RESUMO
The objective of this report is to describe the use and outcome of stereotactic body radiation therapy (SBRT) for treatment of pheochromocytomas in 8 dogs. Pheochromocytomas are an uncommon but challenging tumour to manage. Adrenalectomy is the standard of care for treatment of pheochromocytomas in both animals and humans; however, unpredictable catecholamine secretion from the tumour and vascular and local invasion of the tumour and thrombi can pose life-threatening perioperative and anaesthetic risks. SBRT has been investigated as an alternative to adrenalectomy in human patients with pheochromocytomas. Eight dogs with clinical signs, an adrenal mass, and cytology and/or urine normetanephrine/creatinine ratios consistent with pheochromocytoma were treated with SBRT in lieu of adrenalectomy. Three dogs presented with acute hemoabdomen. Seven dogs had caval tumour invasion, 3 with extension into the right atrium. Following SBRT, all dogs had complete resolution of clinical signs and reduced urine normetanephrine/creatinine ratio and/or tumour size. No significant anaesthetic complications were encountered. Acute radiation toxicity was limited to grade I gastrointestinal signs in 3 dogs and resolved within 1-2 days of symptomatic therapy. Five of 8 dogs were alive at the time of follow up, with a median follow up time of 25.8 months. SBRT resulted in a favourable outcome and mitigated the life-threatening risks of adrenalectomy in these 8 dogs. SBRT may be a safe and effective alternative to adrenalectomy for pheochromocytomas in dogs with non-resectable tumours, or for owners averse to the risks of surgery.
Assuntos
Neoplasias das Glândulas Suprarrenais , Anestésicos , Doenças do Cão , Feocromocitoma , Radiocirurgia , Humanos , Cães , Animais , Adrenalectomia/veterinária , Adrenalectomia/métodos , Feocromocitoma/radioterapia , Feocromocitoma/cirurgia , Feocromocitoma/veterinária , Radiocirurgia/veterinária , Creatinina , Normetanefrina , Doenças do Cão/radioterapia , Doenças do Cão/cirurgia , Neoplasias das Glândulas Suprarrenais/radioterapia , Neoplasias das Glândulas Suprarrenais/cirurgia , Neoplasias das Glândulas Suprarrenais/veterinária , Estudos RetrospectivosRESUMO
Targeted radionuclide therapies (TRT) using 131I-metaiodobenzylguanidine (131I-MIBG) and peptide receptor radionuclide therapy (177Lu or 90Y) represent several of the therapeutic options in the management of metastatic/inoperable pheochromocytoma/paraganglioma. Recently, high-specific-activity-131I-MIBG therapy was approved by the FDA and both 177Lu-DOTATATE and 131I-MIBG therapy were recommended by the National Comprehensive Cancer Network guidelines for the treatment of metastatic pheochromocytoma/paraganglioma. However, a clinical dilemma often arises in the selection of TRT, especially when a patient can be treated with either type of therapy based on eligibility by MIBG and somatostatin receptor imaging. To address this problem, we assembled a group of international experts, including oncologists, endocrinologists, and nuclear medicine physicians, with substantial experience in treating neuroendocrine tumors with TRTs to develop consensus and provide expert recommendations and perspectives on how to select between these two therapeutic options for metastatic/inoperable pheochromocytoma/paraganglioma. This article aims to summarize the survival outcomes of the available TRTs; discuss personalized treatment strategies based on functional imaging scans; address practical issues, including regulatory approvals; and compare toxicities and risk factors across treatments. Furthermore, it discusses the emerging TRTs.
