Long-term follow-up of patients with intermediate-risk neuroblastoma treated with response- and biology-based therapy: A report from the Children's Oncology Group study ANBL0531.

BACKGROUND: We previously reported excellent three-year overall survival (OS) for patients with newly diagnosed intermediate-risk neuroblastoma treated with a biology- and response-based algorithm on the Children's Oncology Group study ANBL0531. We now present the long-term follow-up results. METHODS: All patients who met the age, stage, and tumor biology criteria for intermediate-risk neuroblastoma were eligible. Treatment was based on prognostic biomarkers and overall response. Event-free survival (EFS) and OS were estimated by the Kaplan-Meier method. RESULTS: The 10-year EFS and OS for the entire study cohort (n = 404) were 82.0% (95% confidence interval (CI), 77.2%-86.9%) and 94.7% (95% CI, 91.8%-97.5%), respectively. International Neuroblastoma Staging System stage 4 patients (n = 133) had inferior OS compared with non-stage 4 patients (n = 271; 10-year OS: 90.8% [95% CI, 84.5%-97.0%] vs 96.6% [95% CI, 93.9%-99.4%], p = .02). Infants with stage 4 tumors with ≥1 unfavorable biological feature (n = 47) had inferior EFS compared with those with favorable biology (n = 61; 10-year EFS: 66.8% [95% CI, 50.4%-83.3%] vs 86.9% [95% CI, 76.0%-97.8%], p = .02); OS did not differ (10-year OS: 84.4% [95% CI, 71.8%-97.0%] vs 95.0% [95% CI, 87.7%-100.0%], p = .08). Inferior EFS but not OS was observed among patients with tumors with (n = 26) versus without (n = 314) 11q loss of heterozygosity (10-year EFS: 68.4% [95% CI, 44.5%-92.2%] vs 83.9% [95% CI, 78.7%-89.2%], p = .03; 10-year OS: 88.0% [95% CI, 72.0%-100.0%] vs 95.7% [95% CI, 92.8%-98.6%], p = .09). CONCLUSIONS: The ANBL0531 trial treatment algorithm resulted in excellent long-term survival. More effective treatments are needed for subsets of patients with unfavorable biology tumors.

Maintaining Outstanding Outcomes Using Response- and Biology-Based Therapy for Intermediate-Risk Neuroblastoma: A Report From the Children's Oncology Group Study ANBL0531.

PURPOSE: The primary objective of the Children's Oncology Group study ANBL0531 (ClinicalTrials.gov identifier: NCT00499616) was to reduce therapy for subsets of patients with intermediate-risk neuroblastoma using a biology- and response-based algorithm to assign treatment duration while maintaining a 3-year overall survival (OS) of 95% or more for the entire cohort. PATIENTS AND METHODS: Children younger than age 12 years with intermediate-risk stage 2A/2B or stage 3 tumors with favorable histology; infants younger than age 365 days with stage 3, 4 or 4S disease; and toddlers from 365 to younger than 547 days with favorable histology, hyperdiploid stage 4, or unfavorable histology stage 3 tumors were eligible. Patients with MYCN-amplified tumors were excluded. Patients were assigned to initially receive two (group 2), four (group 3), or eight (group 4) cycles of chemotherapy with or without surgery on the basis of prognostic markers, including allelic status of chromosomes 1p and 11q; ultimate duration of therapy was determined by overall response. RESULTS: Between 2007 and 2011, 404 evaluable patients were enrolled. Compared with legacy Children's Oncology Group studies, subsets of patients had a reduction in treatment. The 3-year event-free survival and OS rates were 83.2% (95% CI, 79.4% to 87.0%) and 94.9% (95% CI, 92.7% to 97.2%), respectively. Infants with stage 4 tumors with favorable biology (n = 61) had superior 3-year event-free survival compared with patients with one or more unfavorable biologic features (n = 47; 86.9% [95% CI, 78.3% to 95.4%] v 66.8% [95% CI, 53.1% to 80.6%]; P = .02), with a trend toward OS advantage (95.0% [95% CI, 89.5% to 100%] v 86.7% [95% CI, 76.6% to 96.7%], respectively; P = .08). OS for patients with localized disease was 100%. CONCLUSION: Excellent survival was achieved with this treatment algorithm, with reduction of therapy for subsets of patients. More-effective treatment strategies still are needed for infants with unfavorable biology stage 4 disease.

