Risk Of Cancer Relapse Research Articles

Complexity in the interpretation and application of multiple guidelines for thyroid nodules: the need for coordinated recommendations for "small" lesions.

Multiple guidelines for thyroid nodule management have been developed by endocrinologists, often in collaboration with surgeons and radiologists. While there is now a lot of scientific information available to meet the needs of healthcare providers, there is not always uniformity and standardization among recommendations. Consequently, the interpretation and application of guidelines in clinical practice remain somewhat limited. In this context, the management of "small" thyroid nodule warrants full discussion. Looking at treatment guidelines, surgery is the first-line option and the risk of cancer relapse can be assessed only after at least thyroidectomy; in addition, according to guidelines of minimally invasive treatment, thermal ablation may be considered for patients with small classical papillary carcinoma. However, the Thyroid Imaging Reporting AndData Systems do not recommend biopsy in nodules less than 1cm; and performing biopsy may yield a result that is suspicious or consistent with malignancy without specifying the cancer subtype. With these premises, facingcases of "small" nodule less than 1cm is challenging. Even if the recommendations of guidelines sound singularly appropriate, they may seem conflicting. Coordinated guidelines are needed.

Nanoparticle-mediated metronomic chemotherapy in cancer: A paradigm of precision and persistence

Current methods of cancer therapy have demonstrated enormous potential in tumor inhibition. However, a high dosage regimen of chemotherapy results in various complications which affect the normal body cells. Tumor cells also develop resistance against the prescribed drugs in the whole treatment regimen increasing the risk of cancer relapse. Metronomic chemotherapy is a modern treatment method that involves administering drugs at low doses continuously, allowing the drug sufficient time to take its effect. This method ensures that the toxicity of the drugs is to a minimum in comparison to conventional chemotherapy. Nanoparticles have shown efficacy in delivering drugs to the tumor cells in various cancer therapies. Combining nanoparticles with metronomic chemotherapy can yield better treatment results. This combination stimulates the immune system, improving cancer cells recognition by immune cells. Evidence from clinical and pre-clinical trials supports the use of metronomic delivery for drug-loaded nanoparticles. This review focuses on the functionalization of nanoparticles for improved drug delivery and inhibition of tumor growth. It emphasizes the mechanisms of metronomic chemotherapy and its conjunction with nanotechnology. Additionally, it explores tumor progression and the current methods of chemotherapy. The challenges associated with nano-based metronomic chemotherapy are outlined, paving the way for prospects in this dynamic field.

A Preliminary Evaluation of Advanced Oxidation Protein Products (AOPPs) as a Potential Approach to Evaluating Prognosis in Early-Stage Breast Cancer Patients and Its Implication in Tumour Angiogenesis: A 7-Year Single-Centre Study.

Breast cancer (BrC) is a highly prevalent tumour among women. The high incidence and mortality rate of BrC prompts researchers to search for new markers that will provide information on the possible impact of the therapy on the risk of cancer-related events. This study aimed to investigate whether the level of advanced oxidation protein products (AOPPs) may have a potential impact on disease-free (DFS) and overall survival (OS) in BrC patients with early-stage cancer. Additionally, we tried to assess the relationship between AOPPs and angiogenic parameters. In this study, the pre- and post-treatment AOPP levels were examined in the serum of 70 newly diagnosed BrC women. The receiver operating characteristic curve identified pre- and post-treatment AOPPs to be above 9.37 μM and 10.39 μM, respectively, as the best cut-off values to predict the risk of cancer relapse. Additionally, Kaplan-Meier survival analysis indicated that pre- and post-treatment AOPPs above 9.37 μM and 10.39 μM were associated with significantly poorer OS. The uni- and multivariate Cox regression analysis highlighted that lower levels of pre- and post-treatment AOPPs were associated with a longer duration without relapse or cancer-related death. A positive correlation between concentrations of pre-treatment AOPPs and vascular endothelial growth factor A, and negative correlations with levels of soluble forms of vascular endothelial growth factor receptor type 1 and 2, were found. In conclusion, AOPPs appear to have an important role in predicting cancer-related events and may potentially serve as a simple prognostic marker in clinical practice.

