy used to treat cancer. Although initially proposed in 1946, the first patients were treated in 1958 at the Lawrence Berkeley National Laboratory in California (Merchant & Farr, 2014; Mitin & Zietman, 2014). The use of proton beam therapy in clinical practice has been slowly introduced but has gained significant ground with increasing public awareness since 2010 (Mitin & Zietman, 2014). One of the reasons this form of radiation has garnered interest is because of theoretical advantages as compared to photon therapy, with specific potential advantages in the pediatric population. About 12,000 new cases of pediatric cancer occur each year in the United States, and about 3,000 require radiation therapy (Merchant, 2013). Although radi-
ation is an important component of many treatment regimens for pediatric cancers, it is associated with early and late side effects that can be more problematic in children because of their developing organs and tissues (Armstrong, Stovall, & Robison, 2010). The possible benefits of proton beam therapy are the reduction in dose to normal tissues and a reduction in adverse effects of radiation treatment (Merchant, 2013).
Background Radiation therapy for patients with cancer commonly uses external beam delivery techniques that include photons. This form of ionizing radiation releases energy and delivers radiation doses to the specific areas of a patient’s body. The standard dose of radiation is the
Clinical Journal of Oncology Nursing • Volume 19, Number 5 • Tech Savvy
Gray (Gy). Photons travel through tissue without stopping, resulting in continuous dosing of radiation beyond the tumor (Merchant & Farr, 2014). Proton therapy is an external radiotherapy modality that uses protons instead of photons. Protons are positively charged particles that are accelerated by a large, expensive particle accelerator called a cyclotron or synchrotron, available at a limited number of specialized centers (Decker & Wilson, 2012). When a proton beam enters the body, it delivers a constant dose within a few millimeters of the end of the particle range, the socalled Bragg peak (see Figure 1). Beyond the Bragg peak, protons deliver almost no additional exit dose beyond the target. The benefit of this is that the proton beam stops within the patient’s tumor region, and the radiation does not extend to normal tissue beyond the tumor. This allows for radiation absorption to deep tumor targets with less scatter of radiation to normal surrounding tissues and the possible safe escalation of radiation doses to enhance tumor control (Daw & Mahajan, 2013; Swisher-McClure, Hahn, & Bekelman, 2015).
Childhood Cancer With multimodality therapies for pediatric malignancies, the five-year survival rate exceeds 80%. As many as 60%–90% of survivors of pediatric cancer experience adverse side effects related to the cancer or the treatment received (Geenen et al., 2007). The challenge for the pediatric cancer population with solid tumors undergoing radiation is the large, irregular volume of tumors close to critical structures in the body. In addition, children, when compared to adults, have longer anticipated life spans and an increased sensitivity to the radiation from 521
investigators that proton therapy is well tolerated and may hold therapeutic benefit with certain types of tumors, such as central nervous system tumors, over other forms of radiation therapy (Merchant & Farr, 2014; Merchant et al., 2008).
100
Dose (%)
80 6 MV
60
250 MeV
40
250 MeV
20
Challenges
0
As the cost of health care has increased, the cost and benefits of this new Photon Modified proton Native proton technology continue to be debated. The evidence to FIGURE 1. Proton and Photon Beams With Bragg support proton beam therapy in terms of outcomes Peak and cost is limited (MoriNote. From “Bragg Peak,” by A.A. Miller, 2005, licensed under arty, Borah, Foote, Pulido, CC BY-SA 3.0. Retrieved from https://commons.wikimedia.org/ & Shah, 2015). Construcwiki/File:BraggPeak.png tion of a proton therapy center is costly, ranging developing organs and tissues, which from $25 million to more than $200 milputs them at greater risk of secondary lion, depending on the size of the facility cancers and late effects of treatment (Swisher-McClure et al., 2015). The costs (Daw & Mahajan, 2013). Depending on of treatment are about two to three times the location of the tumor in the body and greater than photon-based radiation treatthe associated field of radiation, the late ments. In addition, because of the cost of effects include deficits in cognition, enconstructing a facility, these centers are docrine function, vascular abnormality, only available in select locations, adding to dental anomalies, hypothyroidism, carthe financial burden for patients and their diovascular and gastrointestinal toxicity, families because receiving proton beam and secondary malignancies (Armstrong therapy may involve travel, housing, and