Oncological Treatment Research Articles

Is Serum Ferritin a Predictor of Blood Transfusions Outcome and Survival in Childhood Lymphomas and Solid Tumors?

Packed red blood cell (PRBC) transfusions are an important part of supportive treatment in oncology; however, when used frequently, they can be a result of transfusion-related iron overload. The aim of the study was to evaluate the role of ferritin as a non-specific marker of neoplastic growth and transfusion-related iron overload in children with lymphomas and solid tumors. We performed a longitudinal analysis of PRBC transfusions and changes in ferritin concentrations during oncological treatment of 88 children with lymphomas and solid tumors. A ferritin concentration above 500 ng/mL was diagnosed in 14.77% of patients at the moment of admission and 18.18% at the end of treatment. No differences were shown in serum ferritin in the context of tumor type-, sex-, and transfusion-related parameters. Those above the age of 10 demonstrated higher ferritin concentrations compared to subjects younger than 5 years of age. In addition, those over than 10 years old or above 30 kg in weight showed a tendency for better survival. All tested patients demonstrated highly significant correlations between ferritin at the 15th month of treatment or after therapy discontinuation and transfusion-related parameters. Interestingly, ferritin levels were found to lower back to the values before therapy shortly after its discontinuation. Transfusion parameters and ferritin levels had no influence on the survival of the studied cancer patients.

Diabetic Ketoacidosis as a Debut and Immune-Mediated Complication Caused by Pembrolizumab: Case Report

Background/Objectives: Diabetic ketoacidosis (DKA) is an acute and potentially life-threatening complication characterized by the accumulation of ketone bodies in the blood, primarily occurring in patients with type 1 diabetes and occasionally in those with type 2 diabetes under certain conditions. DKA presents with symptoms such as polyuria, polydipsia, polyphagia, and, in severe cases, mental status changes. Identifying the triggering factor is crucial to prevent complications and effectively manage this medical emergency. Methods: This report describes the case of a 58-year-old male patient with stage IIIb nodular melanoma, diagnosed in November 2022. Results: After receiving five cycles of pembrolizumab, the patient developed de novo DKA, presenting with blurred vision, asthenia, adynamia, polyuria, and polydipsia. He was admitted to the emergency department with a blood glucose level of 764 mg/dL, confirming hyperglycemia and metabolic acidosis. He was transferred to the intensive care unit for fluid resuscitation and insulin infusion. After adequate clinical evolution and meeting the criteria for DKA resolution, possible autoimmune endocrinopathies secondary to immunotherapy were considered. Due to this complication, the oncological treatment was changed. Finally, the patient was discharged with the need to continue insulin therapy and oral hypoglycemic agents, along with thyroid hormone supplementation. Conclusions: The novelty of this case lies in the presentation of DKA as an immune-mediated complication induced by pembrolizumab, highlighting the importance of closely monitoring patients receiving immune checkpoint inhibitors to detect and manage emerging autoimmune endocrinopathies. It is essential to adjust oncological treatment according to the patient’s response and promptly manage autoimmune endocrinopathies to improve clinical outcomes and the patient’s quality of life.

A real‑world study of clinical characteristics, treatment sequence and outcomes of patients with non-small cell lung cancer and EGFR exon 20 insertion mutations.

EGFR exon 20 insertion (EGFRex20ins) mutations are found in up to 4% of all patients with non-small cell lung cancer (NSCLC). These patients are often insensitive to EGFR-tyrosine kinase inhibitors (TKIs) and have worse prognosis than patients with more common EGFR mutations. In this multicenter, retrospective, real-world study, we sought to determine whether the administration of recently approved treatments that specifically target EGFRex20ins mutations could significantly improve outcomes in this patient population. We evaluated the clinical features of 41 patients diagnosed with NSCLC and EGFRex20ins mutations, their evolution, and response to treatments received across 7 hospitals in the Valencian Community, Spain, between 31st December 2012 and 31st December 2022. 32 patients (72%) developed metastatic disease, and 29 (71%) of them received oncological treatment. We found that administering a targeted therapy against EGFRex20ins mutations (amivantamab, mobocertinib and/or sunvozertinib) at some point during the course of treatment, significantly increased the median OS of metastatic patients from 8months (95% CI 0-21.7) to 30months (95% CI 11.1-48.8; Hazard ratio = 0.297, p = 0.02). Our findings contribute to the evolving standard of care for this specific population and highlight the clinical benefits of targeted cancer therapies.