Pan-cancer chemoresistance-associated genes, affected pathways and potential therapeutic targets

Background: Chemotherapy is one of the first-line treatment options for cancer. Chemotherapeutic agents exert their anti-cancer effects following different mechanisms. The prevalence of chemoresistance is substantially high worldwide. Resistance to chemotherapeutic agents increases the risk of cancer relapse and metastasis. In this study, we investigated the common chemoresistance-associated genes and pathways in different chemoresistant cancer cells that have been treated with various classes of chemotherapeutics. Method: We used in silico tools to investigate the chemoresistance-associated genes and pathways in 13 different cancer cell types (breast-, colon-, gastric-, ovarian-, pancreatic-, lung-, prostate cancer, chronic myeloid leukemia, hepatocellular-, head and neck squamous cell carcinoma, gestational trophoblastic neoplasia, multiple myeloma, and melanoma) treated with 10 different classes of chemotherapeutic drugs (anthracyclines, methotrexates, nucleoside analogues, cyclin-dependent kinase inhibitors, taxanes, tyrosine kinase inhibitors, platinum-based drugs, vinca alkaloids, proteasome inhibitor and topoisomerase I inhibitor) by analyzing 47 paired (control vs. chemoresistant) global gene expression datasets containing 620 individual samples. Results: We identified 43 differentially expressed genes associated with pan-cancer chemoresistance, among which 21 have significant regulatory roles. Furthermore, gene-disease associations revealed that 13 genes (SRC, PAK1, NFKBIA, ESR1, NFKB1, HRAS, MAPK1, PIK3CA, AURKA, MAPK3, PLCG1, PTPN11, and PRKCA) and associated pathways, particularly the Mitogen-Activated Protein Kinase (MAPK) signaling pathway, PI3K/Akt signaling pathway, JAK-STAT signaling pathway, and regulation of actin cytoskeleton, can heavily influence various cancers and chemoresistance in diverse ways. Conclusion: The findings from this study on chemoresistance-promoting genes and their mechanisms of action may be useful in the in vitro pursuit of common therapeutic targets for inhibiting chemoresistance in cancer cells.

Survival after minimally invasive radical hysterectomy without using uterine manipulator for early-stage cervical cancer: A systematic review and meta-analysis.

Minimally invasive radical hysterectomy has been reported to increase the risk of cancer relapse and death compared with open surgery in women with early-stage cervical cancer. The use of a uterine manipulator is considered one of the risk factors. To investigate whether women with early-stage cervical cancer treated with minimally invasive radical hysterectomy without using uterine manipulator have oncological outcomes similar to those of open surgery. Searches were performed in MEDLINE, Embase and CENTRAL from their inception until 31 March 2022. Inclusion criteria were: (1) randomised controlled trials or observational cohort studies published in English, (2) studies comparing minimally invasive radical hysterectomy without using a uterine manipulator with open radical hysterectomy in women with early-stage cervical cancer, and (3) studies comparing survival outcomes. Two authors independently conducted data extraction and assessed study quality. We calculated the hazard ratios (HR) and the 95% confidence intervals (CI) using the inverse variance approach for survival outcome. Six observational studies with 2150 women were included. The minimally invasive surgery group had a significantly higher risk of cancer relapse compared with open surgery group (HR 1.55, 95% CI 1.15-2.10). Minimally invasive radical hysterectomy without using a uterine manipulator resulted in an inferior recurrence-free survival compared with open radical hysterectomy in the treatment of women with early-stage cervical cancer.

Tumor-stroma ratio can predict lymph-node metastasis in cT1/2N0 oral tongue squamous cell carcinoma independent of tumor budding grade.

