ORCID Profile
0000-0001-7865-2701
Current Organisations
Princess Margaret Hospital Cancer Centre
,
University of Toronto
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Publisher: MDPI AG
Date: 22-08-2021
DOI: 10.3390/IJMS22169044
Abstract: Natural killer (NK) cells and type 1 innate lymphoid cells (ILC1) are specific innate lymphoid cell subsets that are key for the detection and elimination of pathogens and cancer cells. In liver, while they share a number of characteristics, they differ in many features. These include their developmental pathways, tissue distribution, phenotype and functions. NK cells and ILC1 contribute to organ homeostasis through the production of key cytokines and chemokines and the elimination of potential harmful bacteria and viruses. In addition, they are equipped with a wide range of receptors, allowing them to detect “stressed cells’ such as cancer cells. Our understanding of the role of innate lymphoid cells in hepatocellular carcinoma (HCC) is growing owing to the development of mouse models, the progress in immunotherapeutic treatment and the recent use of scRNA sequencing analyses. In this review, we summarize the current understanding of NK cells and ILC1 in hepatocellular carcinoma and discuss future strategies to take advantage of these innate immune cells in anti-tumor immunity. Immunotherapies hold great promise in HCC, and a better understanding of the role and function of NK cells and ILC1 in liver cancer could pave the way for new NK cell and/or ILC1-targeted treatment.
Publisher: Wiley
Date: 13-07-2021
DOI: 10.1002/CAM4.4125
Abstract: In men with metastatic castration‐resistant prostate cancer (mCRPC) with primarily bone metastases, radium‐223 ( 223 Ra) improves overall survival (OS). However, the selection of 223 Ra is not guided by specific validated clinicopathologic factors, and thus outcomes are heterogeneous. This retrospective survival analysis was performed in men with mCRPC treated with 223 Ra at our cancer center. Demographics and disease characteristics were collected. OS was calculated using the Kaplan–Meier method (log‐rank). The potential prognostic factors were determined using both univariable (UVA) and multivariable analysis (MVA) (Cox‐regression) methods. In total, 150 patients with a median age of 74 years (52–93) received 223 Ra between May 2015 and July 2018, and 58% had 6–20 bone metastases. Ninety‐four (63%) patients received 223 Ra doses, and 56 (37%) received ≤4. The following pre‐treatment factors were analyzed (median [range]): eastern cooperative oncology group performance status (ECOG PS), (1 [0–3]) Albumin (ALB), (39 g/L [24–47]) alkaline phosphatase (ALP), (110 U/L [35–1633]) and prostate‐specific antigen (PSA), (49 µg/L [0.83–7238]). The median OS for all patients was 14.5 months (95% CI: 11.2–18). These factors were associated with poor survival outcomes in UVA and MVA: ALB g/L, ALP U/L, ECOG PS 2–3, and PSA µg/L. By assigning one point for each of these factors, a prognostic model was developed, wherein three distinct risk groups were identified: good, 0–1 ( n = 103) intermediate, 2 ( n = 30) and poor risk, 3–4 points ( n = 17). The median OS was 19.4, 10.0, and 3.1 months, respectively ( p 0.001). Pre‐treatment ALB, ALP, ECOG, and PSA, were significantly correlated with OS and could guide treatment selection for men with mCRPC by identifying those who are most or least likely to benefit from 223 Ra. Validation in an independent dataset is required prior to widespread clinical utilization.
Publisher: Wiley
Date: 08-01-2020
DOI: 10.1002/CNCR.32692
Abstract: Patients with cancer who are treated with immune checkpoint modulators (ICMs) have their health-related quality of life (HRQOL) measured using general patient-reported outcome (PRO) tools. To the authors' knowledge, no instrument has been developed to date specifically for patients treated with ICMs. The objective of the current study was to develop a toxicity subscale PRO instrument for patients treated with ICMs to assess HRQOL. Input was collected from a systematic review as well as patients and physicians experienced with ICM treatment. Descriptive thematic analysis was used to evaluate the qualitative data obtained from patient focus groups and interviews, which informed an initial list of items that described ICM side effects and their impact on HRQOL. These inputs informed item generation and/or reduction to develop a toxicity subscale. Focus groups and in idual interviews with 37 ICM-treated patients generated an initial list of 176 items. After a first round of item reduction that produced a shortened list of 76 items, 16 physicians who care for patients who are treated with ICMs were surveyed with a list of 49 patient-reported side effects and 11 physicians participated in follow-up interviews. A second round of item reduction was informed by the physician responses to produce a list of 25 items. To the authors' knowledge, this 25-item list is the first HRQOL-focused toxicity subscale for patients treated with ICMs and was developed in accordance with US Food and Drug Administration guidelines, which prioritize patient input in developing PRO tools. The subscale will be combined with the Functional Assessment of Cancer Therapy-General (FACT-G) to form the FACT-ICM. Prior to recommending the formal use of this PRO instrument, the authors will evaluate its validity and reliability in longitudinal studies involving substantially more patients.
Location: United States of America
No related grants have been discovered for Adrian Sacher.