Branislav Bystricky

Background: Ovarian, fallopian tube, and primary peritoneal cancers often share clinical characteristics and are typically diagnosed at advanced stages due to nonspecific symptoms. The utility of tumor markers, particularly CA125 and HE4, in the diagnosis and follow-up of these cancers remains an area of active investigation. Objectives: The CEEGOG (Central and Eastern European Gynecologic Oncology Group) OX-01 study aimed to evaluate HE4’s role alongside CA125 in follow-up for advanced-stage ovarian, fallopian tube, and primary peritoneal cancers. It assessed the potential for detecting recurrence using marker elevation and imaging methods, examining the necessity of dynamic monitoring and current cut-off values’ accuracy for early relapse detection. Methods: In this multicenter prospective cohort study, 117 eligible patients with Stage III–IV cancers were included. Patients had elevated CA125 or HE4 at diagnosis and achieved complete remission after first-line treatment. HE4 and CA125 levels were monitored every 3–4 months in the first two years and every six months thereafter. CT scans were performed if markers exceeded set thresholds or increased by over 20%. Results: During a median follow-up of 13.7 months, 73% of patients relapsed. Median HE4 levels were significantly higher in relapsed patients. A 10 IU/mL increase from baseline in CA125 had a sensitivity of 83% and specificity of 93%, while a 15 pmol/L increase in HE4 had a sensitivity of 74% and specificity of 92% for predicting relapse up to three months before CT scan detection. Conclusions: The study found that dynamic changes in HE4 and CA125 levels, rather than predefined cut-off values, are crucial for early relapse detection. These markers may offer a significant lead time over imaging, potentially enabling earlier intervention. Further research is needed to validate these findings.

Merkel cell carcinoma (MCC) is a rare skin neuroendocrine tumor presumably arising from Merkel cells in the basal layer of epidermis. It is an aggressive tumor predominantly found on the head and neck area of elderly people, with a mortality rate around 41% for all stages. Complete spontaneous regression of MCC is seldom observed, mostly in elderly women. We describe complete spontaneous regression of large, histologically confirmed MCC in an elderly woman after biopsy, which occurred incidentally, while waiting for radical surgery with skin flap. Next-generation sequencing with SOPHiA Solid Tumor Plus Solution did not reveal any relevant gene mutations or rearrangements. An update of literature for these very rare cases is provided.

Hypotension can be a symptom of paraneoplastic autonomic neuropathy (PAN). Onconeural antibodies (OA) provide strong evidence for the paraneoplastic origin of neurological syndromes. Our goal was to assess the frequency of PAN among patients with advanced malignancies and hypotension using OA. Patients with advanced malignancies and hypotension were screened and enrolled as per protocol. Plasma levels of six classical OAs were assessed in these patients. We prospectively evaluated other symptoms of PAN in these patients. 31 patients out of 740 screened met the criteria of this cross-sectional study. OAs were present in 4 patients (12.9%). Anti-amphiphysin was found in 1 patient (3.23%), anti- CV2 (anti-CRPM5, anti- collapsin- response mediator protein) was present in 1 patient (3.23%), 1 patient (3.23%) was positive for anti-Hu and anti-Ma2 was present in 1 patient (3.23%). No patient was positive for 2 or more OAs. Normalization of blood pressure in concordance with partial remission occurred in 5 patients. The most used criteria for PAN were fulfilled in 9 patients. The frequency of PAN may be underestimated in a busy oncology clinic. Assessing OAs may aid in the differential diagnosis of hypotension of unknown origin.

The cancer burden is rising globally, exerting significant strain on populations and health systems at all income levels. In May 2017, world governments made a commitment to further invest in cancer control as a public health priority, passing the World Health Assembly Resolution 70.12 on cancer prevention and control within an integrated approach. In this manuscript, the 2016 European Society for Medical Oncology Leadership Generation Programme participants propose a strategic framework that is in line with the 2017 WHO Cancer Resolution and consistent with the principle of universal health coverage, which ensures access to optimal cancer care for all people because health is a basic human right. The time for action is now to reduce barriers and provide the highest possible quality cancer care to everyone regardless of circumstance, precondition or geographic location. The national actions and the policy recommendations in this paper set forth the vision of its authors for the future of global cancer control at the national level, where the WHO Cancer Resolution must be implemented if we are to reduce the cancer burden, avoid unnecessary suffering and save as many lives as possible.