cT1/2 oral tongue squamous cell carcinoma (OTSCC) often metastasizes to cervical lymph nodes. However, predicting neck lymph-node metastasis (NLM) remains challenging. Pathomorphological evaluation of tumor budding grade (TBG) and tumor-stroma ratio (TSR) reportedly can predict lymph-node metastases. Hence, this study aimed to evaluate TBG and TSR in OTSCC and investigate their relationship to occult NLM and cancer relapse. Clinicopathological data of patients with cT1/2N0 OTSCC treated at the University of Tokyo Hospital between 2007 and 2017 were collected. TBG and TSR were evaluated using hematoxylin-eosin staining and cytokeratin AE1/AE3 immunostaining. Out of 70 patients, 16 underwent elective neck dissection in addition to primary-tumor resection, whereas 54 did not. During follow-up, NLM was found in 35 patients. NLM correlated with the pathological depth of invasion (pDOI) (p < 0.001), TBG (p = 0.008), and TSR (p < 0.001) in univariate analysis and pDOI (p = 0.01) and TSR (p = 0.02) in multivariate analysis. The 5-year recurrence-free survival rate (RFS) was 78% for patients with a pDOI ≤ 5mm and stroma-poor tumors and 33% for patients with a pDOI > 5mm and stroma-rich tumors. Patients with a pDOI > 5mm and stroma-rich tumors have a high risk for cancer relapse. TSR and pDOI may be promising NLM predictors in cT1/2N0 OTSCC.

Insights into mechanisms of graft-versus-host disease through humanised mouse models.

Graft-versus-host disease (GVHD) is a major complication that occurs following allogeneic haematopoietic stem cell transplantation (HSCT) for the treatment of haematological cancers and other blood-related disorders. GVHD is an inflammatory disorder, where the transplanted donor immune cells can mediate an immune response against the recipient and attack host tissues. Despite over 60 years of research, broad-range immune suppression is still used to prevent or treat GVHD, leading to an increased risk of cancer relapse and infection. Therefore, further insights into the disease mechanisms and development of predictive and prognostic biomarkers are key to improving outcomes and reducing GVHD development following allogeneic HSCT. An important preclinical tool to examine the pathophysiology of GVHD and to understand the key mechanisms that lead to GVHD development are preclinical humanised mouse models. Such models of GVHD are now well-established and can provide valuable insights into disease development. This review will focus on models where human peripheral blood mononuclear cells are injected into immune-deficient non-obese diabetic (NOD)-scid-interleukin-2(IL-2)Rγ mutant (NOD-scid-IL2Rγnull) mice. Humanised mouse models of GVHD can mimic the clinical setting for GVHD development, with disease progression and tissues impacted like that observed in humans. This review will highlight key findings from preclinical humanised mouse models regarding the role of donor human immune cells, the function of cytokines and cell signalling molecules and their impact on specific target tissues and GVHD development. Further, specific therapeutic strategies tested in these preclinical models reveal key molecular pathways important in reducing the burden of GVHD following allogeneic HSCT.

Nutrition et activité physique adaptée (APA) pendant et après les traitements du cancer : bénéfices thérapeutiques, physiopathologie, recommandations, prise en charge clinique

Lifestyle behaviors, such as diet and physical activity, are factors that influence risk of numerous cancers. They are also decisive during and after cancer for the course of oncological treatment, but also in the immediate and long-term prognosis, and quality of life during and after treatment. Separately, physical activity and nutritional support can reduce the risk of sarcopenia and its consequences, and improve quality of life during treatment. Whan introduced early, such a combination, increases the prognostic benefits. In remission, particularly in overweight patients, the APA-diet combination reduces the risk of cancer relapse and improves cardiovascular performance. These programs require a precise assessment of capacities and habits of each patient, and interventions of trained professionals (certified exercise instructor, dietician trained in oncology). The funding conditions for these programs exist for cancer survivors and should be considered for oncological treatment period.

Results Of Clinical Testing Of Infanetim Technology Silver Line Toothpaste

Aim: To assess the impact of daily use of INFANETIM Technology® SILVER LINE hygienic toothpaste in adult volunteers and patients with a history of cancer on the risk of acute respiratory viral infections (ARVI), and its preventive effect on cancer relapse. Patients and Methods: We conducted a controlled clinical observation with the participation of volunteers over 50 years of age, including those with a history of cancer. 612 volunteers were randomly assigned to use INFANETIM Technology Silver Line hygienic toothpaste or another regular hygienic toothpaste daily over the course of 2 years. Results: During clinical follow-up, the incidence of acute respiratory viral infections per 612 volunteers who completed the full program was 64 in the INFANETIM Technology® group versus 229 in the control group (p=0.02; 95% CI 23-31%). In the study group, 9 cases of cancer relapse were registered among those who had a history of cancer, in the control group during the observation period, cancer relapse developed in 23 participants (p=0.046; 95% CI 27-49%). Conclusions: Daily oral hygiene with the use of a specialized toothpaste INFANETIM Technology Silver line reduces the risk of ARVI by more than 3 times (p=0.02; CI 23-31%) and reduces the risk of cancer relapse.

