David J. Pinato, MD, clinician scientist, consultant medical oncologist, Department of Surgery and Cancer, Imperial College of London, discusses guidelines for toxicity management in hepatocellular carcinoma (HCC). 

Although papers have been published on the characteristics of toxicities in HCC, the guidelines set forth by the American Society of Clinical Oncology, the European Society for Medical Oncology, and the Society for Immunotherapy of Cancer offer reliable sources of guidance for toxicity evaluation, Pinato explains. These guidelines include information on diagnosingimmune pathology in the context of checkpoint inhibitors, as well as maintaining broad differentials when a patient develops toxicity, Pinato says. 

It is important to take these differentials into consideration so that the cause of the toxicity can be correctly identified and the treatment can be tailored based on adverse effect ​severity, Pinato continues. Understanding this can ensure patients are not over or undertreated, Pinato concludes.

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David J. Pinato, MD, discusses guidelines for toxicity management in hepatocellular carcinoma (HCC).  


Dr. Pinato on Guidelines for Toxicity Management in HCC 

David J. Pinato, MD, PhD, clinical senior lecturer in medical oncology, clinician scientist, consultant medical oncologist, Department of Surgery and Cancer, Imperial College London, discusses the lack of biomarkers in hepatocellular carcinoma (HCC).

Since the FDA approval of sorafenib (Nexavar) in 2007 for the treatment of patients with unresectable HCC, there had not been a novel therapy introduced to the treatment paradigm, says Pinato. As such, there was little clinical reason to biopsy patients as most of them received the same therapy.

Additionally, there are multiple subtypes of HCC, says Pinato. However, unlike 

-positive non&shy;—small cell lung cancer, for example, these subtypes are largely descriptive and lack actionable biomarkers that drive HCC progression.

Lastly, most institutions have abandoned performing routine biopsies for patients with HCC based on radiologic criteria, explains Pinato. Patients were not biopsied because there were limited therapy options, which led to a lack of molecular knowledge in HCC, which ultimately led to a lack of biomarker development, concludes Pinato.

David J. Pinato, MD, PhD, discusses the lack of biomarkers in hepatocellular carcinoma.

Dr. Pinato on Biomarker Challenges in HCC

David J. Pinato, MD, PhD, clinical senior lecturer in medical oncology, clinician scientist, consultant medical oncologist, Department of Surgery and Cancer, Imperial College London, discusses the molecular makeup of the tumor microenvironment in neuroendocrine malignancies.

Although neuroendocrine tumors (NETs) are a rare subtype of solid malignancies, increased awareness is leading to increased prevalence of this tumor subtype, says Pinato. For patients with slow-growing, low-grade NETs, treatment with somatostatin analogs is possible but patients will eventually progress, he adds. There is a delicate balance that must be found in the management of long-term survivors.

Using a retrospective approach, Pinato and colleagues looked at over 100 patients with neuroendocrine tumors of various sites and grades and examined the interaction between the activation of hypoxia and the expression of antitumor immunity markers, such as PD-L1 and Indoleamine-deoxygenase-1 (IDO-1), as they represent an immunosuppressive microenvironment.

Results showed independence between the two domains; expression of VEGF-A, Hif-1α, and Carbonic Anhydrase-IX—biomarkers of hypoxia&mdash;are independent from PD-L1 expression and other actionable drivers of anticancer immunity, says Pinato.

Pinato and his team also examined the expression of circulating tumor cells and found that 75% of patients had overexpression of PD-L1. Those patients who tested positively also had further disease advancement with a higher tumor burden. These findings support a potential therapeutic role for PD-L1/IDO-1 inhibitors in a subset of NETS, but further exploration is needed, Pinato concludes.

David J. Pinato, MD, PhD, clinical senior lecturer in medical oncology, clinician scientist, consultant medical oncologist, Department of Surgery and Cancer, Imperial College London, discusses the molecular makeup of the tumor microenvironment in neuroendocrine malignancies.
 

Dr. Pinato on Molecular Characterization of Tumor Microenvironment in NETs

David J. Pinato, MD, PhD, NIHR Academic Clinical Lecturer in Medical Oncology, resident, Royal Brompton Hospital and Imperial College London, discusses an analysis of intra-tumor heterogeneity in primary and metastatic hepatocellular carcinoma (HCC).

PD-1/PD-L1 therapies have recently shown efficacy in patients with HCC, says Pinato, adding that approximately 20% of patients will respond to these treatments. However, patient selection is a challenge. PD-L1 expression has been advocated as a stratifying biomarker but, in early-phase trials, PD-L1 has not been predictive of response.

In an analysis, researchers sought to determine, in patients with disseminated disease, whether PD-L1, PD-L2, and other immune-tolerogenic pathways are distributed across primary and metastatic disease. Clinical samples were profiled with immunohistochemistry and Nanostring technologies. Findings showed that PD-L2 was in-adversely distributed across primary and metastatic disease, but PD-L1 was not. Therefore, there was high discordance and this could have been caused by sampling bias, Pinato explains.

David J. Pinato, MD, PhD, NIHR Academic Clinical Lecturer in Medical Oncology, resident, Royal Brompton Hospital and Imperial College London, discusses an analysis of intra-tumor heterogeneity in primary and metastatic hepatocellular carcinoma (HCC).


David J. Pinato, MD, PhD

Articles

Dr. Pinato on Guidelines for Toxicity Management in HCC

Dr. Pinato on Biomarker Challenges in HCC

Dr. Pinato on Molecular Characterization of Tumor Microenvironment in NETs

Dr. Pinato Discusses Intra-tumor Heterogeneity in Primary and Metastatic HCC