Impact of Hypoxia on Radiation-Based Therapies for Liver Cancer

Background: Hypoxia, a state of low oxygen level within a tissue, is often present in primary and secondary liver tumors. At the molecular level, the tumor cells’ response to hypoxic stress induces proteomic and genomic changes which are largely regulated by proteins called hypoxia-induced factors (HIF). These proteins have been found to drive tumor progression and cause resistance to drug- and radiation-based therapies, ultimately contributing to a tumor’s poor prognosis. Several imaging modalities have been developed to visualize tissue hypoxia, providing insight into a tumor’s microbiology. Methods: A systematic literature search was conducted in PubMed, EMBASE, Cochrane, and Google Scholar for all reports related to hypoxia on liver tumors. All relevant studies were summarized. Results: This review will focus on the impact of hypoxia on liver tumors and review PET-, MRI-, and SPECT-based imaging modalities that have been developed to predict and assess a tumor’s response to radiation therapy, with a focus on liver cancers. Conclusion: While there are numerous studies that have evaluated the impact of hypoxia on tumor outcomes, there remains a relative paucity of data evaluating and quantifying hypoxia within the liver. Novel and developing non-invasive imaging techniques able to provide functional and physiological information on tumor hypoxia within the liver may be able to assist in the treatment planning of primary and metastatic liver lesions

Safety and Efficacy of Concurrent Atezolizumab/Bevacizumab or Nivolumab Combination Therapy with Yttrium-90 Radioembolization of Advanced Unresectable Hepatocellular Carcinoma

To evaluate the safety and efficacy of combining yttrium-90 radioembolization (Y90-RE) with immune checkpoint inhibitor therapy, consecutive advanced unresectable hepatocellular carcinoma (HCC) patients treated between 2016 and 2022 with atezolizumab/bevacizumab or nivolumab within three-months pre- and post-Y90-RE were retrospectively evaluated. Tumor response and treatment-related clinical/laboratory adverse events (AE) were assessed at 1 and 6 months, as well as differences in clinical and laboratory variables and median overall survival (OS) from initial treatment (whether it was Y90-RE or systemic therapy) between the two cohorts. A total of 19 patients (10 atezolizumab/bevacizumab; 9 nivolumab), comprising 84% males with median age 69 years, met the inclusion criteria. Compared to the atezolizumab/bevacizumab group, there were less males (100% vs. 67%; p = 0.02) and more ECOG ≥ 2 patients in the nivolumab group (0% vs. 33%; p = 0.02). Baseline characteristics or incidence of 6-month post-treatment any-grade AE (60% vs. 56%; p = 0.7), grade ≥ 3 AE (0% vs. 11%; p = 0.3), objective response (58% total, 60% vs. 56%; p = 0.7), and complete response (16% total; 10% vs. 22%; p = 0.8) were similar between the atezolizumab/bevacizumab and the nivolumab cohorts. Median OS was 12.9 months for the whole cohort, 16.4 months for nivolumab, and 10.7 months for atezolizumab/bevacizumab. Among patients with advanced unresectable HCC, the utilization of Y90-RE concurrently or within 90 days of nivolumab or atezolizumab/bevacizumab immunotherapy, appears to be well-tolerated and with a low incidence of severe AE

Antitumor Activity of Metformin Combined with Locoregional Therapy for Liver Cancer: Evidence and Future Directions

This article aimed to examine the effect of metformin use on improving outcomes after liver-directed therapy in patients with HCC and identify future directions with the adjuvant use of and potential therapeutic agents that operate on similar mechanistic pathways. Databases were queried to identify pertinent articles on metformin’s use as an anti-cancer agent in HCC. Eleven studies were included, with five pre-clinical and six clinical studies. The mean overall survival (OS) and progression-free survival were both higher in the locoregional therapy (LRT) + metformin-treated groups. The outcome variables, including local tumor recurrence rate, reduction in HCC tumor growth and size, tumor growth, proliferation, migration and invasion of HCC cells, HCC cell apoptosis, DNA damage, and cell cycle arrest, showed favorable outcomes in the LRT + metformin-treated groups compared with LRT alone. This systemic review provides a strong signal that metformin use can improve the tumor response after locoregional therapy. Well-controlled prospective trials will be needed to elucidate the potential antitumor effects of metformin and other mTOR inhibitors

