High Risk Of Tumor Recurrence Research Articles

Nanotherapeutics for solid organ transplantation: new kid onthe block.

Nanotherapeutics for solid organ transplantation: new kid onthe block.

The case for adjuvant BRAF-targeted therapy versus adjuvant anti-PD-1 therapy for patients with resected, high-risk melanoma.

The development of highly effective BRAF-targeted therapy and immune checkpoint inhibition for patients with advanced metastatic melanoma has transformed the treatment of this disease. More recently, these advances have moved into the resected, high-risk stage II and III settings. For patients with resected, BRAF-mutant stage III melanoma, there are no head-to-head data to support the use of BRAF-targeted therapy (specifically the combination of dabrafenib and trametinib) with either single-agent nivolumab or pembrolizumab. Because the relapse-free and distant metastasis-free survivals are similar in a cross-trial comparison, it is not clear what the best option for these patients is. In this piece, the authors argue on behalf of and against both approaches. PLAIN LANGUAGE SUMMARY: Two types of therapy exist for patients diagnosed with melanoma who have completed surgery and remain at high risk for tumor recurrence: (1) drugs that target the BRAF mutation (found in ∼50% of patients) and (2) immunotherapy. There are no data showing that either approach is better than the other, so the choice of which therapy is best for an individual patient can be challenging. In this article, we make arguments for and against each option.

Impact of smoking on urologic cancers: a snapshot of current evidence

PurposeThe purpose of this paper is to present evidence regarding the associations between smoking and the following urologic cancers: prostate, bladder, renal, and upper tract urothelial cancer (UTUC).MethodsThis is a narrative review. PubMed was queried for evidence-based analyses and trials regarding the associations between smoking and prostate, bladder, renal, and UTUC tumors from inception to September 1, 2022. Emphasis was placed on articles referenced in national guidelines and protocols.ResultsProstate—multiple studies associate smoking with higher Gleason score, higher tumor stage, and extracapsular invasion. Though smoking has not yet been linked to tumorigenesis, there is evidence that it plays a role in biochemical recurrence and cancer-specific mortality. Bladder—smoking is strongly associated with bladder cancer, likely due to DNA damage from the release of carcinogenic compounds. Additionally, smoking has been linked to increased cancer-specific mortality and higher risk of tumor recurrence. Renal—smoking tobacco has been associated with tumorigenesis, higher tumor grade and stage, poorer mortality rates, and a greater risk of tumor recurrence. UTUC—tumorigenesis has been associated with smoking tobacco. Additionally, more advanced disease, higher stage, lymph node metastases, poorer survival outcomes, and tumor recurrence have been linked to smoking.ConclusionSmoking has been shown to significantly affect most urologic cancers and has been associated with more aggressive disease, poorer outcomes, and tumor recurrence. The role of smoking cessation is still unclear, but appears to provide some protective effect. Urologists have an opportunity to engage in primary prevention by encouraging cessation practices.

Real‑world data indicated that neoadjuvant chemotherapy alone was associated with a higher risk of tumor recurrence in high‑risk breast cancer subgroup patients.

