Pain mitigation and management strategies for anti-GD2 infusions: An expert consensus.

Monoclonal antibodies (mAbs) targeting disialoganglioside 2 (GD2) are an important treatment advance for high-risk neuroblastoma, including in patients with refractory or relapsed disease. Dinutuximab and dinutuximab beta are administered for ≥8 hours (and up to 10 days for dinutuximab beta), whereas naxitamab is administered over 0.5 to 2 hours as tolerated. As acute pain is a class effect of anti-GD2 mAbs, effective pain management is crucial to successful treatment. Here, we provide an overview of current pain-management strategies for anti-GD2 mAb infusions, with a focus on strategies suitable for naxitamab infusions, which cause a more rapid onset of often severe pain. We discuss opioid analgesics, ketamine, gabapentin, and other similar agents and nonpharmacologic approaches. Potential future pain-management options are also discussed, in addition to the use of sedatives to reduce the anxiety that may be associated with infusion-related pain. In this expert consensus paper, specific guidance for pain management during naxitamab infusions is provided, as these infusions are administered over 0.5 to 2 hours and may not need overnight hospitalization based on the physician's assessment, and require rapid-onset analgesia options suitable for potential outpatient administration.

Stent-Graft Placement for Radiation-Induced Abdominal Aortic Stenosis after Renal Autotransplantation.

Renovascular hypertension (RVH) is a common cause of secondary hypertension. However, there have been no reports on RVH due to radiation-induced abdominal aorta stenosis after renal autotransplantation. A 27-year-old woman with a history of neuroblastoma treated by radiation therapy and RVH treated with renal autotransplantation presented with hypertension and dyspnea. At age 19, she had experienced hypertensive heart failure due to RVH from radiation-induced left renal artery stenosis and had undergone renal autotransplantation involving the extraction of her left kidney. Her systolic blood pressure (BP) was well-controlled but had increased progressively. She was diagnosed with hypertensive heart failure and admitted to hospital. Although her dyspnea soon subsided after treatment, her BP remained high. Renal artery ultrasound revealed no obvious stenosis. The ankle brachial pressure index (ABI) showed a significant bilateral decrease to 0.71/0.71 (right/left) from 0.94/0.95 eight years before. Magnetic resonance angiography and aortic angiography revealed severe stenosis in the abdominal aorta, and the systolic pressure gradient of intra-aortic blood flow, distal and proximal to a stenotic lesion, was 58 mmHg. These arterial stenoses in the irradiated area were highly suggestive of radiation-induced vasculopathy. She finally underwent an endovascular VIABAHN VBX balloon-expandable stent-graft placement for this radiation-induced abdominal aorta stenosis, which resolved the pressure gradient. After the procedure, her ABI improved to 0.91/0.88 and her BP was well-controlled. This is the first case of successful stent-graft placement for RVH after renal autotransplantation due to radiation-induced abdominal aorta stenosis as a consequence of neuroblastoma.

Early-phase clinical trial eligibility and response evaluation criteria for refractory, relapsed, or progressive neuroblastoma: A consensus statement from the National Cancer Institute Clinical Trials Planning Meeting.

BACKGROUND: International standardized criteria for eligibility, evaluable disease sites, and disease response assessment in patients with refractory, progressive, or relapsed high-risk neuroblastoma enrolled in early-phase clinical trials are lacking. METHODS: A National Cancer Institute-sponsored Clinical Trials Planning Meeting was convened to develop an international consensus to refine the tumor site eligibility criteria and evaluation of disease response for early-phase clinical trials in children with high-risk neuroblastoma. RESULTS: Standardized data collection of patient and disease characteristics (including specified genomic data), eligibility criteria, a definition of evaluable disease, and response evaluations for primary and metastatic sites of disease were developed. Eligibility included two distinct patient groups: progressive disease and refractory disease. The refractory disease group was subdivided into responding persistent disease and stable persistent disease to better capture the clinical heterogeneity of refractory neuroblastoma. Requirements for defining disease evaluable for a response assessment were provided; they included requirements for biopsy to confirm viable neuroblastoma and/or ganglioneuroblastoma in those patients with soft tissue or bone disease not avid for iodine-123 meta-iodobenzylguanidine. Standardized evaluations for response components and time intervals for response evaluations were established. CONCLUSIONS: The use of international consensus eligibility, evaluability, and response criteria for early-phase clinical studies will facilitate the collection of comparable data across international trials and promote more rapid identification of effective treatment regimens for high-risk neuroblastoma.

