Treatment of spinal involvement in neuroblastoma patients

INTRODUCTION: Considerable controversy exists regarding the appropriate management of spinal involvement in neuroblastoma (NB) patients. We review a large group of such patients and offer treatment recommendations. METHODS: Forty-six patients with epidural and/or neural foraminal involvement treated between 1987 and 1998 were staged according to the International NB Staging System (INSS) and classified as high-risk (INSS stage 4; n = 31) or low-risk (INSS stage <4; n = 15). Of 13 high- risk patients with normal neurologic examinations and no radiographic high-grade spinal cord compression (HGSCC), 12 were treated initially with chemotherapy, and only 1 demonstrated neurologic deterioration. HGSCC was present in 18 patients with high-risk NB; 7 of 10 (70%) treated initially with chemotherapy and 6 of 6 (100%) managed initially with operation improved or remained stable. All 9 low-risk patients with normal neurologic examinations and no HGSCC remained neurologically intact following operations (n = 7) or chemotherapy (n = 2). All 4 low-risk patients with HGSCC treated with operations improved or remained stable, and 0 of 2 (0%) low-risk patients treated initially with chemotherapy remained stable. Spinal deformities occurred in 2 of 16 patients (12.5%) treated nonoperatively and in 9 of 30 (30.0%) who underwent operations. CONCLUSIONS: High-risk NB patients with spinal involvement but normal neurologic examinations should be offered chemotherapy. High-risk patients with HGSCC may respond to chemotherapy, but a small percentage will require operations for progressive neurologic deficits. Chemotherapy may be avoided in low-risk patients who are offered potentially curative operations. Patients treated with operations for epidural disease are at high risk of subsequently developing spinal deformity.     

Lung involvement in neuroblastoma: Incidence and characteristics

The presence of lung metastases in neuroblastoma often leads to doubt about the diagnosis due to rarity of disease at this site. To determine more precisely the incidence and nature of pulmonary disease in neuroblastoma the data base of the European Neuroblastoma Study Group (ENSG) was examined. Information was obtained about 35/746 stage IV patients (and 1 patient who was registered as having stage II disease) documented to have pulmonary disease at presentation. Of these 5 were registered with pleural effusions, 18 pleural infiltrations, and 13 intrapulmonary lesions. Review of these cases, however, suggested that only 9 patients (1.2%; 95% exact confidence interval 0.42–1.99%, binomial distribution) had disease consistent with secondary neuroblastoma in lung or pleura. There was no correlation with clinical features, age, sex, or other disease sites, and outcome was uniformly poor. Med. Pediatr. Oncol. 28:429–432, 1997. © 1997 Wiley-Liss, Inc.     

Bilateral adrenal cystic neuroblastoma with hepatic and splenic involvement in a newborn

Bilateral cystic adrenal neuroblastoma is an unusual variant of neuroblastoma, and only two cases have been reported in the neonatal period until now. The authors describe a newborn with splenic and hepatic involvement of bilateral adrenal cystic neuroblastoma.     

伴有肝脏受累的神经母细胞瘤患儿临床特点及预后分析——单中心10年诊治总结

目的分析并总结单中心10年诊治的伴有肝脏受累的神经母细胞瘤(neuroblastoma,NB)患儿临床特点及预后,为进一步修订完善NB的诊疗方案提供依据。方法连续纳入2007年4月—2017年5月间于我院血液肿瘤病房就诊的、伴有肝脏受累的NB患儿临床资料。随访截止日期为2017年12月31日。采用χ~2检验进行临床特点分析,采用Kaplan-Meier进行生存分析。结果伴有肝脏转移NB患儿共77例,占13%(77/603),中位年龄为31(2～132)个月,男性41例,女性36例,肿瘤原发部位包括腹膜后(69例,占90%),纵膈(6例,占8%),其他部位(2例,占3%)。危险度分组:高危64例(83%),中危4例(5%),低危9例(12%)。影像学表现为肝转移(64%)或肝脏直接浸润(36%)。骨转移发生率为70%,骨髓转移发生率62%,肿瘤邻近脏器受累发生率为52%,进行MYC基因检测的患儿29%伴有MYC基因扩增,17%患者丙氨酸氨基转氨酶升高,18%患儿谷氨酰转移酶升高。77例患儿中59例(77%)规律接受BCH-NB危险度分组分层治疗,中位随访时间为19(6～122)个月。59例患儿5年累积总生存率为52%。单因素分析表明年龄≥12个月、LDH≥上限2倍、伴有N-MYC扩增、危险度分组为高危组患儿预后较差,5年总生存率差异具有显著性(P<0.05)。结论伴有肝脏血行转移且年龄≥12个月NB患儿更易发生远处转移,伴肝脏直接浸润NB患儿更易发生邻近器官的侵犯。丙氨酸氨基转氨酶及谷氨酰转肽酶均不能作为肝脏受累的酶学指标。肿瘤侵袭性强及肿瘤负荷高是影响这类患儿预后的重要因素。     

Stage II neuroblastoma. Adverse prognostic significance of lymph node involvement.