Primitive Resectable Small Bowel Cancer Clinical–Pathological Analysis: A 10-Year Retrospective Study in a General Surgery Unit

Introduction: Small bowel cancer is very rare; although the incidence of adenocarcinoma and other anatomopathological forms has increased recently, the diagnosis and treatment of this disease are still debatable because of the clinical heterogeneity and the absence of studies including a large number of patients. Materials and Methods: We performed a retrospective study over 10 years in which we analyzed the clinical, imaging, and anatomopathological data of 46 patients hospitalized in a surgery clinic and diagnosed with small bowel cancer (duodenum, jejunum, and ileum). Results: After clinical assessment of these patients, including complications (occlusion, bleeding, and perforation), the CT scan established the diagnosis in over 90% of the cases of the complicated form of the disease. Surgery has a curative role in localized cancers; tumor location, local invasion, the presence of locoregional lymph nodes, and the number of multiple tumors influence the type of surgery. The conventional pathological exam was completed via immunohistochemical staining. Adjuvant oncological treatment was performed after surgery (according to the guidelines); in patients with exceptional histopathological forms, the therapy was personalized. Conclusions: Most small bowel cancers were diagnosed with complications (occlusion and bleeding); the tumor type, location, and presence of multiple bowel cancers significantly influenced its management. Independently of the surgical resection (R0/R1 or R2), the prognosis of the disease depends on the tumor aggressivity, location (single/multiple), and locoregional node invasion.

Patients' knowledge about renal secondary effects of anti-tumoral drugs and renal protection measures.

Onco-nephrology is an emerging subspecialty aiming to better understand and prevent renal events in cancer patients. We assessed patients' knowledge about (1) oncological/hematological treatments induced renal toxicity and (2) kidney protective measures. Adult patients receiving systemic anti-tumor treatments in multiple day hospital units in France answered a self-administered questionnaire about their knowledge and expectations related to treatment-associated renal toxicity. In total, 621 questionnaires were collected in 8 units from November 2021 to January 2022. Among respondents, 84.5% were treated for a solid tumor. Overall, 34.3% (n = 208) patients reported they had some knowledge about potential renal adverse events related to their anticancer treatment, and 38.5% (n = 234) about kidney protection measures. Their referring oncologist or hematologist represented the commonest source of knowledge (67.8%). Sufficient hydration was cited as a kidney protection measure by 93.2% (n = 218) of patients declaring some knowledge about renal toxicity; prevention of nausea/vomiting by 52.6% (n = 123). Consumption of still and alkaline water was chosen by respectively 64.4% (n = 400) and 16.8% (n = 104) of participants to correct dehydration. A majority of patients expressed strong interest for receiving more information about renal toxicity and prevention: median Likert scale score was 10/10 (Q1-Q3, 5-10), with online resources mentioned as the most desired source of information. One-third of patients declared they had some knowledge about potential renal toxicity of their oncologic treatment and the ways to prevent them, especially regarding hydration. However, a majority expressed interest for dedicated information, which conducted to the elaboration of free online educational sheets for patients.

Atypical Presentation of Rapidly Progressive Cutaneous Metastases of Clear Cell Renal Carcinoma: A Case Report

Cutaneous metastases from clear cell renal carcinoma (ccRC) are uncommon and often indicate a poor prognosis. These metastases typically occur on the scalp, face, and trunk, and they can be difficult to diagnose due to their resemblance to benign dermatological tumors. We report the case of a 56-year-old patient with a history of ccRC (TNM stage 4) who was referred to our dermatology department with two rapidly enlarging, painful lesions on the left jawline and scalp, which had developed one month and one week earlier, respectively. On examination, the lesions appeared as well-defined, round to oval plaques with a central ulceration and a peripheral red rim, suggestive of an inflammatory appearance. Dermoscopic examination revealed a structureless pink to orange pattern, atypical central vessels, and irregular linear vessels in a corona-like arrangement. Despite the patient’s stable oncological treatment for six months, pain management had recently included paracetamol, tramadol, and NSAIDs. The primary presumptive diagnosis was of cutaneous metastasis, considering the patient’s history of metastatic ccRC. However, given the recent initiation of new pharmacological agents, the rapid progression of the cutaneous lesions, and their clinical presentation, alternative differential diagnoses were considered, including drug-induced reactions such as erythema multiforme or fixed drug eruption. A biopsy of the facial lesion revealed immunohistochemical positivity for CD10, CAIX, and PAX8, confirming the diagnosis of metastatic ccRC with sarcomatoid differentiation. Unfortunately, despite continued targeted therapies and palliative care, the patient’s condition deteriorated rapidly, leading to death two months later. This case highlights the potential for extremely rapidly evolving cutaneous metastases from ccRC and their capacity to occasionally mimic atypical drug eruptions. Additionally, it reaffirms the poor prognosis of such metastases, as evidenced by the patient’s death within two months.

