Adult Cancer Research Articles

Frailty and Malnutrition in Surgical Outcomes of Elderly Breast Cancer Patients.

We evaluate the impact of frailty and malnutrition on breast cancer surgery outcomes in older adults using the ACS 5-factor modified frailty index (MFI) and Global Leadership Initiative on Malnutrition (GLIM) definition. Single institution retrospective review of a prospective database of the older adult (>60 years old) breast cancer surgery patients (2000-2016); cases stratified into groups as per MFI (0-2) and GLIM. Characteristics, 90-day post-op events, and 5-year follow-up data were analyzed to report survival and complication outcomes. Among 436 patients at diagnosis, 213 (48.9%) were >80 years old. 377 (86.5%) were alive at 5 years. 274 (62.8%) had MFI > 0, and 69 (15.8%) had malnutrition. Patients ≥ 80, MFI > 0, and PR-negative tumors had worse 5-year survival. There was no survival difference in patients >80 with/without malnutrition (HR = 1.01, p = 0.971), and there was no difference in mastectomy or lumpectomy (p = 0.560) between patients ≥ 80 or patients younger than 80; however, 94% of immediate reconstruction were in pts < 80. On multivariate regression, complications were associated with age < 80, readmission, MFI > 0, and history of HTN; serious complications were associated with age < 80, readmission, anticoagulation, and not receiving endocrine therapy. MFI showed a significant predictive value for 5-year survival for patients ≥ 80 and should be part of the preoperative evaluation.

Hiding in plain sight: Cooperative Extension as an underutilized approach to improving cancer survivorship outcomes in underserved populations.

Explore the potential utility of a Cooperative Extension-specific program to support post-active treatment cancer survivors. A user-centered study was conducted to identify barriers to and facilitators of the implementation of a program for adult cancer survivors living post primary cancer treatment ("cancer survivors") via Cooperative Extension("Extension"), including interviews analyzed using the Consolidated Framework for Implementation Research. Participants included Cooperative Extension Educators and adult cancer survivors in Oklahoma who completed data collection from July 2023 to September 2023. N = 20 participants were enrolled. Cancer survivors indicated poor familiarity with Extension, or a primary association with agriculture. Some voiced surprise Extension was not already providing cancer-related programming. Many expressed poor support in their communities due to issues secondary to rurality, often relying on non-cancer programs. Educators voiced a strong capability to deliver cancer-related programming if intentionally designed, with many already providing education on relevant topics (e.g., finances, nutrition, physical activity). A salient barrier was poor connectivity with the healthcare system. There is an immense need for improved survivorship care in underserved communities due to poor social connectedness, support structures, and poor mental health. Cooperative Extension is well-poised to deliver cancer survivorship-specific programming. Cooperative Extension provides an extensive network of professionals who can provide support to cancer survivors, particularly those post-active treatment.

Application of deep learning-based fuzzy systems to analyze the overall risk of mortality in glioblastoma multiforme

Abstract Glioblastoma multiforme (GBM) is the most aggressive brain cancer in adults, with 3.2-3.4 cases per 100 thousand. In the US, brain cancer does not rank in the top 10 causes of death, but it remains in the top 15. Therefore, this research proposes a fuzzy-based GRUCoxPH model to identify missense variants associated with a high risk of all-cause mortality in GBM. The study combines various models, including fuzzy logic, Gated Recurrent Units (GRUs), and Cox&amp;#xD;Proportional Hazards Regression (CoxPh), to identify potential risk factors. The dataset is derived from TCGA-GBM clinicopathological information and mutations to create four risk score models: GRU, CoxPH, GRUCoxPHAddition, and GRUCoxPHMultiplication, analyzing 9 risk factors of the dataset. The Fuzzy-based GRUCoxPH model achieves an average accuracy of&amp;#xD;86.97%, outperforming other models. This model demonstrates its ability to classify and identify missense variants associated with mortality in GBM, potentially advancing cancer research.&amp;#xD;

