Family perspectives on the transition from active treatment to survivorship for children with cancer.

BACKGROUND: Completing therapy for childhood cancer is an exciting milestone. However, this adjustment can be extremely stressful for patients and their families as they transition from cancer patient to survivor. A better understanding of the patient and family experience and their needs during this transition is crucial for developing guidelines and leveraging support for future patients and families. PROCEDURE: Participants were recruited from across the United States using a maximum variation sampling strategy. Families were eligible if they had a child diagnosed with cancer before age 15 and had completed treatment at least 1 year prior to their interview. Participants completed a 90-180-minute semi-structured interview either in person or virtually. Interviews focused on the experiences of getting a diagnosis, experiences with treatment, information seeking, impact of cancer on the family, social support, and transitions to survivorship. Inductive thematic analysis revealed a wide variety of themes. This paper examines the transition from active cancer therapy into survivorship. RESULTS: Identified primary themes included (i) feelings about transitioning off therapy; (ii) coping with lingering effects; and (iii) experiences of transitioning off therapy and survivorship care. Subthemes highlighted the need for more support for both patients and families during this transition. CONCLUSION: Patients and families desire more support during the transition off therapy. Suggestions included access to additional resources, earlier transition to receiving survivorship care, and more holistic survivorship care. Further research is needed to determine best models and feasibility of delivering this desired support to all patients and families.

Hopping as an Indicator of Chemotoxicity: Gait Analysis in Patients With Leukemia and Lymphoma.

BACKGROUND: Survivors of acute lymphoblastic leukemia (ALL) can experience chemotherapy-related changes in neuromuscular function, which can persist and impact the quality of life. Clinically, neuromuscular changes are assessed by observing gait. The primary aims of this study were to compare observational gait/functional movement analysis to matched electronic gait analysis in children with ALL and lymphoblastic lymphoma at specific time points during and after treatment. PATIENTS AND METHODS: Participants 2 to 27 years old diagnosed with ALL/lymphoblastic lymphoma who were on or off therapy within 10 years were eligible. Participants underwent electronic gait assessment using GAITRite, observational gait, and functional movement analysis and completed quality of life questionnaires. Parents also completed quality-of-life assessments. RESULTS: Electronic gait parameters were not different in this cohort compared with controls. Mean overall scores on observational gait and functional movement analysis improved over time. Hopping was the most frequent and walking was the least frequent noted deficit. Participants had a lower patient and parent-reported QoL scores compared with the general population. CONCLUSION: Observational gait and functional movement analysis identified more deficits than the electronic gait assessment. Future studies are warranted to determine whether hopping deficits are an early clinical indicator of toxicity and signal for intervention.

Implementation of a provider-focused intervention for maximizing human papillomavirus (HPV) vaccine uptake in young cancer survivors receiving follow-up care in pediatric oncology practices: protocol for a cluster-randomized trial of the HPV PROTECT intervention.

BACKGROUND: Childhood cancer survivors are at high risk for developing new cancers (such as cervical and anal cancer) caused by persistent infection with the human papillomavirus (HPV). HPV vaccination is effective in preventing the infections that lead to these cancers, but HPV vaccine uptake is low among young cancer survivors. Lack of a healthcare provider recommendation is the most common reason that cancer survivors fail to initiate the HPV vaccine. Strategies that are most successful in increasing HPV vaccine uptake in the general population focus on enhancing healthcare provider skills to effectively recommend the vaccine, and reducing barriers faced by the young people and their parents in receiving the vaccine. This study will evaluate the effectiveness and implementation of an evidence-based healthcare provider-focused intervention (HPV PROTECT) adapted for use in pediatric oncology clinics, to increase HPV vaccine uptake among cancer survivors 9 to 17 years of age. METHODS: This study uses a hybrid type 1 effectiveness-implementation approach. We will test the effectiveness of the HPV PROTECT intervention using a stepped-wedge cluster-randomized trial across a multi-state sample of pediatric oncology clinics. We will evaluate implementation (provider perspectives regarding intervention feasibility, acceptability and appropriateness in the pediatric oncology setting, provider fidelity to intervention components and change in provider HPV vaccine-related knowledge and practices [e.g., providing vaccine recommendations, identifying and reducing barriers to vaccination]) using a mixed methods approach. DISCUSSION: This multisite trial will address important gaps in knowledge relevant to the prevention of HPV-related malignancies in young cancer survivors by testing the effectiveness of an evidence-based provider-directed intervention, adapted for the pediatric oncology setting, to increase HPV vaccine initiation in young cancer survivors receiving care in pediatric oncology clinics, and by procuring information regarding intervention delivery to inform future implementation efforts. If proven effective, HPV PROTECT will be readily disseminable for testing in the larger pediatric oncology community to increase HPV vaccine uptake in cancer survivors, facilitating protection against HPV-related morbidities for this vulnerable population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04469569, prospectively registered on July 14, 2020.

