Intensive chemotherapy with autologous PBSCT for advanced adrenocortical carcinoma in a child

Adrenocortical carcinoma (ACC) is a rare tumor in children. Surgical excision is the most effective therapy for ACC. However, the prognosis of ACC with metastases or unresectability is poor and the therapies for these are not well established. We report successful treatment of a 3-year-old girl with ACC and lung metastases. She had adrenalectomy followed by chemotherapy with cisplatinum, etoposide, and bleomycin. Thoracotomy for lung metastases was done after partial response to chemotherapy. Autologous peripheral blood stem-cell transplantation was performed after preconditioning with carboplatinum, etoposide, and melphalan. She has been well for 2 years since the time of diagnosis. Surgical resection of the primary and metastatic lesions with chemotherapy followed by autologous peripheral blood stem-cell transplantation could be an effective treatment for advanced ACC. However, prospective-controlled studies are necessary for firm conclusion as this is a single case report and the follow-up is not long enough.     

Prognostic significance of metastatic site at diagnosis in Wilms' tumor: results from a single center

The purpose of this study was to identify the prognostic significance of pulmonary and liver involvements present at diagnosis in children with Wilms' tumor. From 1971 to 2002, 57 patients with stage IV Wilms' tumor were diagnosed, treated, and followed in the authors' institution. Metastases were detected by chest radiography, abdominal ultrasonography, and/or thoracoabdominal computed tomography. Nephrectomy with tumor resection was performed and appropriate chemotherapy was given to all the patients. The Kaplan-Meier survival method was used to calculate survival. The log-rank test was used to compare the groups with respect to survival. The age range was 1.25 to 15 years (median 4 years). Thirty-seven patients had only lung metastases, 12 had only liver metastases, 6 had both lung and liver metastases, 1 had adrenal gland metastases, and 1 had other site metastases. The overall survival rate in the whole group was 37.1%. The overall survival rates for lung and liver metastases were 50.2% and 16.6%, respectively. The overall survival rates were significantly different between the two groups (P = 0.005). Only one patient survived in the group with liver involvement. Liver involvement at diagnosis indicates a worse prognosis than lung involvement. Wilms' tumor patients with liver metastases should be treated with more intensive regimens than those with lung metastases.     

Treatment of metastatic sialoblastoma with chemotherapy and surgery

Tumors of the salivary gland are very uncommon in children. Sialoblastoma is a rare, aggressive, blastomatous, and potentially malignant congenital tumor. Distant metastases are rare. We present a case of sialoblastoma with lung metastases that developed in a 4-year-old girl adjacent to a congenital nevus in the left cheek. The tumor was inoperable at diagnosis but the largest of the pulmonary metastases was removed surgically. The patient responded well to chemotherapy and underwent surgical excision of the primary tumor, followed by three more courses of chemotherapy.     

Surgical treatment of lung metastases in patients with embryonal pediatric solid tumors: an update

Distant metastases regularly occur in children with solid tumors. The most affected organ is the lung. Nearly in all extracranial pediatric solid tumors, the presence of lung metastases is associated with an adverse prognosis for the children. Therefore, the correct treatment of lung metastases is essential and influences the outcome. Despite different national and international trials for pediatric tumor entities, specific surgical aspects or guidelines for lung metastases are usually not addressed thoroughly in these protocols. The aim of this article is to present the diagnostic challenges and principles of surgical treatment by focusing on the influence of surgery on the outcome of children. Special points of interest are discussed that emphasize sarcomas, nephroblastomas, hepatoblastomas, and other tumors. Surgery of lung metastases is safe, has a positive impact on the patients' prognosis, and should be aggressive depending on the tumor entity. An interdisciplinary approach, including pediatric oncology and radiology, is mandatory in any case.     