Assuntos
3-Iodobenzilguanidina/uso terapêutico , Neoplasias das Glândulas Suprarrenais/radioterapia , Neoplasias das Glândulas Suprarrenais/secundário , Radioisótopos do Iodo/uso terapêutico , Lutécio/uso terapêutico , Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Paraganglioma/radioterapia , Paraganglioma/secundário , Feocromocitoma/radioterapia , Feocromocitoma/secundário , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Radioterapia/métodos , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Humanos , Octreotida/uso terapêutico , Paraganglioma/diagnóstico por imagem , Feocromocitoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia ComputadorizadaRESUMO
CONTEXT: Prognosis of metastatic pheochromocytoma/paraganglioma following 131-Iodine metaiodobenzylguanidine (MIBG) is incompletely characterized due to small samples and shorter follow-up in these rare, often indolent tumors. OBJECTIVE: To describe long-term survival, frequency, and prognostic impact of imaging, biochemical, and symptomatic response to 131-I MIBG. DESIGN: Retrospective chart and imaging review at a tertiary referral center. PATIENTS: Six hundred sixty-eight person-years of follow-up in 125 patients with metastatic pheochromocytoma/paraganglioma with progression through prior multimodal treatment. INTERVENTION: Median 18 800 MBq 131-I MIBG. MAIN OUTCOME MEASURES: Overall survival, Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) imaging response, symptomatic response per chart review, and biochemical response (20% change over 2 consecutive assays of catecholamines, vanillylmandelic acid, metanephrines, or chromogranin A). RESULTS: Median survival standard deviation [SD] from diagnosis was 11.5 years [2.4]; following metastasis, 6.5 years [0.8]; post treatment, 4.3 years [0.7]. Among 88 participants with follow-up imaging, 1% experienced complete response, 33% partial response, 53% stability, and 13% progression. Fifty-one percent showed subsequent progression, median progression-free survival [SD] of 2.0 years [0.6]. Stability/response vs progression at first imaging follow-up (3-6 months) predicted improved survival, 6.3 vs 2.4 years (P = 0.021). Fifty-nine percent of 54 patients demonstrated biochemical response. Fifty percent of these relapsed, with median time to laboratory progression [SD] of 2.8 years [0.7]. Biochemical response did not predict extended survival. Seventy-five percent of 83 patients reported improvement in pretreatment symptoms, consisting primarily of pain (42%), fatigue (27%), and hypertension (14%). Sixty-one percent of these patients experienced subsequent symptomatic progression at median [SD] 1.8 years [0.4]. Symptomatic response did not predict extended survival. CONCLUSIONS: Imaging, symptomatic, and laboratory response to multimodal treatment including high-dose 131-I MIBG were achieved on long-term follow-up in metastatic pheochromocytoma or paraganglioma. Imaging response at 3 to 6 months was prognostic.
Assuntos
3-Iodobenzilguanidina/uso terapêutico , Neoplasias das Glândulas Suprarrenais/radioterapia , Radioisótopos do Iodo/uso terapêutico , Paraganglioma/radioterapia , Feocromocitoma/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Neoplasias das Glândulas Suprarrenais/secundário , Adulto , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Paraganglioma/patologia , Feocromocitoma/patologia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
OBJECTIVE: External beam radiotherapy (EBRT) is recommended as a therapeutic strategy for stage III hepatocellular carcinoma (HCC) in national guidelines of the Chinese Society of Liver Disease and in Korea Liver Cancer Study Group practice guidelines, but has not been considered a therapeutic option for HCC in Western countries. In this study, we review evidence supporting EBRT as an option for HCC treatment. METHODS: Retrospective investigation was made of 775 patient records of intermediate/advanced HCC treated in our hospital during the last 10 years, including 98 patients with confined intrahepatic tumor, 181 with portal vein (PV) or inferior vena cava (IVC) tumor thrombi, 191 with lymph node metastases, 55 with adrenal gland metastases, 205 with bone metastases, 13 with lung metastases and 32 with brain metastases. RESULTS: Transcatheter arterial chemoembolization combined with radiotherapy was found to constitute an improved therapeutic strategy for unresectable but confined intrahepatic HCC with poor lipid accumulation. Survival of HCC patients with PV/IVC tumor thrombi was prolonged to 10.7 months by radiotherapy, and it was 8.0 months in patients with abdominal lymph node metastasis. Radiotherapy also shrinks adrenal and lung metastatic HCC lesions, resulting in median survival times of 13.6 and progression-free survival of 13.4 months, respectively. In bone metastatic HCC, radiotherapy significantly relieved symptoms, although median survival time was only 7.4 months. Radiotherapy is effective for treatment of intermediate/advanced stages of HCC. Although our finding is based only on retrospective analysis, no therapeutic option that provides better treatment than EBRT in this indication has thus far been identified. Because sorafenib has been recommended as a treatment strategy by the National Comprehensive Cancer Network (NCCN) for HCC, we compared the survival after EBRT with sorafenib treatment on the basis of published clinical data. From this comparison, we found that EBRT treatment was more effective than sorafenib for improving patient survival when tested on tumors of comparable metastatic size. CONCLUSION: Based on the evidence reviewed, we propose that EBRT be included in the NCCN guideline as a treatment strategy for intermediate/advanced HCC.
Assuntos
Neoplasias das Glândulas Suprarrenais/radioterapia , Neoplasias Ósseas/radioterapia , Carcinoma Hepatocelular/radioterapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/radioterapia , Neoplasias Pulmonares/radioterapia , Guias de Prática Clínica como Assunto , Neoplasias das Glândulas Suprarrenais/secundário , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/secundário , Carcinoma Hepatocelular/secundário , Carcinoma Hepatocelular/terapia , Terapia Combinada , Intervalo Livre de Doença , Óleo Etiodado/administração & dosagem , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/secundário , Metástase Linfática , Niacinamida/análogos & derivados , Niacinamida/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Estudos Retrospectivos , Sorafenibe , Taxa de SobrevidaRESUMO
A 63-year-old man underwent computed tomography (CT) using intravenous low-osmolar iodine contrast medium (LOCM) 6 days after undergoing high-dose (131)I-MIBG therapy for metastatic pheochromocytoma. Immediately after the CT examination, his blood pressure increased to 260/160 mmHg (from 179/101 mmHg before the examination). Phentolamine mesilate was administered, and the blood pressure rapidly went back to normal. Although hypertensive crisis after administration of LOCM is rare, this case suggests that high-dose (131)IMIBG therapy may be a risk factor for hypertensive crisis after administration of intravenous LOCM.
Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Meios de Contraste/efeitos adversos , Encefalopatia Hipertensiva/induzido quimicamente , Iopamidol/efeitos adversos , Feocromocitoma/diagnóstico por imagem , Compostos Radiofarmacêuticos/uso terapêutico , Tomografia Computadorizada por Raios X/efeitos adversos , 3-Iodobenzilguanidina/uso terapêutico , Neoplasias das Glândulas Suprarrenais/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Feocromocitoma/radioterapia , CintilografiaRESUMO
This is a first of many phase 1 study of Ultratrace Iobenguane I-131 (Ultratrace 131I-MIBG; Molecular Insight Pharmaceuticals, Inc., Cambridge, MA). High-specific-activity Ultratrace 131I-MIBG may provide improved efficacy and tolerability over carrier-added 131I-MIBG. We investigated the pharmacokinetics (PK), radiation dosimetry, and clinical safety in 11 patients with confirmed pheochromocytoma/paraganglioma (Pheo) or carcinoid tumors. A single 5.0-mCi (185 MBq) injection of Ultratrace 131I-MIBG, supplemented with 185 microg of unlabeled MIBG to simulate the amount of MIBG anticipated in a therapeutic dose, was administered. Over 120 hours postdose, blood and urine were collected for PK, and sequential whole-body planar imaging was performed. Patients were followed for adverse events for 2 weeks. Ultratrace 131I-MIBG is rapidly cleared from the blood and excreted in urine (80.3% +/- 2.8% of dose at 120 hours). For a therapeutic administration of 500 mCi (18.5 GBq), our estimate of the projected dose is 1.4 Gy for marrow and 10.4 Gy for kidneys. Safety results showed 12 mild adverse events, all considered unrelated to study drug, in 8 of 11 patients. These findings support the further development of Ultratrace 131I-MIBG for the treatment of neuroendocrine tumors, such as metastatic Pheo and carcinoid.
Assuntos
3-Iodobenzilguanidina/efeitos adversos , 3-Iodobenzilguanidina/farmacocinética , Neoplasias das Glândulas Suprarrenais/radioterapia , Radioisótopos do Iodo/efeitos adversos , Radioisótopos do Iodo/farmacocinética , Paraganglioma/radioterapia , Feocromocitoma/radioterapia , 3-Iodobenzilguanidina/administração & dosagem , Neoplasias das Glândulas Suprarrenais/metabolismo , Adulto , Relação Dose-Resposta à Radiação , Feminino , Humanos , Radioisótopos do Iodo/administração & dosagem , Masculino , Paraganglioma/metabolismo , Feocromocitoma/metabolismo , Doses de Radiação , Radiometria/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/farmacocinéticaRESUMO
PURPOSE: To evaluate the safety and efficacy of high-dose [(131)I]metaiodobenzylguanidine ([(131)I]MIBG) in the treatment of malignant pheochromocytoma (PHEO) and paraganglioma (PGL). METHODS: Fifty patients with metastatic PHEO or PGL, age 10 to 64 years, were treated with [(131)I]MIBG doses ranging from 492 to 1,160 mCi (median, 12 mCi/kg). Cumulative [(131)I]MIBG administered ranged from 492 to 3,191 mCi. Autologous hematopoietic stem cells were collected and cryopreserved before treatment with [(131)I]MIBG greater than 12 mCi/kg or with a total dose greater than 500 mCi. Sixty-nine [(131)I]MIBG infusions were given, which included infusions to 35 patients treated once and infusions to 15 patients who received two or three treatments. Response was evaluated by [(123)I]MIBG scans, computed tomography/magnetic resonance imaging, urinary catecholamines/metanephrines, and chromogranin A. RESULTS: The overall complete response (CR) plus partial response (PR) rate in 49 evaluable patients was 22%. Additionally, 35% of patients achieved a CR or PR in at least one measure of response without progressive disease, and 8% of patients maintained stable disease for greater than 12 months. Thirty-five percent of patients experienced progressive disease within 1 year after therapy. The estimated 5-year overall survival rate was 64%. Toxicities included grades 3 to 4 neutropenia (87%) and thrombocytopenia (83%). Grades 3 to 4 nonhematologic toxicity included acute respiratory distress syndrome (n = 2), bronchiolitis obliterans organizing pneumonia (n = 2), pulmonary embolism (n = 1), fever with neutropenia (n = 7), acute hypertension (n = 10), infection (n = 2), myelodysplastic syndrome (n = 2), and hypogonadism (n = 4). CONCLUSION: Although serious toxicity may occur, the survival and response rates achieved with high-dose [(131)I]MIBG suggest its utility in the management of selected patients with metastatic PHEO and PGL.
