Impact of the COVID-19 pandemic on utilization and cost for care of pediatric and young adult ALL.

OBJECTIVE: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and among the most common malignancies in young adults and requires a unique pattern of healthcare utilization including an acute/emergent presentation and an intensive initial 8 months of therapy followed by two years of outpatient treatment. The COVID-19 pandemic caused massive global disruptions in healthcare use and delivery. This report aims to examine the effects of the COVID-19 pandemic on the presentation, diagnosis and continued management of childhood and young adult ALL in regard to utilization and cost of care among commercially insured individuals in the United States. RESULTS: Utilizing a commercial insurance claims database, 529 pediatric and young adult patients were identified who were diagnosed with ALL between January 2016 and March 2021. New diagnoses were evaluated by era and demographics. Utilization was measured by COVID-related era as number of inpatient and outpatient encounters, inpatient days, and cumulative cost during the initial 8 months of therapy. None of these cost or utilization factors changed significantly during or shortly after the pandemic. These findings reinforce that the necessary care for pediatric and young adult ALL was unwavering despite the massive shifts in the healthcare system caused by the COVID-19 pandemic. This provides a valuable benchmark as we further examine the factors that influence the pandemic's impact on health equity and access to care, especially in vulnerable pediatric and young adult populations. This is the first investigation of the effect of the COVID-19 pandemic on utilization and cost of care in pediatric and young adult cancer.

Healthcare cost and utilization for chimeric antigen receptor (CAR) T-cell therapy in the treatment of pediatric acute lymphoblastic leukemia: A commercial insurance claims database analysis.

BACKGROUND: B-lineage acute lymphoblastic leukemia (B-ALL) is the most common malignancy of childhood. With the introduction of novel cellular therapies, cost of care is a critical component and the financial burden experienced by patients and society requires evaluation. AIMS: This study aims to assess the utilization and cost of care for chimeric antigen receptor T-cell (CAR-T) therapy for pediatric ALL patients with commercial insurance coverage in the United States. METHODS AND RESULTS: Using de-identified commercial insurance data from the OptumLabs® Data Warehouse, a cohort of 37 patients, aged 1-25 years, with B-ALL treated with CAR-T therapy between Oct 2016 and Dec 2021 in the United States was identified. Cost was evaluated for a 90 day period encompassing CAR-T infusion and by administration and complication characteristics. Among the 37 identified B-ALL patients that received a CAR-T product infusion, 14 patients were female, median age at administration was 13 years. The median 90-day total cost was $620,500 (Mean: $589,108). Inpatient cost accounted for approximately 71% of the total cost with an average of 28 inpatient days per patient. Although inpatient cost was slightly higher in the older age group (aged 10-25 years) and in patients with a code for cytokine release syndrome (CRS), these differences were not statistically significant. CONCLUSION: This real-world cost analysis shows for the first time the encompassing cost of CAR-T therapy for pediatric B-ALL patients in the US with commercial insurance. This study provides a valuable benchmark that can be used to analyze the financial implications of CAR-T therapy for pediatric B-ALL therapy on health systems.

Utilization and Cost of Outpatient Rehabilitation Services for Pediatric Patients Treated for Acute Lymphoblastic Leukemia Using a Commercial Claims Database.

