Supportive Care in Pediatric Oncology: Opportunities and Future Directions.

The optimization of outcomes for pediatric cancer patients relies on the successful advancement of supportive care to ease the treatment burden and mitigate the long-term impacts of cancer therapy. Advancing pediatric supportive care requires research prioritization as well as the development and implementation of innovations. Like the prevailing theme throughout pediatric oncology, there is a clear need for personalized or precision approaches that are consistent, evidence-based, and guided by clinical practice guidelines. By incorporating technology and datasets, we can address questions which may not be feasible to explore in clinical trials. Now is the time to listen to patients' voices by using patient-reported outcomes (PROs) to ensure that their contributions and experiences inform clinical care plans. Furthermore, while the extrapolation of knowledge and approaches from adult populations may suffice in the absence of pediatric-specific evidence, there is a critical need to specifically understand and implement elements of general and developmental pediatrics like growth, nutrition, development, and physical activity into care. Increased research funding for pediatric supportive care is critical to address resource availability, equity, and disparities across the globe. Our patients deserve to enjoy healthy, productive lives with optimized and enriched supportive care that spans the spectrum from diagnosis to survivorship.

Thrombocytopenia Associated with Elemental Mercury Poisoning in Two Siblings - Connecticut, July 2022.

Two siblings aged 5 and 15 years from Connecticut were hospitalized with petechial rash, oral mucositis, and severe thrombocytopenia approximately 10 days after they played with a jar of elemental mercury they found in their home. Before the mercury exposure was disclosed, the siblings were treated with platelet transfusions, intravenous immune globulin (IVIG) for possible immune thrombocytopenic purpura, and antibiotics for possible infectious causes. When their conditions did not improve after 6 days, poison control facilitated further questioning about toxic exposures including mercury, testing for mercury, and chelation with dimercaptosuccinic acid. The older sibling soon recovered, but the younger child required a prolonged hospitalization for severe thrombocytopenia, ultimately receiving repeated doses of IVIG, steroids, and romiplostim, a thrombopoietin receptor agonist. Close collaboration among multiple agencies was required to identify the extent of mercury contamination, evaluate and treat the other family members, and decontaminate the home. These cases demonstrate the importance of ongoing public health outreach to promote early detection of elemental mercury toxicity, and the need to evaluate for environmental exposures when multiple close contacts experience similar signs and symptoms.

Treatment of breakthrough and prevention of refractory chemotherapy-induced nausea and vomiting in pediatric cancer patients: Clinical practice guideline update.

This clinical practice guideline update provides recommendations for treating breakthrough chemotherapy-induced nausea and vomiting (CINV) and preventing refractory CINV in pediatric patients. Two systematic reviews of randomized controlled trials in adult and pediatric patients informed the recommendations. In patients with breakthrough CINV, escalation of antiemetic agents to those recommended for chemotherapy of the next higher level of emetogenic risk is strongly recommended. A similar recommendation to escalate therapy is made to prevent refractory CINV in patients who did not experience complete breakthrough CINV control and are receiving minimally or low emetogenic chemotherapy. A strong recommendation to use antiemetic agents that controlled breakthrough CINV for the prevention of refractory CINV is also made.

Feeling scared or worried self-report in children receiving cancer treatments using the Symptom Screening in Pediatrics Tool (SSPedi).

INTRODUCTION: The objectives of this study were to describe reports of bother for feeling scared or worried among children with cancer and pediatric hematopoietic stem cell transplant (HSCT) recipients, and to identify factors associated with it. METHODS: We included children receiving cancer treatments who were 8-18 years of age. Three patient types were enrolled: inpatients receiving active cancer treatment, outpatients receiving maintenance acute lymphoblastic leukemia chemotherapy, and outpatients in survivorship. Amount of bother due to feeling scared or worried yesterday or today was self-reported using the Symptom Screening in Pediatrics Tool (SSPedi) on a 0-4 scale. Risk factors were evaluated using logistic regression. RESULTS: Among the 502 children included, 225 (45.0%) reported any degree of bother (score ≥ 1) and 29 (5.8%) reported severe bother (score ≥ 3) for feeling scared or worried. In multiple regression evaluating any bother, boys were less likely to be bothered (odds ratio (OR) 0.60, 95% confidence interval (CI) 0.41-0.87) and inpatients receiving active cancer treatment were more likely to be bothered compared to outpatients in survivorship (OR 3.58, 95% CI 2.00-6.52). The only factor associated with being severely bothered by feeling scared or worried was clinic visit or admission due to fever (OR 4.57, 95% CI 1.24-13.60). DISCUSSION: We found 45% of children receiving cancer treatments reported being bothered by feeling scared or worried. Girls and inpatients receiving active treatment experienced more bother of any degree, while visiting the hospital due to fever was associated with being severely bothered. Future work should identify interventions to prevent or alleviate this symptom.

