Systemic Treatment Strategies Research Articles

Ranking of Transarterial and Targeted Therapies for Advanced Hepatocellular Carcinoma in the Era of Immuno-Oncology: A Network Meta-Analysis

Background: We aimed to compare and rank all relevant transarterial and targeted treatments competing with atezolizumab plus bevacizumab in the first-line setting for advanced hepatocellular carcinoma (HCC) based on direct and indirect evidence. Methods: This network meta-analysis was conducted in the context of a systematic review of phase 2 and 3 randomized sorafenib-controlled trials investigating systemic treatment strategies for advanced HCC as first-line option published between 2008 and 2021. We ranked the treatments based on overall survival (OS) as the primary outcome, together with progression-free survival (PFS) and grade 3-4 adverse events. Subgroup analyses were also implemented to estimate the efficacies of the interventions in particular groups. Findings: We identified 3,451 publications, and 15 trials comprising 7,158 patients were finally included in the analysis: they involved 14 different therapies including combinations of sorafenib with transarterial chemoembolization (TACE), hepatic arterial chemoinfusion, and radioembolization. Regarding OS, atezolizumab+bevacizumab was the only regimen significantly superior to sorafenib (hazard ratio 0.42; 95% confidence interval [CI] 0.25-0.70), and it ranked first. This combination was also the best in the PFS analysis (0.59; 0.47-0.74), followed by lenvatinib (0.66; 0.57-0.76) and TACE+sorafenib (0.73; 0.59-0.91), which all had significantly better outcomes than sorafenib alone. TACE+sorafenib (0.52; 0.27-1.00) was ranked first based on OS in a subset with portal invasion, but not in the metastatic series, with atezolizumab+bevacizumab second (0.58; 0.38-0.89). Lenvatinib (odds ratio 1.76; 95% CI 1.35-2.30) and TACE+sorafenib (2.02; 1.23-3.32), but not atezolizumab+bevacizumab (1.38; 0.93-2.05), were significantly less safe than sorafenib monotherapy. Interpretation: Our results indicate that atezolizumab+bevacizumab is the best first-line clinically relevant modality in patients with advanced HCC. TACE+sorafenib may also be considered for the disease with portal invasion. Funding Information: National Research Foundation of Korea, Hanyang University. Declaration of Interests: The authors declare no competing interests.

The Management of Brain Metastases-Systematic Review of Neurosurgical Aspects.

Simple SummaryIn this comprehensive review, we focused on the neurosurgical treatment as an integrative part of the challenging multidisciplinary management of cerebral metastases, a neuro-oncologic entity, which has been observed to have an increased incidence over the last years. In selected cases, the surgical removal of the space-occupying mass reduces the intracranial pressure, normalizes the metabolic environment, reduces the symptom burden, and allows for the intensification of local and systemic adjuvant treatment. In detail, we discuss the incidence of brain metastases, the role of surgical resection, as well as the evolution of current neurosurgical techniques, the surgical morbidity and mortality of single and multiple lesions, and we enlighten the role of surgery for recurrent tumors.The multidisciplinary management of patients with brain metastases (BM) consists of surgical resection, different radiation treatment modalities, cytotoxic chemotherapy, and targeted molecular treatment. This review presents the current state of neurosurgical technology applied to achieve maximal resection with minimal morbidity as a treatment paradigm in patients with BM. In addition, we discuss the contribution of neurosurgical resection on functional outcome, advanced systemic treatment strategies, and enhanced understanding of the tumor biology.

Emerging systemic antitarget treatment for differentiated thyroid carcinoma.