Hemoglobin and hematocrit levels are positively correlated with phase angle in mixed cancer patients: an exploratory cross-sectional study.

The aim of this study is to verify the correlationbetween hemoglobin (Hb) and hematocrit (Ht) levels with phase angle (PhA) values in patients with cancer of the gastrointestinal tract and accessory digestive organs. A cross-sectional study was conducted with 82 patients (38 females/44 males) diagnosed with cancer of gastrointestinal tract and accessory organs of digestion. Hb (g/dL) and Ht (%) levels were assessed by the cyanomethemoglobin and microhematocrit methods, respectively. Body composition and PhA were evaluated by the bioelectrical impedance analysis (BIA). The cut-off point used to classify patients with low PhA was set < 4°. Fifty-five (67%) of patients had PhA ≥ 4° values. We observed that body weight, BMI, fat mass, % weight loss, Ht, and Hb were higher in the PhA ≥ 4° group than in the PhA < 4° group. In the regression analysis, we found a positive association between PhA, Ht, and Hb without and after adjustment for sex, age, BMI, and type of treatment. In mixed cancer patients, there was a positive correlation between blood-red cell markers and PhA. This may be evidence that we can use of hematological parameters to suggest changes in PhA values during oncological treatment.

Beyond hazard ratios: appropriate statistical methods for quantifying the clinical effectiveness of immune-oncology therapies – the example of the Netherlands

BackgroundThe Dutch Committee for the Evaluation of Oncological Drugs evaluates the effectiveness of new oncological treatments. The committee compares survival endpoints to the so-called PASKWIL-2023 criteria for palliative treatments, which define if treatment effects are considered clinically relevant. A positive recommendation depends on whether the median overall survival (OS) is below or above 12 months in the comparator arm. If the former applies, an OS benefit of at least 12 weeks, and a hazard ratio (HR) smaller than 0.7 are required. If the latter applies, an OS or progression free survival (PFS) benefit of at least 16 weeks, and an HR smaller than 0.7 are required. Nonetheless, the median survival time may not be reached and the proportional hazards (PH) assumption, quantified by the HR, is likely violated for immuno-oncology (IO) therapies, deeming these criteria inappropriate.MethodsWe conducted a systematic literature review to identify statistical methods used to represent the clinical effectiveness of IO therapies based on trial data. We searched MEDLINE and EMBASE databases from inception to August 31, 2022, limited to English papers. Methodological studies, randomized controlled trials, and discussion papers recognising key issues of survival data analysis of IO therapies were eligible for inclusion.ResultsA total of 1,035 unique references were identified. After full paper screening, 17 publications were included in the review. Additionally, 43 papers were identified through ‘snowballing’. We conclude that the current PASKWIL-2023 criteria are methodologically incorrect under non-PH. In that case, single summary statistics fail to capture the treatment effect and any measure should be interpreted in combination with the Kaplan-Meier curves. We recommend ’parameter-free’ measures, such as the difference in restricted mean survival time, avoiding assumptions on the underlying survival.ConclusionsThe HR is commonly used to assess treatment effectiveness, without investigating the validity of the PH assumption. This happens with the application of the PASKWIL-2023 criteria for palliative oncology treatments, which can only be valid under a PH setting. Under non-PH, alternative treatment effect measures are suggested. We propose a step-by-step approach supporting the choice of the most appropriate methods to quantify treatment effectiveness that can be used to redefine the PASKWIL-2023 criteria, or similar criteria in other clinical areas.

