A gene expression-based model predicts outcome in children with intermediate-risk classical Hodgkin lymphoma.

Classical Hodgkin lymphoma (cHL) is a common malignancy in children and adolescents. Although cHL is highly curable, treatment with chemotherapy and radiation often come at the cost of long-term toxicity and morbidity. Effective risk-stratification tools are needed to tailor therapy. Here, we used gene expression profiling (GEP) to investigate tumor microenvironment (TME) biology, to determine molecular correlates of treatment failure, and to develop an outcome model prognostic for pediatric cHL. A total of 246 formalin-fixed, paraffin-embedded tissue biopsies from patients enrolled in the Children's Oncology Group trial AHOD0031 were used for GEP and compared with adult cHL data. Eosinophil, B-cell, and mast cell signatures were enriched in children, whereas macrophage and stromal signatures were more prominent in adults. Concordantly, a previously published model for overall survival prediction in adult cHL did not validate in pediatric cHL. Therefore, we developed a 9-cellular component model reflecting TME composition to predict event-free survival (EFS). In an independent validation cohort, we observed a significant difference in weighted 5-year EFS between high-risk and low-risk groups (75.2% vs 90.3%; log-rank P = .0138) independent of interim response, stage, fever, and albumin. We demonstrate unique disease biology in children and adolescents that can be harnessed for risk-stratification at diagnosis. This trial was registered at www.clinicaltrials.gov as #NCT00025259.

A comprehensive assessment of the prolonged febrile neutropenia evaluation in pediatric oncology patients.

BACKGROUND: Pediatric oncology patients with prolonged (≥96 hours) febrile neutropenia (absolute neutrophil count < 500/µL) often undergo an evaluation for invasive fungal disease (IFD) and other infections. Current literature suggests that beta-D-glucan (BDG), galactomannan, bronchoalveolar lavage (BAL), and computed tomography (CT) scans (sinus, chest, and abdomen/pelvis) may help determine a diagnosis in this population. METHODS: In a retrospective cohort study of all cancer/stem cell transplant patients (diagnosed 2005-2019) from one pediatric hospital, all episodes with prolonged febrile neutropenia or IFD evaluations (defined as sending a fungal biomarker or performing a CT scan to assess for infection) were identified. RESULTS: In total, 503 episodes met inclusion criteria and 64% underwent IFD evaluations. In total, 36.4% of episodes documented an infection after initiation of prolonged febrile evaluation, most commonly Clostridioides difficile colitis (6.4%) followed by a true bacterial bloodstream infection (BSI) (5.2%), proven/probable IFD (4.8%), and positive respiratory pathogen panel (3.6%). There was no difference in sinus CTs showing sinusitis (74% vs 63%, p = 0.46), whereas 32% of abdomen/pelvis CTs led to a non-IFD diagnosis, and 25% of chest CTs showed possible pneumonia. On chest CT, the positive predictive value (PPV) for IFD was 19% for nodules and 14% for tree and bud lesions. BDG had a PPV of 25% for IFD and GM 50%. BAL diagnosed IFD once and pneumocystis jirovecii pneumonia twice. CONCLUSIONS: Chest CTs and abdomen/pelvis CTs provide clinically relevant information during the prolonged febrile neutropenia evaluation, whereas BDG, galactomannan, BAL, and sinus CTs have less certain utility.

Applying a risk prediction model for bloodstream infection in a febrile, nonseverely neutropenic cohort of pediatric stem cell transplant patients.