Numerous clinical trials have reported equal effects of tumor control between neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC) in patients with breast cancer (BC). However, this conclusion has not been verified in practice. The present retrospective study evaluated if there were different risk profiles for NAC, AC and their combinative modes on disease-free survival (DFS) in patients with BC using real-world data. All women with primary unilateral Stage I-III BC and first recurrence in 2008-2018 at The Fourth Hospital of Hebei Medical University were retrospectively identified for enrollment. The four modes of chemotherapy administered for primary BC were classified as 'None', 'NAC only', 'NAC+AC' and 'AC only'. One multivariate Cox model was used to estimate the adjusted Hazard Ratio (HR) and P-value. Covariates included age, Easter Cooperative Oncology Group grade, T stage, N stage, pathology, grade, lymphovascular invasion (LVI), BC subtype, number of chemotherapy cycles and other therapies. Amongst 637 patients, who had a mean age of 48.2 years at BC diagnosis and 50.9 years at recurrence, the median DFS by the 'None' (n=27), 'NAC only' (n=47), 'NAC+AC' (n=118) and 'AC only' (n=445) modes were 31.4, 16.6, 22.6 and 28.4 months (P<0.001), respectively. Compared with the 'AC only', adjusted HR (P-value) of the 'None', 'NAC only' and 'NAC+AC' modes on tumor recurrence were 1.182 (0.551), 1.481 (0.037) and 1.102 (0.523), respectively. The adjusted HR of 'NAC only' vs. 'AC only' modes were 1.448 (P=0.157) for locoregional recurrence and 2.675 (P=0.003) for distant recurrence. Stratified analyses further indicated that the 'NAC only' mode was associated with a higher recurrence risk in T3-4, N2-3, LVI-positive, or HER2-negative subgroup patients. In conclusion, NAC alone was associated with a higher risk of tumor recurrence in high-risk BC subgroup patients in real-world data. Patient selection of chemotherapy mode was involved in practice but could not fully explain this finding. The 'inadequate' NAC was highly likely to have accounted for this observation.

Tumor deposits are associated with a higher risk of peritoneal disease in non-metastatic colorectal cancer patients.

Tumor deposit (TD) is a poor prognostic factor in colorectal cancer (CRC) patients. This study aimed to determine whether TD carry the same risk of peritoneal recurrence as known high-risk (HR) features in CRC patients. A retrospective cohort-study of stage I-III CRC patients from 2010 to 2015 was conducted. TD group was defined by the presence of TD on histopathology whereas HR group was defined by the presence of obstruction, perforation, or T4-stage. A total of 151 patients with CRC were identified, of which 50 had TD and 101 had a HR feature. The overall risk of peritoneal recurrence was higher in the TD group versus HR group (36.0% vs. 19.8%, p = 0.03). The risk of peritoneum as the site of first recurrence was also higher in the TD group (22.0% vs. 12.9%, p = 0.03). Overall cancer recurrence at any site was also higher in the TD group (56.0% vs. 34.7%, p = 0.01). Median time to first recurrence was 1.2 (0.7-1.9) years in the TD group compared to 1.4 (0.8-2.1) years in the HR group (p = 0.31). In non-metastatic CRC patients, TD might have a higher risk of tumor recurrence versus their HRcounterparts. Alternative strategies for surveillance and treatment should be considered.

Adherence to lifestyle recommendations after non-muscle invasive bladder cancer diagnosis and risk of recurrence

BackgroundPatients with non-muscle invasive bladder cancer (NMIBC) are at a high risk of tumor recurrence. It has not been previously investigated if adherence to cancer prevention recommendations lowers the risk of recurrence. ObjectivesWe examined whether the standardized lifestyle score measuring adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations was associated with the risk of recurrence and progression among patients with NMIBC. MethodsThe study population included patients diagnosed with primary NMIBC between 2014 and 2017 from the prospective cohort UroLife. Lifestyle was assessed at baseline (n = 979; reflecting the prediagnosis period) and 3-mo postdiagnosis (n = 885). The standardized 2018 WCRF/AICR score was constructed based on recommendations for body weight, physical activity, diet, and alcohol intake. We computed multivariable-adjusted HRs and 95% CIs using Cox proportional hazard regression models. ResultsDuring a median follow-up time of 3.7 y, 320 patients developed ≥1 recurrence(s) and 49 experienced progression. Patients in the highest compared with the lowest tertile of postdiagnosis WCRF/AICR scores had a lower risk of first bladder cancer recurrence (HR: 0.74; 95% CI: 0.56, 0.98). No associations were observed for multiple recurrences (HR: 0.90; 95% CI: 0.70, 1.15) or for the baseline score with either first (HR: 1.07; 95% CI: 0.82, 1.40) or multiple recurrences (HR: 1.04; 95% CI: 0.82, 1.31). Improving lifestyle after diagnosis (per 1-point increase) was not significantly associated with the risk of first or multiple recurrence(s) (HR: 0.87; 95% CI: 0.74, 1.02; HR: 0.93; 95% CI: 0.80, 1.08, respectively). No associations were observed for bladder cancer progression, but the power was limited. ConclusionsBetter adherence to the WCRF/AICR cancer prevention recommendations 3 mo after NMIBC diagnosis, but not before diagnosis, is associated with a decreased risk of first bladder cancer recurrence. More studies evaluating postdiagnosis lifestyles are needed to provide solid support for lifestyle recommendations for cancer survivors.

