Effectiveness of immune checkpoint inhibitor therapy on bone metastases in non-small-cell lung cancer.

Background: Bone metastases (BoMs) are prevalent in patients with metastatic non-small-cell lung cancer (NSCLC) however, there are limited data detailing how BoMs respond to immune checkpoint inhibitors (ICIs). The purpose of this study was to compare the imaging response to ICIs of BoMs against visceral metastases and to evaluate the effect of BoMs on survival.

Materials And Methods: A retrospective, multicentre cohort study was conducted in patients with NSCLC treated with nivolumab or pembrolizumab in Alberta, Canada from 2015 to 2020.

Impact of Performance Status on Survival Outcomes and Health Care Utilization in Patients With Advanced NSCLC Treated With Immune Checkpoint Inhibitors.

Introduction: Landmark trials testing immune checkpoint inhibitors (ICIs) in advanced NSCLC are difficult to extrapolate to real-world practice given the exclusion of patients with poor (i.e., ≥2) Eastern Cooperative Oncology Group performance status (ECOG PS).

Combining TMEM Doorway Score and Mena Score Improves the Prediction of Distant Recurrence Risk in HR+/HER2- Breast Cancer Patients.

Purpose: to develop several digital pathology-based machine vision algorithms for combining TMEM and Mena scores and determine if a combination of these biomarkers improves the ability to predict development of distant metastasis over and above that of either biomarker alone.

Methods: This retrospective study included a subset of 130 patients (65 patients with no recurrence and 65 patients with a recurrence at 5 years) from the Calgary Tamoxifen cohort of breast cancer patients. Patients had confirmed invasive breast cancer and received adjuvant tamoxifen therapy.

Effectiveness and Safety of First-Line Pembrolizumab in Older Adults with PD-L1 Positive Non-Small Cell Lung Cancer: A Retrospective Cohort Study of the Alberta Immunotherapy Database.

The emergence of immunotherapy revolutionized the treatment of non-small-cell-lung cancer (NSCLC), with multiple landmark clinical trials establishing the efficacy of these agents. However, many patients who receive immunotherapy in clinical practice would be considered clinical trial ineligible. One such population that is often under-represented in clinical trials is older adults.

A biomarker-guided, prospective, phase 2 trial of pre-emptive graft-versus-host disease therapy using anti-thymocyte globulin.

Background Aims: Intensified immunosuppressive prophylaxis for graft-versus-host disease (GVHD) may be toxic and therefore warranted only in patients at high risk of developing GVHD. In patients who underwent allogeneic hematopoietic cell transplant at the authors' center, high serum soluble IL-2 receptor alpha (sIL-2Rα) and low IL-15 levels on day 7 post-transplant were found to predict a high risk of developing clinically significant GVHD (sGVHD), defined as grade 2-4 acute GVHD or moderate to severe chronic GVHD.

Methods: This was a prospective, phase 2 trial in which high-risk patients (serum sIL-2Rα >4500 ng/L or IL-15 <31 ng/L) received rabbit anti-thymocyte globulin (ATG) 3 mg/kg on day 8 post-transplant.

Evaluation of the modified immune prognostic index to prognosticate outcomes in metastatic uveal melanoma patients treated with immune checkpoint inhibitors.

Background: Metastatic uveal melanoma (MUM) is associated with poor survival and inferior response to immune checkpoint inhibitor (ICI) therapy when compared with metastatic cutaneous melanoma. Currently, prognostic biomarkers are lacking to guide treatment decisions.

Patients And Methods: We conducted a multicenter, retrospective cohort study using a centralized, province-wide cancer database in Alberta, Canada.

The Lung Immune Prognostic Index Discriminates Survival Outcomes in Patients with Solid Tumors Treated with Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICI) have revolutionized the treatment landscape of several solid tumor types. However, as patient outcomes are heterogeneous, clinical tools to aid in prognostication are needed. The Lung Immune Prognostic Index (LIPI) correlates with outcomes in patients with non-small cell lung cancer (NSCLC) treated with ICI, but its applicability beyond NSCLC is poorly defined.