Parental decision making regarding consent to randomization on Children's Oncology Group AALL0932.

BACKGROUND: Within pediatric oncology, parental decision making regarding participation in clinical trials that aim to reduce therapy to mitigate side effects is not well studied. The recently completed Children's Oncology Group trial for standard-risk acute lymphoblastic leukemia (AALL0932) included a reduction in maintenance therapy, and required consent for randomization immediately prior to starting maintenance. At our institution, 40% of children enrolled on AALL0932 were withdrawn from protocol therapy prior to randomization due to parental choice. This study sought to identify factors that impacted parental decision making regarding randomization on AALL0932. PROCEDURE: Parents of children enrolled on AALL0932 at our institution were eligible if their child met criteria for the average-risk randomization. Parents were invited to participate in a 30-50-minute phone interview. Questions focused on factors that shaped parental decision making about randomization, as well as their perspectives about the clinical trial experience more generally. RESULTS: Fear of receiving less therapy and subsequent relapse was the predominant reason to decline randomization. Reasons given for consenting to randomization included trust in the physician, altruism, hope for less therapy, and potential for fewer side effects. Parents also reflected on ways to support future families making decisions about clinical trial participation. CONCLUSION: While many parents recognize the importance of clinical trials aiming to mitigate side effects, the fear of their own child relapsing with less than standard therapy may dissuade them from study participation. Recognizing and addressing these concerns will be important for enrollment and retention in future clinical trials.

An institutional assessment of sperm cryospreservation and fertility counselling in pubertal male cancer survivors.

INTRODUCTION: Improved survivorship after treatment of pediatric malignancies has dramatically increased, while pre-treatment fertility preservation in this population has not kept pace. New guidelines emphasize fertility preservation in young adolescents, but the impact of these guidelines is unknown. OBJECTIVES: We sought to evaluate the rate of fertility preservation among at-risk adolescents diagnosed with cancer at our institution, as well as evaluate barriers to fertility preservation. DESIGN: We performed an IRB-approved historical cohort study of adolescent males 13 years and older evaluated in the Pediatric Hematology-Oncology clinic at Doernbecher Children's Hospital from 2010 to 2018. Electronic chart review was used assess discussion of fertility preservation and barrier to successful preservation in boys with a new diagnosis of cancer who received systemic chemotherapy and/or gonadal or pelvic irradiation. RESULTS: 82 boys were included in the study. Forty-two (51%) received counselling about fertility preservation, and of those 29 (70%) successfully banked sperm. Neither counseling for fertility preservation nor success at sperm banking differed by patient age, but both differed by malignancy. Patients with Hodgkin's lymphoma had the highest rate of counselling, while those with leukemia had the lowest. Acute illness as a barrier to preservation was found in 40% of those who did not receive counselling. DISCUSSION: Our study demonstrates a stagnant rate of fertility counseling and preservation despite increased advocacy. The retrospective nature of our study limited our ability to assess the counselling that occurred, and the lack of granular race data limited study of the implicit selection bias that may be involved in such counseling. As more institutions move toward a multi-disciplinary care model, we believe that pediatric urologists or fertility specialists must play a vocal role in the care of these at-risk adolescents. CONCLUSION: Despite increasing advocacy for fertility preservation, our data shows no significant change in previously reported trends. Patients with Hodgkin's lymphoma have a higher rate of counseling and cryopreservation in comparison to those with other malignancies.

