Onco

Breast cancer is a complex disease that is one of the leading causes of cancer-related mortality in women worldwide. Of the subtypes of breast cancer, the most aggressive subtype is triple negative breast cancer (TNBC) due to its lack of targets that could be leveraged for treatment in other subtypes. Current treatment options for both local and metastatic TNBC include radiation therapy, chemotherapy, surgery, targeted therapy, and immunotherapy, which has been gaining popularity in recent years. The role of targeted therapy in TNBC is somewhat limited due to the paucity of therapeutic personalized targets, and, due to the heterogeneity of the disease, the effectiveness of these different modalities varies from patient to patient. These unique elements are the foundation of personalized medicine where genomics and transcriptomics play a critical role in increasing granularity in patients’ disease and treatment. The purpose of these molecular tools is to identify biomarkers that could be used to further characterize each patient’s unique disease features and to predict how certain treatment modalities will affect patient survival and prognosis. The interplay between these biomarkers and molecular pathways involved in treatment response with disease progression and aggressiveness is a complex phenomenon. In this review, we describe the current state of the literature in regard to biomarkers that show promise in the clinical setting to predict response to treatments such as chemotherapy, radiation, and surgery in locally advanced and metastatic TNBC. Full article

Organoid culture is an emerging and promising 3D culture system by which three-dimensional cell aggregates have been produced from different organs and tissues. This new innovative culture technology preserves parental gene expression, as well as the biological features of parental cells in vitro and ensures maintenance of three-dimensional cell culture for prolonged periods, opening new encouraged scientific scenarios and making them a functioning and valid system for testing new drugs for tissue engineering studies and precision oncology medicine. Various research focused on organoids has been performed in perfusion bioreactors, an advanced device able to mimic the tumor environment, providing a physiological growth state and a long-term culture viability. Perfusion bioreactors have been used for the maintenance and growth of organoids as well as for tumor patient samples improving proliferation while supporting the development of extracellular matrix (ECM). The ability to mimic the tumor environment and to maintain patient-derived biopsies for a long time makes perfusion bioreactors an essential model for preclinical testing. Full article

Peritoneal carcinomatosis is a common presentation found in advanced-stage gastrointestinal (GI) and gynecological cancers. Combined cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with significant survival benefits for select patients. CRS/HIPEC is not currently provided in Newfoundland and Labrador (NL). The Canadian HIPEC Collaborative Group recommends that centres complete a minimum of one case monthly to maintain competency and achieve good outcomes. Thus, we aimed to demonstrate that the annual patient volume in NL justifies the feasibility of implementing a combined surgical and gynecological oncology CRS/HIPEC program. Methods: A retrospective chart review of the NL Cancer Care Registry identified patients with stage IV colorectal, appendiceal, or gastric cancer and stage III to IV epithelial ovarian cancer over a 1-year period (1 January 2020–31 December 2020) to identify the number of patients meeting the criteria for CRS/HIPEC and/or those referred out of province to receive the treatment. The results are presented as proportions and percentages. Results: Thirty-one patients were eligible to receive CRS/HIPEC during the study period (11 GI, 20 gynecological). Of the GI patients, 63% were referred out of province for the procedure. Gynecological patients underwent CRS and systemic therapy +/− outpatient intraperitoneal chemotherapy in NL. Conclusions: Allowing patients to receive this standard of care treatment near home reduces financial, social, and emotional stressors. Our results confirm a sufficient patient volume to support a combined CRS/HIPEC program in NL. The implementation of this program will require multidisciplinary collaboration, specialized training, equipment, and protocol development. Full article

