An approach for cure: PEI-chemotherapy and regional deep hyperthermia in children and adolescents with unresectable malignant tumors

BACKGROUND: Elevated temperatures of 40 - 44 degrees C increase the actions of various anticancer drugs including N-lost derivatives, cytotoxic antibiotics and platinum analoga. In clinical usage thermochemotherapy (TCH) should facilitate surgical resection and ameliorate local tumor control. PATIENTS AND METHODS: From 07/1993 to 12/2002 a total of 39 patients have been enrolled onto a phase-II study (female = 24, male = 15, age 1 - 37.5 years, median 5.2). Among these, 24 patients had extracranial non-testicular germ cell tumors and 15 patients soft tissue or chondrosarcomas. Indication: locoregional relapse (n = 29) or unresectable tumor after neoadjuvant chemotherapy (n = 10). Among these two groups, there were ten patients with poor response or progressive disease under primary or relapse chemotherapy. Ten out of the 29 relapse patients had more than one relapse. Tumor site: pelvis (30), abdomen (4), head and neck (2), proximal leg (2) and lumbar spine (1). Thermochemotherapy (TCH): 1800 - 2000 mg ifosfamide/m (2) and 100 mg etoposide/m (2) on days 1 - 4 and 40 mg cisplatin/m (2) on days 1 + 4 combined with regional deep hyperthermia (42 - 44 degrees C, 1 h) on days 1 + 4. RESULTS: In 39 protocol patients a total of 166 TCH courses (332 heat sessions) were applied. 20 patients achieved complete response, and 10 patients achieved partial response. TCH was followed by surgical tumor resection in 28/39 patients and/or radiotherapy in 13/39 patients. At a median follow-up of 27 months, outcome in this high-risk patient population was 22 NED, 3 AWD, 12 DOD, 2 DOC. Five year event free (EFS) and overall survival (OS) for the whole study cohort was 0.39 +/- 0.11 (20/39 patients) and 0.52 +/- 0.11 (25/39 patients), respectively. CONCLUSION: TCH shows substantial therapeutic efficacy and facilitates complete tumor resection in 14 out of 28 operated patients. Multimodal treatment including TCH, surgical resection and/or radiotherapy leads to sustained remission in the majority of patients with locoregional tumor recurrence. The therapeutic effect is most pronounced, if TCH is administered at first relapse. Due to the clinical and histologic heterogeneity the number of patients eligible for TCH is limited. Therefore, a more valid assessment of treatment efficacy can only be made by a matched-pair comparison in cooperation with the clinical registers.     

不可切除型肝母细胞瘤的术前介入治疗临床研究

目的探讨术前介入性动脉栓塞化疗（TACE）在不可切除型肝母细胞瘤治疗中的可行性。方法分析对8例经检查诊断为不可切除型肝母细胞瘤行TACE的治疗结果。结果8例患儿TACE后均有不同程度呕吐、发热、一过性肝功能损害，1例有骨髓抑制，无心、肾功能损害。有6例复查B超检查，肿瘤体积较前均有明显缩小，缩小比例为22．5％～57．5％；5例手术完整切除，均已无瘤存活1～4年，3例复诊检查发现有肺转移或多发转移，家属放弃进一步治疗后死亡。结论TACE具有化疗药物剂量小、全身副作用少、化疗效果好的优点，可作为一种术前治疗方法应用于不可切除型肝母细胞瘤。     