et al., 2010; Geenen et al., 2007; Greenpotential lost wages (Swisher-McClure et berger et al., 2014; Zhang et al., 2013). al., 2015). Proton beam therapy has been included as a radiation option in pediatric clinical trials for more than a decade, and the number of patients treated has The use of proton beam therapy to treat increased (Merchant, 2013). Guidelines pediatric malignancies is increasing, with that include proton therapy for pediatric the possible benefit that this modality central nervous system, musculoskeletal, may improve quality of life for long-term and solid tumors have been developed by cancer survivors (Palm & Johansson, the Children’s Oncology Group and ap2007; Rombi et al., 2014). Longitudinal, proved by the National Cancer Institute’s comparative clinical trials with long-term Cancer Therapy Evaluation Program follow-up are needed to assess survival (Merchant, 2013). Biologically, protons outcomes and evaluate for late effects and have not demonstrated a significant adsecondary malignancies of proton beam vantage when compared to photons, therapy, as compared to photon therapy. which leads to similar rates of predicted With continued advancement in radiation tumor control, but the physical propdelivery techniques, the development of erties of protons lead to less radiation smaller and less costly proton beam units scatter to normal tissues and a decrease could lead to an increase in the developin acute and late toxicities (Rombi, Venment of proton beam treatment centers narini, Vinante, Ravanelli, & Amichetti, and a decrease in cost to patients (Mitin 2014). However, consensus exists among & Zietman, 2014). 0
10 20 Depth in Tissue (cm)
30
Conclusion
522
References Armstrong, G.T., Stovall, M., & Robison, L.L. (2010). Long-term effects of radiation exposure among adult survivors of childhood cancer: Results from the childhood cancer survivor study. Radiation Research, 174, 840–850. doi:10.1667/ RR1903.1 Daw, N.C., & Mahajan, A. (2013). Photons or protons for non-central nervous system solid malignancies in children: A historical perspective and important highlights. American Society of Clinical Oncology Educational Book. Retrieved from http:// meetinglibrary.asco.org/content/126-132 Decker, R.H., & Wilson, L.D. (2012). Chapter 40: Radiotherapy. In L.A. Goldsmith, S.I. Katz, B.A. Gilchrest, A.S. Paller, D.J. Leffell, & K. Wolff (Eds.), Fitzpatrick’s dermatology in general medicine (8th ed.). Retrieved from http://accessmedicine .mhmedical.com/content.aspx?bookid=3 92&Sectionid=41138978 Geenen, M.M., Cardous-Ubbink, M.C., Kremer, L.C., van den Bos, C., van der Pal, H.J., Heinen, R.C., . . . van Leeuwen, F.E. (2007). Medical assessment of adverse health outcomes in long-term survivors of childhood cancer. JAMA, 297, 2705–2715. doi:10.1001/jama.297.24.2705 Greenberger, B.A., Pulsifer, M.B., Ebb, D.H., MacDonald, S.M., Jones, R.M., Butler, W.E., . . . Yock, T.I. (2014). Clinical outcomes and late endocrine, neurocognitive, and visual profiles of proton radiation for pediatric low-grade gliomas. International Journal of Radiation Oncology, Biology, Physics, 89, 1060–1068. doi:10.1016/j .ijrobp.2014.04.053 Merchant, T.E. (2013). Clinical controversies: Proton therapy for pediatric tumors. Seminars in Radiation Oncology, 23, 97–108. doi:10.1016/j.semradonc.2012.11.008 Merchant, T.E., & Farr, J.B. (2014). Proton beam therapy: A fad or a new standard of care. Current Opinion in Pediatrics, 26, 3–8. doi:10.1097/MOP.0000000000 000048 Merchant, T.E., Hua, C.H., Shukla, H., Ying, X., Nill, S., & Oelfke, U. (2008). Proton versus photon radiotherapy for common pediatric brain tumors: Comparison of models of dose characteristics and their relationship to cognitive function. Pediatric Blood and Cancer, 51, 110–117. doi:10.1002/pbc.21530 Mitin, T., & Zietman, A.L. (2014). Promise and pitfalls of heavy-particle therapy. Journal of Clinical Oncology, 32, 2855– 2863. doi:10.1200/JCO.2014.55.1945
October 2015 • Volume 19, Number 5 • Clinical Journal of Oncology Nursing
Moriarty, J.P., Borah, B.J., Foote, R.L., Pulido, J.S., & Shah, N.D. (2015). Cost-effectiveness of proton beam therapy for intraocular melanoma. PLoS One, 10, e0127814. doi:10.1371/journal.pone.0127814 Palm, A., & Johansson, K.A. (2007). A review of the impact of photon and proton external beam radiotherapy treatment modalities on the dose distribution in field and out-of-field; implications for the long-term morbidity of cancer survivors. Acta Oncologica, 46, 462–473. doi:10.1080/02841860701218626 Rombi, B., Vennarini, S., Vinante, L., Ravanelli, D., & Amichetti, M. (2014). Proton radiotherapy for pediatric tumors: Review of first clinical results. Italian Journal
of Pediatrics, 40, 74. doi:10.1186/s13052 -014-0074-6 Swisher-McClure, S., Hahn, S.M., & Bekelman, J. (2015). Proton beam therapy: The next disruptive innovation in healthcare? Postgraduate Medical Journal, 91, 241–243.