Assuntos
3-Iodobenzilguanidina/administração & dosagem , Neoplasias das Glândulas Suprarrenais/radioterapia , Radioisótopos do Iodo/administração & dosagem , Paraganglioma/radioterapia , Feocromocitoma/radioterapia , Compostos Radiofarmacêuticos/administração & dosagem , 3-Iodobenzilguanidina/efeitos adversos , Adolescente , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/mortalidade , Neoplasias das Glândulas Suprarrenais/secundário , Adulto , Biomarcadores Tumorais/urina , Catecolaminas/urina , Criança , Cromogranina A/urina , Intervalo Livre de Doença , Relação Dose-Resposta à Radiação , Feminino , Humanos , Infusões Intravenosas , Radioisótopos do Iodo/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Paraganglioma/diagnóstico , Paraganglioma/secundário , Feocromocitoma/diagnóstico , Feocromocitoma/mortalidade , Feocromocitoma/secundário , Modelos de Riscos Proporcionais , Estudos Prospectivos , Compostos Radiofarmacêuticos/efeitos adversos , Medição de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Focal nodular hyperplasia (FNH) is a benign, poorly understood hepatic tumor that is rare in children. Although there is no evidence for malignant degeneration, FNH can occur adjacent to a malignancy. Here, the case of a 4-year-old boy with a hepatic mass and history of stage IV neuroblastoma is presented. Initial imaging and core-needle biopsy were consistent with FNH. However, after left lateral segmentectomy, pathologic examination revealed a malignant tumor most consistent with small cell undifferentiated hepatoblastoma as well as 3 foci of FNH in the surrounding parenchyma.
Assuntos
Neoplasias das Glândulas Suprarrenais , Hiperplasia Nodular Focal do Fígado/etiologia , Hepatoblastoma/diagnóstico , Neoplasias Hepáticas/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Neuroblastoma , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/radioterapia , Neoplasias das Glândulas Suprarrenais/cirurgia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Carboplatina/administração & dosagem , Pré-Escolar , Cisplatino/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Etoposídeo/administração & dosagem , Fluoruracila/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Hepatectomia , Hepatoblastoma/complicações , Hepatoblastoma/diagnóstico por imagem , Hepatoblastoma/tratamento farmacológico , Hepatoblastoma/cirurgia , Humanos , Ifosfamida/administração & dosagem , Imunoglobulina G/uso terapêutico , Achados Incidentais , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Masculino , Melfalan/administração & dosagem , Mesna/administração & dosagem , Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/complicações , Segunda Neoplasia Primária/patologia , Neuroblastoma/tratamento farmacológico , Neuroblastoma/radioterapia , Neuroblastoma/cirurgia , Radioterapia Adjuvante/efeitos adversos , Tomografia Computadorizada por Raios X , Vincristina/administração & dosagemRESUMO
Thirty patients with malignant pheochromocytoma (PHEO) or paraganglioma (PGL) were treated with high-dose 131I-MIBG. Patients were 11-62 (mean 39) years old: 19 patients males and 11 females. Nineteen patients had PGL, three of which were multifocal. Six PGLs were nonsecretory. Eleven patients had PHEO. All 30 patients had prior surgery. Fourteen patients were refractory to prior radiation or chemotherapy before 131I-MIBG. Peripheral blood stem cells (PBSCs) were collected and cryopreserved. 131I-MIBG was synthesized on-site, by exchange-labeling 131I with 127I-MIBG in a solid-phase Cu2+-catalyzed exchange reaction. 131I-MIBG was infused over 2 h via a peripheral IV. Doses ranged from 557 mCi to 1185 mCi (7.4 mCi/kg to 18.75 mCi/kg). Median dose was 833 mCi (12.55 mCi/kg). Marrow hypoplasia commenced 3 weeks after 131I-MIBG therapy. After the first 131I-MIBG therapy, 19 patients required platelet transfusions; 19 received GCSF; 12 received epoeitin or RBCs. Four patients received a PBSC infusion. High-dose 131I-MIBG resulted in the following overall tumor responses in 30 patients: 4 sustained complete remissions (CRs); 15 sustained partial remissions (PRs); 1 sustained stable disease (SD); 5 progressive disease (PD); 5 initial PRs or SD but relapsed to PD. Twenty-three of the 30 patients remain alive; deaths were from PD (5), myelodysplasia (1), and unrelated cause (1). Overall predicted survival at 5 years is 75% (Kaplan Meier estimate). For patients with metastatic PHEO or PGL, who have good *I-MIBG uptake on diagnostic scanning, high-dose 131I-MIBG therapy was effective in producing a sustained CR, PR, or SD in 67% of patients, with tolerable toxicity.