Preventive antibiotics in pediatric patients with acute myeloid leukemia (AML).

BACKGROUND: Treatment of acute myeloid leukemia (AML) comes with a significant risk of life-threatening infection during periods of prolonged severe neutropenia. We studied the impact of preventive intravenous (IV) antibiotic administration at onset of absolute neutropenia on the incidence and outcome of life-threatening infections during treatment of childhood AML. PROCEDURES: This is a retrospective study on pediatric patients (aged 0-18 years) consecutively diagnosed with de novo AML and treated at a single institution from April 2005 through February 2013. Patients were treated on the Children's Oncology Group (COG) AAML0531 protocol or with a modified United Kingdom Medical Research Council (UK MRC) AML 10 regimen. Pertinent data were extracted from hard copy or electronic chart review. RESULTS: A total of 76 chemotherapy phases were analyzed from 29 patients. In each phase reported, preventive antibiotics were initiated when the daily absolute neutrophil count was <500 cells/mcl, before onset of fever. Seven episodes of bacteremia were documented with predominantly coagulase-negative staphylococci and viridans group streptococci. One infection-related death occurred, attributed to progressive respiratory failure occurring months after documented candidal pneumonia. CONCLUSIONS: Initiation of preventive antibiotics at the onset of absolute neutropenia was associated with no mortality from bacteremia. This preventive approach appears feasible and safe.

Survivors of standard risk acute lymphoblastic leukemia do not have increased risk for overweight and obesity compared to non-cancer peers: a report from the Children's Oncology Group.

BACKGROUND: We sought to determine whether survivors of standard risk ALL (SR-ALL) treated without cranial radiation have increased risk for obesity by assessing changes in body mass index (BMI) during and after treatment; identifying contributing patient and treatment factors; comparing rates of overweight/obese to national health data. PROCEDURE: Eligibility for this retrospective cohort study included: (i) previous enrollment on legacy therapy trials CCG1922 or CCG1952; (ii) continuous first remission; and (iii) age at follow-up evaluation of 6-16.99 years. Height and weight from diagnosis, consolidation, start of maintenance, last cycle of maintenance, and off-therapy were analyzed. RESULTS: The 269 subjects were a median age of 3.5 years at diagnosis and 13.3 years at follow-up. BMI% significantly increased from induction to consolidation (+17.6 ± 1.6%), start of maintenance to end-of-treatment (+3.3 ± 1.6%) and decreased from end-of-treatment to follow-up (-3.5 ± 1.6%,). Higher BMI% at follow-up was associated with higher BMI% at diagnosis (P < 0.0001), but not age at diagnosis, gender, or race. Patients previously randomized to dexamethasone had a stronger association between BMI% at diagnosis and BMI% at follow-up than those who received prednisone (P = 0.0005). At follow-up, 39% of survivors were overweight or obese; the relative risk of overweight/obese was 1.028 (P = 0.738) compared to the general population. CONCLUSIONS: Our study of patients with SR-ALL found a significant increase in BMI% largely during the first month of therapy that is greater with dexamethasone than prednisone. However, after therapy, there was no increased risk of overweight/obese BMI compared to non-cancer peers.

Health promotion for adolescent childhood leukemia survivors: building on prevention science and ehealth.

Teenage survivors of childhood acute lymphoblastic leukemia (ALL) have increased morbidity likely due to their prior multicomponent treatment. Habits established in adolescence can impact individuals' subsequent adult behaviors. Accordingly, healthy lifestyles, avoiding harmful actions, and appropriate disease surveillance are of heightened importance among teenage survivors. We review the findings from prevention science and their relevance to heath promotion. The capabilities and current uses of eHealth components including e-learning, serious video games, exergaming, behavior tracking, individual messaging, and social networking are briefly presented. The health promotion needs of adolescent survivors are aligned with those eHealth aspects to propose a new paradigm to enhance the wellbeing of adolescent ALL survivors.

Fever and neutropenia in pediatric patients with cancer.