Zhang, R., Howell, R.M., Homann, K., Giebeler, A., Taddei, P.J., Mahajan, A., & Newhauser, W.D. (2013). Predicted risks of radiogenic cardiac toxicity in two pediatric patients undergoing photon or proton radiotherapy. Radiation Oncology, 8, 184. doi:10.1186/1748-717X-8-184
Do You Have an Interesting Topic to Share? Tech Savvy discusses the ways in which technology affects nurses, patients, the healthcare team, and the oncology setting. Length should be no more than 1,000–1,500 words, exclusive of tables, figures, insets, and references. If interested, contact Associate Editor Susan Doyle-Lindrud, DNP, AOCNP®, DCC, at [email protected].
Clinical Journal of Oncology Nursing • Volume 19, Number 5 • Tech Savvy
523
Tech Savvy
Susan Doyle-Lindrud, DNP, AOCNP®, DCC—Associate Editor
Proton Beam Therapy for Pediatric Malignancies Susan Doyle-Lindrud, DNP, AOCNP®, DCC
Although major advances have been made in radiation techniques, concerns still exist about the treatment-related acute and long-term side effects. This issue is most notable in the pediatric population because of developing organs and tissues combined with longer life expectancies. Proton beam therapy has the advantage of a reduced dose of radiation with less scatter to normal tissue, which may lead to fewer adverse side effects. At a Glance • Many pediatric patients with cancer receive radiation therapy. • Radiation treatments can cause significant acute and long-term side effects. • Proton beam therapy reduces radiation scatter to normal tissues and may decrease acute and late toxicities. Susan Doyle-Lindrud, DNP, AOCNP®, DCC, is an assistant dean of Academic Affairs and a director of the Doctor of Nursing Practice Program and Oncology Program in the School of Nursing at Columbia University in New York, NY. The author takes full responsibility for the content of the article. The author did not receive honoraria for this work. No financial relationships relevant to the content of this article have been disclosed by the author or editorial staff. Doyle-Lindrud can be reached at [email protected], with copy to editor at [email protected]. Key words: radiation; survivorship; technology Digital Object Identifier: 10.1188/15.CJON.521-523
P
roton beam therapy is one of the latest advancements in radiation therapy used to treat cancer. Although initially proposed in 1946, the first patients were treated in 1958 at the Lawrence Berkeley National Laboratory in California (Merchant & Farr, 2014; Mitin & Zietman, 2014). The use of proton beam therapy in clinical practice has been slowly introduced but has gained significant ground with increasing public awareness since 2010 (Mitin & Zietman, 2014). One of the reasons this form of radiation has garnered interest is because of theoretical advantages as compared to photon therapy, with specific potential advantages in the pediatric population. About 12,000 new cases of pediatric cancer occur each year in the United States, and about 3,000 require radiation therapy (Merchant, 2013). Although radi-
ation is an important component of many treatment regimens for pediatric cancers, it is associated with early and late side effects that can be more problematic in children because of their developing organs and tissues (Armstrong, Stovall, & Robison, 2010). The possible benefits of proton beam therapy are the reduction in dose to normal tissues and a reduction in adverse effects of radiation treatment (Merchant, 2013).