BACKGROUND: The optimal management of febrile stem cell transplant (SCT) patients presenting without severe neutropenia (absolute neutrophil count [ANC] ≥ 500/µL) is unclear. The authors have developed iterative risk prediction models (Esbenshade Vanderbilt [EsVan] models) that reliably predict bloodstream infections (BSIs) in the febrile general pediatric oncology population without severe neutropenia, but SCT-specific data are limited. METHODS: All SCTs occurring from May 2005 to November 2019 at a single institution were identified. Episodes of fever with a central venous catheter and ANC values ≥ 500/µL were abstracted. All previous versions of the EsVan model were applied to the SCT data, and c-statistics were generated. The models were additionally applied to each type of transplant (autologous/allogeneic), and a new allogeneic model that further adjusted for metrics of immunosuppression, Esbenshade Vanderbilt Allogeneic SCT Model (EsVanAlloSCT), was developed and internally validated. RESULTS: For 429 SCT episodes (221 autologous and 208 allogeneic), the BSI incidence was 19.6% (84 of 429), and it was higher in allogeneic transplant patients (25.5%) than autologous transplant patients (14.0%; p < .01). All versions of the EsVan model performed well for the overall SCT cohort (c-statistics, 0.759-0.795). The EsVan models performed better for the autologous episodes (c-statistics, 0.869-0.881) than the allogeneic SCT episodes (c-statistics, 0.678-0.717). The new allogeneic transplant-specific model, EsVanAlloSCT, which added an adjustment for the extent of immunosuppression, yielded a c-statistic of 0.792 (bootstrap-corrected, 0.750). CONCLUSIONS: The EsVan models work exceptionally well when they are applied to autologous SCT, but they work less well for allogeneic SCT. EsVanAlloSCT appears to improve the predictive ability in allogeneic SCT, but it will need additional external validation.

Subsequent malignant neoplasms among children with Hodgkin lymphoma: a report from the Children's Oncology Group.

Survivors of Hodgkin lymphoma (HL) have an increased risk of subsequent malignant neoplasms (SMNs). Response-adapted treatment may decrease this risk by reducing exposure to therapy associated with SMN risk. The Children's Oncology Group study AHOD0031 evaluated response-adapted therapy for children and adolescents with intermediate-risk HL. We report the SMNs among 1711 patients enrolled in AHOD0031. Patients were treated with 4 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide with or without involved-field radiation therapy (RT). Patients with a slow early response to initial chemotherapy were randomized to 2 additional cycles of dexamethasone, etoposide, cisplatin and cytarabine or no additional chemotherapy, and all received RT. At a median follow-up of 7.3 years, an analysis of SMNs was performed. The 10-year cumulative incidence of SMN was 1.3% (95% confidence interval [CI], 0.6-2.0). SMNs included 3 patients with acute myeloid leukemia (AML), 11 with solid tumors, and 3 with non-Hodgkin lymphoma. Sixteen of 17 patients with an SMN had received combined modality therapy. The standardized incidence ratio for SMN was 9.5 (95% CI, 4.5-15.2) with an excess absolute risk of 1.2 per 1000 person-years. The cumulative incidence of SMNs was higher among patients who received RT (P = .037). In multivariate analysis, RT, B symptoms, and race were associated with SMN risk. Given the latency from exposure, we have likely captured all cases of secondary leukemia and myelodysplastic syndrome (MDS). Longer follow-up is needed to determine the risk of solid tumors. Avoidance of RT without sacrificing disease control should remain a goal for future therapeutic approaches. This trial was registered at www.clinicaltrials.gov as #NCT00025259.

NCCN Guidelines® Insights: Survivorship, Version 1.2023.

The NCCN Guidelines for Survivorship are intended to help healthcare professionals address the complex and varied needs of cancer survivors. The NCCN Guidelines provide screening, evaluation, and treatment recommendations for psychosocial and physical problems resulting from adult-onset cancer and its treatment; recommendations to help promote healthy behaviors and immunizations in survivors; and a framework for care coordination. These NCCN Guidelines Insights summarize recent guideline updates and panel discussions pertaining to sleep disorders, fatigue, and cognitive function in cancer survivors.

Posttraumatic stress symptoms and financial toxicity among adolescent and young adult oncology patients and their caregivers at cancer diagnosis.

