Neuroblastoma in adolescents and adults: the Memorial Sloan-Kettering experience

BACKGROUND: We reviewed the utility of different treatment modalities in a large series of adolescents/adults with neuroblastoma (NB). PROCEDURE: The 30 adolescents/adults (median age, 19 years) had stage 2B (n = 1), 3 (n = 2), or 4 (n = 27) NB. Treatments included conventional and myeloablative therapy; local radiotherapy (RT); immunotherapy with anti-G(D2) 3F8 monoclonal antibody +/- granulocyte-macrophage colony-stimulating factor (GM-CSF); and 3F8 alternating with low-dose oral etoposide. RESULTS: Seven patients are in first (n = 4) or second (n = 3) complete/very good partial remission (CR/VGPR) at 9+ to 181+ (median, 45+) months. Among 13 newly diagnosed or minimally prior-treated patients, no major responses were seen in 4/4 treated with N4/N5 chemotherapy, but 6/9 treated with the higher dose N6/N7 regimens and surgery had major responses, and immunotherapy produced CR in BM in three patients. Among 17 patients referred because of resistant NB, favorable responses occurred in 6/12 treated with high-dose cyclophosphamide-based salvage therapy, including one patient who is in CR 170+ months after myeloablative consolidation and five patients who achieved CR/VGPR after 3F8/GM-CSF (n = 4) or 3F8/oral etoposide (n = 1). With a median follow-up of 32+ months post-RT, no local relapses occurred in 10/10 patients who received hyperfractionated 21 Gy RT to prevent regrowth of soft tissue masses that had been resected. CONCLUSIONS: High-dose chemotherapy and surgery can achieve a minimal disease state in >50% of newly diagnosed older NB patients. In that setting, local RT, and the use of agents with recently confirmed anti-NB activity, including anti-G(D2) antibodies, and cis-retinoic acid, may improve the poor prognosis of these patients reported to date.     

High-dose chemotherapy and autologous blood stem cell transplantation in children with metastatic neuroblastoma

High-dose chemotherapy (HDC) followed by autologous blood stem cell transplantation (ABSCT) was performed to improve the prognosis of children with metastatic neuroblastoma over 1 year of age at diagnosis. Seven stage IV neuroblastoma patients with a median age of 3.9 years (range 1.6–11.4 years) received conventional chemotherapy before leukapheresis for ABSCT. The median duration of chemotherapy before harvest was 8 months (range 3–23 months). Peripheral blood stem cells (PBSC) were harvested from them after the use of cytotoxic drugs plus granulocyte colony-stimulating factor. The median number of granulocyte-macrophage colony forming units collected after harvest was 23.2 × 10⁴/kg (range 10.1–45.3 × 10⁴/kg). The patients were administered HDC consisting of carboplatin, etoposide, and melphalan followed by ABSCT. Hematopoietic reconstitution after ABSCT was favorable; recovery of granulocytes count > 0.5 × 10⁹/L occurred within 2 weeks and stable platelet engraftment occurred at a median duration of 23 days (range 7–33 days). The toxicity of ABSCT was well tolerable. Two of the four patients who received ABSCT at their first complete remission remained in remission 67 and 68 months after ABSCT. One with partial remission also showed a good response for 8 months. The other two at first relapse showed a transient regression of the tumor. The prognosis of seven patients who received ABSCT was significantly better than that of 13 patients who received conventional therapy alone. These findings suggest that HDC followed by ABSCT is safe and useful as consolidation therapy for the treatment of patients with metastatic neuroblastoma.     

Relapse of Hodgkin disease after extended-field radiotherapy

Thirteen relapses occurred among 51 consecutive surgically staged patients with I, IIA, and IIIA Hodgkin disease who achieved complete remission following extended-field radiotherapy. The median disease-free interval was 14 months, but three disseminated relapses occurred at 36, 36, and 39 months. In 6 of the 13 cases, relapses occurred within treated fields. Relapse frequency was greater with advancing stage, but was not related to histology. In 9 of 12 evaluable cases the patients achieved complete remission with MOPP combination chemotherapy. All responders continue in complete remission a median time of 23 months after completing MOPP. This report emphasizes the need for sustained, close follow-up after radical radiotherapy and the excellent response rate of relapsed patients to MOPP combination chemotherapy.     

