Combined therapy for malignant tumors of the chest wall in children.

Of 1168 children with malignant solid tumors who were admitted to St. Jude Hospital between 1962 and 1976, 22 (1.8%) had primary malignancies of the chest wall, excluding the mediastinum. The treatment plan for these patients varied with the resectability of the tumor, but always included chemotherapy with or without irradiation. Six children had totally resectable tumors and another two had initially unresectable tumors converted to a resectable state with preoperative therapy. All 8 patients have been disease-free for 3–90 mo (median 18.5). Of 11 children with unresectable disease, 4 remain disease-free for 7–175 mo following chemotherapy and irradiation only (3 of 9) or both modalities plus partial resection (1 of 2). The 3 remaining children received en bloc resections for recurrent rhabdomyosarcoma following chemotherapy and irradiation: 2 died at 15 and 18 mo after diagnosis and 1 remains disease-free for 13 mo.The availability of effective combined therapy methods for local control of primary tumors and prevention of metastases made possible a more conservative surgical approach for 4 of 8 patients with resectable disease and permitted conversion of initially unresectable tumors to a resectable state in 2 patients. Moreover, these measures resulted in decreased morbidity without apparent compromise of tumor-free survival. Overall, 13 of 22 patients survive without evidence of disease: 3 of 3 patients with neuroblastoma, 4 of 6 with rhabdomyosarcoma, 4 of 10 with Ewing's sarcoma, 1 of 2 with osteosarcoma, and 1 patient with malignant histiocytoma.     

Preoperative therapy for unresectable malignant tumors in children.

Thirty-six children with initially unresectable malignant tumors were managed with pre- and postoperative therapy combined with reduction of primary tumor burden by total or subtotal resection. The proportion of patients achieving long-term tumor-free survival after surgery was 0.48 in the Wilms' tumor group and 0.60 among patients with other regionally unresectable malignant neoplasms. These results are encouraging in an otherwise high mortality situation.     

Stereotactic intratumoral photodynamic therapy for recurrent malignant brain tumors.

Photodynamic therapy (PDT) using purified hematoporphyrin derivative and stereotactic intratumorally implanted optical laser fiber(s) was used to treat patients with recurrent malignant gliomas and metastatic melanoma of the brain. Tumor response to PDT was evaluated by recording changes in the volume and pattern of tumor enhancement between computed tomographic and magnetic resonance imaging scans done before and after PDT, metabolic changes in tumor tissue by 31P magnetic resonance spectroscopy, and patient outcome. Toxicity of PDT to brain was evaluated on the basis of changes in the patients' neurological examinations and correlated with changes in brain adjacent to tumor seen on postoperative imaging studies. Dramatic tumor responses to PDT were seen in all gliomas, but no response of tumor to treatment was seen with melanoma. Transient signs and symptoms of increased peritumoral cerebral edema caused by PDT were seen in all patients. Two patients suffered permanent neurological sequelae, monocular blindness and a partial visual field defect, as a result of treatment. Two patients with recurrent anaplastic astrocytomas remain in remission at 45 and 35 weeks after PDT. We conclude that intratumoral photoradiation therapy of hematoporphyrin derivative-photosensitized malignant gliomas effectively produces necrosis of the solid component of malignant gliomas; however, intratumoral photoradiation may not reach the portion of tumor that invades normal brain.     

Combined intra-arterial and systemic chemotherapy for recurrent malignant brain tumors.

Seventy-nine patients harboring recurrent brain tumors received four cycles of infraophthalmic carotid injections of 160 mg of carmustine. Two milligrams of intravenous vincristine and 50 mg of oral procarbazine was also administered three times daily for 1 week in conjunction with each BCNU treatment. The response rate was 60% with a median survival for patients with astrocytomas, anaplastic astrocytomas, and glioblastomas of 32, 20, and 6.5 months, respectively. The median survival of the responding patients was 20 months, and the survival at 30 months was 45%. The survival in patients not responding to treatment was 5 months, reflecting the natural history of the tumor. There have been no deaths related to the treatment procedure. No incidents of severe or permanent eye complications or leukoencephalopathy were observed. Based on multivariate survival analysis, only patients with a good performance status who are not steroid dependent are candidates for this treatment.     

Antifibrinolytic therapy of experimentally grown malignant brain tumors

This study was designed to evaluate the effect of an inhibitor of plasminogen activation on the growth of a human glioblastoma line grown in nude mice up to the seventh passage. The tumors produced plasminogen activators and showed histological characteristics similar to those of the original tumor. Three groups of mice were studied. Group A received 5% epsilon aminocaproic acid (EACA); Group B received 2.5% EACA; and Group C served as a control. There was no statistical difference among the three groups with regard to: 1) age at time of tumor transplantation; 2) the interval between implant and treatment; or 3) tumor volume at time of treatment. Blood measurements of EACA, performed in a limited number of animals, have shown that the drug at 5% concentration had reached toxic levels. Statistically significant differences between the three groups were noted in the following categories: 1) rate of tumor growth; 2) tumor volume at time of death, where Group A had smaller tumors than Group C; and 3) mean survival times of Groups A and B as compared to Group C. A statistically significant negative correlation was found between the rate of tumor growth and the length of survival of animals in Group C, while no correlation could be found for either Group A or B, indicating that the antifibrinolytic therapy modified this important biological variable. This study supports the hypothesis that the fibrinolytic system plays a role in the growth and development of malignant gliomas and that interference with the fibrinolytic system may retard the growth of these tumors grown in nude mice.     

