Fluorescent-guided surgery and the use of indocyanine green sentinel lymph node mapping in the pediatric and young adult oncology population.

BACKGROUND: Technetium-99 (99m Tc) lymphoscintigraphy with blue dye injection is an accepted method for sentinel lymph node (SLN) mapping, but blue dye has known adverse effects, and injection of 99m Tc may increase time under anesthesia for pediatric patients. Indocyanine green (ICG) may serve as an adjunct to assist with visibility and identification of SLNs. We hypothesized that sensitivity of ICG was similar to blue dye in SLN biopsies. METHODS: Thirty patients (36 procedures with 96 total specimens) underwent preoperative intradermal injection of 99m Tc, followed by intradermal injection of isosulfan blue and ICG. Test characteristics of blue dye, ICG, and 99m Tc included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: ICG had a sensitivity of 87% and PPV of 83% for detection of 99m Tc-hot lymph nodes; blue dye had a sensitivity of 44% and PPV of 97%. For detection of pathologically confirmed lymph nodes, ICG had a sensitivity of 84% and a positive predictive value (PPV) of 91%. 99m Tc had a sensitivity of 82% and a PPV of 94%. ICG had no significant difference in odds of being positive in pathology-confirmed lymph nodes compared to 99m Tc (odds ratio [OR], 0.818; 95% confidence interval [CI], 0.3-2.172; p = .823) and had higher odds than isosulfan blue (OR, 0.025, 95% CI, 0.001-0.148; p < .001). CONCLUSION: This study established the efficacy of ICG as an adjunct to SLNB in the pediatric and young adult population. ICG was safe, more efficacious than blue dye, and may obviate the need for lymphoscintigraphy in selected patients resulting in reduced time under anesthesia.

Pediatric and Young Adult Image-Guided Percutaneous Bone Biopsy-A New Standard of Care?

BACKGROUND: There are no consensus guidelines regarding the use of percutaneous needle biopsy for the diagnosis of soft tissue and bone tumors. The aim of this study was to understand the efficacy of image-guided percutaneous biopsy for pediatric patients with soft tissue and bony masses, the role of intraoperative image guidance, and diagnostic accuracy. PATIENTS AND METHODS: A retrospective institutional chart review was performed on patients who underwent percutaneous biopsy of soft tissue or bone tumors between 2007 and 2017. Data collected included preoperative imaging, type of biopsy, demographics, insurance status, number of samples taken, and pathologic results. RESULTS: One hundred forty-one children and young adults underwent 169 biopsies. Female patients received 48.2% of biopsies. The mean age was 14.3 ± 7.0 years. Core needle biopsies made up 89.4% of procedures, while 10.6% were fine needle aspirate. The mean number of samples per patient was 3.6 ± 2.5. All patients had imaging guidance, with computed tomography used in 44.7% of patients, 9.9% using fluoroscopy, 7.1% using ultrasound for guidance, and 53 (37.6%) patients had more than one modality. Diagnostic specimens were obtained in 97.9% of biopsies. The most common overall pathology was osteoid osteoma. The most common malignant tumors were osteosarcoma and Ewing's sarcoma. CONCLUSION: Image-guided percutaneous biopsy is a safe and effective method of obtaining accurate tissue samples in children and young adults with soft tissue or bone masses. LEVEL OF EVIDENCE: Level 4-Study of diagnostic test.

Chemotherapy-induced thrombocytopenia in Ewing sarcoma: Implications and potential for romiplostim supportive care.

BACKGROUND: Maintaining dose-dense, interval-compressed chemotherapy improves survival in patients with Ewing sarcoma but is limited by myelosuppression. Romiplostim is a thrombopoietin receptor agonist that may be useful in the treatment of chemotherapy-induced thrombocytopenia (CIT). METHODS: Patients aged between 3 and 33 years with Ewing sarcoma from 2010 to 2020 were reviewed. CIT was defined as a failure to achieve 75,000 platelets per microliter by day 21 after the start of any chemotherapy cycle. Fisher's exact test was used for univariate analysis and Pearson's correlation coefficient was used for the association between continuous variables. RESULTS: Twenty-seven out of 42 patients (64%) developed isolated CIT, delaying one to four chemotherapy cycles per patient. CIT occurred during consolidation therapy in 24/27(88.9%) and with ifosfamide/etoposide cycles in 24/27 (88.9%). Univariate analysis failed to identify risk factors for CIT. The use of radiation approached significance (p-value = .056). Ten patients received romiplostim. The median starting dose was 3 µg/kg (range 1-5). Doses were escalated weekly by 1-2 to 4-10 µg/kg and continued throughout chemotherapy. A higher romiplostim dose was associated with a higher change in average platelet counts from baseline, r = .73 (p = .04). No romiplostim-related adverse events were identified aside from mild headache. CONCLUSIONS: CIT is the primary reason for the inability to maintain treatment intensity in Ewing sarcoma. The concurrent use of romiplostim with chemotherapy was safe and feasible, and efficacy was associated with higher romiplostim doses.