A Tri-Institutional Approach to Address Disparities in Children's Oncology Group Clinical Trial Accrual for Adolescents and Young Adults and Underrepresented Minorities.

Purpose: Enrollment in Children's Oncology Group (COG) clinical trials has led to significant improvements in survival; however, disparities in survival persist, particularly among ethnic minorities, adolescents and young adults (AYAs), and the underinsured, partly due to inadequate access to cooperative group cancer clinical trials. In 2008, two COG sites University of Illinois at Chicago (UIC) and Rush University Medical Center, and a nonmember institution, John H Stroger Hospital, created a unified COG program utilizing one lead Institutional Review Board and research team. This study assesses the impact that the tri-institutional COG program had on clinical trial accrual for minority, AYA, and uninsured patients. Methods: Analysis and comparison of COG enrollment data from 2002 to 2008 (pre-merger) and 2008 to 2017 (post-merger) by age, ethnicity, insurance type, clinical trial type, oncologic diagnosis, and specialty of the enrolling physician were completed. Results: Following the merger, the total studies open to enrollment increased by 100%, enrollments increased by 446%, and, for each diagnoses, increased by more than 200%. Enrollment of ethnic minorities rose by 533%, most significantly for Hispanic patients by 925%. AYA enrollments increased by 822%. There was a 28-fold increase in enrollment of uninsured patients. Significantly more providers from various oncology specialties were engaged in enrolling patients and a consistent increase in the percentile standing of the program occurred after the merger. Conclusions: Creation of a tri-institutional COG research program was associated with significant increases in clinical trial enrollments, especially for underrepresented minorities, AYAs, and uninsured patients. The UIC/Rush/Stroger COG Program provides a novel and exemplary approach to address cancer health disparities for these vulnerable populations.

Defining Risk Factors for Chemotherapeutic Intervention in Infants With Stage 4S Neuroblastoma: A Report From Children's Oncology Group Study ANBL0531.

PURPOSE: Infants with stage 4S neuroblastoma usually have favorable outcomes with observation or minimal chemotherapy. However, young infants with symptoms secondary to massive hepatomegaly or with unfavorable tumor biology are at high risk of death. Our aim was to improve outcomes for patients with symptomatic and/or unfavorable biology 4S neuroblastoma with a uniform treatment approach using a biology- and response-based algorithm. PATIENTS AND METHODS: The subset of patients with 4S disease with MYCN-not amplified tumors with impaired or impending organ dysfunction, or with unfavorable histology and/or diploid DNA index, were eligible. Patients were assigned to receive two, four, or eight cycles of chemotherapy on the basis of histology, diploid DNA index, chromosome arm 1p or 11q loss of heterozygosity (LOH) status, and symptoms. RESULTS: Forty-nine eligible patients were enrolled: 41 were symptomatic and 28 had unfavorable biology. Seventeen patients (symptomatic, favorable biology) were assigned two cycles, 21 patients (any unfavorable biologic feature without 1p or 11q LOH) were assigned four cycles, and 11 patients (unfavorable biology including 1p and/or 11q LOH [n = 7] or symptomatic with unknown biology [n = 4]), were assigned eight cycles. The 3-year overall survival was 81.4% ± 5.8%. Eight of nine deaths were in patients younger than 2 months of age at diagnosis (median, 9 days [range, 1 to 68 days]): five acute deaths were a result of hepatomegaly and associated toxicities; two were a result of late relapse in patients with unfavorable biology; and two were a result of treatment complications. No deaths occurred after protocol-mandated pre-emptive treatment of infants younger than 2 months with hepatomegaly, regardless of symptoms. A new scoring algorithm for emergent chemotherapy in patients with 4S disease was developed on the basis of this experience. CONCLUSION: The outcome for 4S neuroblastoma can be improved with pre-emptive chemotherapy for evolving hepatomegaly or other baseline comorbidities in infants younger than 2 months of age.

Exploring intentions of physician-scientist trainees: factors influencing MD and MD/PhD interest in research careers.

