Oncological Therapy Research Articles

Mucocutaneous toxicities from MEK inhibitors: a scoping review of the literature.

MEK inhibitors cause a wide spectrum of mucocutaneous toxicities which can delay or interrupt life-saving therapy. To summarize the morphology, incidence, and clinical presentation of mucocutaneous toxicities from MEK inhibitors via a scoping review of the literature. We conducted a scoping review of the published literature, including clinical trials, retrospective and prospective studies, reviews, and case reports and series. All included literature was analyzed by a panel of pediatric and adult oncodermatologists. Of 1626 initial citations, 227 articles met final inclusion criteria. Our review identified follicular reactions, ocular toxicities, xerosis, eczematous dermatitis, edema, and paronychia as the most common mucocutaneous side effects from MEK inhibitor therapy. Grade 1 and 2 reactions were the most prevalent and were typically managed while continuing treatment; however, grade 3 toxicities requiring dose reductions or treatment interruptions were also reported. Mucocutaneous toxicities to MEK inhibitor therapy are common and most often mild in severity. Early recognition and treatment can mitigate disruptions in oncologic therapy.

Comparison of Sitting versus Nonsitting Position for the Resection of Brain Metastases in the Posterior Fossa in a Contemporary Cohort.

For surgery of brain metastases, good immediate postoperative functional outcome is of utmost importance. Improved functional status can enable further oncologic therapies and adverse events might delay them. Pros and cons of either sitting or prone positioning for resective surgery of the posterior fossa are debated, but contemporary data on direct postoperative outcome are rare. The aim of our study was to compare the functional outcome and adverse events of surgery for brain metastases in the sitting versus the nonsitting position in the direct postoperative setting. We retrospectively compared surgery of metastases located in the posterior fossa over a 3-year period in two level-A neurosurgical centers. Center 1 performed surgery exclusively in the sitting, while center 2 performed surgery only in the nonsitting position. Worse functional outcome (Karnofsky performance scale) and functional deterioration were seen in the "sitting" group. We found significantly more "sitting" patients to deteriorate to a KPS score of ≤60%. In this study, treating patients with brain metastases in the sitting position resulted in a number needed to harm (NNH) of 2.3 and was associated with worse outcome and more adverse events. Therefore, we recommend the nonsitting position for surgery of brain metastases of the posterior fossa.

Clinical value of guideline recommended molecular targets and genome targeted cancer therapies: cross sectional study

ObjectiveTo assess the clinical benefit and actionability of molecular targets for genome targeted cancer drugs recommended for clinical practice by the National Comprehensive Cancer Network (NCCN).DesignCross sectional study.Participants/settingGenome targeted cancer...

Mimics of Host Defense Peptides Derived from Dendronized Polylysines for Antibacterial and Anticancer Therapy.

Bacteria in tumor microenvironments promote carcinogenesis and trigger complications, suggesting the significance of intervening in bacterial growth in cancer treatment. Here, dendrimer-derived mimics (DMs) of host defense peptides (HDPs) were designed for antibacterial and anticancer therapy, which feature a dendronized polylysine core and polycaprolactone arms. DMs displayed not only remarkable activities against Staphylococcus aureus and human lung cancer cells, but also exceptional selectivity. The membranolytic mechanism revealed by morphology analysis explained their low susceptibility to induce resistance. Further, the optimized DM inhibited tumor growth in the subcutaneous tumor model when administered via intraperitoneal injection and exhibited negligible toxicity to tissues. Overall, we combined the superiority of dendrimers and the mechanism from HDPs to design agents with dual antibacterial and anticancer activities that possess great potential for clinical oncology therapy.

Advancements in Early Detection and Screening Strategies for Pancreatic Cancer: From Genetic Susceptibility to Novel Biomarkers.