Global incidence and prevalence in uveal melanoma

PurposeThe most common intraocular cancer in adults is uveal melanoma (UM). This study aimed to investigate and report the incidence and prognosis of UM in different regions of the world. MethodsWe retrieved relevant data on UM from the PubMed database and analyzed its global incidence and prognosis. All data was obtained from a national population-based registry, with publication dates ranging from 2013 to 2023. ResultsThe incidence rates of UM vary across different regions: in the United States, rates were 5.1 per million (1993–2008) and 5.2 per million (1973–2013); in Canada, rates ranged from 3.34 per million (1992–2010) to 5.09 per million (2011–2017); in Republic of Korea, the rate was 0.42 per million (1999–2011); in New Zealand, it was 5.56 per million (2000–2020); in Australia, it was 7.6 per million (1982–2014); and in Europe, rates ranged from 3.1 to 5.8 per million (1995–2002). Among European countries, Sweden (5.6 per million (1960–2009)), Germany (6.41 per million (2009–2015)), Poland (6.67 per million (2010–2017)), and the United Kingdom (10 per million (1999–2010)). ConclusionsThe most common site of occurrence for UM is in the choroid. Limited data suggest a stable trend in UM incidence rates across the included countries, but significant differences in incidence rates exist among different countries and regions, with notably lower rates in Asian countries compared to Europe, North America, and Oceania. In general, the incidence rate in males is slightly higher compared to that in females.

Photoeducation strategy through emerging technologies

Excessive exposure to ultraviolet radiation, added to the large amount of time that children spend exposed to the sun, causes lesions on their skin, significantly increasing the risk of suffering from skin cancer or melanoma in adulthood; Emerging technologies, such as mobile apps and UV-sensitive bracelets, offer practical and effective solutions to address the lack of knowledge and awareness about the risks of sun exposure, transforming the way we learn and engage with the world. particularly preschoolers.Objective: propose an educational strategy through emerging technology with the integration of AI in health education programs, aimed at children under 5 years of age. Methodology: a qualitative, ethnographic study was carried out, with the participation of 13 caregivers, 1 teacher, considering inclusion and exclusion criteria. The data were processed manually for exhaustive knowledge and meticulous review that can guide a complete and accurate interpretation of the participants' experiences. Results and conclusion: the study highlights the need for comprehensive and preventive education in photoprotection, using innovative technological tools to reach both children and their parents and teachers. Emerging technologies, such as mobile apps and UV-sensitive bracelets, offer practical and effective solutions to the risks of sun exposure. However, for this strategy to be effective, it is essential that it be implemented in an educational environment that supports and reinforces its use.

Prevalence of cancer survivors diagnosed during adolescence and young adulthood in the United States.

Adolescent and young adult (AYA) cancer incidence rates are rising, and survivors are at risk for numerous cancer- and treatment-related consequences. Despite growing attention to this population, prevalence estimates are lacking. To estimate the number of individuals living in the United States with a history of cancer diagnosed during the AYA period. Prevalence of cancer survivors diagnosed between the ages of 15 and 39 years was estimated using data from the Surveillance, Epidemiology, and End Results (SEER) program as of January 1, 2020. Limited duration prevalence data were also used to generate complete prevalence by sex, years since diagnosis (0-<1, 1-<5, 5-<10, 10-<15, 15-<20, 20+), and attained age (15-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70+) for the 15 most common AYA cancer sites. There were an estimated 2,111,838 survivors of AYA cancers in the United States as of January 1, 2020. More survivors were female (66%) and long-term (>5 years from diagnosis, 83%) or very long-term survivors (>10 years from diagnosis, 68.8%). A large percentage (44%) were more than 20 years from diagnosis. The most common cancer sites among females were breast (24%) and thyroid cancers (23%) and, among males, testicular cancer (31%). Across the population, the highest percentage of survivors of AYA cancers were 40- to 49-years of age (25.3%). There are over 2.1 million cancer survivors diagnosed in the AYA period who are living in the United States; most are more than 10 years from diagnosis.

Evaluation of long-term stability of L-asparaginase encapsulated PLL-g-PEG nanoparticles in solution to aid in therapeutic delivery