Optimal light dose for interstitial photodynamic therapy in treatment for malignant brain tumors

BACKGROUND AND OBJECTIVE:The primary goal was to determine the maximal tolerable light dose that can be administered to patients undergoing multifiber interstitial photodynamic therapy (PDT) of malignant brain tumors at a fixed dose of photosensitizer. STUDY DESIGN/MATERIALS AND METHODS: Eighteen patients (12 glioblastomas, 5 anaplastic astrocytoma, and 1 malignant ependymoma) were included in this study. The total light dose delivered to the tumor was divided into three groups of six patients each: 1,500-3,700 J, 3,700-4,400 J, and 4,400-5,900 J. RESULTS: Five patients (all glioblastomas) demonstrated postoperative permanent neurologic deficits. None of the patients in 1,500-3,700 J, two patients in 3,700-4,400 J, and three patients in 4,400-5,900 J had neurologic deficits. Glioblastomas recurred more often than anaplastic astrocytomas. Increasing the light dose did not make a difference in local/regional control of glioblastomas. Patients with anaplastic astrocytomas survived (mean, 493 days) longer than patients with glioblastomas (mean, 116.5 days) after PDT. Four patients had prolonged survival (more than a year) after PDT. CONCLUSIONS: Increasing the total light dose delivered to the tumor increases the odds of having a permanent neurologic deficit but does not increase survival or time to tumor progression. There was no difference in local or marginal recurrence with increasing light dose. Recurrent anaplastic astrocytomas tend to do better than recurrent glioblastomas with PDT.     

Correlation of neurosurgical subspecialization with outcomes in children with malignant brain tumors

OBJECTIVE: This study was performed to evaluate the association between the type of neurosurgeon (general or pediatric) and either the extent of tumor removal or the frequency of complications in children undergoing malignant brain tumor resections. METHODS: Data were analyzed from three recent Children's Cancer Group studies: two on medulloblastomas/primitive neuroectodermal tumors and one on malignant gliomas. Neurosurgeons were classified as general neurosurgeons, as designated pediatric neurosurgeons in their institutions, or as members of the American Society of Pediatric Neurosurgeons (ASPN), which requires pediatric neurosurgical experience and practice standards. RESULTS: Data forms from 732 children were analyzed; 485 were from children with medulloblastomas/primitive neuroectodermal tumors, and 247 were from children with malignant gliomas. Operations were performed by 269 neurosurgeons, including 213 general neurosurgeons, 29 designated pediatric neurosurgeons, and 27 ASPN members. The mean number of operations per surgeon was 1.8, 4.9, and 7.6 for general neurosurgeons, designated pediatric neurosurgeons, and ASPN members, respectively. There was a significant relationship between the extent of tumor resection or the amount of residual tumor and the type of neurosurgeon. Designated pediatric neurosurgeons and ASPN members were more likely to remove more than 90% of the tumor and to leave less than 1.5 cc of residual tumor than were general neurosurgeons (P<0.05). In these studies, the probability of extensive tumor removal correlated with the number of operations the neurosurgeon performed (P<0.01). Neurological complications occurred in the following proportion of cases: general neurosurgeons, 23%; designated pediatric neurosurgeons, 32%; and ASPN members, 18%. CONCLUSION: Pediatric neurosurgeons are more likely than general neurosurgeons to extensively remove malignant pediatric brain tumors. In these tumors, extent of removal has been demonstrated to influence survival.     

恶性骨肿瘤的介入治疗（附38例报告）

笔者对３８例恶性骨肿瘤做了介入治疗。全部病例经动脉内灌注化疗，并对其中发生于骨盆区域的１６例肿瘤加做了动脉内栓塞治疗，５例肢体肿瘤采用带囊导管阻断血流后再灌注化疗。手术及病理证实：肿瘤均有不同程度的坏死、液化和囊变。笔者认为，在介入治疗中，动脉内栓塞较灌注更为重要。并提出了一种改进单纯化疗的方法和对栓塞材料的选择，最后对介入治疗的评价进行了探讨。     

Intra-arterial ACNU therapy for malignant brain tumors. Experimental studies and preliminary clinical results

