Search Results (125)

Background/Objective: Candidemia is a serious complication following intensive chemotherapy and is associated with high mortality in pediatric patients. This study aimed to identify the factors associated with 28-day mortality in pediatric patients with candidemia. Methods: We retrospectively analyzed 63 pediatric patients diagnosed with acute leukemia and candidemia following intensive chemotherapy. Clinical characteristics, laboratory findings, and epidemiological data were collected. Antifungal susceptibility data were available for 60 patients. Kaplan–Meier survival analysis was used to estimate the 28-day mortality rate, and Cox regression was performed to identify prognostic factors. Results: The 28-day mortality rate among the 63 patients (57.1% male, median age 9.74 years) was 36.5%. Candida tropicalis was the predominant species (96.8%). Antifungal susceptibility rates were 100% for amphotericin B and caspofungin and 22.2% for fluconazole. The factors independently associated with reduced 28-day mortality were an absolute lymphocyte count (ALC) ≥ 0.2 G/L at the time of candidemia diagnosis (5.3% vs. 50% mortality; hazard ratio [HR] = 0.08; 95% confidence interval [CI], 0.01–0.61), the use of antifungal prophylaxis (AFP) (26.3% vs. 52%; HR 0.31; 95% CI, 0.13–0.74), and granulocyte transfusion (GTX) combined with granulocyte colony-stimulating factor (G-CSF) (20% vs. 47.4%; HR = 0.31; 95% CI, 0.11–0.85). Conclusions: Our findings suggest that an ALC ≥ 0.2 G/L, AFP, and the administration of a GTX combined with G-CSF may be considered favorable prognostic factors. Full article

Anal cancer is a rare malignancy with rising incidence. Definitive treatment with radiation and concurrent chemotherapy represent the standard of care for patients with non-metastatic disease. Advances in radiation delivery through the use of intensity-modulated radiotherapy have significantly reduced the toxic effects of treatment. Adaptive radiotherapy (ART) has emerged as a strategy to further enhance treatment precision and individualize therapy in response to patient-specific changes during the course of chemoradiotherapy. The rationale for ART in anal cancer stems from the recognition that significant anatomic and tumor changes can occur throughout the 5–6-week treatment course, including tumor shrinkage, weight loss, and variable rectal/bladder filling. This review discusses the role of ART in contemporary anal cancer management. We overview the principles of ART, delineate the technical workflows (including both computed tomography (CT) and MR-guided approaches), and examine how adaptive techniques are applied in treatment planning and delivery. We also review the clinical evidence to date, including dosimetric studies and emerging clinical trial data on ART in anal cancer, particularly its impact on outcomes and toxicity. Full article

Despite advances in surgery, chemotherapy, and radiation treatments for pancreatic ductal adenocarcinoma (PDAC), 5-year survival rates remain at nearly 11%. Cholangiocarcinoma, while not as severe, also possesses similar survival rates. Fewer than 20% of patients are surgical candidates at time of diagnosis; therefore, it is imperative that alternative therapies are effective for non-surgical patients. There are several thermal ablative techniques, including radiofrequency ablation (RFA), high-intensity focused ultrasound (HIFU), microwave ablation (MWA), alcohol ablation, stereotactic body radiotherapy (SBRT), cryoablation, irreversible electroporation (IRE), biliary intraluminal brachytherapy, and biliary photodynamic therapy (PDT). Emerging literature in animal models and human patients has demonstrated that endoscopic ultrasound (EUS)-guided RFA (EUS-RFA) prevents tumor progression through coagulative necrosis, protein denaturation, and activation of anticancer immunity in local and distant tumor tissue (abscopal effect). RFA treatment has been shown to not only reduce tumor-associated immunosuppressive cells but also increase functional T cells in distant tumor cells not treated with RFA. The remarkable ability to reduce tumor progression and promote tumor microenvironment (TME) remodeling makes RFA a very promising non-surgical therapy technique that has the potential to reduce mortality in this patient population. EUS-RFA offers superior precision and safety compared to other ablation techniques for pancreatic and biliary cancers, due to real-time imaging capabilities and minimally invasive nature. Future research should focus on optimizing RFA protocols, exploring combination therapies with chemotherapy or immunotherapy, and expanding its use in patients with metastatic disease. This review article will explore the current data and underlying pathophysiology of EUS-RFA while also highlighting the role of ablative therapies as a whole in immune activation response. Full article