Carcinoma of the choroid plexus: A pediatric experience

Carcinoma of the choroid plexus (CCP) is a rare tumor of the central nervous system which occurs more frequently in patients under 3 years of age. We report 10 cases of CCP in children. There were 5 males and 5 females, aged 5 to 84 months at diagnosis (median 32 months). Eight CCP were located in the lateral ventricle and 2 in the fourth ventricle. All patients underwent initial surgery, with complete resection in 5 cases. Postoperative treatment included radiotherapy alone in 4 patients, chemotherapy alone in 4, both in 1 patient, and no further treatment in one patient. Six patients remain in first continuous complete remission with a follow-up of 12 to 156 months (mean 34 months). Five of these six patients had a complete surgical resection of their tumor and 4 of them received chemotherapy alone. A comparison with the series in the literature suggests that total resection of the tumors is the major prognostic factor for survival. Recourse to additional treatments to prevent local relapses and CNS dissemination seems necessary. In our opinion, radiotherapy should be avoided as far as possible because of its deleterious effect in very young children. As some of the long term survivors did not receive radiation treatment, we conclude that CCP can be treated post operatively using chemotherapy protocols designed for infants with malignant brain tumors. © 1993 Wiley-Liss, Inc.     

Immune reconstitution after autologous purged bone marrow transplantation in children

PURPOSE: Immune reconstitution was studied in 30 children who had received purged autologous bone marrow transplantation for neuroblastoma or acute myeloid leukemia (AML). METHODS: Patients with neuroblastoma received high-dose chemotherapy and total body irradiation, and patients with AML received chemotherapy alone. Marrows were purged ex vivo with either antineuroblastoma monoclonal antibodies (neuroblastoma) or 4-hydroperoxycyclophosphamide (AML). Lymphocyte subsets, mitogen stimulation studies, and immunoglobulin levels were studied every 4 months. RESULTS: There were no significant differences between the two groups of patients in lymphocyte number or subsets over time. In both groups, CD2+ and CD4+ cells were below normal in 33% of patients at 12 months. CD4+/CD8+ ratios were below normal for up to 8 months after transplantation and natural killer cells were elevated for up to 2 years in most patients. Median IgG and IgA levels were below the age mean even at 2 years after transplantation, although patients with AML had significantly higher IgG levels at 12 months compared with those with neuroblastoma. Lymphocyte proliferative responses to mitogens were markedly reduced at 4 months but returned to normal at 8 months. Despite the delay in immune reconstitution, there were no life-threatening infections. CONCLUSIONS: There appeared to be little difference in the overall kinetics of immune reconstitution between the children with neuroblastoma, who received total body irradiation and high-dose chemotherapy, and those with AML, who received high-dose chemotherapy alone as their pretransplant preparative regimen.     

Clinical efficacy of combined therapy in children with stage 4 neuroblastoma北大核心CSCD

目的 观察4期神经母细胞瘤联合治疗的早期疗效,探讨提高生存率及改善生活质量的治疗方案。 方法 对2016年1月至2021年6月在香港大学深圳医院确诊的14例4期神经母细胞瘤患儿的临床资料、治疗及随访情况进行回顾性分析。 结果 14例患儿中位发病年龄为3岁7.5个月。骨髓检查阳性9例,N-Myc基因扩增4例,神经元特异性烯醇化酶增高13例,尿香草扁桃酸增高7例。病理结果：分化型6例,未分化型1例,混合型1例,分化差型6例。N7方案化疗10例（含2例N7方案+三氧化二砷化疗患儿）,Rapid COJEC方案化疗4例。手术13例;自体造血干细胞移植14例;放疗10例。Ch14.18/CHO免疫治疗8例,其中1例因在治疗过程中出现过敏性休克而停止免疫治疗;其余7例完成治疗,期间未观察到严重不良反应。完成免疫治疗患儿中1例复发后进行3次Lu177 Dotatate治疗,目前仍在化疗中。14例患儿中位随访时间为45个月。2年内复发4例,2年内总生存率100%;3年内复发4例,3年内无病存活7例。 结论 儿童4期神经母细胞瘤建议选择多学科联合方案治疗,使4期神经母细胞瘤患儿获得更好的生存及预后。     

