Search Results (50,359)

Background and Objectives: Cornerstone therapies for metastatic prostate cancer include androgen deprivation and androgen receptor pathway inhibition, but cognitive impairment is a recognized, life-altering potential adverse effect of this treatment. Abiraterone acetate (AA), an androgen receptor pathway and CYP17A1 inhibitor, suppresses androgen synthesis and may contribute to cognitive changes. This cell culture-based study uses the BE(2)M17 human male neuroblastoma model to investigate AA-induced alterations in gene and protein expression that may underlie cognitive decline, laying the foundation for a mechanistic investigation aimed at identifying molecular targets to mitigate cognitive impairment in men with prostate cancer receiving androgen-directed therapies. Materials and Methods: BE(2)M17 cells were pretreated for 12 h with dihydrotestosterone (DHT; 5 nM) or vehicle control, then exposed to AA (0, 5, 10 µM, 24 h). RNA and protein were analyzed by qRT-PCR and Western blot for markers of amyloid processing, neuronal health, and mitochondrial function. Results: AA significantly altered multiple neurobiological markers. BACE1 mRNA increased in DHT + 10 µM AA compared to control and DHT alone (p = 0.0416 and p = 0.0118). However, BACE1 protein decreased in 10 µM AA + DHT versus DHT alone (p = 0.0132). Immunoblot revealed reduced amyloid precursor protein (APP) in 10 µM AA versus control (p = 0.0057) and 10 µM versus 5 µM (p = 0.0263). APP was reduced in 10 µM AA + DHT versus control (p = 0.0015) and versus DHT alone (p = 0.0467). LRP1 and BDNF were significantly reduced with 10 µM AA versus 5 µM AA (p = 0.0092 and p = 0.0081), while synaptophysin decreased in 10 µM AA + DHT versus DHT alone (p = 0.0049). BDNF also declined in 10 µM AA + DHT compared to 5 µM AA + DHT (p = 0.0301). PGC1α mRNA increased in AA + DHT versus DHT alone (p = 0.0332). MitoTracker analysis showed reduced fluorescence with 5 µM AA alone but increased fluorescence with 5 µM AA + DHT relative to control and DHT (p = 0.0019; p < 0.0001), while 10 µM AA + DHT reduced fluorescence compared to 5 µM AA + DHT (p = 0.0003). Conclusions: AA, alone or combined with DHT, disrupts key pathways involved in neuronal health, amyloid processing, and mitochondrial function. These findings suggest a potential mechanistic link between AA treatment and cognitive impairment. Full article

Boron neutron capture therapy (BNCT) is a radiotherapeutic modality that enables tumor-targeted cell killing. The nuclear capture reaction between boron-10 (¹⁰B) and low-energy thermal neutrons produces high linear energy transfer (LET) particles (α-particles and recoiling lithium nuclei), each of which have short path lengths within the diameter of a single mammalian cell. The deposited energy creates clustered DNA double-strand breaks that are cytotoxic in these tumor cells while sparing the surrounding healthy tissues. This advantage makes BNCT a highly attractive treatment modality compared to conventional radiotherapy. Nevertheless, despite its theoretical precision, the clinical translation of BNCT remains constrained by suboptimal tumor-selective boron delivery; insufficient intracellular accumulation; and heterogeneous biodistribution profiles associated with conventional small-molecule-based boron agents, such as boronophenylalanine (BPA) and sodium borocaptate (BSH). While the development of new accelerator-based neutron sources (ABNSs) has renewed interest in BNCT, effective ¹⁰B delivery remains a major challenge. To address this, nanomedicine has been steadily on the rise in cancer research. In recent years, nanocarrier-based delivery systems have emerged as a transformative alternative delivery strategy. Nanodrugs offer several advantages over conventional small-molecule drugs, such as improved solubility, increased plasma half-life, enhanced permeability and retention in tumors, and active targeting, as well as decreased systemic toxicity and drug resistance. In recent years, nanocarrier-based delivery systems have emerged as a transformative strategy for ¹⁰B delivery. In this focused review, we will discuss various types of nanocarriers used for boron drug delivery that enhance boron loading efficiency and evaluate what enables their selective delivery to and accumulation within tumor cells. Full article