BACKGROUND: Prior studies have described the career paths of physician-scientist candidates after graduation, but the factors that influence career choices at the candidate stage remain unclear. Additionally, previous work has focused on MD/PhDs, despite many physician-scientists being MDs. This study sought to identify career sector intentions, important factors in career selection, and experienced and predicted obstacles to career success that influence the career choices of MD candidates, MD candidates with research-intense career intentions (MD-RI), and MD/PhD candidates. METHODS: A 70-question survey was administered to students at 5 academic medical centers with Medical Scientist Training Programs (MSTPs) and Clinical and Translational Science Awards (CTSA) from the NIH. Data were analyzed using bivariate or multivariate analyses. RESULTS: More MD/PhD and MD-RI candidates anticipated or had experienced obstacles related to balancing academic and family responsibilities and to balancing clinical, research, and education responsibilities, whereas more MD candidates indicated experienced and predicted obstacles related to loan repayment. MD/PhD candidates expressed higher interest in basic and translational research compared to MD-RI candidates, who indicated more interest in clinical research. Overall, MD-RI candidates displayed a profile distinct from both MD/PhD and MD candidates. CONCLUSIONS: MD/PhD and MD-RI candidates experience obstacles that influence their intentions to pursue academic medical careers from the earliest training stage, obstacles which differ from those of their MD peers. The differences between the aspirations of and challenges facing MD, MD-RI and MD/PhD candidates present opportunities for training programs to target curricula and support services to ensure the career development of successful physician-scientists.

Chemotherapy in Children with Head and Neck Cancers: Perspectives and Review of Current Therapies.

Cancers of the head and neck in children represent a heterogeneous group of malignancies requiring a variety of treatment modalities. In many instances of childhood head and neck cancers, chemotherapy will be required for treatment, often in conjunction with surgery and/or radiation therapy. Chemotherapy in children with head and neck cancers poses unique challenges in terms of immediate as well as long-term toxicities. This article focuses on the common chemotherapeutic agents, with a particular focus on early and late effects, used in the treatment of children with head and neck cancers.

A unique description of stage IV extranodal marginal zone lymphoma (EMZL) in an adolescent associated with gamma heavy chain disease.

Extranodal Marginal zone lymphoma (EMZL) is a rare, usually localized disease in children. Advanced stage EMZL in adults is considered incurable, with prolonged remissions after chemotherapy. Gamma heavy chain disease (γHCD) is a rare disease of adults associated with lympho-proliferative processes with no comparable reports in children. A case of stage-IV EMZL with γHCD in an adolescent is discussed including treatment with Bendamustine plus Rituximab. The patient remains disease free 18 months from diagnosis. This case highlights necessity for careful diagnostic work-up to identify indolent lymphomas in children which may respond to less toxic chemotherapy than used for common pediatric lymphomas.

Health behaviors of minority childhood cancer survivors.

BACKGROUND: Available data have suggested that childhood cancer survivors (CCSs) are comparable to the general population with regard to many lifestyle parameters. However, to the authors' knowledge, little is known regarding minority CCSs. This cross-sectional study describes and compares the body mass index and health behaviors of African American, Hispanic, and white survivors with each other and with noncancer controls. METHODS: Participants included 452 adult CCSs (150 African American, 152 Hispanic, and 150 white individuals) recruited through 4 childhood cancer treating institutions and 375 ethnically matched noncancer controls (125 in each racial/ethnic group) recruited via targeted digit dial. All participants completed a 2-hour in-person interview. RESULTS: Survivors and noncancer controls reported similar health behaviors. Within survivors, smoking and physical activity were found to be similar across racial/ethnic groups. African American and Hispanic survivors reported lower daily alcohol use compared with white individuals, but consumed unhealthy diets and were more likely to be obese. CONCLUSIONS: This unique study highlights that many minority CCSs exhibit lifestyle profiles that contribute to an increased risk of chronic diseases and late effects. Recommendations for behavior changes must consider the social and cultural context in which minority survivors may live.

Electronic Personal Health Records for Childhood Cancer Survivors: An Exploratory Study.

