JOURNAL OF PALLIATIVE MEDICINE Volume 18, Number 2, 2015 ª Mary Ann Liebert, Inc. DOI: 10.1089/jpm.2014.0219
Radiation Therapy at End of Life in Children Joseph Panoff, MD,1 R. Victor Simoneaux, RTT,2 Nikesh Shah, BS,1 Michael Scott, MD,1 Jeffrey C. Buchsbaum, MD, PhD, AM,2,3 Peter A.S. Johnstone, MD, FACR,2,3 and Kevin P. McMullen, MD 2,3
Abstract
Objective: Few data exist on evaluating utilization patterns of radiotherapy (RT) at the end of life (EOL) in children. Metastatic disease in pediatric patients is not pathognomonic for palliative treatment intent; further complicating the issue are complexities surrounding the very select population of children receiving proton therapy (PrT). We compared data for RT and PrT in terms of death rate within 30 days. Methods: We performed chart reviews for patients receiving radiation therapy at age £ 21 years treated at Indiana University Health Proton Therapy Center (IUHPTC) between June 2008 and June 2013 and University of Miami Radiation Oncology Department (UM) between June 2000 and June 2013. Included were patients not completing prescribed courses of RT, and those dying within 30 days of therapy. Comparison was made of differences between practice data for PrT and conventional RT. Results: At IUHPTC, 2 children of 272 did not complete their courses and died within 30 days (0.7%). At UM, data are available for 425 children; 9 did not complete their courses and 7 died within 30 days (1.6%). Neither the number of patients who did not complete treatment nor the 30-day death rates (P = .21) for PrT and RT were significantly different. Conclusions: Delivery of RT for children at EOL is complex. Frequency of RT at EOL in children occurs in is < 2% of cases, and is not significantly less frequent in the proton milieu. This appears to be about an order of magnitude less than in adults.
Introduction
P
ressures related to the substantial resources devoted to patient treatments with advanced incurable conditions has led to an emerging literature in the adult population describing use of radiotherapy (RT) at the end of life (EOL). For purposes of this manuscript we define EOL as the 30 days preceding death. EOL RT carries with it minimal palliative benefit in most cases, and nonexistent survival benefit in adults.1,2 Dual pressures of decreasing cost of care while simultaneously improving access to care for more patients make it critical that a national discussion continue regarding which aspects of RT at EOL in adults may justifiably be considered futile care. The landscape of the discussion for children is far different. Unlike adults, for example, meningeal spread of cancer in children is not uniformly fatal,3 and significant palliation and cure may be accomplished even in the direst cases.4 Thus we anticipate that RT would be less frequently delivered at EOL for pediatric cancer patients.
Intense selection is involved in treating children with RT, and in particular with proton therapy (PrT). The relative scarcity of this technology5,6 requires that geographic, financial, and availability variables all coincide to allow PrT access to highly selected patients. Thus, we anticipate that the population of pediatric PrT patients would be even less likely to be treated at EOL than standard pediatric RT patients. We sought to quantify the practice of providing RT at EOL to children and to assess the impact of PrT as a scarce technology. Methods
After approval by institutional review boards, the records of the Indiana University Health Proton Therapy Center (IUHPTC) and University of Miami Radiation Oncology Department (UM) were reviewed for patients receiving radiation therapy at age £ 21 years between June 1, 2008 and June 1, 2013. Of these patients, specific analysis was made of patients not completing prescribed courses of RT and of patients dying within 30 days of receiving their final fraction of RT.
1
Department of Radiation Oncology, University of Miami School of Medicine, Miami, Florida. Indiana University Health Proton Therapy Center, Bloomington, Indiana. Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana. Accepted July 9, 2014.
2 3
167
168
PANOFF ET AL.