Status of and Challenges in Therapy of Mucinous Ovarian Cancer Associated with Pseudomyxoma Peritonei Syndrome: Review of Current Options and Future Treatment Trends

Objective: Pseudomyxoma peritonei (PP) is a rare condition, and differentiating between primary and secondary ovarian causes is crucial for determining the appropriate oncological therapy. Given the resistance of ovarian mucinous carcinoma to standard platinum-based chemotherapy, the objective of this review is to present the current therapeutic approaches and summarize the emerging trends in the treatment of this disease. Methods: The authors conducted an exhaustive evaluation of studies published over a 14-year period (June 2010–May 2024) concerning pseudomyxoma peritonei, mucinous ovarian carcinoma, ovarian causes of PP, and ovarian cancer using the following databases: PubMed, Scopus, and Science Direct. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The results were organized into seven subchapters and analyzed. Results: The analyzed studies present surgery followed by HIPEC as the current therapy with the best long-term survival results. However, the oncological treatment is unsatisfactory, and the choice of therapy depending on the primary origin of the tumor becomes particularly important. For the differential diagnosis between pseudomyxoma due to a gastrointestinal cause and that of ovarian origin, genetic analyses are recommended; these include the characteristics of the mucin present in the lesion, as the therapeutic response can have contradictory results depending on the primary origin of the tumor. Conclusions: Surgery followed by HIPEC remains the standard for resectable cases. However, oncological treatment has controversial results in the case of mucinous ovarian carcinoma compared to other types of ovarian cancer and to metastatic ovarian tumors associated with pseudomyxoma of the peritoneum. Based on the articles included in this review, it was found that the current trend is the study of mucin as a resistance factor against chemotherapy based on platinum products and the targeting of oncological therapy according to the tumor’s genetic characteristics.

Metastatic Adenoid Cystic Carcinoma at the Base of the Tongue and Duplicate Breast Cancer Diagnosed During Restaging.

Adenoid cystic carcinoma (AdCC) is a rare malignant tumor that primarily affects the salivary glands but can also occur in other organs. Low incidence and unpredictable clinical behavior make AdCC one of the most difficult head and neck tumors to treat. We present the case of a 54-year-old woman with AdCC localized at the base of the tongue, following radical surgical and oncological therapy. Due to advances in palliative oncological treatment, there is a more than five-year survival period before the progression of metastatic disease. Considering the rare occurrence of this disease, a literature search was also conducted, and therapy options are discussed. Ensuring a sufficient extent of the surgical procedure is still a challenge, and most specialists agree that subsequent postoperative radiotherapy reduces the risk of local recurrence. The effective dose of radiotherapy to the area of the primary tumor and lymph nodes is not clearly defined. The distinct biological behavior of AdCC results in varying sensitivity to chemotherapy or radiotherapy compared to treatments commonly used for head and neck squamous cell carcinomas. Treatment recommendations for these rarer tumors are based mainly on case reports and small clinical trials. The acquired therapeutic experience can contribute to prolonging the survival period of patients and improving their prognosis and quality of life.

Adverse Myocardial and vascular side effects of Immune Checkpoint Inhibitors: a prospective multimodal cardiovascular assessment (AMICI study)

Abstract Background Immune checkpoint inhibitors (ICIs) are transformative treatments in oncology, yet they are also associated with a range of cardiovascular (CV) events. Purpose To identify the incidence of CV events (including subclinical) in patients receiving ICIs for solid cancer, either alone or in association with other cancer therapies (e.g., chemotherapies, target therapies). Objectives and methods The Adverse Myocardial and vascular side effects of Immune Checkpoint Inhibitors(AMICI) study prospectively assessed the incidence of CV changes by means of a thorough multimodal assessment. This included repeated CV imaging (transthoracic echocardiograms (TTE), cardiac magnetic resonance imaging (CMR)), serum biomarkers (troponin, brain natriuretic peptides in a single laboratory), and ambulatory ECG monitoring, before and during (at 6 weeks and at 6 months) ICI therapy (Figure). Cardiovascular events included myocarditis, pericarditis, acute coronary syndrome, heart failure (HF), high degree conduction abnormalities (defined as new grade 2 or 3 atrioventricular block) or sustained ventricular arrhythmias (defined as 3 or more ventricular beats at a rate ≥ 120/min), CV death as a composite endpoint, validated by an independent expert panel Results Out of 130 solid cancer patients considered for ICI therapy, 49 patients (38 (77.6%) male; mean age 64.3 (­SD 11.0) years old) were included (June 2020 -December 2021). 22 (55.1%) suffered from kidney or bladder cancer; 7 (14.3%) had CV disease prior to cancer diagnosis; 4 (8.2%) received PD1 and CTLA4 inhibitors. Early CV events were observed in 9 (18.4%) patients at mean 40.1 (SD 5.9) days, with heart failure (HF) in 5 (10.2%), ventricular arrhythmias or new conduction disorders in 4 (8.2%) patients. History of AF (HR 4.49 (CI 1.11-18.14), P=0.035) predicted early CV events at 6 weeks (Table). At 6 months follow-up, 18 CV events were observed in 15/49 (31%) patients, with 6 (12.2%) HF events, 5 (10.2%) significant ventricular arrhythmias or conduction disorders and 4 (8.2%) AF. There was a significant decline in LVEF (P&amp;lt;0.001) in patients even in the absence of CV event (P=0.003) or HF (P=0.003). Higher creatinine at inclusion (HR 0.99 [0.98-1.00], P=0.006) predicted HF. Conclusions Cardiovascular complications arising during cancer treatment with ICIs are primarily due to the exacerbation of pre-existing HF or the onset of non-inflammatory heart rhythm disorders. The majority of these CV changes manifest shortly after starting ICIs and do not need hospital admission. Our results suggest that more close follow-up may be needed in patients with underlying CV conditions when starting ICI therapy, by means of CMR and ambulatory ECG holter monitoring.