Very long-term molecular follow-up of minimal residual disease in patients with neuroblastoma.

In high-risk neuroblastoma (HR-NB), the clinical significance of long-term minimal residual disease (MRD) monitoring using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for neuroblastoma mRNAs has not been investigated. We report long-term MRD follow-ups of four patients with HR-NB throughout the disease (diagnosis, remission, and relapse) and treatment course (chemotherapy, autologous and allogeneic stem cell transplantation, and donor lymphocyte and natural killer cell infusions). The results showed the stability of mRNA marker expression after different treatments and demonstrated their validity to predict relapse and assess therapeutic response. This opens up the possibility of investigating the utility of long-term molecular monitoring of MRD in prospective multicenter studies.

Fetal neck tumors - antenatal and intrapartum management.

In this review article we describe the ante- and perinatal management of fetal neck tumors. Although there are rare congenital anomalies, the clinical consequences for the fetus may be fatal and include airways obstruction, heart insufficiency, pulmonary hypoplasia and cosmetic effect. The right management allows to decrease the fetal and neonatal mortality and morbidity associated with the disease. It includes intrauterine therapy in some cases, mostly in a goitrus hypothyroidism of the fetus, but firstly, an assessment of the fetal airways patency with a subsequent, eventual Ex-Utero Intrapartum Treatment (EXIT).

Surgical treatment of pediatric retroperitoneal tumors with invasion of major blood vessels: a single-center experience.

BACKGROUND: This study assessed operative experiences with common pediatric retroperitoneal tumors invading major blood vessels. METHODS: Forty-seven pediatric patients with retroperitoneal tumors were enrolled. They included 22 neuroblastomas, 6 gangliocytomas and 19 Wilms' tumors, and underwent primary surgical resection after vascular skeletonization and manipulations of involved vessels. RESULTS: In the above tumors, the one-stage gross total resection rates of, respectively, 95.45%, 100% and 100% were obtained. There was only one complication, namely post-operational early acute renal failure that recovered with dialysis. There were no deaths. CONCLUSIONS: Vascular skeletonization and other vessel manipulations prior to surgery improve the gross total resection rates of pediatric retroperitoneal tumors.

Long-term efficacy of current thyroid prophylaxis and future perspectives on thyroid protection during 131I-metaiodobenzylguanidine treatment in children with neuroblastoma.

PURPOSE: Treatment with (131)I-MIBG is associated with significant thyroid damage. This study was undertaken to investigate the long-term efficacy of current thyroid prophylaxis, to explore the relationship between thyroid dysfunction and thyroid volume after exposure to (131)I-MIBG and to evaluate the possible negative effects of (131)I(-) on the parathyroid glands. METHODS: Of 81 long-term surviving patients with neuroblastoma treated with (131)I-MIBG during the period 1999-2012, 24 were finally evaluated. Patients received thyroxine (T4), methimazole and potassium iodide as thyroid protection. In all patients (para)thyroid function was evaluated and ultrasound investigation of the (para)thyroid gland(s) was performed. Thyroid dysfunction was defined as a plasma thyrotropin concentration >5.0 mU/L (thyrotropin elevation, TE) or as the use of T4 at the time of follow-up. Hyperparathyroidism was defined as a serum calcium concentration above the age-related reference range in combination with an inappropriately high parathyroid hormone level. RESULTS: At a median follow-up of 9.0 years after (131)I-MIBG treatment, thyroid disorders were seen in 12 patients (50 %; 9 with TE, 5 with a thyroid nodule and 1 patient was subsequently diagnosed with differentiated thyroid carcinoma). No significant risk factors for the occurrence of thyroid damage could be identified. In 14 of 21 patients (67 %) in whom thyroid volume could be determined, the volume was considered small (<-2SD) for age and gender. Patients treated with T4 at the time of follow-up had significantly smaller thyroid volumes for age than patients without T4 treatment (p = 0.014). None of the patients was diagnosed with hyperparathyroidism. CONCLUSION: Thyroid protection during treatment with (131)I-MIBG needs attention and must be further improved, as thyroid disorders are still frequently seen despite current thyroid prophylaxis. Reduced thyroid volume in neuroblastoma survivors may be related to previous (131)I-MIBG therapy or current T4 treatment. No deleterious effects of (131)I-MIBG on the parathyroid glands could be found.