Pancreatic cancer is a rare but lethal cancer due to its biologically aggressive nature, advanced stage at the time of diagnosis, and poor response to oncologic therapies. The risk of pancreatic cancer is significantly higher to 5% in certain high-risk individuals with inherited genetic susceptibility. Screening for pancreatic cancer in these individuals from high-risk groups can help with the early detection of pancreatic cancer as well as the detection of precursor lesions leading to early surgical resection and improved overall outcomes. The advancements in radiological imaging as well as advanced endoscopic procedures has made a significant impact on the early diagnosis, surveillance, and staging of pancreatic cancer. There is also a significant advancement in the development of biomarkers for the early detection of pancreatic cancer, which has also led to the development of liquid biopsy, allowing for microRNA detection in serum and circulating tumor cells. Various societies and organizations have provided guidelines for pancreatic cancer screening and surveillance in high-risk individuals. In this review, we aim to discuss the hereditary risk factors for developing pancreatic cancer, summarize the screening recommendations by different societies, and discuss the development of novel biomarkers and areas for future research in pancreatic cancer screening for high-risk individuals.

Combined EUS and ERCP in patients with malignant distal biliary obstruction is associated with reduced time to oncological therapy compared to ERCP and sampling alone.

Standard ERCP sampling techniques for pancreaticobiliary malignancy have modest yields that could lead to delays in treatment. We aimed to evaluate whether combining EUS guided tissue acquisition (EUS-TA) with ERCP versus ERCP alone at the time of index procedure improved time to first outpatient evaluation and oncological treatment. All patients without a prior pathological diagnosis who underwent index ERCP at Leeds Teaching Hospitals NHS Trust, United Kingdom, for malignant distal biliary obstruction from 2015 to 2020 were considered. A total of 292 patients were included, of whom 74.7% (n = 202) underwent EUS-TA/ERCP. A combined approach was more likely to establish a positive diagnosis (96.5% (n = 195) vs 57.8% (n = 52), p < 0.01) and less likely to require further sampling procedures (2.0% (n = 4) vs 17.8% (n = 16), p < 0.01). Mean times to first outpatient evaluation (16.9 vs 24.5 days (p = 0.01)) and oncological treatment (55.1 vs 79.3 days (p = 0.03)) were significantly shorter in the EUS-TA/ERCP group. A third (n = 86) of patients with a positive diagnosis did not receive oncological/surgical treatment. In our cohort of patients, a combined approach was associated with improved diagnostic yield, reduced need for repeat sampling procedures and reduced time to evaluation and treatment, with similar therapeutic success and adverse event rates. Careful multidisciplinary discussion is recommended to avoid performing unnecessary EUS procedures on patients who will not benefit from further treatment.

The impact of congenital heart disease on treatment and survival of patients with hepatoblastoma: A single-center experience.

Patients with hepatoblastoma (HB) have a higher risk of congenital heart defects (CHD). There is limited literature on the management and outcomes of these patients. The purpose of this study was to identify demographics and outcomes of these patients in a single tertiary referral center. An Institutional Review Board (IRB)-approved retrospective chart review of patients with newly diagnosed HB from October 2004 to January 2021 was performed. CHD was defined as the presence of a septal defect, patent ductus arteriosus, pulmonary atresia, or bicuspid aortic valve. Chi-square and t-test were utilized for statistical analyses. Of the 151 patients diagnosed with HB during the study timeframe, 29 patients were found to have CHD. Five-year overall survival (OS) for non-CHD HB patients was 81.9% compared to 68.9% in the CHD cohort (p=.12). The 5-year OS for patients without surgically intervened CHD was 63.6% compared to 70.5% for those with surgically repaired CHD (p=.88). Pre-treatment extent of tumor IV was present more often in patients with HB and CHD who passed away (6/9, 66.7%) compared to those who survived (3/16,18.8%, p=.01). Patients with HB and CHD have similar survival compared to those without CHD. Our data support that patients with HB and CHD should be treated with curative intent including cardiac surgical intervention, medical oncology therapy, and oncological surgery for their HB.

Immune Checkpoint Inhibitor (ICI) Induced Sinonasal Disease: Review of Literature and FDA Database.