Data were collected beginning in September 2013 in both sites. This allowed for 30 days to elapse from the children treated in June 2013: the ending date for both sites. Further analysis was made of differences between children (defined as ages £ 12) and adolescents/young adults (AYA; ages 13 to 21). Finally, comparison data for PrT and conventional RT was performed. Descriptive statistics were sufficient for this analysis. Results
On January 1, 2010, IUHPTC became accredited by the American Association for Accreditation of Ambulatory Surgical Facilities. As part of that process, the center is required to submit cases of patients dying within 30 days of the end of their treatment, so processes were instituted to rigorously collect those data. These data were analyzed in October 2013. Only 2 children died of 272 treated (0.7%) (patients #8, 9 in Table 1). The first experienced aspiration at home that required hospitalization and subsequent discharge to hospice, and one developed progressive disease on treatment. Neither child received RT on the day they died. At UM, corresponding data between June 2000 and June 2013 revealed 9 truncated courses of 464 pediatric conventional RT treatments (2%). Five of these children survived 30 days after RT and four died within 30 days. Of 425 patients for whom full follow-up data are available, another 3 patients were found to have died with 30 days of RT for a total of 7 children dying either on treatment or within 30 days afterwards (1.6%). Four patients received RT on the day they died. The 30-day death rates for PrT and conventional RT were not significantly different (Fisher’s exact test, p = 0.21). These data were no different for children versus AYA patients because of limited events. Discussion
We were able to find no other publications describing prevalence of RT at EOL in children. In 2012 we published RT at EOL results of a targeted review of adult patients presented at a departmental morbidity and mortality (M&M) conference.1 In this select population, over half of patients receiving RT within 30 days of death were being treated at time of death, and most of them were less than halfway through the prescribed RT course. Six patients received RT on the day they died. A subsequent multi-institution review2 included an entire
year’s patients; in that cohort, 6.3% died within 30 days of receiving their last treatment, and 2.3% received RT within their last week of life. For patients treated at EOL, the median time until death from completion of therapy was only 12.5 days. Similarly, Kapadia and associates7 analyzed a population of nonsmall cell lung cancer patient outcomes. The authors reported 10% of patients who died had received RT at EOL, and nearly half did not complete the prescribed course. Guadagnolo and colleagues8 described congruent results in patients older than 65 years from SEER-Medicare data. In this series, 7.6% received RT in the last month of life, and of these, only 17.8% received more than 10 treatments. It appears that RT at EOL in children is less frequent than in adults by about an order of magnitude (1.6% with photons, 0.7% with protons). There are several important clinical differences between the adult and pediatric populations in this arena. First: many adult patients have comorbid conditions that might impact survival even if their cancer is controlled; this is rarely the case with children. Next, adults often have less capacity to tolerate treatment toxicities. Finally, adults, especially elderly adults, process risks and benefits differently from children, AYA, or their caretakers. Thus, deciding when to forego or decline therapy may be clearer in adults. The situation for children is further complicated by the curative intent possible in situations that would be otherwise palliative in adult patients. For instance, in children, leptomeningeal spread of disease is not uniformly fatal3,4 as it is in adults. Earlier integration of palliative care and hospice should be considered for patients of any age approaching EOL to help facilitate aggressive symptom management, advanced-care planning, and improve quality-of-life. Cost-effective palliative RT at EOL to address active symptoms should be limited to abbreviated courses, as evidenced by recent recommendations by the American Society for Radiation Oncology (ASTRO) regarding palliative treatment of bone metastases.9 While RT is considered to be a ‘‘mainstay for the treatment of pain and/or prevention of the morbidity caused by bone metastases,’’ there are a number of available fractionation schedules that can provide symptom palliation of symptoms. At EOL, in general, briefer is better. We consider RT utilization at EOL to be an overuse metric in adults, but we are analyzing whether hypofractionated regimens (single fractions, perhaps including five-fraction courses in some clinical scenarios) might be acceptable interventions.