Purpose: Childhood cancer survivors have complex healthcare needs that may be effectively communicated using electronic personal health records. This study explores the knowledge, interest, and attitudes of a sample of survivors and some of their caregivers towards electronic personal health records (ePHRs). Methods: This descriptive study was conducted in a pediatric hematology-oncology clinic and associated survivorship clinic with a convenience sample of caregivers of survivors who were <14 years old and survivors ≥14 years old along with their caregivers when present. A semi-structured interview was conducted with survivors and some caregivers to understand their knowledge, interest, and attitudes towards adoption of ePHRs. Results: Interviews were completed with 11 caregivers of young survivors, four survivors alone, and five survivor-caregiver dyads. Survivors ranged in age at diagnosis from 1 to 17 years old. Among the ethnically diverse sample, approximately half of the nine survivors and 25% of 16 caregivers reported having some knowledge of ePHRs. Eighty-nine percent (8/9) of the survivors and 81% (13/16) of the caregivers reported that they were somewhat or very comfortable using the internet. All nine survivors and 75% of caregivers were interested in the adoption of ePHRs. Data security and privacy were the primary concerns expressed. Conclusions: Interest in adoption of ePHRs to manage cancer survivorship-related health information was high. Most felt that the privacy and security concerns would not prevent adoption. Additional research is needed on larger and more representative samples of survivors to understand what types of support and education are needed to effectively implement ePHRs.

Ototoxicity in children with high-risk neuroblastoma: prevalence, risk factors, and concordance of grading scales--a report from the Children's Oncology Group.

PURPOSE: Platinum-based therapy is the mainstay for management of high-risk neuroblastoma. Prevalence of platinum-related ototoxicity has ranged from 13% to 95% in previous reports; variability is attributable to small samples and disparate grading scales. There is no consensus regarding optimal ototoxicity grading. Furthermore, prevalence and predictors of hearing loss in a large uniformly treated high-risk neuroblastoma population are unknown. We address these gaps in our study. PATIENTS AND METHODS: Audiologic testing was completed after administration of cisplatin alone (< 400 mg/m(2); exposure one) or after cisplatin (400 mg/m(2)) plus carboplatin (1,700 mg/m(2); exposure two). Hearing loss was graded using four scales (American Speech-Language-Hearing Association; Brock; Chang; and Common Terminology Criteria for Adverse Events, version 3 [CTCAEv3]). RESULTS: Of 489 eligible patients, 333 had evaluable audiologic data. Median age at diagnosis was 3.3 years. Prevalence of severe hearing loss differed by scale. For those in the exposure-one group, prevalence ranged from 8% per Brock to 47% per CTCAEv3 (Brock v CTCAEv3 and Chang, P < .01; CTCAEv3 v Chang, P = .16); for those in the exposure-two group, prevalence ranged from 30% per Brock to 71% per CTCAEv3 (all pair-wise comparisons, P < .01). In patients requiring hearing aids, hearing loss was graded as severe in 49% (Brock), 91% (Chang), and 100% (CTCAEv3). Risk factors for severe hearing loss included exposure to cisplatin and carboplatin compared with cisplatin alone and hospitalization for infection. CONCLUSION: Severe hearing loss is prevalent among children with high-risk neuroblastoma. Exposure to cisplatin combined with myeloablative carboplatin significantly increases risk. The Brock scale underestimates severe hearing loss and should be used with caution in this setting.

Discordant parent reports of family functioning following childhood neuroblastoma: a report from the children's oncology group.

This study examined whether late effects and poor survivor quality of life (QOL) characterize discordant parent dyads and "unhealthy" family functioning in neuroblastoma survivors. Parents of 135 neuroblastoma survivors (78 two-parent dyads) completed measures of late effects and family functioning, and survivors completed the Pediatric Quality of Life Inventory 4.0 (PedsQL). Although average family functioning scores were "healthy," parent concordance was lower for family functioning than late effects reports. Parent concordance did not differ by late effects or QOL. Family functioning scores were poorer when survivors had more late effects and low physical QOL scores. Parent data should be considered separately when examining child cancer outcomes.

A prospective study of expectant observation as primary therapy for neuroblastoma in young infants: a Children's Oncology Group study.