We review the new systemic treatment strategies for differentiated thyroid carcinoma, as well as the acquaintance of its molecular biology. Multiple kinase inhibitor drugs have become the standard therapy for thyroid cancer, albeit several adverse effects. In the last few years, new molecules have raised with an overall safety profile. Most of them, are considered targeted therapies directed toward driven-molecules alterations, such as neurotrophic tyrosine kinase receptor (NTRK) inhibitors for NTRK-fusion thyroid cancer and rearranged during transfection (RET) inhibitors for RET-fusion thyroid cancer. Recently, promising outcomes and safety data have been presented. Furthermore, other novel strategies for advanced thyroid carcinoma are currently investigated in clinical trials.The ability to provide precision medicine to patients in routine clinical settings depends on the availability of molecular profiling test at their cancer centers. The impossibility to perform molecular characterization could turn out to be a diagnostic and treatment limitation for some patients. The treatment of advanced differentiated thyroid carcinoma has undergone rapid evolution in the last decade. An emerging treatment era is coming. From now to then, we will need to face the different types of diagnostic tools for molecular characterization, their interpretation and, finally the access to targeted therapies.

Atezolizumab and bevacizumab combination compared with sorafenib as the first-line systemic treatment for patients with unresectable hepatocellular carcinoma: A cost-effectiveness analysis in China and the United states.

In patients with unresectable hepatocellular carcinoma (HCC), the combination of atezolizumab and bevacizumab improved progression-free survival (PFS) and overall survival compared with sorafenib in the IMbrave150 trial. However, whether the price of the combination could be affordable is unknown. The current study assessed the cost-effectiveness of the combination of atezolizumab and bevacizumab as first-line systemic therapy for patients with unresectable HCC from the Chinese and American payers' perspective. A Markov model was built based on a global, multicentre, open-label, phase III randomized trial (IMbrave150, NCT03434379) that included three states of the patient's health: stable disease (SD), progressive disease (PD) and death. Data for all medical costs were acquired from the Red Book, published literature and West China Hospital. Quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were the primary outcomes. Sensitivity analyses were performed to evaluate the model uncertainty. The treatment consisting of a combination of atezolizumab and bevacizumab yielded an additional 0.53 QALYs compared with sorafenib alone, leading to an ICER of $145,546.21 per QALY in China and $168,030.21 per QALY in the USA, both beyond the willing-to-pay threshold ($28,527.00/QALY in China and $150,000.00 /QALY in the USA). The utility of the PD state was the most influential factor in the Chinese model, and the American model was the most sensitive to the price of sorafenib. The results of the models were robust across sensitivity analyses. The combination of atezolizumab and bevacizumab was not a cost-effective strategy for the first-line systemic treatment of unresectable HCC from the Chinese and American payers' perspective.

Gold nanoparticle-based nanoprobes with enhanced tumor targeting and photothermal/photodynamic response for therapy of osteosarcoma

AbastractPlasmonic nanomaterials, especially a wide variety of gold nanoparticles, demonstrate great potential for theranostics of cancer. Herein, a gold nanotriangle with CD133 and hyaluronic acid on its surface loaded with a near-infrared photosensitizer was prepared for enhanced photodynamic/photothermal combined anti-tumor therapy. CD133 and hyaluronic acid provide the nanoprobe with dual tumor targeting, while the hyaluronic acid also protects photosensitive drugs from photodegradation. Thus, the nanoprobe has enhanced photothermal/photodynamic effects. This integrated treatment strategy significantly enhanced photodynamic/photothermal destruction of osteosarcoma cells. In addition, this treatment, induced by mild irradiation with a single wavelength laser, inhibited tumor growth in an osteosarcoma mouse model. These results indicate that this systemic treatment strategy can achieve enhanced anti-tumor therapeutic effects through active tumor targeting and protection of the loaded drugs.

Metaplastic Breast Carcinoma: Experience of a Tertiary Cancer Center in the Middle East.