Assuntos
3-Iodobenzilguanidina/uso terapêutico , Neoplasias das Glândulas Suprarrenais/radioterapia , Radioisótopos do Iodo/uso terapêutico , Paraganglioma/radioterapia , Feocromocitoma/radioterapia , 3-Iodobenzilguanidina/efeitos adversos , Adolescente , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/metabolismo , Adulto , Criança , Diagnóstico Diferencial , Relação Dose-Resposta à Radiação , Feminino , Humanos , Radioisótopos do Iodo/efeitos adversos , Masculino , Pessoa de Meia-Idade , Paraganglioma/diagnóstico , Feocromocitoma/diagnóstico , Feocromocitoma/metabolismoRESUMO
Malignant pheochromocytomas/paragangliomas (PCs/PGs) often have distant metastases to the skeleton, liver, and lungs. Radionuclide therapy is valuable for treatment of disseminated tumor disease and could be used as adjuvant therapy after surgery. Patients with local and/or distant metastases of PC/PG should be investigated preoperatively by scintigraphy using both 123I-MIBG and 111In-DTPA-D-Phe1-octreotide, to evaluate the possibilities for radionuclide therapy (i.e., a dosimetric estimation of radiation dose to the tumor tissue versus critical normal tissues). Individual patient dose-planning should be performed. For patients in whom positive therapeutic effects are anticipated radionuclide therapy can be applied. Therapy with both 131I-MIBG and 177Lu-octreotate might be favorable in individual patients with lesions visualized by both metaiodobenzylguanidine (MIBG) and octreotide scintigraphy with enhanced therapeutic effects and reduced side effects.
Assuntos
3-Iodobenzilguanidina/uso terapêutico , Neoplasias das Glândulas Suprarrenais/radioterapia , Radioisótopos do Iodo/uso terapêutico , Feocromocitoma/radioterapia , HumanosRESUMO
BACKGROUND/PURPOSE: Gross total resection of the primary tumor in treatment of high-risk neuroblastoma remains controversial. Furthermore, there are few reports of the effect of primary tumor resection on local control as opposed to overall survival. The authors reviewed their institutional experience to assess the effect of primary tumor resection on local control and overall survival. METHODS: A total of 141 patients were treated on protocol between November 1, 1979 and June 25, 2002 and are the subject of this report. Gross total resection was assessed by review of operative notes, postoperative computerized axial tomograms, and postoperative meta-iodobenzyl guanidine (MIBG)1 scans when available. RESULTS: The median age was 3.3 years, and all patients were International Neuroblastoma Staging System (INSS) stage 4 with 79% having metastases to cortical bone. The primary site was the adrenal gland in 74%, the central abdominal compartment in 13%, the posterior mediastinum in 7%, and other sites in 6%. Gross total resection was accomplished in 103 (73%) but was more than 90% for the last 3 protocols. Five kidneys were lost overall. The probability of local progression was 50% in unresected patients compared with 10% in patients undergoing gross total resection (P <.01). Overall survival rate in resected patients was 50% compared with 11% in unresected patients (P <.01). CONCLUSIONS: Our data indicate that local control and overall survival rate are correlated with gross total resection of the primary tumor in high-risk neuroblastoma. Gross total resection should be part of the management of stage 4 neuroblastoma in patients greater than 1 year of age.
Assuntos
Neoplasias Abdominais/tratamento farmacológico , Neoplasias Abdominais/cirurgia , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/cirurgia , Neoplasias do Mediastino/tratamento farmacológico , Neoplasias do Mediastino/cirurgia , Neuroblastoma/tratamento farmacológico , Neuroblastoma/cirurgia , Neoplasias Abdominais/mortalidade , Neoplasias Abdominais/patologia , Neoplasias Abdominais/radioterapia , Adolescente , Neoplasias das Glândulas Suprarrenais/mortalidade , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/radioterapia , Adulto , Análise de Variância , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Progressão da Doença , Humanos , Lactente , Radioisótopos do Iodo , Neoplasias do Mediastino/mortalidade , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/radioterapia , Estadiamento de Neoplasias , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Neuroblastoma/radioterapia , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
INTRODUCTION: Iodine 131-meta-iodobenzylguanidine ((131)I-MIBG) has been applied to the palliative treatment of metastatic pheochromocytoma in small studies. We report our institutional experience for the treatment of metastatic pheochromocytoma and paraganglioma. METHODS: We performed a retrospective review of 33 patients with metastatic pheochromocytoma (n=22) and paraganglioma (n=11) treated at our institution with (131)I-MIBG over a 10-year period. RESULTS: Patients received a mean dose of 388+/-131 mCi (131)I-MIBG. Median survival after treatment was 4.7 years. Most patients experienced a symptomatic response leading to an improved survival (4.7 years vs 1.8 years, P<.01). Patients with a measurable hormone response demonstrated an increased survival in comparison to those with no response (4.7 years vs 2.6 years, P=.01). Patients who received a high dose (>500 mCi) as their initial therapy also had improved survival (3.8 years vs 2.8 years, P=.02). CONCLUSION: These data support (131)I-MIBG treatment for select patients with metastatic pheochromocytoma. In our experience, prolonged survival was best predicted by symptomatic and hormone response to (131)I-MIBG treatment. An initial dose of 500 mCi may be optimal. The benefit of (131)I-MIBG treatment for metastatic pheochromocytoma must also be weighed against its side effects.