OBJECTIVE: To investigate the temporal trends and factors associated with outpatient rehabilitation utilization and costs for pediatric acute lymphoblastic leukemia (ALL). DESIGN: Deidentified administrative claims data and longitudinal health information on patients representing a mixture of ages, ethnicities, and geographic regions across the United States were accessed using Optum Labs Data Warehouse. Regression models were constructed to assess associations of outpatient rehabilitation with age, sex, race and ethnicity, year of diagnosis, and region. SETTING: Outpatient rehabilitation. PARTICIPANTS: 1000 Patients aged 1-30 years with a new diagnosis of ALL between 1993 and 2017 and continuous insurance coverage (N=1000). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Outpatient rehabilitation service utilization and cost based on reimbursed charge codes, summarized over 36 months after cancer diagnosis. RESULTS: In 1000 patients, utilization of outpatient rehabilitation services increased from 20% in 1993-2002 to 55% in 2013-2017. In the earliest era examined, physical and/or occupational therapy was provided to 18% and increased to 54% in the latest years. Speech service utilization remained between 5%-8% across timepoints. Inflation-adjusted cost for provision of services did not change significantly across time and remained low, accounting for a median of 1.3% (Q1, Q3 0.3, 3.4) of total treatment cost in 1993-2002 and decreasing to a median 0.4% (Q1, Q3, 0.1, 1.0) in 2013-2017. Age 1 to 5 years at ALL diagnosis was associated with increased rehabilitation visit number and cost, and treatment in the Midwest was associated with increased likelihood of outpatient rehabilitation service utilization compared to other geographic regions. CONCLUSIONS: Outpatient rehabilitation services are being increasingly provided to patients with ALL at a relatively low cost per patient, yet geographic variability in care utilization is evident. These services do not add excessively to the overall cost of leukemia care and thus cost containment should not be an excuse to limit access.

Association Between Laboratory Values and Adverse Events in Adults Post-Hematopoietic Stem Cell Transplant During and After Rehabilitation.

OBJECTIVE: The objective of this study was to examine the relationship between adverse events (AEs) and critical events (CEs) during and after rehabilitation in cancer patients post-hemopoietic stem cell transplant (HSCT) or bone marrow transplant (BMT) and to identify whether particular laboratory values are associated with increased risk of AEs or CEs. DESIGN: A retrospective chart review (2012-2017) of hospitalized patients ages 18-75 years who received a diagnosis of cancer and BMT or HSCT receiving rehabilitation services SETTING: Urban Midwest tertiary, research and academic hospital. PARTICIPANTS: In total, 99 hospitalized adults with HSCT or BMT participated in 300 rehabilitation sessions. INTERVENTIONS: Physical or occupational therapy using a symptom-based approach in which patient symptoms were monitored and therapy was adjusted in real time MAIN OUTCOME MEASURES: Incidence of AEs or CEs occurring during or within 48 hours of rehabilitation. RESULTS: A total of 300 rehabilitation sessions were carried out where 99.7% had 1 or more laboratory values outside reference range. In only 3.3% of therapy sessions an AE occurred during or within 2 hours of rehabilitation. Within 48 hours postrehabilitation, AEs occurred in 22.3% and CEs in 4%. No laboratory value was significantly associated with increased risk of AEs or CEs during rehabilitation. A hemoglobin <8.0 g/dL conferred an increased risk of AEs (odds ratio [OR], 2.85-6.89) depending on timeframe analyzed and overall risk of CE (OR, 3.75). Lower hemoglobin levels (<7.5 g/dL and <7.0 g/dL) did not increase this risk. Low platelets (<25 k/µL) increased the risk of AEs on day 1, 2 and overall (OR, 2.5-2.72) and overall risk of CEs (OR, 6.62). CONCLUSIONS: Our research demonstrates a low rate of AEs and CEs during or within 2 hours of rehabilitation but supports the need to monitor patients when hemoglobin is <8 g/dL or platelets are <25 k/µL due to the increased risk of events.

Rehabilitation interventions for the management of breast cancer-related lymphedema: developing a patient-centered, evidence-based plan of care throughout survivorship.

PURPOSE: A work group from the American Physical Therapy Association Academy of Oncologic Physical Therapy developed and published a clinical practice guideline (CPG) to aid clinicians in identifying interventions for individuals with breast cancer-related lymphedema (BCRL). This guideline reviewed the evidence for risk mitigation and volume reduction beginning at cancer diagnosis and continuing through survivorship. Application of CPGs can be challenging due to the variability of clinical settings, heterogeneous patient populations, and range of rehabilitation clinician expertise. The purpose of this paper is to assist these clinicians in implementing the recommendations from the CPG to develop a patient-centered, evidence-based plan of care. METHODS/RESULTS: This publication presents important considerations for the implementation of recommended rehabilitation interventions across the trajectory of BCRL. CONCLUSION: Current evidence supports specific interventions to treat or mitigate the risk for the various stages of BCRL. As clinicians implement these recommendations into practice, they also need to address other impairments that may exist in every individual. Continued collaboration between clinicians and researchers is necessary to further develop optimal treatment modalities and parameters. IMPLICATIONS FOR CANCER SURVIVORS: By implementing evidence-based interventions as outlined in the CPG, clinicians can improve the quality of care for survivors of breast cancer.