Background/Objectives: The incidence of cardiac morbimortality in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) is unknown. Methods: We analyze the characteristics, incidence, risk factors, and outcomes of cardiac events in AML patients treated for second-line (2L) or third-line (3L) episodes. Results: Among 327 2L AML patients (median age 62 years old), 135 experienced cardiac events, with an incidence of 38.6% non-fatal and 1.3% fatal events at 6 months. The grade 1–2 incidence was 16.8%, and the grade 3–4 incidence was 23.5% at 6 months. Overall, 207 cardiac events occurred in the 2L cohort, the most frequent being hypertension (n = 45), bradycardia (n = 39), QTc prolongation (n = 35), heart failure (n = 33), syncope/presyncope (n = 22), arrhythmia (n = 18), and myocardial ischemia (n = 8). Median OS in the 2L cohort was 9.4 months, 21.4 months in patients with grade 1–2, 8.8 months in patients without a cardiac event, 7.6 months in grade 3–4 patients, and 2.1 months with in 5 patients (p = 0.0035). The multivariate analysis showed prior cardiologic antecedents (p = 0.013), intensive 2L chemotherapy (p = 0.01), and inclusion in a 2L clinical trial (p < 0.001) as independent risk factors for non-fatal cardiac events. Among 189 patients of the 3L cohort, the incidence of non-fatal and fatal cardiac events was 49.2% and 0% at 6 months, respectively. Non-fatal cardiac events were more frequent in patients with prior cardiac antecedents (p = 0.004). Conclusions: In summary, cardiotoxicity is a frequent and challenging complication in R/R AML patients. We identified the risk factors that could be relevant to implementing risk-adapted management guidelines, aiming to reduce morbi-mortality in this difficult-to-treat setting. Full article

Background/Objectives: Doxorubicin (DOX), a widely used anthracycline chemotherapeutic agent, is recognized for its efficacy in treating various malignancies. However, its clinical application is critically limited due to dose-dependent cardiotoxicity, predominantly induced by oxidative stress and compromised antioxidant defenses. Photobiomodulation (PBM), a non-invasive intervention that utilizes low-intensity light, has emerged as a promising therapeutic modality in regenerative medicine, demonstrating benefits such as enhanced tissue repair, reduced inflammation, and protection against oxidative damage. This investigation sought to evaluate the cardioprotective effects of PBM preconditioning in human-induced pluripotent stem cell-derived ventricular cardiomyocytes (hiPSC-vCMs) subjected to DOX-induced toxicity. Methods: Human iPSC-vCMs were allocated into three experimental groups: control cells (untreated), DOX-treated cells (exposed to 2 μM DOX for 24 h), and PBM+DOX-treated cells (preconditioned with PBM, utilizing 660 nm ±10 nm LED light at an intensity of 10 mW/cm² for 500 s, delivering an energy dose of 5 J/cm², followed by DOX exposure). Cell viability assessments were conducted in conjunction with evaluations of oxidative stress markers, including antioxidant enzyme activities and malondialdehyde (MDA) levels. Furthermore, transcriptional profiling of 40 genes implicated in cardiac dysfunction was performed using TaqMan quantitative polymerase chain reaction (qPCR), complemented by analyses of protein expression for markers of cardiac stress, inflammation, and apoptosis. Results: Exposure to DOX markedly reduced the viability of hiPSC-vCMs. The cells exhibited significant alterations in the expression of 32 out of 40 genes (80%) after DOX exposure, reflecting the upregulation of markers associated with apoptosis, inflammation, and adverse cardiac remodeling. PBM preconditioning partially restored the cell viability, modulating the expression of 20 genes (50%), effectively counteracting a substantial proportion of the dysregulation induced by DOX. Notably, PBM enhanced the expression of genes responsible for antioxidant defense, augmented antioxidant enzyme activity, and reduced oxidative stress indicators such as MDA levels. Additional benefits included downregulating stress-related mRNA markers (HSP1A1 and TNC) and apoptotic markers (BAX and TP53). PBM also demonstrated gene reprogramming effects in ventricular cells, encompassing regulatory changes in NPPA, NPPB, and MYH6. PBM reduced the protein expression levels of IL-6, TNF, and apoptotic markers in alignment with their corresponding mRNA expression profiles. Notably, PBM preconditioning showed a diminished expression of BNP, emphasizing its positive impact on mitigating cardiac stress. Conclusions: This study demonstrates that PBM preconditioning is an effective strategy for reducing DOX-induced chemotherapy-related cardiotoxicity by enhancing cell viability and modulating signaling pathways associated with oxidative stress, as well as inflammatory and hypertrophic markers. Full article