Assuntos
3-Iodobenzilguanidina/uso terapêutico , Neoplasias das Glândulas Suprarrenais/radioterapia , Paraganglioma/radioterapia , Feocromocitoma/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Adulto , Idoso , Relação Dose-Resposta à Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de SobrevidaRESUMO
[(131)I]Metaiodobenzylguanidine ([(131)I]MIBG) targeted radiotherapy is effective in debulking childhood neuroblastoma. The high-energy beta-emitter [(131)I]MIBG is, however, not very well suited to treat submillimeter tumors. The [(125)I]MIBG emission is more fully absorbed in small target volumes and therefore advocated for treatment of microscopic neuroblastoma. We investigated whether i.v. [(125)I]MIBG can have a therapeutic advantage over i.v. [(131)I]MIBG in realistic animal models. We used BALB/c nu/nu mice, bearing neuroadrenergic xenografts which differ in MIBG handling, i.e., extragranular vs. granular MIBG storage in the SK-N-SH human neuroblastoma and PC12 rat pheochromocytoma, respectively. Groups of 4-9 animals were treated with 10-100 MBq radioiodinated MIBG. Responses were calibrated against the effect of 4-5 Gy of external beam X-rays. SUBCUTANEOUS XENOGRAFTS: Due to the more extensive MIBG accumulation, the estimated MIBG exposure of the PC12 tumor was nearly 20-fold higher compared with the SK-N-SH xenograft which corresponded with a marked, i.e., nine-fold increased tumor growth delay after radioiodinated MIBG therapy. Both xenografts were equally sensitive to high-dose rate local irradiation. In neuroblastoma as well as pheochromocytoma, the therapeutic efficacy of [(131)I]MIBG was 6 times higher compared to the [(125)I]MIBG which is in reasonable agreement with the reported "131-I over 125-I" ratio of approximately 9 for the calculated absorbed radiation doses per unit of radioactivity. Apparently, the neuroblastoma was not relatively more sensitive to the (ultra)short range emitter [(125)I]MIBG than the pheochromocytoma, indicating that its therapeutic efficacy is independent of the intracellular MIBG storage mode. MICROSCOPIC TUMORS: The pheochromocytoma model consisted of widespread disease after i.v. cell injection with survival as endpoint. For the neuroblastoma, we induced focal intrahepatic microscopic tumors by intrasplenic injection and evaluated total liver weights 26 days after therapy. Theoretically, the therapeutic potential of [(125)I]MIBG at the cellular level should be at least as high as [(131)I]MIBG, but we failed to show any effect of [(125)I]MIBG therapy in both models. In contrast, measurable responses were obtained with [(131)I]MIBG, but these were lower than in the s.c. tumors when related to the responses induced by external X-rays. In conclusion, [(131)I]MIBG is decreasingly effective in microscopic disease and can therefore not be curative as a single agent. Our results strongly argue against the clinical use of [(125)I]MIBG and indicate that conventional total body irradiation was superior to [(131)I]MIBG for microscopic neuroblastoma. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 312-325 (2000).
Assuntos
3-Iodobenzilguanidina/uso terapêutico , Neoplasias das Glândulas Suprarrenais/radioterapia , Antineoplásicos/uso terapêutico , Radioisótopos do Iodo/uso terapêutico , Neuroblastoma/radioterapia , Feocromocitoma/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , 3-Iodobenzilguanidina/efeitos adversos , Animais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Células PC12 , Ratos , Transplante HeterólogoRESUMO
Malignant pheochromocytomas are rare. Although 5-year survival is less than 50%, the prognosis varies. Some patients, even those with extensive metastases, have been followed up for many years. If the tumor tissue's uptake is adequate (> 5 Gy/100 mCi) the therapeutic use of 131I-meta-iodobenzylguanidin (131I-MIBG) is at present the therapy of first choice. The use of cytostatic chemotherapy should be limited to patients with rapidly progressive disease.
