Outcomes following autologous hematopoietic stem cell transplant for patients with relapsed Wilms' tumor: a CIBMTR retrospective analysis.

Despite the marked improvement in the overall survival (OS) for patients diagnosed with Wilms' tumor (WT), the outcomes for those who experience relapse have remained disappointing. We describe the outcomes of 253 patients with relapsed WT who received high-dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplant (HCT) between 1990 and 2013, and were reported to the Center for International Blood and Marrow Transplantation Research. The 5-year estimates for event-free survival (EFS) and OS were 36% (95% confidence interval (CI); 29-43%) and 45% (95 CI; 38-51%), respectively. Relapse of primary disease was the cause of death in 81% of the population. EFS, OS, relapse and transplant-related mortality showed no significant differences when broken down by disease status at transplant, time from diagnosis to transplant, year of transplant or conditioning regimen. Our data suggest that HDT followed by autologous HCT for relapsed WT is well tolerated and outcomes are similar to those reported in the literature. As attempts to conduct a randomized trial comparing maintenance chemotherapy with consolidation versus HDT followed by stem cell transplant have failed, one should balance the potential benefits with the yet unknown long-term risks. As disease recurrence continues to be the most common cause of death, future research should focus on the development of consolidation therapies for those patients achieving complete response to therapy.

Mycotic aneurysm of the thoracic aorta due to Aspergillus terreus: case report and review.

Mycotic aneurysms of the aorta caused by fungi are uncommon. We describe an unusual case of aortic aneurysm infection caused by Aspergillus terreus, which most likely spread from an adjacent pulmonary focus. Successful treatment included partial pneumonectomy, resection of the aneurysm with graft repair, and prolonged sequential administration of amphotericin B and itraconazole. A review of the published experience with aortic aneurysms caused by Aspergillus species is also presented. When invasive aspergillosis is suspected in proximity to areas with major vascular structures in immunocompromised patients, further investigation to rule out vascular invasion may be warranted. If the diagnosis is confirmed, aggressive and prompt treatment with antifungal agents combined with surgical debridement is essential to improve outcome.

Feasibility and toxicity of chemoembolization for children with liver tumors.

PURPOSE: To determine the feasibility, toxicity, and efficacy of hepatic arterial chemoembolization (HACE) in pediatric patients with refractory primary malignancies of the liver. PATIENTS AND METHODS: Six patients with hepatoblastoma (HB), three with hepatocellular carcinoma (HCC), and two with undifferentiated sarcoma of the liver were treated with HACE every 2 to 4 weeks until their tumors became surgically resectable or they showed signs of disease progression. All but one newly diagnosed patient with HCC had previously received systemic chemotherapy. RESULTS: All patients with HB and HCC responded to HACE, as measured by imaging studies and alpha-fetoprotein levels. Surgical resection (complete or microscopic residual disease) was feasible in five of 11 patients, and three patients remain alive with no evidence of disease. Elevated liver transaminase and bilirubin levels were seen after each one of the 46 courses of HACE. Other toxicities included fever, pain, nausea, vomiting, and transient coagulopathy. CONCLUSION: HACE is feasible, well tolerated, and effective in inducing surgical resectability of primary hepatic tumors in children.

Complications of cancer therapy in children: a radiologist's guide.

As advances in cancer therapy improve the prognosis of patients with childhood malignancies, awareness of the consequences of treatment methods assumes increasing importance. All cancer treatment modalities are associated with toxic effects, and the spectrum of therapy-induced complications involves all organ systems. Radiologists have a pivotal role in detecting these sequelae, which can be categorized by the affected organ system and by whether they occur (a) at diagnosis or during initial therapy or (b) after the completion of treatment. The first group consists of oncologic emergencies, infectious complications, and irritant effects. Oncologic emergencies can be further categorized as space-occupying lesions (e.g., superior vena cava syndrome or spinal cord compression), vascular abnormalities (e.g., hyperleukocytosis, anemia, coagulopathy), and metabolic emergencies (e.g., tumor lysis syndrome). Common complications developing after completion of treatment include leukoencephalopathy and neurocognitive defects; cataract formation; cardiomyopathy and congestive heart failure; hepatic dysfunction, fibrosis, and cirrhosis; radiation enteritis; renal dysfunction or failure; scoliosis and short stature; hypothyroidism; gonadal dysfunction; graft-versus-host disease; and development of secondary malignancies. Physician awareness of these complications will permit more effective patient surveillance, which may afford patients the opportunity for earlier intervention in these situations and improved quality of life.

Risk factors for early infection of central venous catheters in pediatric patients.