Patient education for breast cancer-related lymphedema: a systematic review.

PURPOSE: The aim was to identify the impact of the (a) components of breast cancer-related lymphedema (BCRL) educational content, (b) modes of education, and (c) timing of education on arm volume, quality of life, function, complications associated with BCRL, adherence to interventions, and knowledge acquisition in individuals diagnosed with breast cancer (BC). METHODS: This review followed the Preferred Reported Items for Systematic Review and Meta-analysis (PRISMA) guidelines (PROSPERO CRD42021253084). Databases searched included PubMed, CINAHL, Web of Science, Google Scholar, and Scopus from January 2010 to December 2021. Study quality and bias were assessed using the American Physical Therapy Association's Critical Appraisal Tool for Experimental Intervention Studies. RESULTS: Forty-five studies were eligible, and 15 met the inclusion criteria (4 acceptable and 11 low quality). This review was unable to determine the optimal content, mode, and timing for BCRL education across survivorship. Content included a brief overview of BCRL, early signs and symptoms, risk reduction practices, and a point of contact. Delivery was multi-modal, and knowledge acquisition was rarely assessed. Education was provided pre/post operatively and after BCRL developed. CONCLUSIONS: Individualized BCRL education via a multi-modal approach, repeated at multiple time points, and assessment of survivors' knowledge acquisition is recommended. Consideration of the survivors' phase of treatment, content volume, and time required to complete the program is advised when developing the educational intervention. IMPLICATIONS FOR CANCER SURVIVORS: Survivors of BC may need to advocate for BCRL education based on their individual risk and needs, request a point of contact for questions/follow up, and express their preferred style of learning.

Impact of the COVID-19 Pandemic on Utilization and Cost for Care of Pediatric ALL.

Objective: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and requires a unique pattern of healthcare utilization including an acute/emergent presentation and an intensive initial 8 months of therapy followed by two years of outpatient treatment. The COVID-19 pandemic caused massive global disruptions in healthcare use and delivery. This report aims to examine the effects of the COVID-19 pandemic on the presentation, diagnosis and continued management of childhood ALL in regard to utilization and cost of care. Results: Utilizing a commercial insurance claims database, 529 pediatric patients were identified who were diagnosed with ALL and completed their initial 8 months of treatment between January 2016 and December 2021. New diagnoses were evaluated by era and demographics. Utilization was measured by COVID-related era as number of inpatient and outpatient encounters, inpatient days, and cumulative cost. None of these cost or utilization factors changed significantly during or shortly after the pandemic. These findings reinforce that the necessary care for pediatric ALL is largely inflexible and was unwavering despite the massive shifts in the healthcare system caused by the COVID-19 pandemic. This provides a valuable benchmark as we further examine the factors that influence the pandemic's impact on health equity and access to care, especially in vulnerable pediatric populations. This is the first investigation of the effect of the COVID-19 pandemic on utilization and cost of care in pediatric cancer.

Real-World Cost of Pediatric Acute Lymphoblastic Leukemia Care Among Commercially Insured Individuals in the United States: Effect of Era and Age at Diagnosis.

