Management of childhood cancer survivors at risk for thyroid function abnormalities: A Delphi study.

BACKGROUND: Thyroid function abnormalities can occur after treatment for childhood cancer. Evidence for the management of thyroid dysfunction among asymptomatic childhood cancer survivors (CCS) is lacking. We used a Delphi consensus methodology to expand guidelines for screening asymptomatic CCS at risk for thyroid dysfunction and explore recommendations for the clinical management of abnormal results. PROCEDURE: A Delphi panel of 40 expert physicians representing oncology, endocrinology, and primary care participated in three rounds of anonymous, iterative questionnaires formatted as clinical scenarios. Consensus is defined as ≥ 90% of panelists agree with recommendation and disagreement as < 70% agree. RESULTS: Panelists reached consensus that CCS treated with radiation including neck, total body, whole brain, brain including the hypothalamic-pituitary axis (HPA), and therapeutic meta-iodobenzylguanidine (MIBG) should have annual, lifelong screening using serum thyroid-stimulating hormone (TSH) and free T4 starting within one year off-treatment (98%). Panelists disagreed on continuing to screen CCS for thyroid dysfunction after immunotherapy associated with acute thyroid injury (31%-50%). There was also disagreement on indications for brain (17%-43%) or thyroid (50%-65%) imaging, laboratory tests to assess the HPA (29%-75%), and TSH threshold to initiate treatment of subclinical hypothyroidism. Lack of evidence was the most frequent rationale panelists offered for not recommending additional testing or medications. Panelists' recommendations did not vary by geography, specialty, or survivorship clinical experience. CONCLUSIONS: Consensus was reached on most recommendations for screening and management of cancer treatment-related thyroid dysfunction. Screening after completion of thyroid-toxic immunotherapy, indications for imaging, and treatment of subclinical hypothyroidism are areas of disagreement for further investigation.

Regional practice norms for the care of childhood cancer survivors at risk for cardiomyopathy: A Delphi study.

BACKGROUND: Treatment-associated cardiomyopathy is a leading cause of morbidity and mortality for childhood cancer survivors (CCS). As evidence is not available to guide the management of CCS at risk for cardiomyopathy, we aim to describe the collective opinion of regional experts for the care of these patients using a consensus-based Delphi methodology. PROCEDURE: Nineteen physicians from the New England region who care for CCS treated with cardiotoxic therapy (anthracyclines, thoracic radiation) participated in a Delphi panel querying their management approach, using three rounds of anonymous questionnaires formatted as five clinical scenarios. Consensus ≥ 89% agreement. RESULTS: The response rate was 100% for the first round and 95% for subsequent rounds. Panelists reached consensus on screening asymptomatic CCS with serial echocardiograms (94%) and electrocardiograms (89%), with some disagreement on frequency during pregnancy (83%). All panelists agreed with exercise promotion, with no restrictions on weight training. Consensus was reached on indications for referrals; cardiology for asymptomatic left ventricular dysfunction (ALVD) (100%) and maternal-fetal medicine for pregnancy (94%). In the scenario of ALVD, there was disagreement on the benefit of additional cardiac testing (50% cardiologists recommended cardiac MRI), and although all panelists endorsed treating with angiotension-converting enzyme (ACE) inhibitors, most adult cardiologists (75%) also recommended therapy with beta blockers, compared with none of the pediatric cardiologists or primary-care physicians. CONCLUSIONS: Despite a lack of evidence to guide the management of CCS at risk for cardiomyopathy, a panel of regional physicians reached consensus on managing most clinical scenarios. A controversial area requiring further study is the medical management of ALVD.

The management of childhood cancer survivors at risk for stroke: A Delphi survey of regional experts.

