Background: Accurate childhood cancer survival estimates are critical for policy-makers and clinicians for priority-setting and planning decisions. However, observed survival estimates are lacking for many countries, and where available, wide variation in outcomes is reported. Understanding the barriers to optimizing survival can help improve childhood cancer outcomes. We aimed to provide estimates of global childhood cancer survival, accounting for the impact of multiple factors that influence cancer outcomes. Methods: We developed a microsimulation model to simulate childhood cancer survival for 200 countries/territories worldwide, taking into account clinical and epidemiologic factors, including country-specific treatment variables, such as availability of chemotherapy/radiation/surgery. To ensure model results were consistent with reported survival data, we calibrated the model to estimates from the CONCORD 2 and 3 studies using an Approximate Bayesian Computation approach. We estimated five-year net survival for diagnosed childhood cancer cases in each country/territory and estimated potential survival gains if seven policy interventions focused on improving treatment availability and delivery were implemented in isolation or as packages. Findings: Our model estimates that global five-year net childhood cancer survival is currently 37•4% (95% uncertainty interval [UI] 34•7%-39•8%), with large variation by region, ranging from 8•1% (95% UI 4•4%-13•7%) in Eastern Africa to 83•0% (95% UI 81•6%-84•4%) in North America. Among the seven policy interventions modeled, each individually provided limited gains, increasing global five-year net survival to between 38•4% and 44•6%. When bundled into packages of interventions that either improved service delivery or expanded treatment access, five-year net survival increased to 50•2% (95% UI 47•3%-53•0%) and 54•1% (95% UI 50•1%-58•5%), respectively. A comprehensive systems approach consisting of all policy interventions yielded super-additive gains with global five-year net survival of 53•6% (95% UI 51•5%-55•6%) at 50% scale-up and 80•8% (95% UI 79•5%-82•1%) at full implementation. Interpretation: Childhood cancer survival varies widely by region, with especially poor survival in Africa. While expanding access to treatment (chemotherapy/radiation/surgery) and addressing financial toxicity are essential, investments that improve the quality of care, at both the health system and facility-level, are needed to improve childhood cancer outcomes globally.
PURPOSE The histology of brain tumors determines treatment and predicts outcome. Population-based survival reflects the effectiveness of a health care system in managing cancer. No systematic review of worldwide variation and time trends in survival from brain tumors in children is currently available. PATIENTS AND METHODS We considered longitudinal, observational studies comprising children diagnosed with intracranial astrocytic or embryonal tumors. We searched six electronic databases from database inception to September 30, 2018, using complex search strategies. The outcome measure was 5-year survival, estimated through a time-to-event analysis. This study is registered with PROSPERO, number CRD42018111981. RESULTS Among 5,244 studies, we identified 47 eligible articles that provided 228 survival estimates. Only five studies were entirely or partially conducted in low-income or middle-income countries. Five-year survival from embryonal tumors increased from 37% in 1980 to approximately 60% in 2009. Although survival for medulloblastoma improved substantially (from 29% to 73% during 1959-2009), survival for primitive neuroectodermal tumors wavered over time (1973-2009) and between countries. Five-year survival from astrocytoma changed very little over the 27 years between 1982 and 2009 (from 78% to 89%). Interpretation of the literature was made difficult by the heterogeneity of study designs. CONCLUSION Survival has improved for embryonal tumors, but little change has been observed for astrocytic tumors. We found a striking gap in knowledge about survival from childhood brain tumor subtypes in middle-income and low-income countries, where half of these tumors are diagnosed. Larger studies are needed, including in under-represented countries and based on standardized data collection, to provide up-to-date survival estimates.
Treatment with the angiogenesis inhibitors bevacizumab, sunitinib, and sorafenib as single agents or in combination with conventional chemotherapy is becoming a cornerstone of modern anticancer therapy. However, the potential toxicity of these drugs, mainly to the cardiovascular system, is still being investigated. Patient assessment at baseline, of crucial importance in candidates for treatment, involves the evaluation of risk factors and screening for past or present cardiovascular disease. Strict monitoring of treatment-related adverse effects must be conducted in order to allow the early detection of cardiovascular toxicities and their prompt medication. In the present paper, the most frequent cardiovascular toxicities and their underlying mechanisms are investigated, with a view to providing indications for effective patient management. The Oncologist 2010;15:683-694
The Cher-LOB randomised phase II study showed that the combination of lapatinib-trastuzumab plus chemotherapy increases pathologic complete response (pCR) rate compared with chemotherapy plus either trastuzumab or lapatinib. Here, we report the post hoc survival analysis as per treatment arm, pCR and biomarkers. Methods: The Cher-LOB study randomised 121 patients with human epidermal growth factor receptor 2epositive, stage IIeIIIA breast cancer. A specific protocol to collect recurrence-free survival (RFS) and overall survival (OS) data was designed. Tumour-infiltrating lymphocytes (TILs) and PAM50-intrinsic subtyping were evaluated at baseline. Results: At 9-year median follow-up, a trend towards RFS improvement with lapatinibtrastuzumab over trastuzumab was observed (hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.18e1.05). Combining treatment arms, pCR was significantly associated with both RFS (HR 0.12, 95% CI 0.03e0.49) and OS (HR 0.12, 95% CI 0.03e0.49). TILs were significantly associated with RFS (HR Z 0.978 for each 1% increment). Luminal-A subtype was a significant and independent predictor of improved RFS as compared with other PAM50-based intrinsic subtypes at the multivariate analysis including the most relevant clinicopathologic variables (HR 0.29, 95% CI 0.09e0.94, p Z 0.040). Conclusions: Cher-LOB trial survival analysis confirmed the prognostic role of pCR and TILs and showed a signal for a better outcome with lapatinib-trastuzumab over trastuzumab. Trial registration: NCT00429299.
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