The authors examined the growth rate of mouse 203 glioma cells in vitro and found it to be markedly inhibited after exposure to ACNU for 5 minutes at a drug concentration of 100 micrograms/ml. Rats that had undergone intracranial implantation of T1 neurogenic tumor were treated by 5 mg/kg of ACNU administered either intravenously or intra-arterially. The median survival times for the control animals and the animals undergoing intravenous or intracarotid administration of ACNU were 23, 29, and 46 days, respectively. The difference in survival time between the intravenous and intracarotid administration groups was statistically significant (p less than 0.01) when examined by the Cox-Mantel test. In a clinical trial, 17 patients with glioblastoma were treated by ACNU, eight intravenously and nine by the intra-arterial route. The drug was given in doses of 2 to 3 mg/kg at least twice before and twice after a course of postoperative radiotherapy. Intra-arterial administration was performed over a period of 5 minutes under local anesthesia. The median postoperative survival time for the patients in the intra-arterial group was 12.5 months, compared with 9.0 months for those in the intravenous group. The survival rate for the intra-arterial group was slightly higher, although statistically not significant, probably because the number of cases was small. The degree of thrombocytopenia due to ACNU tended to be less marked in the intra-arterially treated patients. The theoretical advantages of the intra-arterial administration of ACNU are discussed.     

Gene therapy of malignant tumors

New techniques in molecular biology and increasing insights in the genetic basis of tumorigenesis led to the development of therapeutic agents composed of genetic information. The majority of gene therapy trials is targeted towards cancer therapy. The most frequently used strategy is immunotherapy which comprises transfer of genes encoding cytokines, costimulatory molecules or tumorspecific antigens to enable cells of the immune system to identify and destroy tumor cells. The second important strategy makes use of suicide genes to selectively kill tumor cells. Compensation of genetic defects by the downregulation of activated oncogenes or the restoration of tumor suppressor gene functions is the third concept to revert the malignant phenotype of cancer cells.     

Palliative therapy for malignant hepatic tumors with hyperthermia

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with an annual occurrence of one million new cases. The incidence of liver metastasis is much higher than the incidence of HCC. Overall nearly 50% of the patients with colorectal adenocarcinoma will develop liver metastasis. Surgical resection remains the "gold standard" for resectable hepatic neoplasms, but only a minority of patients present with lesions which are potentially curable. In these nonresectable hepatic tumors palliative treatment using focal necrosis by hyperthermia (radiofrequency, microwave coagulation therapy, interstitial laser photocoagulation, thermo-ablation with hot water steam) appear as a valuable alternative. Best results are reported in the case of associations of thermo-necrosis with general or intraarterial chemotherapy. These methods of treatment can be performed by percutaneous, laparoscopic or open approach. Precise guidance of the focal necrosis can be realized using CT scan, IRM and intraoperative ultrasound exam and the results are evaluated by the same techniques. The key element in the management of the malignant tumors of the liver is the cooperation between surgeon, intensive care physician, oncologist and specialist in interventional radiology, to appreciate the indication of therapy. Further controlled trials are required to define the precise indications and long term results of these methods of treatment.     

Immunocorrective effect of hemosorption in the comprehensive therapy of malignant tumors in children]

In 25 children with malignant tumours of the retroperitoneal space and mediastinum, hemosorption was performed before and after operation in combination with chemotherapy with the aim of immunocorrection and detoxication of an organism. Under the influence of hemosorption, the general state of the patients improved, their immune status normalized permitting not to interrupt a course of chemotherapy.     

Growth hormone deficiency following radiation therapy of primary brain tumors in children

The medical records of 123 patients treated for brain tumors at Children's Hospital and Medical Center, Seattle, Washington, between 1985 and 1987 were reviewed. The endocrinological complications of radiation therapy and the effectiveness of growth hormone (GH) replacement therapy were assessed. These were the first 2 years after synthetic GH became available. The disease pathology was confirmed at craniotomy or biopsy in 108 patients. Ninety-five children completed radiation therapy and 65 of these were alive at the time of review; these 65 children represent the study population. The most common tumor types were medulloblastoma, craniopharyngioma, and ependymoma. Endocrine evaluation was initiated with changes in the patients' growth velocity. Patient workup included skeletal x-ray films for determination of bone and analysis of thyroxin, thyroid-stimulating hormone, and somatomedin-C levels. Following 1-dopa and clonidine stimulation, provocative studies of GH levels were performed. Growth hormone failure and short stature were observed in 26 children, most commonly in the 2nd year after tumor treatment. Eight patients with GH failure were also hypothyroid. Hormone replacement therapy was initiated with recombinant GH, 0.05 mg/kg/day, and all children so treated showed an increase in height, with eight patients experiencing catch-up growth. There were no complications of therapy or tumor recurrence. Studies of baseline bone age and somatomedin-C levels on completion of radiation therapy are recommended. Comprehensive endocrine studies should follow changes in the patients' growth velocity. With early GH replacement, catch-up growth is possible and normal adult heights may be achieved.