小儿肝脏恶性肿瘤血管再生性特点的研究

目的：研究小儿原发性肝脏恶性肿瘤中血管内皮生长因子（VEGF）和微血管密度（MVD）的特点。方法：采用SPTM免疫组化方法检查14例小儿原发性肝脏恶性肿瘤VEGF阳性表达以及MVD计数。病理分类：肝细胞癌7例，肝母细胞瘤5例，恶性间叶瘤和横纹肌肉瘤各1例。另选12例成年人肝癌手术切除标本作为对照。结果：小儿肝肿瘤组VEGF阳性表达面积显著高于成人肝癌组（P＜0．05）；尤其小儿肝癌组与成人组对比差异有极显著性意义（P＜0．01）。小儿肝肿瘤组的MVD也显著高于成人肝癌（P＜0．05）。小儿肝癌组患儿均在2年内死亡；非肝癌肝脏肿瘤预后较好，2例存活超过5年。结论：小儿肝脏恶性肿瘤存在有高度血管再生性的特点，肿瘤的生长快，预后差，以小儿肝癌最为突出。长期存活患儿的VEGF表达均为阴性。     

Postoperative course in children with malignant tumors following preoperative chemotherapy

Postoperative course is reported in 52 children with malignant tumors (neuroblastoma, Wilms-tumor, non-Hodgkin-lymphoma, osteosarcoma etc.) who were operated on between 1979 and 1987. 26 children received chemotherapy prior to surgery, whereas 26 children were operated on without preceding chemotherapy (control group). Most children were under six years of age. 15 Children (57.7%) with preoperative chemotherapy developed early postoperative complications, such as sepsis, pneumonia, suture dehiscence, woundhealing disturbances and ileus, whereas this was the case in only 5 children (19.2%) without preoperative chemotherapy (P 0.0005). Four of the children with preoperative chemotherapy (15.4%) sustained late complications, such as local recurrence or mechanical bowel obstruction, whereas none of the control children did so. Lethality rate from underlying disease did not differ in both groups during follow-up (5 = 19.2% vs. 5 = 19.2%). This demonstrates that the surgeon must carefully be aware of an increased possibility of early and late complications in children who have to undergo surgery for malignant tumors following preoperative chemotherapy.     

Primitive malignant nonepithelial hepatic tumors in children

Primary intrahepatic malignant nonepithelial tumors are very rare in children and account for 2% of all malignant mesenchymatous tumors under the age of 15 years. Clinical presentation, radiologic features, and histologic types are not unequivocal. The predominant role of surgery takes place either initially in small localized tumors or later, after initial reductive chemotherapy. In all cases, complete resection is the necessary but not sufficient condition for cure. Additional radiotherapy seems ineffective. High-dose chemotherapy and/or liver transplantation can be proposed for resistant cases. The disease-free survival rate is 37% at 2 years for the whole series. © 1993 Wiley-Liss, Inc.     

Abdominal transplantation for unresectable tumors in children: the zooming out principle

Purpose

To present our experience in abdominal transplantations to manage unresectable abdominal neoplasms in children and to describe the role of extensive surgeries in such cases.

Methods

This is a retrospective study of 22 abdominal transplantations in 21 patients for abdominal tumors over 16 years. Transplantation techniques included liver transplant (LT), multivisceral transplant (MVTx), and intestinal autotransplant (IA). Follow-up intervals ranged from 0.3 to 168 months (median 20 months).

Results

LT alone was performed in 15 patients for primary malignant (11) and benign (4) liver tumors. Pathological classification included HB hepatoblastoma (6), HCC hepatocellular cancer (3), hepatic epithelioid hemangioendothelioma HEH (1), angiosarcoma (1), benign vascular tumors (3), and adenoma (1). IA was performed in four patients for lesions involving the root of the mesentery; tumors of the head of pancreas (3) and mesenteric hemangioma (1). MVTx was performed in 2 patients for malignancies; pancreaticoblastoma (1), recurrent hepatoblastoma (1), and in one patient as a rescue procedure after IA failure. Four of the eleven patients who underwent LT for malignant liver tumor had metastatic disease at presentation. Six of them died of recurrent neoplasm (3), transplant-related complications (2), and underlying disease (1). All LT patients who had benign tumors are alive with functioning grafts. All IA patients survived and are on an oral diet, with one patient requiring TPN supplementation. One of the three patients who underwent MVTx died of metastatic disease.

Conclusions

Allo/auto transplantation for abdominal tumors is a valuable modality when conventional treatments fail or are not feasible.