Classification of the acute emetogenicity of chemotherapy in pediatric patients: A clinical practice guideline.

This clinical practice guideline (CPG) provides clinicians with recommendations regarding chemotherapy emetogenicity classification in pediatric oncology patients. This information is critically important for the appropriate selection of antiemetic prophylaxis. Recommendations are based on a systematic review limited to pediatric patients and a framework for classification when antiemetic prophylaxis is provided. Findings of 87 publications informed the emetogenicity classification of 49 single-agent and 13 combination-agent regimens. Information required for the classification of many chemotherapies commonly administered to pediatric patients is lacking. In the absence of pediatric data, consultation of methodologically sound CPGs aimed at adult oncology patients may be appropriate.

Taste changes in children with cancer and hematopoietic stem cell transplant recipients.

BACKGROUND: Objectives were to describe bothersome self-reported changes in taste in pediatric oncology and hematopoietic stem cell (HSCT) patients and to identify patient and treatment-related factors associated with bothersome taste changes. METHODS: We prospectively enrolled children and adolescents with cancer or pediatric HSCT recipients 8-18 years of age from three groups: inpatients receiving cancer treatments; outpatients in maintenance therapy for acute lymphoblastic leukemia (ALL); and outpatients in survivorship. Bothersome changes in taste was self-reported using the Symptom Screening in Pediatrics Tool (SSPedi); nausea was self-reported using the Pediatric Nausea Assessment Tool (PeNAT). RESULTS: Among the 502 children included, 226 (45.0%) reported bothersome taste changes and 48 (9.6%) reported severely bothersome taste changes. In multiple regression, factors independently associated with severely bothersome taste changes were: inpatients receiving cancer treatments vs outpatients in survivorship (odds ratio (OR) 12.28, 95% confidence interval (CI) 2.50-222.27), ALL in maintenance vs outpatients in survivorship (OR 7.43, 95% CI 1.06-147.77), current nausea (OR 1.59, 95% CI 1.04-2.42), vomiting (OR 2.18, 95% CI 1.06-4.38), and first language not English (OR 2.09, 95% CI 0.97-4.28). CONCLUSIONS: We found that 45% of children with cancer and pediatric HSCT recipients reported bothersome changes in taste and these were severely bothersome in 9.6% of children. Inpatients receiving cancer treatment, those experiencing more nausea and vomiting and children whose first language was not English were at greater risk of severely bothersome changes in taste. Future work should evaluate systematic symptom screening in clinical practice and identify interventions focused on addressing bothersome taste changes.

2016 updated MASCC/ESMO consensus recommendations: Prevention of acute chemotherapy-induced nausea and vomiting in children.

PURPOSE: To update the 2009 recommendations for the prevention of acute chemotherapy-induced emesis in children. METHODS: We updated the original systematic literature search. Randomized studies were included in the evidence to support this guideline if they were primary studies fully published in full text in English or French; included only children less than 18 years old or, for mixed studies of adults and children, reported the pediatric results separately or the median or mean age was no more than 13 years; evaluated acute chemotherapy-induced nausea and vomiting (CINV) prophylaxis; provided sufficient information to permit determination of the emetogenicity of the antineoplastic therapy administered or the study investigators stated the emetogenicity of the chemotherapy administered; included an implicit or explicit definition of complete acute CINV response; described the antiemetic regimen in full; and reported the complete acute CINV response rate as a proportion. RESULTS: Twenty-five randomized studies, including eight published since 2009, met the criteria for inclusion in this systematic review. Prophylaxis with a 5-HT3 antagonist (granisetron or ondansetron or palonosetron or tropisetron) ± dexamethasone ± aprepitant is recommended for children receiving highly or moderately emetogenic chemotherapy. For children receiving chemotherapy of low emetogenicity, a 5-HT3 antagonist is recommended. CONCLUSIONS: The findings of several randomized trials were used to update recommendations for the prevention of acute CINV. However, significant research gaps remain and must be addressed before CINV control in children can be optimized.