BACKGROUND: Adolescent and young adult oncology (AYAO) patients and caregivers may experience significant psychosocial dysfunction and financial toxicity. Understanding early risk factors is critical to improving survivorship trajectories. METHODS: The authors conducted a cross-sectional study of baseline survey data from a prospective cohort of AYAO patient-caregiver dyads enrolled within 1 month of medical oncology treatment initiation. Posttraumatic stress symptoms (PTSS) were measured by the Impacts of Events Scale-Revised, and financial toxicity was measured with the Comprehensive Score (COst). The authors fit models of linear association between PTSS, financial toxicity, and other end points and pairwise associations of PTSS and financial toxicity within dyads. RESULTS: The analytic cohort contained 41 patients, 37 caregivers, and 34 complete dyads. Clinically-concerning PTSS were observed among patients (44%) and caregivers (52%). The median COst scores were 20.0 for patients (quartiles, 12.5-29.5) and 22.0 for caregivers (quartiles, 12.8-26.0), which were consistent with high financial toxicity (patients, 46%; caregivers, 44%). PTSS were positively associated with financial toxicity (P = .013 for patients, P = .039 for caregivers), subjective distress (P < .001 for all), depressive (P < .001 for all) and anxiety symptoms (P = .005 for patients, P = .024 for caregivers), and poorer quality of life (P < .001 for patients, P = .003 for caregivers). A significant paired association was not found in PTSS (Pearson correlation coefficient [PCC], 0.23; 95% confidence interval [CI], -0.15 to 0.56). Financial toxicity was positively associated within dyads (PCC, 0.65; 95% CI, 0.36-0.83). CONCLUSIONS: At diagnosis, AYAO patients and caregivers exhibit substantial PTSS, which are associated with greater financial toxicity and other psychosocial distress.

NCCN Guidelines® Insights: Survivorship, Version 1.2022.

The NCCN Guidelines for Survivorship are intended to help healthcare professionals who work with survivors to ensure that the survivors' complex and varied needs are addressed. The NCCN Guidelines provide screening, evaluation, and treatment recommendations for the consequences of adult-onset cancer and its treatment; recommendations to help promote physical activity, weight management, and immunizations in survivors; and a framework for care coordination. This article summarizes updates to the NCCN Guidelines pertaining to preventive health for cancer survivors, including recommendations about alcohol consumption and vaccinations.

Oncologist counseling practice and COVID-19 vaccination outcomes for patients with history of PEG-asparaginase hypersensitivity.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an effective strategy to prevent serious coronavirus disease 2019 (COVID-19) and is important for oncology patients. mRNA-based COVID-19 vaccines are contraindicated in those with a history of severe or immediate allergy to any vaccine component, including polyethylene glycol (PEG)2000. Patients with acute lymphoblastic leukemia/lymphoma receive asparaginase conjugated to PEG5000 (PEG-ASNase) and those with PEG-ASNase-associated hypersensitivity may be unnecessarily excluded from receiving mRNA COVID-19 vaccines. We, therefore, surveyed oncologists on COVID-19 vaccine counseling practice and vaccination outcomes in COVID-19 vaccination-eligible patients and show safe receipt of mRNA vaccines despite PEG-ASNase hypersensitivity.

Isolated CNS Relapse in 2 High-Risk B-cell Acute Lymphoblastic Leukemia Patients Following SARS-CoV-2 Infection.

B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric malignancy with a highly favorable overall prognosis. Central nervous system (CNS) relapse of B-ALL is relatively rare and is associated with inferior survival outcomes. We present two patients with B-ALL who developed isolated CNS relapse following confirmed infection with severe acute respiratory syndrome coronavirus 2. In addition to individual and disease factors, we posit that delays in therapy together with immune system modulation because of severe acute respiratory syndrome coronavirus 2 may account for these 2 cases of CNS relapsed B-ALL. We report on this clinical observation to raise awareness of this potential association.

CNS-Directed Cancer Treatment and Child Adjustment: Moderating Effects of Maternal Parenting.

