Malignant Pleural Mesothelioma: A Population-Based Study of Survival

Introduction:This study characterizes the overall survival (OS) and variables affecting OS in patients with malignant pleural mesothelioma.Methods:A total of 9701 patients with malignant pleural mesothelioma, diagnosed from 1973 to 2006, were retrospectively analyzed using the population-based surveillance, epidemiology, and end results database.Results:The 6-month, 1-year, and 5-year OS were 55, 33, and 5%, respectively. Significantly adverse prognostic factors from univariate analyses included older age, male gender, higher tumor grade, nonepithelioid histology, higher stage, no cancer-directed surgery, and no radiotherapy. Race was not significant. Patients undergoing cancer-directed surgery and radiotherapy, when grouped by stage, histology, or grade, had the best median survival (versus radiotherapy or surgery alone or no surgery/radiotherapy). From Cox proportional hazards analyses, grade (range, 1–4) was associated with a hazard ratio (HR) of >1.5 (p < 0.0001), and not undergoing cancer-directed surgery was associated with a HR of >1.4 (p < 0.0001). Male gender and older age were also significantly adverse factors. Tumor histology (HR = 1.5) and nonlocalized stage (HR = 1.3) were significant in a Cox model omitting tumor grade. With grade and histology included in the Cox model, the HRs of histology and stage were of smaller magnitude and not significant.Conclusions:From a population-based registry analysis of patients with malignant pleural mesothelioma, tumor grade and cancer-directed surgery seem to have the greatest impact on OS. Although being amenable to surgery likely reflects more indolent disease and/or better performance status and cardiopulmonary function, the significantly favorable impact of surgery, accounting for tumor grade, histology, and stage, may reflect a therapeutic benefit

The Impact of Timing of Concurrent Chemoradiation in Patients With High-Grade Glioma in the Era of the Stupp Protocol

Background: The purpose of this study is to provide a critical review of current evidence for the impact of time to initiation of chemoradiation on overall survival in patients with newly diagnosed high-grade gliomas treated with radiation and concurrent temozolomide chemotherapy.Methods: A literature search was conducted using PubMed/MEDLINE and EMBASE databases. Studies were included if they provided separate analysis for patients treated with current standard of care: radiation and concurrent temozolomide. Bias assessment was performed for each included study using the Newcastle-Ottawa Assessment Scale, with Karnofsky Performance Status (KPS) and extent of resection used for comparability.Results: The initial search yielded 575 citations. Based on the inclusion/exclusion criteria, a total of 10 retrospective cohort studies were included in this review for a total of 30,298 patients. Of these, one study described an indirect relationship between time to initiation of treatment and overall survival. One study found decreased survival only with patients with significantly longer time to treatment. Four studies found no significant effect of time to treatment on overall survival. The four remaining studies found that patients with moderate time to initiation had the best overall survival.Conclusion: This review provides evidence that moderate time to initiation of chemoradiotherapy in patients with high-grade gliomas does not lead to a significant decrease in overall survival, though the effect of significant delays in treatment initiation remains unclear

Hypofractionated Stereotactic Radiotherapy for Non-breast or Prostate Cancer Oligometastases: A Tail of Survival Beyond 10 Years

Purpose and Objective(s): We sought to analyze the long-term follow-up of patients treated with hypofractionated, stereotactic radiotherapy (HSRT) for oligometastases from malignancies other than breast or prostate cancer.Materials and Methods: From 2001 to 2006, 82 cancer patients with 1–5 radiographically apparent metastatic lesions (in 1–3 organs) from primary sites other than breast or prostate cancer, were enrolled on a prospective study of HSRT. Freedom from widespread metastasis (FFWM) was defined from date of enrollment until death, an event (i.e., widespread distant metastasis not amenable to local therapy), or last radiographic study. Local recurrence was scored as an event if pathologically confirmed or if a treated lesion increased by ≥20% using RECIST criteria. Prognostic variables were assessed using Cox regression analysis.Results: The mean age was 61 ± 11 years, with a male to female ratio of 46:36. The most common metastatic sites were liver (50%), lung (48%), thoracic lymph nodes (18%), and bone (5%). Sixty-one patients (74%) had 1 involved organ and 18 (22%) had 1 lesion treated. The preferred dose-fractionation scheduled was 50 Gy in 10 fractions (52 patients). The median follow-up was 1.7 years. Eleven patients lived &gt;5 years, and 6 lived &gt;10 years. The 5-year OS, PFS, FFWM, and LC rates were 13.4, 7.3, 18.3, and 63.4%, and the 10-years OS, PFS, FFWM, and patient LC rates were 7.3, 6.1, 13.4, and 62.2%, respectively. A greater net gross tumor volume (GTV) was significantly adverse for OS (p &lt; 0.01) and LC (p &lt; 0.01). For FFWM, net GTV was not a significant factor (p = 0.14). Four patients remain alive at &gt;13 years from enrollment and treatment, without evidence of active disease.Conclusion: A small subset of select non-breast, non-prostate cancer patients with limited metastasis treated with HSRT are long-term survivors. Net GTV is a significant factor for tumor control and survival. Further research is needed to help better select patients most likely to benefit from local therapy for metastatic disease

Simple Factors Associated With Radiation-Induced Lung Toxicity After Stereotactic Body Radiation Therapy of the Thorax: A Pooled Analysis of 88 Studies

To study the risk factors for radiation-induced lung toxicity (RILT) after stereotactic body radiotherapy (SBRT) of the thorax

Multicentre results of stereotactic body radiotherapy for secondary liver tumours