PURPOSE: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Five-year survival is approaching 90%. In efforts to further improve outcomes, it is critical to consider the cost of ALL care. MATERIALS AND METHODS: Commercial insurance data from OptumLabs Data Warehouse were used to identify patients with ALL, age 1-30 years, diagnosed in 1993-2017 in the United States, with 36 months of continuous insurance coverage. Patients treated with hematopoietic cell transplantation were excluded. Inpatient and outpatient utilization and cumulative reimbursements (inflation-adjusted to December 2020) were computed 8 and 36 months from diagnosis and stratified by age (1-9, 10-12, and ≥ 13 years) as proxies for National Cancer Institute risk groups. Regression models were constructed to assess associations with demographic and clinical characteristics. RESULTS: Among 927 patients (median age, 6 years; interquartile range, 3-12 years; 43% female), individuals age ≥ 10 years had 23-25 more inpatient days and 22 more outpatient encounters compared with younger patients. The 36-month median cost was $394,000 (USD) (interquartile range, $256,000-$695,000 [USD]), and 64% of the total cost was incurred during the initial 8 months. The 36-month cost was 1.5-fold higher for those age 10-12 years and 1.7-fold higher for those age ≥ 13 years compared with 1-9 years. The cost for those diagnosed in 2013-2017 was 70% higher compared with 1993-2002, and was not different on the basis of sex, race, or ethnicity. CONCLUSION: Older age was associated with higher utilization and cost, and the cost of treatment increased significantly over time. These data provide valuable benchmarks for future studies examining the cost-benefit of ALL therapy modifications.

Characteristics and patterns of pediatric chemotherapy-induced peripheral neuropathy: A systematic review.

This systematic review provides a high-quality synthesis of the empirical evidence regarding chemotherapy-induced peripheral neuropathy (CIPN) characteristics and patterns described in studies of children who received neurotoxic chemotherapy to treat cancer. PubMed, CINAHL, PsycINFO, and Embase were searched for articles published 2009 - 2019, yielding 861. Forty-two papers met the eligibility criteria, including 31 that described characteristics and patterns of vincristine-induced CIPN. Fifty-seven percent of articles were of low to moderate quality; measurement flaws were the most common limitations. The reported CIPN incidence varies widely (2.8%-100%) depending on risk factors (e.g., race) and the measurement approach. Incidence rates of sensory, motor, autonomic CIPN, and pain were 12-28%, 50-72%, 0.8-83% and 5.7-44%, respectively. The evidence suggests that sensory and motor neuropathy, pain, and functional deficits are common and can persist into adulthood. Caucasian race is a risk factor and, contrary to prior thinking, cumulative chemotherapy dosage alone does not predict CIPN severity. The influence of other risk factors is less clear, and studies to date have not explored potential interactions among race, genetics, age, sex, drug metabolism, and nutritional status, among other factors.

Assessment of Pediatric Chemotherapy-Induced Peripheral Neuropathy Using a New Patient-Reported Outcome Measure: The P-CIN.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is commonly experienced by children receiving neurotoxic chemotherapy. No validated pediatric CIPN patient-reported outcome (PRO) measures exist. Purpose: To test sensitivity, internal consistency reliability, content and convergent validity, and feasibility of the Pediatric Chemotherapy-Induced Neuropathy (P-CIN), an electronic PRO measure for assessing CIPN in children who received neurotoxic chemotherapy. Method: Five experts evaluated content validity of the 14-item P-CIN. Children 5 to 17 years old with CIPN (N = 79) completed the P-CIN via tablet computer; a subset (n = 26) also underwent neurological examinations using the Pediatric-Modified Total Neuropathy Score. Following preliminary analyses, one item was deleted and three others modified. The revised P-CIN was retested with patients (n = 6) who also completed the Bruininks-Oseretsky Test of Motor Proficiency motor function assessment. Means, item response ranges, standard deviations, content validity indexes, Cronbach's alphas, and correlation coefficients were calculated. Results: Mean participant age was 11.25 (SD = 4.0) years. Most had acute leukemia (62.5%) and received vincristine (98.7%). Content validity index coefficients ranged from .80 to 1.0 (p = .05). For 9 of 14 items, responses ranged from 0 to 4 or 5; response ranges for toe numbness, pick up a coin, and three of four pain items were 0 to 3. After deleting one item, Cronbach's alpha coefficient was .83. P-CIN scores were strongly associated with Pediatric-Modified Total Neuropathy Score (r = .52, p < .01) and Bruininks-Oseretsky Test of Motor Proficiency (r = -.83, p = .04) scores. Sixty-eight percent of children 6 to 17 years old completed P-CIN independently. Discussion: Preliminary evidence suggests that the 13-item P-CIN is internally consistent, is valid, and can be completed independently by children ≥ 6 years. However, we recommend additional testing.