Assuntos
Neoplasias das Glândulas Suprarrenais/radioterapia , Radioisótopos do Iodo/uso terapêutico , Iodobenzenos/uso terapêutico , Feocromocitoma/radioterapia , 3-Iodobenzilguanidina , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Humanos , Metástase Neoplásica , Feocromocitoma/tratamento farmacológico , Feocromocitoma/mortalidade , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Pretreatment with [131I] metaiodobenzylguanidine (MIBG) followed by surgical resection in advanced neuroblastoma (stage 3 and 4) has been studied in relation to resectability, morbidity and mortality, survival rate after two years, control of distant metastasis and serum levels of LDH as prognostic factors. Twenty-one patients with advanced neuroblastoma were primarily treated with MIBG radiotherapy, followed by surgical resection. Sixteen patients had stage 4 disease. Between 2 and 6 courses of MIBG treatment were given per patient. In 17 patients gross complete resection was achieved. Two patients developed complications directly related to the operation, one died as a result of this. The overall mortality was 38%. MIBG therapy resulted in partial response in 13 patients and in stable disease in 8 patients. Two years survival in the group with partial response was 86% and in the group with stable disease 28%. Because of the resulting excellent general condition of the patients the interval between pretreatment with MIBG and surgery could be very short. Follow-up till December 1994 showed that 13 children were alive for 3 to 47 months. Seven had no evidence of disease. Preoperative MIBG de novo treatment in advanced neuroblastoma is equal to induction chemotherapy, but less toxic.
Assuntos
Neoplasias das Glândulas Suprarrenais/radioterapia , Antineoplásicos/uso terapêutico , Radioisótopos do Iodo/uso terapêutico , Iodobenzenos/uso terapêutico , Neuroblastoma/radioterapia , Neoplasias do Sistema Nervoso Periférico/radioterapia , 3-Iodobenzilguanidina , Adolescente , Neoplasias das Glândulas Suprarrenais/mortalidade , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Humanos , Lactente , Masculino , Estadiamento de Neoplasias , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Neuroblastoma/cirurgia , Neoplasias do Sistema Nervoso Periférico/mortalidade , Neoplasias do Sistema Nervoso Periférico/patologia , Neoplasias do Sistema Nervoso Periférico/cirurgia , Radioterapia Adjuvante , Taxa de Sobrevida , Sistema Nervoso Simpático/patologia , Sistema Nervoso Simpático/efeitos da radiação , Sistema Nervoso Simpático/cirurgiaRESUMO
The avidity of many metastatic pheochromocytomas and neuroblastomas for metaiodobenzylguanidine (MIBG) observed at diagnostic scintigraphy has led to attempts to treat these lesions with large doses of MIBG. We and others have achieved therapeutic responses with 131I-MIBG (usually partial) in about a third of malignant pheochromocytomas. A small but important subgroup of advanced, poor prognosis neuroblastomas which have been resistant to all other therapies have also shown responses including occasional long-term survival (> 5 years) and apparent complete responses to 131I-MIBG. Because the physical properties of 131I are suboptimal for the delivery of therapeutic radiation to bone marrow micrometastases, a frequent problem in neuroblastoma, we have performed preliminary studies in poor prognosis Stage III and VI neuroblastoma using 125I-MIBG which has more satisfactory emissions. This has led to prolonged tumor stabilization and survival (> 19 to > 52 months) in 5 of 10 patients. MIBG radiopharmaceutical treatment of neuroendocrine tumor patients must still be considered an experimental but nevertheless promising treatment modality.
Assuntos
Neoplasias das Glândulas Suprarrenais/radioterapia , Radioisótopos do Iodo/uso terapêutico , Iodobenzenos/uso terapêutico , Neuroblastoma/radioterapia , Feocromocitoma/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , 3-Iodobenzilguanidina , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Adulto , Neoplasias da Medula Óssea/radioterapia , Neoplasias da Medula Óssea/secundário , Criança , Humanos , Radioisótopos do Iodo/administração & dosagem , Radioisótopos do Iodo/química , Iodobenzenos/administração & dosagem , Recidiva Local de Neoplasia/radioterapia , Estadiamento de Neoplasias , Neoplasia Residual/radioterapia , Neuroblastoma/diagnóstico por imagem , Neuroblastoma/secundário , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/secundário , Prognóstico , Cintilografia , Compostos Radiofarmacêuticos/administração & dosagem , Dosagem Radioterapêutica , Indução de Remissão , Taxa de SobrevidaRESUMO
Adrenocortical carcinoma is a rare disease which is primarily approached surgically. There have been few reports of the efficacy of radiation therapy and, for the most part, these have been anecdotal. This paper reports on the potential adjuvant role of radiation therapy after surgical excision of primary adrenal cortical carcinoma and also comments about the efficacy of palliative radiation therapy for metastases. We have identified eight patients treated for adrenal cortical carcinomas at Hahnemann University Hospital (HUH) from 1962 until the present and have also identified five patients with the same diagnosis at Philadelphia General Hospital (PGH) from 1962 until its close in 1975. These two groups are examined separately. In the PGH group, in which two patients were diagnosed at autopsy and only one patient was treated by radiation therapy, the median survival was between 0 and 1 month for Stage IV disease with the only patient surviving to 6 months being that patient receiving radiation therapy. In the HUH group, five of eight patients were treated adjunctively after diagnosis, one was not and two received palliative therapy. The median survival for treated Stage III patients was between 34 months and 7 years. The suggestion, based on a limited patient series, is that patients treated postoperatively to the tumor bed and nodal areas in Stage III disease may have improved survival over historic series and improved local control.