BACKGROUND: In an effort to avoid infections that can lead to the premature removal of indwelling central venous catheters (CVCs), the surgical technique and host factors present in pediatric recipients of permanent CVCs were reviewed. STUDY DESIGN: All patients receiving CVCs over a 17-month period were identified. Those patients with fever and positive blood cultures drawn through the CVC within 45 days of line placement were labeled as having early infection. A case-control design was used to select two control patients for each infected patient. Charts from both the infection and control groups were reviewed for several factors present at the time of CVC placement, including fever, neutropenia (absolute neutrophil count [ANC] < 500 and ANC < 1,000), use of perioperative antibiotics, diagnosis, CVC site, and type of CVC. Chi-square test with Yates correction was used to compare the groups. Odds ratios (ORs) and 95% confidence intervals were derived. RESULTS: Among the 473 CVCs placed, early infections developed in 53 patients (12%). The control group consisted of 106 patients. Neutropenia was present in 16 of 53 infected patients versus 8 of 106 controls (p = 0.004, OR = 5.30). Perioperative antibiotics were given to 25 of 53 infected patients versus 72 of 106 controls (p = 0.02, OR = 0.42). Fever was present in 12 of 53 infected patients versus 14 of 106 controls (p = 0.19, OR = 1.92). Factors that were equally prevalent between the groups and that did not appear to influence the CVC infection rate included a diagnosis of malignancy, CVC type, and site of placement. Of the 53 infected catheters, 16 (30%) could not be cleared of infection and were removed. CONCLUSIONS: This study documents that neutropenia and failure to administer prophylactic antibiotics are risk factors for the development of early CVC infection in pediatric patients. To avoid early infection and possible premature CVC removal, we recommend that placement of permanent CVCs be postponed until the ANC is > 1,000. Perioperative antibiotics should be given. A trend toward higher infection rates was seen in patients with preoperative fever.

Results of treatment of malignant germ cell tumors in 93 children: a report from the Childrens Cancer Study Group.

We report treatment results in 93 children entered on study from 1978 to 1984 with malignant germ cell tumors (MGCTs), excluding dysgerminoma and tumors of the testis or brain. The estimated 4-year survival and event-free survival (EFS) for all 93 patients were 54% and 49%, respectively. For 30 children with ovarian tumors, the estimated 4-year survival was 67% and EFS was 63%. For 63 children with nongonadal tumors, survival and EFS were 48% and 42%, respectively. The comparison of EFS between ovarian and nongonadal tumors was significant at P = .03. The treatment plan included a second-look surgical procedure after 18 weeks of chemotherapy. Over half of 36 patients evaluated as having a residual mass present immediately before second-look surgery had no malignant tumor after review of surgical specimens. Age greater than 11 years at diagnosis, incomplete removal of tumor at first surgery, and more than one structure or organ involved at diagnosis increased the risk for adverse event. The histologic subtype of the primary tumor was not related to outcome. Diagnosis was verified by independent pathologic review, and treatment was uniform. Seventeen percent of all registered patients (21 of 127) were excluded because of ineligible pathologic diagnoses; sixty percent (13 of 21) were immature teratomas.

Germ cell tumors in infancy and childhood: a 45-year experience.

The clinical and pathologic features of germ cell tumors in 188 patients seen at the Childrens Hospital of Los Angeles from 1941 to 1986 are reviewed. There were 129 females and 59 males 19 years of age or younger. Tumors were seen in the ovary (73, 39%), sacrococcygeal region (67, 36%), testis (13, 7%), pineal region (10, 5%), mediastinum (8, 4%), and other sites (17, 9%). The mean age at diagnosis of patients with sacrococcygeal tumors was 11 months, and for those with ovarian tumors it was 9.3 years. Histologically, 56% of the tumors were benign, 15% had immature tissues, and 29% had frankly malignant tumors. Patients with immature tumors and elevated serum alpha-fetoprotein levels at diagnosis had a higher incidence of tumor relapse (p = .004). The histology of the recurrent tumors in these patients was embryonal carcinoma. Of 54 patients with malignant tumors, 27 are alive with no evidence of recurrence, 5 died of non-disease-related causes, and 22 (41%) had tumor recurrence within 3 years of initial diagnosis and eventually died of tumor progression. The 5-year survival rate for patients with benign tumors was 96%; for those with immature tumors, 83%; and for those with malignant tumors, 42%.

Immature teratomas: identification of patients at risk for malignant recurrence.

We investigated the significance of immature elements in an otherwise benign teratoma in 28 patients with immature teratomas diagnosed and treated at the Childrens Hospital of Los Angeles from 1941 to 1986. Different characteristics, including age, sex, primary tumor site, type of surgery (complete resection vs. partial resection or biopsy), and preoperative levels of alpha-fetoprotein (AFP) were analyzed to evaluate their association with risk of subsequent local malignant recurrence. After a median follow-up of 6 years, 21 patients are alive with no recurrence of the tumor (72% event-free survival). One patient died from infection after surgery and six patients had local malignant tumor recurrence within 1 year from diagnosis. Of the 28 patients, 12 had AFP levels measured at diagnosis. Eight patients had normal levels with no further evidence of tumor recurrence, and four had elevated levels with three tumor recurrences. Our experience demonstrates that only at the time of diagnosis do AFP levels correlate with a subsequent malignant behavior of these tumors (P = .004). Those patients with immature teratomas and elevated AFP levels at diagnosis should receive adjuvant chemotherapy after the initial surgical resection.

Tracing expert thinking in clinical trial design.

This paper describes a method for the analysis of the clinical trial design process used by experts. With this procedure, the scientific ideas and their sources can be identified and related to the clinical trial protocol actually prepared by the experts. An example is given using the work of the Intergroup Rhabdomyosarcoma Study Committee (IRS). That committee has been the primary contributor of information dealing with the treatment of rhabdomyosarcoma in children. The IRS-III protocol was used in this analysis of expert behavior because the protocol was adopted by the leading pediatric oncology clinical trial groups in North America and Europe. The analysis showed that the experts rely heavily, for much of the design, on ideas presented in numerical displays in published documents. Further, those aspects of the design which are innovative can be traced and better understood by applying the new procedure.