Inflammation-Related Marker NrLR Predicts Prognosis in AFP-Negative HCC Patients After Curative Resection.

The role of inflammation-related markers in alpha-fetoprotein (AFP) negative hepatocellular carcinoma (HCC) is not well known. This study aimed to investigate the clinical significance of inflammation-related markers in AFP-negative HCC patients after curative resection. One thousand one hundred and seventy-nine AFP-negative HCC patients after curative resection were included. Survival rate and prognostic analysis were performed using Kaplan-Meier and Cox regression analysis. Propensity score matching (PSM) was used for patient selection. Multivariate Cox regression showed that neutrophil times γ-glutamyl transpeptidase to lymphocyte ratio (NrLR) was the independent risk factor associated with OS (p = 0.002) and RFS (p = 0.017). Low NrLR groups (n = 628) had lower rates of albumin-bilirubin (ALBI) grade 2 (p < 0.001), lower rates of bleeding and blood transfusion (p < 0.001) than high NrLR groups. Considering tumor features, low NrLR groups had lower AFP levels (p < 0.001), smaller tumor size (p < 0.001), and lower rates of Edmondson grade III-IV (p = 0.024) than high NrLR groups. After PSM, the 1-year, 3 year-, and 5-year OS rates in the low NrLR and high NrLR groups were 96.3%, 86.9%, 64.9%, and 91.4%, 76.7%, 59.5% (p < 0.001), respectively. The 1-year, 3-year, and 5-year RFS rates in the low NrLR and high NrLR groups were 80.0%, 62.9%, 47.5%, and 71.7%, 52.6%, 39.5% (p < 0.001), respectively. NrLR was a poor prognostic factor for mortality and tumor recurrence in AFP-negative HCC patients after curative resection. The simple and low-cost marker could help physician to determine patients at high risk of tumor recurrence for frequent clinical surveillance.

MRI-Based Radiomics Approach Predicts Tumor Recurrence in ER + /HER2 − Early Breast Cancer Patients

Oncotype Dx Recurrence Score (RS) has been validated in patients with ER + /HER2 − invasive breast carcinoma to estimate patient risk of recurrence and guide the use of adjuvant chemotherapy. We investigated the role of MRI-based radiomics features extracted from the tumor and the peritumoral tissues to predict the risk of tumor recurrence. A total of 62 patients with biopsy-proved ER + /HER2 − breast cancer who underwent pre-treatment MRI and Oncotype Dx were included. An RS > 25 was considered discriminant between low-intermediate and high risk of tumor recurrence. Two readers segmented each tumor. Radiomics features were extracted from the tumor and the peritumoral tissues. Partial least square (PLS) regression was used as the multivariate machine learning algorithm. PLS β-weights of radiomics features included the 5% features with the largest β-weights in magnitude (top 5%). Leave-one-out nested cross-validation (nCV) was used to achieve hyperparameter optimization and evaluate the generalizable performance of the procedure. The diagnostic performance of the radiomics model was assessed through receiver operating characteristic (ROC) analysis. A null hypothesis probability threshold of 5% was chosen (p < 0.05). The exploratory analysis for the complete dataset revealed an average absolute correlation among features of 0.51. The nCV framework delivered an AUC of 0.76 (p = 1.1∙10−3). When combining “early” and “peak” DCE images of only T or TST, a tendency toward statistical significance was obtained for TST with an AUC of 0.61 (p = 0.05). The 47 features included in the top 5% were balanced between T and TST (23 and 24, respectively). Moreover, 33/47 (70%) were texture-related, and 25/47 (53%) were derived from high-resolution images (1 mm). A radiomics-based machine learning approach shows the potential to accurately predict the recurrence risk in early ER + /HER2 − breast cancer patients.