BACKGROUND: Evidence is not available to guide management of childhood cancer survivors (CCS) at risk for radiation-associated cerebral vascular disease (CVD) and stroke. We propose to use a consensus-based methodology to describe the collective opinion of regional experts for the care of these patients and identify areas of controversy. PROCEDURE: Thirty physicians from the New England region who care for CCS participated in a Delphi panel querying their management approach (imaging, laboratory tests, medications, counseling, referrals) to a CCS treated with cranial radiation formatted as five clinical scenarios (asymptomatic, small- and large-vessel CVD, transient ischemia, stroke) in three rounds of anonymous questionnaires. Consensus defined as ≥90% agreement. RESULTS: Response rate was 100% for all three rounds. Panelists reached consensus on laboratory tests to assess stroke risk factors, stroke risk and prevention counseling, brain imaging to monitor survivors with known CVD, and acute care for stroke symptoms. Only 67% panelists agreed with MRI screening asymptomatic survivors with no history of CVD, 87% endorsed aspirin as stroke prevention for large-vessel CVD and 57% for small-vessel CVD. There was no consensus on specialty referrals. Overall, panelists practicing at large institutions and neurology subspecialists were more likely to advocate for screening, interventions, and referrals. CONCLUSIONS: Despite lack of evidence to guide stroke prevention in CCS treated with cranial radiation, a panel of regional physicians reached consensus on managing most clinical scenarios. Controversial areas requiring further study are surveillance imaging for asymptomatic survivors, aspirin for stroke prevention, and indications for specialty referral.

Delphi Panel Consensus Recommendations for Screening and Managing Childhood Cancer Survivors at Risk for Cardiomyopathy.

Background: Cardiomyopathy is a leading cause of late morbidity and mortality in childhood cancer survivors (CCS). Evidence-based guidelines recommend risk-stratified screening for cardiomyopathy, but the management approach for abnormalities detected when screening asymptomatic young adult CCS is poorly defined. Objectives: The aims of this study were to build upon existing guidelines by describing the expert consensus-based cardiomyopathy screening practices, management approach, and clinical rationale for the management of young adult CCS with screening-detected abnormalities and to identify areas of controversy in practice. Methods: A multispecialty Delphi panel of 40 physicians with expertise in cancer survivorship completed 3 iterative rounds of semi-open-ended questionnaires regarding their approaches to the management of asymptomatic young adult CCS at risk for cardiomyopathy (screening practices, referrals, cardiac testing, laboratory studies, medications). Consensus was defined as ≥90% panelist agreement with recommendation. Results: The response rate was 100% for all 3 rounds. Panelists reached consensus on the timing and frequency of echocardiographic screening for anthracycline-associated cardiomyopathy, monitoring during pregnancy, laboratory testing for modifiable cardiac risk factors, and referral to cardiology for ejection fraction ≤50% or preserved ejection fraction with diastolic dysfunction. Controversial areas (<75% agreement) included chest radiation dose threshold to merit screening, indications for advanced cardiac imaging and cardiac serum biomarkers for follow-up of abnormal echocardiographic findings, and medical management of asymptomatic left ventricular systolic dysfunction. Conclusions: Expert practice is largely consistent with existing risk-based screening guidelines. Some recommendations for managing abnormalities detected on screening echocardiography remain controversial. The rationale offered by experts for divergent approaches may help guide clinical decisions in the absence of guidelines specific to young adult CCS.

Consensus Recommendations for Managing Childhood Cancer Survivors at Risk for Stroke After Cranial Irradiation: A Delphi Study.

BACKGROUND AND OBJECTIVES: There is insufficient evidence to support stroke prevention guidelines for childhood cancer survivors (CCS) treated with cranial irradiation for CNS tumors or other childhood cancers involving the CNS. We used a systematic consensus-building methodology to develop expert recommendations and define areas of controversy in managing asymptomatic CCS at risk for stroke. METHODS: A Delphi process was used to query a multispecialty panel of 45 physicians from the United States/Canada, with expertise in CCS, about their stroke screening and management practices (imaging, referrals, laboratory testing, and medications). Three iterative rounds of anonymous, scenario-based questionnaires, building on panelists' aggregate responses, were used to reach consensus (≥90% agreement), agreement (89%-70% agree), or to understand the rationale for disagreement (<70% agree). RESULTS: All 45 physicians participated in the first 2 rounds and 44 in the third. Panelists reached consensus on indications for referral to neurology and laboratory screening for modifiable cerebral vascular disease (CVD) risk factors in most scenarios. Panelists agreed that aspirin therapy is not recommended in the scenario of normal neuroimaging (86% agreed). Decisions about aspirin therapy in scenarios with abnormal neuroimaging were deferred to specialists; almost all agreed with not using aspirin for cavernomas with no evidence for previous hemorrhage (93%) and using aspirin for both large vessel CVD (93%) and small vessel CVD with evidence of previous stroke (86%). Clinical decisions that remain controversial (less than 70% agreement) include neuroimaging to screen asymptomatic CCS for CVD, referral to neurology for cavernomas, aspirin use in the setting of cavernomas with previous hemorrhage, or with evidence for small vessel CVD and no previous stroke, and indications for statins. Overall, pediatric neurologists/neuro-oncologists and radiation oncologists were more likely to advocate for screening and interventions. DISCUSSION: Despite lack of evidence to guide the management of CCS at risk for stroke, expert recommendations and rationale developed by consensus methodology are helpful to support clinical decision-making.