Table 1. Demographic Data and Cause of Death for Truncated Courses of RT Patient #
Histology
Age 3
Tx site TBI
Gender
Cause of death
Dose received
M
Engraftment syndrome leading to multiorgan failure Midbrain glioma Glioblastoma multiforme Neuroblastoma, liver neoplasm, respiratory failure, sepsis Stage IV neuroblastoma Wilms ARDS Compromised brainstem function Lung metastases
13.2 Gy, 1.7 Gy/fraction (bid) 3.6 Gy, 1.8 Gy/fraction 38.0 Gy, 2.0 Gy/fraction 9.6 Gy, 1.2 Gy/fraction (bid) 7.2 Gy, 1.8 Gy/fraction 7.5 Gy, 1.5 Gy/fraction 55.8 Gy, 1.8 Gy/fraction 1.8 Gy, 1 tx
1
ALL
2 3 4
GBM GBM Neuroblastoma
5 6 7 8
Ganglioneuroblastoma 11 Wilms 5 Ewings 14 Astrocytoma 4
Pancreas Abdomen Iliac wing Brain
M F M F
9
ATRT
CSI
M
7 Brain 10 Brain 0.1 Liver
1
F F F
30.6 Gy, 1.8 Gy/fraction
ALL, acute lymphocytic leukemia; GBM, glioblastoma; TBI, total body irradiation; Gy, gray; bid, twice daily; ATRT, atypical teratoid/ rhabdoid tumor; CSI, craniospinal irradiation; ARDS, acute respiratory distress syndrome.
PEDIATRIC RADIOTHERAPY AT EOL
Pediatric patients provide a far more complex decision making scenario. The benefit of an additional year of life for a 10-year-old has a different societal value than a similar length of time to a retiree. Further, there are far, far fewer children dealing with EOL issues than adults. Thus, the societal cost of aggressive intervention for these children is a small fraction of the national expense for EOL care. It may be possible that the role of radiation is less well understood by our pediatric oncology colleagues. In a recent publication,10 a survey of Canadian pediatric oncologists revealed that only about 60% considered they had adequate knowledge about clinical indications for palliative RT. Over half of respondents thought that RT was underutilized in palliation of children’s symptoms. Their perceived barriers to its more frequent use included (1) patient or family reluctance, (2) travel distance to the cancer center, (3) belief that PRT has little impact on quality of life, and (4) concerns about toxicity.10 Thus, given that pediatric patients as a percentage enroll in more trials, and can tolerate more extensive courses of chemotherapy than adults in general, it is possible that they are simply being triaged more commonly toward chemotherapy as the primary palliative option. With fewer concerns regarding the significant late effects of RT in children treated with curative intent,11,12 pediatric RT at EOL is an area that requires increased study. The role of PrT is murky at best in the pediatric population in any case. For instance, there is no benefit to using protons in patients requiring whole-brain radiotherapy. While we have proposed that it is ethically sound to refer children requiring craniospinal RT for protons,13 no such case may be made for children with extremity lesions. The national discourses on EOL care for children, and for the role of protons in that timeframe, are just beginning. Conclusion
Two points may be made about current practice of RT at EOL in children from data presented here: (1) It is far less frequent in children than in adults; and (2) It appears to be no different using PrT compared to conventional RT. Author Disclosure Statement
No competing financial interests exist. References
1. Toole M, Lutz S, Johnstone PAS: Radiation oncology quality: Aggressiveness of cancer care near the end-of-life. J Am Coll Radiol 2012;9:199–202
169