Background Radiation therapy for patients with cancer commonly uses external beam delivery techniques that include photons. This form of ionizing radiation releases energy and delivers radiation doses to the specific areas of a patient’s body. The standard dose of radiation is the
Clinical Journal of Oncology Nursing • Volume 19, Number 5 • Tech Savvy
Gray (Gy). Photons travel through tissue without stopping, resulting in continuous dosing of radiation beyond the tumor (Merchant & Farr, 2014). Proton therapy is an external radiotherapy modality that uses protons instead of photons. Protons are positively charged particles that are accelerated by a large, expensive particle accelerator called a cyclotron or synchrotron, available at a limited number of specialized centers (Decker & Wilson, 2012). When a proton beam enters the body, it delivers a constant dose within a few millimeters of the end of the particle range, the socalled Bragg peak (see Figure 1). Beyond the Bragg peak, protons deliver almost no additional exit dose beyond the target. The benefit of this is that the proton beam stops within the patient’s tumor region, and the radiation does not extend to normal tissue beyond the tumor. This allows for radiation absorption to deep tumor targets with less scatter of radiation to normal surrounding tissues and the possible safe escalation of radiation doses to enhance tumor control (Daw & Mahajan, 2013; Swisher-McClure, Hahn, & Bekelman, 2015).
Childhood Cancer With multimodality therapies for pediatric malignancies, the five-year survival rate exceeds 80%. As many as 60%–90% of survivors of pediatric cancer experience adverse side effects related to the cancer or the treatment received (Geenen et al., 2007). The challenge for the pediatric cancer population with solid tumors undergoing radiation is the large, irregular volume of tumors close to critical structures in the body. In addition, children, when compared to adults, have longer anticipated life spans and an increased sensitivity to the radiation from 521
investigators that proton therapy is well tolerated and may hold therapeutic benefit with certain types of tumors, such as central nervous system tumors, over other forms of radiation therapy (Merchant & Farr, 2014; Merchant et al., 2008).
100
Dose (%)
80 6 MV
60
250 MeV
40
250 MeV
20
Challenges
0
As the cost of health care has increased, the cost and benefits of this new Photon Modified proton Native proton technology continue to be debated. The evidence to FIGURE 1. Proton and Photon Beams With Bragg support proton beam therapy in terms of outcomes Peak and cost is limited (MoriNote. From “Bragg Peak,” by A.A. Miller, 2005, licensed under arty, Borah, Foote, Pulido, CC BY-SA 3.0. Retrieved from https://commons.wikimedia.org/ & Shah, 2015). Construcwiki/File:BraggPeak.png tion of a proton therapy center is costly, ranging developing organs and tissues, which from $25 million to more than $200 milputs them at greater risk of secondary lion, depending on the size of the facility cancers and late effects of treatment (Swisher-McClure et al., 2015). The costs (Daw & Mahajan, 2013). Depending on of treatment are about two to three times the location of the tumor in the body and greater than photon-based radiation treatthe associated field of radiation, the late ments. In addition, because of the cost of effects include deficits in cognition, enconstructing a facility, these centers are docrine function, vascular abnormality, only available in select locations, adding to dental anomalies, hypothyroidism, carthe financial burden for patients and their diovascular and gastrointestinal toxicity, families because receiving proton beam and secondary malignancies (Armstrong therapy may involve travel, housing, and et al., 2010; Geenen et al., 2007; Greenpotential lost wages (Swisher-McClure et berger et al., 2014; Zhang et al., 2013). al., 2015). Proton beam therapy has been included as a radiation option in pediatric clinical trials for more than a decade, and the number of patients treated has The use of proton beam therapy to treat increased (Merchant, 2013). Guidelines pediatric malignancies is increasing, with that include proton therapy for pediatric the possible benefit that this modality central nervous system, musculoskeletal, may improve quality of life for long-term and solid tumors have been developed by cancer survivors (Palm & Johansson, the Children’s Oncology Group and ap2007; Rombi et al., 2014). Longitudinal, proved by the National Cancer Institute’s comparative clinical trials with long-term Cancer Therapy Evaluation Program follow-up are needed to assess survival (Merchant, 2013). Biologically, protons outcomes