Immune checkpoint inhibitors (ICIs) are a rapidly expanding class of oncologic therapies whose mechanism of action can result in unique immune-related adverse events (irAEs) not seen in other cancer therapeutics. The objective of this study was to determine the presence of sinonasal irAEs with these medications. A case report of chronic rhinosinusitis with nasal polyps (CRSwNP) caused by an ICI is presented and was the impetus for this review. Review of the literature using Pubmed and Cochrane Database of Systematic Reviews was performed. Additionally, we searched the FDA adverse event reporting system (FAERS) database for sinonasal AEs in the 7 FDA-approved ICIs. We demonstrate an emerging scientific literature describing cases of CRS associated with multiple ICIs with a particular predilection toward TH2 driven phenotypes. Review of the FAERS also demonstrates a small percentage of patients who report sinonasal complaints after initiating ICI therapy. Sinonasal symptoms and the development of CRS, in particular, are not currently well recognized as potential irAEs for ICIs. Increased awareness and further study may help to elucidate if these are more common than currently reported and if irAE-related CRS is a unique phenotype.

MXene-Polydopamine-antiCEACAM1 Antibody Complex as a Strategy for Targeted Ablation of Melanoma.

Photothermal therapy (PTT) is a method for eradicating tumor tissues through the use of photothermal materials and photosensitizing agents that absorb light energy from laser sources and convert it into heat, which selectively targets and destroys cancer cells while sparing healthy tissue. MXenes have been intensively investigated as photosensitizing agents for PTT. However, achieving the selectivity of MXenes to the tumor cells remains a challenge. Specific antibodies (Ab) against tumor antigens can achieve homing of the photosensitizing agents toward tumor cells, but their immobilization on MXene received little attention. Here, we offer a strategy for the selective ablation of melanoma cells using MXene-polydopamine-antiCEACAM1 Ab complexes. We coated Ti3C2Tx MXene with polydopamine (PDA), a natural compound that attaches Ab to the MXene surface, followed by conjugation with an anti-CEACAM1 Ab. Our experiments confirm the biocompatibility of the Ti3C2Tx-PDA and Ti3C2Tx-PDA-antiCEACAM1 Ab complexes across various cell types. We also established a protocol for the selective ablation of CEACAM1-positive melanoma cells using near-infrared irradiation. The obtained complexes exhibit high selectivity and efficiency in targeting and eliminating CEACAM1-positive melanoma cells while sparing CEACAM1-negative cells. These results demonstrate the potential of MXene-PDA-Ab complexes for cancer therapy. They underline the critical role of targeted therapies in oncology, offering a promising avenue for the precise and safe treatment of melanoma and possibly other cancers characterized by specific biomarkers. Future research will aim to refine these complexes for clinical use, paving the way for new strategies for cancer treatment.

Sonoinduced Tumor Therapy and Metastasis Inhibition by a Ruthenium Complex with Dual Action: Superoxide Anion Sensitization and Ligand Fracture.

Photoresponsive ruthenium(II) complexes have recently emerged as a promising tool for synergistic photodynamic therapy and chemotherapy in oncology, as well as for antimicrobial applications. However, the limited penetration power of photons prevents the treatment of deep-seated lesions. In this study, we introduce a sonoresponsive ruthenium complex capable of generating superoxide anion (O2•-) via type I process and initiating a ligand fracture process upon ultrasound triggering. Attaching hydroxyflavone (HF) as an "electron reservoir" to the octahedral-polypyridyl-ruthenium complex resulted in decreased highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) energy gaps and triplet-state metal to ligand charge transfer (3MLCT) state energy (0.89 eV). This modification enhanced the generation of O2•- under therapeutic ultrasound irradiation at a frequency of 1 MHz. The produced O2•- rapidly induced an intramolecular cascade reaction and HF ligand fracture. As a proof-of-concept, we engineered the Ru complex into a metallopolymer platform (PolyRuHF), which could be activated by low-power ultrasound (1.5 W cm-2, 1.0 MHz, 50% duty cycle) within a centimeter range of tissue. This activation led to O2•- generation and the release of cytotoxic ruthenium complexes. Consequently, PolyRuHF induced cellular apoptosis and ferroptosis by causing mitochondrial dysfunction and excessive toxic lipid peroxidation. Furthermore, PolyRuHF effectively inhibited subcutaneous and orthotopic breast tumors and prevented lung metastasis by downregulating metastasis-related proteins in mice. This study introduces the first sonoresponsive ruthenium complex for sonodynamic therapy/sonoactivated chemotherapy, offering new avenues for deep tumor treatment.

The Role of Cannabinoids in Advancing Cancer Treatment: Insights from Evidence-Based Medicine.