OBJECTIVE: The aim of this study was to examine whether maternal parenting behaviors (i.e., warmth, behavioral/psychological control) moderate the association between central nervous system (CNS)-directed treatment and adjustment among pediatric cancer survivors at 3 years post-diagnosis or relapse. METHODS: Three years after their child's cancer diagnosis or relapse, mothers (N = 84) reported on their child's academic and social competence, as well as their internalizing and externalizing problems. Children (N = 84; Mage = 13.21 years, 52.4% male) reported on maternal parenting behaviors. Using medical chart data, children were separated into CNS (i.e., received cranial radiation, intrathecal chemotherapy, and/or neurosurgery; N = 45) or non-CNS-directed treatment (N = 39) groups. Twelve moderation models were tested when examining two-way interactions between CNS treatment group and maternal parenting behaviors. RESULTS: Children in the CNS-directed treatment group demonstrated significantly worse academic and social competence. Moderation analyses revealed four significant two-way interactions between CNS treatment group and maternal parenting behaviors when predicting children's adjustment. High levels of maternal behavioral control buffered the negative impact of CNS-directed treatment on children's social competence. In addition, maternal warmth had a contrasting effect, as CNS-directed treatment was associated with worse academic competence at high levels of warmth. Analyses with psychological control revealed that low levels of this parenting style were not protective against internalizing or externalizing problems among those with CNS-directed treatment. CONCLUSIONS: Children who receive CNS-directed treatment may benefit from a different pattern of parenting during early cancer survivorship. Findings highlight the importance of considering the broader family context when conceptualizing the impact of illness-related factors on adjustment among pediatric cancer survivors.

Enhancing Cancer care of rural dwellers through telehealth and engagement (ENCORE): protocol to evaluate effectiveness of a multi-level telehealth-based intervention to improve rural cancer care delivery.

BACKGROUND: Despite lower cancer incidence rates, cancer mortality is higher among rural compared to urban dwellers. Patient, provider, and institutional level factors contribute to these disparities. The overarching objective of this study is to leverage the multidisciplinary, multispecialty oncology team from an academic cancer center in order to provide comprehensive cancer care at both the patient and provider levels in rural healthcare centers. Our specific aims are to: 1) evaluate the clinical effectiveness of a multi-level telehealth-based intervention consisting of provider access to molecular tumor board expertise along with patient access to a supportive care intervention to improve cancer care delivery; and 2) identify the facilitators and barriers to future larger scale dissemination and implementation of the multi-level intervention. METHODS: Coordinated by a National Cancer Institute-designated comprehensive cancer center, this study will include providers and patients across several clinics in two large healthcare systems serving rural communities. Using a telehealth-based molecular tumor board, sequencing results are reviewed, predictive and prognostic markers are discussed, and treatment plans are formulated between expert oncologists and rural providers. Simultaneously, the rural patients will be randomized to receive an evidence-based 6-week self-management supportive care program, Cancer Thriving and Surviving, versus an education attention control. Primary outcomes will be provider uptake of the molecular tumor board recommendation and patient treatment adherence. A mixed methods approach guided by the Consolidated Framework for Implementation Research that combines qualitative key informant interviews and quantitative surveys will be collected from both the patient and provider in order to identify facilitators and barriers to implementing the multi-level intervention. DISCUSSION: The proposed study will leverage information technology-enabled, team-based care delivery models in order to deliver comprehensive, coordinated, and high-quality cancer care to rural and/or underserved populations. Simultaneous attention to institutional, provider, and patient level barriers to quality care will afford the opportunity for us to broadly share oncology expertise and develop dissemination and implementation strategies that will enhance the cancer care delivered to patients residing within underserved rural communities. TRIAL REGISTRATION: Clinicaltrials.gov , NCT04758338 . Registered 17 February 2021 - Retrospectively registered, http://www.clinicaltrials.gov/.

Intravitreal melphalan hydrochloride vs propylene glycol-free melphalan for retinoblastoma vitreous seeds: Efficacy, toxicity and stability in rabbits models and patients.