and evaluate for late effects and have not demonstrated a significant adsecondary malignancies of proton beam vantage when compared to photons, therapy, as compared to photon therapy. which leads to similar rates of predicted With continued advancement in radiation tumor control, but the physical propdelivery techniques, the development of erties of protons lead to less radiation smaller and less costly proton beam units scatter to normal tissues and a decrease could lead to an increase in the developin acute and late toxicities (Rombi, Venment of proton beam treatment centers narini, Vinante, Ravanelli, & Amichetti, and a decrease in cost to patients (Mitin 2014). However, consensus exists among & Zietman, 2014). 0
10 20 Depth in Tissue (cm)
30
Conclusion
522
References Armstrong, G.T., Stovall, M., & Robison, L.L. (2010). Long-term effects of radiation exposure among adult survivors of childhood cancer: Results from the childhood cancer survivor study. Radiation Research, 174, 840–850. doi:10.1667/ RR1903.1 Daw, N.C., & Mahajan, A. (2013). Photons or protons for non-central nervous system solid malignancies in children: A historical perspective and important highlights. American Society of Clinical Oncology Educational Book. Retrieved from http:// meetinglibrary.asco.org/content/126-132 Decker, R.H., & Wilson, L.D. (2012). Chapter 40: Radiotherapy. In L.A. Goldsmith, S.I. Katz, B.A. Gilchrest, A.S. Paller, D.J. Leffell, & K. Wolff (Eds.), Fitzpatrick’s dermatology in general medicine (8th ed.). Retrieved from http://accessmedicine .mhmedical.com/content.aspx?bookid=3 92&Sectionid=41138978 Geenen, M.M., Cardous-Ubbink, M.C., Kremer, L.C., van den Bos, C., van der Pal, H.J., Heinen, R.C., . . . van Leeuwen, F.E. (2007). Medical assessment of adverse health outcomes in long-term survivors of childhood cancer. JAMA, 297, 2705–2715. doi:10.1001/jama.297.24.2705 Greenberger, B.A., Pulsifer, M.B., Ebb, D.H., MacDonald, S.M., Jones, R.M., Butler, W.E., . . . Yock, T.I. (2014). Clinical outcomes and late endocrine, neurocognitive, and visual profiles of proton radiation for pediatric low-grade gliomas. International Journal of Radiation Oncology, Biology, Physics, 89, 1060–1068. doi:10.1016/j .ijrobp.2014.04.053 Merchant, T.E. (2013). Clinical controversies: Proton therapy for pediatric tumors. Seminars in Radiation Oncology, 23, 97–108. doi:10.1016/j.semradonc.2012.11.008 Merchant, T.E., & Farr, J.B. (2014). Proton beam therapy: A fad or a new standard of care. Current Opinion in Pediatrics, 26, 3–8. doi:10.1097/MOP.0000000000 000048 Merchant, T.E., Hua, C.H., Shukla, H., Ying, X., Nill, S., & Oelfke, U. (2008). Proton versus photon radiotherapy for common pediatric brain tumors: Comparison of models of dose characteristics and their relationship to cognitive function. Pediatric Blood and Cancer, 51, 110–117. doi:10.1002/pbc.21530 Mitin, T., & Zietman, A.L. (2014). Promise and pitfalls of heavy-particle therapy. Journal of Clinical Oncology, 32, 2855– 2863. doi:10.1200/JCO.2014.55.1945
October 2015 • Volume 19, Number 5 • Clinical Journal of Oncology Nursing
Moriarty, J.P., Borah, B.J., Foote, R.L., Pulido, J.S., & Shah, N.D. (2015). Cost-effectiveness of proton beam therapy for intraocular melanoma. PLoS One, 10, e0127814. doi:10.1371/journal.pone.0127814 Palm, A., & Johansson, K.A. (2007). A review of the impact of photon and proton external beam radiotherapy treatment modalities on the dose distribution in field and out-of-field; implications for the long-term morbidity of cancer survivors. Acta Oncologica, 46, 462–473. doi:10.1080/02841860701218626 Rombi, B., Vennarini, S., Vinante, L., Ravanelli, D., & Amichetti, M. (2014). Proton radiotherapy for pediatric tumors: Review of first clinical results. Italian Journal
of Pediatrics, 40, 74. doi:10.1186/s13052 -014-0074-6 Swisher-McClure, S., Hahn, S.M., & Bekelman, J. (2015). Proton beam therapy: The next disruptive innovation in healthcare? Postgraduate Medical Journal, 91, 241–243.
Zhang, R., Howell, R.M., Homann, K., Giebeler, A., Taddei, P.J., Mahajan, A., & Newhauser, W.D. (2013). Predicted risks of radiogenic cardiac toxicity in two pediatric patients undergoing photon or proton radiotherapy. Radiation Oncology, 8, 184. doi:10.1186/1748-717X-8-184
Do You Have an Interesting Topic to Share? Tech Savvy discusses the ways in which technology affects nurses, patients, the healthcare team, and the oncology setting. Length should be no more than 1,000–1,500 words, exclusive of tables, figures, insets, and references. If interested, contact Associate Editor Susan Doyle-Lindrud, DNP, AOCNP®, DCC, at [email protected].
Clinical Journal of Oncology Nursing • Volume 19, Number 5 • Tech Savvy
523