Background: The increasing use of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in patients with breast cancer has led to a growing number of incidentally detected thyroid lesions. Thyroid incidentaloma refers to a focal area of increased metabolic activity within the thyroid gland. Up to 35% of focal thyroid incidentalomas are malignant. Early detection of thyroid carcinoma may allow less invasive surgical management and reduce the need for more extensive treatment associated with advanced disease, including total thyroidectomy, neck dissection, and radioactive iodine therapy. The objective of this study was to estimate the prevalence of focal thyroid incidentaloma and incidental thyroid carcinoma detected on PET/CT scans performed in breast cancer patients at a single tertiary medical center serving a highly ethnically diverse population. Methods: Medical records and PET/CT scans were retrospectively reviewed at a single medical center. Data collected included the presence of thyroid incidentaloma, maximum standardized uptake value (SUVmax), thyroid cytology, primary malignancy type, breast cancer status, ethnicity, and age. A total of 1233 patients with cancer who underwent PET/CT imaging and received treatment at ZIV Medical Center between August 2018 and December 2024 were included. Forty-two patients with primary thyroid carcinoma or head and neck carcinoma were excluded. Patients were categorized into breast cancer and non-breast cancer groups and compared regarding the prevalence of thyroid incidentaloma, referral rates for further evaluation by head and neck specialists, and the rate of incidental thyroid carcinoma. Results: Among 330 patients with breast cancer, 16 (4.8%) had a focal incidental thyroid finding, compared with 24 (2.8%) of 861 patients with non-breast malignancies who underwent PET/CT imaging. Among the 16 breast cancer patients with thyroid incidentaloma, thyroid carcinoma was subsequently confirmed in 4 patients (25%) who underwent further evaluation. The proportion of patients with confirmed thyroid carcinoma among those with incidentalomas was 1.2% (4/330) in the breast cancer group compared with 0.46% (4/861) in the non-breast cancer group. Approximately half of the patients in both groups were referred for further thyroid evaluation. Among breast cancer patients, non-significant trends toward higher referral rates were observed in patients with non-advanced disease, higher SUVs, and Jewish ethnicity. Nearly all patients evaluated by head and neck specialists underwent fine-needle aspiration (FNA). The mean SUV among patients diagnosed with papillary thyroid carcinoma (PTC) on FNA (n = 8; breast and non-breast cancer combined) was 15.2 (IQR: 7.3–17.0), compared with 5.2 (IQR: 5.0–6.0) among patients with benign cytology (n = 5; p = 0.011). Conclusions: Thyroid incidentalomas identified on PET/CT scans in breast cancer patients were relatively common in this cohort, and a proportion of evaluated lesions were subsequently diagnosed as thyroid carcinoma. Referral and diagnostic follow-up rates were variable, with approximately half of patients referred for further evaluation and only one-third attending a head and neck clinic. Given the retrospective design, limited number of biopsy-confirmed cases, and potential verification bias, these findings should be interpreted with caution. Nevertheless, they highlight the importance of clinical awareness and support individualized assessment of PET/CT-detected thyroid incidentalomas rather than broad management recommendations. Full article

The vitamin D receptor (VDR) has been implicated in tumor progression, but its functional role in pancreatic ductal adenocarcinoma (PDAC) metastasis remains unclear. Here, using pharmacological modulation, gain- and loss-of-function approaches, transcriptomic profiling, and an experimental lung colonization model, we demonstrate that VDR acts as a suppressor of PDAC metastasis. Pharmacological activation of VDR by calcipotriol did not affect tumor cell proliferation but markedly inhibited the migratory and invasive capacities of multiple PDAC cell lines. In contrast, genetic deletion or pharmacological inhibition of VDR significantly enhanced metastatic phenotypes. To investigate the underlying mechanisms, we performed RNA sequencing on PDAC cells with differential VDR expression following calcipotriol treatment. Pathway enrichment analysis identified MAPK/ERK signaling as one of the most prominently altered pathways upon VDR activation. Functional studies further demonstrated that ERK inhibition abrogated the pro-metastatic effects induced by VDR loss or inhibition. In vivo lung colonization assays confirmed that VDR deficiency markedly promoted pulmonary metastatic colonization. Collectively, these findings identify VDR as a critical suppressor of PDAC cell metastatic colonization and reveal a previously unrecognized VDR–ERK regulatory axis that may represent a potential therapeutic target for limiting metastatic progression in pancreatic cancer. Full article

