EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment.

BACKGROUND: Four international study groups undertook a large study in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based on histological response. PATIENTS AND METHODS: Patients with resectable osteosarcoma aged ≤40 years were treated with the MAP regimen, comprising pre-operatively of two 5-week cycles of cisplatin 120 mg/m(2), doxorubicin 75 mg/m(2), methotrexate 12 g/m(2) × 2 (MAP) and post-operatively two further cycles of MAP and two cycles of just MA. Patients were randomised after surgery. Those with ≥10% viable tumour in the resected specimen received MAP or MAP with ifosfamide and etoposide. Those with <10% viable tumour were allocated to MAP or MAP followed by pegylated interferon. Longitudinal evaluation of quality of life was undertaken. RESULTS: Recruitment was completed to the largest osteosarcoma study to date in 75 months. Commencing March 2005, 2260 patients were registered from 326 centres across 17 countries. About 1334 of 2260 registered patients (59%) were randomised. Pre-operative chemotherapy was completed according to protocol in 94%. Grade 3-4 neutropenia affected 83% of cycles and 59% were complicated by infection. There were three (0.13%) deaths related to pre-operative chemotherapy. At definitive surgery, 50% of patients had at least 90% necrosis in the resected specimen. CONCLUSIONS: New models of collaboration are required to successfully conduct trials to improve outcomes of patients with rare cancers; EURAMOS-1 demonstrates achievability. Considerable regulatory, financial and operational challenges must be overcome to develop similar studies in the future. The trial is registered as NCT00134030 and ISRCTN 67613327.

A prognostic model based on nodal status and Ki-67 predicts the risk of recurrence and death in breast cancer patients with residual disease after preoperative chemotherapy.

BACKGROUND: Preoperative chemotherapy (PCT) allows for in vivo testing of treatment effects on tumor and its microenvironment. Aim of this analysis was to evaluate the effect of PCT on tumor biomarker expression and to evaluate the prognostic role of treatment-induced variation of these biomarkers (molecular response). METHODS: Two hundred and twenty-one stage II-III breast cancer patients were included. The following parameters were evaluated at baseline and on surgical specimens after PCT: estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), Ki-67, p53, human epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor 2 (VEGFR2), and apoptosis. RESULTS: A pathological complete response was observed in 8.8% of the patients. PCT induced a significant reduction in the expression of ER, PgR, Ki-67, and apoptosis. As by multivariable model, Ki-67 > or = 15% and nodal positivity after preoperative chemotherapy (PCT) were significant predictors of worse disease-free survival [hazard ratio (HR) 3.79, P < 0.0001 and HR 2.31, P = 0.037, respectively]. Ki-67 > or = 15% after PCT was also a significant predictor of overall survival (HR 3.75, P = 0.013). On the basis of these two parameters, patients were classified into three groups: (i) low risk (negative nodes and Ki-67 <15%), (ii) intermediate risk (nodal positivity or Ki-67 > or = 15%), and (iii) high risk (nodal positivity and Ki-67 > or = 15%). As compared with the low-risk group, the HRs for recurrence were 3.1 and 9.3 for the intermediate- and high-risk group, respectively (P = 0.0001); the HRs for death were 2.4 and 6.5 for the intermediate- and high-risk group, respectively (P = 0.042). CONCLUSIONS: Ki-67 and nodal status have been used to generate a simple and easily reproducible prognostic model, able to discriminate patients with worse prognosis among the heterogeneous group of women with residual disease after PCT.

Cancrum oris: management, incidence, and implications of human immunodeficiency virus in Zambia.

The University Teaching Hospital is situated in the Zambian capital, Lusaka. In a 15-year period (1979 to 1993), 81 child patients with cancrum oris were admitted to the pediatric plastic surgery unit. There were 29 boys and 52 girls, of whom 58 were below 3 years of age. The majority of them were from certain provinces where the population is comparatively much lower than in other provinces of Zambia. The dietary habits in cancrum orisprone provinces are quite different than those of other provinces of Zambia. Of 81 patients, 3 refused surgery, 11 died during early medical treatment, and 12 died following early minor surgery. A total of 55 patients had reconstructive surgery by one of the authors (Nath). Problems encountered during management, such as anesthesia, trismus, and choice of appropriate flaps, are discussed in this paper. The implication of human immunodeficiency virus is also addressed.

Total loss of upper and lower lips: challenges in reconstruction.

A 2-year-old girl lost both lips after an aggressive attack of noma (gangrenous stomatitis). After an unsuccessful attempt to reconstruct her upper lip, a bipedicled chin flap was used to reconstruct both lips. The cosmetic result was good and the functional result was acceptable.

Cardiac toxicity of trastuzumab in metastatic breast cancer patients previously treated with high-dose chemotherapy: a retrospective study.

HER-2 overexpression is associated to a poor prognosis in high-risk and metastatic breast cancer (MBC) patients treated with high-dose chemotherapy (HDC). HER-2 status is also a predictive factor and when trastuzumab is administered in combination with or sequentially to chemotherapy, a significant disease-free and/or overall survival improvement has been observed in HER-2+ early and MBC. Unfortunately, in both settings, trastuzumab is associated with an increased risk of cardiac dysfunction (CD). We have reviewed the clinical charts of HER-2-overexpressing MBC patients treated with trastuzumab after HDC. Age, baseline left ventricular ejection fraction (LVEF), radiation therapy on cardiac area, exposure to anthracycline, single or multiple transplant, high-dose agents, trastuzumab treatment duration were recorded as potential risk factors. In total, 53 patients have been included in the analysis. Median LVEF at baseline was 60.5%; at the end of trastuzumab (data available for 28 patients only), it was 55% (P = 0.01). Five out of the 28 (17.9%) patients experienced CD. Two out of 53 (3.8%) patients developed a congestive heart failure. Age > or = 50 years and multiple transplant procedure were potential risk factors for CD. The overall incidence of CD observed in this population of HER-2+ MBC patients treated with trastuzumab after HDC is not superior to that reported with concomitant trastuzumab and anthracyclines. However, patients with age > or = 50 years or receiving multiple course of HDC should be considered at risk for CD.

Paediatric plastic surgery in the University Teaching Hospital, Lusaka, Zambia: a 13-year audit.

An audit of paediatric plastic surgical procedures performed over a period of 13 years (1981-1993) at the University Teaching hospital, Lusaka, Zambia is presented. There are few publications of precise data from developing countries and no audit of this nature has been published from the area of Africa encompassed by this study. The purpose of the audit was to analyse the number and pattern of paediatric plastic surgical cases and to identify problems associated with their management. The pattern could be considered representative of the whole of sub-Saharan Africa. In addition to the audit, the basic principles of management and associated problems of some of the conditions have been outlined with particular respect to the local circumstances. It is hoped that an audit such as this will serve to upgrade the plastic surgical services and lead to the subject being incorporated into the undergraduate and postgraduate curriculums. It might also form the basis for establishing regional and provincial paediatric plastic surgical units. A balanced improvement in the provision of both general and plastic surgery within the health care services of the African continent is seen as important. Finally, this audit might enable surgeons in more developed nations to understand the pattern of disease and need in Africa and familiarise those who intend to work in the continent with the situation.