Primary thromboprophylaxis in cancer outpatients - real-world evidence.

INTRODUCTION: Cancer-associated thrombosis (CAT) is a significant concern among patients with malignant diseases, leading to increased mortality. While current guidelines recommend primary thromboprophylaxis for venous thromboembolism (VTE) in medium-to-high-risk outpatients, this practice remains controversial. A better understanding of primary thromboprophylaxis is crucial, yet there is a lack of Real-World Evidence (RWE) in Portugal. AIMS: This RWE study aimed to elucidate primary thromboprophylaxis practices among cancer outpatients in Portugal. METHODS: A five-year observational multicentric study in eight Portuguese health institutions enrolled 124 adult cancer outpatients under primary thromboprophylaxis for VTE. The endpoints were CAT, bleeding, cancer progression and death. RESULTS: High thrombotic risk tumours were prevalent, with 57% (71) of the patients presenting with pancreatic and gastric cancers. Regarding primary thromboprophylaxis, 55% (68) received Low-Molecular-Weight Heparin (LMWH). VTE was presented in 11% (14) of the patients and major bleeding in 2% (2). Vascular compression, elevated D-dimer and previous VTE were significantly associated with VTE occurrence under primary thromboprophylaxis. The Onkotev model was shown to be the best risk assessment model (RAM) in this population (p = 0.007). CAT patients exhibited a lower progression-free survival than non-CAT patients (p = 0.021), while thrombosis did not influence overall survival (p = 0.542). CONCLUSION: Primary thromboprophylaxis in medium-to-high-risk cancer outpatients is a safe and effective practice in real-world settings. This study is the first Portuguese RWE on primary thromboprophylaxis, highlighting evidence for improving prophylactic strategies in this population.

Haemostatic gene variations in cervical cancer-associated venous thrombosis: considerations for clinical strategies.

Venous thromboembolism (VTE) is a life-threatening haemostatic disease frequently diagnosed among the cancer population. The Khorana Score is currently the primal risk assessment model to stratify oncological patients according to their susceptibility to VTE, however, it displays a limited performance. Meanwhile, intensive research on VTE pathophysiology in the general population has uncovered a range of single-nucleotide polymorphisms (SNPs) associated with the condition. Nonetheless, their predictive ability concerning cancer-associated thrombosis (CAT) is controversial. Cervical cancer (CC) patients undergoing chemoradiotherapy often experience VTE, which negatively affects their survival. Thus, aiming for an improvement in thromboprophylaxis, new thrombotic biomarkers, including SNPs, are currently under investigation. In this study, the predictive capability of haemostatic gene SNPs on CC-related VTE and their prognostic value regardless of VTE were explored. Six SNPs in haemostatic genes were evaluated. A total of 401 CC patients undergoing chemoradiotherapy were enrolled in a retrospective cohort study. The implications for the time to VTE occurrence and overall survival (OS) were assessed. CAT considerably impacted the CC patients' OS (log-rank test, P < 0.001). SERPINE1 rs2070682 (T > C) showed a significant association with the risk of CC-related VTE (CC/CT vs. TT, log-rank test, P = 0.002; C allele, Cox model, hazard ratio (HR) = 6.99 and P = 0.009), while F2 rs1799963 (G > A) demonstrated an important prognostic value regardless of VTE (AA/AG vs. GG, log-rank test, P = 0.020; A allele, Cox model, HR = 2.76 and P = 0.026). For the remaining SNPs, no significant associations were detected. The polymorphisms SERPINE1 rs2070682 and F2 rs1799963 could be valuable tools in clinical decision-making, aiding in thromboprophylaxis and CC management, respectively.

Comprehensive look at rectal squamous cell carcinoma.

Rectal squamous cell carcinoma (rSCC) is a rare cancer (0.5% of all rectal cancers). It typically presents at an advanced stage and has a poor prognosis. Recently, chemoradiotherapy with organ preservation has become an option for complete response (CR). Surveillance is essential to prompt recognition of recurrence due to its high risk. We present a case of an elderly woman with rSCC stage cT4N1aM0 who underwent a combination of chemotherapy (mitomycin and fluoropyrimidine) and radiotherapy with CR and organ preservation. The patient has been in follow-up for 2 years with digital rectal examination, tumour markers, pelvic MRI, thoracic and upper abdominal CT, proctoscopy and positron emission tomography, with no disease recurrence. This highlights the success of chemoradiotherapy for rSCC treatment, allowing organ preservation.

Thrombogenesis-associated genetic determinants as predictors of thromboembolism and prognosis in cervical cancer.