This document critically examines the role of cannabinoids in cancer care during an era marked by rapid advancements in oncology and changing perceptions on cannabis. It traces the historical context of cannabis in medicinal use, navigating its journey from widespread acceptance, subsequent criminalization, to its resurgence in modern therapeutic applications, particularly within the framework of Evidence-Based Medicine (EBM). Anchored in EBM principles, this study synthesizes current research from clinical trials, systematic reviews, and meta-analyses to evaluate the efficacy and safety of cannabinoids in oncology. The focus is on their palliative effects, considering the nuances of effectiveness, risk assessment, and challenges inherent in translating these findings into clinical guidelines. The study seeks to bridge the gap between scientific research and clinical practice, offering insights to inform future oncological therapies and symptom management strategies involving cannabinoids. The potential benefits and risks of cannabinoid use in cancer treatment are assessed to guide clinicians and researchers in developing comprehensive, evidence-based approaches to patient care.

A Systematic Review of the Cardiotoxic Effects of Targeted Therapies in Oncology.

Cancer therapy advancements have improved survival rates but also introduced significant cardiotoxic risks. Cardiotoxicity, a critical adverse effect of cancer treatments such as doxorubicin, trastuzumab, and radiotherapy, poses substantial challenges. This systematic review synthesizes findings from studies on cardiotoxicity induced by cancer therapies, focusing on detection and management. Key predictors of chemotherapy-induced myocardial toxicity (CIMT) include advanced age, hypertension, hyperlipidemia, diabetes, and elevated N-terminal pro-B-type natriuretic peptide levels. Regular echocardiographic assessments, particularly of the left ventricular global longitudinal strain (LVGLS) and left ventricular ejection fraction (LVEF), are essential for early detection. The CardTox-Score, incorporating these risk factors, shows high sensitivity and specificity in predicting CIMT. Advanced imaging techniques and biomarkers play crucial roles in identifying at-risk patients before functional decline. Early biomarkers and imaging techniques such as LVGLS and LVEF are effective in diagnosing and managing cardiotoxicity, allowing timely interventions. Cardiology involvement in patient care significantly enhances adherence to cardiac monitoring guidelines and reduces cardiotoxicity risks. Management strategies emphasize regular cardiac monitoring, patient education, and the use of cardioprotective agents. A collaborative approach between cardiologists and oncologists is vital to assess cardiovascular risks, minimize vascular toxicity, and manage long-term adverse effects, ensuring the safety and efficacy of cancer therapies. This review underscores the importance of early detection and proactive management of cardiotoxicity in cancer patients to optimize treatment outcomes and improve quality of life.

Patient management with Head and Neck tumors-A nationwide data collection in oral and maxillofacial surgery.

This study analyzed oncologic patient management from initial tumor diagnosis to tumor follow-up in oral and maxillofacial surgery (OMFS) in Germany. A dynamic online questionnaire with a total of 44 questions was used to generate general and specific data regarding oncologic patient management with head and neck malignancies, supportive care, and (pre-) rehabilitation from initial tumor diagnosis to tumor follow-up and head and neck cancer center (HNCC) structures in OMFS in Germany. The questionnaire was sent to 81 OMFS departments affiliated with the German-Austrian-Swiss Working Group for Tumors of the Jaw and Facial Region (DÖSAK) and the German Association of Oral and Maxillofacial Surgery (DGMKG). Data analysis was conducted descriptively. Forty-eight OMFS departments participated (response rate 59.26%), of which 36/48 (75%) were certified HNCC. 28/34 (82.4%) reported subjective improvements in oncologic care, most often interdisciplinary collaboration (21/33, 63.64%) and clinic structure changes (21/34, 61.76%). Nearly all OMFS departments present patients in multidisciplinary tumor boards (45/46, 97.83%) and aim for osseous reconstruction post-tumor resection (43/44, 97.73%). Significant discrepancies regarding the frequency of masticatory-functional dental rehabilitation following osseous reconstruction were observed. Before oncologic therapy, patients are offered various supportive services, mostly psychotherapy and psycho-oncological support (24/26, 92.31%). Post-therapy, speech therapy (43/43, 100%), physiotherapy (40/43, 93.02%), lymphatic drainage, and follow-up rehabilitation (39/43, 90.7%, respectively) are most often offered. 17/43 (39.53%) have oncological nursing staff. 36/40 (90%) manage patients and side effects during adjuvant therapy, while 5/41 (12.2%) provide proprietary palliative care. 36/41 (87.8%) offer counseling to patients and families. Oncologic patient care in OMFS is highly standardized and potentially attributable to many certified HNCCs in Germany. Certain treatment aspects are handled differently, possibly due to institution-specific reasons. The high homogeneity in treatment protocols reflects the widespread high and comparable treatment quality of head and neck malignancies in OMFS in Germany.