Management of localized thoracic neuroblastoma

Thirteen children with localized (Evans stage I or II) thoracic primary neuroblastoma were divided into two groups according to the type of therapy administered, in order to compare the therapeutic efficacy and morbidity of excisional surgery followed by either irradiation alone or irradiation plus chemotherapy (group A) with similar surgery alone (group B). Group A consisted of 6 children (mean age 1 year, 2 months). Complete surgical excision was accomplished in 2 patients, while 4 had microscopic residual. All 6 patients are free of disease at 26--76 months (mean 47 months), including 2 who had recurrent tumor and received additional therapy. Two have developed congestive heart failure and one severe scoliosis secondary to irradiation. Of the 7 children in group B (mean age 2 years, 2 months), 3 had microscopic residual tumor and 2 had adjacent lymph node involvement. After 12--47 months (mean 23 months), no recurrence or surgery-related morbidity has been observed. From these limited data it appears that surgery alone may provide adequate therapy for localized thoracic neuroblastoma and obviate the morbidity associated with multimodal therapy.     

Autologous bone marrow transplantation for pediatric Wilms' tumor: The experience of the European bone marrow transplantation solid tumor registry

This survey includes 25 children with Wilms' tumor undergoing high-dose chemotherapy associated with autologous bone marrow transplantation (ABMT) in the period June 1984-December 1991 and enrolled in the European Bone Marrow Transplantation Registry for Solid Tumors. At diagnosis, 12 children presented stage IV disease, 5 stage III, 3 stage II, and 5 stage I. Before ABMT, 21 children had 1 to 4 relapses (median 1); 13 achieved a second or subsequent complete remission (CR), four stage IV children failed to respond to first line treatment and achieved either CR (3 patients), or partial remission (PR) after second line therapy. At high-dose chemotherapy, 17 children were in CR and 8 had measurable disease. Seven different high-dose regimens were administered, even if 20 children received melphalan mostly associated with vincristine and 8 involved field radiotherapy. Three children died early of pneumonitis; 2 developed an acute transient renal failure, 1 a chronic renal failure. Out of the 8 children with target disease at graft, 2 died of toxicity, 5 achieved CR, 1 obtained PR, and only 1 is presently alive in CCR at 39 months after ABMT. Of the 17 children grafted in CR, 8 are alive event-free at 14-90 months (median 34) from ABMT; 7 relapsed at 3-23 months (median 7 months); 1 died of toxicity and 1 was lost to follow-up in CR at 12 months. A salvage attempt with high-dose chemotherapy in children with resistant or poor prognosis recurrent Wilms' tumor seems to be justified. An international cooperative protocol taking into account the increased risk of lung and renal toxicity is necessary. © 1994 Wiley-Liss, Inc.     

Long-term neurologic outcome in children with opsoclonus-myoclonus associated with neuroblastoma: A report from the Pediatric Oncology Group

A retrospective data collection was performed on 29 children diagnosed with neuroblastoma and opsoclonus-myoclonus between 1983–1993 from Pediatric Oncology Group institutions. The aim was to describe neurologic outcome in children with neuroblastoma and opsoclonus-myoclonus. Age at diagnosis ranged from one month to 4 years (median age, 18 months). The duration of opsoclonus-myoclonus symptoms prior to the diagnosis of neuroblastoma ranged from 6 days to 17 months (median duration, 6 weeks). There was a prevalence of low stage disease according to the POG staging system; stage A (n = 18), stage B (n = 3), stage C (n = 7), stage D (n = 1). There was a predominance of paraspinal primary tumors. There was no case of N-myc amplification (0/17), and 2/8 cases were diploid. Treatment for neuroblastoma consisted of surgery alone in 19/29 (18 stage A, 1 stage C in thorax), and surgery plus chemotherapy in 10/29. No patient received radiotherapy. Treatment for opsoclonus-myoclonus ranged varied. Six children received no treatment for opsoclonus-myoclonus. The following agents were used aCTH (n = 14), prednisone (n = 12), IV IgG (n = 6), immuran (n = 2), depakote (n = 1), and inderal (n = 1). Eighteen of 29 children (62%) had resolution of opsoclonus-myoclonus symptoms. The range of time for recovery was a few days to 3 years. However the majority recovered over several months. Twenty of 29 children (69%) had persistent neurologic deficits including speech delay, cognitive deficits, motor delay, and behavioral problems. Of the 9 children who had complete recovery of opsoclonus-myoclonus without neurologic sequelae, age at diagnosis and duration of symptoms were not different from the entire group. Interestingly, 6/9 children with complete recovery received chemotherapy as part of their treatment. In conclusion, persistent neurologic deficits are characteristic for children with neuroblastoma and opsoclonusmyoclonus. Treatment with chemotherapy may improve the neurologic outcome. Med. Pediatr. Oncol. 28:284–288. © 1997 Wiley-Liss, Inc.     