Abstract L-asparaginase (L-ASNase) is a therapeutic enzyme that is widely used for the treatment of hematopoietic diseases such as acute lymphoblastic leukemia and lymphomas. L-ASNase destroys asparagine dependent tumors by degrading circulating L-asparagine and thereby destroying malignant cells. As a protein drug, L-ASNase carries a few inherent drawbacks including short circulating half-life, low stability, and low catalytic activity under physiological conditions. Moreover, due to the bacterial origin of L-ASNase used in treatments, there have been reports with high frequency of hypersensitivity reactions in patients. The use of this drug in adult cancer populations has largely been hindered not only due to its immunological side effects but also due to non-immunogenic toxicities such as pancreatitis, liver toxicities, coagulopathy, and neurotoxicity. Therefore, it is vital to find new methods to decrease its immunogenic/toxicity profile while increasing the stability and half-life. The purpose of this study is to achieve a new L-ASNase polymer nanocarrier to improve stability of the enzyme while masking it from the immune system of the host. We designed and characterized a nanoparticle (NP) where a poly-L-lysine-grafted-poly(ethylene) glycol co-polymer was used to encapsulate L-ASNase. The primary focus of the study was to evaluate the stability and encapsulation efficiency of this NP construct over time. There was no aggregation of NPs observed during the study period of 6 months in solution and NPs had a 0.436 mV surface charge. L-ASNase NPs showed a percent asparaginase activity of 31% compared to free L-ASNase. Under physiological conditions NPs were found to be intact and retained the encapsulated proteins for up to 6 months in solution. Together, these results demonstrate that L-ASNase loaded PLL-g-PEG NPs may serve as a fundamental platform to design nanocarriers to prolong stability in solution.

Effect of anesthetic technique on antitumor immunity in patients undergoing surgery for gall bladder cancer: A prospective randomized comparative study.

There is a paucity of literature regarding the effect of anesthetic techniques on antitumor immunity, especially in gall bladder malignancies. We designed a study to compare the effect of propofol-based total intravenous anesthesia and sevoflurane-based general anesthesia-on antitumor immunity, including tumor growth factor-β (TGF-β), T-helper cell profile, and inflammatory markers. A pilot prospective randomized trial was conducted in 64 patients undergoing surgery for gall bladder malignancy under general anesthesia in a tertiary specialty cancer hospital. Adult cancer patients of ASA physical status I-III fulfilling the inclusion criteria were randomized to either group S (sevoflurane-based general anesthesia) or group T (propofol-based total intravenous anesthesia). Preoperative (morning of surgery) and postoperative (24 h and 1 month after surgery) blood samples were obtained. Demographic profile and preoperative parameters were comparable between both groups. There was a statistically significant difference in the postoperative value of TGF-β (higher in group T). There was a statistically significant difference in postoperative interleukin-17A value (indicative of TH17 cells), and it was found to be higher in group S. Propofol-based TIVA increases serum TGF-β levels. At the same time, Sevoflurane modulates T-helper cells-based immunity to increase TH17 cells in patients with gall bladder cancer. Multiple larger studies will be required to validate the results and provide useful recommendations.

Organisation and management of multi-professional care for cancer patients at end-of-life: state-of-the-art from a survey to community and hospital-based professionals.

Providing timely and satisficing End-of-Life care (EOLC) is a priority for healthcare systems since aging population and chronic diseases are boosting the global demand for care at end-of-life (EOL). In OECD countries the access to EOLC is insufficient. In Italy, the average rate of cancer patients assisted by the palliative care (PC) network at EOL was 28% in 2021, with high variability in the country. Among theItalian regions offering the best coverages, Tuscany has a rate of about 40%, but intraregional variation is marked as well. The study aims to explore the delivery of EOLC to adult cancer patients in public facilities in the Tuscany region through survey data collection among professionals. Two online surveys were delivered to Directors of community-based PC Functional-Units (FUs) and Directors of hospital-based medical-oncology units. All FU Directors responded to the survey (n = 14), and a response rate of 96% was achieved from hospital-unit Directors (n = 27). The results highlight the availability of numerous dedicated services, but reveal heterogeneity among and within organisations, including variations in the professionals involved, pathways, and tools adopted. Care continuity is supported by institutionalized collaboration between hospital and community settings, but hindered by fragmented care processes and heterogeneous transition pathways. Late referral to PC is perceived as a major constraint to EOLC. Developing structured pathways for patient transition to end-stage PC is crucial, and practices/processes should be uniformly implemented to ensure equity. Multi-professional care should be facilitated through tailored supporting tools. Both hospital-unit and FU Directors suggest developing shared pathways between organisations/professionals (82% and 80% respectively) and digital information sharing (61% and 80% respectively). Hospital and community-based professionals have similar perceptions about the concerns and challenges to EOLC provision in the region, but community-based professionals are more sensitive to the importance of improving communication on PC to the public and early discussing EOLC with caregivers. This finding suggests the need of enhancing hospital personnel's awareness about these issues. Professional training and the capacity to assess patients' needs and preferences should be improved. The identified needs can inform future research and interventions to improve the quality and outcomes of EOLC for cancer patients.