Primary lung metastases in pediatric malignant non-Wilms renal tumors: data from SIOP 93-01/GPOH and SIOP 2001/GPOH

Malignant non-Wilms renal tumors (NWRT) are a small but relevant subgroup of renal neoplasms in children. In this study we analyzed corresponding data from the trials SIOP 93-01/GPOH and SIOP 2001/GPOH of the Society of Pediatric Oncology and Hematology.Data of 22 patients with NWRT and primary lung metastases were retrospectively reviewed. Analyses included epidemiology, tumor characteristics, chemotherapy, local treatment, and outcome.The following diagnoses were registered: Malignant Rhabdoid tumor of the kidney (MRTK, n=15), Renal-cell carcinoma (RCC, n=3), Clear-cell sarcoma of the kidney (CCSK, n=3), and primitive neuro ectodermal tumor (PNET, n=1). Median age of patients at diagnosis was 14 months. Overall survival was 36.36% (8/22). Of the 15 children with MRTK 3 survived, 3/3 patients with RCC, 1/3 patients with CCSK, and 1/1 patient with PNET survived. Lung metastases disappeared in 6 patients after initial chemotherapy, 6/8 patients undergoing local treatment of lung metastases (surgery, irradiation, or both) achieved complete remission. Only patients with complete clearance of lung lesions, either through neoadjuvant chemotherapy or subsequent local treatment, survived. Mean Follow up was 31 months (1-137).Survival of patients with stage IV NWRT is dismal. Complete removal of lung metastases seems mandatory for survival. An aggressive diagnostic and therapeutic approach seems justified in affected children.     

Dactinomycin Potentiation of Radiation Pneumonitis: a Forgotten Interaction

No mention of dactinomycin potentiation of pulmonary radiation was found in a review of the literature of the past 12 years. Before that, this complication was well described and investigators had calculated that dactinomycin increased the toxic effect of lung radiation by a factor of 1.3 and reduced the radiation tolerance of the lung by at least 20%. An example of such a toxic effect is described in the treatment of a 7-year-old girl with lung metastases from Ewing's sarcoma. The chemotherapy protocol followed contained cyclophosphamide, vincristine, dactinomycin, adriamycin, cisplatinum, VP16, and radiotherapy. The treatment was associated with fatal pulmonary fibrosis following the reintroduction of dactinomycin after radiotherapy.

Our experience suggests that there is clinical significance to this complication in sarcoma therapy when dactinomycin-containing protocols are used with radiation in the treatment of pulmonary metastases.     

Extracranial metastases of glioblastoma in a child: case report and review of the literature

Glioblastoma (GBM) is the most common adult malignant brain tumor but is notably less common in children. Primary brain tumors rarely metastasize outside the central nervous system and when metastases occur, it is often in patients with diversionary shunting of the cerebrospinal fluid. This report details the case of a 13(1/2)-year-old boy who was diagnosed with GBM. He survived 10 months after diagnosis. At autopsy, the tumor was found to extensively infiltrate the leptomeninges as well as the cranial skin and soft tissue. Further examination disclosed multiple liver and lung metastatic GBM nodules. This pattern of spread is very uncharacteristic of gliomas and emphasizes the importance of adequate metastatic evaluation.     

Metastatic sites in stage IV and IVS neuroblastoma correlate with age, tumor biology, and survival.

PURPOSE: The goal of this study was to determine the incidence of metastatic sites in neuroblastoma and the extent to which metastatic sites correlate with age, tumor biology, and survival. PATIENTS AND METHODS: All 648 patients with stage IV and IVS neuroblastoma registered on Children's Cancer Group protocols 3881 and 3891 were analyzed. Metastatic site data were provided by treating institutions and reviewed in patients with central nervous system (CNS), intracranial, lung, or "other" metastases. RESULTS: The incidence of metastatic sites at diagnosis was 70.5% in bone marrow, 55.7% in bone, 30.9% in lymph nodes, 29.6% in liver, 18.2% in intracranial and orbital sites, 3.3% in lung, and 0.6% in CNS. Event-free survival (EFS) was decreased in patients with bone, bone marrow, CNS, intracranial/ orbital, lung, and pleural metastases, and improved in those with liver and skin metastases. In infants, MYCN amplification and unfavorable Shimada histopathology correlated with increased frequencies of bone and intracranial or orbital metastases. In older patients, MYCN amplification correlated with increased frequencies of intracranial or orbital, liver, and lung metastases. Multivariate analysis revealed that metastatic site is not an independent prognostic factor. CONCLUSIONS: Metastatic pattern in neuroblastoma differs with age and correlates with tumor biological features and EFS. These correlations could reflect changes in host or tumor biological features with age resulting in differences in metastatic capacity or tumor affinity for specific sites.     