Cardiovascular outcomes in acute coronary syndrome patients with cancer: a statewide population-linkage study

Abstract Background Advances in oncology treatment have led to an increase in the number of cancer survivors. As a result, the number of acute coronary syndrome (ACS) patients with cancer is increasing and the outcomes of these patients are not well described. Purpose This study aimed to examine revascularisation strategies and all cause and cardiovascular death in ACS patients with and without cancer. Methods Hospitalised patients in New South Wales, Australia, from July 2006 to December 2020 with a primary diagnosis of ACS were identified from the statewide Admitted Patient Data Collection database. Patients were stratified into those with or without a history of cancer (non-melanoma skin cancers excluded). Propensity scoring matching (PSM) for the variables of age, gender and cardiovascular risk factors was performed with each cancer patient matched to two non-cancer patients. Cox proportional hazards regression model was used to evaluate the hazard ratios of all-cause mortality between individuals with a history of cancer in the 5 years preceding their hospital admission, and those without. Additionally, Fine-Gray competing risk analysis was performed for cardiovascular death with non-cardiovascular mortality as the competing event. Results During the study period, 193,848 patients were admitted with ACS. 12,543 patients had a history of cancer and were PSM to 25,085 patients without cancer. The median age was 75 (Q1-Q3 67-82) years with 69% male and hypertension the most prevalent risk factor (55%) (Table 1). ACS patients with cancer had clinically comparable, rates of percutaneous revascularisation (36 vs 37%, p=0.07) and coronary artery bypass grafting (11 vs 13%, p&amp;lt;0.001) with ACS patients without cancer. During a median follow up of 8.6 (95% CI 8.4-8.8) years, ACS patients with a history of cancer had a significant higher risk of all cause death (HR 1.42 95% CI [1.38-1.46]) and cardiovascular death (SHR 1.14 [1.11-1.18]). The cumulative incidence function demonstrated cardiovascular death in those with a cancer history occurred in 20% by approximately 1.4 years follow up compared to 2.5 years in those without cancer (Figure 1). Conclusion ACS patients with cancer have a higher risk of all cause death and cardiovascular death compared to those without a history of cancer with clinically comparably revascularisation rates. Further studies to determine the cause of increased cardiovascular death in ACS patients with cancer are required.Figure 1

Spontaneous recovery of postsurgical progressive cervical spine kyphosis following intramedullary spinal cord tumor resection in a 4-year-old boy: illustrative case.

Postsurgical kyphosis is relatively common in children who have undergone resection of intramedullary spinal cord tumors. Progressive kyphosis almost always requires instrumentation and fusion surgery, which can delay or interfere with adjuvant oncological treatments and can deleteriously impact the long-term performance status of the patient. Here, the authors report a case of near-complete spontaneous recovery (i.e., without spinal fusion surgery) of postsurgical progressive cervical spine kyphosis following intramedullary spinal cord tumor resection and discuss the potential factors that may have contributed to this positive outcome. This case serves as a reminder that spontaneous recovery from postsurgical progressive cervical spine kyphosis can occur and that some patients (i.e., those without neurological deficits) can be monitored closely, with a watch-and-wait approach, before subjecting them to additional surgical risks, delays in other treatments, and potential morbidity. https://thejns.org/doi/10.3171/CASE24187.