Interventions for breast cancer-related lymphedema: clinical practice guideline from the Academy of Oncologic Physical Therapy of APTA

A work group from the American Physical Therapy Association (APTA) Academy of Oncologic Physical Therapy developed a clinical practice guideline to aid clinicians in identifying interventions for people with breast cancer-related lymphedema, targeting volume reduction, beginning at breast cancer diagnosis and continuing through cancer treatments and survivorship. Following a systematic review of published studies and a structured appraisal process, recommendations were developed to guide physical therapists and other health care clinicians in their intervention selection. Overall, clinical practice recommendations were formulated based on the evidence for each intervention and were assigned a grade based on the strength of the evidence. The evidence for each specific intervention was synthesized and appraised by lymphedema stage, when the information was available. In an effort to make recommendations clinically applicable, they were presented by modality throughout the care trajectory. Methodology and research populations varied significantly across studies, and it will be important for future research to use standardized definitions for participant characteristics, diagnostic criteria, and interventions.

Interventions for Breast Cancer-Related Lymphedema: Clinical Practice Guideline From the Academy of Oncologic Physical Therapy of APTA.

A work group from the American Physical Therapy Association (APTA) Academy of Oncologic Physical Therapy developed a clinical practice guideline to aid clinicians in identifying interventions for people with breast cancer-related lymphedema, targeting volume reduction, beginning at breast cancer diagnosis and continuing through cancer treatments and survivorship. Following a systematic review of published studies and a structured appraisal process, recommendations were developed to guide physical therapists and other health care clinicians in their intervention selection. Overall, clinical practice recommendations were formulated based on the evidence for each intervention and were assigned a grade based on the strength of the evidence. The evidence for each specific intervention was synthesized and appraised by lymphedema stage, when the information was available. In an effort to make recommendations clinically applicable, they were presented by modality throughout the care trajectory. Methodology and research populations varied significantly across studies, and it will be important for future research to use standardized definitions for participant characteristics, diagnostic criteria, and interventions.

Proactive Rehabilitation for Chemotherapy-Induced Peripheral Neuropathy.

OBJECTIVE: To review assessment and management approaches for chemotherapy-induced peripheral neuropathy-related physical function deficits. DATA SOURCES: Peer-reviewed articles from PubMed, Ovid MEDLINE, CINAHL PsycINFO, SPORTDiscus, Scopus, and key studies' reference lists. CONCLUSION: Brief clinical tests (eg, gait, Timed Up and Go) can screen for neuropathy-related physical function deficits. Exercise and physical therapy may be promising treatments, but the efficacy and optimal dose of such treatments for chemotherapy-induced peripheral neuropathy are unclear. IMPLICATIONS FOR NURSING PRACTICE: Screening and assessment of neuropathy-associated physical function deficits should occur throughout neurotoxic chemotherapy treatment. If such deficits are identified, referral for rehabilitation (ie, physical or occupational therapy) and/or exercise interventions is warranted.

Switching to Bortezomib may Improve Recovery From Severe Vincristine Neuropathy in Pediatric Acute Lymphoblastic Leukemia.