Medulloblastoma represents a rare yet complex embryonal tumor of the posterior cranial fossa that, while predominantly affecting pediatric populations, occurs with increasing recognition among adolescents and young adults (AYAs, 15–39 years). The scarcity of medulloblastoma within this demographic creates substantial obstacles in diagnosis, treatment selection, and psychosocial management that differ markedly from established pediatric approaches. Emerging data reveal that AYA patients exhibit distinctive tumor biology, including altered molecular subgroup patterns, variable therapeutic responses, and unique survival trajectories when compared to younger patients. Current investigations examining autologous stem cell transplantation following intensive chemotherapy protocols in metastatic cases demonstrate encouraging preliminary results. Evidence increasingly supports adapting pediatric treatment paradigms for adult application, potentially improving therapeutic outcomes while reducing treatment burden. These cross-disciplinary approaches between pediatric and adult oncology demonstrate considerable promise for enhancing clinical results and minimizing therapy-associated morbidity, emphasizing the critical need for collaborative care models in managing this challenging malignancy across diverse age groups. Full article

Background: Primary cutaneous peripheral T-cell lymphoma, not otherwise specified (pcPTCL-NOS), is a rare and aggressive form of lymphoma. Its characteristics and treatment outcomes remain poorly understood. Methods: We identified 15 patients who were diagnosed with pcPTCL-NOS between January 2014 and August 2024 at Tianjin Medical University Cancer Institute and Hospital (TMUCIH) in this retrospective study. The clinical and immunophenotypic features, treatment regimens, and outcomes of these patients were investigated. Results: All patients (4 men, 11 women; median age 54 years) presented with skin lesions, including five stage T1, four stage T2 and six stage T3 lesions. pcPTCL-NOS manifests clinically either with solitary or disseminated rapidly growing nodules/tumors and papules and, less often, ulcers. The lesion sites in patients presenting with solitary/localized tumors (stage T1 and T2) were the head and limbs, and those in patients presenting with disseminated lesions (stage T3) were the trunk, head, and limbs. The CD4/CD8 immunophenotypic characteristics were as follows: CD4+/CD8− 53.33%; CD4+/CD8+ 26.67%; CD4−/CD8− 13.33%; and CD4−/CD8+ 6.67%. One patient had a T follicular helper (TFH) phenotype. Five patients had aberrant expression of the B-cell marker CD20 by tumor cells. All patients received CHOP or CHOP-like regimens as the initial treatment, with three patients undergoing complete lesion resection before chemotherapy, seven patients receiving treatment combined with chidamide (tucidinostat), two patients receiving treatment combined with brentuximab vedotin, two patients receiving treatment combined with mitoxantrone liposomes (Lipo-Mit), three patients receiving treatment combined with radiotherapy, and two patients receiving ASCT after the first-line treatment. The OS rates at 1 year, 2 years, and 3 years were 80%, 77.8%, and 77.8%, respectively; the PFS rates were 60%, 44.4%, and 33.3%, respectively. With a median follow-up of 40 months, the median PFS was 21 months, and the median OS was not reached. Univariate analyses revealed that patients with B symptoms and the CD4−/CD8− phenotype had inferior outcomes (p < 0.05). Age, sex, tumor stage, PIT score, Ki-67 index, elevated β2-MG levels, expression of CD20 or PD1, and treatment selection were not associated with the prognosis. A trend of a survival benefit in patients with solitary (T1) tumors compared with patients with disseminated (T2, T3) tumors was observed, suggesting that it is possible to reduce the intensity of treatment in patients with T1 tumors in the future. Conclusions: pcPTCL-NOS is an aggressive but poorly characterized lymphoma that may require early and active systemic treatment. However, for patients with T1 tumors, reducing the intensity of treatment with CHOP should be appropriately considered. Full article