Promise and challenges of traditional Chinese medicine, specifically Calculus bovis, in liver cancer treatment

Liver cancer, one of the most common malignancies worldwide, ranks sixth in incidence and third in mortality. Liver cancer treatment options are diverse, including surgical resection, liver transplantation, percutaneous ablation, transarterial chemoembolization, radiotherapy, chemotherapy, targeted therapy, immunotherapy, and traditional Chinese medicine (TCM). A multidisciplinary team (MDT) is essential to customize treatment plans based on tumor staging, liver function, and performance status (PS), ensuring individualized patient care. Treatment decisions require a MDT to tailor strategies based on tumor staging, liver function, and PS, ensuring personalized care. The approval of new first-line and second-line drugs and the establishment of standard treatments based on immune checkpoint inhibitors have significantly expanded treatment options for advanced liver cancer, improving overall prognosis. However, many patients do not respond effectively to these treatments and ultimately succumb to the disease. Modern oncology treatments, while extending patient survival, often come with severe side effects, resistance, and damage to the body, negatively impacting quality of life. Huang et al 's study published at World Journal of Gastroenterology rigorously validates the anticancer properties of Calculus bovis , enhancing our understanding of TCM and contributing to new liver cancer treatment strategies. For over 5000 years, TCM has been used in East Asian countries like China to treat various diseases, including liver conditions. Analysis of real-world clinical data suggests that for patients with advanced-stage tumors lacking effective treatments, integrated TCM therapies could provide significant breakthroughs.

Oncogenic Alterations, Race, and Survival in US Veterans with Metastatic Prostate Cancer Undergoing Somatic Tumor Next Generation Sequencing.

National guidelines recommend next generation sequencing (NGS) of tumors in patients diagnosed with metastatic prostate cancer (mPCa) to identify potential actionable alterations. We sought to describe the spectrum and frequency of alterations in PCa-related genes and pathways, as well as associations with self-identified race/ethnicity, and overall survival in US Veterans. This retrospective cohort study included Non-Hispanic Black (NHB) and Non-Hispanic white (NHW) Veterans with mPCa who obtained NGS through the Veterans Affairs National Precision Oncology Program. 45 genes in seven canonical or targetable mPCa pathways were evaluated in addition to TMB and MSI status. Multivariable logistic regression evaluated associations between race/ethnicity and genomic alteration frequencies. Cox proportional hazards models were used to determine associations between race/ethnicity, specific gene/pathway alteration, and overall survival. 5,015 Veterans with mPCa who had NGS conducted were included (1,784 NHB, 3,231 NHW). NHB Veterans were younger, had higher PSA at diagnosis, were less likely to report Agent Orange exposure, and resided in more deprived neighborhoods compared to NHW Veterans. Nine of the top ten most commonly altered genes were the same in NHB v NHW Veterans; however, the frequencies of alterations varied by race/ethnicity. NHB race/ethnicity was associated with higher odds of genomic alterations in SPOP (OR 1.7 [1.2-2.6]) as well as immunotherapy targets (OR 1.7 [1.1-2.7]) including MSI high status (OR 3.1 [1.1-9.4]). Furthermore, NHB race/ethnicity was significantly associated with lower odds of genomic alterations in the AKT/PI3K pathway (OR 0.6 [0.4-0.7]), AR axis (OR 0.7 [0.5-0.9]), and tumor suppressor genes (OR 0.7 [0.5-0.8]). Cox proportional hazards modelling stratified by race/ethnicity demonstrated alterations in tumor suppressor genes including TP53 were associated with shorter OS in both NHB (HR 1.54 [1.13-2.11] and NHW individuals (HR 1.52 [1.25-1.85]). In the equal access VA healthcare setting, Veterans undergoing NGS for mPCa exhibited differences in alteration frequencies in both actionable and non-actionable pathways that may be associated with survival. This analysis affirms the utility of genomic testing for identifying candidates irrespective of race/ethnicity for precision oncology treatments, which could contribute to equitable outcomes in patients with mPCa.

A Multiple Targeting Genome Editing System for Remodulation of Circulating Malignant Cells to Eliminate Cancer Immunosuppression and Restore Immune Responses.

