Progression-free survival as a surrogate endpoint for overall survival in modern ovarian cancer trials: A meta-analysis

Background: Progression-free survival (PFS) has been adopted as the primary endpoint in many randomized controlled trials, and can be determined much earlier than overall survival (OS). We investigated whether PFS is a good surrogate endpoint for OS in trials of first-line treatment for epithelial ovarian cancer (EOC), and whether this relationship has changed with the introduction of new treatment types. Methods: In a meta-analysis, we identified summary data [hazard ratio (HR) and median time] from published randomized controlled trials. Linear regression was used to assess the association between treatment effects on PFS and OS overall, and for subgroups defined by treatment type, postprogression survival (PPS) and established prognostic factors. Results: Correlation between HRs for PFS and OS, in 26 trials with 30 treatment comparisons comprising 24,870 patients, was modest (r2 = 0.52, weighted by trial sample size). The correlation diminished with recency: preplatinum/paclitaxel era, r2 = 0.66; platinum/paclitaxel, r2 = 0.44; triplet combinations, r2 = 0.22; biologicals, r2 = 0.30. The median PPS increased over time for the experimental (Ptrend = 0.03) and control arms (Ptrend = 0.003). The difference in median PPS between treatment arms strongly correlated with the difference in median OS (r2 = 0.83). In trials where the control therapy had median PPS of less than 18 months, correlation between PFS and OS was stronger (r2 = 0.64) than where the median PPS was longer (r2 = 0.48). Conclusions: In EOC, correlation in the relative treatment effect between PFS and OS in first-line platinum-based chemotherapy randomized controlled trials is moderate and has weakened with increasing availability of effective salvage therapies

Pathways to diagnosis of non-small cell lung cancer: a descriptive cohort study

Little has been published on the diagnostic and referral pathway for lung cancer in Australia. This study set out to quantify general practitioner (GP) and lung specialist attendance and diagnostic imaging in the lead-up to a diagnosis of non-small cell lung cancer (NSCLC) and identify common pathways to diagnosis in New South Wales (NSW), Australia. We used linked health data for participants of the 45 and Up Study (a NSW population-based cohort study) diagnosed with NSCLC between 2006 and 2012. Our main outcome measures were GP and specialist attendances, X-rays and computed tomography (CT) scans of the chest and lung cancer-related hospital admissions. Among our study cohort (N = 894), 60% (n = 536) had ≥4 GP attendances in the 3 months prior to diagnosis of NSCLC, 56% (n = 505) had GP-ordered imaging (chest X-ray or CT scan), 39% (N = 349) attended a respiratory physician and 11% (N = 102) attended a cardiothoracic surgeon. The two most common pathways to diagnosis, accounting for one in three people, included GP and lung specialist (respiratory physician or cardiothoracic surgeon) involvement. Overall, 25% of people (n = 223) had an emergency hospital admission. For 14% of people (N = 129), an emergency hospital admission was the only event identified on the pathway to diagnosis. We found little effect of remoteness of residence on access to services. This study identified a substantial proportion of people with NSCLC being diagnosed in an emergency setting. Further research is needed to establish whether there were barriers to the timely diagnosis of these cases

When is a GIST not a GIST? A case report of synchronous metastatic gastrointestinal stromal tumor and fibromatosis

<p>Abstract</p> <p>Background</p> <p>A number of non-malignant diseases that share similar morphological features as gastrointestinal stromal tumor (GIST) have been reported. Co-existence of GIST with these other diseases is rarely recognized or reported.</p> <p>Case presentation</p> <p>We report a case of a 62 year-old man with long-term stable control of metastatic GIST with systemic therapy, presented with an apparent intra-abdominal progression but not supported by imaging with positron emission tomography. Subsequent resection of the intra-abdominal tumor identified a non-malignant fibroid.</p> <p>Conclusion</p> <p>Differentiating localized progression of GIST from other diseases has important prognostic and therapeutic implications. The potential for co-existence of non-malignant soft tissue neoplasm should always be considered.</p

A signal-seeking Phase 2 study of olaparib and durvalumab in advanced solid cancers with homologous recombination repair gene alterations

