Preoperative chemotherapy for patients with Wilms tumor in Malawi is feasible and efficacious.

BACKGROUND: Wilms tumor has a survival rate of 85-90% in well resourced countries but in low income countries survival is lower. Malawi is a country with very limited resources. We studied the feasibility, toxicity and efficacy of preoperative chemotherapy for Wilms tumor in Malawian children. METHODS: All patients diagnosed with a Wilms tumor, admitted in Blantyre, Malawi, from 2006 to 2008, were included. These patients received SIOP-based preoperative chemotherapy followed by surgery and risk-stratified post-operative chemotherapy. Social support and counseling were provided to prevent abandonment of treatment. RESULTS: Twenty patients were included. Mean tumor volume at diagnosis was 2,500 ml and eight patients (40%) had metastases. Ninety-five percent of patients presented with hypertension, 80% with microscopic hematuria and 60% with a raised platelet count. Preoperative chemotherapy resulted in >50% tumor reduction in 55% of patients with localized disease and 75% of patients with metastatic disease. During preoperative chemotherapy, 11 of 18 patients experienced >or= grade 3 anaemia, 7 patients experienced >or= grade 3 neutropenia. In 12 patients the tumor was resected. Reasons of treatment failure were: abandonment of treatment (N = 3), death during anaesthesia induction (N = 1), inoperability (N = 5, due to metastatic disease in N = 4) and relapse (N = 2). One patient died of malaria 2 months after completion of chemotherapy. Eight patients (40%) are alive with a median follow up of 8 months (range 0-1.5 years). CONCLUSION: Preoperative chemotherapy for Wilms tumor is feasible, tolerated and efficacious in Malawi. Continued efforts are needed to encourage early presentation and to prevent abandonment.

Respiratory symptoms in a boy revealing Carney triad.

The association of gastrointestinal stromal cell tumor (GIST), paraganglioma, and pulmonary chondroma is known as the Carney triad, occurring predominantly in young adult females. We present the case of a 14-year-old male with respiratory symptoms resulting in the diagnosis Carney triad.

Colour Doppler ultrasound predicts chemotherapy response, but not survival in paediatric osteosarcoma.

BACKGROUND: Histological response to chemotherapy is an important prognostic factor in osteosarcoma, influencing therapeutic considerations. It would be advantageous to be able to assess chemotherapy response, and predict survival, prior to tumour resection. Colour Doppler US (CDUS) is non-invasive, non-demanding for the patient, and easy to plan. This makes the method especially suitable for children, who comprise the majority of patients. OBJECTIVE: To establish the value of CDUS for pre-operative prediction of chemotherapy response and survival, using widely available US equipment. MATERIALS AND METHODS: CDUS was performed in 21 consecutive patients before and after chemotherapy. Peak systolic velocity (PSV) in the soft-tissue component of the tumour and quotient of resistive index (QRI) of the feeding artery and contralateral control were calculated. A pathologist, unaware of CDUS results, assessed the response to chemotherapy after resection. RESULTS: QRI change after chemotherapy was significantly higher in histological responders. No correlation of QRI change with survival was found. There was no significant difference in PSV change comparing any subgroup. CDUS appeared useful in predicting chemotherapy response (sensitivity 83%, specificity 86%), especially for negative response (predictive value 92%). Survival could not be predicted accurately. CONCLUSIONS: CDUS can predict chemotherapy response, but not survival. The method could be useful in planning treatment prior to definitive surgery.

Conditionally replicative adenovirus with tropism expanded towards integrins inhibits osteosarcoma tumor growth in vitro and in vivo.

PURPOSE: The clinical course of osteosarcoma (OS) demands the development of new therapeutic options. Conditionally replicative adenoviruses (CRAds) represent promising agents for the treatment of solid tumors, because CRAds have an intrinsic replication capacity that allows in situ amplification and extensive tumor infection through lateral spread. The CRAd AdDelta24 has been developed to replicate selectively in cells with a defective retinoblastoma (Rb) pathway. Because genetic alterations in the Rb pathway are frequently observed in OS, AdDelta24 might be useful in the treatment of this cancer. EXPERIMENTAL DESIGN: Because the lack of Coxsackie adenovirus receptor on OS cells limits the efficacy of CRAd treatment, we explored alternative target molecules on OS. Insertion of an Arg-Gly-Asp (RGD-4C) integrin-targeting motif into the adenovirus fiber knob expanded tropism toward the alpha(nu)beta(3) and alpha(nu)beta(5) integrins. The oncolytic capacity of the CRAd Ad5-Delta24RGD was tested on primary OS cells in vitro and in vivo. RESULTS: The alpha(nu)beta(3)and alpha(nu)beta(5) integrins are abundantly expressed on OS cells. RGD-mediated infection augmented adenovirus infection of primary OS cells by two orders of magnitude. Ad5-Delta24RGD was shown to be highly active in killing human OS cell lines, as well as primary cell cultures. Furthermore, intratumoral injections with Ad5-Delta24RGD into established human OS xenografts that were derived directly from a patient with OS refractory for chemotherapeutic treatment caused a significant tumor-growth delay. Furthermore, adenoviral particles could be detected in tumor cells 25 days posttumor injection. CONCLUSIONS: Targeting adenovirus toward integrins rendered OS cells more sensitive to killing by Ad5-Delta24RGD. These findings suggest that Ad5-Delta24RGD has potential for use in OS treatment.