Aggressive treatment of childhood cancers including systemic antineoplastic and radiation therapy has secondary effects on a variety of normal cells including hematopoietic elements of the bone marrow, often causing neutropenia. Neutropenia increases the risk for serious infection and is associated with significant morbidity and mortality. The approach to the treatment of the febrile neutropenic pediatric patient has evolved considerably because high- and low-risk criteria have been defined and broad-spectrum antibiotics developed. This article reviews the concepts involved in the evaluation and management of febrile, neutropenic, pediatric cancer patients.

Successful intermittent prophylaxis with trimethoprim/sulfamethoxazole 2 days per week for Pneumocystis carinii (jiroveci) pneumonia in pediatric oncology patients.

OBJECTIVE: This study was conducted to determine the efficacy of dosing trimethoprim/sulfamethoxazole on 2 consecutive days per week for the prevention of Pneumocystis carinii (jiroveci) pneumonia in a pediatric leukemia and lymphoma population and to determine whether trimethoprim/sulfamethoxazole contributes to neutropenia during maintenance therapy. METHODS: Charts were reviewed for all pediatric patients with leukemia and lymphoma diagnosed between January 1, 1993, and December 31, 2002. Data were collected through April 1, 2004. RESULTS: A total of 575 charts were reviewed; 529 patients were included in the analysis. A total of 482 (345 leukemia, 137 lymphoma) patients were evaluated on trimethoprim/sulfamethoxazole dosed 2 consecutive days per week for 268074 patient-days. No breakthrough cases were documented in compliant patients; 2 noncompliant patients developed P. carinii pneumonia. A total of 238 patients who were on trimethoprim/sulfamethoxazole prophylaxis and 13 patients who were receiving an alternative medication prophylaxis were evaluated for neutropenia during maintenance therapy. The median number of maintenance days on trimethoprim/sulfamethoxazole was 605.5 days and on alternative drug was 617 days. The median number of neutropenic maintenance days on trimethoprim/sulfamethoxazole was 15.5 days and on the alternative drug was 16 days. The median proportion of neutropenic days per patient was 0.029 on trimethoprim/sulfamethoxazole and 0.022 on the alternative drug. CONCLUSIONS: Intermittent dosing of trimethoprim/sulfamethoxazole on 2 consecutive days per week is an effective alternative prophylactic regimen for P. carinii pneumonia in pediatric patients with leukemia and lymphoma. This analysis does not support a difference in neutropenia during maintenance therapy between patients who are treated with trimethoprim/sulfamethoxazole versus an alternative drug.

Intrathecal triple therapy decreases central nervous system relapse but fails to improve event-free survival when compared with intrathecal methotrexate: results of the Children's Cancer Group (CCG) 1952 study for standard-risk acute lymphoblastic leukemia, reported by the Children's Oncology Group.

The Children's Cancer Group (CCG) 1952 clinical trial for children with standard-risk acute lymphoblastic leukemia (SR-ALL) compared intrathecal (IT) methotrexate (MTX) with IT triples (ITT) (MTX, cytarabine, and hydrocortisone sodium succinate [HSS]) as presymptomatic central nervous system (CNS) treatment. Following remission induction, 1018 patients were randomized to receive IT MTX and 1009 ITT. Multivariate analysis identified male sex, hepatomegaly, CNS-2 status, and age younger than 2 or older than 6 years as significant predictors of isolated CNS (iCNS) relapse. The 6-year cumulative incidence estimates of iCNS relapse are 3.4% +/- 1.0% for ITT and 5.9% +/- 1.2% for IT MTX; P = .004. Significantly more relapses occurred in bone marrow (BM) and testicles with ITT than IT MTX, particularly among patients with T-cell phenotype or day 14 BM aspirate containing 5% to 25% blasts. Thus, the estimated 6-year event-free survivals (EFS) with ITT or IT MTX are equivalent at 80.7% +/- 1.9% and 82.5% +/- 1.8%, respectively (P = .3). Because the salvage rate after BM relapse is inferior to that after CNS relapse, the 6-year overall survival (OS) for ITT is 90.3% +/- 1.5% versus 94.4% +/- 1.1% for IT MTX (P = .01). It appears that ITT improves presymptomatic CNS treatment but does not improve overall outcome.