Association between sarcopenia and clinical outcomes in patients with hepatocellular carcinoma: an updated meta-analysis

Although numerous studies have reported the association between sarcopenia and the prognosis of hepatocellular carcinoma (HCC) patients, there is lack of a newer and more comprehensive meta-analysis. Herein, a comprehensive literature search was performed on PubMed, Web of Science, the Cochrane Library, and Embase databases to identify relevant studies published up to February 2022. The outcomes were overall survival (OS), recurrence, progression‐free survival, tumor response, severe postoperative complications, and toxicity of drugs. A total of 57 studies involving 9790 HCC patients were included in the meta-analysis. The pooled prevalence of sarcopenia in HCC patients was 41.7% (95% CI 36.2–47.2%). Results demonstrated that sarcopenia was significantly associated with impaired OS (HR: 1.93, 95% CI 1.73–2.17, P < 0.001), higher risk of tumor recurrence (HR: 1.75, 95% CI 1.56–1.96, P < 0.001), lower objective response rate (OR: 0.37 95% CI 0.17–0.81, P = 0.012), and more drug-related adverse events (OR: 2.23, 95% CI 1.17–4.28, P = 0.015) in HCC patients. The subgroup analyses revealed that the OS of patients at the early stage of tumor was more severely affected by sarcopenia than for patients at other stages. Moreover, the presence of cirrhosis and Child Pugh class B increased the hazard of mortality from sarcopenia. This study has shown that sarcopenia is highly associated with poor prognosis in HCC patients. In addition, cirrhosis and poor liver functional reserve increase the danger of sarcopenia. OS was more impaired in HCC patients with sarcopenia at early stage of tumor than at other tumor stages.

The Progress of Chitosan-Based Nanoparticles for Intravesical Bladder Cancer Treatment

Bladder cancer (BC) is the most frequently occurring cancer of the urinary system, with non-muscle-invasive bladder cancer (NMIBC) accounting for 75-85% of all the bladder cancers. Patients with NMIBC have a good survival rate but are at high risk for tumor recurrence and disease progression. Intravesical instillation of antitumor agents is the standard treatment for NMIBC following transurethral resection of bladder tumors. Chemotherapeutic drugs are broadly employed for bladder cancer treatment, but have limited efficacy due to chemo-resistance and systemic toxicity. Additionally, the periodic voiding of bladder and low permeability of the bladder urothelium impair the retention of drugs, resulting in a weak antitumoral response. Chitosan is a non-toxic and biocompatible polymer which enables better penetration of specific drugs to the deeper cell layers of the bladder as a consequence of temporarily abolishing the barrier function of urothelium, thus offering multifaceted biomedical applications in urinary bladder epithelial. Nowadays, the rapid development of nanoparticles significantly improves the tumor therapy with enhanced drug transport. This review presents an overview on the state of chitosan-based nanoparticles in the field of intravesical bladder cancer treatment.