N7: a novel multi-modality therapy of high risk neuroblastoma (NB) in children diagnosed over 1 year of age

BACKGROUND: The N7 protocol for poor-risk neuroblastoma uses dose-intensive chemotherapy (as in N6 protocol [Kushner et al.: J Clin Oncol 12:2607-2613, 1994] but with lower dosing of vincristine) for induction, surgical resection and 2100 cGy hyperfractionated radiotherapy for local control, and for consolidation, targeted radioimmunotherapy with 131I-labeled anti-GD2 3F8 monoclonal antibody and immunotherapy with unlabeled/unmodified 3F8 (400 mg/m2). PROCEDURE: The chemotherapy consists of: cyclophosphamide 70 mg/kg/d x 2 and a 72-hr infusion of doxorubicin 75 mg/m2 plus vincristine 2 mg/m2, for courses 1, 2, 4, and 6; and cisplatin 50 mg/m2/d x 4 and etoposide 200 mg/m2/d x 3, for courses 3, 5, and 7. 131I-3F8 is dosed at 20 mCi/kg, which is myeloablative and therefore necessitates stem-cell support. RESULTS: Of the first 24 consecutive previously untreated patients more than 1 year old at diagnosis, 22 were stage 4 and two were unresectable stage 3 with MYCN amplification. Chemotherapy achieved CR/VGPR in 21 of 24 patients. Twenty patients to date have completed treatment with 131I-3F8, and 15 patients have completed all treatment. With a median follow-up of 19 months, 18 of 24 patients remain progression-free. CONCLUSIONS: Major toxicities were grade 4 myelosuppression and mucositis during chemotherapy, and self-limited pain and urticaria during antibody treatment. Late effects include hearing deficits and hypothyroidism.     

CEM为预处理方案的自体外周血造血干细胞移植治疗晚期神经母细胞瘤相关毒性及疗效观察

目的　观察以CEM (卡铂 +VP 16 +马法兰 )为预处理方案的自体外周血造血干细胞移植治疗晚期神经母细胞瘤患儿的毒性和疗效。方法　研究经大剂量放、化疗及手术治疗达完全缓解的IV期神经母细胞瘤患儿 6例 ,采用CEM预处理方案 (卡铂每日 4 2 5mg/m2 共 4d ,VP 16每日 338mg/m2 共 4d ,马法兰每日 70mg/m2 共 3d)的自体外周血造血干细胞移植 ,并依据Bearman标准对预处理毒性进行评价 ,对其造血重建、并发症及预后进行观察。结果　预处理后髓外毒性除 1例为I级肝损害外 ,主要表现在口腔粘膜 (I级 6例 )和胃肠道 (I级 5例 ,II级 1例 )损害。白细胞于移植后 3± 0 .5d达到 0 ,移植后 33± 3.1d稳定于 1× 10 9/L以上。除 1例患儿移植后 11个月颅内转移外 ,余 5例患儿均健康存活。随诊时间分别为 8、10、2 3、36及 4 8个月。结论　以CEM为预处理方案的自体外周血造血干细胞移植可以安全、有效的治疗IV期神经母细胞瘤。     

Experience of the Izmir Pediatric Oncology Group on Neuroblastoma: IPOG-NBL-92 Protocol