Irinotecan and temozolomide for treatment of neuroblastoma in a patient with renal failure on hemodialysis.

Renal failure is a rare complication of neuroblastoma or its therapy. To our knowledge, no reports describe treatment of children with neuroblastoma with chemotherapy in the setting of renal failure and maintenance hemodialysis. We report a 6-year-old child with high-risk neuroblastoma who developed renal failure requiring long-term hemodialysis. She was subsequently treated with 13 cycles of intravenous irinotecan 20 mg/m(2)/day and oral temozolomide 100 mg/m(2)/day for 5 days before disease progression without any dose adjustments, transfusions, febrile neutropenia or diarrhea. This case demonstrates that irinotecan and temozolomide can be safely administered in children with renal failure requiring hemodialysis.

[Perioperative treatment of a patient with abdominal compartment syndrome due to neuroblastoma and hepatomegaly].

A male infant developed abdominal compartment syndrome (ACS) due to stage-4S neuroblastoma and hepatic enlargement. Because of tumor lysis syndrome by chemotherapy and radiationtherapy, his condition deteriorated and he underwent emergent abdominal counterincision surgical operation in the intensive care unit. General anesthesia was maintained with O2 (100%), midazolam (0.25-0.3 mg x kg(-1) x hr(-1)), fentanyl, and rocuronium infusion. By removal of the ACS, the breathing improved. At the end of the operation, we inserted GamCath catheter from his internal jugular vein for CHDF performed after the operation. We used midazolam, fentanyl and rocuronium for sedation. Subsequently, 8 days later, his general condition markedly improved, and we could evade performing CHDF.

Forearm skeletal muscle neuroblastoma in a child: a rare primary location.

Neuroblastoma is the most common neoplasm in the first year of life and almost always arises from the adrenal glands or the sympathetic nervous system chain. We present an original case of an isolated forearm neuroblastoma in a 17-month-old child. The case was not treated with adjuvant chemotherapy after surgical resection because we interpreted it as a peripheral, INSS-stage 1, favorable histology neuroblastoma. Up to date the child remains in complete remission 4 years after diagnosis. Management of peripheral skeletal muscle neuroblastoma is discussed together with a review of the literature.

Hospitalizations in Australian children with neuroblastoma: A population-based study.

BACKGROUND: An increasing number of children diagnosed with both low- and high-risk neuroblastoma are surviving. Yet, treatment can be intensive and often multimodal, especially for high-risk neuroblastoma, resulting in significant long-term health problems. We aimed to describe neuroblastoma survivors' pediatric hospitalizations, readmissions, and their associated costs. METHOD: We conducted a population-based study of all children (<18 years) residing in New South Wales (NSW), Australia, and hospitalized with a recorded diagnosis of neuroblastoma during 2001-2020. We used linked NSW Admitted Patient Data Collection and death registration data to examine the frequency, length of stay, and readmissions following the first admission when neuroblastoma was diagnosed (i.e., the index admission), and the associated hospitalization costs by age and timing postindex admission discharge. RESULTS: In total, 300 children (64% aged <3 years) were hospitalized for neuroblastoma over the study period. The median number of readmissions and length of stay within 2 years postdischarge were 17 (interquartile range IQR: 5.5-25) and 45.5 (IQR: 10-125) days, and median cost per child was AUD$124,058 (IQR $34,217-$264,627). Following discharge from the index admission, there were 7088 readmissions (median: 20 per child, IQR: 7-29). Fifty-eight percent of readmissions occurred within 1-year postdischarge, primarily due to fever, nausea, abdominal pain, and respiratory conditions. CONCLUSION: The burden of health problems requiring hospitalization among neuroblastoma survivors results in significant associated healthcare costs, warranting further efforts to optimize health care for neuroblastoma survivors that focuses on early intervention and long-term monitoring.