Варианты сохранения фертильности у пациенток с пограничными опухолями яичников

Aim: To study the main strategies for maintaining fertility in patients with borderline ovarian tumors (BOT). Key points. A detailed systematic analysis of modern domestic and foreign literature on BOT and preservation of fertility in patients was carried out. The study used data hosted on such electronic resources as eLIBRARY, Scopus, PubMed, MEDLINE, ScienceDirect and Cochrane Library (from January 2010 to 2022). This article discusses current views on the management of patients of reproductive age with BOT in order to implement the reproductive function. Since BOTs often develop in women of reproductive age, one of the main goals in their treatment is to preserve fertility, but with minimizing the risk of recurrence. Conclusion. One of the central tasks in the management of patients with BOT is the preservation of fertility. The key approaches to its solution are organ-preserving interventions (including conservative ones), cryopreservation of embryos, and the use of assisted reproductive technologies (ART). Nevertheless, taking into account the rather high risk of tumor recurrence, further studies are required to evaluate the efficacy and safety of ART in patients with BOT. Keywords: borderline ovarian tumors, tumors of potentially low malignancy, assisted reproductive technologies, fertility preservation.

Expression of transcription, growth factors, steroid hormone receptors, LC3B in papillary thyroid cancer tissue, association with prognosis and risk of recurrence

Introduction. Biological characteristics of the tumor play a major role in it’s development and progression. Currently, using the molecular markers aimed at resolving the problems in clinical oncology is becoming more important, including thyroid carcinomas. Heterogeneous contradictory data had been accumulated to date showing the ability of tumors genetic and biological parameters to predict the diseases outcome.Aim. To investigate prognostic value of transcription, growth factors, components of AKT / mTOR signaling pathway and autophagy protein LC3B in patients with papillary thyroid cancer in relation to recurrences and overall survival.Materials and methods. The study included 65 patients with T1–4N0–1M0 papillary thyroid cancer. According to the criteria of the American Thyroid Association (ATA) (2015), patients were divided into groups of patients with high, low and intermediate risk. 30 patients were classified as low risk, 23 as intermediate risk, and 12 as high risk. The BRAFV600 mutation was identified in 18 samples. The expression of transcription factors (p65 and p50 subunits of nuclear factor kappa B (NF-κB p65, NF-κB p50), hypoxia-inducible factor 1 (HIF-1), hypoxia-inducible factor 2 (HIF-2), growth factors (vascular endothelial growth factor (VEGF), receptor VEGF (VEGF-2), carbonic anhydrases of type 9 (CAIX)), AKT, c-RAF, GSK- 3β, p70S6, mammalian target of rapamycin (m-TOR), PDK, PTEN, 4E-BP1 in the tumor was assessed by real-time polymerase chain reaction (PCR). The BRAFV600 mutation was investigated using real-time allele-specific PCR. The content of the LC3B protein was examined using the Western Blot method.Results. As a result of the study, there is an increase in c-RAF expression with an increase in risk from low to high, which was accompanied by a decrease in 4E-BP1 expression. c-RAF mRNA levels were increased 3.0- and 2.8‑fold in the intermediate and high-risk groups, respectively, compared to low risk patients. There is a change in the expression of Brn-3α depending on the relapse risk. The maximum mRNA levels were found in patients with intermediate risk, where the figure was 4.3 and 6.2 times higher than in patients with low and high risk, respectively. An increase in LC3B expression by 56.0 and 28.0 times was shown in the tumor tissue of patients with intermediate risk compared with patients with low and high risk. This fact corresponds with an increasing content of the protein itself, which was higher in patients with intermediate risk. Patients with a negative BRAF gene status had an intermediate and high risk of tumor recurrence. The prognostic significance of the estrogen receptor β (ER-β) and NF-κB p50 expression level had been revealed in relation with relapse-free and overall survival of patients with papillary thyroid cancer.Conclusion. As a result of the study, additional molecular markers were found in order to for predict the tumors recurrence risk. The study showed the significance of ERβ and NF-κB p50 expression levels for predicting disease outcomes.

Higher Risk of Tumor Recurrence in NASH-Related Hepatocellular Carcinoma Following Curative Resection.