Serum bilirubin levels and risk of colorectal cancer in Korean adults: results from the Korean Genome and Epidemiology Study-Health Examinee (KoGES-HEXA) Cohort Study.

Current evidence on associations between circulating bilirubin and colorectal cancer (CRC) risk is inconsistent. In this prospective study, we investigated associations of pre-diagnostic circulating levels of total and indirect bilirubin with CRC risk in 78,467 Korean adults aged 40-78 years at recruitment, considering potential non-linearity and sex differences. Hazard ratios (HR) and 95% confidence intervals (CI) for associations with CRC risk were estimated with Cox proportional hazard regression. During a median 7.9-year follow-up, 539 incident CRC cases were recorded. In multivariable-adjusted models, higher levels of total bilirubin were associated with a 26% (CI: 42% to 7%) lower risk of CRC among men and women combined, comparing the highest with the lowest tertile (P-linear trend = 0.003). A U-shaped association was observed in men, with the lowest risk at approximately 0.8 mg/dL (=13.7 μmol/L) of total bilirubin (P for non-linearity = 0.01). Although the association was largely null in women, there was no evidence for effect modification by sex (P-interaction = 0.73). Associations between indirect bilirubin and CRC risk were similar. Higher circulating levels of total and indirect bilirubin were inversely associated with the risk of CRC among Korean adults. The associations were strongly inverse and U-shaped among men.

Posttreatment health interventions for adult cancer survivors and their families: an integrated review

PurposeThis review aimed to synthesize the literature regarding health interventions delivered to adult cancer survivors and their families during posttreatment phase.MethodsAn integrative literature review was conducted that included quantitative and qualitative studies. The search was carried out in four databases using the same terms or MeSH terms and included data from January 2012 to February 2024. After quality assessment, data were extracted and synthesized. The protocol was registered in PROSPERO.ResultsAmong the seven studies included, two studies were randomized controlled trials, three were observational, and two utilized a qualitative approach. The studies originated from France, Australia, Canada, the UK, and the USA. In total, 704 participants were included, 294 were cancer survivors, 40 were non-cancer patients, 271 were family and caregivers, and 99 were healthcare professionals. The studies assessed survival durations after cancer treatment, ranging from 18 months to 6 years. The sparse interventions found across the studies used a multifaceted approach tailored to address various aspects of cancer survivorship and caregiver support.ConclusionThis review provides insights into the complex landscape of posttreatment support requirements for cancer survivors and their family caregivers. This finding underscores the critical necessity for additional intervention research involving comprehensive, accessible, and supportive services that address the multifaceted dimensions of survivorship for the patient and family as a unit.

Dexmedetomidine-propofol versus ketamine-propofol for sedation of cancer patients undergoing computerized tomography guided bone biopsy: a randomized double-blind trial

Background &amp; Objective: Patients suffering from malignancy, often need to undergo computed tomography (CT) for evaluation or for CT-guided bone biopsy. They are shifted to the radio-diagnostic suite and require sedation and analgesia during this procedure. We compared the efficacy and safety of combining dexmedetomidine (DEX) or ketamine with propofol for better sedation among these patients undergoing CT-guided bone biopsy. Methodology: This randomized, double-blind study was done on 60 adult cancer patients undergoing CT-guided bone biopsy. Patients were randomized into two equal groups. Group D received DEX 1 µg/kg (over 10 min) + propofol 2.5 mg/kg intravenous (IV). It was followed by DEX 0.5 µg/kg/h + propofol 2.5 mg/kg/h infusion. Group K received ketamine 1 mg/kg + propofol 2.5 mg/kg IV, followed by ketamine 0.25 mg/kg/h + propofol 2.5 mg/kg/h infusion. Results: The total intra-procedure propofol consumption was significantly decreased in Group D than in Group K (P &lt; 0.05). The visual analog scale score at 15 min and 30 min post-procedure, number of patients requiring morphine and paracetamol within one hour of procedure and the recovery times were significantly decreased in Group D than in Group K (P &lt; 0.05). Mean arterial pressure (MAP) and heart rate (HR) measurements at 10 min, 20 min, end of the procedure, and 15 min, 30 min post-procedure was significantly decreased in Group D than in Group K (P &lt; 0.05). Adverse events, e.g., postoperative nausea and vomiting, hypotension, and bradycardia, were comparable. Conclusion: DEX-propofol combination had superior sedation efficacy as noted through lower pain scores, intraprocedural propofol or postprocedural morphine and paracetamol consumption, and the shorter recovery time during CT-guided bone biopsy compared to ketamine-propofol combination. However, ketamine-propofol combination exhibited superior hemodynamic stability, as shown by more consistent HR and MAP. Keywords: Dexmedetomidine; Ketamine; Propofol; Computed tomography; Bone biopsy; Morphine Citation: Abdelgalil AS, Mohammed AM, Abdelrahman AS, Zayed NOA. Dexmedetomidine-propofol versus ketamine-propofol for sedation of cancer patients undergoing computerized tomography guided bone biopsy: a randomized double-blind trial. Anaesth. pain intensive care 2024;28(5):809−815; DOI: 10.35975/apic.v28i5.2554 Received: Jun 17, 2024; Reviewed: Jul 31, 2024; Accepted: Aug 19, 2024

