Genome-wide Detection of Chimeric Transcripts in Early-stage Non-small Cell Lung Cancer.

Background/aim: Lung cancer remains the main culprit in cancer-related mortality worldwide. Transcript fusions play a critical role in the initiation and progression of multiple cancers. Treatment approaches based on specific targeting of discovered driver events, such as mutations in EGFR, and fusions in NTRK, ROS1, and ALK genes led to profound improvements in clinical outcomes.

A Comparison of Patients' and Physicians' Knowledge and Expectations Regarding Precision Oncology Tests.

(1) Background: As genomic testing is becoming a part of the mainstream oncology practice, it is vital to ensure that our patients fully understand the implications of these tests. This study aimed to compare the attitudes and expectations of cancer patients with those of their physicians regarding the role of biomarker testing in clinical decision making. (2) Methods: Two separate, complimentary, self-administered questionnaires for patients with cancer and their physicians, respectively, were collected in Calgary, Alberta, Canada.

Estimating the Impact of Delayed Access to Oncology Drugs on Patient Outcomes in Canada.

Introduction: New requirements in Canada's pricing processes for patented drugs may exacerbate delays in regulatory and reimbursement reviews. This study seeks to better understand the impact of any additional delays on non-small cell lung cancer (NSCLC) patients by measuring the following: (a) durations and outcomes of regulatory and reimbursement reviews of NSCLC drugs in Canada and reference countries; (b) delays in Canada's reviews of three NSCLC drugs (nivolumab, afatinib, and pemetrexed [NAP]); and (c) estimating clinical, patient, and economic impacts of delays in Canada's reviews on access to NAP.

Methods: Information from the Context Matters database and the literature (2005-2020) was used to evaluate the durations and outcomes of reimbursement reviews of NSCLC drugs in Canada and comparator countries.

Feasibility of a multimodal exercise, nutrition, and palliative care intervention in advanced lung cancer.

Background: Advanced lung cancer patients face significant physical and psychological burden leading to reduced physical function and quality of life. Separately, physical activity, nutrition, and palliative symptom management interventions have been shown to improve functioning in this population, however no study has combined all three in a multimodal intervention. Therefore, we assessed the feasibility of a multimodal physical activity, nutrition, and palliative symptom management intervention in advanced lung cancer.

A phase IB study of durvalumab with or without tremelimumab and platinum-doublet chemotherapy in advanced solid tumours: Canadian Cancer Trials Group Study IND226.

This multicenter phase Ib study aimed to establish a recommended phase II dose for durvalumab (Du) ± tremelimumab (Tr) in combination with standard platinum-doublet chemotherapy. Eligible patients were enrolled into one of six dose levels (DL) of Du ± Tr which included concomitant treatment with standard platinum-doublet regimens; (pemetrexed, gemcitabine, etoposide, (each with cisplatin or carboplatin) or nab-paclitaxel (with carboplatin)). Dose escalation was according to a Rolling Six type design.

The Broad Application of Prepectoral Direct-to-Implant Breast Reconstruction with Acellular Dermal Matrix Drape and Fluorescent Imaging in a Community Setting.

Background: Much has been written regarding the new paradigm of prepectoral direct-to-implant reconstruction, but patient selection continues to be unclear. Prepectoral direct-to-implant (PDTI) reconstruction with acellular dermal matrix drape and fluorescent imaging (ADFI) was offered to all patients.

Methods: The PDTI with ADFI protocol is (1) fluorescent imaging following mastectomy, (2) acellular dermal matrix prepectoral drape construction, (3) direct-to-implant placement beneath drape, and (4) repeated fluorescent imaging with implant in place.

Current landscape of immunotherapy in the treatment of solid tumours, with future opportunities and challenges.

Immunotherapy has emerged as a new standard of care, showing survival benefit for solid tumours in multiple disease sites and indications. The survival improvements seen in diseases that were highly resistant to traditional therapies, with a poor prognosis, are unprecedented. Although the benefits observed in clinical trials are undeniable, not all patients derive those benefits, leading to emerging combination strategies and an ongoing quest for biomarker selection.

Demographic and clinical correlates of accelerometer assessed physical activity and sedentary time in lung cancer survivors.

Objective: To determine demographic and clinical correlates of accelerometer assessed physical activity and sedentary time among a population-based sample of lung cancer survivors.

Methods: Lung cancer survivors in Southern Alberta, Canada (N = 527) were invited to complete a mailed survey assessing socio-demographics and wear an Actigraph® GT3X+ accelerometer for 7 days. Average daily minutes of physical activity and sedentary time were derived from the accelerometer data.

Expression of DNA damage response proteins in cervical cancer patients treated with radical chemoradiotherapy.

Objective: The management of locally advanced cervical cancer has improved significantly with the advent of cisplatin-based chemoradiotherapy (CRT) as the primary treatment regimen. Nevertheless, a significant proportion of patients fail to respond or relapse on this treatment and have a very poor prognosis. Our goal was to determine the prognostic value of a panel of proteins involved in detection and repair of DNA damage.

Low Ki67/high ATM protein expression in malignant tumors predicts favorable prognosis in a retrospective study of early stage hormone receptor positive breast cancer.

Introduction: This study was designed to investigate the combined influence of ATM and Ki67 on clinical outcome in early stage hormone receptor positive breast cancer (ES-HPBC), particularly in patients with smaller tumors (< 4 cm) and fewer than four positive lymph nodes.

Methods: 532 formalin-fixed paraffin-embedded specimens of resected primary breast tumors were used to construct a tissue microarray. Samples from 297 patients were suitable for final statistical analysis.

