In the phase II PHranceSCa study (NCT03674112), 85% of patients preferred the fixed-dose combination of pertuzumab (P) and trastuzumab (H) for subcutaneous injection (PH FDC SC) over PH infused intravenously (IV) as adjuvant treatment for HER2-positive early breast cancer, with no new safety signals with PH FDC SC. We present efficacy and safety data after continuation of treatment and follow-up. Patients with locally advanced, inflammatory, or early breast cancer who had completed neoadjuvant PH + chemotherapy and surgery were randomised 1:1 to 3 cycles of PH FDC SC (600 mg P/600 mg H in 10 mL) followed by 3 cycles of PH IV (P 420 mg; H 6 mg/kg) or 3 cycles of PH IV followed by 3 cycles of PH FDC SC. If needed, loading doses were P 1200 mg /H 600 mg in 15 mL for PH FDC SC and P 840 mg/H 8 mg/kg for PH IV. After the crossover period, patients continued treatment by their preferred method (continuation period, up to 18 cycles total). Efficacy (invasive disease-free survival [IDFS]) and overall survival (OS), safety and quality of life (EORTC QLQ-C30) were assessed after 3 years. 159/160 patients were treated in the continuation period (138 PH FDC SC, 21 PH IV, median 8 cycles for both) and 148 completed follow-up. The table shows safety in the continuation period. Most adverse events (AEs), including all cardiac AEs (n = 2) and anaphylaxis/hypersensitivity (n = 2), were grades 1/2. No grade 4/5 AEs occurred. There were six IDFS events (3.8%: 3-year IDFS 97.4%, 95% confidence interval [CI] = 94.9, 99.9) and two deaths (1.3%: 3-year OS 98.7%, 95% CI = 96.9, 100.0). Mean changes from baseline in EORTC QLQ-C30 were generally minimal. PH FDC SC was well tolerated, with safety consistent with that of PH IV (except injection-site reactions) and no grade ≥3 anaphylaxis/hypersensitivity or new safety signals in the continuation period. Efficacy data are immature but show high IDFS and OS rates at 3 years.
The novel concept of immune thrombocytopenia (ITP) pathogenesis is focused on CD4 + T cells, currently considered indispensable in stimulating B cells to produce anti-platelet antibodies.In this in vitro study, we have investigated CD4 + T cell profiles of ITP patients and immunomodulatory effects of TGF-β treatment.CD4 + T cells were isolated from peripheral blood mononuclear cells of healthy controls and ITP patients.After brief incubation, the levels of T helper signature cytokines and the number of T regulatory cells (Tregs) were determined.TGF-β immunomodulatory proprieties were analyzed by the alterations in cytokine production of IFNγ, IL-4, IL-10, IL-17, and IL-2 and Treg frequency, after six-day treatment.ITP patients had decreased level of IL-4 and IL-10, increased IL-17 level and augmented both IFNγ/IL-4 and IL-17/IL-10 ratio.Interestingly, in the six-day CD4 + T cell cultures without TGF-β, no statistically significant differences in cytokine levels between the control and ITP group were documented, except for IL-10 which was significantly lower.In ITP group treated with TGF-β, a significant increase of IL-10 as well as a decrease in IL-17/IL-10 ratio was detected, compared to TGF-β untreated ITP group.There was also an increase in the Treg frequency.The results of our study suggest that ITP patients have Th1 and Th17 biased cell-mediated immune response that can be corrected by enhanced TGF-β signaling.However, it appears that long-term culturing of the CD4 + T cells may not be a suitable experimental model for studying immunomodulating effects in ITP due to dynamic phenotype fluctuations of these cells in ex vivo conditions.
