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.

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.

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.

Pencil Beam Scanning Proton Therapy for Paediatric Neuroblastoma with Motion Mitigation Strategy for Moving Target Volumes.

AIMS: More efforts are required to minimise late radiation side-effects for paediatric patients. Pencil beam scanning proton beam therapy (PBS-PT) allows increased sparing of normal tissues while maintaining conformality, but is prone to dose degradation from interplay effects due to respiratory motion. We report our clinical experience of motion mitigation with volumetric rescanning (vRSC) and outcomes of children with neuroblastoma. MATERIALS AND METHODS: Nineteen patients with high-risk (n = 16) and intermediate-risk (n = 3) neuroblastoma received PBS-PT. The median age at PBS-PT was 3.5 years (range 1.2-8.6) and the median PBS-PT dose was 21 Gy (relative biological effectiveness). Most children (89%) were treated under general anaesthesia. Seven patients (37%) underwent four-dimensional computed tomography for motion assessment and were treated with vRSC for motion mitigation. RESULTS: The mean result of maximum organ motion was 2.7 mm (cranial-caudal), 1.2 mm (left-right), 1.0 mm (anterior-posterior). Four anaesthetised children (21%) showing <5 mm motion had four-dimensional dose calculations (4DDC) to guide the number of vRSC. The mean deterioration or improvement to the planning target volume covered by 95% of the prescribed dose compared with static three-dimensional plans were: 4DDC no vRSC, -0.6%; 2 vRSC, +0.3%; 4 vRSC, +0.3%; and 8 vRSC, +0.1%. With a median follow-up of 14.9 months (range 2.7-49.0) there were no local recurrences. The 2-year overall survival was 94% and distant progression-free survival was 76%. Acute grade 2-4 toxicity was 11%. During the limited follow-up time, no late toxicities were observed. CONCLUSIONS: The early outcomes of mainly high-risk patients with neuroblastoma treated with PBS-PT were excellent. With a subset of our cohort undergoing PBS-PT with vRSC we have shown that it is logistically feasible and safe. The clinical relevance of vRSC is debatable in anaesthetised children with small pre-PBS-PT motion of <5 mm.

Usefulness of Renal Autotransplantation for Radiotherapy-induced Renovascular Hypertension.

We experienced a young woman with congestive heart failure (CHF) caused by renovascular hypertension (RVH) and subsequent hypertensive heart disease. She underwent tumor resection and intraoperative radiation therapy because of neuroblastoma at age 2. She was diagnosed with RVH and hypertensive heart disease due to radiation-induced renal artery stenosis at age 12. Thereafter, she was hospitalized with CHF caused by uncontrolled RVH at age 19, and renal autotransplantation with extraction of left kidney was performed after the recovery of CHF. Her blood pressure has been well controlled without CHF readmission during four years of follow-up after the operation.

Treatment of neuroblastoma using the fused imaging guided radiotherapy (FIGURA) system.

PURPOSE: The purpose of this study was to describe our department's experience with the fused imaging-guided radiotherapy (FIGURA) system for planning radiation treatment of high-risk neuroblastoma. PATIENTS AND METHODS: Between 1999 and 2002, 11 patients received radiation therapy as consolidation after chemotherapy in 9 and for palliation in 2. Diagnostic metaiodobenzylguanidine (MIBG) imaging was used, which is specific for neuroblastoma, to identify the residual tumor, followed by computed tomography scanning in the radiation treatment position. The FIGURA software fused the images obtained by the 2 modalities and transferred the result to a 3-dimensional radiation treatment planning system. Radiation was delivered at a total dose of 25.2 Gy according to the FIGURA. RESULTS: Five patients achieved complete remission and 2 partial remission; 3 were stabilized. One child with a highly rapid progressive course died of the disease. CONCLUSION: FIGURA is a new, feasible technique for defining target volumes. By using standard hospital equipment, it is possible to treat residual disease identified by sensitive metaiodobenzylguanidine imaging and localized with the anatomic computed tomography scan. Treating a more accurate target volume spares normal tissue and organs and minimizes side effects.

¹³¹I-Metaiodobenzylguanidine Theranostics in Neuroblastoma: Historical Perspectives; Practical Applications.

