The effectiveness of atorvastatin for the prevention of deep vein thrombosis in cancer patients undergoing chemotherapy : A randomised controlled trial: open label.

BACKGROUND: Deep vein thrombosis (DVT) is a common complication in cancer. Although thromboprophylaxis in cancer patients is recommended by the guidelines, clinicians' use of thromboprophylaxis remains limited due to cost, bleeding complications, and reluctance to give injectable anticoagulants. Inflammation plays essential roles in the pathogenesis of cancer-associated thrombosis. Owing to its ability to decrease proinflammatory cytokines, statins have anti-inflammatory properties. Thus, statins can be possibly utilized as thromboprophylaxis therapy in cancer patients undergoing chemotherapy. OBJECTIVE: To compare the effectiveness of atorvastatin and rivaroxaban for DVT prevention in high-risk thrombosis patients with cancer undergoing chemotherapy. METHODS: Double-blind, randomized controlled trial involving cancer patients with high-risk of thrombosis undergoing chemotherapy. We randomly assigned patients without deep-vein thrombosis at screening to receive atorvastatin 20 mg or rivaroxaban 10 mg daily for up to 90 days. Doppler ultrasonography was performed 90 days following chemotherapy to diagnose DVT. Average cost-effectiveness analysis was performed to analyze the cost of atorvastatin compared to rivaroxaban. RESULTS: Of the eighty six patients who underwent randomization, primary efficacy end point was observed in 1 of 42 patients (2.3%) in the atorvastatin group and in 1 of 44 (2.2%) in the rivaroxaban group (Odds Ratio [OR], 0.953; 95% confidence interval [CI], 0.240 to 3.971; p = 1.000). There was a significant difference in the incidence of major bleeding, 2 of 42 patients (4.8%) in the atorvastatin group and 12 of 44 (27.3%) in the rivaroxaban group (OR, 0.257; 95% CI, 0.07 to 0.94; p = 0.007). The average cost-effectiveness ratio of using atorvastatin was lower than that of rivaroxaban. CONCLUSION: Atorvastatin did not differ significantly from rivaroxaban in reducing the incidence of DVT, lower bleeding risk, and cost-effectiveness for thromboprophylaxis in high-risk thrombosis patients with cancer undergoing chemotherapy. The presence of limited statistical power and wide confidence intervals in this study needs further study to strengthen the efficacy of atorvastatin as DVT prophylaxis in cancer patients. TRIAL REGISTRATION: ISRCTN71891829, Registration Date: 17/12/2020.

Advancing The Cardiovascular Care in Cancer Patients on Chemotherapy.

Cardiotoxicity associated with chemotherapy, also known as Cancer Therapy-Related Cardiac Dysfunction (CTRCD), affects 10% of patients undergoing chemotherapy and is the most undesirable side effect of chemotherapy. Over time, it is anticipated that there would be an increase in the number of cancer patients receiving treatments that could harm their cardiovascular systems. Physicians should choose whether to continue, halt, delay, or reduce the dose of chemotherapeutic drugs to reduce the impact of cardiotoxicity. Cardiotoxicity screening and diagnosis need a variety of methods, primarily echocardiography to evaluate Left Ventricular Ejection Fraction (LVEF) and Global Longitudinal Strain (GLS). Depending on the clinical state, these procedures may be carried out prior to, during, or following chemotherapy. It's critical to reduce cardiovascular risk factors and offer advice on leading a healthy lifestyle before giving cancer patients medicines. There are a lot of cancer treatment facilities all around the world that don't have evidence-based perspective cardiotoxicity scores to stratify the risk of cardiovascular problems caused by cancer therapy. Additionally, comorbid conditions like diabetes and hypertension are frequently present in cancer patients, which can have a significant impact on clinical outcomes and cancer treatment. Therefore, this article aims to discuss assessment methods, clinical practice guidance, and prevention of CTRCD.

Effect of Extra-Virgin Olive Oil on Hand Foot Syndrome and hs-CRP in Patients Receiving Capecitabine: A Randomized Trial.