Personalized therapy in oncology: melanoma as a paradigm for molecular-targeted treatment approaches.

In recent decades, the field of systemic cancer treatment has seen remarkable changes due to advancements in the understanding of cancer's biology, immunology, and genetic makeup. As a result, individuals with late-stage cancers are now achieving survival rates that were previously unattainable. The goal of personalized cancer therapy is to enhance clinical outcomes by customizing drug treatments to suit the unique genetic and/or epigenetic profiles of each patient's tumor. This approach aims to reduce the side effects commonly associated with ineffective treatments. Advances in genetic sequencing and molecular cytogenetics have been instrumental in identifying cancer-driving mutations and epigenetic irregularities, leading to the development of specific molecular therapies. This review article highlights the progress and success of targeted molecular therapies in treating malignant melanoma, illustrating the concept of personalized cancer treatment.

Changes in Technical Equipment and Patient Perspectives Navigating Towards Enhanced Digitalization in Breast Cancer Across Pre-COVID-19 and Early COVID-19 Eras

IntroductionThe potential benefits of eHealth support in enhancing patient care, satisfaction, and cancer outcomes are well-established; however, its integration into routine care has been gradual. The emergence of the COVID-19 pandemic in 2020 dramatically affected cancer patients, imposing multifaceted challenges that impede traditional doctor-patient interactions. Consequently, there has been a surge in the adoption of eHealth for supporting oncological therapies. This study investigates the fundamental prerequisites for transitioning to a more digitally oriented routine care, focusing on the availability of appropriate technical equipment and the cultivation of a positive mindset towards eHealth among breast cancer patients. Patients and MethodsIn 2013, 2016, and 2020, breast cancer patients participated in surveys utilizing a comprehensive paper questionnaire encompassing 29 inquiries about their health status, technical equipment, and attitudes toward digital therapy support. ResultsA total of 959 patients participated in the interviews. Comparative analyses between the 2013, 2016, and 2020 surveys revealed a widespread increase in internet access and device ownership across various age groups. By 2020, 3 quarters of patients were utilizing the internet for health-related topics. Notably, there has been a considerable improvement in patients' personal attitudes towards eHealth and their expectations for future digital therapy support. DiscussionOver the seven years spanned by the surveys, there has been a substantial positive shift in the attitudes of breast cancer patients towards eHealth, accompanied by a marked improvement in their technical equipment. This study reveals that the essential prerequisites for digital therapy support now appear to be prevalent among breast cancer patients.

Frailty in Oncology: Updated Recommendations for Clinical Practice

Frailty is a clinical condition associated with aging and resulting in increased risk of adverse outcomes upon exogenous or endogenous stressors. In oncology, cancer treatment itself can be a stressor event. In older cancer patients, frailty therefore not only enhances the probability of age-related health events such as institutionalization or falls, but also of treatment complications such as toxicity and interruption or discontinuation of therapy. As demonstrated by recent randomized-controlled trials conducted in older cancer patients receiving systemic treatment, the evaluation of frailty by geriatric assessment (GA) followed by an adjustment of the oncological therapy as well as targeted frailty interventions help to improve cancer treatment tolerability and feasibility. Based on these data, the American Society of Clinical Oncology (ASCO) updated the clinical practice guidelines for the assessment and management of vulnerabilities in older adults receiving systemic cancer therapy. The guideline recommends the use of a new GA-tool named 'practical geriatric assessment' (PGA) to foster the implementation of GA-based frailty assessment and management in routine cancer care. This article describes the background and key aspects of these recent advances.