Pulmonary blastoma in a 13-year-old boy. Case report and review of the literature

On examining a 13-year-old boy, a skull tumor and multiple pulmonary tumors were discovered. He was given three cycles of multidrug chemotherapy in accordance with Rosen's T-11 protocol. The skull tumor disappeared after the first cycle, but the lung masses remained unchanged. The diagnosis of pulmonary blastoma was made on the surgically removed specimen. Local recurrence occurred in the skull and widespread metastases developed later, despite high dose melphalan treatment with autologous bone-marrow rescue. The patient died 9 months after the debut. The case is presented to show the diagnostic difficulties in this rare tumor and to illustrate its varying biological behavior in the published cases. Child, high dose melphalan, pulmonary blastoma     

Successful treatment of unresectable advanced hepatoblastoma: Living liver transplantation after surgical removal of lung metastasis

Miyamura T, Yoshida R, Yagi T, Matsukawa H, Chayama K, Ishida T, Washio K, Morishita N, Oda M, Morishima T. Successful treatment of unresectable advanced hepatoblastoma: Living liver transplantation after surgical removal of lung metastasis.
Pediatr Transplantation 2011: 15: E87–E91. © 2010 John Wiley & Sons A/S. Abstract: Hepatoblastoma is a rare malignant tumor of the liver in children. Intensive combination chemotherapy has increased the number of surgically resectable cases and improved prognosis markedly. However, unresectable cases and cases with residual metastasis, including lung metastases, have a poor prognosis. In these refractory cases, treatment strategy has not been established. On the other hand, living liver transplantation has been shown to be effective in cases of advanced hepatoblastoma, but its effectiveness in cases with residual distant metastases after chemotherapy remains unclear. We report one successful case of advanced unresectable hepatoblastoma with multiple lung metastases. Intensive chemotherapy consisting of high‐dose chemotherapy with autologous hematopoietic stem cell transplantation was not effective. We performed living liver transplantation after surgical resection of residual lung metastases, which were histologically viable. After liver transplantation, the level of tumor marker decreased gradually. The patient experienced no severe complications. This case suggested that living liver transplantation could be effective in cases of advanced refractory hepatoblastoma after control of distant metastases.     

Analysis of treatment outcome for children with recurrent or metastatic hepatoblastoma

For better total survival rate of children with hepatoblastoma, the therapeutic strategy for recurrent or metastatic hepatoblastoma should be improved. From 1991 to 1999, 134 cases of hepatoblastoma were treated by surgery and combination chemotherapy of cisplatin (CDDP) and THP-Adriamycin (THP-ADR) based on the JPLT-1 protocol. In 114 non-metastatic cases, 90 primary liver tumors were resected completely by partial hepatectomy, but 12 recurrences were observed in the liver (4 cases) and the lungs (8 cases). Distant metastases on the diagnosis were observed in 20 cases. The treatment outcome of these 12 recurrent and 20 metastatic tumors was analyzed. In four recurrent liver tumors, surgical resection was performed in all four cases, and all the patients were alive and well. In eight recurrent lung tumors, surgical resection was performed completely in six cases with unilateral lung disease, and five of the six patients were alive and well. In stage IV tumors, the survival rate of the patients having primary tumors within two hepatic sections was significantly higher than that of the patients having primary tumors over three hepatic sections. Active surgical intervention to lung metastases and a more intensive chemotherapy to facilitate complete resection of primary hepatic tumor could improve survival rate of children with refractory hepatoblastoma.     

Remaining problems in the treatment of patients with Wilms' tumor.

Major advances have been made in the treatment of children with Wilms' tumor. Remaining areas of investigation include the role of adriamycin and the treatment of children with stage III and IV disease and the role of whole lung radiation therapy in the treatment of children with pulmonary metastases. Long-term follow up of successfully treated patients will provide valuable insight into the importance of genetic factors in the cause of Wilms' tumor.     

Effects of therapeutic irradiation delivered in early childhood upon subsequent lung function.

