OBJECTIVE. Studies of symptoms in children dying a cancer-related death typically rely on medical chart reviews or parental responses to symptom checklists. However, the mere presence of a symptom does not necessarily correspond with the distress it can cause the child's parents. The purpose of this study was to identify the cancer-related symptoms that most concerned parents during the last days of their child's life and the strategies parents identified as helpful with their child's care. METHODS. Sixty-five parents of 52 children who had died a cancer-related death within the previous 6 to 10 months participated in telephone interviews. Eligibility criteria included being the parent or guardian of a child aged 0 to 21 years who had died within the previous 6 to 10 months after being treated at a pediatric cancer center, having been with their child during the last week of the child's life, speaking English, being willing to participate, and having access to a telephone. RESULTS. Eighteen symptoms of concern were identified as occurring during their child's final week and final day of life. The most frequently reported symptoms at both times included changes in behavior, changes in appearance, pain, weakness and fatigue, and breathing changes. The proportion of reported symptoms did not differ according to patient gender, disease, or location of death (intensive care, elsewhere in the hospital, or home). The most helpful strategies used by health care professionals to assist the child or parents included giving pain and anxiety medications, spending time with the child or family, providing competent care, and giving advice. CONCLUSIONS. This knowledge can guide professionals in preparing parents for the symptoms that a child imminently dying of cancer is likely to experience and in providing care that will be helpful to parents.
ABSTRACT Importance Early reports suggest adverse events following proton therapy (PT) for childhood cancer are more prevalent given the increased number of PT centers and use in clinical trials. Objective To assess treatment-failure and toxicity events following Pencil Beam Scanning (PBS)-PT in children. Design, Setting, and Participants The single-institution Phase IV surveillance trial screened 856 children, of which 528 were eligible for PBS-PT, and 500 enrolled in SJPROTON1 from 2017–2020. The median follow-up was 2.1 years (range 1.1-4.4). PBS-RT attributable toxicities were systematically identified, and graded at baseline to four years following PBS-PT. Interventions All patients underwent PBS-PT or combined photon/PBS-PT. Main Outcomes and Measures The primary objective was the CI of ≥grade 3 non-hematologic, PBS-PT attributable Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. Additional outcomes included PBS-PT attributable hospitalization, toxicity related procedures, and treatment-related mortality. Pre-specified toxicities including necrosis, vasculopathy, neurologic deficits, and fracture/osteoradionecrosis were further characterized (any grade) as a secondary objective. Medical record review augmented in-person visits for failure and adverse event reporting. Competing risk regression was used to evaluate predictors of ≥grade 3 PBS-PT attributable toxicity. Results At two years, the event-free survival was 73.2% (95% CI, 68.9%-77.8%). Distant and local failure predominated with a 2-year cumulative incidence (CI) of 16.5% (95% CI 13.1-20.4) and 6.8% (95% CI 4.6-9.5) respectively. The CI of ≥ grade 3 toxicity events at four years was 24.5%; including necrosis (3.7%), permanent neurologic deficit (2.9%), and fracture/osteoradionecrosis (0.79%). The rates of hospitalization and procedures due to PBS-PT– attributable toxicity was 3.9% and 7.6%, respectively. Predictors of an increased event-specific hazard for any ≥ grade 3 toxicity included baseline total toxicity burden (TTB) (HR 1.043, 95% CI 1.012-1.07, p=0.007), use of mixed photon/PBS-PT (HR 2.62, 95% CI 1.51-4.54, p=0.006) in the CNS population, and treatment of the pelvic body site (HR 4.25, 95% CI 1.08-16.72, p=0.038), and TTB (HR 1.1, 95% CI 1.04-1.16, p=0.002) in the non-CNS population, respectively. Conclusions and Relevance Children treated with PBS-PT experience a low incidence of toxicity, but subsets may be at increased risk, and experience toxicity that requires additional procedures or hospitalization. Key Points Question What is the efficacy and safety profile of Pencil Beam Scanning Proton therapy (PBS-PT) in children? Findings In this single institution phase IV trial, the rate of local failure and clinically significant ≥grade 3 PBS-RT attributable toxicity were low, but a subset of patients may be at increased risk for hospitalization and procedures related to managing PBS-RT attributable adverse events. Meaning PBS-RT has an acceptable therapeutic ratio in children but the risk of adverse events requiring hospitalization or subsequent procedures may be increased in select populations.