Background:Metaplastic breast cancer (MetBC) represents a therapeutic challenge. We evaluated the impact of clinicopathological characteristics and treatment modalities on outcomes among MetBC patients treated at our center.Methods:Women with stage I-III MetBC were reviewed from our database from 2005-2018. Kaplan-Meier method was used to calculate locoregional-failure-free survival (LRFFS), overall-survival (OS) and distant-metastases-free survival (DMFS). We assessed associations with survival outcomes by log-rank tests. Multivariate Cox proportional-hazards models were used to identify independent predictors of LRFFS, OS and DMFS.Results:81 patients were eligible for the study. Median age at diagnosis was 48 years. 90.1% had G-III tumors, 64.2% were pathologically node negative and lympho-vascular invasion (LVI) was absent in 72.8%. 67.8% were triple negative, and 7.4% were HER2-neu positive. Most (66.7%) patients underwent mastectomy. Free margins were achieved in the entire cohort, however, 17.3% had close margin (<2 mm). Almost all patients received chemotherapy. 75.3% received radiotherapy, 23.5% received hormonal therapy and 6.2% received Trastuzumab. With a median follow-up of 54 months, 18.5% developed loco-regional recurrence and 34.6% relapsed distally. Five-year OS was 66.0%. On multivariate analysis: adjuvant radiotherapy correlated with better OS (P < .0001), and tumor size >5 cm, nodal involvement and LVI correlated with worse OS, (P = .019, P = .021, P = .028, respectively). There were no survival differences with respect to age, triple negativity, and morphologic subtype.Conclusion:We report the largest single institutional series on MetBC in the Middle East region. MetBC confers worse survival outcomes, and more aggressive local and systemic treatment strategies should be investigated.

Treatment planning facilitates clinical decision making for hyperthermia treatments

Background: Treatment quality is important in clinical hyperthermia. Guideline-based treatment protocols are used to determine system settings and treatment strategies to ensure effective tumor heating and prevent unwanted treatment-limiting normal tissue hot spots. Realizing both these goals can prove challenging using generic guideline-based and operator-dependent treatment strategies. Hyperthermia treatment planning (HTP) can be very useful to support treatment strategies. Although HTP is increasingly integrated into the standard clinical workflow, active clinical application is still limited to a small number of hyperthermia centers and should be further stimulated. Purpose: This paper aims to serve as a practical guide, demonstrating how HTP can be applied in clinical decision making for both superficial and locoregional hyperthermia treatments. HTP in clinical decision making: Seven problems that occur in daily clinical practice are described and we show how HTP can enhance insight to formulate an adequate treatment strategy. Examples use representative commercially available hyperthermia devices and cover all stages during the clinical workflow. Problems include selecting adequate phase settings, heating ability analysis, hot spot suppression, applicator selection, evaluation of target coverage and heating depth, and predicting possible thermal toxicity in case of an implant. Since we aim to promote a general use of HTP in daily practice, basic simulation strategies are used in these problems, avoiding a need for the application of dedicated advanced optimization routines that are not generally available. Conclusion: Even fairly basic HTP can facilitate clinical decision making, providing a meaningful and clinically relevant contribution to maintaining and improving treatment quality.

Primary Tumor Lymph Node Status Affects Overall and Recurrence-free Survival after Curative Resection of Colorectal Liver Metastases

Purpose: The primary cause of mortality in colorectal cancer is metastatic disease. This study investigated the effect of lymph node status of the primary tumor, on long-term outcomes of patients undergoing curative resection for colorectal liver metastases (CRLM). Methods: Patients in our institutional tissue bank, who underwent curative resection for CRLM, were included in this retrospective study. Patients were split into two groups according to the lymph node status from resection of the primary tumor, either N0/N1 or N2. Overall survival (OS) and recurrence-free survival (RFS) were analyzed, and risk factors were identified using Cox regression analysis. Results: After excluding resections of recurrent metastases, 181 patients were included, of which 123 (68%) and 58 (32%) were in the N0/N1 and N2 groups, respectively. The N2 group showed a more advanced T-stage (p = 0.001), a higher incidence of distant metastases (p = 0.048), more frequent non-R0 resection of the primary tumor (p = 0.047) and younger age (p = 0.003). There were no other significant differences in population characteristics or treatment strategies. Significantly reduced OS (p=0.024) and RFS (p = 0.004) were observed in the N2 group, which was confirmed in the multivariate analysis for both OS (p = 0.017; HR 11.935: 95% CI 1.560 – 91.306) and RFS (p < 0.002; HR 4.058; 95% CI 1.637 – 10.060). Conclusion: Patients with advanced lymphatic metastasis of the primary tumor have reduced overall and recurrence-free survival after curative resection of CRLM. Closer follow-ups and a more aggressive postoperative systemic treatment strategy may be of benefit to these patients.