Much efficacy is gained in clinical practice if a single agent can be used for both diagnosis and therapy, a practice termed theranostics. Metaiodobenzylguanidine (mIBG), a norepinephrine analogue with high sensitivity and specificity for neuroblastoma, is an exemplar of theranostics. The physiologic biodistribution of mIBG, with absence of uptake in bone and bone marrow, allows ready detection not only of primary soft tissue tumors but also of disease in bone and marrow, the two most common sites of metastases in those with neuroblastoma. Owing to its increased sensitivity and specificity in disease detection compared to the Technetium-99m methylene diphosphonate bone scan, (123)I-mIBG has become the cornerstone of staging and therapeutic response monitoring in patients with neuroblastoma. More recently, semiquantitative scoring systems have been developed to evaluate disease burden and response to treatment based on (123)I-mIBG scans. Initial data suggest that the use of these semiquantitative scoring methods has prognostic value in assessing outcomes for patients with high-risk neuroblastoma. When labeled with (131)I, mIBG can be used as a systemic therapeutic agent to treat high-risk disease, and to date, over 1000 patients with neuroblastoma have been treated worldwide with this agent. This article reviews the evolution of (131)I-mIBG therapy from its initial use as a single therapeutic agent to modern applications involving high-dose chemotherapy and autologous stem-cell transplant as well as its use as a front-line agent in high-risk neuroblastoma.

Anti-G(D2) antibody treatment of minimal residual stage 4 neuroblastoma diagnosed at more than 1 year of age.

PURPOSE: To eradicate minimal residual disease with anti-G(D2) monoclonal antibody 3F8 in stage 4 neuroblastoma (NB) diagnosed at more than 1 year of age. PATIENTS AND METHODS: Thirty-four patients were treated with 3F8 at the end of chemotherapy. Most had either bone marrow (n=31) or distant bony metastases (n=29). Thirteen patients were treated at second or subsequent remission (group I) and 12 patients in this group had a history of progressive/persistent disease after bone marrow transplantation (BMT); 21 patients were treated in first remission following N6 chemotherapy (group II). RESULTS: Before 3F8 treatment, 23 patients were in complete remission CR, eight in very good partial remission (VGPR), one in partial remission (PR), and two had microscopic foci in marrow. Twenty-five had evidence of NB by at least one measurement of occult/minimal tumor (iodine 131[(131)I]-3F8 imaging, marrow immunocytology, or marrow reverse-transcriptase polymerase chain reaction [RT-PCR]). Acute self-limited toxicities of 3F8 treatment were severe pain, fever, urticaria, and reversible decreases in blood counts and serum complement levels. There was evidence of response by immunocytology (six of nine), by GAGE RT-PCR (seven of 12), and by (131)I-3F8 scans (six of six). Fourteen patients are alive and 13 (age 1.8 to 7.4 years at diagnosis) are progression-free (40 to 130 months from the initiation of 3F8 treatment) without further systemic therapy, none with late neurologic complications. A transient anti-mouse response or the completion of four 3F8 cycles was associated with significantly better survival. CONCLUSION: Despite high-risk nature of stage 4 NB, long-term remission without autologous (A)BMT can be achieved with 3F8 treatment. Its side effects were short-lived and manageable. The potential benefits of 3F8 in consolidating remission warrant further investigations.

Spatial aspects of combined modality radiotherapy.

BACKGROUND AND PURPOSE: A combined modality radiotherapy (CMRT) incorporates both external beam radiotherapy (EBT) and targeted radionuclide therapy (TRT) components. The spatial aspects of this combination were explored by utilising intensity modulated radiotherapy (IMRT) to provide a non-uniform EBT dose distribution. PATIENTS AND METHODS: Three methods of prescribing the required non-uniform distribution of EBT dose are described, based on both physical and biological criteria according to the distribution of TRT uptake. The results and consequences of these prescriptions are explored by application to three examples of patient data. RESULTS: The planning procedure adopted allowed IMRT plans to be produced that met the prescription requirements. However, when the treatment was planned as a CMRT, compared with the use of EBT alone, more satisfactory target doses could be achieved with lower doses to normal tissues. The effects of errors in EBT delivery and in the functional data were found to cause a non-uniform prescription to tend towards the uniform case. CONCLUSIONS: The methods and results are relevant for more general biological treatment planning, in which IMRT may be used to produce dose distributions prescribed according to tumour function. The effects of delivery and dose calculation errors can have a significant impact on how such treatments should be planned.

First line targeted radiotherapy, a new concept in the treatment of advanced stage neuroblastoma.

33 previously untreated advanced stage neuroblastoma patients were treated with [131I]meta-iodobenzylguanidine (MIBG). The number of treatments varied between 2 and 7 per patient (mean 3). Toxicity was seldom severe. Only thrombocytopenia WHO-grade 4 was noticed. Response was documented before surgery for the primary tumour was performed. There was one complete response (CR), 18 partial responses (PR), 11 had stable disease (SD) and 3 had progressive disease (PD). After MIBG therapy and surgery, 12 of 33 patients achieved a CR. This approach is feasible, comparable to multidrug chemotherapy in efficacy and less toxic. Long term results are not known yet.

[Retroperitoneal neuroblastoma in the adult: case report and review of the literature]. / Le neuroblastome rétropéritonéal chez l'adulte: à propos d'un cas et revue de la littérature.