Background: Few studies have compared the risk of reoperation by timing in breast reconstruction surgery after mastectomy. We evaluated the first and total number of reoperations by reconstruction timing in women with breast cancer undergoing primary mastectomy. Methods: A cohort study of 23,301 primary mastectomies in women with breast cancer undergoing either immediate breast reconstruction (IBR) or delayed reconstruction was carried out within Kaiser Permanente between 2010 and 2022. The first reoperation rate was calculated using cause-specific Cox Proportional Hazards Models, while Multiplicative Cox Proportional Hazards Models were used to account for mortality and timing in reoperation. Patients were continuously monitored for death, outcome of interest, loss to follow-up through healthcare membership termination, or study end date (31 December 2022). Results: In total, 78.4% (n = 18,276) of the cohort underwent IBR. The average follow-up time was 5.9 years (±3.8). The following covariates were imbalanced (standardized mean difference [SMD] ≥ 0.20) between IBR and delayed groups: BMI, smoking status, year of mastectomy, bilateral procedures, and reconstruction type. The crude incidence of first reoperation was 33.04% vs. 31.72% in IBR vs. delayed patients and the risk of reoperation was 18% higher in IBR patients (HR = 1.18, 95% CI = 1.12–1.25). There was no difference in the risk of reoperation by timing (p > 0.05) when assessing multiple reoperations. The reoperation risk was the highest for IBR patients who did not complete reconstruction or single-stage reconstruction. In addition, the first reoperation rate of IBR patients was higher in those who underwent expander–implant-based reconstruction. Conclusions: The first reoperation rate was higher in IBR patients compared to those who delayed reconstruction, although we failed to detect a difference for multiple returns to surgery, except in certain subgroups. Assessing reoperation risk by timing among different reconstruction modalities can aid patients in making informed decisions about the type of breast reconstruction to undergo. Full article

This paper reviews the surgical management of peritoneal carcinomatosis as new surgical methods have been developed within the past few decades. Traditional methods included cytoreductive surgery with hyperthermic intraperitoneal chemotherapy; however, a new method has been developed, Pressurized Intraperitoneal Aerosol Chemotherapy. This method is minimally invasive while allowing for promising outcomes in those who have exhausted therapy options or require palliative therapy. The goal of this paper is to compare and contrast the traditional and standard method with the newer method for intraoperative delivery of chemotherapy. Full article

Bladder cancer, a highly heterogeneous disease, necessitates precise diagnostic and therapeutic strategies to enhance patient outcomes. Metabolomics, through comprehensive small-molecule analysis, provides valuable insights into cancer-associated metabolic alterations at the cellular, tissue, and systemic levels. Concurrently, molecular imaging modalities like PET, MRI, and CT enable the non-invasive, real-time visualization of tumor biology, facilitating the spatial and functional assessment of biomarkers. Key findings highlight the identification of metabolomic profiles correlated with cancer progression, recurrence, and treatment responses across serum, urine, and tissue samples. Advanced analytical platforms, such as LC-MS and NMR, uncover distinct metabolic signatures and pathway alterations in glycolysis, amino acid metabolism, and lipid biosynthesis. Molecular imaging further enhances staging accuracy and treatment monitoring by visualizing metabolic activity and receptor expression. The integration of these technologies addresses the limitations of invasive diagnostic methods and paves the way for precision oncology. Future advancements should focus on multi-omics integration, AI-driven analysis, and large-scale clinical validation to ensure broad accessibility and transformative impacts on bladder cancer management. Full article

Background: Multimodal treatment of bone sarcomas has improved survival and allowed limb salvage surgery in the majority of these patients. Periprosthetic joint infection (PJI) constitutes a challenging complication. Controversy remains regarding the risk factors for PJI. Here, we aim to identify them. We also discuss pathogens and treatments. Methods: The authors reviewed the institutional database to retrieve endoprostheses implanted after bone sarcoma resection from 2014 to 2021. In total, 66 eligible patients were identified. Results: A total of 14 (21.21%) periprosthetic infections were diagnosed. Of these, 10 occurred in men (71.43%, p = 0.143). Mean BMI, age at the time of surgery, and ASA score were significantly higher among patients who developed PJI (p = 0.003, 0.044, and 0.033, respectively). Site was an important factor as well (p = 0.029). The number of comorbidities and the Charlson Comorbidity Index were also higher among these patients (p = 0.264, 0.060, respectively). Histology did not play a role in PJI (p = 0.385). Conclusions: Our data allow surgeons to better understand and control risk factors for PJI. We identified BMI, age, ASA score, site, and the Charlson Comorbidity Index as the main risk factors. Polymicrobial infections and methicillin-resistant Staphylococcus aureus are associated with recurrent infections. A multicentric study with a larger cohort is needed. Full article

