Tuberculosis is associated with hypercoagulation; however, there are few reports of cases thromboembolism and tuberculosis at the same time in the real world. The purpose of this study was to report the incidence and clinical course of thromboembolism in patients diagnosed with tuberculosis. We retrospectively analyzed the data of patients who were diagnosed with both tuberculosis and thromboembolism including pulmonary thromboembolism (PTE) or deep vein thrombosis (DVT) at Seoul National University Boramae Medical Center from January 2000 through March 2015. Among the 7905 tuberculosis patients, 49 (0.6%) exhibited PTE, DVT, or both at or after the time of tuberculosis diagnosis. All patients treated for tuberculosis started with isoniazid, ethambutol, rifampicin, and pyrazinamide. Eight patients were switched to treatment with second-line medication because of resistance or adverse events. About half of the patients (n = 21, 44.7%) had thrombosis at the time of tuberculosis diagnosis. Of 48 patients treated for thromboembolism, 36 received warfarin. A total of 20 patients improved symptom caused by thrombosis, and 10 patients were confirmed cure by image study such as computed tomography or doppler ultrasonography. Eight patients who were treated with warfarin had persistent thrombosis. Five patients (10.2%) experienced major bleeding that required hospitalization. All of these bleeding events were associated with warfarin therapy. Careful attention to PTE/DVT is needed at the time of diagnosis of tuberculosis and during anti-tuberculosis therapy. Warfarin therapy administered with anti-tuberculosis medication requires frequent monitoring to prevent major bleeding.

Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology, focusing on infrastructure, efficacy, and safety. We systematically reviewed and analyzed the target studies. EMBASE and PubMed searches from 2015 to 2023 generated 29 eligible trials. Data extraction included infrastructure, biomarker screening methodologies, efficacy, and safety profiles. Government agencies, cancer hospitals, and academic societies with accumulated experiences led investigator-initiated precision oncology clinical trials (IIPOCTs), which later guided sponsor-initiated precision oncology clinical trials (SIPOCTs). Most SIPOCTs were international studies with basket design. IIPOCTs primarily used the central laboratory for biomarker screening, but SIPOCTs used both central and local laboratories. Most of the studies adapted next-generation sequencing and/or immunohistochemistry for biomarker screening. Fifteen studies included an independent central review committee for outcome investigation. Efficacy assessments predominantly featured objective response rate as the primary endpoint, with varying results. Nine eligible studies contributed to the United States Food and Drug Administration’s marketing authorization. Safety monitoring was rigorous, but reporting formats lacked uniformity. Health-related quality of life and patient-reported outcomes were described in some protocols but rarely reported. Our results reveal that precision oncology trials with adaptive design rapidly and efficiently evaluate anticancer drugs’ efficacy and safety, particularly in specified biomarker-driven cohorts. The evolution from IIPOCT to SIPOCT has facilitated fast regulatory approval, providing valuable insights into the precision oncology landscape.

Ha H, et al. Brain Tumor Res Treat. 2022 Jul;10(3):158-163. https://doi.org/10.14791/btrt.2022.0018

Although approximately 50% of patients with acute myeloid leukemia (AML) are diagnosed over the age of 60 years, there is currently no established consensus on the treatment of elderly AML patients. Herein, we aimed to explore the incidence, medical expenditure, treatment, and outcomes of elderly AML patients in Korea by analyzing a nationwide cohort. We employed the Korean National Health Insurance Service-Senior cohort, which represents 10% of a random selection from a total of 5.5 million subjects aged 60 years or older. AML patients were identified according to the main diagnostic criteria of acute leukemia. Treatment for AML was divided into high- (high-dose cytarabine ± idarubicin) and low- (low-dose cytarabine or hypomethylating agents) intensity chemo-therapy and classified according to the chemotherapeutics protocol. We analyzed the survival outcomes and medical expenditures. Among 558,147 elderly patients, 471 were diagnosed with AML, and 195 (41.4%) were treated with chemotherapy. The median age was 65 years, and the median overall survival (OS) was 4.93 months (95% confidence interval, 4.47–5.43). Median OS was longer in patients undergoing chemotherapy than those in the best supportive care group (6.28 vs. 3.45 months, p < 0.001), and the difference was prominent in patients aged < 70 years. Twenty-eight (5.9%) patients received high-intensity chemotherapy, while 146 (31.0%) received low-intensity chemotherapy. The difference in median OS according to dose intensity was 4.6 months, which was longer in the high-intensity chemotherapy group (9.8 vs. 5.2 months in low-intensity group); however, the difference was not statistically significant. Patients who received high-intensity chemotherapy recorded longer hospital stays and incurred greater expenses on initial hospitalization. Elderly AML patients in Korea exhibited clinical benefits from chemotherapy. Although patients should be carefully selected for intensive treatment, chemotherapy, including low-intensity treatment, can be considered in elderly patients. Moreover, prospective studies on new agents or new treatment strategies are needed.

Purpose: Rapid development of novel therapeutics in renal cell carcinoma (RCC) has led to financial burden for patients and society. Value including clinical benefit, toxicity affecting quality of life and cost-effectiveness are a concern, prompting the need for tools to facilitate value assessment of therapeutics. This study reviews the value assessment tools, and evaluates the value of emerging therapeutics in RCC. Materials and methods: Two medical oncologists used American Society of Clinical Oncology value framework (ASCO VF) v2.0 and European Society for Medical Oncology-magnitude of clinical benefit scale (ESMO-MCBS) v1.1 to phase 3 trials evaluating first-line therapy in patients with metastatic RCC. Follow-up (FU) reports and extended survival data were included. Equivocal aspects and limitations of the tools were discussed. Results: Six trials (COMPARZ, CheckMate 214, JAVELIN renal 101, Keynote 426, CLEAR, and CheckMate 9ER) were assessed. The control arm was standard-of-care sunitinib in all trials. ASCO VF’s net health benefit, calculated as clinical benefit, toxicity and other bonus point was 11 in pazopanib, 41.9 in nivolumab plus ipilimumab, 22.4 in axitinib plus avelumab, 48.7 in axitinib plus pembrolizumab, 35.2 in lenvatinib plus pembrolizumab, and 50.8 in cabozantinib plus nivolumab. A higher score means a greater treatment benefit. ESMO-MCBS gave grade 5 to nivolumab plus ipilimumab, 4 to pazopanib, lenvatinib plus pembrolizumab and cabozantinib plus nivolumab, 3 to axitinib plus avelumab or pembrolizumab. Both tools had unclear aspects to be applied to clinical practice, and should be more clearly defined, such as endpoint for determining survival benefits or how to standardize quality of life and toxicity. Conclusions: ASCO VF and ESMO-MCBS were applied to evaluate the newly emerging drugs in RCC and assessed their value. In-depth discussion by experts in various fields is required for appropriate clinical application in a real-world setting.

Renal cell carcinoma (RCC) remains a significant challenge in oncology, prompting thorough investigations into adjuvant treatments aimed at enhancing both survival and quality of life for patients. In this review, we explore the complex landscape of adjuvant treatments for managing RCC, highlighting the pivotal roles and efficacy of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). This review article presents a detailed exploration of both historical and contemporary trials involving TKIs, spotlighting their capabilities, successes, and limitations in the adjuvant setting. Furthermore, we examine the emerging significance of ICIs, analyzing recent trials and assessing their impact on outcomes such as disease-free survival and overall survival. Additionally, this review provides insights into the application, adaptation, and outcomes of these adjuvant therapies within the specific context and circumstances of Korean healthcare.