Background: Acute myeloid leukemia (AML) primarily affects older adults and is associated with poor prognosis, particularly in patients aged ≥ 60 years with comorbidities and adverse disease characteristics. Standard intensive chemotherapy, such as the “7 + 3” regimen, has shown limited efficacy and substantial toxicity in this population, underscoring the need for alternative treatment strategies. In recent years, venetoclax-based regimens have emerged as an important option, demonstrating promising outcomes in elderly patients traditionally considered unfit for intensive therapy and, more recently, even in selected fit patients. Methods: This narrative review provides a comprehensive comparative analysis of intensive chemotherapy and venetoclax-based regimens in elderly AML patients. This review synthesizes evidence from prospective and retrospective clinical trials, with focuses on treatment efficacy, safety, and the ability to bridge patients to curative allogeneic hematopoietic stem cell transplantation (allo-HSCT). Results: Intensive chemotherapy has achieved complete remission (CR) rates of 40–60% in elderly AML patients, though the median overall survival (OS) rarely exceeds 12 months. Conversely, venetoclax combined with hypomethylating agents has recently demonstrated CR rates of up to 74%, with 83% of responders proceeding to allo-HSCT in selected studies. Venetoclax-based regimens have also been associated with improved tolerability and reduced treatment-related mortality. Discussion: This review highlights a paradigm shift in the management of AML in the elderly. While intensive chemotherapy remains a standard option for selected patients, the increasing use of venetoclax-based regimens represents a novel and effective strategy with the potential to overcome traditional limitations, especially in patients previously deemed ineligible for curative approaches. The high remission and transplantation rates observed with non-intensive therapies support their role not only as a palliative alternative but as a bridge to cure. Conclusions: Venetoclax-based regimens are reshaping the treatment landscape of AML in the elderly, offering high response rates and facilitating access to allo-HSCT. Further research is needed to optimize treatment sequencing, explore novel combinations, and reduce relapse rates after transplants, ultimately improving the long-term outcomes in this high-risk population. Full article

Cancer treatment has historically depended on conventional methods like chemotherapy, radiation, and surgery; however, these strategies frequently present considerable limitations, including toxicity, resistance, and negative impacts on healthy tissues. In addressing these challenges, drug-free cancer therapies have developed as viable alternatives, utilizing advanced physical and biological methods to specifically target tumor cells while reducing damage to normal tissues. This review examines several drug-free cancer treatment strategies, such as high-intensity focused energy beams, nanosecond pulsed electric fields, and photothermal therapy as well as the use of inorganic nanoparticles to promote selective apoptosis. We also investigate the significance of targeting the tumor microenvironment, precision medicine, and immunotherapy in the progression of personalized cancer therapies. Although these approaches demonstrate significant promise, challenges including scalability, safety, and regulatory obstacles must be resolved for clinical application. This paper presents an overview of current research in drug-free cancer therapies, emphasizing recent advancements, underlying scientific principles, and the steps required for clinical implementation. Full article