Since decades, surgery of pancreatic adenocarcinoma is confronted with two major challenges. First, the prognosis of pancreatic adenocarcinoma is the worst of all gastrointestinal malignancies, characterized by late diagnosis and aggressive tumor biology. Second, postoperative mortality and morbidity have been exceptionally high, giving pancreatic resection a reputation of being one of the most dangerous procedures. This narrative review concentrates on the progress in decreasing postoperative mortality by centralization and standardization, the exertion of extended resections for local tumor clearance and multimodal strategies to improve oncologic survival. Research regarding surgical techniques, especially robotic assistance, indicated further progress in minimizing the perioperative trauma. Multimodal treatment concepts have been implemented with adjuvant therapy in resectable and neoadjuvant regimen in borderline and locally advanced cancer. However, significant problems have to be solved. Postoperative morbidity remains high, hindering the administration of adjuvant therapy, and toxicity is an essential factor in neoadjuvant strategies. Despite neoadjuvant therapies, resection rates of locally advanced carcinoma are modest and tumor progression hinders resection of borderline and resectable carcinomas. Obviously, deficits in understanding tumor biology are a central obstacle in improving resection rates and overall survival. Hence, improvement in selection of patients for surgical resection apart from using preoperative anatomical findings is mandatory. The progression of current standards, future developments and the status of surgery in multimodal concepts to treat pancreatic adenocarcinoma are delineated using historical and recent reports, registry data, meta-analysis and randomized controlled trials. Full article

Background: Chemotherapy-induced alopecia (CIA) significantly impacts patient quality of life (QoL). Scalp cooling therapy (SCT) is effective, but its success in clinical settings remains variable. Objective: To evaluate the association between a refined multidisciplinary team-based approach, integrating appearance care professionals, and SCT efficacy in breast cancer patients. Methods: This retrospective before–after single-institution study compared SCT outcomes before (Group A, n = 66) and after (Group B, n = 79) implementing a refined care model among patients who completed their full planned chemotherapy courses. The baseline characteristics were comparable except for a significantly higher proportion of patients starting a weekly regimen in Group B (54.4% vs. 30.3%, p = 0.004). The model featured enhanced staff training, a specialized hair/scalp charting system, and task-sharing between nurses and integrated certified hairdressers. The primary endpoint was the number of cycles with Grade 2 or higher alopecia (CTCAE v5.0). Results: The refined approach was associated with improved scalp cooling outcomes. The percentage of patients with Grade 2+ alopecia at treatment completion decreased from 53.0% in Group A to 32.9% in Group B (p = 0.015). The overall proportion of time spent with Grade 2+ alopecia fell from 17.3% to 6.5% (p < 0.001). In the ddAC f/b wPTX regimen, the median number of Grade 2+ cycles reduced from 10.0 to 4.0 (p = 0.033). While the wPTX f/b ddAC regimen showed a numerical reduction (1.0 vs. 0.0 cycles), it did not reach statistical significance (p = 0.326). Conclusions: The refined multidisciplinary approach, including the integration of appearance care professionals, was associated with improved scalp cooling outcomes and lower median cycle numbers across regimens. Although these findings may be partly influenced by the baseline imbalance in chemotherapy regimens, this comprehensive team-based care model offers a feasible strategy for enhancing patient support in oncology settings. Full article