Long-term follow-up of surgical outcomes for patients with Wilms tumor and neuroblastoma.

BACKGROUND: There are minimal data on long-term surgical outcomes of patients who have undergone resection for Wilms tumor (WT) and neuroblastoma (NB). METHODS: A retrospective review of patients in a long-term survivor clinic between the years 1967 and 2016 in a pediatric tertiary care hospital (>5 years posttreatment) was performed. RESULTS: Eighty-six survivors of WT and 86 survivors of NB who had ongoing follow-up in the survivors' clinic were identified. The median age at diagnosis was 2.5 years (range, 0.4-15.7 years) with a mean follow-up of 22.3 years (±10.4 years) for WT. The median age at diagnosis for patients with NB was 0.9 years (range, 0.1-8.6 months); mean follow-up of 21.7 years (±7.9 years). Twelve patients with WT (14.0%) had at least 1 repeat laparotomy, 11.1% for bowel obstruction, at a median of 3 months from initial surgery. Twelve patients (14.0%) with NB required laparotomy and 8.1% for bowel obstruction, at a median of 12 years after initial surgery. The incidence of hypertension in patients with WT who had undergone nephrectomy was not outside of population norms. Patients who underwent thoracotomy for a NB have a higher incidence of scoliosis and Horner syndrome. CONCLUSIONS: Small bowel obstruction requiring laparotomy is significantly higher than the literature norms for both tumor patient populations and typically occurs in the early postoperative period for patients with WT and remotely in patients with NB. The long-term surgical complications of patients who underwent resection for NB and WT clearly merit follow-up and patient education within multidisciplinary long-term survivorship clinics.

Relationship Between Caregiver Uncertainty, Problem-Solving, and Psychological Adjustment in Pediatric Cancer.

OBJECTIVE: The current study examined the roles of constructive and dysfunctional problem-solving strategies in the relationships between illness uncertainty and adjustment outcomes (i.e., anxious, depressive, and posttraumatic stress symptoms) in caregivers of children newly diagnosed with cancer. METHODS: Two hundred thirty-eight caregivers of children (0-19 years of age) newly diagnosed with cancer (2-14 weeks since diagnosis) completed measures of illness uncertainty, problem-solving strategies, and symptoms of anxiety, depression, and posttraumatic stress. RESULTS: A mediation model path analysis assessed constructive and dysfunctional problem-solving strategies as mediators between illness uncertainty and caregiver anxious, depressive, and posttraumatic stress symptoms. Dysfunctional problem-solving scores partially mediated the relationships between illness uncertainty and anxious, depressive, and posttraumatic stress symptoms. Constructive problem-solving scores did not mediate these relationships. CONCLUSIONS: The current findings suggest that illness uncertainty and dysfunctional problem-solving strategies, but not constructive problem-solving strategies, may play a key role in the adjustment of caregivers of children newly diagnosed with cancer. Interventions aimed at managing illness uncertainty and mitigating the impact of dysfunctional problem-solving strategies may promote psychological adjustment.

The impact of proton therapy on cardiotoxicity following radiation treatment.

Cardiac disease following radiation therapy represents a major consideration in the treatment of a variety of malignancies. Damage to the heart can manifest in a variety of pathologies including ischemic cardiac disease, cardiomyopathy, valvular dysfunction, arrhythmias, and pericarditis. This damage has been shown to directly relate to cardiac radiation dose and to stem from a range of cellular pathways that are often related to fibrosis. The importance of minimizing radiation dose to the heart is especially critical in the pediatric population and when treating disease sites adjacent to the heart. Proton therapy represents a promising approach to minimize dose to normal tissues such as the heart. The cardiac dosimetry reductions due to proton therapy have been demonstrated in multiple cancers and further long-term follow-up will determine the clinical significance of these reductions to cardiac structures. Future approaches using advanced techniques such as FLASH therapy could provide even further benefit by reducing post-radiation fibrosis.

Can a children's hospital still cut it? Comparing outcomes of pediatric, adolescent and young adult patients undergoing thoracic surgery for lung metastases.