2. Patel A, Dunmore-Griffith J, Lutz S, Johnstone PAS: Radiation therapy in the last month of life. Rep Pract Onc Radiother 2013:19:191–194. 3. Ray G, Buchsbaum JC, McMullen KP, et al.: Definitive treatment of leptomeningeal spinal metastases in children. Pediatr Blood Cancer 2013;60:1839–1841. 4. Shapiro RH, Chang AL: Urgent radiotherapy is effective in the treatment of metastatic medulloblastoma causing symptomatic brainstem edema. Pediatr Blood Cancer. 2011;57: 1077–1080. 5. Johnstone PAS, Durachta SL, Kerstiens J, Helsper R: Charitable care and scarce medical technology. J Am Coll Radiol 2009;6:609–612. 6. Jagsi R, DeLaney TF, Donelan K, Tarbell NJ: Real-time rationing of scarce resources: The Northeast Proton Therapy Center experience. J Clin Oncol 2004;22:2246–2250. 7. Kapadia NS, Mamet R, Zornosa C, et al.: Radiation therapy at the end of life in patients with incurable nonsmall cell lung cancer. Cancer 2012;118:4339–4345. 8. Guadagnolo BA, Liao KP, Elting L, et al.: Use of radiation therapy in the last 30 days of life among a large populationbased cohort of elderly patients in the United States. J Clin Oncol 2013;31:80–87. 9. Lutz S, Berk L, Chang E, et al.: Palliative radiotherapy for bone metastases: An ASTRO evidence-based guideline. Int J Radiat Oncol Biol Phys 2011;79:965–976. 10. Tucker TL, Samant RS, Fitzgibbon EJ: Knowledge and utilization of palliative radiotherapy by pediatric oncologists. Curr Oncol 2010;17:48–55. 11. McMullen KP, Buchsbaum JC, Douglas J, et al.: Growth abnormalities of the spine after radiation therapy: Respecting the past while moving forward in proton craniospinal irradiation. Pract Radiat Oncol 2013;3:337–343. 12. Di Pinto M, Conklin HM, Li C, Merchant TE: Learning and memory following conformal radiation therapy for pediatric craniopharyngioma and low-grade glioma. Int J Radiat Oncol Biol Phys 2012;84:e363–e369. 13. Johnstone PAS, McMullen KP, Buchsbaum JC, et al.: Are protons the only ethical approach? Int J Radiat Oncol Biol Phys 2013;87:228–230.
Address correspondence to: Peter A.S. Johnstone, MD Department of Radiation Oncology Moffitt Cancer Center 12902 Magnolia Drive Tampa, FL 33612 E-mail: [email protected]
Radiation Therapy at End of Life in Children Joseph Panoff, MD,1 R. Victor Simoneaux, RTT,2 Nikesh Shah, BS,1 Michael Scott, MD,1 Jeffrey C. Buchsbaum, MD, PhD, AM,2,3 Peter A.S. Johnstone, MD, FACR,2,3 and Kevin P. McMullen, MD 2,3
Abstract
Objective: Few data exist on evaluating utilization patterns of radiotherapy (RT) at the end of life (EOL) in children. Metastatic disease in pediatric patients is not pathognomonic for palliative treatment intent; further complicating the issue are complexities surrounding the very select population of children receiving proton therapy (PrT). We compared data for RT and PrT in terms of death rate within 30 days. Methods: We performed chart reviews for patients receiving radiation therapy at age £ 21 years treated at Indiana University Health Proton Therapy Center (IUHPTC) between June 2008 and June 2013 and University of Miami Radiation Oncology Department (UM) between June 2000 and June 2013. Included were patients not completing prescribed courses of RT, and those dying within 30 days of therapy. Comparison was made of differences between practice data for PrT and conventional RT. Results: At IUHPTC, 2 children of 272 did not complete their courses and died within 30 days (0.7%). At UM, data are available for 425 children; 9 did not complete their courses and 7 died within 30 days (1.6%). Neither the number of patients who did not complete treatment nor the 30-day death rates (P = .21) for PrT and RT were significantly different. Conclusions: Delivery of RT for children at EOL is complex. Frequency of RT at EOL in children occurs in is < 2% of cases, and is not significantly less frequent in the proton milieu. This appears to be about an order of magnitude less than in adults.