Purpose: To determine the safety and efficacy of PARP plus PD-L1 inhibition (olaparib + durvalumab, O + D) in patients with advanced solid, predominantly rare cancers harbouring homologous recombination repair (HRR) defects. Patients and methods: In total, 48 patients were treated with O + D, 16 with BRCA1/2 alterations (group 1) and 32 with other select HRR alterations (group 2). Overall, 32 (66%) patients had rare or less common cancers. The primary objective of this single-arm Phase II trial was a progression-free survival rate at 6 months (PFS6). Post hoc exploratory analyses were conducted on archival tumour tissue and serial bloods. Results: The PFS6 rate was 35% and 38% with durable objective tumour responses (OTR) in 3(19%) and 3(9%) in groups 1 and 2, respectively. Rare cancers achieving an OTR included cholangiocarcinoma, perivascular epithelioid cell (PEComa), neuroendocrine, gallbladder and endometrial cancer. O + D was safe, with five serious adverse events related to the study drug(s) in 3 (6%) patients. A higher proportion of CD38 high B cells in the blood and higher CD40 expression in tumour was prognostic of survival. Conclusions: O + D demonstrated no new toxicity concerns and yielded a clinically meaningful PFS6 rate and durable OTRs across several cancers with HRR defects, including rare cancers

Evaluating Temporal Factors in Combined Interventions of Workforce Shift and School Closure for Mitigating the Spread of Influenza

10.1371/journal.pone.0032203PLoS ONE7

Breast Cancer Classification, according to Immunohistochemistry Determination of Oestrogen, Progesterone and HER2 Receptor, has Important Prognostic Value

Oestrogen, progesterone and HER2 receptor expression in breast cancer is of prognostic importance and influences treatment recommendations. This study classifies breast cancer into four subtypes based on receptor status

INTER-APARTMENTAL SALE-PRICE DIFFERENTIALS : A CASE STUDY

Bachelor'sBACHELOR OF SCIENCE (ESTATE MANAGEMENT

Impact of EGFR Inhibitor in Non-Small Cell Lung Cancer on Progression-Free and Overall Survival: A Meta-Analysis

Background The epidermal growth factor receptor (EGFR) signaling pathway is crucial for regulating tumorigenesis and cell survival and may be important in the development and progression of non-small cell lung cancer (NSCLC). We examined the impact of EGFR-tyrosine kinase inhibitors (TKIs) on progression-free survival (PFS) and overall survival (OS) in advanced NSCLC patients with and without EGFR mutations. ;Methods Randomized trials that compared EGFR-TKIs monotherapy or combination EGFR-TKIs-chemotherapy with chemotherapy or placebo were included. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of EGFR-TKIs for the EGFR mutation-positive (EGFRmut(+)) and EGFR mutation-negative (EGFRmut(-)) subgroups were calculated with the fixed-effects inverse variance weighted method. All statistical tests were two-sided. ;Results We included 23 eligible trials (13 front-line, 7 second-line, 3 maintenance; n = 14 570). EGFR mutation status was known in 31% of patients. EGFR-TKIs treatment prolonged PFS in EGFRmut+ patients, and EGFR mutation was predictive of PFS in all settings: The front-line hazard ratio for EGFRmut+ was 0.43 (95% confidence interval [CI] = 0.38 to 0.49; P&lt;.001), and the front-line hazard ratio for EGFRmut(-) was 1.06 (95% CI = 0.94 to 1.19; P=.35; P-interaction &lt; .001). The second-line hazard ratio for EGFRmut(+) was 0.34 (95% CI = 0.20 to 0.60; P&lt;.001), and the second-line hazard ratio for EGFRmut(-) was 1.23 (95% CI = 1.05 to 1.46; P=.01; P-interaction &lt; .001). The maintenance hazard ratio for EGFRmut(+) was 0.15 (95% CI = 0.08 to 0.27; P &lt; .001), and the maintenance hazard ratio for EGFRmut(-) was 0.81 (95% CI = 0.68 to 0.97; P = .02; P-interaction &lt; .001). EGFR-TKIs treatment had no impact on OS for EGFRmut(+) and EGFRmut(-) patients. ;Conclusions EGFR-TKIs therapy statistically significantly delays disease progression in EGFRmut+ patients but has no demonstrable impact on OS. EGFR mutation is a predictive biomarker of PFS benefit with EGFR-TKIs treatment in all settings. These findings support EGFR mutation assessment before initiation of treatment. EGFR-TKIs should be considered as front-line therapy in EGFRmut(+) advanced NSCLC patients