Does socioeconomic status impact physical activity and sleep among children with cancer?

BACKGROUND: Compared with healthy children, pediatric oncology patients have impaired sleep and engage in less physical activity (PA). Socioeconomic status (SES) may be one determinant of PA and sleep among pediatric oncology patients. PROCEDURE: Between November 12, 2009 and March 27, 2013, 50 pediatric oncology patients between the ages of 8 and 18 years were recruited from an urban children's hospital. PA and sleep were assessed by actigraphy and diaries over 7 days. Fatigue was assessed using the Fatigue Scale. SES was defined by primary payer status of insurance (state or private) and by Median Household Income (MHI) obtained from 2010 U.S. Census block data for residences. MHI was compared to Connecticut state median income ($67,000). Multivariate regression models examined the relationship between SES and PA, sleep and fatigue. RESULTS: PA and sleep efficiency were strongly correlated (r = 0.31, P = 0.03). Children with state insurance had higher average PA (P = 0.004) than children on private insurance. There were no significant differences in PA or sleep efficiency by block MHI. The 7-day fatigue score was lower among the participants aged 8-12 years in the group with MHI less than $67,000 (P = 0.03), although there was no significant difference among participants aged 13-18 years in the group. There was no difference in mean fatigue scores by insurance status. CONCLUSIONS: Participants on state insurance had higher PA than those with private insurance. Although block MHI did not influence PA or sleep efficiency among children with cancer, participants aged 8-12 years in a lower MHI block had less fatigue. Future research is needed to further understand how SES influences PA.

Physical activity (PA) and sleep among children and adolescents with cancer.

BACKGROUND: Although sleep and physical activity often are impaired among adult cancer patients, there is limited data among pediatric oncology populations. We conducted a prospective study to investigate the relationship between physical activity (PA) and sleep among children with cancer. PROCEDURE: Between 11/12/09 and 02/06/12, PA while awake and sleep variables were assessed by actigraphy collected over 7 days in 36 children (age range 8-18 years) with cancer (23 leukemia/lymphoma, 5 brain tumor, 8 solid tumor). Sleep diaries were used to determine sleep time, sleep quality, and morning mood. Fatigue was assessed at study initiation using fatigue instruments. RESULTS: Participants had impaired sleep based upon normative data compiled from multiple studies of more than 1,700 healthy children from 1 to 18 years of age [1], including decreased total sleep time (mean 6.6 hours, standard deviation (SD) 1.3 hours), increased wake after sleep onset (WASO; mean 2 hours, SD 1.4 hours), increased awakenings during sleep (mean 28.3 wake bouts, SD 7.8 bouts), and decreased sleep efficiency (mean 74.2%, SD 13.3%). Fatigue correlated with self-reported sleep quality but not with disturbances in sleep as measured by actigraphy. In longitudinal models that controlled for age, diagnosis group, gender, race, and steroid use, higher average activity, as measured by actigraphy, was associated with improved sleep quantity (P = 0.005) and efficiency (P = 0.001). CONCLUSION: Pediatric oncology patients demonstrate impaired sleep. Greater PA was significantly associated with improved sleep quantity and efficiency in pediatric oncology participants. As a potentially modifiable factor, PA may offer a mechanism to improve sleep in pediatric oncology patients.

Variation in receipt of opioids by pediatric oncology patients who died in children's hospitals.

BACKGROUND: Opioids are a cornerstone of palliation of pain. We sought to assess variation in opioid prescription during the last week of life among a cohort of pediatric oncology patients who died while hospitalized. PROCEDURE: We used detailed hospital administrative data from the Pediatric Health Information System (PHIS) regarding 1,466 subjects 0-24 years of age who were treated at 33 hospitals between 2001 and 2005. RESULTS: Among the 1,466 subjects hospitalized at the time of their death, 56% received opioids every day during the hospitalized portion of their last week of life, while 44% did not. This proportion varied substantially across hospitals (range 0-90.5%). After multivariate adjustment for individual-level characteristics, the hospital-level effect on the odds of continuous prescription of opioids during the hospitalized portion of the last 7 days of life continued to vary significantly among hospitals, accounting for 10.5% of the variance in the receipt of daily opioid (P < 0.001). CONCLUSION: Opioid prescription during the hospitalized portion of the last week of life varies substantially among hospitals, even after adjustment for clinical characteristics of the patients. The reasons for this significant variation, especially the component explained by hospital-level and not patient-level factors, warrant more scrutiny.