Venous thromboembolism (VTE) is a leading cause of death among cancer patients. Khorana score (KS) is the most studied tool to predict cancer-related VTE, however, it exerts poor sensitivity. Several single-nucleotide polymorphisms (SNPs) have been associated with VTE risk in the general population, but whether they are predictors of cancer-related VTE is a matter of discussion. Compared to other solid tumours, little is known about VTE in the setting of cervical cancer (CC) and whether thrombogenesis-related polymorphisms could be valuable biomarkers in patients with this neoplasia. This study aims to analyse the effect of VTE occurrence on the prognosis of CC patients, explore the predictive capability of KS and the impact of thrombogenesis-related polymorphisms on CC-related VTE incidence and patients' prognosis regardless of VTE. A profile of eight SNPs was evaluated. A retrospective hospital-based cohort study was conducted with 400 CC patients under chemoradiotherapy. SNP genotyping was carried on by using TaqMan® Allelic Discrimination methodology. Time to VTE occurrence and overall survival were the two measures of clinical outcome evaluated. The results indicated that VTE occurrence (8.5%) had a significant impact on the patient's survival (log-rank test, P < 0.001). KS showed poor performance (KS ≥ 3, χ2, P = 0.191). PROCR rs10747514 and RGS7 rs2502448 were significantly associated with the risk of CC-related VTE development (P = 0.021 and P = 0.006, respectively) and represented valuable prognostic biomarkers regardless of VTE (P = 0.004 and P = 0.010, respectively). Thus, thrombogenesis-related genetic polymorphisms may constitute valuable biomarkers among CC patients allowing a more personalized clinical intervention.

Thrombosis and cachexia in cancer: Two partners in crime?

Among cancer patients, thrombosis and cachexia are major causes of morbidity and mortality. Although the two may occur together, little is known about their possible relationship. Thus, a literature review was conducted by screening the databases PubMed, Scopus, SciELO, Medline and Web of Science. To summarize, cancer-associated thrombosis (CAT) and cancer-associated cachexia (CAC) seem to share several patient-, tumour- and treatment-related risk factors. Inflammation alongside metabolic and endocrine derangement is the potential missing link between CAT, CAC and cancer. Many key players, including specific pro-inflammatory cytokines, immune cells and hormones, appear to be implicated in both thrombosis and cachexia, representing attractive predictive markers and potential therapeutic targets. Altogether, the current evidence suggests a link between CAT and CAC, however, epidemiological studies are required to explore this potential relationship. Given the high incidence and negative impact of both diseases, further studies are needed for the better management of cancer patients.

Priapism Secondary to Low-Molecular-Weight Heparins: A Case Report.

Priapism may be a side effect of low-molecular-weight heparins, and its mechanism remains unknown. The authors present a clinical case of a 51-year-old male patient with oligodendroglioma. The patient presented ischemic priapism on the third month after starting tinzaparin, without other recent changes to his medication and he denied the use of other new medicines. The patient went through surgery and the erection was resolved but presented fibrosis of the cavernous body which left him with erectile dysfunction. Since this event, the patient is no longer receiving Heparin and has had no other episodes of priapism. The prompt recognition of this side effect may decrease its morbidity and consequent impact on the quality of life. More studies are needed to better understand its pathophysiology.

O priapismo pode ser um efeito adverso das heparinas de baixo peso molecular, cuja fisiopatologia não é totalmente compreendida. Os autores apresentam o caso de um doente, do sexo masculino, 51 anos, com diagnóstico de oligodendroglioma. O doente apresentou um episódio de priapismo, no terceiro mês sob tinzaparina, sem nenhuma outra alteração recente da sua medicação habitual e com consumo de outros medicamentos negado. Foi submetido a cirurgia, com resolução do priapismo, mas apresentou fibrose sequelar dos corpos cavernosos, com consequente disfunção eréctil. Desde então o doente não retomou heparina e não apresentou novos episódios de priapismo. Um célere reconhecimento do quadro pode contribuir para menores sequelas, com consequente diminuição da morbilidade e impacto na qualidade de vida. Mais investigação é necessária para aumentar o conhecimento sobre a fisiopatologia desta situação.

Long Non-Coding RNAs: Bridging Cancer-Associated Thrombosis and Clinical Outcome of Ovarian Cancer Patients.

Ovarian cancer (OC) and venous thromboembolism (VTE) have a close relationship, in which tumour cells surpass the haemostatic system to drive cancer progression. Long non-coding RNAs (lncRNAs) have been implicated in VTE pathogenesis, yet their roles in cancer-associated thrombosis (CAT) and their prognostic value are unexplored. Understanding how these lncRNAs influence venous thrombogenesis and ovarian tumorigenesis may lead to the identification of valuable biomarkers for VTE and OC management. Thus, this study evaluated the impact of five lncRNAs, namely MALAT1, TUG1, NEAT1, XIST and MEG8, on a cohort of 40 OC patients. Patients who developed VTE after OC diagnosis had worse overall survival compared to their counterparts (log-rank test, p = 0.028). Elevated pre-chemotherapy MEG8 levels in peripheral blood cells (PBCs) predicted VTE after OC diagnosis (Mann-Whitney U test, p = 0.037; Χ2 test, p = 0.033). In opposition, its low levels were linked to a higher risk of OC progression (adjusted hazard ratio (aHR) = 3.00; p = 0.039). Furthermore, low pre-chemotherapy NEAT1 levels in PBCs were associated with a higher risk of death (aHR = 6.25; p = 0.008). As for the remaining lncRNAs, no significant association with VTE incidence, OC progression or related mortality was observed. Future investigation with external validation in larger cohorts is needed to dissect the implications of the evaluated lncRNAs in OC patients.