The Role of Ketogenic Diet in the Treatment of Neuroblastoma.

The ketogenic diet (KD) was initially used in 1920 for drug-resistant epileptic patients. From this point onward, ketogenic diets became a pivotal part of nutritional therapy research. To date, KD has shown therapeutic potential in many pathologies such as Alzheimer's disease, Parkinson's disease, autism, brain cancers, and multiple sclerosis. Although KD is now an adjuvant therapy for certain diseases, its effectiveness as an antitumor nutritional therapy is still an ongoing debate, especially in Neuroblastoma. Neuroblastoma is the most common extra-cranial solid tumor in children and is metastatic at initial presentation in more than half of the cases. Although Neuroblastoma can be managed by surgery, chemotherapy, immunotherapy, and radiotherapy, its 5-year survival rate in children remains below 40%. Earlier studies have proposed the ketogenic diet as a possible adjuvant therapy for patients undergoing treatment for Neuroblastoma. In this study, we seek to review the possible roles of KD in the treatment of Neuroblastoma.

Application of a tungsten apron for occupational radiation exposure in nursing care of children with neuroblastoma during 131I-meta-iodo-benzyl-guanidine therapy.

The use of effective shielding materials against radiation is important among medical staff in nuclear medicine. Hence, the current study investigated the shielding effects of a commercially available tungsten apron using gamma ray measuring instruments. Further, the occupational radiation exposure of nurses during 131I-meta-iodo-benzyl-guanidine (131I-MIBG) therapy for children with high-risk neuroblastoma was evaluated. Attachable tungsten shields in commercial tungsten aprons were set on a surface-ray source with 131I, which emit gamma rays. The mean shielding rate value was 0.1 ± 0.006 for 131I. The shielding effects of tungsten and lead aprons were evaluated using a scintillation detector. The shielding effect rates of lead and tungsten aprons against 131I was 6.3% ± 0.3% and 42.1% ± 0.2% at 50 cm; 6.1% ± 0.5% and 43.3% ± 0.3% at 1 m; and 6.4% ± 0.9% and 42.6% ± 0.6% at 2 m, respectively. Next, we assessed the occupational radiation exposure during 131I-MIBG therapy (administration dose: 666 MBq/kg, median age: 4 years). The total occupational radiation exposure dose per patient care per 131I-MIBG therapy session among nurses was 0.12 ± 0.07 mSv. The average daily radiation exposure dose per patient care among nurses was 0.03 ± 0.03 mSv. Tungsten aprons had efficient shielding effects against gamma rays and would be beneficial to reduce radiation exposures per patient care per 131I-MIBG therapy session.

Neuroblastoma presented with polyhydramniosis.

Neuroblastoma is the most common extracranial solid tumor in pediatric age group. Clinical presentation of neuroblastoma is mostly related to origin of the tumor, extent of disease, and the presence of paraneoplastic syndromes. Here the authors report a neonate with neuroblastoma with an atypical presentation, diagnosed with postnatal abdominal ultrasonography performed due to polyhydramniosis in her mother during pregnancy.

A rare case of pediatric primary central nervous system differentiating neuroblastoma: an unusual and rare intracranial primitive neuroectodermal tumor (a case report).

Neuroblastoma represents the most common solid extracranial tumor in children under 5, accounting for 8% to 10% of all childhood cancers. Primary central nervous system (CNS) neuroblastomas are a very rare location and only few cases are available in the literature. It was first described in 1973 by Hart and Earl as supratentorial primitive neuroectodermal tumors. Clinical presentation is highly variable and depends on the initial location of the tumor. Regarding imaging, primary brain neuroblastoma shows no pathognomonic appearance on brain computed tomography (CT) whether or not enhanced or magnetic resonance imaging (MRI). There were no standard guidelines available for the adjuvant treatment in case of primary CNS neuroblastoma. Surgery remains the main and the first tool toward these lesions. Radiotherapy associated or not to chemotherapy is offered based on patient´s age. Here, the authors report a new pediatric case of primitive central nervous system neuroblastoma revealed by an intracranial hypertension syndrome and confirmed by both histopathological and immunohistochemistry study after a gross total surgical excision. The postoperative course was uneventful and the child had good recovery.