Triple-negative breast cancers denote malignant epithelial tumors showing complete hormonal independence with negative HER2 expression.Histologically, in most cases these are high-grade tumors, showing fields of central necrosis, lymphocytic infiltration, and fibrosis.The aim of the study was to examine morphometric parameters related to nuclear size depending on the type of carcinoma, as well as tumor proliferation.The entire research was conducted at the Center for Pathology and Pathological Anatomy, Clinical Center Niš.Sixty-four biopsy samples of triple-negative breast cancers were analysed, including 40 ductal, 6 lobular, 6 medullary, 4 ductulolobular, 4 metaplastic, 2 adenoid cystic and 2 apocrine carcinomas.The morphometric analysis was performed in the software package "ImageJ" version 1.52a.The statistical analysis of data was done in the software package SPSS 15.0.By comparing the values of the studied morphometric parameters, statistically significantly higher parameter values for Area, Perim and Feret were found in the group of medullary carcinomas, as well as the parameters for Integrated Optical Density.The value of integrated optical density was also very high in the ductal carcinoma group, but with no statistically significant differences due to high standard deviation.Metaplastic carcinoma showed the highest proliferative activity.Numerous similar studies have been trying to identify a specific marker of these carcinomas, which is still a challenge due to its aggressiveness.These are high-grade tumors with a broad spectrum of polymorphisms, usually with an overlapping morphological presentation, therefore, additional analyses are required in order to set adequate diagnosis.
Mantle cell lymphoma (MCL) is a distinct subtype of lymphoma identified as a particular entity in the early 1990s. The prognosis of MCL is generally poor, and is considered one of the worst among all B-cell lymphomas. In general, conventional chemotherapy is only palliative and the median duration of remissions is only 1-2 years. With the exception of allogeneic hematopoietic stem cell transplantation (allo-SCT), current treatment approaches are not curative and the corresponding survival curve is characterized by a relatively steep and continuous decline, with a median survival of about 4 years and <15% long-term survivors. Only a small proportion of patients may be exempted from this disappointing picture, because they have an indolent course of the disease and could be handled with watch and wait strategy. Optimal first-line therapy in MCL is not established yet. Very intensive regimens, including autologous (auto-SCT) and allo-SCT, seem to be required to improve the outcome. Allogeneic stem cell transplantation is the only therapy that can achieve a plateau in the survival curve, but, however, it is not applicable in most of the cases due to the patients' older age when the disease mostly occurs. Molecular knowledge of MCL has progressed and therefore a large number of molecular targeted therapies have been introduced in relapsed and refractory disease.
Colorectal cancer (CRC) is the third most common cancer and the second cause of cancer-related deaths worldwide. Despite early diagnosis and treatment improvement, the majority of patients will still suffer from metastatic disease (mCRC), which has a poor prognosis. Molecular diversity of CRC requires personalized targeted approach for improving patient outcomes. Antiangiogenic agents proved to be beneficial in the continuum of mCRC treatment. For efficient epidermal growth factor receptor (EGFR) directed therapy, subtle molecular selection and better strategies to overcome resistance are needed. BRAF mutant and HER-2 positive mCRC will soon be provided with approved targeted treatments and check-point inhibitors demonstrated effectiveness in microsatellite instability (MSI) - high mCRC. Moreover, numeorous promising agents are entering clinical trial arena. This review summarizes actual and possible targets and current and promising agents for mCRC treatment. With broader accessibility of liquid biopsy we could track molecular evolution of CRC and target genetic alterations as they emerge.
Introduction: Cancer treatment, in terms of chemotherapy and radiotherapy has evolved significantly from its beginning. Both therapies, especially used in combination, had the potential to cause side effects, that potentially decrease in quality of life and lead to increased mortality rate in patients with cancer. The aim of the study: The effects of radiotherapy and chemotherapy were described. The oral complications which consequently occurred could be classified into following categories: mucositis, oral dryness, fungal, viral and bacterial infections, disgeusia, disfagio, profuse bleeding, osteonecrosis and muscle trismus. Conclusion: Because of the wide range of preventive and curative measures, it is necessary to create a special team for caring of patients before, during and after radiotherapy and chemotherapy. In such case, dentist, oral medicine specialists should be an active member of oncology team.