In-hospital patients who are in the gynecologic oncology setting often suffer from malnutrition, which is one of the primary problems, the rate of which reportedly ranges from 28% to 70%. Malnutrition is a significant risk factor for immunosuppression, negatively impacting immune response and postoperative recovery capacity. At the time of the surgeries, due to their wide scope and aggressive treatments such as chemotherapy and radiotherapy, the situation becomes more serious. Those micronutrients taking part in immunonutrition, namely, arginine, omega-3 fatty acids, nucleotides, and antioxidants, have the potential to prevent inflammation, protect against infections, and promote healing after the surgery. Research has shown that immunonutrition can lower the risk of postoperative infection, promote the normal healing of wounds, and reduce the hospital stays of patients, as well as support malnutrition status during chemotherapy. This review is based on a literature search conducted in Medline, Scopus, Clinicaltrials.gov, Cochrane CENTRAL, and Google Scholar, with the last search date being November 2024. Some studies. found that perioperative immunonutrition decreases wound infections and affects some immune indexes in gynecologic oncology patients positively. However, factors such as non-compliant patients, high costs, and non-standard formulations can deter its wider use. Patient adherence drops postoperatively mainly due to nausea and decreased appetite, whereas the cost of enriched formulations acts as an economic barrier. Postoperative compliance drops from ~78% prior to surgery to ~28% due to nausea, anorexia, and chemotherapy. Additionally, cost remains a constraining factor since special formulas are 2–4 times that of normal nutrition. While immunonutrition reduces hospital stay (by ~2–3 days) and infection rate (by 25–40%), access is hindered by prohibitive initial costs and lack of insurance coverage. Approaches such as subsidized schemes, enhanced palatability, and cost–benefit analyses are required to increase adoption. In addition, the lack of standardized protocols makes the clinical community hesitant to adopt this approach. Immunonutrition is, despite these problems, still hoped to be the new adjunct to gynecologic oncology patients. In future studies, it is imperative to pay attention to the best formulations that produce the best outcomes and evaluate and implement guidelines that are based on evidence. Together, with these improvements, immunonutrition could very well be an integral part of perioperative care thus completing the process by which patients in intense treatments are benefited not only via treatment but also via quality of life. Full article

Photodynamic therapy (PDT) is an innovative and non-invasive approach to treating apparent tumours with minimal toxicity. PDT has a long-standing application in antitumor treatment utilizing various photosensitizers (PSs) for different tumours. Historically, light has served as a therapeutic tool in many diseases. PDT involves a dual treatment process in which light energy and PSs are combined to ablate tumour cells following light activation. In general, PDT exhibits reduced side effects and toxicity compared to chemotherapy and radiotherapy, as it spares the extracellular matrix, facilitating excellent tissue healing and minimizing scarring. In addition, PSs can serve in diagnostic roles in tumour identification, termed photodynamic diagnosis (PDD). Advancements in flexible light sources that produce uniform illumination could significantly enhance the consistency of light delivery. This review outlines the clinical applications of OLEDs in PDT for cancer, addressing both diagnostic and therapeutic methods. Furthermore, we will explore various tumour cases using PDT with OLEDs. In particular, antimicrobial PDT targets antibiotic-resistant strains in diabetic foot ulcers, while metronomic PDT promotes cancer cell apoptosis through prolonged, low-intensity light exposure. Our emphasis is on PDT employing organic light-emitting diodes (OLEDs). Furthermore, the combination of PDT with NIR-OLEDs is examined for its potential to enhance tumour-targeting effectiveness, possibly exceeding the results of standalone treatments. Full article