BACKGROUND: Hand Foot Syndrome (HFS) is a frequent adverse effect observed in patients undergoing capecitabine chemotherapy, often leading to treatment disruptions and dose adjustments. Elevated C-Reactive Protein (hs-CRP) levels have been associated with the development of HFS. This study aimed to assess the potential of unrefined Extra Virgin Olive Oil (EVOO) supplementation in mitigating HFS and hs-CRP elevation among individuals receiving capecitabine chemotherapy. METHODS: Between November 2022 and May 2023, forty-five eligible participants were enrolled in this randomized trial. Patients with advanced colorectal or breast cancer were randomly allocated into three groups: an intervention group receiving unrefined EVOO supplementation (30 mL per day) alongside capecitabine, a placebo group receiving refined extra light olive oil (ELOO) supplementation (30 mL per day) alongside capecitabine, and a control group receiving capecitabine alone. The masking of both placebo and intervention groups was ensured through identical packaging and instructions, maintaining participant and physician blindness to the assigned treatments. Randomization, achieved via computer-generated sequences, ensured even distribution among the three groups. RESULTS: HFS incidences were notably lower in the EVOO group (13.3%) compared to the placebo (66.7%) and control (80%) groups. Instances of Grade 2 or more severe HFS were observed in 20% of placebo and 40% of control group patients. No cases of severe HFS were reported in the EVOO group. Moreover, EVOO supplementation led to a significant reduction in hs-CRP levels when contrasted with the placebo and control groups. These findings suggest that EVOO may serve as a preventive measure against HFS and exhibit anti-inflammatory effects in patients undergoing capecitabine chemotherapy. CONCLUSION: This study demonstrates the potential benefits of incorporating unrefined EVOO into the regimen of patients undergoing capecitabine chemotherapy. EVOO supplementation was associated with lower incidences of HFS and a reduction in hs-CRP levels, indicating its possible role in preventing HFS development and mitigating inflammation.

The Association of Immune Cell Infiltration with Metastasis Location in De Novo Metastatic Triple Negative Breast Cancer: A Multicenter Cross-Sectional Study in Indonesia.

BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive cancer subtype, with limited treatments and a high metastasis risk. The varying location of metastasis in TNBC patients often leads to in prognosis in breast cancer. Therefore, this study aimed to investigate the potential association between immune cells profiles in the tumor microenvironment and metastatic patterns. METHODS: We conducted a multicenter cross-sectional study in 2022 to examine formalin-fixed paraffin-embedded (FFPE) and medical record data from 2015 to 2020 in de novo metastatic TNBC patients. The medical records provided crucial information about the sites of metastasis. Immunohistochemistry (IHC) analysis was carried out on primary breast tumor tissues to evaluate the expressions of cluster of differentiation (CD)4 T-cells, CD8 T-cells, CD163, FOXP3 Tregs, and programmed death-ligand 1 (PD-L1), along with immune cells ratios showing antitumor-to-protumor activity (CD4/FOXP3, CD8/FOXP3, CD4/CD163, CD8/CD163). Metastatic locations were grouped into bone-only, visceral, lung, liver, and brain metastasis.  Results: A total of 120 metastatic TNBC patients were documented for their metastatic location and IHC report. The clinical and histopathological characteristics showed that the majority of the patients were within the 40-65 years old group, and 34.2% had standard body mass index (BMI). Furthermore, the majority (89.22%) of the patients showed No Special Type (NST), (56.7%) had histopathology grade III, high Ki-67 ≥20% (85.8%), and positive PD-L1 expression (30.8%), with visceral metastasis indicating the highest proportion of 75.8%. Patients with a high CD8/FOXP3 and CD4/FOXP3 ratio were significantly prone to have bone-only metastasis compared to visceral metastasis (p= 0.028 and p=0.024, respectively).  Conclusion: The ratio of antitumor to protumor T-lymphocytes had a significant relevance in the metastatic location patterns in TNBC.

The relationship between high ratios of CD4/FOXP3 and CD8/CD163 and the improved survivability of metastatic triple-negative breast cancer patients: a multicenter cohort study.