MET-08 Air in cistern or ventricle after brain metastasis surgery is a predictor of early postoperative intracranial recurrence

INTRODUCTION: The operations of brain metastasis are on the increase as a result of more routine diagnostic imaging and improved extracranial systemic treatment strategies. Opening of the cistern or ventricle during tumor resection may promote local recurrence and cerebrospinal fluid dissemination. We investigated whether the air found in the cistern/ventricle on postoperative Computed tomography (CT) was a predictor of postoperative recurrence.METHODS: Between 2012 and 2019, 27 patients with single brain metastasis were treated with gross total resection at our hospital. The patients in which air was found in the cistern or ventricle of the head CT on the day after surgery was designated as air(+) group, and the patients without air was designated as air(-) group. The primary outcome was the local recurrence, as diagnosed with neuroimaging. The death due to other than brain metastasis was defined as competing risk.RESULTS: CT air(+) group was 17 patients, whereas CT air(-) group was 10 patients. There was no significant difference between the two groups, such as age and sex. Estimated 1-year brain tumor recurrence rate was 70% in the air(+) group and 5.9% in the air(-) group. (p = 0.004). On the other hand, no significant difference was observed in estimated 1-year competing risk between in the air(+) group (10%) and in the air(-) group (2.4%).CONCLUSION: En bloc resection of brain metastasis is effective, but there was no report on the risk of opening the cistern or ventricle. Our results indicate that postoperative air presence in the cistern or ventricle could be a predictor of early postoperative recurrence. In metastatic brain tumor removal, the cistern and ventricle should not be opened, and close follow-up should be done if air in the cistern or ventricle is detected on postoperative CT.

TGF-β signaling in liver metastasis.

The presence of liver metastases drastically worsens the prognosis of cancer patients. The liver is the second most prevalent metastatic site in cancer patients, but systemic therapeutic opportunities that target liver metastases are still limited. To aid the discovery of novel treatment options for metastatic liver disease, we provide insight into the cellular and molecular steps required for liver colonization. For successful colonization in the liver, adaptation of tumor cells and surrounding stroma is essential. This includes the formation of a pre‐metastatic niche, the creation of a fibrotic and immune suppressive environment, angiogenesis, and adaptation of tumor cells. We illustrate that transforming growth factor β (TGF‐β) is a central cytokine in all these processes. At last, we devise that future research should focus on TGF‐β inhibitory strategies, especially in combination with immunotherapy. This promising systemic treatment strategy has potential to eliminate distant metastases as the efficacy of immunotherapy will be enhanced.

Observational Study Comparing Efficacy and Safety between Neoadjuvant Concurrent Chemoradiotherapy and Chemotherapy for Patients with Unresectable Locally Advanced or Metastatic Gastric Cancer.