Neuroblastoma of the Lumbar Spine.

Neuroblastoma is a primitive small-round-blue-cell tumor predominately found in pediatric patients. Few cases of neuroblastoma involving the adult spine have been reported. Herein we present the case of a healthy 34-year-old man treated for a large neuroblastoma involving the L3-5 vertebral bodies and prevertebral great vessels. Neoadjuvant chemotherapy led to significant cytoreduction, enabling en bloc resection of the initially unresectable tumor. Adjuvant differentiating therapy was employed, and curative radiation therapy was used to address the first instance of locoregional recurrence. The patient remains alive with stable disease more than 2 years after his initial diagnosis.

Clinical features and surgical outcome of a suprarenal mass detected before birth.

PURPOSE: With the widespread use of the obstetrical ultrasound, identification of a fetal suprarenal mass has become more common. Most of these masses prove to be congenital neuroblastomas (CNB), but the diagnosis is often confused with other benign lesions and the postnatal management remains to be controversial. METHODS: The medical records of 18 patients that underwent primary surgical excision for an antenatally detected suprarenal mass, between January 1995 and April 2009, were reviewed. The clinical, radiological, surgical, and pathological data were collected. Staging evaluation was performed after histological confirmation of the CNB. RESULTS: There were 13 cases of CNB, 1 adrenal cyst, 2 adrenal hemorrhages, and 2 pulmonary sequestrations. The differential diagnosis was impossible before surgery. Most of the CNBs were stage I (N = 11), with 1 stage IV and 1 stage IV-S. Four patients (3 stage I and 1 stage IV-S) had more than one copy of N-myc gene. The stage I patients were cured by surgery alone, and stage IV patients underwent nine cycles of adjuvant chemotherapy and currently have no evidence of disease. The five benign lesions were cured with excision alone. There were no postoperative complications. CONCLUSION: For early diagnosis and treatment, surgical excision should be considered as the primary therapy for an antenatally detected suprarenal mass. The surgery can be safely performed during the neonatal period and provides a cure in most cases.

Myelofibrosis in children: experience at a single tertiary care center in India.

The authors describe 10 cases of myelofibrosis diagnosed and managed at their center over 16 years. There were 2 and 8 cases, respectively, of primary and secondary myelofibrosis. All patients presented with fever, pallor, hepatosplenomegaly, and/or lymphadenopathy. Hodgkin's lymphoma (n = 4), neuroblastoma (n = 1), thrombasthenic thrombopathy (n = 1), and retroperitoneal-mass (n = 1) were causal in 7 patients, whereas the diagnosis could not be established in a sole case of secondary myelofibrosis. Patients were managed with chemotherapy and appropriate care. However, outcome was poor. The authors emphasize variable clinical-laboratory spectrum of myelofibrosis, highlight management concerns, and demonstrate that prognosis/outcome depends upon appropriate management of the underlying condition.

Persistent hyperinsulinemic hypoglycemia of infancy associated with congenital neuroblastoma: a case report.

The authors report a rare case of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) with congenital neuroblastoma without feature(s) of Beckwith-Wiedemann syndrome. A term newborn with a birth weight of 3,900 g developed hypoglycemia one hour after birth and required up to 20 mg/kg/min of intravenous glucose infusion to maintain euglycemia. Investigations during the critical period revealed an inappropriately high insulin level. An abdominal CT scan revealed a normal pancreas, right suprarenal mass, and liver nodules. A condition of stage 4S neuroblastoma was suspected and supported by an increased ratio of urine vanillylmandelic acid to creatinine. The bone marrow smear was normal. She underwent near total pancreatectomy at the age of 2 months. The suprarenal mass and liver nodules were not found during the operation or during repeated abdominal CT scans at 3 month of age. Spontaneous regression of neuroblastoma was suspected. The pathology of the pancreas was compatible with PHHI.