Cholecystectomy in children: indications, clinical, laboratory and histopathological findings and cost analysis.

The most common indication for cholecystectomy in children is cholelithiasis, and routine histopathological examination is performed on all gallbladder specimens. Currently, selective histopathological examination is suggested instead of routine examination due to the low frequency of gallbladder cancer in adults. The purpose of this study was to evaluate the indications, clinical, laboratory and histopathological findings of the cholecystectomy in children. We also questioned the contribution and cost-effectiveness of routine histopathological evaluation in diagnosis and treatment. A total of 114 children underwent cholecystectomy between the years 2008 and 2022. The clinical findings, laboratory, and imaging results of the patients and histopathological findings of the gallbladder specimens were evaluated retrospectively. Cholelithiasis were diagnosed in 71%, choledochal malformation in 15.8%, hydrops of gallbladder and/or biliary sludge in 12.3%, and hypoplasia of gallbladder in 0.9% of the patients. Histopathologically significant findings were observed in only 3 patients (2.6%); adenomyomatosis in 2 and angiodysplasia and pyloric metaplasia in 1. While the cost of a cholecystectomy and histopathologic examination combined amounted to 27.77% of the minimum wage in Türkiye in 2024, the histopathologic examination alone constitutes just 0.67% of the minimum wage and 2.4% of the operation fee. In children undergoing cholecystectomy, histopathological examination does not provide any significant contribution to the patient's diagnosis and follow-up management. In children, selective gallbladder histopathological examination might reduce health costs and save time for pathologists.

The Critical Role of Social Work in Addressing the Global Burden of Gastric Cancer in Adolescents and Young Adults.

The Critical Role of Social Work in Addressing the Global Burden of Gastric Cancer in Adolescents and Young Adults.

In vivo perturb-seq of cancer and microenvironment cells dissects oncologic drivers and radiotherapy responses in glioblastoma.

Genetic perturbation screens with single-cell readouts have enabled rich phenotyping of gene function and regulatory networks. These approaches have been challenging in vivo, especially in adult disease models such as cancer, which include mixtures of malignant and microenvironment cells. Glioblastoma (GBM) is a fatal cancer, and methods of systematically interrogating gene function and therapeutic targets in vivo, especially in combination with standard of care treatment such as radiotherapy, are lacking. Here, we iteratively develop a multiplex in vivo perturb-seq CRISPRi platform for single-cell genetic screens in cancer and tumor microenvironment cells that leverages intracranial convection enhanced delivery of sgRNA libraries into mouse models of GBM. Our platform enables potent silencing of drivers of in vivo growth and tumor maintenance as well as genes that sensitize GBM to radiotherapy. We find radiotherapy rewires transcriptional responses to genetic perturbations in an in vivo-dependent manner, revealing heterogenous patterns of treatment sensitization or resistance in GBM. Furthermore, we demonstrate targeting of genes that function in the tumor microenvironment, enabling alterations of ligand-receptor interactions between immune and stromal cells following in vivo CRISPRi perturbations that can affect tumor cell phagocytosis. In sum, we demonstrate the utility of multiplexed perturb-seq for in vivo single-cell dissection of adult cancer and normal tissue biology across multiple cell types in the context of therapeutic intervention, a platform with potential for broad application.