Background and Objectives: Neoadjuvant dual HER2 blockade combined with chemotherapy is the standard treatment approach for patients with high-risk early-stage or locally advanced HER2-positive breast cancer. However, the optimal chemotherapy backbone and the predictive value of systemic inflammatory biomarkers remain subjects of ongoing investigation. This study aimed to compare pathologic complete response (pCR) rates between neoadjuvant dose-dense doxorubicin/cyclophosphamide followed by paclitaxel plus trastuzumab and pertuzumab (ddAC+THP) and docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP), and to evaluate the predictive performance of pretreatment inflammatory biomarkers. Materials and Methods: In this multicenter retrospective study, patients with HER2-positive breast cancer treated with neoadjuvant ddAC+THP or TCHP between 2019 and 2025 at three tertiary centers were evaluated. Pretreatment inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and hemoglobin, albumin, lymphocyte, and platelet (HALP) score, were calculated from baseline laboratory parameters. Receiver operating characteristic analyses were performed to determine optimal cutoff values, and logistic regression analyses were used to identify predictors of pCR. Results: A total of 197 patients were included, of whom 138 received ddAC+THP and 59 received TCHP. Overall, 125 patients (63.5%) achieved pCR. The pCR rate was numerically higher in the ddAC+THP group than in the TCHP group (65.2% vs. 59.3%), although the difference was not statistically significant (p = 0.431). Among the evaluated biomarkers, SIRI demonstrated the highest discriminatory performance for predicting pCR (AUC: 0.725, 95% CI: 0.652–0.797), followed by NLR (AUC: 0.673, 95% CI: 0.595–0.750). In multivariable analysis, hormone receptor positivity (OR: 0.291, 95% CI: 0.131–0.645; p = 0.002) and elevated SIRI (>0.845) (OR: 0.088, 95% CI: 0.036–0.216; p < 0.001) were independently associated with lower odds of achieving pCR. No significant difference in pCR was observed between treatment regimens across predefined subgroup analyses. Conclusions: Neoadjuvant ddAC+THP and TCHP achieved comparable pCR outcomes in patients with HER2-positive breast cancer. SIRI was independently associated with a lower likelihood of achieving pCR and showed acceptable discriminatory performance. These findings suggest that SIRI may represent an exploratory, readily available inflammatory biomarker for pCR risk stratification; however, prospective validation is required before clinical application. Full article

There is a growing interest in preventive and complementary therapies to support health, increase the effectiveness of conventional medical treatments, and improve quality of life (QoL). This review summarizes the effects of β-glucans, triterpenes and nucleoside analogs of edible and/or medicinal mushrooms with results of clinical trials that investigated these effects in diabetes, breast-, prostate-, lung- and colorectal cancer patients. The results support that these components effectively alleviate symptoms and improve quality of life of these patients. Higher than 3 g of mushrooms, or equivalent extracts, per day are able to diminish metabolic parameters associated with diabetes, i.e., hyperglycemia, hyperlipidemia, and inflammation. The found survival benefit of mushrooms in breast cancer patients was subgroup- or marker-specific. Additionally, their immunomodulatory effects were more complex—different immunological parameters could be either activated or suppressed by different amounts. Data are limited for prostate cancer patients to date, but lentinan intake may increase the survival time of these patients. The survival of lung cancer patients is significantly improved with the use of beta-glucan as complementary therapy. However, its immunomodulatory role was not confirmed. The application of these mushroom components in patients with colorectal cancer may improve QoL. However, survival benefits are inconsistent across different clinical trials of these patients. In summary, although further randomized clinical trials are still required to evaluate optimal dosage and long-term mechanisms of actions in humans, edible and medicinal mushrooms may serve as valuable tools in preventive or in complementary therapies beside the conventional medical treatments of diabetes and cancer. Full article