BACKGROUND: Triple-negative breast cancer (TNBC) has been documented as the most aggressive subtype of breast cancer. This study aimed to analyze antitumor and protumor immune activities, and their ratios as significant prognostic biomarkers in metastatic TNBC (mTNBC). METHODS: A multicenter cohort study was conducted among 103 de novo mTNBC patients. The expression of CD8 and CD163 was evaluated using immunohistochemistry staining, CD4 and FOXP3 using double-staining immunohistochemistry, and PD-L1 using immunohistochemistry and RT-PCR. RESULTS: Multivariate analysis revealed that high CD4/FOXP3 (HR 1.857; 95% CI 1.049-3.288; p = 0.034) and the CD8/CD163 ratio (HR 2.089; 95% CI 1.174-3.717; p = 0.012) yield significantly improved 1 year overall survival (OS). Kaplan-Meier analysis showed that high levels of CD4 (p = 0.023), CD8 (p = 0.043), CD4/FOXP3 (p = 0.016), CD8/FOXP3 (p = 0.005), CD8/CD163 (p = 0.005) ratios were significantly associated with higher rate of 1 year OS. Furthermore, 1 year OS was directly correlated with antitumor CD4 (R = 0.233; p = 0.018) and CD8 (R = 0.219; p = 0.026) and was indirectly correlated with protumor CD163 and FOXP3 through CD4/FOXP3 (R = 0.282; p = 0.006), CD4/CD163 (R = 0.239; p = 0.015), CD8/FOXP3 (R = 0.260; p = 0.008), and CD8/CD163 (R = 0.258; p = 0.009). CONCLUSION: This is the first study to demonstrate that high levels of CD4/FOXP3 and CD8/CD163 significantly improved the 1 year OS in de novo mTNBC patients. Thus, we recommend the application of these markers as prognosis determination and individual treatment decision.

Cancer Survivors' Experiences With and Preferences for Medical Information Disclosure and Advance Care Planning: An Online Survey Among Indonesian Cancer Support Groups.

PURPOSE: To understand the experiences and preferences of Indonesian cancer survivors regarding medical information disclosure and advance care planning. METHODS: On the basis of systematic reviews of the scientific literature, qualitative studies, and expert-panel input, we developed an online survey that was distributed to nine cancer survivor support groups in Indonesia. RESULTS: A total of 1,030 valid responses were received. Most participants were younger than 60 years (92%), female (91%), married (78%), Muslim (75%), diagnosed with breast cancer (68%), highly educated (64%), and more than one year beyond diagnosis of their cancer. If diagnosed with a life-limiting illness, participants wished to be informed about their diagnosis (74%), disease severity (61%), estimated curability (81%), expected disease trajectory (66%), and estimated life expectancy (37%). Between 46%-69% of the participants wished to discuss four topics of advance care planning (end-of-life treatments, resuscitation, health care proxies, and what matters at the end of life); 21%-42% had done so. Of those who wished to discuss these topics, 36%-79% preferred to do so with their family members. The most important reasons for not being willing to engage in advance care planning were the desire to surrender to God's will and to focus on here and now. CONCLUSION: In a group of cancer survivors, most of them were highly educated, young, female, and diagnosed with breast cancer. Their preferences for medical information and advance care planning varied, with the majority wishing for information and involvement in advance care planning. Culturally sensitive advance care planning involves health care professionals eliciting individuals' preferences for medical information disclosure and discussing different topics in advance care planning conversations.

Molecular profile of colorectal cancer in Indonesia: is there another pathway?

Colorectal cancer is an emerging public health problem in Indonesia and currently ranks among the three highest cancers. Lack of a colonoscopy screening and lifestyle changes might contribute to it. In the last few decades, there is an increasing interest towards the contribution of genetic-environment interaction in colorectal carcinogenesis. Some studies have indicated that CRC might develop through several different pathways; the three major routes are chromosomal instability (CIN), microsatellite instability (MSI), and inflammatory pathways. An earlier study on clinical epidemiology of CRC in Indonesia showed that the majority of patients were diagnosed between 45 and 50 years old, with a mean age around 47 years old. Further studies showed that most young Indonesian cases of CRC do not have hereditary characteristics; however, the CRC did not follow the conventional pathways of sporadic CRC (the CIN) pathway. Rather, it is a mixed of MSI and inflammatory pathways. Immunohistochemical studies showed that the proportion of patients with negative mismatch repair proteins was 43.5% for MSH2 and 83.5% for MLH1. Along the sporadic colorectal carcinogenesis pathway, there was a specific role of cyclooxygenase-2 (COX-2) enzyme during the polyp formation. COX-2 expression was reported in about 80% CRC cases worldwide. However, our study found only 49% of COX-2 expression among the CRC patients. Interestingly, an inflammatory marker, the nucleus factor κB (NF-κB), was expressed in about 73.5% cases, in line with a previous study. More recently, KRAS has been used as a potential tumor marker to select treatment and its expression was reported to be as high as 30%-40% worldwide. However, we found that KRAS gene expression was only 16.3%. Our findings support that CRC patients in Indonesian might follow a distinct pathway, a hypothesis that deserves further exploration.