Low ATM protein expression in malignant tumor as well as cancer-associated stroma are independent prognostic factors in a retrospective study of early-stage hormone-negative breast cancer.

Introduction: The serine/threonine protein kinase ataxia telangiectasia mutated (ATM) is critical in maintaining genomic integrity. Upon DNA double-strand breaks, ATM phosphorylates key downstream proteins including p53 and BRCA1/2, thereby orchestrating complex signaling pathways involved in cell cycle arrest, DNA repair, senescence and apoptosis. Although sporadic mutation of ATM occurs rarely in breast cancer, the status of its protein expression and its clinical significance in breast cancer remain not well established.

Characterization of a murine model of metastatic human non-small cell lung cancer and effect of CXCR4 inhibition on the growth of metastases.

Despite successful preclinical testing carried out through the use of subcutaneous xenografted tumors, many anti-cancer agents have gone on to fail in human trials. One potential factor accounting for this discrepancy may relate to the inadequacy of the commonly employed preclinical models to recapitulate the human disease, particularly when it comes to discovery of agents that are effective against advanced disease. Herein, we report the characterization of a NSCLC model and an exploration of the impact that a CXCR4 inhibitor, AMD3100, had on NCI-H1299-derived metastasis.

ATM, THMS, and RRM1 protein expression in nasopharyngeal carcinomas treated with curative intent.

Background: In advanced nasopharyngeal carcinoma (NPC), biomarkers may help predict survival.

Methods: Tumoral expression of ataxia-telangiectasia mutated (ATM), thymidylate synthetase (THMS), and ribonucleotide reductase subunit M1 (RRM1), was correlated with survival in patients with nonmetastatic NPC using quantitative fluorescence immunohistochemistry with automated quantitative digital image analysis.

Results: Of the 146 patients included, 58 patients (40%) received concurrent chemoradiation therapy; the remainder was treated with radiation.

Shame, guilt, and communication in lung cancer patients and their partners.

Lung cancer patients report the highest distress levels of all cancer groups. In addition to poor prognosis, the self-blame and stigma associated with smoking might partially account for that distress and prevent patients from requesting help and communicating with their partners. The present study used innovative methods to investigate potential links of shame and guilt in lung cancer recovery with distress and marital adjustment.

The emerging role of nimotuzumab in the treatment of non-small cell lung cancer.

Current non-small cell lung cancer (NSCLC) chemotherapy and radiotherapy regimens, although showing definite survival benefit, still leave patients with a disappointing 15% 5-year overall survival rate. Because of the need to improve traditional outcomes, research has focused on identifying specific tumorigenic pathways that may serve as therapeutic targets. The most successful strategies to date are those aimed at the epidermal growth factor receptor (EGFR), which is found to be upregulated in 40%-80% of NSCLC.

Phase I clinical trial of the anti-EGFR monoclonal antibody nimotuzumab with concurrent external thoracic radiotherapy in Canadian patients diagnosed with stage IIb, III or IV non-small cell lung cancer unsuitable for radical therapy.

Purpose: Many patients with non-small cell lung cancer (NSCLC) are eligible only for palliative radiation (RT) at presentation. This study was designed to assess the feasibility of adding the anti-EGFR monoclonal antibody nimotuzumab to palliative thoracic RT.

Methods: Patients with stage IIB, III or IV NSCLC considered unsuitable for radical radiation or chemo-radiation received nimotuzumab weekly 8× (100, 200 or 400 mg) with radiation (30 or 36 Gy in 3 Gy fractions).

Susceptibility of mantle cell lymphomas to reovirus oncolysis.

Mantle cell lymphoma (MCL) an incurable B-cell, non-Hodgkin lymphoma (NHL) urgently requires new treatments. We assessed reovirus mediated oncolysis in a panel of human MCL cell lines. In vitro, we found the cytopathic effect of reovirus infection ranged from high to very limited and correlated with levels of Ras activation.

Nimotuzumab: a novel anti-EGFR monoclonal antibody that retains anti-EGFR activity while minimizing skin toxicity.

Due to the broad importance of EGFR to tumorogenesis, targeted therapy against it has rapidly developed into a novel paradigm for cancer treatment. Two promising classes of drugs are now in use and undergoing development that target this receptor: tyrosine kinase inhibitors (TKIs) and mAbs that inhibit EGFR's extracellular domain. Nimotuzumab, a humanized murine mAb created in Cuba, has demonstrated antitumor activity similar to that of other anti-EGFR mAbs and shows promise as a single agent and as an adjunct to radiation in Phase I and II clinical trials.

The CXCR4/SDF-1 chemokine receptor axis: a new target therapeutic for non-small cell lung cancer.

Chemokines are proinflammatory chemoattractant cytokines that regulate cell trafficking and adhesion. The CXCR4 chemokine receptor and its ligand, stromal cell derived factor (SDF-1), constitute a chemokine/receptor axis that has attracted great interest because of an increasing understanding of its role in cancer, including lung cancer. The CXCR4/SDF-1 complex activates several pathways that mediate chemotaxis, migration and secretion of angiopoietic factors.

Correlations of EGFR mutations and increases in EGFR and HER2 copy number to gefitinib response in a retrospective analysis of lung cancer patients.

Background: Gefitinib, a small molecule tyrosine kinase inhibitor of the Epidermal Growth Factor Receptor (EGFR), has shown limited efficacy in the treatment of lung cancer. Recognized clinical predictors of response to this drug, specifically female, non-smoker, Asian descent, and adenocarcinoma, together suggest a genetic basis for drug response. Recent studies have addressed the relationship between response and either sequence mutations or increased copy number of specific receptor tyrosine kinases.