Background/Aim: Annexin A2 (ANXA2) is a phospholipid-binding protein involved in fibrinolysis, cell proliferation, migration and metastatic dissemination. Circulating tumor cells (CTCs) are cells responsible for tumor dissemination and have a prognostic value in several types of cancers including breast cancer. Previously, we found correlation between CTCs and activation of coagulation. This study aimed to correlate CTCs with ANXA2 expression on CTCs, tumor cells and tumor associated stroma in primary breast cancer (PBC) patients. Patients and Methods: This prospective study included 101 PBC patients treated by primary surgery. CTCs were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay for the expression of epithelial (CK19) or epithelial-mesenchymal transition (EMT) genes [TWIST1, SNAI1, SNAI2, zinc finger E-box-binding homeobox 1 (ZEB1)]. ANXA2 expression on CTCs was detected by qRT-PCR, while expression of ANXA2 in tumor specimen was evaluated by immunohistochemistry and expressed by a weighted histoscore, evaluating both the percentage of positive cells and the intensity of membrane and cytoplasmic staining. Results of hormone receptors, HER2 status, B-cell lymphoma 2 (bcl-2) protein expression and protein p53 were reported as either positive or negative on histopathology report without further quantification. Results: CTCs were detected in 24.8% patients. Patients with epithelial CTCs had a significantly higher ANXA2 expression on CTCs than those of patients without CTCs (p=0.01). There was no association between CTCs and ANXA2 protein expression in tumor cells. However, patients, whom CTCs with EMT phenotype were detected in, had higher ANXA2 expression in tumor stroma when compared to those with absent EMT CTCs (p=0.04). Hormone-negative tumors had significantly higher ANXA2 expression in tumor cells compared to hormone-positive tumors (p=0.03). Similarly, tumors without bcl-2 protein expression had higher tumor levels of ANXA2 compared to tumor cells that were bcl-2 positive (p=0.05). Conclusion: ANXA2 stromal expression might play a key role in aggressive tumor phenotype associated with increased EMT CTCs release, however, other factors beyond ANXA2 are responsible for coagulation activation mediated by CTCs in breast cancer patients.

Aim: Cancer increases the risk of venous thromboembolism (VTE) and circulating tumor cells (CTCs) are associated with an increased risk of VTE and, thus, with increased D-dimers as a product of fibrinolysis. Tissue plasminogen activator (tPA) is one of the key enzymes in the fibrinolytic pathway. Its activity is crucial in maintaining the balance between blood coagulation and fibrinolysis. This study aimed to analyze the association between CTCs and tPA in patients with primary breast cancer before surgery. Patients and Methods: This prospective study included 110 patients in whom CTCs were detected by quantitative reverse transcription polymerase chain reaction targeted at epithelial (CK19) or epithelial–mesenchymal transition (EMT)-associated genes[TWIST1, SNAI1, SNAI2, zinc finger E-box-binding homeobox 1 (ZEB1), forkhead box protein C2 (FOXC2)]. Plasma tPA protein was detected using enzyme-linked immunosorbent assay (ELISA). Results: CTCs were detected in 31 (28.2%) patients. There was no association between plasma tPA and CTCs. Although on average, higher levels of tPA were detected in patients with CTCs expressing EMT-associated genes, this difference did not reach statistical significance. There was no association of plasma tPA with any of the observed patient or tumor characteristics. Conclusion: Even though the blood coagulation pathway may be activated in more aggressive disease related to an elevated CTC count, in this study, we did not find any association between CTCs and plasma concentrations of tPA.

We present results of retrospective real-life data of nonsquamous lung cancer patients treated in first-line (platinum-based chemotherapy with gemcitabine without bevacizumab). 56 patients with satisfactory performance status for cytotoxic chemotherapy were treated in 2010–2014. Median progression-free survival was 6.48 months (95% CI: 4.44–9.48), time to progression was 10.19 months (95% CI: 7.59–12.19). Median overall survival was 10.8 months (95% CI: 6.72–14.52). Although our group of patients had higher proportion of elderly patients with somewhat limited performance status, progression-free survival rate was comparable to large registration studies. Overall survival, despite intervening comorbidities and subsequent limited use of second-line treatment was analogous to large gemcitabine/platinum Phase III studies in nonsquamous population. We believe our data represent real-life survival rates of unselected patients with advanced NSCLC of nonsquamous type from mostly rural catchment area.

Primary angiosarcoma of the spleen is a rare diagnosis with poor prognosis. Morphologically, it demonstrates conventional blood vessel differentiation. We present a case of 65-year-old female who underwent radical splenectomy for primary angiosarcoma of the spleen. After three-year disease-free interval, she was diagnosed with bone-only metastatic disease. Palliative radiotherapy and bisphosphonates kept her disease reasonably stable for another four years. After development of lung metastases, six cycles of single agent doxorubicin kept her progression-free for six years. Upon further progression in lungs, thirteen years after original diagnosis, lung biopsy confirmed metastatic splenic angiosarcoma in the lungs. She started weekly paclitaxel chemotherapy. Although splenic angiosarcoma generally carries grave prognosis, some patients may enjoy prolonged periods of disease stabilization. Durable benefit can be achieved in some patients with multimodality management. We review the literature focusing on systemic treatment for this rare tumor.