The use of intravitreal chemotherapy has revolutionized the treatment of advanced intraocular retinoblastoma, as intravitreal melphalan has enabled difficult-to-treat vitreous tumor seeds to be controlled, leading to many more eyes being saved. However, melphalan hydrochloride (MH) degrades rapidly in solution, increasing logistical complexity with respect to time between medication preparation and administration for intravitreal administration under anesthesia for retinoblastoma. A new propylene glycol-free melphalan (PGFM) formulation has greater stability and could therefore improve access and adoption of intravitreal chemotherapy, allowing more children to retain their eye(s). We compared the efficacy and toxicity of both formulations, using our rabbit xenograft model and clinical patient experience. Three weekly 12.5 µg intravitreal injections of MH or PGFM (right eye), and saline (left eye), were administered to immunosuppressed rabbits harboring human WERI-Rb1 vitreous seed xenografts. Residual live cells were quantified directly, and viability determined by TUNEL staining. Vitreous seeds were reduced 91% by PGFM (p = 0.009), and 88% by MH (p = 0.004; PGFM vs. MH: p = 0.68). All residual cells were TUNEL-positive (non-viable). In separate experiments to assess toxicity, three weekly 12.5 µg injections of MH, PGFM, or saline were administered to non-tumor-bearing rabbits. Serial electroretinography, optical coherence tomography (OCT) and OCT-angiography were performed. PGFM and MH both caused equivalent reductions in electroretinography amplitudes, and loss of retinal microvasculature on OCT-angiography. The pattern of retinal degeneration observed on histopathology suggested that segmental retinal toxicity associated with all melphalan formulations was due to a vitreous concentration gradient-effect. Efficacy and toxicity were assessed for PGFM given immediately (within 1 h of reconstitution) vs. 4 h after reconstitution. Immediate- and delayed-administration of PGFM showed equivalent efficacy and toxicity. In addition, we evaluated efficacy and toxicity in patients (205 eyes) with retinoblastoma vitreous seeds, who were treated with a total of 833 intravitreal injections of either MH or PGFM as standard of care. Of these, we analyzed 118 MH and 131 PGFM monotherapy injections in whom serial ERG measurements were available to model retinal toxicity. Both MH and PGFM caused reductions in electroretinography amplitudes, but with no statistical difference between formulations. Comparing those patient eyes treated exclusively with PGFM versus those treated exclusively with MH, efficacy for tumor control and globe salvage was equivalent (PGFM vs. MH: 96.2% vs. 93.8%, p = 0.56), but PGFM-treated eyes received fewer injections than MH-treated eyes (average 3.2 ± 1.9 vs. 6.4 ± 2.1 injections, p < 0.0001). Taken together, these rabbit experiments and our clinical experience in retinoblastoma patients demonstrate that MH and PGFM have equivalent efficacy and toxicity. PGFM was more stable, with no decreased efficacy or increased toxicity even 4 h after reconstitution. We therefore now use PGFM over traditional MH for our patients for intravitreal treatment of retinoblastoma.

Survivorship, Version 1.2021.

The NCCN Guidelines for Survivorship are intended to help healthcare professionals working with cancer survivors to ensure that each survivor's complex and varied needs are addressed. The Guidelines provide screening, evaluation, and treatment recommendations for consequences of adult-onset cancer and its treatment; recommendations to help promote healthful lifestyle behaviors, weight management, and immunizations in survivors; and a framework for care coordination. This article summarizes the recommendations regarding employment and return to work for cancer survivors that were added in the 2021 version of the NCCN Guidelines.

Prognostic value of baseline metabolic tumor volume in children and adolescents with intermediate-risk Hodgkin lymphoma treated with chemo-radiation therapy: FDG-PET parameter analysis in a subgroup from COG AHOD0031.