Introduction
P
ressures related to the substantial resources devoted to patient treatments with advanced incurable conditions has led to an emerging literature in the adult population describing use of radiotherapy (RT) at the end of life (EOL). For purposes of this manuscript we define EOL as the 30 days preceding death. EOL RT carries with it minimal palliative benefit in most cases, and nonexistent survival benefit in adults.1,2 Dual pressures of decreasing cost of care while simultaneously improving access to care for more patients make it critical that a national discussion continue regarding which aspects of RT at EOL in adults may justifiably be considered futile care. The landscape of the discussion for children is far different. Unlike adults, for example, meningeal spread of cancer in children is not uniformly fatal,3 and significant palliation and cure may be accomplished even in the direst cases.4 Thus we anticipate that RT would be less frequently delivered at EOL for pediatric cancer patients.
Intense selection is involved in treating children with RT, and in particular with proton therapy (PrT). The relative scarcity of this technology5,6 requires that geographic, financial, and availability variables all coincide to allow PrT access to highly selected patients. Thus, we anticipate that the population of pediatric PrT patients would be even less likely to be treated at EOL than standard pediatric RT patients. We sought to quantify the practice of providing RT at EOL to children and to assess the impact of PrT as a scarce technology. Methods
After approval by institutional review boards, the records of the Indiana University Health Proton Therapy Center (IUHPTC) and University of Miami Radiation Oncology Department (UM) were reviewed for patients receiving radiation therapy at age £ 21 years between June 1, 2008 and June 1, 2013. Of these patients, specific analysis was made of patients not completing prescribed courses of RT and of patients dying within 30 days of receiving their final fraction of RT.
1
Department of Radiation Oncology, University of Miami School of Medicine, Miami, Florida. Indiana University Health Proton Therapy Center, Bloomington, Indiana. Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana. Accepted July 9, 2014.
2 3
167
168
PANOFF ET AL.
Data were collected beginning in September 2013 in both sites. This allowed for 30 days to elapse from the children treated in June 2013: the ending date for both sites. Further analysis was made of differences between children (defined as ages £ 12) and adolescents/young adults (AYA; ages 13 to 21). Finally, comparison data for PrT and conventional RT was performed. Descriptive statistics were sufficient for this analysis. Results
On January 1, 2010, IUHPTC became accredited by the American Association for Accreditation of Ambulatory Surgical Facilities. As part of that process, the center is required to submit cases of patients dying within 30 days of the end of their treatment, so processes were instituted to rigorously collect those data. These data were analyzed in October 2013. Only 2 children died of 272 treated (0.7%) (patients #8, 9 in Table 1). The first experienced aspiration at home that required hospitalization and subsequent discharge to hospice, and one developed progressive disease on treatment. Neither child received RT on the day they died. At UM, corresponding data between June 2000 and June 2013 revealed 9 truncated courses of 464 pediatric conventional RT treatments (2%). Five of these children survived 30 days after RT and four died within 30 days. Of 425 patients for whom full follow-up data are available, another 3 patients were found to have died with 30 days of RT for a total of 7 children dying either on treatment or within 30 days afterwards (1.6%). Four patients received RT on the day they died. The 30-day death rates for PrT and conventional RT were not significantly different (Fisher’s exact test, p = 0.21). These data were no different for children versus AYA patients because of limited events. Discussion