Retroperitoneal neuroblastoma is a rare embryonic tumor of the sympathetic nervous system that is specific to the child. In this study, the case is reported of an infant who underwent median laparotomy at the age of 14 months for a tumor which occupied the left half of the abdomen. The lesion was large, hard, and not very mobile. It was considered to be unresectable, and the histological findings after biopsy showed it to be a neuroblastoma. Radiotherapy was then initiated, which successfully reduced the tumor size. A second investigation at the age of three years detected an unresectable tumor of 5 cm. A further biopsy was performed, and the histological findings showed the lesion to be a partially developed ganglioneuroblastoma. The patient has been followed up regularly by ultrasonography which has shown no increase in tumor size. She is now 20 years old, and is asymptomatic. The last computed tomography scan visualized a 62-mm retroperitoneal mass with no metastases. Surgery was decided against in favor of regular monitoring. This case is particular due to the prolonged survival of the patient, regression of histological stage, and reduction in size of the tumor after radiotherapy. It is remarkable that the diagnosis of neuroblastoma was made when the patient was 14 months old, and that she is still alive at 20 years old.

Intraoperative phosphorus-32 brachytherapy plaque for multiply recurrent high-risk epidural neuroblastoma.

Achieving local control is a crucial component in the management of neuroblastoma, but this may be complicated in the setting of prior radiation treatment, especially when the therapeutic target is in proximity to critical structures such as the spinal cord. The authors describe a pediatric patient with multiply recurrent neuroblastoma and prior high-dose radiation therapy to the spine who presented with progressive epidural disease. The patient was managed with resection and intraoperative high-dose-rate brachytherapy using a phosphorus-32 ((32)P) plaque previously developed for the treatment of brain and spine lesions.

Differentiated thyroid carcinoma after 131I-MIBG treatment for neuroblastoma during childhood: description of the first two cases.

BACKGROUND: It is well known that the thyroid gland is sensitive to the damaging effects of irradiation (X-radiation or (131)I¯). For this reason, during exposure to (131)I- metaiodobenzylguanidine (MIBG) in children with neuroblastoma (NBL), the thyroid gland is protected against radiation damage by the administration of either potassium iodide (KI) or a combination of KI, thyroxine, and methimazole. Although hypothyroidism and benign thyroid nodules are frequently encountered during follow-up of these children, differentiated thyroid carcinoma (DTC) has never been reported after treatment with (131)I-MIBG in children who have not been given external beam irradiation. Here, we describe the first two cases of DTC after (131)I-MIBG-therapy. PATIENT FINDINGS: A 6-year-old boy, treated with (131)I-MIBG for NBL at the age of 4 months, and a 13-year-old girl, treated at the age of 9 months, were both diagnosed with DTC at 5 and 12 years after (131)I-MIBG treatment, respectively. Both children received thyroid protection during exposure to (131)I-MIBG. In each child DTC was discovered in nonpalpable nodules by thyroid ultrasound. SUMMARY: The first two pediatric patients with DTC after treatment with (131)I-MIBG are reported. CONCLUSIONS: Both these cases of DTC after (131)I-MIBG for childhood NBL underline the importance of adequate thyroid protection against radiation exposure during treatment for NBL. Children who have been treated with (131)I-MIBG should be given life-long follow-up, not only with regard to thyroid function, but also with surveillance for the development of thyroid nodules and thyroid cancer.

Iodine-131-labeled meta-iodobenzylguanidine therapy of children with neuroblastoma: program planning and initial experience.

Patients with high-risk neuroblastoma have a poor prognosis, especially in cases of recurrent or relapsed disease. Iodine-131-labeled meta-iodobenzylguanidine ((131)I-MIBG) can be an effective and relatively well-tolerated agent for the treatment of refractory neuroblastoma. Establishing an MIBG therapy program requires a great deal of planning, availability of hospital resources, and the commitment of individuals with training and expertise in multiple disciplines. Providing (131)I-MIBG therapy requires physical facilities and procedures that permit patient care in compliance with the standards for occupational and community exposure to radiation. Establishment of a successful (131)I-MIBG therapy program also requires a detailed operational plan and appropriate education for caregivers, parents, and patients.

177Lu-DOTATATE molecular radiotherapy for childhood neuroblastoma.