BACKGROUND: Positron emission tomography (PET)-based measures of baseline total-body tumor burden may improve risk stratification in intermediate-risk Hodgkin lymphoma (HL). MATERIALS AND METHODS: Evaluable patients were identified from a cohort treated homogeneously with the same combined modality regimen on the Children's Oncology Group AHOD0031 study. Eligible patients had high-quality baseline PET scans. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were each measured based on 15 thresholds for every patient. Univariate and multivariable Cox regression and Kaplan-Meier survival analyses assessed for an association of MTV and TLG with event-free survival (EFS). RESULTS: From the AHOD0031 cohort (n = 1712), 86 patients were identified who (i) were treated with four cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE-PC) chemotherapy followed by involved field radiotherapy, and (ii) had a baseline PET scan that was amenable to quantitative analysis. Based on univariate Cox regression analysis, six PET-derived parameters were significantly associated with EFS. For each of these, Kaplan-Meier analyses and the log-rank test were used to compare patients with highest tumor burden (i.e., highest 15%) to the remainder of the cohort. EFS was significantly associated with all six PET parameters (all p < .029). In a multivariable model controlling for important covariates including disease bulk and response to chemotherapy, MTV2BP was significantly associated with EFS (p = .012). CONCLUSION: Multiple baseline PET-derived volumetric parameters were associated with EFS. MTV2BP was highly associated with EFS when controlling for disease bulk and response to chemotherapy. Incorporation of baseline MTV into risk-based treatment algorithms may improve outcomes in intermediate-risk HL.

Facebook Recruitment for Children with Advanced Cancer and Their Parents: Lessons from a Web-based Pediatric Palliative Intervention Study.

Participant recruitment for pediatric palliative intervention studies is a chronic challenge for researchers. Digital recruitment strategies, or digital technology-assisted recruitment methods used to remotely reach and enroll research subjects, can help address these recruitment challenges for pediatric palliative care clinical trials. This study (a) describes Facebook recruitment procedures targeting children with cancer and their parents for a pediatric palliative intervention randomized clinical trial, (b) reports recruitment results, and (c) discusses successful strategies to recruit pediatric populations via Facebook advertisements. Researchers used Facebook advertisements to recruit children with advanced cancer (aged 7 to 17 years) for a web-based legacy intervention. Between years 2015 and 2018, our research team enrolled 150 child-parent dyads (N= 300) to participate in the web-based legacy program. Results suggest that Facebook advertisements can be a successful tool to access and recruit pediatric populations with life-threatening conditions. Further research is needed to determine how innovative social-media recruitment strategies could be used in other populations of patients with serious illnesses and their caregivers to further advance the science in palliative care.

Improved Parent-Child Communication following a RCT Evaluating a Legacy Intervention for Children with Advanced Cancer.

Although legacy-building is a priority for quality palliative care, research has rarely examined effects of legacy interventions in children, particularly their impact on parent-child communication.We examined the impact of a web-based legacy intervention on parent-child communication. We hypothesized that compared to usual care, legacy-making would improve quality of parent-child communication.Between 2015 and 2018, Facebook advertisements were used to recruit families of children (ages 7-17) with relapsed/refractory cancer. Parent-child dyads were randomly assigned to the intervention or usual care group. The intervention website guided children to create digital storyboards over 2 weeks by directing them to answer legacy questions about themselves and upload photographs, videos, and music. Families received a copy of the child's final digital story. Children and parents completed the Parent-Adolescent Communication Scale pre- (T1) and post-intervention (T2). Linear regressions tested for differences in change from T1 to T2 between the groups controlling for T1 values using an alpha of p < .05. Intervention effects were measured using Cohen's d. Ninety-seven parent-child dyads were included for analysis. Changes in parent-child communication were not statistically significantly different between the groups, yet meaningful intervention effects were observed. The strongest effects were observed for improving father-child communication (Cohen's d = -0.22-0.33). Legacy-making shows promise to facilitate improved parent-child communication, particularly for fathers. Future studies should include fathers and measure expression of feelings and parent-child interaction. Providers should continue to facilitate family communication for children with advanced disease and realize that legacy interventions may impact mother-child versus father-child communication differently.

Childhood cancer survivors: The integral role of the cardiologist and cardiovascular imaging.