Background: Early reports suggest adverse events following proton therapy (PT) for childhood cancer are more prevalent. We evaluated treatment-failure and toxicity following Pencil Beam Scanning (PBS)-PT in children.Methods: The single-institution Phase IV trial screened 856 children, of which 528 were eligible for PBS-PT, and 500 enrolled in SJPROTON1 from 2017–2020. The median follow-up was 2.1 years (range 1.1-4.4). The primary objective was the cumulative incidence (CI) of ≥grade 3 non-hematologic, PBS-PT attributable toxicity by CTCAE v4.0. Additional outcomes included PBS-PT toxicity attributable hospitalization, procedures, and treatment-related mortality. Toxicities including necrosis, vasculopathy, neurologic deficits, and fracture/osteoradionecrosis were further characterized (any grade). Competing risk regression was used to evaluate predictors of ≥grade 3 PBS-PT attributable toxicity.Findings: At two years, the event-free survival was 73.2% (95% CI, 68.9%-77.8%). Distant and local failure predominated with a 2-year CI of 16.5% (95% CI 13.1-20.4) and 6.8% (95% CI 4.6-9.5) respectively. The 4 year CI of ≥grade 3 toxicity was 24.5%; including necrosis (3.7%), neurologic deficit (2.9%), and fracture/osteoradionecrosis (0.79%). The rates of PBS-PT-toxicity attributable hospitalization and procedures were 3.9% and 7.6%. Predictors of any ≥grade 3 toxicity included baseline total toxicity burden (TTB) (HR 1.043, 95% CI 1.012-1.07, p=0.007), and mixed photon/PBS-PT (HR 2.62, 95% CI 1.51-4.54, p=0.006) in CNS patients, and pelvic radiotherapy (HR 4.25, 95% CI 1.08-16.72, p=0.038), and TTB (HR 1.1, 95% CI 1.04-1.16, p=0.002) in non-CNS patients. Interpretation: PBS-PT yields a low incidence of toxicity, but subsets are at increased risk, and may require additional procedures or hospitalization.Funding: This work was supported by ALSAC and Cancer Center Core Grant CA21765.Declaration of Interest: None to declare. Ethical Approval: The SJPROTON1 trial was reviewed and approved by the Institutional Review Board at St. Jude. Informed consent was obtained from the parent, caregiver, or patient, with assent from the patient, as appropriate.
Terminally ill and dying children and adolescents and their family members may be eligible to participate in research studies about the end of life. They may also be eligible to receive innovative care in place of or in addition to standard care. Each of these options requires decision making. Factors that can influence the inclusion of children or adolescents in such decision making include their ability to understand their health status and their options, their legal standing, the preferences of their family, and the critical nature of their health status. We recommend that, whenever possible, end-of-life decision making about research and innovative care options be initiated when the child or adolescent is able to participate.
Background: End-of-life care (EOLC) discussions and decisions are common in pediatric oncology. Interracial differences have been identified in adult EOLC preferences, but the relation of race to EOLC in pediatric oncology has not been reported. We assessed whether race (white, black) was associated with the frequency of do-not-resuscitate (DNR) orders, the number and timing of EOLC discussions, or the timing of EOLC decisions among patients treated at our institution who died. Methods: We reviewed the records of 380 patients who died between July 1, 2001 and February 28, 2005. χ2 and Wilcoxon rank-sum tests were used to test the association of race with the number and timing of EOLC discussions, the number of DNR changes, the timing of EOLC decisions (i.e., DNR order, hospice referral), and the presence of a DNR order at the time of death. These analyses were limited to the 345 patients who selfidentified as black or white. Results: We found no association between race and DNR status at the time of death (p = 0.57), the proportion of patients with DNR order changes (p = 0.82), the median time from DNR order to death (p = 0.51), the time from first EOLC discussion to DNR order (p = 0.12), the time from first EOLC discussion to death (p = 0.33), the proportion of patients who enrolled in hospice (p = 0.64), the time from hospice enrollment to death (p = 0.2) or the number of EOLC discussions before a DNR decision (p = 0.48). Conclusion: When equal access to specialized pediatric cancer care is provided, race is not a significant factor in the presence or timing of a DNR order, enrollment in or timing of enrollment in hospice, or the number or timing of EOLC discussions before death.