Oncolytic virotherapy, a new approach in graft-versus-host disease

Background: Despite recent advances in hematopoietic stem cell transplantation (HSCT), graft-versus-host disease (GVHD) is still one of the most challenging post-transplant complications with a considerable mortality rate. Various strategies, including chemotherapy, depletion of T lymphocytes, monoclonal antibodies, corticosteroids, and other immunosuppressive drugs are used to reduce GVHD incidence, which usually increases the risk of cancer relapse and various infections in patients. The recently conducted studies have introduced oncolytic virotherapy as a promising solution to prevent GVHD and enhance the graft-versus-tumor effects. Oncolytic viruses are non-pathogenic viruses capable of selective lysis of cancer cells. These viruses can differentiate between allogeneic T lymphocytes and hematopoietic stem cells, and suppress allogeneic T cells. This review study aimed to discuss the mechanisms of oncolytic virotherapy in reducing the incidence of GVHD.

Understanding Adolescent and Young Adult 6-Mercaptopurine Adherence and mHealth Engagement During Cancer Treatment: Protocol for Ecological Momentary Assessment.

BackgroundAdolescents and young adults (AYAs) with cancer demonstrate suboptimal oral chemotherapy adherence, increasing their risk of cancer relapse. It is unclear how everyday time-varying contextual factors (eg, mood) affect their adherence, stalling the development of personalized mobile health (mHealth) interventions. Poor engagement is also a challenge across mHealth trials; an effective adherence intervention must be engaging to promote uptake.ObjectiveThis protocol aims to determine the temporal associations between daily contextual factors and 6-mercaptopurine (6-MP) adherence and explore the proximal impact of various engagement strategies on ecological momentary assessment survey completion.MethodsAt the Children’s Hospital of Philadelphia, AYAs with acute lymphoblastic leukemia or lymphoma who are prescribed prolonged maintenance chemotherapy that includes daily oral 6-MP are eligible, along with their matched caregivers. Participants will use an ecological momentary assessment app called ADAPTS (Adherence Assessments and Personalized Timely Support)—a version of an open-source app that was modified for AYAs with cancer through a user-centered process—and complete surveys in bursts over 6 months. Theory-informed engagement strategies will be microrandomized to estimate the causal effects on proximal survey completion.ResultsWith funding from the National Cancer Institute and institutional review board approval, of the proposed 30 AYA-caregiver dyads, 60% (18/30) have been enrolled; of the 18 enrolled, 15 (83%) have completed the study so far.ConclusionsThis protocol represents an important first step toward prescreening tailoring variables and engagement components for a just-in-time adaptive intervention designed to promote both 6-MP adherence and mHealth engagement.International Registered Report Identifier (IRRID)DERR1-10.2196/32789

Predictive markers based on transcriptome modules for vinorelbine-based adjuvant chemotherapy for lung adenocarcinoma patients

ObjectivesMicrotubule inhibitors (MTIs) are widely used as anti-cancer drugs for various types of tumors. Vinorelbine, an MTI, is utilized in postoperative adjuvant chemotherapy, especially for lung adenocarcinoma. However, no molecular markers are able to identify patients for whom MTIs would be effective. In this study, we attempted to identify practical markers to predict the efficacy of MTI-based adjuvant chemotherapy. Materials and methodsWe explored a novel combination of molecular marker candidates, based on gene expression network analysis constructed using an omics panel of 26 lung adenocarcinoma cell lines. We then applied the obtained classification method to predict the efficacy of MTI treatment in patients who received adjuvant chemotherapy. RNA sequencing (RNA-seq) analysis was conducted using surgical specimens from 24 Japanese lung adenocarcinoma patients treated postoperatively with vinorelbine. ResultsWe identified four modules within the network with module activities that were significantly associated with sensitivity to MTIs. Two modules were associated with high sensitivity to MTIs: genes with low differentiation or transdifferentiation of lung adenocarcinomas. On the other hand, MTI-low sensitivity modules were enriched in common epithelial genes and markers of well-differentiated lung adenocarcinomas. We also classified lung adenocarcinoma cases using the module activities associated with MTI efficacy and stratify the cases with MTI resistance. ConclusionWe demonstrate that the constructed classification method is useful for identifying patients with MTI resistance which results in a high risk of cancer relapse.