Population pharmacokinetic model of ABL001/CTX-009 (anti-VEGF/DLL4) in adult cancer patients with solid tumor.

ABL001/CTX-009 is a bispecific antibody targeting delta-like ligand-4 and vascular endothelial growth factor A. In this study, we developed a population pharmacokinetic (PK) model of ABL001/CTX-009 in patients with solid tumors. A total of 712 plasma concentrations from 30 patients with relapsed or refractory solid tumors were collected from a phase 1 study (NCT03292783). A population PK model was developed using a nonlinear mixed-effect method and was evaluated by graphical and numerical methods. Using the model, the steady-state concentrations were simulated to compare weight-based and fixed-dose regimens and to find optimal dosing intervals. The PK of ABL001/CTX-009 was well described by a two-compartment model with a parallel first-order and Michaelis-Menten elimination kinetics. Body weight was selected as a significant covariate on V1. Model evaluation results suggested that the model was adequate and robust with good precision. Simulations after administrations of fixed or weight-based doses showed similar plasma concentrations. Additionally, 10 mg/kg for every other week and 15 mg/kg for every three-week administration showed comparable plasma concentrations. In conclusion, the model well described the plasma concentrations of ABL001/CTX-009 in patients with solid tumors. The simulation suggested that weight-based dose and fixed dose can provide equivalent systemic exposure.

Step-by-step: A clinical pathway for stepped care management of fear of cancer recurrence-results of a three-round online delphi consensus process with Australian health professionals and researchers.

Fear of cancer recurrence (FCR) is not routinely addressed in clinical practice, meaning many cancer survivors forego effective interventions. We established expert consensus on a clinical pathway to help health professionals identify and manage FCR in early-stage cancer survivors. Australian health professionals and researchers working with adult cancer survivors participated in a three-round Delphi study promoted via oncology professional bodies and social media. The Round 1 online survey presented 38 items regarding FCR screening, triage, assessment, referral, and stepped care, based on a literature review, related pathways/guidelines, and expert input. Participants rated how representative of best-practice items were on a 5-point scale (strongly disagree-strongly agree), with optional qualitative feedback. Consensus was defined as ≥ 80% of participants strongly/agreeing with items. Items not reaching consensus were re-presented to Round 1 participants in two subsequent rounds with new items, derived from content analysis of qualitative feedback. From 94 participants in Round 1 (89% health professionals), 26/38 (68%) items reached consensus. By round 3, 35/38 (92%) items, including 8 new items, reached consensus. Routine FCR screening and triage conversations and stepped care management (i.e. tailored and staged treatment) were endorsed. However, the timing of FCR screening/triage did not reach consensus. This world-first FCR clinical pathway incorporating contemporary evidence and expert opinion recommends routine screening and triage to stepped care management of FCR. Some pathway components, such as screening or triage timing, may need tailoring for different contexts. Implementation of the pathway could aid routine identification and management of FCR, reducing its burden on cancer survivors and the healthcare system.

Молекулярно-генетический анализ персональных культур клеток увеальной меланомы

Relevance. Uveal melanoma (UM) is a subtype of melanoma that represents the majority of adult ocular cancers. The rare frequency of the disease does not allow to conduct large-scale clinical trials of new agents and approaches, which limits progress in its treatment. Half of patients with UM develop metastatic forms of the disease, which generally have unfavorable prognosis. Therefore, personal cell cultures derived from tumor material of patients are relevant for determining molecular and genetic features of tumor melanocytes and for testing new antitumor drugs. Purpose. To evaluate the aggressiveness of choroidal melanoma by molecular and genetic characterization of melanocytes isolated from the tumor. Material and methods. The study was performed using personal cultures of human UM cells. Karyotyping of cells was performed by GTG staining analysis of the metaphase plates, mutational burden was assessed by NGS sequencing, protein products were evaluated by western blotting. Results. In this work, three personal cultures of human UM cells, uMel1, uMel3 and uMel5, cultured for at least 22 passages, were obtained from tumor material of patients diagnosed with UM for the analysis of molecular and genetic characteristics. Since the development of the metastatic form of UM correlates with chromosomal alterations in tumor melanocytes, karyotyping was performed, which showed that in all cultures, most cells had a near-diploid phenotype. Only in uMel1 and uMel3 cells were chromosomal rearrangements specific for UM – in chromosomes 3, 6, and 8. In uMel5 cells, a deletion was found in the region of the long arm of chromosome 11. In addition, the patient with uMel5 tumor had a history of skin melanoma, for which the typical somatic mutation profile differs from that of UM. Somatic mutations in hotspots of ALK, BRAF, EGFR, HER2, IL17RA, KRAS, METand NRASgenes were analyzed by NGS-sequencing method. No mutations were detected at the tested loci in cells from all cultures tested. Analysis of tumor suppressor BAP1 (BRCA-associated protein) showed its low level in uMel3 and uMel5 cell cultures, which may indicate a high risk of metastasis. Conclusion. The obtained personalized cultures of UM cells are models that allow in vitroand in vivoinvestigation of UM with different molecular and genetic signatures. Key words: uveal melanoma, personalized cell cultures, karyotype, BAP1, BRAF, NGS-sequencing