Thirty-three children aged between 1 month and 16 years (median 1 year, 7 months), were treated for stage II neuroblastoma with surgery, radiotherapy, or chemotherapy, alone or in combination. After 3 years 70% were living, 6 children had died from the disease, and 4 had died as a result of treatment. Patient characteristics (age, gender) and tumour characteristics primary site, presence of lymph node involvement, catecholamine excretion, histology) were reviewed in an attempt to determine prognostic features. While age under 1 year at diagnosis was, as expected, favourable in this series, the most important prognostic variable was the presence or absence of regional lymph node involvement. No patient with uninvolved nodes died of neuroblastoma and the difference in the 3-year survival rate between these patients and those with positive nodes was statistically significant. Although this study of patients treated between 1970 and 1977 provided no clear evidence that either postoperative radiotherapy or contemporary chemotherapy was of benefit, our findings suggest that subclassification of stage II patients into ''node-positive'' and ''node-negative'' groups will help to define those who might benefit from improved adjuvant postsurgical treatment.     

Liver involvement in neuroblastoma: the Memorial Sloan-Kettering Experience supports treatment reduction in young patients

BACKGROUND: We reviewed clinical and biologic findings in a series of infants with neuroblastoma (NB) in liver. The aim was to gain insights into improving therapy. PATIENTS AND METHODS: Among 19 newly or recently diagnosed infants with NB in liver, 1987-2002, those with stage 4 involving bone received chemotherapy, while those without bone or extensive bone marrow (BM) involvement were observed or received limited treatment if NB caused life-threatening symptoms. We assessed results in the context of NB treatment risk stratification, which is based on age, stage, and selected biologic features (MYCN, ploidy, histology). RESULTS: Six of eight infants with bone involvement became long-term event-free survivors including 1/2 with MYCN amplification and four who received only 4-6 cycles of chemotherapy; at the end of treatment, four infants had abnormalities in liver +/- the primary site, but these resolved. All 11 infants without bone lesions became long-term survivors with either no cytotoxic therapy or only one cycle of chemotherapy (+/- radiotherapy to liver), including four who had stage 4 and one stage 4S patient who still had NB in BM at age 15 months. CONCLUSIONS: Treatment reduction should be considered for subsets of infants with non-MYCN-amplified widespread NB: stage 4 without bone or extensive BM involvement may not require cytotoxic therapy, stage 4S with symptomatic hepatomegaly may not require multiple cycles of chemotherapy, and classic stage 4 may do well with limited chemotherapy. Persistent liver abnormalities post-treatment may not require continued therapy to achieve a radiologic complete remission.     

Detection of bone marrow involvement by neuroblastoma: Comparison of two cytological methods

In order to improve the assessment of bone marrow (BM) involvement by neuroblastoma, a study has been designated on aspirated material from ten BM sites. The classical method of smearing each BM aspirate (TK1) was compared to cytocentrifugation of the pool of BM samples after gradient density separation (TK2). Twenty smears from each technique were screened for the presence of tumor clumps. The screening was much easier and more rapid by TK2 than by TK1. Of the 103 procedures performed, 100 results were found concordant by both techniques, 3 were found negative by TK1 and positive by TK2. None was found positive by TK1 and negative by TK2. Of the 25 positive procedures, two had an equal number of positive smears by both techniques and 23 had more positive smears by TK2 than by TK1 (p < 0.001). Cytological examination of cytocentrifuge smears from the pool of BM samples after gradient density separation appears a simple, rapid and accurate technique for routine detection of BM involvement in neuroblastoma.     

Value of MRI and MIBG-I123 scintigraphy in the diagnosis of spinal bone marrow involvement in,neuroblastoma in children

The results of MRI and MIBG scintigraphy performed on the spine of 14 children with neuroblastoma are reported. In 6 cases of diffuse spinal bone marrow tumor infiltration, diagnosis is easier with MIBG scintigraphy than with MRI. In 5 cases, MRI detected hyposignal of the vertebral body without any spinal abnormality on MIBG scintigraphy. A discussion of the reasons for negative MIBG scintigraphy is presented and in these 5 cases, it is suggested that a lateral view of MIBG scintigraphy and HMDP-Tc^99m scintigraphy may be performed, even vertebral body biopsy in order to assess bone marrow tumoral infiltration.     

Myelofibrosis in neuroblastoma

Myelofibrosis, a rare childhood disorder, has been reported as an associated complication of certain hematologic malignancies or as an isolated idiopathic process. In this report, we describe a patient with metastatic neuroblastoma whose initial presentation included the findings of myelofibrosis and leukoerythroblastosis. The myelofibrosis regressed with chemotherapy and did not recur when the patient's tumor reappeared.