Project description:IntroductionLung cancer in never smokers represents a distinct epidemiological, clinical, and molecular entity.ResultsMost 712 never smoking lung cancer patients were female (72%) with a median age at diagnosis of 62.2 years (18-94). Caucasians (46%), East Asians (42%), adenocarcinoma histology (87%) and presentation with metastatic disease at diagnosis (59%) were common. Of 515 patients with available archival tissue, the most common identified single mutations were EGFR (52.2%), followed by ALK (7.5%), KRAS (2.3%), TP53 (1.3%), ERBB2 (1%), BRAF (0.4%), PIK3CA (0.4%), SMAD4 (0.4%), CTNNB1 (0.2%), AKT1 (0.2%), and NRAS (0.2%); 8% tumors had multiple mutations, while 25.8% had none identified. Median overall survival (mOS) was 42.2 months (mo) for the entire cohort. Patients with mutations in their tumors had significantly better mOS (69.5 mo) when compared to those without (31.0 mo) (HR = 0.59; 95% CI: 0.44-0.79; p < 0.001). Earlier stage (p < 0.001), adenocarcinoma histology (p = 0.012), good performance status (p < 0.001) and use of targeted therapy (p < 0.001) were each independently associated with longer survival. Patients with ALK-translocation-positive tumours have significantly longer OS compared to those without any mutations (p = 0.0029) and to those with other and null mutations (p = 0.022).ConclusionsLung cancer in never smokers represents a distinct clinical and molecular entity characterized by a high incidence of targetable mutations and long survival.MethodsWe analyzed retrospectively the data from electronic patient records of never smokers diagnosed with lung cancer treated at the Princess Margaret Cancer Centre (Toronto) between 1988-2015 to characterize demographic and clinical features, pathology, molecular profile (using hotspot or targeted sequencing panels), treatment and survival.
Project description:The Genetic Association Information Network (GAIN) Data Access Committee was established in June 2007 to provide prompt and fair access to data from six genome-wide association studies through the database of Genotypes and Phenotypes (dbGaP). Of 945 project requests received through 2011, 749 (79%) have been approved; median receipt-to-approval time decreased from 14 days in 2007 to 8 days in 2011. Over half (54%) of the proposed research uses were for GAIN-specific phenotypes; other uses were for method development (26%) and adding controls to other studies (17%). Eight data-management incidents, defined as compromises of any of the data-use conditions, occurred among nine approved users; most were procedural violations, and none violated participant confidentiality. Over 5 years of experience with GAIN data access has demonstrated substantial use of GAIN data by investigators from academic, nonprofit, and for-profit institutions with relatively few and contained policy violations. The availability of GAIN data has allowed for advances in both the understanding of the genetic underpinnings of mental-health disorders, diabetes, and psoriasis and the development and refinement of statistical methods for identifying genetic and environmental factors related to complex common diseases.
Project description:The PMCC AML RNAseq dataset consists of 81 AML patient samples (clinical data in Supplemental Table 11), processed in two batches. These patient samples are able to engraft in the NSG (NOD.Cg PrkdcscidIl2rgtm1Wjl /SzJ) mouse model. Five patients (90543, 598, 90240, 110484, 100500) were included in both batches.
Project description:The objective of this protocol is to develop an institution-wide liquid biopsy protocol that will establish a common process for collecting blood and corresponding archived tumor specimens for future research studies at the University Health Network’s Princess Margaret Cancer Centre. Circulating cell-free nucleic acids (cfNA), including cell-free DNA (cfDNA) and cell-free RNA (cfRNA), are non-invasive, real-time biomarkers that can provide diagnostic and prognostic information before cancer diagnosis, during cancer treatment, and at disease progression. Cancer research scientists and clinicians at the Princess Margaret are interested in incorporating the collection of peripheral blood samples ("liquid biopsies") into research protocols as a means of non-invasively assessing tumor progression and response to treatment at multiple time points during a patient’s course of disease.
Project description:The clinical utility of molecular profiling of tumor tissue to guide treatment of patients with advanced solid tumors is unknown. Our objectives were to evaluate the frequency of genomic alterations, clinical "actionability" of somatic variants, enrollment in mutation-targeted or other clinical trials, and outcome of molecular profiling for advanced solid tumor patients at the Princess Margaret Cancer Centre (PM).Patients with advanced solid tumors aged ?18 years, good performance status, and archival tumor tissue available were prospectively consented. DNA from archival formalin-fixed paraffin-embedded tumor tissue was tested using a MALDI-TOF MS hotspot panel or a targeted next generation sequencing (NGS) panel. Somatic variants were classified according to clinical actionability and an annotated report included in the electronic medical record. Oncologists were provided with summary tables of their patients' molecular profiling results and available mutation-specific clinical trials. Enrolment in genotype-matched versus genotype-unmatched clinical trials following release of profiling results and response by RECIST v1.1 criteria were evaluated.From March 2012 to July 2014, 1893 patients were enrolled and 1640 tested. After a median follow-up of 18 months, 245 patients (15 %) who were tested were subsequently treated on 277 therapeutic clinical trials, including 84 patients (5 %) on 89 genotype-matched trials. The overall response rate was higher in patients treated on genotype-matched trials (19 %) compared with genotype-unmatched trials (9 %; p?<?0.026). In a multi-variable model, trial matching by genotype (p?=?0.021) and female gender (p?=?0.034) were the only factors associated with increased likelihood of treatment response.Few advanced solid tumor patients enrolled in a prospective institutional molecular profiling trial were treated subsequently on genotype-matched therapeutic trials. In this non-randomized comparison, genotype-enrichment of early phase clinical trials was associated with an increased objective tumor response rate.NCT01505400 (date of registration 4 January 2012).