IMPORTANCE: With 80% of childhood cancer survivors (CCS) alive 30 years after diagnosis, preventable causes of death, such as cardiovascular disease resulting from initial cancer therapy, becomes an important metric. This leads to a more pronounced role for cardiologists in the care of CCS. OBSERVATIONS: While routine cardiovascular screening has been traditionally performed by the hematologist/oncologist or primary care provider, our understanding of cardiovascular disease in CCS has advanced. The measurement of left ventricular ejection fraction (LVEF) can now be complemented with additional assessments of strain, LV mass, right ventricular function, diastolic function, valve function, the pericardium, coronary perfusion, and biomarkers. Risk factor modification, prophylaxis, and timing of treatment are also critical. CONCLUSIONS AND RELEVANCE: Early cardiovascular screening and treatment in asymptomatic CCS can be nuanced and complex. As a result, there is a renewed opportunity for the cardiologist to play an integral role in the care of CCS. KEY POINTS: Question/Purpose: Review cardiovascular disease and the role of the cardiologist in the care of asymptomatic childhood cancer survivors (CCS). FINDINGS: Cardiovascular care in CCS benefits from a multi-faceted approach that does not overly rely on LVEF. Meaning: Adequate screening and treatment of cardiovascular disease in asymptomatic CCS may often be optimized by the involvement of a cardiologist.

NCCN Guidelines Insights: Survivorship, Version 2.2020.

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for consequences of adult-onset cancer and its treatment, with the goal of helping healthcare professionals who work with survivors, including those in primary care. The guidelines also provide recommendations to help clinicians promote physical activity, weight management, and proper immunizations in survivors and facilitate care coordination to ensure that all of the survivors' needs are addressed. These NCCN Guidelines Insights summarize additions and changes made to the guidelines in 2020 regarding cardiovascular disease risk assessment and screening for subsequent primary malignancies.

NCCN Guidelines Insights: Survivorship, Version 2.2019.

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for consequences of cancer and cancer treatment to aid healthcare professionals who work with survivors of adult-onset cancer. Guidance is also provided to help promote physical activity, weight management, and proper immunizations in survivors and to facilitate care coordination to ensure that all needs are addressed. These NCCN Insights summarize some of the topics discussed by the NCCN Survivorship Panel during the 2019 update of the guidelines, including the survivorship population addressed, ways to improve care coordination, and pain management.

Impact of IgG Monitoring and IVIG Supplementation on the Frequency of Febrile Illnesses in Pediatric Acute Lymphoblastic Leukemia Patients Undergoing Maintenance Chemotherapy.

Monitoring serum immunoglobulin G (IgG) levels in pediatric oncology patients and treating subtherapeutic levels with intravenous immunoglobulin (IVIG) may prevent infections; however, evidence is limited. This retrospective study assessed pediatric acute lymphoblastic leukemia patients diagnosed 2006 to 2011 to evaluate if monitoring/supplementing IgG would reduce febrile illnesses during maintenance chemotherapy. A subject was categorized as "ever IgG monitored" if they had ≥1 IgG levels checked and their risk days were stratified into not IgG monitored days and IgG monitored days. IgG monitored days were further stratified into IgG monitored with IVIG supplementation, monitored with no IVIG supplementation (IgG level >500 mg/dL) and monitored with no IVIG supplementation days (IgG level <500 mg/dL). Generalized linear mixed effects poisson models were used to compare events (febrile episode, positive blood culture, and febrile upper respiratory infection rates among these groups. In 136 patients, the febrile episode rate was higher in the ever IgG monitored cohort than the never monitored cohort (5.26 vs. 3.78 episodes/1000 d). Among monitored patients, IVIG monitoring and supplementation did not significantly impact the febrile episode, febrile upper respiratory infection, or the positive blood culture rates. These data suggest that monitoring/supplementing low IgG is not indicated for infection prophylaxis in acute lymphoblastic leukemia patients during maintenance chemotherapy.