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

Accuracy and Safety of Scout Dose Resin Yttrium-90 Microspheres for Radioembolization Therapy Treatment Planning: A Prospective Single-Arm Clinical Trial

PURPOSE: To compare the accuracy and safety of 0.56 GBq resin yttrium-90 ( MATERIALS AND METHODS: This prospective single-arm clinical trial (Clinicaltrials.gov: NCT04172714) recruited patients with HCC. Patients underwent same-day mapping with MAA and scout RESULTS: Thirty patients were treated using 19 segmental and 14 nonsegmental (ie, 2 contiguous segments or nonsegmental) therapies. MAA had weak LSF, moderate TNR, and moderate TD linear correlation with Rx CONCLUSIONS: Compared with MAA, scou

Voxel-Based Dosimetry Predicting Treatment Response and Related Toxicity in Hcc Patients Treated With Resin-Based Y90 Radioembolization: A Prospective, Single-Arm Study

BACKGROUND: There is an increasing body of evidence indicating Y90 dose thresholds for tumor response and treatment-related toxicity. These thresholds are poorly studied in resin Y90, particularly in hepatocellular carcinoma (HCC). PURPOSE: To evaluate the efficacy of prospective voxel-based dosimetry for predicting treatment response and adverse events (AEs) in patients with HCC undergoing resin-based Y90 radioembolization. MATERIALS AND METHODS: This correlative study was based on a prospective single-arm clinical trial (NCT04172714), which evaluated the efficacy of low/scout (555 MBq) activity of resin-based Y90 for treatment planning. Partition model was used with goal of tumor dose (TD) \u3e 200 Gy and non-tumoral liver dose (NTLD) \u3c 70 Gy for non-segmental therapies. Single compartment dose of 200 Gy was used for segmentectomies. Prescribed Y90 activity minus scout activity was administered for therapeutic Y90 followed by Y90-PET/CT. Sureplan® (MIM Software, Cleveland, OH) was used for dosimetry analysis. Treatment response was evaluated at 3 and 6 months. Receiver operating characteristic curve determined TD response threshold for objective response (OR) and complete response (CR) as well as non-tumor liver dose (NTLD) threshold that predicted AEs. RESULTS: N = 30 patients were treated with 33 tumors (19 segmental and 14 non-segmental). One patient died before the first imaging, and clinical follow-up was excluded from this analysis. Overall, 26 (81%) of the tumors had an OR and 23 (72%) had a CR. A mean TD of 253 Gy predicted an OR with 92% sensitivity and 83% specificity (area under the curve (AUC = 0.929, p \u3c 0.001). A mean TD of 337 Gy predicted a CR with 83% sensitivity and 89% specificity (AUC = 0.845, p \u3c 0.001). A mean NTLD of 81 and 87 Gy predicted grade 3 AEs with 100% sensitivity and 100% specificity in the non-segmental cohort at 3- and 6-month post Y90, respectively. CONCLUSION: In patients with HCC undergoing resin-based Y90, there are dose response and dose toxicity thresholds directly affecting outcomes. CLINICAL TRIAL NUMBER: NCT04172714

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

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