Objective Dismal outcomes in patients with locally advanced or metastatic gastric cancer (GC) highlight the need for effective systemic neoadjuvant treatment strategies to improve clinical results. Neoadjuvant multimodality strategies vary widely. This study compared the efficacy, safety, and clinical outcomes of neoadjuvant CCRT and chemotherapy for such patients. Materials and Methods Sixty-five patients with histologically confirmed locally advanced or metastatic GC following neoadjuvant CCRT or computed tomography (CT) were retrospectively enrolled between January 2010 and April 2019. Clinical outcomes included response, progression-free survival (PFS), and overall survival (OS), and toxicity was compared between the two groups. Results Of the 65 patients, 18 (27.7%) were in the response group (2 patients with a complete response and 16 with a partial response) and 47 (72.3%) in the nonresponse group (29 patients with a stable disease and 18 with a progressive disease). Multivariate analysis revealed no independent response predictor between CCRT and chemotherapy groups (all P > 0.05). Furthermore, results revealed no statistical differences in toxicity between the two groups (all P > 0.05). With a follow-up median of 12 months (ranging 6–48 months), 12-month OS and PFS were 39.7% and 20.4% in the CCRT group and 30.3% and 13.2% in the chemotherapy group, respectively. The median OS and PFS were 14.0 months (95% CI 9.661–18.339) and 9.0 months (95% CI 6.805–11.195) in the CCRT group and 10.0 months (95% CI 6.523–13.477) and 8.0 months (95% CI 6.927–9.073) in the chemotherapy group, respectively. Both OS (P=0.011) and PFS (P=0.008) in patients with CCRT were significantly better than those in patients with chemotherapy alone. Conclusion Neoadjuvant CCRT achieved more favorable OS and PFS than did neoadjuvant chemotherapy alone, without significant increases of toxicity in patients. However, prospective randomized trials comparing treatment modalities are necessary to confirm the potential advantages of neoadjuvant CCRT.

Nanotechnological strategies for systemic microbial infections treatment: A review.

Systemic infections is one of the major causes of mortality worldwide, and a shortage of drug approaches applied for the rapid and necessary treatment contribute to increase the levels of death in affected patients. Several drug delivery systems based in nanotechnology such as metallic nanoparticles, liposomes, nanoemulsion, microemulsion, polymeric nanoparticles, solid lipid nanoparticles, dendrimers, hydrogels and liquid crystals can contribute in the biological performance of active substances for the treatment of microbial diseases triggered by fungi, bacteria, virus and parasites. In the presentation of these statements, this review article present and demonstrate the effectiveness of these drug delivery systems for the treatment of systemic diseases caused by several microorganisms, through a review of studies on scientific literature worldwide that contributes to better information for the most diverse professionals from the areas of health sciences. The studies demonstrated that the drug delivery systems described can contribute to the therapeutic scenario of these diseases, being classified as safe, active platforms and with therapeutic versatility.

Patterns of failure after adjuvant "sandwich" chemo-radio-chemotherapy in locally advanced (stage III-IVA) endometrial cancer.

To investigate oncological outcomes and patterns of recurrence of patients undergoing adjuvant "sandwich" chemo-radio-chemotherapy for locally advanced endometrial cancer. This is a multi-institutional retrospective study evaluating chart of consecutive patients undergoing chemo-radio-chemotherapy for FIGO stage III-IVA endometrial caner. The study population included 45 patients who had adjuvant sandwich regimen. Median age of the study population was 66years. The majority of patients were diagnosed with endometrioid histology and with stage III disease. After a median follow-up of 35months, 15 patients developed recurrent disease. Three-year disease-free and overall survivals was 45% and 81%, respectively. Three-years site-specific disease-free survival was 85%, 92% and 48% for local, loco-regional, and distant recurrence, respectively. All patients included in the study had nodal dissection. Nodal assessment included: sentinel node mapping, sentinel node mapping plus backup lymphadenectomy and lymphadenectomy in 15, 6 and 24 patients, respectively. The latter group included four patients detected by suspected enlarged nodes, intraoperatively. Even after the exclusion of patients with enlarged nodes, the type of nodal assessment did not impact on survival outcomes (p > 0.2). Positive peritoneal cytology was the only factor associated with an increased risk of developing (any site) recurrence and distant-specific recurrence, independently. No factor predicted for overall survival. Adjuvant "sandwich" chemo-radio-chemotherapy for locally advanced endometrial cancer guarantee promising local and loco-regional controls, but distant failure rate is high, thus suggesting the need for applying other systemic treatment strategies for these patients.