Ifosfamide-induced encephalopathy and movement disorder.

Ifosfamide is a widely used chemotherapeutic agent for the treatment of a broad spectrum of solid tumors. CNS toxicity is a well-described side effect of ifosfamide, but the mechanism of ifosfamide-induced neurotoxicity remains poorly defined. We present two pediatric cases of hemiballismic limb movements in the setting of ifosfamide-associated encephalopathy. To our knowledge, there have been no prior reports of ifosfamide-induced hemiballism in pediatric patients. One of our patient's encephalopathy and abnormal movements may have improved after the administration of methylene blue and thiamine.

Empiric antibiotics are justified for infants with respiratory syncytial virus lower respiratory tract infection presenting with respiratory failure: a prospective study and evidence review.

OBJECTIVE: Although some studies indicate a low risk of serious bacterial infection in infants with respiratory syncytial virus (RSV), these studies focused on patients who did not progress to respiratory failure. We hypothesized the composite diagnosis of concomitant bacterial pneumonia (CBP) is common in lower risk infants with RSV who present in respiratory failure. The aim of the study was to investigate the incidence of CBP in low-risk infants mechanically ventilated for RSV respiratory failure and to compare the results with other studies searched for in MEDLINE. DESIGN: Prospective, descriptive study, and literature review. Two MEDLINE searches were done using the terms 1) respiratory syncytial virus (RSV) and pneumonia, and 2) RSV, pneumonia, and antibiotics. SETTING: Tertiary pediatric intensive care unit (PICU) in the Northeast United States. PATIENTS: We prospectively enrolled 23 infants admitted to our PICU with RSV infection and respiratory failure over a 27-month period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All infants were intubated on arrival or soon thereafter; 22 had diagnostic tracheal aspiration performed, and 20 had blood cultures obtained shortly after admission. All had white blood cell count, temperature measured, and chest radiograph. Only one had antibiotics before culture. The length of mechanical ventilation, PICU course, and hospital stay were recorded.The primary outcome variable was the composite diagnosis of CBP as determined by the following criteria: 1) isolation of pathogenic bacteria from a tracheal aspirate, 2) blood culture, 3) chest radiograph, 4) temperature abnormality, and 5) peripheral white blood cell count. In our study, 7 infants met four criteria (probable pneumonia); 6 met three criteria (possible pneumonia); and 10 infants met less than three criteria. By tracheal aspirate criteria alone, 9 of 23 (39%) had probable pneumonia and 9 of 23 had possible pneumonia by previously published criteria. The mean length of mechanical ventilation for 7 infants who met four criteria was 10 +/- 2.7 (sem) days; for 6 infants who met three criteria, 10.5 +/- 2.1 days; and for infants who met less than three criteria 7.4 +/- 0.9 days. The mean PICU stay was 14.3 +/- 3.6 days for infants who met four criteria; 14.3 +/- 3.0 days for infants who met three criteria; and 9.9 +/- 1.4 days for infants who met less than three criteria. The mean hospital stay was 16.3 +/- 3.4 for infants who met four criteria; 18.7 +/- 2.8 days for infants who met three criteria; and 24.8 +/- 9.6 days for infants who met less than three criteria. These differences were not statistically significant. A MEDLINE search was performed using the terms 1) RSV and pneumonia, and 2) RSV, pneumonia, and antibiotics. CONCLUSIONS: While the small size of this study does not permit definitive conclusions, these data, in combination with other data from the literature, suggest that composite evidence of bacterial pneumonia in otherwise low-risk infants with RSV presenting with respiratory failure is 20% or higher and the use of empirical antibiotics for 24 to 48 hrs pending culture results may be justified and could be used until CBP is excluded.