To determine the long-term effects of therapeutic pulmonary irradiation and treatment with actinomycin D during a period of lung growth, 12 patients treated for Wilms' tumor metastatic to the lung and 8 patients treated for Wilms' tumor with no evidence of pulmonary metastases were studied 7 to 14 years after their initial tumor therapy. All patients had received irradiation to the tumor bed and treatment with actinomycin D. Group 1 had received a single course of bilateral pulmonary irradiation; group 2 had received additional pulmonary irradiation and/or thoracic surgery; group 3 had received no therapeutic irradiation directed primarily to the chest. Total lung capacity (TLC) averaged 71% of predicted value in group 1, 58% in group 2, and 94% in group 3. Diffusing capacity in groups 1 and 2 was reduced to the same extent as lung volume. Quasi-static pressure-volume relationships, studied in three of six patients in group 1, were within the normal range when lung volume was expressed as percentage of observed TLC. Airway resistance, evaluated by spirometry, maximum expiratory flow-volume curves, and resistance of the total respiratory system, was normal or reduced. The data support the hypothesis that therapeutic irradiation during a period of lung growth primarily affects the lung parenchyma and produces a decrease in subsequent size of both the lung and chest wall. No effect of actinomycin D alone upon the lung could be demonstrated.     

Are growth rates of tumors of any clinical importance?

The tumor doubling times were determined in 142 rounded pulmonary lesions of 78 patients (13 bronchial carcinomas, 7 benign pulmonary tumors, and 122 pulmonary metastases). They varied between +12 and +8863 days of tumor growth and of -1810 days of decrease in tumor mass. Forty-four percent of all pulmonary metastases doubled their volume within 60 to 250 days. The growth rates during the period of observation varied greatly in several pulmonary metastases of the same patient, even for the same solitary circular lung focus of the same person. There is no relationship between tumor doubling time and histological type of the tumor, nor between the interval between operative removal of the primary tumor and the occurrence of pulmonary metastases. In patients between the ages of 10 and 30 years only rapidly growing pulmonary metastases with a tumor doubling time of less than 60 days could be found; even though there is no proved relationship between growth rate and age. The tumor doubling time gives no useful information on the nature of a circular lung focus, and there are no clinical consequences for diagnosis.     

Metastasis of an intracranial germinoma through a ventriculoperitoneal shunt: Recurrence as a yolk-sac tumor

Extraneural metastases of intracranial germinomas, although infrequent, are associated with a generally poor prognosis despite the high radiosensitivity of localized primary tumors. Ventriculoperitoneal shunts have been implicated in facilitating metastatic spread of primary intracranial germinomas. We present a case of a successfully irradiated suprasellar germinoma recurring after 13 months as an intra-abdominal yolk-sac tumor in a young man. The tumor was eradicated with a combination of systemic chemotherapy and local irradiation, with no residual viable tumor cells confirmed at final surgical extirpation. The role of cerebrospinal fluid (CSF) shunts in metastases, mixed germ-cell tumor histology, and tumor markers in recurrences as well as radiation doses and volumes for treating primary tumors are discussed. Systemic chemotherapy may be utilized as prophylaxis against shunt metastases when CSF drainage is necessary.     

Metastatic Ewing sarcoma/PNET of bone at diagnosis: prognostic factors--a report from Saudi Arabia

BACKGROUND: To evaluate outcome and prognostic factors in Saudi Arabian patients with metastatic Ewing sarcoma and PNET of bone (PMES) at diagnosis. PROCEDURE: Ninety-nine of 304 (33%) consecutive patients with Ewing sarcoma and PNET of bone registered at our centre from 1975 to 1998, had metastatic disease at registration and 93 were available for analysis. The maximum x-axis diameter of the primary tumor was used as the measure of primary tumor size. Usually a trial of systemic treatment was undertaken before a decision was made on local treatment. Standard chemotherapy regimens were used in all treated patients. Forty-one (44%) patients did not receive radical local treatment due to an inadequate response to chemotherapy, or a decision not to undertake more than palliative treatment. Radical treatment of the primary site was radiation alone 41 (79%), resection alone 7 (13%), and resection and radiation 4 (8%). RESULTS: The 5-year survival rates were 9% for all 93 evaluable patients, 16% for 52 patients who received chemotherapy and radical local treatment, 0% for 41 patients who received lesser treatment, 19% for 43 patients with lung metastases alone, and 0% (P = 0.002) for 50 patients with other sites involved. For 60 patients with imaging data, 5-year survivals were 34 and 0% when the maximum transverse diameter of the primary tumor was < 10 cm (N = 20) and > or = 10 cm (N = 40), respectively. CONCLUSIONS: Small primary tumor size and the presence of lung metastases alone were the only significant favorable prognostic factors. Earlier diagnosis will be the basis for better results.     