Association of Indoor Tanning Exposure With Age at Melanoma Diagnosis and BRAF V600E Mutations.

There is limited information on how indoor tanning promotes melanoma development. We investigated indoor tanning use in patients with melanomas in sun-exposed skin and studied the clinicopathological and molecular characteristics in relation to indoor tanning exposure. Patients from a multidisciplinary clinic for cutaneous cancers completed standardized questionnaires on risk factors for melanoma as a component of medical history at their initial consultations.

Oncolytic Reovirus and Immune Checkpoint Inhibition as a Novel Immunotherapeutic Strategy for Breast Cancer.

As the current efficacy of oncolytic viruses (OVs) as monotherapy is limited, exploration of OVs as part of a broader immunotherapeutic treatment strategy for cancer is necessary. Here, we investigated the ability for immune checkpoint blockade to enhance the efficacy of oncolytic reovirus (RV) for the treatment of breast cancer (BrCa). In vitro, oncolysis and cytokine production were assessed in human and murine BrCa cell lines following RV exposure.

Oncolytic virotherapy as an immunotherapeutic strategy for multiple myeloma.

Multiple Myeloma (MM), a clonal malignancy of antibody-producing plasma cells, is the second most common hematologic malignancy and results in significant patient morbidity and mortality. The high degree of immune dysregulation in MM, including T cell imbalances and up-regulation of immunosuppressive checkpoint proteins and myeloid derived suppressor cells, allows this malignancy to escape from host immune control. Despite advances in the therapeutic landscape of MM over the last decade, including the introduction of immunomodulatory drugs, the prognosis for this disease is poor, with less than 50% of patients surviving 5 years.

Current Immunotherapeutic Strategies to Enhance Oncolytic Virotherapy.

Oncolytic viruses (OV) represent a promising strategy to augment the spectrum of cancer therapeutics. For efficacy, they rely on two general mechanisms: tumor-specific infection/cell-killing, followed by subsequent activation of the host's adaptive immune response. Numerous OV genera have been utilized in clinical trials, ultimately culminating in the 2015 Food and Drug Administration approval of a genetically engineered herpes virus, Talminogene laherparepvec (T-VEC).

Evaluation of three commercial progesterone receptor assays in a single tamoxifen-treated breast cancer cohort.

Estrogen receptor and progesterone receptor status are routinely assessed using immunohistochemistry assays to assist in patient prognosis and clinical management. Three commonly utilized autostainer vendors-Dako, Leica and Ventana-provide ready-to-use progesterone receptor assays; however, they have never been directly compared in a single breast cancer cohort. We looked at three immunohistochemical progesterone receptor assays, in addition to original ligand-binding assay results, in a single retrospective, tamoxifen-treated breast cancer cohort to investigate inter- and intra-observer agreement, concordance, prognostic ability and measures of test performance.

A systematic comparison of three commercial estrogen receptor assays in a single clinical outcome breast cancer cohort.

Breast cancers are routinely assessed for estrogen receptor status using immunohistochemical assays to assist in patient prognosis and clinical management. Specific assays vary between laboratories, and several antibodies have been validated and recommended for clinical use. As numerous factors can influence assay performance, many laboratories have opted for ready-to-use assays using automated stainers to improve reproducibility and consistency.

Oncolytic Viral Therapy Using Reovirus.

Current mainstays in cancer treatment such as chemotherapy, radiation therapy, hormonal manipulation, and even targeted therapies such as Trastuzumab (herceptin) for breast cancer or Iressa (gefitinib) for non-small cell lung cancer among others are limited by lack of efficacy, cellular resistance, and toxicity. Dose escalation and combination therapies designed to overcome resistance and increase efficacy are limited by a narrow therapeutic index. Oncolytic viruses are one such group of new biological therapeutics that appears to have a wide spectrum of anticancer activity with minimal human toxicity.

Immunotherapy for Lung Cancer: Has it Finally Arrived?