OBJECTIVE: To demonstrate that expectant observation of young infants with small adrenal masses would result in excellent event-free and overall survival. BACKGROUND: Neuroblastoma is the most common malignant tumor in infants, and in young infants, 90% of neuroblastomas are located in the adrenal gland. Although surgical resection is standard therapy, multiple observations suggest that expectant observation could be a safe alternative for infants younger than 6 months who have small adrenal masses. METHODS: A prospective study of infants younger than 6 months with small adrenal masses and no evidence of spreading beyond the primary tumor was performed at participating Children's Oncology Group institutions. Parents could choose observation or immediate surgical resection. Serial abdominal sonograms and urinary vanillylmandelic acid and homovanillic acid measurements were performed during a 90-week interval. Infants experiencing a 50% increase in the volume of the mass, urine catecholamine values, or an increase in the homovanillic acid to vanillylmandelic acid ratio greater than 2, were referred for surgical resection. RESULTS: Eighty-seven eligible patients were enrolled: 83 elected observation and 4 chose immediate surgery. Sixteen observational patients ultimately had surgery; 8 had International Neuroblastoma Staging System stage 1 neuroblastoma, 2 had higher staged neuroblastoma (2B and 4S), 2 had low-grade adrenocortical neoplasm, 2 had adrenal hemorrhage, and 2 had extralobar pulmonary sequestration. The 2 patients with adrenocortical tumors were resected because of a more than 50% increase in tumor volume. The 3-year event-free survival for a neuroblastoma event was 97.7 ± 2.2% within the entire cohort of patients (n = 87). The 3-year overall survival was 100%, with a median follow-up of 3.2 years. Eighty-one percent of patients on the observation arm were spared resection. CONCLUSIONS: Expectant observation of infants younger than 6 months with small adrenal masses led to excellent event-free survival and overall survival while avoiding surgical intervention in a large majority of the patients.

Outcome after surgery alone or with restricted use of chemotherapy for patients with low-risk neuroblastoma: results of Children's Oncology Group study P9641.

PURPOSE: The primary objective of Children's Oncology Group study P9641 was to demonstrate that surgery alone would achieve 3-year overall survival (OS) ≥ 95% for patients with asymptomatic International Neuroblastoma Staging System stages 2a and 2b neuroblastoma (NBL). Secondary objectives focused on other low-risk patients with NBL and on those who required chemotherapy according to protocol-defined criteria. PATIENTS AND METHODS: Patients underwent maximally safe resection of tumor. Chemotherapy was reserved for patients with, or at risk for, symptomatic disease, with less than 50% tumor resection at diagnosis, or with unresectable progressive disease after surgery alone. RESULTS: For all 915 eligible patients, 5-year event-free survival (EFS) and OS were 89% ± 1% and 97% ± 1%, respectively. For patients with asymptomatic stage 2a or 2b disease, 5-year EFS and OS were 87% ± 2% and 96% ± 1%, respectively. Among patients with stage 2b disease, EFS and OS were significantly lower for those with unfavorable histology or diploid tumors, and OS was significantly lower for those ≥ 18 months old. For patients with stage 1 and 4s NBL, 5-year OS rates were 99% ± 1% and 91% ± 1%, respectively. Patients who required chemotherapy at diagnosis achieved 5-year OS of 98% ± 1%. Of all patients observed after surgery, 11.1% experienced recurrence or progression of disease. CONCLUSION: Excellent survival rates can be achieved in asymptomatic low-risk patients with stages 2a and 2b NBL after surgery alone. Immediate use of chemotherapy may be restricted to a minority of patients with low-risk NBL. Patients with stage 2b disease who are older or have diploid or unfavorable histology tumors fare less well. Future studies will seek to refine risk classification.

Prognostic value of the stage 4S metastatic pattern and tumor biology in patients with metastatic neuroblastoma diagnosed between birth and 18 months of age.

PURPOSE: Patients with neuroblastoma younger than 12 months of age with a 4S pattern of disease (metastases limited to liver, skin, bone marrow) have better outcomes than infants with stage 4 disease. The new International Neuroblastoma Risk Group (INRG) staging system extends age to 18 months for the 4S pattern. Our aim was to determine which prognostic features could be used for optimal risk classification among patients younger than 18 months with metastatic disease. METHODS: Event-free survival (EFS) and overall survival were analyzed by log-rank tests, Cox models, and survival tree regression for 656 infants with stage 4S neuroblastoma younger than 12 months of age and 1,019 patients with stage 4 disease younger than 18 months of age in the INRG database. RESULTS: Unfavorable biologic features were more frequent in infants with stage 4 disease than in infants with 4S tumors and higher overall in those age 12 to 18 months (although not different for stage 4 v 4S pattern). EFS was significantly better for infants younger than 12 months with 4S pattern than with stage 4 disease (P < .01) but similar for toddlers age 12 to 18 months with stage 4 versus 4S pattern. Among 717 patients with stage 4S pattern, patients age 12 to 18 months had worse EFS than those age younger than 12 months (P < .01). MYCN, 11q, mitosis-karyorrhexis index (MKI), ploidy, and lactate dehydrogenase were independently statistically significant predictors of EFS and more highly predictive than age or metastatic pattern. MYCN, 11q, MKI, histology, and 1p were combined in a survival tree for improved risk stratification. CONCLUSION: Tumor biology is more critical than age or metastatic pattern for prognosis of patients age younger than 18 months with metastatic neuroblastoma and should be considered for risk stratification.