Background: Mucinous adenocarcinoma (MAC) of the colorectum is a biologically distinct histological subtype whose prognostic significance may vary substantially according to primary tumor location. The impact of anatomical site on clinicopathological characteristics and long-term survival in MAC remains incompletely characterized. This study aimed to evaluate the influence of tumor location on oncological outcomes in patients with mucinous colorectal cancer using a large population-based dataset. Methods: Patients diagnosed with mucinous colorectal adenocarcinoma between 2000 and 2023 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Operated patients were stratified by anatomical location into three groups: right colon (cecum, ascending colon, hepatic flexure, transverse colon), left colon (splenic flexure, descending colon, sigmoid colon, rectosigmoid junction), and rectum. The primary endpoints were overall survival (OS) and cancer-specific survival (CSS). Survival analyses were performed using the Kaplan–Meier method with log-rank testing. Multivariable Cox proportional hazards regression was used to assess the independent association of tumor location with survival outcomes, adjusting for age at diagnosis, year of diagnosis, sex, AJCC (American Joint Committee on Cancer) stage, tumor grade, receipt of radiotherapy and chemotherapy. Temporal trends in survival were evaluated across four consecutive diagnostic periods: 2000–2005, 2006–2011, 2012–2017, and 2018–2023. Results: A total of 40,698 patients with mucinous colorectal cancer were identified, of whom 40,174 underwent cancer-directed surgery (right colon n = 25,317; left colon n = 10,408; rectum n = 4449). The right colon was the predominant site of disease (62.9%). Median age was highest in the right colon group (74.0 years) and lowest in the rectum (65.0 years), while female sex predominated in right-sided tumors (55.7%) and male sex in rectal tumors (61.1%). Chemotherapy and radiotherapy utilization were markedly higher in the rectal group (68.6% and 64.5%, respectively) compared with the right colon (28.8% and 1.1%). Median OS was equivalent in the right and left colon groups (87.0 months each) but declined to 80.0 months in the rectal group. All pairwise CSS comparisons were statistically significant (all p < 0.001). On multivariable analysis, using the right colon as reference, the adjusted hazard ratios for CSS were 1.33 (95% CI: 1.28–1.39) for the left colon and 1.45 (95% CI: 1.34–1.57) for the rectum (both p < 0.001). Despite receiving the highest rates of multimodal therapy, rectal MAC demonstrated the worst long-term CSS across all anatomical groups. Temporal analyses revealed consistent CSS improvements in right-sided and left-sided MAC over the study period, whereas rectal MAC showed a non-linear trajectory with a plateau in the most recent diagnostic cohort (2018–2023). Conclusions: Mucinous colorectal adenocarcinoma demonstrates substantial biological and prognostic heterogeneity according to anatomical tumor location. Right-sided MAC was the most prevalent subtype and exhibited superior cancer-specific survival despite older patient age and lower treatment intensity. Rectal MAC demonstrated the worst long-term outcomes despite high utilization of multimodal neoadjuvant therapy, consistent with the established reduced responsiveness of mucinous tumors to conventional chemoradiotherapy. These findings underscore the necessity of incorporating anatomical location and tumor biology into individualized risk stratification and therapeutic planning for patients with mucinous colorectal cancer. Full article

Background: Although gemcitabine-based palliative chemotherapy remains widely used for advanced biliary tract cancer (BTC), practical pretreatment prognostic factors are needed. This study identified baseline prognostic factors associated with overall survival (OS) and explored a simple risk stratification approach for 12-month survival in advanced BTC patients treated with gemcitabine-based chemotherapy. Methods: This retrospective cohort study included advanced BTC patients treated with gemcitabine-based palliative chemotherapy between 2011 and 2025. Baseline clinical and laboratory variables were collected at treatment initiation. The Kaplan–Meier method estimated OS. Univariable and multivariable Cox proportional hazards regression analyses identified prognostic factors. A post hoc exploratory risk score was developed using routinely available factors independently associated with OS. Results: A total of 154 patients were included, gemcitabine plus cisplatin was administered to 95 patients, whereas 59 received gemcitabine plus carboplatin. Median OS was 9.43 months. Multivariable analysis showed that ECOG performance status ≥ 2 (adjusted HR, 5.68; 95% CI, 2.52–12.81), alkaline phosphatase (ALP) ≥ 2 × ULN (adjusted HR, 1.53; 95% CI, 1.01–2.33), and neutrophil-to-lymphocyte ratio (NLR) ≥ 3 (adjusted HR, 1.51; 95% CI, 1.03–2.20) were associated with worse OS. An exploratory score assigning one point to each factor stratified patients into low-, intermediate-, and high-risk groups. The estimated 12-month OS rates were 59.6%, 40.4%, and 10.8%, respectively. Conclusions: Poor performance status, elevated ALP, and elevated NLR were associated with worse OS in advanced BTC patients receiving gemcitabine-based palliative chemotherapy. However, the associations for ALP and NLR were modest and should be interpreted cautiously. A simple exploratory score based on routinely available factors demonstrated distinct 12-month survival across risk groups and may help inform prognostic discussions in routine practice. This approach should be considered hypothesis-generating, and external validation is warranted. Full article