Cancer immunotherapy, which aims to eliminate cancer immunosuppression and reactivate anticancer immunity, holds great promise in oncology treatments. However, it is challenging to accurately study the efficacy of immunotherapy based on human-derived cells through animal experiments due to xenogeneic immune rejection. Herein, a personalized and precise strategy to evaluate the effectiveness of immunotherapy using the blood samples of cancer patients is presented. Through the utilization of multiple cancer-targeting delivery system decorated with the epidermal growth factor receptor (EGFR)-specific aptamer CL4 and the AXL-specific aptamer GL21.T to achieve superior efficiency in delivering the genome editing plasmid for MUC1 knockout, effective modulation on the behavior of circulating malignant cells (CMCs) is realized. After genome editing, both mucin 1 (MUC1) and programmed death-ligand 1 (PD-L1) are significantly downregulated in CMCs. The elimination of immunosuppression results in markedly enhanced secretion of pro-inflammatory anticancer cytokines encompassing interleukins 2, 12, and 15 and interferon-γ by immune cells. The study not only provides a strategy to overcome immunosuppression but also yields critical insights for personalized immunotherapy approaches.

A causal network model to estimate the cardiotoxic effect of oncological treatments in young breast cancer survivors

A causal network model to estimate the cardiotoxic effect of oncological treatments in young breast cancer survivors

Towards verifiable cancer digital twins: tissue level modeling protocol for precision medicine.

Cancer exhibits substantial heterogeneity, manifesting as distinct morphological and molecular variations across tumors, which frequently undermines the efficacy of conventional oncological treatments. Developments in multiomics and sequencing technologies have paved the way for unraveling this heterogeneity. Nevertheless, the complexity of the data gathered from these methods cannot be fully interpreted through multimodal data analysis alone. Mathematical modeling plays a crucial role in delineating the underlying mechanisms to explain sources of heterogeneity using patient-specific data. Intra-tumoral diversity necessitates the development of precision oncology therapies utilizing multiphysics, multiscale mathematical models for cancer. This review discusses recent advancements in computational methodologies for precision oncology, highlighting the potential of cancer digital twins to enhance patient-specific decision-making in clinical settings. We review computational efforts in building patient-informed cellular and tissue-level models for cancer and propose a computational framework that utilizes agent-based modeling as an effective conduit to integrate cancer systems models that encode signaling at the cellular scale with digital twin models that predict tissue-level response in a tumor microenvironment customized to patient information. Furthermore, we discuss machine learning approaches to building surrogates for these complex mathematical models. These surrogates can potentially be used to conduct sensitivity analysis, verification, validation, and uncertainty quantification, which is especially important for tumor studies due to their dynamic nature.

Cancer Therapy-Induced Encephalitis

Encephalitis associated with cancer therapies is a rare but serious complication that can significantly impact patients’ quality of life and it requires prompt identification and management. Over the past two decades, immunotherapy—particularly immune checkpoint inhibitors—has become a cornerstone of cancer treatment, with up to half of metastatic cancer patients in economically developed countries now receiving these therapies. The widespread adoption of immunotherapy has led to improved survival rates and long-term remissions, even in patients with advanced metastatic disease. However, as immune modulators, these therapies can trigger a range of immune-related adverse events, including a variety of novel neurological toxicities. Among these, encephalitis is of particular concern due to its potential severity, which can compromise treatment outcomes. This review aims to provide a comprehensive overview of the literature on this condition, highlighting optimal diagnostic strategies and management approaches to mitigate the risk of significant morbidity, while also comparing encephalitis induced by immunotherapy with that caused by traditional chemotherapies and targeted oncologic treatments.

Treatment sequencing in gastroenteropancreatic neuroendocrine tumors

SummaryThe oncological treatment of neuroendocrine tumors (NET) has improved significantly in the last few years. Several informative clinical studies on NET have been conducted recently and updated NET guidelines have been published by the European Neuroendocrine Tumor Society (ENETS) in 2023 and 2024. With the growing number of positive phase III trials in NET, the main difficulty today is selecting the most appropriate treatment for a patient at the right time. The purpose of this short review is to delineate the main concepts and important changes in the therapy sequences for gastroenteropancreatic NET (gepNET) outlined in current European guidelines. In clinical practice, more individualized treatment decisions are often required that go beyond these general recommendations.