PURPOSE: The purpose of this study was to evaluate the impact of switching patients being treated for acute lymphoblastic leukemia (ALL) from vincristine to bortezomib. PATIENTS AND METHODS: A total of 20 patients with ALL were switched from vincristine to bortezomib (1.3 mg/m/dose) because of worsening neuropathy despite physical therapy interventions (n=18) or at increased risk of neuropathy (n=2). Relapse rates were compared with 56 vincristine-only patients matched by prognostic factors. Maintenance blood counts in bortezomib patients were compared with cooperative group data using vincristine during maintenance. In addition, 6 evaluable patients were assessed for neuropathy using the pediatric-modified total neuropathy score. Neuropathy scores were collected during treatment with vincristine and after switching to bortezomib. RESULTS: After a median follow-up of 3.5 years the relapse rate in patients switched to bortezomib was nonsignificantly different than those remaining on vincristine. Patients on monthly bortezomib had statistically significantly lower platelet counts that did not require transfusions or dose adjustment. Total neuropathy for all 6 cases decreased significantly when switched to bortezomib from vincristine (P=0.015), with motor neuropathy declines in 5 of 6 subjects. CONCLUSIONS: Bortezomib substitution for vincristine in ALL treatment is a potential strategy to mitigate severe vincristine neuropathy. These findings should be confirmed in a randomized clinical trial to further assess benefits and risks of this approach.

Long-Term Survivorship Care After Cancer Treatment: A New Emphasis on the Role of Rehabilitation Services.

In May 2018, the National Cancer Policy Forum (NCPF) of the National Academies of Sciences, Engineering, and Medicine (formerly the Institute of Medicine) released a report, Long-Term Survivorship Care After Cancer Treatment: Proceedings of Workshop. NCPF-published reports have historically played a significant role in driving policy and payment model changes in oncology care, in addition to raising awareness about the needs of individuals with cancer. This 2018 report provides a specific set of recommendations for improving symptom management and rehabilitation that suggest the integration of rehabilitation services at the point of cancer diagnosis and throughout the continuum of cancer care to effectively screen for and manage the anticipated functional morbidity associated with cancer treatment. The specificity of these recommendations is of significant relevance to the physical therapy profession and should encourage bold steps to effectively increase the presence of physical therapists as members of interdisciplinary cancer care teams. The profession must act to implement models of prospective care, develop targeted education and training initiatives to assure the knowledge and skills of our workforce for this complex population, and augment the current evidence base with greater attention to health services research aiming to understand the effectiveness of rehabilitation services in improving costs, utilization, and meaningful functional outcomes.

Peripheral neuropathy in children and adolescents treated for cancer.

Peripheral neuropathy is a well recognised treatment-related toxicity in children with cancer, associated with exposure to neurotoxic chemotherapy agents. Acute damage can occur in sensory, motor, or autonomic neurons, with symptoms that are rarely life threatening, but often severe enough to interfere with function during therapy and after treatment ends. The type of neuropathy and specific symptoms are associated with multiple factors including age at time of therapy, genetic predisposition, chemotherapy type and cumulative dose, and exposure to other agents during therapy. In this Review, we describe the peripheral neuropathy phenotype in children during cancer therapy and among survivors who have completed therapy, to summarise genetic and treatment-related risk factors for neuropathy, and to outline strategies to monitor and detect neuropathy during and after therapy. Additionally, we outline strategies for medical management of neuropathy during treatment and potential rehabilitation interventions to prevent or remediate functional loss.

Short-Term Recovery of Balance Control: Association With Chemotherapy-Induced Peripheral Neuropathy in Pediatric Oncology.

PURPOSE: To describe the incidence and short-term recovery of balance control in children and adolescents receiving neurotoxic treatment for noncentral nervous system cancers and to investigate the association of chemotherapy-induced peripheral neuropathy and balance control. METHODS: Sixty-five children and adolescents diagnosed with leukemia, lymphoma, or other solid tumors were tested 3 to 6 months into treatment and 3 and 6 months following treatment using the Bruininks-Oseretsky Balance Subscale and Pediatric Modified Total Neuropathy Scale scores of chemotherapy-induced peripheral neuropathy (CIPN). RESULTS: Seventy-eight percent of the participants scored 1 standard deviation or more below population means on the balance subscale while on treatment, and this improved to 53% by 6 months posttreatment, with the leukemia group performing worse at both time points. On-treatment balance scores were moderately associated with motor CIPN, while at 6 months posttreatment they were more closely associated with sensory CIPN. CONCLUSIONS: Mild to moderate balance impairments improve but can persist, even when CIPN has improved, 6 months after treatment for childhood cancer.