The outcomes for patients with NASH-related HCC after curative resection have not been clarified. This study compared the overall survival (OS), time-to-tumor recurrence (TTR), and recurrence-free survival (RFS) associated with NASH-related HCC and virus-related HCC after resection. Methods: Patients with HCC who underwent curative resection were retrospectively enrolled. Baseline characteristics, including disease etiologies and clinical and tumor features, were reviewed. The primary outcomes were OS, TTR, and RFS. Results: Two hundred and six patients were enrolled (HBV: n = 121, HCV: n = 54, NASH: n = 31). Of those with virus-related HCC, 84.0% achieved viral suppression. In both the overall and propensity-score-matched cohorts, those with NASH-related HCC experienced recurrence significantly earlier than those with virus-related HCC (median TTR: 1108 days vs. non-reached; p = 0.03). Through multivariate analysis, NASH-related HCC (hazard ratio (HR), 2.27; 95% confidence interval (CI), 1.25-4.12) was independently associated with early recurrence. The unadjusted RFS rate of the NASH-related HCC group was lower than the virus-related HCC group. There was no difference in the OS between the two groups. Conclusions: NASH-related HCC was associated with earlier tumor recurrence following curative resection compared to virus-related HCC. Post-surgical surveillance is crucial for detecting early recurrence in patients with NASH-related HCC.

Determination of Microvessel Density by CD34 Immunoreactivity in Female Breast Cancer and its Relation with Grading and Staging

Background: Angiogenesis is a basic process that enables neoplasm to thrive. Microvessel density (MVD) evaluation is an accepted parameter for assessing the angiogenesis process within a tumour. The research was focused to evaluate angiogenesis by using CD34 immunomarker in invasive breast cancer and to correlate the microvessel density with grades and stages. Objective: To determine microvessel density by CD34 immunoreactivity in female breast cancer and its relation with grading and staging. Methods: This cross-sectional descriptive type of study was conducted in the Department of Pathology, Rajshahi Medical College. Forty-five untreated cases of breast cancer were included in this study between the period of July 2019 to June 2021 and paraffin embedded sections were obtained from representative mastectomy specimen. The sections were stained with hematoxylin and eosin stain followed by evaluation of angiogenesis by using CD34 antibody. Results: In this study, most of the patients (71.1%) belonged to age &lt; 50 years where the mean age was found 47.5 + 12.4 years. In 45 cases, tumour sizes ranged from 1-8 cm. 86.7% (39 cases) ranges from 0-5 cm, where only (6 cases) 13.3% were more than 5 cm. About 30 cases (66.7%) lymph nodes were positive for metastasis. According to histopathological grade 51.1% belonged to grade III followed by 28.9% grade II and 20% grade I. Histological stage showed most of the cases was stage II (48.9 %) followed by stage I (26.7 %) then stage III (24.4 %). Upon statistical analysis, a significant relation was obtained between MVD with increasing histologic grades and stages. Conclusion: As a new prognostic marker it would be of great value in diagnosis and in identifying patients at high risk of tumor recurrence more accurately. By this way breast cancer patients might be benefited from adjuvant therapies.

130 (PB120) - Characterization of KRAS-driven NSCLC cell lines with diverse mutational landscape and assessment of their response to MYC inhibition

Introduction: Lung cancer is the second most common cancer type both in males and females and the leading cause of cancer death worldwide. Inside lung cancer, Non-Small-Cell Lung Cancer (NSCLC) represents around 85% of the cases, where KRAS is the leading mutated oncogene (∼25%) and confers poor prognosis and a high risk of tumor recurrence. Subsets of mutant KRAS NSCLC have been described based on the presence of concurrent mutations in tumor suppressor genes (TSGs), being the most common TP53, KEAP1 and LKB1 (also called STK11).