UNLABELLED: This study tested the principle that (68)Ga-DOTATATE PET/CT may be used to select children with primary refractory or relapsed high-risk neuroblastoma for treatment with (177)Lu-DOTATATE and evaluated whether this is a viable therapeutic option for those children. METHODS: Between 2008 and 2010, 8 children with relapsed or refractory high-risk neuroblastoma were studied with (68)Ga-DOTATATE PET/CT. The criterion of eligibility for (177)Lu-DOTATATE therapy was uptake on the diagnostic scan equal to or higher than that of the liver. RESULTS: Of the 8 children imaged, 6 had abnormally high uptake on the (68)Ga-DOTATATE PET/CT scan and proceeded to treatment. Patients received 2 or 3 administrations of (177)Lu-DOTATATE at a median interval of 9 wk and a median administered activity of 7.3 GBq. Of the 6 children treated, 5 had stable disease by the response evaluation criteria in solid tumors (RECIST). Of these 5 children, 2 had an initial metabolic response and reduction in the size of their lesions, and 1 patient had a persistent partial metabolic response and reduction in size of the lesions on CT, although the disease was stable by RECIST. One had progressive disease. Three children had grade 3 and 1 child had grade 4 thrombocytopenia. No significant renal toxicity has been seen. CONCLUSION: (68)Ga-DOTATATE can be used to image children with neuroblastoma and identify those suitable for molecular radiotherapy with (177)Lu-DOTATATE. We have shown, for what is to our knowledge the first time, that treatment with (177)Lu-DOTATATE is safe and feasible in children with relapsed or primary refractory high-risk neuroblastoma. We plan to evaluate this approach formally in a phase I-II clinical trial.

Conformal proton radiation treatment for retroperitoneal neuroblastoma: introduction of a novel technique.

BACKGROUND: Postoperative irradiation for locoregionally advanced neuroblastoma requires coverage of the paraspinal retroperitoneum. The proximity of both kidneys and the liver, and a more complex target configuration, can pose a dosimetric challenge for conventional X-ray treatment and intraoperative irradiation. We utilized proton radiation therapy (PRT) to reduce dose to uninvolved kidneys, liver, intestine, and spinal cord. PROCEDURE: A 4-year-old male underwent PRT for neuroblastoma of the right adrenal gland, following chemotherapy and delayed surgical resection. Clinical target volume (CTV), boost volume, and normal structures were outlined on the 3D treatment planning CT scan. The patient received 25.2 CGE (cobalt Gray equivalent) to the CTV and 34.2 CGE to the boost region, using 1.8 CGE per fraction, five treatments per week. Dose-volume histograms (DVHs) were obtained for target and nontarget structures. RESULTS: The 95% isodose volume enclosed CTV and boost volumes. The dose to 50% of the ipsilateral kidney, with tumor involvement of the medial renal surface, was < or = 16 CGE (47% of prescribed total dose). Doses to 50% and 20% of the contralateral kidney in close proximity to deep left-side, paraspinal soft tissue involvement were restricted to 1 CGE and 10 CGE, respectively. Eighty percent of the liver received 27 CGE (80% of prescribed dose). Using a patch technique, unique to charged particle therapy, the spinal cord was almost completely spared during boost volume irradiation. CONCLUSIONS: PRT can achieve excellent dose conformity for advanced retroperitoneal, paraspinal lesions, while respecting normal tissue tolerance levels.

131I MIBG therapy in neuroblastoma: mechanisms, rationale, and current status.

131I MIBG has been used as palliative treatment of neuroblastoma patients with recurrent or persistent disease who failed other modalities of treatment. Since the results were promising, the concept arose of using it in conjunction with other modalities, either as an up-front treatment or as combination therapy. This article reviews the principle of 131I MIBG treatment, in conjunction with other modalities currently used for the treatment of neuroblastoma, in an attempt to improve the final outcome.

The use of an investigational radiopharmaceutical in neuroblastoma: a nursing perspective.

Children with advanced-stage neuroblastoma usually have a poor prognosis. While conventional treatment with surgery, chemotherapy, and radiation may provide some palliation, long-term survival is rare. A number of investigational therapies are being performed nationwide in an attempt to improve the prognosis for children with neuroblastoma. One such treatment is the use of 131I-metaiodobenzylguanidine. This article will review the pathophysiology of neuroblastoma, give an overview of this investigational treatment, and discuss the nursing care associated with radioactive treatment.

Treatment of neuroblastoma with intraspinal extensions.

Neuroblastoma is the most common malignant cause of spinal compression in the paediatric population. Chemotherapy is commonly considered as the first-line treatment for these patients. The role of neurosurgical decompression and radiotherapy are still controversial. Thirteen children diagnosed as having neuroblastoma with intraspinal extension were included in this report. All patients presented with neurological deficits and were treated with chemotherapy initially, after which 3 patients recovered, 4 improved and 6 were aggravated into paraplegia. Two of the 6 aggravated patients received emergent laminectomy with removal of intraspinal tumour and recovered satisfactorily. Although spread of tumour into the spinal canal indicates an advanced disease, aggressive treatments such as chemotherapy and surgical resection can often improve neurological symptoms and life quality. Neurological decompression is recommended for patients with intraspinal neuroblastoma and rapid neurological deterioration during chemotherapy.