Cancer vaccines offer an exciting option for active immunotherapy, providing a potentially safe and effective treatment that also prevents or minimizes toxic side effects in vaccinated patients. Clinical results from previous phase III clinical trials have suggested that the efficacy of cancer vaccines largely depends on their potential to trigger robust immunological responses. A preexisting immune response to cancer-specific peptides is crucial for achieving a meaningful clinical outcome during vaccinations. However, various factors may hinder the effectiveness of therapeutic vaccines. By overcoming these challenges, cancer vaccines have the potential to become a cornerstone in immunotherapy. This review aims to share our insights on the major challenges that are encountered when optimizing the potential of cancer vaccines, particularly focusing on important aspects regulating their clinical efficacy, such as vaccine composition, the adjuvant to be used and the HLA-restricting element for the tumor peptides targeted by a particular vaccine. Additionally, we discuss several obstacles which hindered the successful clinical development of therapeutic cancer vaccines, such as the standard of care, the clinical design, and the choice of the antigen(s) to be included in vaccine formulation. The identification of patients that are most likely to respond to vaccinations by developing immunological responses and the desirable clinical efficacy are also crucial, and, therefore, predictive biomarkers are strictly required. Finally, we present our views on future prospects that may lead to an enhancement of the anticancer effects of vaccines, ensuring their pivotal role in cancer immunotherapy. Full article

During the last decade, a new therapeutic revolution has involved the management of hepatocellular carcinoma (HCC). This is made possible thanks to the documented efficacy of immunotherapy for this disease. In addition, new evidence has demonstrated the role of the gut–liver axis and gut microbiota in host homeostasis, tumor development, and response to therapies. In particular, intestinal dysbiosis can alter the tumor microenvironment, leading to the activation of intracellular signaling pathways that promote carcinogenesis. The composition of gut microbiota proved to influence the immune checkpoint inhibitors (ICIs) efficacy and drug toxicities. Therefore, this review aims to deepen knowledge about the immunomodulatory role of gut microbiota and its possible employment as diagnostic and predictive biomarkers in diagnosis and response to HCC immunotherapy, respectively. The research was conducted through the analysis of Pubmed and Web of Science (WoS) databases for literature studies on the relationship between gut microbiota and HCC from 2015 to 2025. Full article

Background/Objectives: The accurate prediction of overall survival (OS) in cancer patients is crucial for personalized treatment strategies. Methods: In this study, we developed machine learning models to predict OS by integrating clinical and mutational features from a cohort of 25,508 cancer patients. Key features included tumor mutational burden (TMB), microsatellite instability (MSI), fraction of genome altered (FGA), copy number alterations (CNA), age, sex, race, cancer type, and metastasis status. Results: We applied multiple Random Forest, Gradient Boosting, and Ensemble models, achieving an accuracy of 74% for overall survival status, and a C-Index of 0.76 using the Random Survival Forest model. Importantly, FGA, age, MSI score, TMB, cancer type, and metastasis status were identified as major predictors of OS across all models. We also integrated treatment data from 16,603 patients, demonstrating that therapies like platinum, carboplatin, and taxanes are associated with differences in survival predictions, with some therapeutic regimens showing minimal impact. Conclusions: Our findings highlight the potential of using machine learning to predict OS by incorporating both clinical and mutational features. These models offer a promising approach for improving patient outcomes and could be further validated in prospective studies for clinical use. Full article