Metastatic Intracranial Chordoma in a Child with Massive Pulmonary Tumor Emboli

A 27-month-old boy of Hispanic background developed multiple cranial nerve palsies, difficulty swallowing, bloody nasal discharge, and irritability. Radiographic evaluations showed extensive destruction of the clivus by a large tumor that invaded the sphenoid bone, left cavernous sinus, ethmoid sinus, nasal cavity, and left orbit. Multiple pulmonary nodules were also noted. The bone marrow and spinal fluid showed no evident tumor cells. Transnasal biopsy revealed a chordoma. Treatment was initiated with a combination of ifosfamide, mesna, and etoposide along with radiation therapy to the cranial tumor. Shifting pulmonary densities were noted on serial films. Despite some clinical improvement, the child developed rapidly progressive hypoxemia 3 weeks after admission and died. Autopsy showed persistent viable tumor in the primary site and massive pulmonary arteriolar tumor emboli, infarcts, and widespread lung parenchymal metastases. No other sites of tumor involvement were discovered. This is the second child reported with intracranial chordoma, pulmonary metastases at diagnosis, and early death attributed to pulmonary tumor emboli.     

Brain metastases in Wilms' tumor: case report and literature review

A 2-year-old girl who had a stage 2, favorable-histology Wilms tumor diagnosed when she was age 10 months presented with multiple brain metastases at second recurrence. She had been treated with combined radiotherapy, surgery, and chemotherapy; at 2 months after treatment, recurrent disease developed in the central nervous system and she died. Brain metastases are rare in the natural history of Wilms tumor. Although it does not appear that cerebral metastases are a barrier to tumor eradication and long-term survival if treated with combined modality therapy, treatment should be individualized.     

Chest radiography versus chest CT in the evaluation for pulmonary metastases in patients with Wilms' tumor: a retrospective review

BACKGROUND: Determination of the presence of pulmonary metastases in children with Wilms' tumor is an important part of staging and treatment. We sought to compare the efficacy of chest radiography (CXR) and chest CT in the evaluation for pulmonary metastases in patients with Wilms' tumor. MATERIALS AND METHODS: This retrospective study included 83 children with Wilms' tumor diagnosed between 1980 and 1993. All patients with pulmonary nodules (n = 12) as well as 14 Wilms' tumor patients without pulmonary metastases (control group) had blinded review of the CXR and chest CTs by three pediatric radiologists. Presence, size, and certainty of metastatic diagnosis were recorded. Medical records were reviewed. The remaining 57 patients had review of their medical and imaging records to confirm the absence of pulmonary metastases. RESULTS: Ten of the 12 with pulmonary masses had imaging available for review. Eight had both positive CXR and chest CT examinations. Two patients had pulmonary nodules seen by CT only: one had a right cardiophrenic angle mass and died as a result of liver metastases. The other had a solitary nodule, which proved to be a plasma-cell granuloma. Overall, the CXR and chest CT data concur in 79/81 (98%). CONCLUSION: CXR alone appears adequate for the diagnosis or exclusion of pulmonary metastases in patients with Wilms' tumor.     

Fibromyxoid sarcoma in a four-year-old child: Case report and review of the literature

We present a child with a rare and chemotherapy-resistant form of soft-tissue cancer, low-grade fibromyxoid sarcoma, first noted when he was 4 years old. He is the youngest patient reported to date. An 11-year-old white male presented to The University of Texas M. D. Anderson Cancer Center's Department of Pediatrics with a 7-year history of right thigh mass and pulmonary nodules, confirmed on examination. He had undergone extensive prior chemotherapy and surgery. He received chemotherapy with high-dose cyclophosphamide (7 g/m²) and later etoposide (150 mg/m²/day × 5), with only slight shrinkage of the thigh mass and none in the lungs. Subsequently the tumor in his proximal thigh and his lung metastases were resected, and radiation therapy was administered to the thigh. His disease remained stable for 12 months, but he then developed a pleural-based metastasis on the left side and new, bilateral lung metastases also. The tumors on the left side were removed; residual disease is stable after treatment for 6 months with subcutaneous alpha-interferon-2b. Low-grade fibromyxoid sarcoma is very uncommon in children. It grows slowly and metastasizes to distant organs, chiefly to the lungs. It is resistant to conventional chemotherapy, and thus far only surgery seems to have a life-prolonging effect. Newer chemotherapeutic and possibly biologic agents should be tried in future patients, in order to find an effective way to control the disease. © 1996 Wiley-Liss, Inc.