Conjunctival marginal zone b-cell lymphoma in a 13-year-old child.

Ocular adnexal lymphoma is a hematopoietic tumor that arises in the conjunctiva, orbit, eyelid, lacrimal gland, or lacrimal sac. The treatment options in children have not been addressed in the literature. The authors describe a 13-year-old child with ocular adnexal lymphoma and discuss the treatment options.

Medical radiation exposure and risk of retinoblastoma resulting from new germline RB1 mutation.

Although ionizing radiation induces germline mutations in animals, human studies of radiation-exposed populations have not detected an effect. We conducted a case-control study of sporadic bilateral retinoblastoma, which results from a new germline RB1 mutation, to investigate gonadal radiation exposure of parents from medical sources before their child's conception. Parents of 206 cases from nine North American institutions and 269 controls participated; fathers of 184 cases and 223 friend and relative controls and mothers of 204 cases and 260 controls provided information in telephone interviews on their medical radiation exposure. Cases provided DNA for RB1 mutation testing. Of common procedures, lower gastrointestinal (GI) series conferred the highest estimated dose to testes and ovaries. Paternal history of lower GI series was associated with increased risk of retinoblastoma in the child [matched odds ratio (OR) = 3.6, 95% confidence interval (CI) = 1.2-11.2, two-sided p = 0.02], as was estimated total testicular dose from all procedures combined (OR for highest dose=3.9, 95% CI = 1.2-14.4, p = 0.02). Maternal history of lower GI series was also associated with increased risk (OR = 7.6, 95% CI = 2.8-20.7, p < 0.001) as was the estimated total dose (OR for highest dose = 3.0, 95% CI = 1.4-7.0, p = 0.005). The RB1 mutation spectrum in cases of exposed parents did not differ from that of other cases. Some animal and human data support our findings of an association of gonadal radiation exposure in men and women with new germline RB1 mutation detectable in their children, although bias, confounding, and/or chance may also explain the results.

Control of disseminated intravascular coagulation in Klippel-Trenaunay-Weber syndrome using enoxaparin and recombinant activated factor VIIa: a case report.

INTRODUCTION: Vascular malformation is associated with coagulopathies, especially when hemostasis is challenged. CASE PRESENTATION: We present the case of an 11-year-old Hispanic girl with Klippel-Trenaunay-Weber syndrome that developed disseminated intravascular coagulation after minor surgery, which was controlled by blood product transfusions and enoxaparin to address an ongoing consumptive coagulopathy. The patient, however, developed bacteremia and liver trauma that resulted in severe bleeding. To the best of our knowledge, we report here the first known instance of administering recombinant coagulation factor VIIa to control acute bleeding in a patient with Klippel-Trenaunay-Weber syndrome. CONCLUSIONS: This case illustrates the concept of enoxaparin maintenance to suppress an ongoing consumptive coagulopathy and the use of recombinant coagulation factor VIIa to control its potentially fatal severe bleeding episodes.

Online ethics discussion forum facilitates medical center clinical ethics case reviews.

Clinical ethics consultants are increasingly called upon to give counsel in the clinical arena on issues including but not limited to withdrawal or withholding of specific medical treatments, assisting minors and mentally impaired patients with care decisions, working with difficult patients and families, identifying appropriate surrogate decision makers, and executing advance directives and end-of-life decisions. Often, the consultant may need to convene the ethics committee members to review and provide feedback for a given case. This process may be difficult to schedule in a timely way because of member's clinical and other work-related obligations. To this end, the University of Illinois Medical Center in Chicago has set up a unique Web board to facilitate ongoing case discussions via a secured, password-protected ethics committee online forum. This allows for real-time review by all ethics committee members. We will explain our online process as well as discuss our clinical case experiences.