We were able to find no other publications describing prevalence of RT at EOL in children. In 2012 we published RT at EOL results of a targeted review of adult patients presented at a departmental morbidity and mortality (M&M) conference.1 In this select population, over half of patients receiving RT within 30 days of death were being treated at time of death, and most of them were less than halfway through the prescribed RT course. Six patients received RT on the day they died. A subsequent multi-institution review2 included an entire
year’s patients; in that cohort, 6.3% died within 30 days of receiving their last treatment, and 2.3% received RT within their last week of life. For patients treated at EOL, the median time until death from completion of therapy was only 12.5 days. Similarly, Kapadia and associates7 analyzed a population of nonsmall cell lung cancer patient outcomes. The authors reported 10% of patients who died had received RT at EOL, and nearly half did not complete the prescribed course. Guadagnolo and colleagues8 described congruent results in patients older than 65 years from SEER-Medicare data. In this series, 7.6% received RT in the last month of life, and of these, only 17.8% received more than 10 treatments. It appears that RT at EOL in children is less frequent than in adults by about an order of magnitude (1.6% with photons, 0.7% with protons). There are several important clinical differences between the adult and pediatric populations in this arena. First: many adult patients have comorbid conditions that might impact survival even if their cancer is controlled; this is rarely the case with children. Next, adults often have less capacity to tolerate treatment toxicities. Finally, adults, especially elderly adults, process risks and benefits differently from children, AYA, or their caretakers. Thus, deciding when to forego or decline therapy may be clearer in adults. The situation for children is further complicated by the curative intent possible in situations that would be otherwise palliative in adult patients. For instance, in children, leptomeningeal spread of disease is not uniformly fatal3,4 as it is in adults. Earlier integration of palliative care and hospice should be considered for patients of any age approaching EOL to help facilitate aggressive symptom management, advanced-care planning, and improve quality-of-life. Cost-effective palliative RT at EOL to address active symptoms should be limited to abbreviated courses, as evidenced by recent recommendations by the American Society for Radiation Oncology (ASTRO) regarding palliative treatment of bone metastases.9 While RT is considered to be a ‘‘mainstay for the treatment of pain and/or prevention of the morbidity caused by bone metastases,’’ there are a number of available fractionation schedules that can provide symptom palliation of symptoms. At EOL, in general, briefer is better. We consider RT utilization at EOL to be an overuse metric in adults, but we are analyzing whether hypofractionated regimens (single fractions, perhaps including five-fraction courses in some clinical scenarios) might be acceptable interventions.
Table 1. Demographic Data and Cause of Death for Truncated Courses of RT Patient #
Histology
Age 3
Tx site TBI
Gender
Cause of death
Dose received
M
Engraftment syndrome leading to multiorgan failure Midbrain glioma Glioblastoma multiforme Neuroblastoma, liver neoplasm, respiratory failure, sepsis Stage IV neuroblastoma Wilms ARDS Compromised brainstem function Lung metastases
13.2 Gy, 1.7 Gy/fraction (bid) 3.6 Gy, 1.8 Gy/fraction 38.0 Gy, 2.0 Gy/fraction 9.6 Gy, 1.2 Gy/fraction (bid) 7.2 Gy, 1.8 Gy/fraction 7.5 Gy, 1.5 Gy/fraction 55.8 Gy, 1.8 Gy/fraction 1.8 Gy, 1 tx
1
ALL
2 3 4
GBM GBM Neuroblastoma
5 6 7 8
Ganglioneuroblastoma 11 Wilms 5 Ewings 14 Astrocytoma 4
Pancreas Abdomen Iliac wing Brain
M F M F
9
ATRT
CSI
M
7 Brain 10 Brain 0.1 Liver
1
F F F
30.6 Gy, 1.8 Gy/fraction
ALL, acute lymphocytic leukemia; GBM, glioblastoma; TBI, total body irradiation; Gy, gray; bid, twice daily; ATRT, atypical teratoid/ rhabdoid tumor; CSI, craniospinal irradiation; ARDS, acute respiratory distress syndrome.