P-324 Advanced hepatocellular cancer: Current systemic treatment sequencing and outcomes in the United States

There are several systemic treatment strategies for advanced hepatocellular carcinoma (HCC), including tyrosine kinase inhibitors (TKIs) and immunotherapy. This study assessed the current utilization of systemic HCC treatment strategies in the United States and associated outcomes.

Profile of Cabozantinib for the Treatment of Hepatocellular Carcinoma: Patient Selection and Special Considerations.

Management of advanced hepatocellular carcinoma is challenging. With an increasing number of options for the first and second-line treatment, understanding and developing optimal systemic treatment strategies are crucial. In second line, two tyrosine kinase inhibitors (TKI) and one monoclonal antibody have been approved after sorafenib by both the European Medicines Agency and the Food and Drug Administration based on the results of phase 3 trials: cabozantinib, regorafenib and ramucirumab. Cabozantinib has demonstrated an improved overall survival and progression-free survival in the phase 3 CELESTIAL study in second and third line, in patients in good general condition (performance status 0–1) and with a normal liver function Child-Pugh class A. Analysis of subgroups has shown that even elderly patients over 65 years, or patients with high baseline alpha-fetoprotein ≥400 ng/mL benefit from cabozantinib. The choice in second-line between the three drugs should be based on factors such as previous tolerance of sorafenib, safety profile of drugs and quality of life. In this review, we will analyze clinical data available on cabozantinib, clarifying the choice between the different possible treatments. However, the upcoming of a new standard in first line with the combination atezolizumab and bevacizumab will change the game and will warrant further investigations to define the accurate subsequent sequence of TKIs. Cabozantinib is also actually tested in first-line in combination with atezolizumab, results of the phase 3 COSMIC trial are eagerly awaited.

Breast Cancer-Related Lymphedema: Risk Factors, Screening, Management, and the Impact of Locoregional Treatment.

Patients fear lymphedema as an unpredictable daily reminder of breast cancer treatment. The medical community has assumed for years that the development of breast cancer–related lymphedema (BCRL) stemmed solely from the primary surgical extirpation of the axillary lymph nodes. However, contemporary data suggest that BCRL development is multifactorial, influenced by multimodality locoregional and systemic treatment strategies and perhaps by the individual patient’s ability to form collateral lymphatic pathways after injury, as well as potentially modifiable risk factors such as body mass index (BMI). Understanding the interaction between comprehensive locoregional treatment strategies and their collective impact on overall survival and long-term adverse effects such as BCRL is critical to providing patients individualized treatment recommendations. Herein, we review important factors for the development, diagnosis, prevention, and treatment of BCRL that should be considered when determining the contemporary locoregional management of breast cancer.

Modulation of the Autophagy-lysosomal Pathway in Hepatocellular Carcinoma Using Small Molecules.

Hepatocellular carcinoma (HCC) accounts for approximately 90% of all cases of primary liver cancer; it is the third most frequent cause of cancer-related death worldwide. In early-stage disease, surgical resection and liver transplantation are considered curative treatments. However, the majority of HCC patients present with advanced-stage disease that is treated using palliative systemic therapy. Since HCC is heterogeneous owing to its multiple etiologies, various risk factors, and inherent resistance to chemotherapy, the development of an effective systemic treatment strategy for HCC remains a considerable challenge. Autophagy is a lysosome-dependent catabolic degradation pathway that is essential for maintaining cellular energy homeostasis. Autophagy dysfunction is closely linked with the pathogenesis of various cancers; therefore, the discovery of small molecules that can modulate autophagy has attracted considerable interest in the development of a systemic treatment strategy for advanced HCC. Here, we reviewed the roles of autophagy in HCC and the recent advances regarding small molecules that target autophagy regulatory mechanisms.

Initial Clinical Impressions of the Critical Care of COVID-19 Patients in Seattle, New York City, and Chicago.