Relationship between Tertiary Lymphoid Structure and the Prognosis and Clinicopathologic Characteristics in Solid Tumors.

Background: An increasing number of studies had shown that tertiary lymphoid structure (TLS) plays an important role in tumor progression. However, the prognostic role of TLS in various tumors remains controversial. This meta-analysis aims to investigate the clinicopathological and prognostic values of TLS in solid tumors.Methods: A systematic search was conducted in PubMed, EMBASE and Cochrane Library undated to November 2, 2020. Odds ratios of clinical parameters, hazard ratio (HR) of overall survival (OS), relapse-free survival (RFS), disease-free survival (DFS) and relapse rate were calculated in order to evaluate the relationship between TLS expression and clinicopathological or prognostic values in different tumors.Result: 27 eligible studies including 6647 patients with different types of tumors were analyzed. High TLS expression was associated with a longer OS (HR = 0.66, 95% CI: 0.50 - 0.86, P = 0.002) and RFS (HR = 0.61, 95% CI: 0.47 - 0.79, P = 0.0001). Moreover, high TLS levels in tumor were associated with a low risk of recurrence (HR = 0.43, 95% CI: 0.32 - 0.57, P < 0.0001). However, there was no relationship between TLS expression and DFS. Meanwhile, high TLS expression was associated with smaller tumor size (P < 0.00001) and higher tumor infiltrating lymphocytes (TILs). Furthermore, the subgroup analysis showed high TLS expression that may be associated with a lower clinical grading and N stage in breast cancer and colorectal cancer.Conclusion: High TLS expression is associated with the longer OS and RFS in solid tumors, and a lower risk of cancer relapse. Meanwhile, high TLS expression is also associated with a smaller tumor size, higher infiltration of TILs, lower clinical grading and N stage in the tumor. Therefore, high TLS expression in the tumor is a favorable prognostic biomarker for solid tumor patients.

Proteomic analysis of circulating extracellular vesicles identifies potential markers of breast cancer progression, recurrence, and response.

Proteomic profiling of circulating small extracellular vesicles (sEVs) represents a promising, noninvasive approach for early detection and therapeutic monitoring of breast cancer (BC). We describe a relatively low-cost, fast, and reliable method to isolate sEVs from plasma of BC patients and analyze their protein content by semiquantitative proteomics. sEV-enriched fractions were isolated from plasma of healthy controls and BC patients at different disease stages before and after surgery. Proteomic analysis of sEV-enriched fractions using reverse phase protein array revealed a signature of seven proteins that differentiated BC patients from healthy individuals, of which FAK and fibronectin displayed high diagnostic accuracy. The size of sEVs was significantly reduced in advanced disease stage, concomitant with a stage-specific protein signature. Furthermore, we observed protein-based distinct clusters of healthy controls, chemotherapy-treated and untreated postsurgery samples, as well as a predictor of high risk of cancer relapse, suggesting that the applied methods warrant development for advanced diagnostics.

Identifying CpG methylation signature as a promising biomarker for recurrence and immunotherapy in non–small-cell lung carcinoma

Epigenetic alterations are crucial to oncogenesis and regulation of gene expression in non–small-cell lung carcinoma (NSCLC). DNA methylation (DNAm) biomarkers may provide molecular-level prediction of relapse risk in cancer. Identification of optimal treatment is warranted for improving clinical management of NSCLC patients. Using machine learning algorithm we identified 4 recurrence predictive CpG methylation markers (cg00253681/ART4, cg00111503/KCNK9, cg02715629/FAM83A, cg03282991/C6orf10) and constructed a risk score model that potently predicted recurrence-free survival and prognosis for patients with NSCLC (P = 0.0002). Integrating genomic, transcriptomic, proteomic and clinical data, the DNAm-based risk score was observed to significantly associate with clinical stage, cell proliferation markers, somatic alterations, tumor mutation burden (TMB) as well as DNA damage response (DDR) genes, and potentially predict the efficacy of immunotherapy. In general, our identified DNAm signature shows a significant correlation to TMB and DDR pathways, and serves as an effective biomarker for predicting NSCLC recurrence and response to immunotherapy. These findings demonstrate the utility of 4-DNAm-marker panel in the prognosis, treatment decision-making and evaluation of therapeutic responses for NSCLC.