The effect of adjuvant transarterial chemoembolization for hepatocellular carcinoma after liver resection based on risk stratification

BackgroundThere is currently no standard adjuvant treatment proven to prevent hepatocellular carcinoma (HCC) recurrence. Recent studies suggest that postoperative adjuvant transarterial chemoembolization (PA-TACE) is beneficial for patients at high risk of tumor recurrence. However, it is difficult to select the patients. The present study aimed to develop an easy-to-use score to identify these patients. MethodsA total of 4530 patients undergoing liver resection were recruited. Independent risk factors were identified by Cox regression model in the training cohort and the Primary liver cancer big data transarterial chemoembolization (PDTE) scoring system was established. ResultsThe scoring system was composed of ten risk factors including alpha-fetoprotein (AFP), albumin-bilirubin (ALBI) grade, operative bleeding loss, resection margin, tumor capsular, satellite nodules, tumor size and number, and microvascular and macrovascular invasion. Using 5 points as risk stratification, the patients with PA-TACE had higher recurrence-free survival (RFS) compared with non-TACE in > 5 points group (P < 0.001), whereas PA-TACE patients had lower RFS compared with non-TACE in ≤ 5 points group (P = 0.013). In the training and validation cohorts, the C-indexes of PDTE scoring system were 0.714 [standard errors (SE) = 0.010] and 0.716 (SE = 0.018), respectively. ConclusionsThe model is a simple tool to identify PA-TACE for HCC patients after liver resection with a favorable performance. Patients with > 5 points may benefit from PA-TACE.

Prognostic factors and survival of patients with uterine sarcoma: a German unicenter analysis

PurposeUterine sarcoma (US) as a histologically heterogeneous group of tumors is rare and associated with poor prognosis. Prognostic factors based on systematic data collection need to be identified to optimize patients’ treatment.MethodsThis unicenter, retrospective cohort study includes 57 patients treated at the University Hospital Freiburg, Germany between 1999 and 2017. Progression-free survival (PFS) and overall survival (OS) were calculated and visualized in Kaplan–Meier curves. Prognostic factors were identified using log-rank test and Cox regression.Results44 Leiomyosarcoma (LMS), 7 low-grade endometrial stromal sarcoma (LG-ESS), 4 high-grade ESS and 2 undifferentiated US patients were identified. The median age at time of diagnosis was 51.0 years (range 18–83). The median follow-up time was 35 months. PFS for the total cohort was 14.0 (95%-Confidence-Interval (CI) 9.7–18.3) and OS 36.0 months (95%-CI 22.1–49.9). Tumor pathology was prognostically significant for OS with LG-ESS being the most favorable (mean OS 150.3 months). In the multivariate analysis, patients over 52 years showed a four times higher risk for tumor recurrence (hazard ratio (HR) 4.4; 95%-CI 1.5–12.9). Progesterone receptor negativity was associated with a two times higher risk for death (HR 2.8; 95%-CI 1.0–7.5). For LMS patients age ≥ 52 years (p = 0.04), clear surgical margins (p = 0.01), FIGO stage (p = 0.01) and no application of chemotherapy (p = 0.02) were statistically significant factors for OS.ConclusionTumor histology, age at time of diagnosis and progesterone receptor status were prognostic factors for US. Unfavorable OS in LMS patients was associated with advanced FIGO stage, suboptimal cytoreduction and application of chemotherapy.

MODL-21. Multi-omics investigation of medulloblastoma resistant models reveals functional association between intracellular regulatory networks and drug susceptibility

Abstract Medulloblastoma (MB) is the most common malignant brain tumor of childhood. Despite high-dose radio/chemotherapy treatment, 15-30% of patients still display a high risk of tumor recurrence. In this context, the characterization of innovative cellular models resembling therapy-induced drug resistance represents an unprecedented opportunity for selecting relevant therapies for chemotherapy-refractory patients. In order to unveil the molecular mechanisms sustaining chemotherapy resistance in MB, we setup in vitro models of MB drug resistance by exposing Patient-Derived MB (PD-MB) cells to a combination of the commonly used chemotherapeutics for pediatric MB treatment. Integration of multi-omics data, including transcriptional, proteomic and kinase activation profiling, disclosed that drug resistant PD-MB cells are characterized by a significant deregulation of several cancer-related pathways converging to metabolism of xenobiotics, adaptation of the biochemical processes sustaining energetic metabolic demand, cell proliferation and survival, protein homeostasis, RNA processing and modification, and immune response. Moreover, this intriguing regulatory network was functionally associated to the response of drug-resistant MB cells to a large library of compounds through a semi-automated High-Throughput drug Screening (HTS) workflow, suggesting the antimetabolite class of drugs as relevant therapeutics displaying high selectivity and efficacy against resistant MB models, together with a significant synergistic action when combined with standard chemotherapeutic agents. Collectively, our results suggest that drug-resistant MB cells are subjected to a peculiar adaptation of multiple intracellular processes during adaptation to chemotherapy, which protects them from the toxic environment but, at the same time, provides targetable vulnerabilities for therapeutic purposes.