This multicentric study aimed to bring neuroblastoma patients together under IPOG-NBL-92 protocol and evaluate the results within the period between 1992 and 2001 in Izmir. Sixty-seven neuroblastoma patients from 4 pediatric oncology centers in Izmir were included in the study. IPOG-NBL-92 protocol modified from German Pediatric Oncology (GPO)-NB-90 protocol was applied: Patients in stage 1 received only surgery, while surgery plus 4 chemotherapy courses (cisplatin, vincristine, ifosfamide) were given in stage 2 and surgery plus 6 chemotherapy courses (cisplatin, vincristine, ifosfamide, epirubicin, cyclophosphamide) were given in stages 3 and 4 patients. In patients who were kept in complete remission (CR), a maintenance therapy of one year was applied. Radiotherapy was given to the primary site following induction chemotherapy plus surgery in stages 3 and 4 patients with partial remission (PR). The stages of the patients were as follows: 5% in stage 1, 39% in stage 3, 49% in stage 4, and 7% in stage 4S. Primary tumor site was abdomen in 88% of cases. CR rates were as 100% in stage 1, 76% in stage 3, 35% in stage 4, and 75% in stage 4S. Relapse was observed in 32% of patients in a median of 19 months. The median follow-up time for survivors was 33 (17-102) months. Five-year OS rate was 31% and the EFS rate was 30% in all patients. Five-year overall and event-free survival rates were 63 and 30% in stage 3, but 6 and 5%, respectively, in stage 4 patients. Univariate analysis established that the age, stage, primary tumor site, and high LDH and NSE levels conferred a significant difference. The IPOG-NBL-92 protocol has proved to be satisfactory with tolerable toxicity and reasonable CR and survival rates. However, more effective treatments suitable to Turkey's social and economic conditions are urgently needed for children over 1 year of age with advanced neuroblastoma.     

Desmoplastic small round cell tumour in children and adolescents

BACKGROUND: Desmoplastic small round cell tumour (DSRCT) is a rare highly aggressive neoplasm, and clinical studies are scarce. PROCEDURE: We report six cases of children and adolescents (median age 14 years, range 6.9-17.5) with DSRCT (5 abdominal, 1 paratesticular) registered by the Italian Cooperative Group (ICG) for soft tissue sarcoma over a 9-year period. Patients received a multidisciplinary treatment, including aggressive initial or delayed surgery and radiotherapy. Chemotherapy regimen was based on the use of ifosfamide, vincristine, dactinomycin, and a few doses of antharacyclines (doxorubicin or epirubicin). RESULTS: Complete surgical resection was possible only for the paratesticular tumour. Among the patients with abdominal lesions, macroscopically radical excision was possible in only one case. All patients received multidrug chemotherapy, and tumour reduction was obtained in the 4 evaluable patients. No relapses were evident in the irradiated fields in the 4 patients who received radiotherapy. Two patients remained progression-free 22 and 63 months after diagnosis, one is in third complete remission, whereas three died 10-25 months after diagnosis. CONCLUSIONS: DSRCT is a chemosensitive tumour, but survival rates remain disappointing despite aggressive multimodality therapy. Our results support surgical tumour removal and radiotherapy to achieve local control. Our experience and a review of the literature suggest that patients with localised abdominal tumours or a paratesticular primary may have a better prognosis.     

Isolated breast relapse after allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia

Unusual sites of relapses following bone marrow transplantation (BMT) for childhood acute lymphoblastic leukemia (ALL) are rarely reported. We report the case of a 16-year-old girl who presented with an isolated right breast relapse 8 months after allogeneic BMT for ALL in second remission. Biopsy showed an ALL infiltrate. Bone marrow and CSF were normal. The girl never showed before extramedullary involvement. She was treated with local radiotherapy and mild systemic chemotherapy. Nine months after breast relapse, she presented an isolated central nervous system relapse. The treatment of isolated extramedullary relapses following BMT is still controversial.     

Isolated breast relapse after allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia.

Unusual sites of relapses following bone marrow transplantation (BMT) for childhood acute lymphoblastic leukemia (ALL) are rarely reported. We report the case of a 16-year-old girl who presented with an isolated right breast relapse 8 months after allogeneic BMT for ALL in second remission. Biopsy showed an ALL infiltrate. Bone marrow and CSF were normal. The girl never showed before extramedullary involvement. She was treated with local radiotherapy and mild systemic chemotherapy. Nine months after breast relapse, she presented an isolated central nervous system relapse. The treatment of isolated extramedullary relapses following BMT is still controversial.     