Assuntos
Neoplasias das Glândulas Suprarrenais/radioterapia , Carcinoma/radioterapia , Neoplasias das Glândulas Suprarrenais/cirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma/secundário , Carcinoma/cirurgia , Criança , Terapia Combinada , Feminino , Humanos , Linfonodos/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Mitotano/uso terapêutico , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Cuidados Paliativos , Dosagem Radioterapêutica , Taxa de SobrevidaRESUMO
The selective uptake and accumulation of 131J-Metaiodobenzylguanidine in neuroblastoma cells in vivo may be utilized for targeted irradiation. The experience with 32 neuroblastoma patients refractory to conventional high dose chemotherapy is reported. At diagnosis 8 patients had Evans stage III and 22 stage IV. 11/32 experienced recurrences after complete tumor disappearance and before mIBG treatment, 16/32 progressed from residual or nonresponding tumor and in 3/32 insufficient tumor regression by chemotherapy was observed. 2 children received one mIBG course each with no evidence of disease. Mean applied activity was 128 mCi per course (35-300 mCi), 360 mCi per patient (80-1033 mCi) and 19.2 mCi/kg per patient (3.2-37.9 mCi/kg), respectively. A total of 84 courses was given (mean 2.6 per patient). Pain relief was noticed in 14/14 patients with bone pain. Complete or very good partial remission was achieved in 5/32, partial remission in 11/32 and stable disease in 6/32 patients. In 8 children progression occurred and 2 patients were not evoluable. 20 children died, 12 are still alive (6 patients with initial stage IV, 6 with stage III disease). Main side effect was transient thrombocytopenia, which became more severe with increasing number of courses. We conclude that mIBG treatment is effective in some patients with refractory neuroblastoma and may be utilized in the future as front line therapy for patients achieving only incomplete regressions after high dose chemotherapy.
Assuntos
Neoplasias das Glândulas Suprarrenais/radioterapia , Radioisótopos do Iodo/uso terapêutico , Iodobenzenos/uso terapêutico , Neuroblastoma/radioterapia , 3-Iodobenzilguanidina , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Criança , Terapia Combinada , Humanos , Metástase Neoplásica , Neuroblastoma/tratamento farmacológicoRESUMO
Following a case report that oral nifedipine can suppress the secretion of noradrenaline by phaeochromocytoma, we examined the effect of nifedipine on the tumour kinetics of tracer 131I-meta-iodobenzylguanidine (131I-mIBG) in five patients referred for mIBG radionuclide therapy for disseminated malignant phaeochromocytoma. In one subject a striking modification of mIBG kinetics was found that resulted in a doubling of the absorbed dose to tumour while the patient was taking nifedipine. At the same time, urinary excretion of noradrenaline was suppressed by a factor of three. The effect of nifedipine in this patient was confirmed when tracer studies were repeated nine months later. The changes in tumour kinetics were shown to be due to prolonged retention of mIBG rather than increased tumour blood flow or alteration of the curve of mIBG plasma concentration as a function of time.
Assuntos
Neoplasias das Glândulas Suprarrenais/radioterapia , Radioisótopos do Iodo/uso terapêutico , Iodobenzenos/farmacocinética , Nifedipino/farmacologia , Feocromocitoma/radioterapia , 3-Iodobenzilguanidina , Neoplasias das Glândulas Suprarrenais/metabolismo , Humanos , Iodobenzenos/uso terapêutico , Nifedipino/uso terapêutico , Feocromocitoma/metabolismoRESUMO
Radioiodinated meta-iodobenzylguanidine, a recently developed radiopharmaceutical, has been shown to permit safe, noninvasive, sensitive, and specific scintigraphic location of pheochromocytomas of all types. The technique is especially efficacious in the case of extraadrenal primary lesions and locally recurrent and metastatic tumors. In addition to being taken up by pheochromocytomas, meta-iodobenzylguanidine may be used to image neuroblastomas, nonfunctioning paragangliomas, and carcinoid tumors. Lesions with high 131I-meta-iodobenzylguanidine uptake may respond to treatment with large doses of this radiopharmaceutical.