BACKGROUND: Adolescents and young adults (AYAs) with cancer have unique medical challenges compared with younger children and older adults. Dedicated centers have been established to deliver cancer therapy to the AYA population; many of these programs are located in pediatric hospitals. Outcomes of AYA patients on pediatric protocols are generally superior to those on adult protocols. Little is understood about the impact of care within a pediatric environment for surgical care of young adults. METHODS: A retrospective institutional review was performed of patients undergoing thoracic metastectomy between 2012 and 2017. Demographics, procedural factors, cost, and outcomes were analyzed. Patients were divided into two groups: > 18 and <18 years. RESULTS: Ninety-one procedures were performed: 61.5% (n = 56) were in patients <18 years old and 38.5% (n = 35) were > 18 years old. The median age was 6.5 years for <18 years old and 28 years for > 18 years old. Older patients had a significantly longer operative time on thoracoscopic cases; 91 versus 63 minutes. Fifty percent of the > 18 group had > 1 lesion resected compared with one lesion resected in 80.8% in <18 years old. No significant differences were found between the two groups in the duration of chest tube or length of stay. The AYA group demonstrated more "adult type" comorbidities. CONCLUSION: AYA patients have unique developmental and emotional challenges. Surgical intervention in this special population of patients cared for within a pediatric environment shows no significant difference in outcome compared with pediatric patients undergoing the same procedure. AYA patients with "adult type" comorbidities can safely undergo multidisciplinary care including surgery within a pediatric environment without the need to fragment care.

Solitary myofibroma preceding the development of multicentric myofibromatosis: A report of two cases with surveillance recommendations.

Infantile myofibroma is the most common fibrous tumor of infancy. Despite the frequency of these tumors, the natural history is incompletely understood. We present two cases with a unique pattern of disease: solitary myofibromas with subsequent progression to diffuse myofibromatosis. Given the variable spectrum of disease and the corresponding difference in morbidity and potential mortality based on the extent of disease, we propose surveillance recommendations.

Risk of solid subsequent malignant neoplasms after childhood Hodgkin lymphoma-Identification of high-risk populations to guide surveillance: A report from the Late Effects Study Group.

BACKGROUND: Survivors of Hodgkin lymphoma (HL) in childhood have an increased risk of subsequent malignant neoplasms (SMNs). Herein, the authors extended the follow-up of a previously reported Late Effects Study Group cohort and identified patients at highest risk for SMNs to create evidence for risk-based screening recommendations. METHODS: The standardized incidence ratio was calculated using rates from the Surveillance, Epidemiology, and End Results program as a reference. The risk of SMN was estimated using proportional subdistribution hazards regression. The cohort included 1136 patients who were diagnosed with HL before age 17 years between 1955 and 1986. The median length of follow-up was 26.6 years. RESULTS: In 162 patients, a total of 196 solid SMNs (sSMNs) were identified. Compared with the general population, the cohort was found to be at a 14-fold increased risk of developing an sSMN (95% confidence interval, 12.0-fold to 16.3-fold). The cumulative incidence of any sSMN was 26.4% at 40 years after a diagnosis of HL. Risk factors for breast cancer among females were an HL diagnosis between ages 10 years and 16 years and receipt of chest radiotherapy. Males treated with chest radiotherapy at age <10 years were found to be at highest risk of developing lung cancer. Survivors of HL who were treated with abdominal/pelvic radiotherapy and high-dose alkylating agents were found to be at highest risk of developing colorectal cancer and females exposed to neck radiotherapy at age <10 years were at highest risk of thyroid cancer. By age 50 years, the cumulative incidence of breast, lung, colorectal, and thyroid cancer was 45.3%, 4.2%, 9.5%, and 17.3%, respectively, among those at highest risk. CONCLUSIONS: Survivors of childhood HL remain at an increased risk of developing sSMNs. In the current study, subgroups of survivors of HL at highest risk of specific sSMNs were identified, and evidence for screening provided.

Sentinel lymph node biopsy in head and neck rhabdomyosarcoma.

Head and neck rhabdomyosarcoma lymph node staging is challenging due to varied patterns of lymphatic drainage and the suboptimal predictive value of available imaging modalities. Furthermore, regional relapse rates are unacceptably high, and the toxicity of empiric radiation is undesirable in the pediatric and young adult population. In an attempt to improve locoregional control without excess morbidity, we have adopted routine sentinel lymph node biopsy in head and neck rhabdomyosarcoma, which is safe and feasible in pediatric patients. Of six procedures reported here, pathologic findings led to intensification of regional and/or systemic therapy in two patients.