Abstract 08: Advancing precision medicine combination drug screening: A miniaturized single-cell imaging platform for evaluating immunotherapy-small molecule combination therapeutics in individuals

Abstract Major efforts are under way to develop combination therapies to target multiple biologic pathways for effective synergistic cell killing and decrease the risk of cancer relapse. However, a major technical challenge is the lack of screening platforms that allow assessment of optimal combinations directly in individuals. Flow cytometry is a widely used option; however, the large amount of sample required limits the number of drug combinations that can be tested on primary patient samples. Moreover, many protein targets, especially intracellular proteins (e.g., phosphoproteins, immune modulatory molecules) are often present at low levels, making it challenging to detect via flow cytometry or other means—especially in conditions of drug inhibition whereby signal cannot be conclusively discriminated from background noise. We have developed a next-gen miniaturized single-cell imaging platform that evaluates the effect of drug combinations in primary patient tumor and immune cells, with quantitative detection sensitivity and single-cell granularity. We demonstrate the use of this platform technology to screen interactions between targeted agents and immune checkpoint inhibitors (ICIs) in individuals with acute myeloid leukemia (AML). In many tumor types, including AML, targeting tumor cells with small-molecule drugs while concomitantly inducing an antitumor immune response has the possibility of synergistic activities that avoid therapeutic resistance (1). However, many of the pathways of proliferation and survival that are targeted with small-molecule drugs are also important for the ability of tumor-reactive T cells to expand and function (2). For this reason, there is a distinct possibility that many drugs designed to kill tumor cells will also impair T-cell responses and thus not be compatible with immunotherapies such as ICIs. We show how platform functional readouts of ex vivo T-cell activation and tumor-cell killing, along with conventional and machine learning image-based single-cell analysis, provide new information on the effect of specific combination/single agents in individuals. We report observations of ICI rescue of T-cell proliferation and the synergistic effects of TIM3, MEK, and other combination agents. These results demonstrate the advantages of this precision technology to obtain new functional information that helps identify promising combinations—and to do so directly on samples that represent the functional and genetic diversity seen in AML (3).

Torque Teno Virus as a Potential Biomarker for Complications and Survival After Allogeneic Hematopoietic Stem Cell Transplantation.

Impaired immune reconstitution after allogeneic hematopoietic stem cell transplantation (HSCT) contributes to increased risk of cancer relapse and infection resulting in significant morbidity and mortality. Unfortunately, effective strategies to functionally assess the quality of immune reconstitution are still missing. Quantification of in vivo replication of the ubiquitous, non-pathogenic virus Torque Teno Virus (TTV) has been reported in small series as a test to functionally evaluate the quality of post-transplant immune reconstitution. In the present study, we analyzed by quantitative PCR TTV titers in plasma samples from a large cohort of 168 allogeneic HSCT recipients. Our analysis confirms that TTV titers peaked at 100 days post-transplant, followed by progressive normalization thereafter. Negative correlation of TTV titers with T cell absolute numbers during the first year post-transplant points to the restoration of an active anti-TTV immunity. Univariable and multivariable linear regression analysis demonstrated that donor CMV positive serostatus, donor type and immune suppression resulting from GVHD treatment affected the restoration of anti-TTV immunity. Importantly, higher TTV titers at 100 days after transplantation were associated with worse overall survival and higher risk of acute GVHD and infections. Our results provide new insights into the factors affecting the dynamics of TTV replication and indicate that TTV is a potentially useful biomarker to assess immune reconstitution and to predict complications and outcomes of allogeneic HSCT.