Validation of New York/California Score in the Preoperative Period of Liver Transplant for Hepatocellular Carcinoma at University of Campinas's Hospital

Liver transplant is the main treatment for hepatocellular carcinoma and there is currently an important demand from patients waiting in transplant queues. Thus, it is extremely important to improve the criteria for selecting patients who will undergo transplant to mitigate graft loss and reduce cases of recurrence. Thus, it becomes necessary to use models, such as the New York/California (NYCA), that include alpha fetoprotein as a marker of recurrence and prognosis. The aim of this study was to assess whether the NYCA score correlated with the presence of tumor recurrence after transplant in patients undergoing orthotopic liver transplant at the Clinics Hospital of the University of Campinas. We had 214 patients undergoing liver transplant who met the inclusion Milan criteria. The age of the patients ranged from 34 to 77 years, with a median age of 61 years. The mean waiting time on the transplant list was 6.12 months. After calculating the NYCA score, it was possible to stratify 13 patients (6.1%) as high risk, 64 patients (29.9%) as medium risk, and 137 patients (64%) as low risk. Patients with recurrence had higher scores with a mean of 4 points in relapse and 2 points in the absence of relapse (P=.0011). Patients with recurrence had statistically higher high- and medium-risk scores (P=.0010). Therefore, the NYCA score was higher in patients with recurrence. Therefore, in this study, our findings suggest the possibility of using the NYCA score as an aid to detect patients with a higher risk of tumor recurrence.

In silico recognition of a prognostic signature in basal-like breast cancer patients.

BackgroundTriple-negative breast cancers (TNBCs) display poor prognosis, have a high risk of tumour recurrence, and exhibit high resistance to drug treatments. Based on their gene expression profiles, the majority of TNBCs are classified as basal-like breast cancers. Currently, there are not available widely-accepted prognostic markers to predict outcomes in basal-like subtype, so the selection of new prognostic indicators for this BC phenotype represents an unmet clinical challenge.ResultsHere, we attempted to address this challenging issue by exploiting a bioinformatics pipeline able to integrate transcriptomic, genomic, epigenomic, and clinical data freely accessible from public repositories. This pipeline starts from the application of the well-established network-based SWIM methodology on the transcriptomic data to unveil important (switch) genes in relation with a complex disease of interest. Then, survival and linear regression analyses are performed to associate the gene expression profiles of the switch genes with both the patients’ clinical outcome and the disease aggressiveness. This allows us to identify a prognostic gene signature that in turn is fed to the last step of the pipeline consisting of an analysis at DNA level, to investigate whether variations in the expression of identified prognostic switch genes could be related to genetic (copy number variations) or epigenetic (DNA methylation differences) alterations in their gene loci, or to the activities of transcription factors binding to their promoter regions. Finally, changes in the protein expression levels corresponding to the so far identified prognostic switch genes are evaluated by immunohistochemical staining results taking advantage of the Human Protein Atlas.ConclusionThe application of the proposed pipeline on the dataset of The Cancer Genome Atlas (TCGA)-Breast Invasive Carcinoma (BRCA) patients affected by basal-like subtype led to an in silico recognition of a basal-like specific gene signature composed of 11 potential prognostic biomarkers to be further investigated.