Head and neck cancer (HNC) includes various malignancies and represents the seventh most common cancer worldwide. The early diagnosis of HNC results in a 70–90% five-year survival rate, which declines with locally advanced stages of disease. Current care employs a multimodal strategy encompassing surgery, radiation therapy (RT), chemotherapy, and immunotherapy, while treatment options vary according to the stage, tumor features, and patient characteristics. About 75% of patients with HNC will benefit from RT, either as a primary treatment or as adjuvant therapy following surgical resection. Technological improvements in RT, such as intensity-modulated RT (IMRT) and image-guided RT (IGRT), have enhanced tumor targeting and minimized adjacent healthy tissue irradiation while also expanding RT to the recurrent or metastatic setting. Innovative therapeutic strategies for HNC integrate RT with immunotherapy, gene therapy, molecular targeted therapy, photodynamic therapy, photothermal therapy, and nanoparticles (NPs), with the objective of optimizing tumor control while reducing damage to normal tissues. NPs are emerging as possible radiosensitizers in HNC treatment, enhancing the efficacy of RT, chemotherapy, and immunotherapy. In vivo and in vitro studies on the irradiation of tumors containing gold (Au), gadolinium (Gd), and hafnium oxide (HfO₂) NPs show promising results in enhancing tumor destruction and survival rates, indicating their potential for clinical application. Hyperthermia, investigated as an adjunct treatment, potentially improves outcomes when combined with RT or chemotherapy, with advancements in nanotechnology renewing interest in this approach in HNC. At present, NBTXR3 is the sole NP that is being investigated in clinical trials for the enhancement of HNC RT. Full article

Background: Recently proposed brain-tumor treatment strategies prioritize fast reduction of tumor cell population while often neglecting the radiation or chemotherapeutic drug dosage requirements to achieve it. Moreover, these techniques provide chemotherapy based treatment strategies, while ignoring the toxic side effects of the drugs employed by it. Methods: This study updates the recently proposed brain-tumor system dynamics by incorporating radiotherapy along with chemotherapy to simultaneously initiate both therapies for a more comprehensive and effective response against tumor proliferation. Afterwards, based on the upgraded system dynamics, this study proposes a novel multi-input sigmoid-based smooth synergetic nonlinear controller with the aim to reduce the dosage requirements of both therapies while keeping the overall system response robust and efficient. The novelty of this study lies in the combination of radiotherapy and chemotherapy inputs in a way that prioritizes patients health and well-being, while integrating advanced synergetic control technique with a sigmoid function based smoothing agent. Results: The proposed method reduced baseline radiation and chemo drug dosages by 57% and 33% respectively while effectively suppressing tumor growth and proliferation. Similarly, the proposed controller reduced the time required for complete tumor mitigation by 60% while reducing the radiation and chemotherapeutic drug intensity by 93.8% and 21.3% respectively. Conclusions: This study offers significant improvement in tumor treatment methodologies by providing a safer, less riskier brain-tumor treatment strategy that has promising potential to improve survival rates against this menacing health condition so that the affected patients may lead a healthier and better quality of life. Full article

Background/Objectives: The objective of our study was to evaluate the safety and efficacy of granulocyte colony-stimulating factor (G-CSF) as primary prophylaxis in adult patients with acute myeloid leukemia (AML) undergoing intensive chemotherapy. Methods: We retrospectively analyzed 112 AML patients treated with intensive chemotherapy at Fondazione Policlinico Tor Vergata in Rome between January 2014 and March 2024. Patients were divided into G-CSF and non-G-CSF (nG-CSF) groups. We assessed the incidence of neutropenia, its severity and duration; duration of hospitalization and its costs; incidence of febrile neutropenia (FN) and septic shock; duration of antibiotic therapy (ABT) and antifungal therapy (AFT); complete remission (CR) rates; measurable residual disease (MRD) status; relapse rates; and outcomes. Results: G-CSF administration significantly reduced the duration of neutropenia (median 14 vs. 18 days, p < 0.05) and length of hospitalization (median 28 vs. 35 days, p < 0.05), in both induction and consolidation therapy. There were no significant differences in CR rates (73% vs. 67%, p = 0.64), MRD negativity achievement (52% vs. 48%, p = 0.68), leukemia relapse rates (43% vs. 62%, p = 0.14), or overall survival (OS) (median 16.7 vs. 12.3 months, p = 0.3) between G-CSF and nG-CSF groups. Thanks to a shorter hospitalization, the use of G-CSF led to €300,000 in savings over the last 4 years. Conclusions: Our findings support the safety of G-CSF in AML patients, demonstrating no adverse impact on treatment response. G-CSF abbreviated the duration of neutropenia and hospitalization, highlighting its potential clinical and cost-effective role in AML treatment. Full article