Expression of RARRES1 and AGBL2 and progression of conventional renal cell carcinoma

BackgroundApproximately 15% of clinically localised conventional renal cell carcinoma (RCC) will develop metastasis within 5 years of follow-up. The aim of this study was to identify biomarkers predicting the postoperative tumour relapse.MethodsTissue microarrays of conventional RCC from a cohort of 691 patients without metastasis at the time of operation were analysed by immunohistochemistry for the expression of carboxypeptase inhibitor RARRES1 and its substrate carboxypeptidase AGBL2. Univariate and multivariate Cox regression models were addressed to postoperative tumour relapse and the metastasis-free survival time was estimated by Kaplan–Meier analysis.ResultsIn multivariate analysis, the lack of staining or cytoplasmic staining of RARRES1 was a significant risk factor indicating five times higher risk of cancer relapse. Combining its co-expression with AGBL2, we found that RARRES1 cytoplasmic/negative and AGBL2-positive/negative staining is a significant risk factor for tumour progression indicating 11–15 times higher risk of cancer relapse, whereas the membranous RARRES1 expression, especially its co-expression with AGBL2, associated with excellent disease outcome.ConclusionsRARRES1 and AGBL2 expression defines groups of patients at low and high risk of tumour progression and may direct an active surveillance to detect metastasis as early as possible and to apply adjuvant therapy.

3 Dimensions of Treatment Decision Making in Adolescents and Young Adults With Cancer.

Adolescents and young adults (AYAs) experience treatment nonadherence rates as high as 60%, which can increase the risk of cancer relapse. Involvement of AYAs in treatment decisions might support adherence to medical treatment. The aim of this study was to explore the involvement of AYAs, aged 15 to 20 years, in cancer treatment decision making (TDM). Using interpretive focused ethnography, we conducted interviews with 16 AYAs (total of 31 interviews) receiving cancer treatment within 1 year of diagnosis. Participants reflected on a major recent TDM experience (eg, clinical trial, surgery) and other treatment decisions. Participants distinguished important major cancer treatment decisions from minor supportive care decisions. We identified 3 common dimensions related to AYAs' involvement in cancer TDM: (1) becoming experienced with cancer, (2) import of the decision, and (3) decision-making roles. The preferences of AYAs for participation in TDM varied over time and by type of decision. We have proposed a 3-dimensional model to illustrate how these dimensions might interact to portray TDM during the first year of cancer treatment for AYAs. As AYAs accumulate experience in making decisions, their TDM preferences might evolve at different rates depending on whether the decisions are perceived to be minor or major. Parents played a particularly important supportive role in TDM for AYA participants. Clinicians should consider the AYAs' preferences and the role they want to assume in making different decisions in order to support and encourage involvement in their TDM and care.

Stratification of papillary thyroid cancer relapse risk based on the results of molecular genetic studies

Introduction. Post-transcriptional mechanisms play a crucial role in the biological course and clinical manifestations of papillary thyroid cancer (PTC). Recent studies show that an increased content of oncogenic or reduced content of oncosuppressive microRNAs increases the aggressiveness of the tumor and correlates with an unfavorable prognosis of treatment, which allows them to be used in personalizing the treatment tactics of patients with PTC. The study objective is to compare the level of expression of 12 PTC-specific microRNAs and the frequency of V600E mutation of the BRAF gene in patients with different risk of relapse. Materials and methods. The study included 175 patients with PTC. For quantitative analysis of microRNA expression, a reverse transcription reaction followed by a real-time polymerase chain reaction in formalin-fixed paraffin blocks was used. Correlations between 12 microRNA expression and BRAF mutation with different clinical and anatomical features of PTC the risk of relapse according to the American Thyroid Association Risk Stratification System (2009) were analyzed. Results. We demonstrated that miR-146b, miR-221, miR-144, miR-451a, and miR-7 expression correlated with features such as extrathyroid tumor growth, larger size, multifocus, lymph node metastasis, and the presence of distant metastases of the PTC. Most importantly, miR-221, miR-144, miR-451a, and miR-7 expression correlated with risk levels, suggesting their potential significance in stratifying the risk of relapsing PTC. The dependence of the clinical behavior of PTC on the BRAF mutation has not been established.Conclusion. The result of the study will contribute to the individual choice of preoperative treatment tactics for patients with PTC.