Mirtrons represent a new subclass of microRNAs (miRNAs) that are processed through non-canonical biogenesis pathways. Unlike canonical miRNAs, which require Drosha-mediated cleavage, mirtrons are generated via the splicing of short intronic sequences, bypassing Drosha entirely. While mirtrons are found across a variety of organisms, their conservation between species is relatively low. This evolutionary divergence has resulted in mirtrons acquiring species-specific regulatory functions. In humans, mirtrons remain an understudied group of regulatory RNAs. However, emerging evidence highlights their critical roles in cancer biology. These small RNAs influence a range of oncogenic processes, including tumor initiation, progression, metastasis, and resistance to therapy. By directly regulating the expression of oncogenes and tumor suppressor genes, mirtrons serve as key molecular mediators within cellular signaling pathways. What sets mirtrons apart from canonical miRNAs is their unique mode of biogenesis and structural attributes, which reveal alternative regulatory mechanisms that could be exploited in cancer biology. Recent advances in understanding their functions suggest that mirtrons hold significant potential as biomarkers for cancer diagnosis and prognosis. Additionally, their role as modulators of cancer pathways positions them as promising therapeutic targets in precision oncology. This review delves into the growing body of research on mirtrons, focusing on their biogenesis, biological roles, and implications in cancer. By emphasizing their distinct features and clinical relevance, it aims to provide a comprehensive perspective on the potential applications of mirtrons in advancing cancer diagnostics and therapeutics. Full article

Background/Objectives: Treatment options for advanced HCC are limited. Immunotherapy, a promising new therapeutic, has recently been incorporated as a first-line systemic treatment. This study evaluates immunotherapy uptake and disparities in its adoption prior to first-line approval, which are currently unknown. Methods: Patients diagnosed with stage IV HCC between 2014 and 2019 were identified in the National Cancer Database (NCDB). Multivariable logistic regression analysis was performed for demographic and clinical variables to determine their association with the receipt of immunotherapy. Results: A total of 18,248 patients were diagnosed with stage IV HCC, of which 977 (5.35%) received immunotherapy. From 2014 to 2019, the rate of immunotherapy uptake increased each year, with an approximate 25-fold increase overall. On multivariable analysis, patients with a more recent period of diagnosis (OR: 30.19, 95% CI: 16.47–55.33), with private insurance (OR: 2.56, 95% CI: 1.62–4.04), with treatment at an academic or research center (OR: 1.97, 95% CI: 1.37–2.82), or with an income ≥ USD 63,333 (OR: 1.27, 95% CI: 1.01–1.59) were more likely to receive immunotherapy. Conclusions: Various demographic factors impact the receipt of immunotherapy in the pre-approval setting, such as income, insurance status, and treatment center. As immunotherapy use will likely further expand and these disparities may potentially persist following first-line approval, strategies to mitigate them are especially important. Full article

Background/Objectives: Lip cancer represents one of the most prevalent malignant neoplasms in the oral cavity worldwide. This study investigated the prevalence, epidemiological profile, and survival rates of lip squamous cell carcinoma cases at the Liga Norte Riograndense Contra o Câncer (LNRCC) through a 15-year retrospective analysis. Methods: Data collection included sociodemographic characteristics, risk factors, tumor features, staging, and treatment modalities from 348 patient records. Statistical analysis was performed using Stata 12.0 and SPSS 22.0. Results: Results showed a predominance of male patients (70.4%), with a mean age of 65.51 years, mostly brown-skinned, illiterate individuals working in rural areas and residing in the state’s eastern region. Moderately differentiated squamous cell carcinoma (82.8%) affecting the lower lip (89.1%) was most frequent, with a tendency toward advanced staging. The overall survival rate was 88.90%, with lower rates observed among white, illiterate, and substance-using patients, as well as those with advanced-stage disease and chemotherapy treatment. Conclusions: Notably, race emerged as the most significant survival predictor, with white individuals showing consistently lower survival rates regardless of disease characteristics or treatment approach. Full article

Tumor dormancy plays a pivotal role in cancer relapse. Dormant tumor cells have been identified in distant sites, even in early-stage tumors, and are associated with worse outcomes. This review explores the current understanding of the molecular and cellular mechanisms behind tumor dormancy, including the role of the immune system and the microenvironment. Targeting dormant tumor cells could be a therapeutic strategy to offer long-term remission and potentially cure cancer. Unfortunately, the translation of this knowledge in clinical practice is lacking. We assess the feasibility of detecting and measuring dormant tumor cells in clinical practice, and give an overview of potential therapeutic targets, both in terms of maintaining tumor cells in a dormant state, and in terms of eradicating this tumor population. Full article