Background: Intrahepatic cholangiocarcinoma (ICC), a malignancy originating from the epithelial cells of bile ducts, has shown a notable rise in its incidence over the years. It ranks as the second most frequent primary liver cancer after hepatocellular carcinoma. This study investigates how independent prognostic factors, specifically, age and tumor stage, interact to impact mortality in ICC patients. Furthermore, it examines the clinical features, survival rates, and prognostic indicators of ICC cases diagnosed between 2010 and 2017. Methods: Using data from 5083 patients obtained from the Surveillance, Epidemiology, and End Results (SEER) database, this study evaluated demographic and clinical factors alongside overall mortality (OM) and cancer-specific mortality (CSM). Variables achieving a p-value below 0.1 in univariate Cox regression analysis were incorporated into multivariate Cox regression models to identify independent prognostic factors. Hazard ratios (HRs) exceeding 1 were interpreted as markers of poor prognosis. Additionally, this study explored the interaction between age and tumor stage in shaping survival outcomes. Results: The multivariate Cox proportional hazards analysis indicated higher OM in males (HR = 1.19, 95% CI: 1.12–1.26, p < 0.01) and residents of metropolitan counties with populations exceeding 250,000 (HR = 1.15, 95% CI: 1.01–1.31, p < 0.05). Conversely, lower OM was observed in individuals aged 40–59 years (HR = 0.58, 95% CI: 0.38–0.89, p < 0.05), those aged 60–79 years (HR = 0.65, 95% CI: 0.43–0.98, p < 0.05), and patients who received radiation therapy (HR = 0.78, 95% CI: 0.72–0.85, p < 0.01), chemotherapy (HR = 0.54, 95% CI: 0.51–0.58, p < 0.01), or surgery (HR = 0.29, 95% CI: 0.26–0.31, p < 0.01). For CSM, males exhibited higher risks (HR = 1.17, 95% CI: 1.10–1.25, p < 0.01), as did individuals in metropolitan counties with populations over 250,000 (HR = 1.18, 95% CI: 1.03–1.35, p < 0.05). Reduced CSM was observed in patients aged 40–59 years (HR = 0.52, 95% CI: 0.34–0.79, p < 0.01), those aged 60–79 years (HR = 0.57, 95% CI: 0.38–0.86, p < 0.01), and those undergoing radiation therapy (HR = 0.76, 95% CI: 0.70–0.83, p < 0.01), chemotherapy (HR = 0.55, 95% CI: 0.51–0.59, p < 0.01), or surgery (HR = 0.27, 95% CI: 0.25–0.30, p < 0.01). When examining the interaction between age and tumor stage, higher OM was observed in patients aged 40–59 with tumors involving lymph nodes (HR = 1.26, 95% CI: 1.14–2.67, p < 0.05). Similarly, CSM was elevated in patients aged 40–59 with lymph node involvement alone (HR = 2.60, 95% CI: 1.26–5.36, p < 0.05) or with direct spread (HR = 2.81, 95% CI: 1.04–7.61, p < 0.05). Among those aged 60–79, higher CSM was noted in cases with lymph node involvement only (HR = 2.24, 95% CI: 1.11–4.50, p < 0.05) or lymph node involvement accompanied by direct extension (HR = 2.93, 95% CI: 1.10–7.82, p < 0.05). Conclusions: This retrospective analysis, utilizing data from the SEER database, provides new insights into mortality patterns in intrahepatic cholangiocarcinoma (ICC). This study identifies a significant interplay between two key prognostic factors, emphasizing their collective role in influencing mortality outcomes. Despite the predominance of advanced-stage diagnoses, our analysis underscores the substantial survival benefits associated with treatment interventions, with surgical procedures demonstrating the most pronounced impact. These findings highlight the importance of recognizing patients who may benefit from timely and intensive therapeutic strategies. Furthermore, the results underscore the need for future prospective randomized studies to deepen our understanding of these interactions in ICC, particularly as advancements in precision oncology continue to refine patient care. Full article