AbstractBackgroundSurgical resection is the standard treatment for liver metastases, although for the majority of patients this is not possible. Stereotactic body radiotherapy (SBRT) is an alternative local-regional therapy. The purpose of this study was to evaluate the results of SBRT for secondary liver tumours from a combined multicentre database.MethodsVariables from patients treated with SBRT from four Academic Medical Centres were entered into a common database. Local tumour control and 1-year survival rates were calculated.ResultsIn total, 153 patients (91 women) 59±8.4 years old with 363 metastatic liver lesions were treated with SBRT. The underlying primary tumour arose from gastrointestinal (GI), retroperitoneal and from extra-abdominal primaries in 56%, 8% and 36% of patients, respectively. Metastases, with a gross tumour volume (GTV) of 138.5±126.8cm3, were treated with a total radiation dose of 37.5±8.2Gy in 5±3 fractions. The 1-year overall survival was 51% with an overall local control rate of 62% at a mean follow-up of 25.2±5.9 months. A complete tumour response was observed in 32% of patients. Grade 3–5 adverse events were noted in 3% of patients.ConclusionSecondary liver tumours treated with SBRT had a high rate of local control with a low incidence of adverse events

Stereotactic ablative radiotherapy for comprehensive treatment of oligometastatic tumors (SABR-COMET): Study protocol for a randomized phase II trial

<p>Abstract</p> <p>Background</p> <p>Stereotactic ablative radiotherapy (SABR) has emerged as a new treatment option for patients with oligometastatic disease. SABR delivers precise, high-dose, hypofractionated radiotherapy, and achieves excellent rates of local control. Survival outcomes for patients with oligometastatic disease treated with SABR appear promising, but conclusions are limited by patient selection, and the lack of adequate controls in most studies. The goal of this multicenter randomized phase II trial is to assess the impact of a comprehensive oligometastatic SABR treatment program on overall survival and quality of life in patients with up to 5 metastatic cancer lesions, compared to patients who receive standard of care treatment alone.</p> <p>Methods</p> <p>After stratification by the number of metastases (1-3 vs. 4-5), patients will be randomized between Arm 1: current standard of care treatment, and Arm 2: standard of care treatment + SABR to all sites of known disease. Patients will be randomized in a 1:2 ratio to Arm 1:Arm 2, respectively. For patients receiving SABR, radiotherapy dose and fractionation depends on the site of metastasis and the proximity to critical normal structures. This study aims to accrue a total of 99 patients within four years. The primary endpoint is overall survival, and secondary endpoints include quality of life, toxicity, progression-free survival, lesion control rate, and number of cycles of further chemotherapy/systemic therapy.</p> <p>Discussion</p> <p>This study will provide an assessment of the impact of SABR on clinical outcomes and quality of life, to determine if long-term survival can be achieved for selected patients with oligometastatic disease, and will inform the design of a possible phase III study.</p> <p>Trial registration</p> <p>Clinicaltrials.gov identifier: NCT01446744</p

Normal tissue toxicity after small field hypofractionated stereotactic body radiation

Stereotactic body radiation (SBRT) is an emerging tool in radiation oncology in which the targeting accuracy is improved via the detection and processing of a three-dimensional coordinate system that is aligned to the target. With improved targeting accuracy, SBRT allows for the minimization of normal tissue volume exposed to high radiation dose as well as the escalation of fractional dose delivery. The goal of SBRT is to minimize toxicity while maximizing tumor control. This review will discuss the basic principles of SBRT, the radiobiology of hypofractionated radiation and the outcome from published clinical trials of SBRT, with a focus on late toxicity after SBRT. While clinical data has shown SBRT to be safe in most circumstances, more data is needed to refine the ideal dose-volume metrics

PPAR? Downregulation by TGF in Fibroblast and Impaired Expression and Function in Systemic Sclerosis: A Novel Mechanism for Progressive Fibrogenesis

The nuclear orphan receptor peroxisome proliferator-activated receptor-gamma (PPAR-γ) is expressed in multiple cell types in addition to adipocytes. Upon its activation by natural ligands such as fatty acids and eicosanoids, or by synthetic agonists such as rosiglitazone, PPAR-γ regulates adipogenesis, glucose uptake and inflammatory responses. Recent studies establish a novel role for PPAR-γ signaling as an endogenous mechanism for regulating transforming growth factor-ß (TGF-ß)- dependent fibrogenesis. Here, we sought to characterize PPAR-γ function in the prototypic fibrosing disorder systemic sclerosis (SSc), and delineate the factors governing PPAR-γ expression. We report that PPAR-γ levels were markedly diminished in skin and lung biopsies from patients with SSc, and in fibroblasts explanted from the lesional skin. In normal fibroblasts, treatment with TGF-ß resulted in a time- and dose-dependent down-regulation of PPAR-γ expression. Inhibition occurred at the transcriptional level and was mediated via canonical Smad signal transduction. Genome-wide expression profiling of SSc skin biopsies revealed a marked attenuation of PPAR-γ levels and transcriptional activity in a subset of patients with diffuse cutaneous SSc, which was correlated with the presence of a ''TGF-ß responsive gene signature'' in these biopsies. Together, these results demonstrate that the expression and function of PPAR-γ are impaired in SSc, and reveal the existence of a reciprocal inhibitory cross-talk between TGF-ß activation and PPAR-γ signaling in the context of fibrogenesis. In light of the potent anti-fibrotic effects attributed to PPAR-γ, these observations lead us to propose that excessive TGF-ß activity in SSc accounts for impaired PPAR-γ function, which in turn contributes to unchecked fibroblast activation and progressive fibrosis. © 2010 Wei et al