Impact of Hypoxia on Radiation-Based Therapies for Liver Cancer

Background: Hypoxia, a state of low oxygen level within a tissue, is often present in primary and secondary liver tumors. At the molecular level, the tumor cells’ response to hypoxic stress induces proteomic and genomic changes which are largely regulated by proteins called hypoxia-induced factors (HIF). These proteins have been found to drive tumor progression and cause resistance to drug- and radiation-based therapies, ultimately contributing to a tumor’s poor prognosis. Several imaging modalities have been developed to visualize tissue hypoxia, providing insight into a tumor’s microbiology. Methods: A systematic literature search was conducted in PubMed, EMBASE, Cochrane, and Google Scholar for all reports related to hypoxia on liver tumors. All relevant studies were summarized. Results: This review will focus on the impact of hypoxia on liver tumors and review PET-, MRI-, and SPECT-based imaging modalities that have been developed to predict and assess a tumor’s response to radiation therapy, with a focus on liver cancers. Conclusion: While there are numerous studies that have evaluated the impact of hypoxia on tumor outcomes, there remains a relative paucity of data evaluating and quantifying hypoxia within the liver. Novel and developing non-invasive imaging techniques able to provide functional and physiological information on tumor hypoxia within the liver may be able to assist in the treatment planning of primary and metastatic liver lesions

Prospective longitudinal quality of life and survival outcomes in patients with advanced infiltrative hepatocellular carcinoma and portal vein thrombosis treated with Yttrium-90 radioembolization

Abstract Background To determine the effect of Yttrium-90 (Y90) radioembolization on health-related quality of life (HRQOL) and its effect on overall survival advanced, unresectable infiltrative hepatocellular carcinoma (HCC) patients with concurrent portal vein thrombosis (PVT). Methods Consecutive patients with unresectable infiltrative HCC and PVT were recruited. The Short-Form 36 (SF-36) questionnaire was used to assess HRQOL for consecutive patients treated with glass-based Y90 based on a prospective phase II trial. MR imaging was used to determine tumor progression every 3 months post-treatment. Overall survival (OS) from treatment and time to progression (TTP) was analyzed using Kaplan-Meier estimation and log-rank test. Results Thirty patients were treated and followed for 17.4 months; physical and mental component summary scores (PCS & MCS) remained unchanged at one, three, and six months. While no difference was observed in baseline SF-36 scores for patients with prolonged TTP (≥4 months) and OS (≥ 6 months), corresponding 1-month PCS were significantly higher than those with TTP < 4 months and OS < 6 months. At 1 month, patients with normalized Physical Function (PF), Role Physical (RP) and PCS within 2 standard deviations (SD) of US normalized baseline scores had a significantly prolonged median OS (15.7 vs. 3.7 months; p < 0.001) and TTP (12.4 vs. 1.8 mo; p < 0.001) compared those with physical component scores greater than 2SD below normalized US population values. Conclusion Y90 radioembolization for HCC demonstrated long-term preservation of HRQOL. Lower baseline HRQOL scores were predictive of poorer OS. Early (1 month post-treatment) significant decreases in PCS were independent predictors of poorer OS and TTP. Trial registration ClinicalTrials.gov identifier NCT01556282 , registered March 16, 2012

Clone of Cardiac Action Potential Imaging System (CAPIS)

Prosthetic eyes have been used to replace fatally diseased human eyes since the beginning of the 19 th century. Even though the cosmetic aspects of the artificial eyes have come a long way since its inception, a major short coming still exists in modern designs of these eyes. Ocularists, people who custom-make the prosthetic eyes, have quite improved the cosmetic aspects of these eyes as far as color matching between the real eye and the artificial eye in a patient is concerned, both in the eye ball and the iris. Being able to utilize a dynamic pupil in an artificial eye would tremendously improve the esthetic of such eye and make them very similar to a functioning healthy human eye