PEDIATRIC RADIOTHERAPY AT EOL
Pediatric patients provide a far more complex decision making scenario. The benefit of an additional year of life for a 10-year-old has a different societal value than a similar length of time to a retiree. Further, there are far, far fewer children dealing with EOL issues than adults. Thus, the societal cost of aggressive intervention for these children is a small fraction of the national expense for EOL care. It may be possible that the role of radiation is less well understood by our pediatric oncology colleagues. In a recent publication,10 a survey of Canadian pediatric oncologists revealed that only about 60% considered they had adequate knowledge about clinical indications for palliative RT. Over half of respondents thought that RT was underutilized in palliation of children’s symptoms. Their perceived barriers to its more frequent use included (1) patient or family reluctance, (2) travel distance to the cancer center, (3) belief that PRT has little impact on quality of life, and (4) concerns about toxicity.10 Thus, given that pediatric patients as a percentage enroll in more trials, and can tolerate more extensive courses of chemotherapy than adults in general, it is possible that they are simply being triaged more commonly toward chemotherapy as the primary palliative option. With fewer concerns regarding the significant late effects of RT in children treated with curative intent,11,12 pediatric RT at EOL is an area that requires increased study. The role of PrT is murky at best in the pediatric population in any case. For instance, there is no benefit to using protons in patients requiring whole-brain radiotherapy. While we have proposed that it is ethically sound to refer children requiring craniospinal RT for protons,13 no such case may be made for children with extremity lesions. The national discourses on EOL care for children, and for the role of protons in that timeframe, are just beginning. Conclusion
Two points may be made about current practice of RT at EOL in children from data presented here: (1) It is far less frequent in children than in adults; and (2) It appears to be no different using PrT compared to conventional RT. Author Disclosure Statement
No competing financial interests exist. References
1. Toole M, Lutz S, Johnstone PAS: Radiation oncology quality: Aggressiveness of cancer care near the end-of-life. J Am Coll Radiol 2012;9:199–202
169
2. Patel A, Dunmore-Griffith J, Lutz S, Johnstone PAS: Radiation therapy in the last month of life. Rep Pract Onc Radiother 2013:19:191–194. 3. Ray G, Buchsbaum JC, McMullen KP, et al.: Definitive treatment of leptomeningeal spinal metastases in children. Pediatr Blood Cancer 2013;60:1839–1841. 4. Shapiro RH, Chang AL: Urgent radiotherapy is effective in the treatment of metastatic medulloblastoma causing symptomatic brainstem edema. Pediatr Blood Cancer. 2011;57: 1077–1080. 5. Johnstone PAS, Durachta SL, Kerstiens J, Helsper R: Charitable care and scarce medical technology. J Am Coll Radiol 2009;6:609–612. 6. Jagsi R, DeLaney TF, Donelan K, Tarbell NJ: Real-time rationing of scarce resources: The Northeast Proton Therapy Center experience. J Clin Oncol 2004;22:2246–2250. 7. Kapadia NS, Mamet R, Zornosa C, et al.: Radiation therapy at the end of life in patients with incurable nonsmall cell lung cancer. Cancer 2012;118:4339–4345. 8. Guadagnolo BA, Liao KP, Elting L, et al.: Use of radiation therapy in the last 30 days of life among a large populationbased cohort of elderly patients in the United States. J Clin Oncol 2013;31:80–87. 9. Lutz S, Berk L, Chang E, et al.: Palliative radiotherapy for bone metastases: An ASTRO evidence-based guideline. Int J Radiat Oncol Biol Phys 2011;79:965–976. 10. Tucker TL, Samant RS, Fitzgibbon EJ: Knowledge and utilization of palliative radiotherapy by pediatric oncologists. Curr Oncol 2010;17:48–55. 11. McMullen KP, Buchsbaum JC, Douglas J, et al.: Growth abnormalities of the spine after radiation therapy: Respecting the past while moving forward in proton craniospinal irradiation. Pract Radiat Oncol 2013;3:337–343. 12. Di Pinto M, Conklin HM, Li C, Merchant TE: Learning and memory following conformal radiation therapy for pediatric craniopharyngioma and low-grade glioma. Int J Radiat Oncol Biol Phys 2012;84:e363–e369. 13. Johnstone PAS, McMullen KP, Buchsbaum JC, et al.: Are protons the only ethical approach? Int J Radiat Oncol Biol Phys 2013;87:228–230.
Address correspondence to: Peter A.S. Johnstone, MD Department of Radiation Oncology Moffitt Cancer Center 12902 Magnolia Drive Tampa, FL 33612 E-mail: [email protected]