The possible link between infection/inflammation/immune activation and a cancer patient's outcome from both a causative and outcome point of view has long been postulated. Substantial progress in the understanding of tumor-associated antigens/epitopes, immune cellular subpopulations, cytokine pathways/expression, the tumor microenvironment, and the balance between tumor-immune suppression and stimulation have been made over the past decade. This knowledge has heralded a new era of tumor immunotherapy utilizing vaccines, immune checkpoint inhibition, and oncolytic viruses.

Reovirus modulates autophagy during oncolysis of multiple myeloma.

Multiple myeloma (MM) is a clonal plasma cell malignancy that accounts for 10-15% of newly diagnosed hematological cancers. Although significant advances have been made in the treatment of MM the disease still remains incurable. The oncolytic potential of reovirus has previously been demonstrated by others and us and is currently in phase III clinical trials for solid tumors.

Clinical trials involving the oncolytic virus, reovirus: ready for prime time?

The use of oncolytic viruses as a potential cancer therapeutic has been studied extensively over the past 15 years and is now in Phase III human clinical testing. One of the most promising of the viruses is the nonattenuated reovirus type-3 Dearing (RT3D; Reolysin(®), Oncolytics Biotech Inc., AB, Canada).

REO-001: A phase I trial of percutaneous intralesional administration of reovirus type 3 dearing (Reolysin®) in patients with advanced solid tumors.

Purpose: This open-labeled, phase I clinical trial was designed to determine the safety and tolerability of percutaneous intralesional administration of wild-type oncolytic revovirus type 3 Dearing (Reolysin®) in cancer patients with accessible and evaluable disease, who had otherwise failed to improve on standard cancer interventions.

Experimental Design: An escalating dose of Reolysin® starting from up to 10(10) plague forming units (PFU) was administered to each cohort of three patients per dose level. Viral shedding, reovirus neutralizing antibody response, toxicity and clinical response were assessed.

Reovirus as a viable therapeutic option for the treatment of multiple myeloma.

Purpose: Despite the recent advances made in the treatment of multiple myeloma, the disease still remains incurable. The oncolytic potential of reovirus has previously been shown and is currently in phase III clinical trials for solid tumors. We tested the hypothesis that reovirus can successfully target human multiple myeloma in vitro, ex vivo, and in vivo without affecting human hematopoietic stem cell (HHSC) re-population/differentiation in a murine model that partially recapitulates human multiple myeloma.

Oncolytic virotherapy for renal cell carcinoma: a novel treatment paradigm?

Introduction: Despite the development of novel targeted therapies, metastatic renal cell carcinoma (mRCC) remains an incurable disease. The known responsiveness of mRCC to immunotherapy and the molecular aberrations characteristic of this disease make it an attractive malignancy for treatment with oncolytic viruses (OVs), as these agents are capable of usurping common oncogenic signaling pathways and generating anti-tumor immune responses.

Areas Covered: The current evidence to support the use of oncolytic virotherapy against mRCC is discussed with emphasis on the molecular and immunological features of this disease that may be exploited by these biologic agents.

Oncolytic virotherapy for multiple myeloma: past, present, and future.

Multiple myeloma (MM) is a B-cell malignancy that is currently felt to be incurable. Despite recently approved novel targeted treatments such as lenalidomide and bortezomib, most MM patients' relapse is emphasizing the need for effective and well-tolerated therapies for this deadly disease. The use of oncolytic viruses has garnered significant interest as cancer therapeutics in recent years, and are currently under intense clinical investigation.

Oncolytic viral therapy for prostate cancer: efficacy of reovirus as a biological therapeutic.

Reovirus is a nonattenuated double-stranded RNA virus that exploits aberrant signaling pathways allowing selective cytotoxicity against multiple cancer histologies. The use of reovirus as a potential treatment modality for prostate cancer has not previously been described, and in this study evidence of in vitro and in vivo activity against prostate cancer was seen both in preclinical models and in six patients. The human prostate carcinoma cell lines PC-3, LN-CaP, and DU-145 exposed to replication-competent reovirus showed evidence of infection as illustrated by viral protein synthesis, cytopathic effect, and release of viral progeny.