The integration of small interfering RNA (siRNA) with traditional cancer therapies represents a promising frontier in oncology aimed at enhancing treatment effectiveness, reducing side effects, and overcoming drug resistance. This review highlights the potential of siRNA to selectively silence genes that are overexpressed or uniquely expressed in cancer cells, thereby disrupting critical pathways that support tumor growth and survival. Key target genes discussed include survivin, VEGF, EGFR, c-MET, HER2, MUC1, and Bcl-2, all of which play vital roles in tumor proliferation, angiogenesis, and resistance to therapies. Clinical trials investigating various siRNA candidates, such as EZN-3042 and ALN-VSP, indicate that these therapies are generally well-tolerated; however, significant challenges persist, including the effective delivery and stability of siRNA. Recent advancements in nanoparticle-based delivery systems have shown promise in addressing these issues. Future research will focus on optimizing siRNA delivery methods, personalizing therapies based on individual genetic profiles, and establishing clearer regulatory guidelines for approval. As the field evolves, siRNA-based combination therapies are poised to become an integral part of precision oncology, offering new therapeutic options and hope for patients with difficult-to-treat cancers. Full article

Background/Objectives: Multiple immune-modulatory strategies have been tested in efforts to mitigate the pro-tumor microenvironment in pediatric high-grade glioma. HSV1716 is an oncolytic virus that previously demonstrated evidence of response in adult and pediatric patients. PBTC-037 was a single-center phase I trial developed and performed by the Pediatric Brain Tumor Consortium (PBTC) to estimate the maximum tolerated dose or recommended phase II dose of HSV1716 administered during surgical resection. Methods: Patients aged 12 to 21 years with recurrent or refractory high-grade glioma for whom surgical resection was clinically indicated were eligible. After maximal tumor resection, patients received one intraoperative dose of HSV1716. Results: Two patients were enrolled; one was later deemed ineligible yet was continued in follow up for safety. Both patients underwent complete tumor resection with the administration of HSV1716. Shortly after the enrollment of the two patients, this study was closed to accrual due to a change in the sponsor’s investment focus. One patient completed the 8-week reporting period without toxicity. The second patient who was later deemed ineligible had no evidence of dose-limiting toxicity. The two patients had progressive disease at 1.9 and 2.9 months after enrollment; both eventually died due to progressive disease at 7.5 months. Conclusion: We describe the administration of HSV1716 to two pediatric patients with recurrent high-grade glioma, without evidence of dose-limiting toxicity. Oncolytic viruses are currently being tested in pediatric patients in larger combinatorial trials. Despite the limited numbers, the data presented here will hopefully provide incremental steps toward improved immunovirotherapy of pediatric brain tumors. Full article

Background: Patients with lung cancer experience higher rates of hospitalization due to their elevated mortality and associated comorbidities. Hospital admissions among oncology patients often indicate organ vulnerability and are linked to poor prognosis. This study aimed to assess the characteristics and potential prognostic factors of hospitalized lung cancer patients. Methods: We retrospectively analyzed 646 patients admitted from June 2021 to May 2022 to the Medical Oncology Service at La Paz University Hospital (Madrid, Spain). Results: During this period, 158 patients admitted had lung cancer (24.5%). The median overall survival since admission (mOSSA) was 3.3 months (95%CI: 1.86–7.74). In the univariate analysis, poorer mOSSA was associated with admission for tumor-related causes (1.33 vs. 7.30 months, p < 0.001), ECOG ≥ 2 (2.43 vs. 8.50 months, p < 0.001), NLR ≥ 6 (1.87 vs. 7.40 months), PNI ≤ 40 (1.67 vs. 4.97 months), and LDH ≥ 210 (2.27 vs. 7.87 months, p = 0.044). In the multivariate analysis, independent prognostic factors included admission for tumor-related causes (p = 0.032, aHR 1.81, 95%CI: 1.05–3.11) and ECOG ≥ 2 (p = 0.041, aHR 1.80, 95%CI: 1.03–3.16). Conclusions: Hospital admission for lung cancer is a poor prognostic event, particularly when associated with tumor-related causes or a decline in performance status. Full article