Since the first recognition of a cluster of novel respiratory viral infections in China in late December 2019, intensivists in the United States have watched with growing concern as infections with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus―now named Coronavirus Disease of 2019 (COVID-19)―have spread to hospitals in the United States. Because COVID-19 is extremely transmissible and can progress to a severe form of respiratory failure, the potential to overwhelm available critical care resources is high and critical care management of COVID-19 patients has been thrust into the spotlight. COVID-19 arrived in the United States in January and, as anticipated, has dramatically increased the usage of critical care resources. Three of the hardest-hit cities have been Seattle, New York City, and Chicago with a combined total of over 14,000 cases as of March 23, 2020.In this special article, we describe initial clinical impressions of critical care of COVID-19 in these areas, with attention to clinical presentation, laboratory values, organ system effects, treatment strategies, and resource management. We highlight clinical observations that align with or differ from already published reports. These impressions represent only the early empiric experience of the authors and are not intended to serve as recommendations or guidelines for practice, but rather as a starting point for intensivists preparing to address COVID-19 when it arrives in their community.

DCST1-AS1 Promotes TGF-β-Induced Epithelial-Mesenchymal Transition and Enhances Chemoresistance in Triple-Negative Breast Cancer Cells via ANXA1.

Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer subtype, and the primary systemic treatment strategy involves conventional chemotherapy. DC-STAMP domain containing 1-antisense 1 (DCST1-AS1) is a long non-coding RNA that promotes TNBC migration and invasion. Studying the role of DCST1-AS1 in promoting epithelial–mesenchymal transition (EMT) and chemoresistance will provide a new strategy for TNBC therapy. In the present study, we found that DCST1-AS1 regulates the expression or secretion of EMT-related proteins E-cadherin, snail family zinc finger 1 (SNAI1), vimentin, matrix metallopeptidase 2 (MMP2), and matrix metallopeptidase 9 (MMP9). Interference with DCST1-AS1 impaired TGF-β-induced TNBC cell invasion and migration. DCST1-AS1 directly binds to ANXA1 in BT-549 cells and affects the expression of ANXA1. DCST1-AS1 enhances TGF-β/Smad signaling in BT-549 cells through ANXA1 to promote EMT. The combination of DCST1-AS1 and ANXA1 also contributes to enhancement of the resistance of BT-549 cells to doxorubicin and paclitaxel. In conclusion, DCST1-AS1 promotes TGF-β-induced EMT and enhances chemoresistance in TNBC cells through ANXA1, and therefore represents a potentially promising target for metastatic breast cancer therapy.

Ретинобластома. Часть 2. Принципы терапии интраокулярной ретинобластомы

Retinoblastoma is one of the most common retinal tumors in young children. Current early diagnostic and treatment strategies focus on the possibility to implement eye-preserving therapies. The 5-year overall survival for children with retinoblastoma is now 100%. First-line eye removal is recommended in extensive intraocular seeding and poor visual prognosis. The volume of adjuvant therapy is based on the histological risk factors for disease progression. This paper discusses the algorithms to determine risk factors and further systemic treatment strategy in several large study groups. Eye and even vision preservation is now possible in at least 65–75% of retinoblastoma patients. The paper also describes in detail the methods of locally administering chemotherapy which are considered eye-preserving treatment options, i.e., selective intra-arterial chemotherapy and intravitreal chemotherapy. Various physical methods of eye-preserving treatment which underwent significant development over the past decade are highlighted. In conclusion, the authors emphasize that retinoblastoma survivors, their siblings and offspring should be carefully monitored.Keywords: children, retinoblastoma, enucleation, polychemotherapy, selective intra-arterial chemotherapy, intravitreal chemotherapy, laser photocoagulation, transpupillary thermotherapy, cryotherapy, brachytherapy, monitoring.For citation: Ivanova S.V., Kuleva S.A., Sadovnikova N.N. et al. Retinoblastoma. Part 2. Treatment strategies for intraocular retinoblastoma. Russian Journal of Clinical Ophthalmology. 2020;20(4):197–203. DOI: 10.32364/2311-7729-2020-20-4-197-203.