A Systematic Review of Laser Photobiomodulation Dosimetry and Treatment Protocols in the Management of Medications-Related Osteonecrosis of the Jaws: A Rationalised Consensus for Future Randomised Controlled Clinical Trials.

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating adverse effect of bisphosphates, antiresorptive therapy or antiangiogenic agents that can potentially increase oxidative stress, leading to progressive osteonecrosis of the jaws. Despite the large number of published systematic reviews, there is a lack of potential MRONJ treatment protocols utilising photobiomodulation (PBM) as a single or adjunct therapy for preventive or therapeutic oncology or non-oncology cohort. Hence, this systematic review aimed to evaluate PBM laser efficacy and its dosimetry as a monotherapy or combined with the standard treatments for preventive or therapeutic approach in MRONJ management. The objectives of the review were as follows: (1) to establish PBM dosimetry and treatment protocols for preventive, therapeutic or combined approaches in MRONJ management; (2) to highlight and bridge the literature gaps in MRONJ diagnostics and management; and (3) to suggest rationalised consensus recommendations for future randomised controlled trials (RCTs) through the available evidence-based literature. This review was conducted according to the PRISMA guidelines, and the protocol was registered at PROSPERO under the ID CRD42021238175. A multi-database search was performed to identify articles of clinical studies published from their earliest records until 15 December 2023. The data were extracted from the relevant papers and analysed according to the outcomes selected in this review. In total, 12 out of 126 studies met the eligibility criteria. The striking inconsistent conclusions made by the various authors of the included studies were due to the heterogeneity in the methodology, diagnostic criteria and assessment tools, as well as in the reported outcomes, made it impossible to conduct a meta-analysis. PBM as a single or adjunct treatment modality is effective for MRONJ preventive or therapeutic management, but it was inconclusive to establish a standardised and replicable protocol due to the high risk of bias in a majority of the studies, but it was possible to extrapolate the PBM dosimetry of two studies that were close to the WALT recommended parameters. In conclusion, the authors established suggested rationalised consensus recommendations for future well-designed robust RCTs, utilising PBM as a monotherapy or an adjunct in preventive or therapeutic approach of MRONJ in an oncology and non-oncology cohort. This would pave the path for standardised PBM dosimetry and treatment protocols in MRONJ management.

Remote organ cancer adversely alters renal function and induces kidney injury, inflammation, and fibrosis.

Approximately 30% of cancer patients experience kidney complications, which hinder optimal cancer management, imposing a burden on patients' quality of life and the healthcare system. The etiology of kidney complications in cancer patients is often attributed to nephrotoxic oncological therapies. However, the direct impact of cancer on kidney health is underestimated, as most nephrotoxic oncological therapies have been studied in animal models that do not have cancer. Our previous study demonstrated that advanced lung cancer adversely alters kidney physiology and function, and exacerbates chemotherapy-induced nephrotoxicity, indicating lung cancer-kidney crosstalk. This study examines whether this phenomenon is specific to the employed cancer model. Female and male mice of various strains were injected with different cell lines representing human and mouse lung cancer, breast cancer, and melanoma, and their kidney tissues were analyzed for toxicity and fibrosis. The impact of cancer on the kidney varied by cancer type. Breast cancer and specific subtypes of lung cancer, including KRAS- and EGFR-mutant cancer, pathologically altered kidney physiology and function in a manner dependent on the metastatic potential of the cell line. This was independent of mouse strain, sex, and cancer cell line origin. Moreover, tumor DNA was not detected in the renal tissue, excluding metastases to the kidney as a causative factor for the observed pathological alterations. Lewis lung carcinoma and B16 melanoma did not cause nephrotoxicity, regardless of the tumor size. Our results confirm cancer-kidney crosstalk in specific cancer types and highlight gaps in understanding the risk of renal complications in cancer patients. In the era of precision medicine, further research is essential to identify at-risk oncology populations, enabling early detection and management of renal complications.