Tapentadol is a unique opioid analgesic due to its dual mechanism of action. Compared to other opioids with a classical mechanism of action, its analgesic potential is not far behind them, and its advantages are: a better safety profile in terms of a lower potential for drug-drug interactions and a lower potential for causing adverse events, and it is safe to use in sensitive populations. Tapentadol in the form of a immediate release formulation is an adequate drug of choice for achieving a pharmacotherapeutic analgesic response in acute pain conditions, while in the form of a extended release formulation it is an adequate pharmacotherapeutic analgesic solution for chronic pain syndromes of various etiology. Due to the specificity of the mechanism of action, tapentadol adequately relieves both pain components - nociceptive and neuropathic, and has an indication area for mixed pain syndrome as well. Based on this, the need for the use of co-analgesics is reduced, and thus the incidence of possible interactions and adverse events is reduced.
HER2-positive hormone-sensitive (HER2+/HR+) breast cancers have recently been singled out as a separate entity.It has been suggested that elevated estrogen receptor (ER) expression and/or activity may represent an avoidance mechanism or an alternative pathway leading to resistance to anti-HER2 therapy.The aim of the study was to examine the disease outcome as the clinical benefit rate (CBR), progression-free survival (PFS), and overall survival (OS), both in the group of patients with HER2-positive metastatic breast cancer treated with first-line systemic therapy of trastuzumab along with chemotherapy and in patients with different status of hormone receptors HR+/HER2+ (ER+ and/or PR+/HER2+) compared to HR-/HER2+ (ER-/PR-/HER2+).The study included 121 patients with pathohistologically confirmed HER2+ metastatic breast cancer treated with trastuzumab along with chemotherapy during 2017 and monitored until June 2020.The mean age of the patients was 55.45 ± 9.83 years.53.7% of the patients were HRpositive and 46.3% HR-negative.Progression-free survival was statistically significantly different regarding the HR status.Patients with HR-have longer PFS compared to patients with HR + (15 and 8 months, respectively).Patients with HR-tumors have a 62% lower risk of disease progression compared to HR+ tumors (HR 0.382; 95% CI 0.261-0.558,p < 0.001).The overall survival was statistically significantly different regarding the HR status (p = 0.034).Patients with HR-have longer survival compared to patients with HR+ (43 and 35 months, respectively).Hormone receptor negative tumors have a 43% lower risk of fatal outcome compared to hormone-sensitive tumors (HR 0.576; 95% CI 0.342-0.972,p = 0.039).Given that HR+/HER2-tumors have a poorer outcome with trastuzumab treatment, future clinical trials should focus on the combination of hormonotherapy and anti-HER2 therapy in this subtype of breast cancers.
Introduction. Recommended biological agents for the first-line treatment of left-sided metastatic colorectal cancer (mCRC) without mutations in RAS/BRAF genes are cetuximab or panitumumab, while for rightsided mCRC bevacizumab is advised instead. For transversal colon mCRC the data about biological treatment efficacy is lacking. We present a patient with right-sided mCRC originated from transversal colon where panitumumab and chemotherapy treatment resulted in an excellent outcome. Case outline. A 56-year-old woman was diagnosed with transversal colon adenocarcinoma, without RAS genes mutations, with multiple liver metastases disseminated in both lobes. After the operation of the primary tumor, the patient was treated with panitumumab and FOLFOX4 chemotherapy regimen. After two months of treatment, the dramatic response was evident ? The diameter sum of the target lesions decreased by 70.5%. After two more months of therapy, further decrease by 22.5% was evident. Liver metastases were operated on. Histopathology revealed fibrotic and necrotic tissue in all suspicious lesions, except in one focus, where adenocarcinoma was found, but with 90% of surrounding necrosis. Twelve months after liver surgery the patient is without signs of the progressive disease. Conclusion. Detailed comprehensive studies of genetic features of mCRC hold a key to personalized treatment options and better outcomes for patients with mCRC.