National Utilization, Survival, and Costs Analysis of Treatment Options for Stage I Non-Small Cell Lung Cancer: A SEER-Medicare Database Analysis

RATIONALE AND OBJECTIVES: To compare utilization, outcomes, and costs of surgery, radiation therapy, and percutaneous ablation for the treatment of stage I non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Using 2006-2016 Medicare-linked Surveillance, Epidemiology, and End Results (SEER) databases, stage I NSCLC patients who underwent surgery, radiotherapy, or percutaneous ablation were identified using relevant billing codes. National utilization rates were determined. Overall survival for treatment arms were compared using log-rank test and Cox-proportional hazard modeling. Mean direct costs for each treatment strategy during the first year after diagnosis were compared using Analysis of Variance. RESULTS: A total of 15,847 Stage I NSCLC patients were identified; mean age at diagnosis was 75.5 years (minimum age = 66 years) and 59.2% were female. A total of 10,732 patients (67.7%) underwent only surgery, 5013 (31.6%) only radiotherapy, and 102 (0.6%) only ablation. Utilization of surgery and ablation decreased while radiotherapy utilization increased from 2007 to 2015 (p \u3c 0.0001). Compared to the ablation group, overall survival was greater for the surgery group (HR: 0.7, 95% CI of HR: 0.6-0.9, p = 0.0047) and lower for the radiotherapy group (HR: 1.4, 95% CI of HR: 1.1-1.8, p = 0.002). The mean first year cost of therapy for ablation = $11,976) was significantly less (p \u3c 0.05) than for radiotherapy ($15,447) and surgery ($22,669). CONCLUSION: In Medicare patients with stage I NSCLC, the utilization of radiation therapy has increased and surgery has declined, while utilization of percutaneous ablation has remained uniformly low. Although overall survival is best for surgery, then ablation, and then radiation therapy, first year treatment costs are lowest for ablation

Sinistral Portal Hypertension: Presentation, Radiological Findings, and Treatment Options - A Case Report

Sinistral portal hypertension occurs when a pathological process causes occlusion of the splenic vein. The resultant elevated splenic bed venous pressure causes formation of gastric varices which can lead to hematemesis as a common presentation for this disease process. We present a case of sinistral portal hypertension in a patient with acute hematemesis as the primary presentation. Despite the challenging diagnosis process, the patient underwent splenectomy and was managed appropriately according to previously published literature

The Role of Diffusion-Weighted Imaging (DWI) in Locoregional Therapy Outcome Prediction and Response Assessment for Hepatocellular Carcinoma (HCC): The New Era of Functional Imaging Biomarkers

Reliable response criteria are critical for the evaluation of therapeutic response in hepatocellular carcinoma (HCC). Current response assessment is mainly based on: (1) changes in size, which is at times unreliable and lag behind the result of therapy; and (2) contrast enhancement, which can be difficult to quantify in the presence of benign post-procedural changes and in tumors presenting with a heterogeneous pattern of enhancement. Given these challenges, functional magnetic resonance imaging (MRI) techniques, such as diffusion-weighted imaging (DWI) have been recently investigated, aiding specificity to locoregional therapy response assessment and outcome prediction. Briefly, DWI quantifies diffusion of water occurring naturally at a cellular level (Brownian movement), which is restricted in multiple neoplasms because of high cellularity. Disruption of cellular integrity secondary to therapy results in increased water diffusion across the injured membranes. This review will provide an overview of the current literature on DWI therapy response assessment and outcome prediction in HCC following treatment with locoregional therapies

Radioembolization of Secondary Hepatic Malignancies

Cancer has become the leading cause of mortality in America, and the majority of patients eventually develop hepatic metastasis. As liver metastases are frequently unresectable, the value of liver-directed therapies, such as transarterial radioembolization (TARE), has become increasingly recognized as an integral component of patient management. Outcomes after radioembolization of hepatic malignancies vary not only by location of primary malignancy but also by tumor histopathology. This article reviews the outcomes of TARE for the treatment of metastatic colorectal cancer, metastatic breast cancer, and metastatic neuroendocrine tumors, as well as special considerations when treating metastatic disease with TARE