[Artículo traducido] Asciminib para el tratamiento de la leucemia mieloide crónica en tercera línea: análisis coste-efectividad basado en el enfoque de remisión libre de tratamiento

IntroductionThe first targeted therapy in oncology, imatinib, revolutionized chronic myeloid leukemia (CML) treatment and spurred research in targeted therapies for various cancers. CML results from a chromosomal translocation, forming the BCR-ABL1 fusion gene. Asciminib has been recently approved for 3rd-line refractory or intolerant patients. Treatment-free remission (TFR) is attainable with sustained deep molecular response (DMR) and this approach could be incorporated into pharmacoeconomic models. AimsTo establish a cost-effectiveness model comparing asciminib to approved third-generation tyrosine kinase inhibitors (TKIs) (bosutinib and ponatinib) with a focus on achieving TFR. Additionally, the budgetary impact of incorporating asciminib as a therapeutic alternative is assessed. MethodsThis model is based on a Markov chain with seven states. The condition for achieving TFR is to remain for 5 years in DMR state. Efficacy of the model was measured in QALYs, and the costs included in the base case analysis are based in Spain. A probabilistic (PSA) and deterministic analysis (DSA) were carried out to assess the variability of the model. There were achieved two independent models comparing asciminib vs. bosutinib and asciminib vs. ponatinib. ResultsAsciminib, when compared with ponatinib, is a cost-saving alternative, as efficacy is similar between alternatives, and asciminib has a lower cost of 30,275 €. Asciminib showed 4.33 more QALYs and a higher cost (203,591 €) than bosutinib, resulting in an ICER of €47,010.49 per QALY. PSA shows that the parameters with higher influence in the variability of the model were the probability of transitioning to BP and probabilities of achieving MMR and DMR. A one-way analysis reports that the drug cost has a higher influence on both models, and the discount rate significantly affects the asciminib vs. bosutinib model. ConclusionAsciminib broadens therapeutic choices for patient’s refractory or intolerant to two prior lines of treatment in a cost-effective manner. The costs of drugs significantly impact the overall cost of the disease, emphasizing the importance of the selected discount rates for each drug. Given the relatively low incidence of CML, the introduction of asciminib has a limited budgetary impact, warranting individualized decisions based on patient`s clinical characteristics.

Clinical characteristics and factors associated with survival rate of patients with non-muscle invasive bladder cancer attending at a Tertiary Hospital in Somalia

BackgroundA few studies regarding the epidemiology and risk factors of Non-muscle Invasive Bladder Cancer (NMIBC) are reported from Sub-Saharan African countries (SSA), including Somalia, and the African literature is scant on the management of NMIBC. The present study aims to evaluate the clinical-histopathological characteristics and factors associated with the survival rate of patients with NMIBC.MethodThis six-year cohort study included 196 patients with NMIBC. It reviewed the clinical and histopathological characteristics and factors predicting cancer-specific survival for these patients.ResultsThe mean patient age was 59.01 ± 11.50 years, with a male-to-female ratio of 2.8:1. Urothelial carcinoma (UC) constituted the most common pathological type, accounting for 90.8%; Ta LG and T1HG were the most common histopathological tumour stage and grade (n = 90, 45.9%, vs. n = 56, 28.6%), respectively. The mean tumour size was 4.72 ± 2.81 cm. The cancer-specific mortality(CSM) was 13.3%. Age [2.252(2.310–2.943], p < 0.001], Gender [1.031(0.981-1.1.242),p < 0.001], tumour stage and grade [4.902(3.607–5.614),p < 0.001], tumour location [1.135(0.806–1.172),p < 0.001], number [0.510(0.410–0.920),p = 0.03], tumour size [1.523(0.936–1.541),p < 0.001], use of intravesical chemotherapy or BCG [2.810(1.972–4.381),p < 0.001], preoperative hydronephrosis grade [1.517(1.172–2.154),p < 0.001], and follow-up compliance [3.376(2.633–5.018),p < 0.001] were all associated with CSM. The 5-year overall survival was 57.1%, and cardiovascular diseases were the leading cause of mortality (n = 34), followed by diabetes (n = 28).ConclusionOur study findings revealed that UC constituted the most common pathological subtype, though less than forty per cent of our patients receive intravesical adjuvant therapies, which are crucial to minimizing disease morbidity and mortality. Initiatives improving uro-oncological care, including subspecialty training in oncology and essential cancer therapies, better access to urology services, and cancer screening programs, are much needed for optimal management plans and care in the country.