Hypothalamo-hypophyseal-testicular function in prepubertal boys with acute lymphoblastic leukemia following chemotherapy and testicular radiotherapy

Hypothalamo-hypophyseal-testicular function was studied in twenty-eight prepubertal boys with ALL in clinical and haematological remission. Eighteen were treated with combined systemic chemotherapy (24-36 months) and the other ten, who had testicular leukemic infiltrates, received chemotherapy (38-60 months) and testicular radiotherapy (2 000 rad). Plasma levels of LH and FSH were measured before and after stimulation with LHRH (100 micrograms i.v.) and plasma levels of testosterone before and after stimulation with hCG (1 500 IU/48 h/7 doses). In patients treated with chemotherapy alone, mean basal LH and FSH, mean responses to LHRH stimulation and mean testosterone levels after stimulation with hCG did not significantly differ from those of the controls. Five of these patients who had normal testosterone values after three doses of hCG had testosterone values below the normal range after seven doses. In patients treated with chemotherapy and testicular radiotherapy, mean basal FSH and mean responses to LHRH stimulation were significantly higher than those of the controls. Testosterone values after stimulation with hCG were low in three and very low in the other seven. In both groups of patients data from testicular biopsies were consistent with functional results. We conclude that chemotherapy causes slight testicular damage, but chemotherapy and testicular radiotherapy produce severe testicular damage in patients with testicular leukemic infiltrates.     

Nasopharyngeal carcinoma in Turkish children: review of 33 cases.

A retrospective and prospective analysis is reported of epidemiological, clinical, and therapeutic aspects of 33 children with nasopharyngeal carcinoma who were treated in a single institution over a period of 10 years. Twenty-three male and 10 female children ranging from 9 to 17 years were referred to our center. Histopathology was WHO type 3 carcinoma in 21, WHO type 2 in 8, WHO type 1 in 1, and unclassified in 3 patients. Disease extent was T2a (n = 15), T2b (n = 2), T3 (n = 11), and T4 (n = 5); N1 (n = 5), N2 (n = 12), and N3a (n = 16). Five patients had base of skull invasion. Four patients had M1 disease on admission. Four patients were treated with irradiation only. Three patients received neoadjuvant, 4 patients received adjuvant, and 22 patients received neoadjuvant + adjuvant chemotherapy in addition to radiotherapy. Patients received 50-72 Gy to the primary tumor and involved nodes and 45-50 Gy to uninvolved regions. Chemotherapy consisted of combinations of cisplatin, fluorouracil or Adriamycin, vincristine, and cyclophosphamide. Twenty-nine patients (88%) attained locoregional control. Overall, 10 patients died with progressive disease or infectious complications, and 2 patients are still receiving therapy. Three patients are still living with multiple metastases and stable disease. Eight patients were lost to follow-up. Twelve patients are alive without relapse 3 and 63 months from diagnosis. Seven patients had 6 relapses at distant and 1 relapse at local site. The median time for first relapse was 8 months. Overall, the 5-year survival rate was 63% and disease-free survival rate was 53%. Although the locoregional control rate is high, long-term survival rates will be the real test of the impact of chemotherapy. Further studies are needed to confirm the optimal combination of effective chemotherapeutic agents and radiotherapy.     

儿童横纹肌肉瘤23例临床分析

目的：探讨儿童横纹肌肉瘤的临床特点、治疗和转归。方法：对1998年1月至2008年10月收治的23例横纹肌肉瘤患儿临床资料进行回顾性分析。结果：23例患儿中,男15例,女8例,平均发病年龄5岁(7个月至12岁)。依据美国横纹肌肉瘤研究组(IRS)的分期标准,I期2例,Ⅱ期4例,Ⅲ期8例,Ⅳ期9例。原发于头颈部14例,四肢4例,膀胱2例,肾脏、腹膜后及胆道各1例。所有患儿均经病理活检及免疫组织化学染色确诊。临床表现无特异性,主要为肿瘤组织占位、压迫、浸润后引起。治疗严格依照患儿IRS分期进行。2002年前化疗方案以VDCA、VAC 和VadrC 为主,2002年后采用美国肿瘤学中心研究组（COG）横纹肌肉瘤化疗方案。其中19例接受手术、化疗和放疗综合治疗的患儿2年生存率为63%,4例接受单纯手术或手术结合单一化疗或放疗的患儿生存期均未超过2年。结论：儿童横纹肌肉瘤临床表现无特异性;联合手术、放疗、化疗是治疗横纹肌肉瘤的有效方法。     

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.     

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.