Survival rate comparisons of angioembolization and neoadjuvant targeted therapy on unresectable renal cell carcinoma patients: A systematic review.

Renal cell cancer (RCC) is the most typical form of kidney cancer in adults, which accounts for 80% to 85% of all primary renal neoplasms. RCC develops inside the renal cortex. This study aimed to systematically review the survival rate of patients treated with targeted therapy and/or RC. Surgery is the standard therapy for RCC, even though after surgery, 20%-40% of patients with localized RCC would experience distant metastases. Metastases or large RCC are not amenable to surgery. Unresectable RCC can be treated palliatively with angioembolization or neoadjuvant therapy. This study aims to review the survival rate comparisons of angioembolization and neoadjuvant targeted therapy on unresectable renal cell carcinoma. A thorough search across databases such as PubMed, Cochrane Library, and ProQuest was conducted for articles published from 2018 to 2023. To uphold research integrity, duplicates, reviews, and incomplete articles were excluded, ensuring only pertinent and original research findings for subsequent analysis. Database search yielded 247 articles, which were systematically eliminated, leaving 6 relevant articles. Analyzed articles showed the overall survival of patients treated with angioembolization and neoadjuvant agents. Unresectable RCC can be treated palliatively with angioembolization. Angioembolization may improve clinical effectiveness and lessen side effects by boosting local concentrations of drugs. Drug-eluting bead transarterial chemoembolization is a novel embolization option that can embolize the arteries that feed the tumor and cutoff the blood supply to the tumor. Sunitinib, the most studied medicinal agent, was found to have higher effectiveness when combined with angioembolization.

Medicine needs of children not addressed in the National Cancer Strategic Framework: insights from a triangulation study

Aim A better understanding of the scope of the National Cancer Strategic Framework (NCSF) could lead to improvements aiding the framework’s ultimate objective of reducing the burden of cancer. Accordingly, this report evaluates whether the 2017-2022 NCSF adequately addressed issues related to childhood cancer treatment, in particular paediatric oncology medicines. Methods To identify determinants of current access to childhood oncology medicines in South Africa, in-depth interviews were conducted with 29 stakeholders in South Africa’s public and private healthcare sectors. Key health system stakeholders included policy makers and regulators, medical insurance scheme informants, medicine suppliers, healthcare providers and civil society stakeholders. Identified barriers were categorised according to the components of the pharmaceutical value chain, and combined with a health systems approach to acknowledge the linkages of medicines with other building blocks of the health system. Identified barriers were then compared to the limitations and interventions as discussed in the 2017-2022 NCSF to identify areas for improvement in the framework. Findings Three recurrent gaps in the NCSF in relation to childhood cancers were identified, representing a range of issues throughout the pharmaceutical value chain: 1) childhood cancers are neglected compared to adult cancers, in both the policy arena and the organisation of healthcare services; 2) there are particular challenges for childhood cancers due to their rarity, thus requiring targeted interventions (e.g., regulatory incentives, tailored pricing solutions, and customised evidence requirements by decision-making bodies); and 3) children must be accompanied by a caregiver during treatment, causing several social and financial issues for their families. Conclusions There is a pressing need for a strategic cancer plan that makes proper provisions for children. Such an endeavour must commence with acknowledging the areas in which childhood cancers are different from adult cancers, and which demand targeted intervention in an update of the NCSF.