Background: Next-generation sequencing (NGS) and the initiation of biomarker-driven first-line (1L) treatment on overall survival (OS) was evaluated in advanced/metastatic non-small-cell lung cancer (a/mNSCLC). By applying a time-dependent regression modeling approach accounting for fluidity of clinical care, this study aimed to capture the dynamic interplay between NGS testing, turnaround time (TaT), treatment decisions and timing of initiation, and outcomes more comprehensively than traditional static analyses. Methods: This study was a retrospective observational study using the US Flatiron Health EHR-derived de-identified database. Eligible adults had non-squamous a/mNSCLC and received blood-based (B-NGS) or tissue-based (T-NGS) NGS within 90 days of diagnosis (1 January 2018–30 June 2023). A time-dependent covariate captured the NGS TaT, presence of a targetable alteration, time to 1L initiation, and 1L regimen (targeted concordant vs. discordant). OS was measured from the NGS order date to death. Results: A total of 1806 patients underwent B-NGS and 2583 underwent T-NGS. Starting empiric discordant 1L therapy before NGS results was associated with higher mortality versus initiating targeted concordant therapy after biomarker identification: B-NGS hazard ratio (HR): 1.58 (95% CI, 1.10–2.26); T-NGS HR: 1.07 (0.82–1.39). Considering discordant 1L therapy irrespective of timing, mortality remained higher versus targeted concordant therapy: B-NGS HR: 1.35 (1.04–1.74); T-NGS HR: 1.24 (0.98–1.56). Conclusions: This study demonstrates that waiting for comprehensive molecular profiling results before starting 1L treatment enables the delivery of appropriate biomarker-driven therapy, which translates into improved patient outcomes. Delays in NGS result availability or treatment initiation were linked to worse survival, underscoring the need for streamlined diagnostic workflows and rapid testing modalities. Full article

Oral squamous cell carcinoma (OSCC) represents a significant global health challenge characterized by high morbidity and mortality, frequently driven by therapeutic resistance and tumor aggressiveness. Metabolic reprogramming has emerged as a hallmark of OSCC, enabling tumor cells to sustain proliferation, survive under adverse microenvironmental conditions, and evade therapeutic stress. Recent advances in cancer metabolism have identified metabolic plasticity as a central determinant of OSCC progression and treatment failure, highlighting the need to integrate evidence on metabolic vulnerabilities and therapeutic opportunities. This narrative review aims to provide an updated overview of metabolic reprogramming in OSCC, with particular emphasis on the interplay between glycolysis, mitochondrial metabolism, glutamine metabolism, and fatty acid oxidation, and to discuss how these interconnected pathways may be therapeutically exploited. Although OSCC cells exhibit enhanced aerobic glycolysis, mitochondria remain functionally active and play critical roles in energy production, redox homeostasis, and metabolic adaptation. The therapeutic potential of targeting tumor metabolism is discussed, highlighting dichloroacetate (DCA) as a promising metabolic modulator capable of inhibiting pyruvate dehydrogenase kinase (PDK), restoring mitochondrial glucose oxidation, and partially reversing the glycolytic phenotype. The review also examines the current translational limitations of DCA, including toxicity, pharmacokinetic constraints, and compensatory metabolic adaptations that restrict its efficacy as a standalone therapy. Furthermore, potential synergistic strategies are explored, particularly the combination of DCA with paclitaxel, which enhances therapeutic efficacy through concurrent disruption of cytoskeletal integrity and metabolic homeostasis, thereby increasing cellular susceptibility to apoptosis and overcoming chemoresistance. Full article

Background: The Martini and Melamed criteria for diagnosing multiple primary lung cancers (MPLCs) have remained in use for half a century despite substantial changes in lung cancer epidemiology, risk factors, imaging technologies, and treatment approaches. Correspondingly, the landscape of MPLC has likely changed, necessitating revisions to their diagnostic guidelines. Research Question: What are the clinicopathologic profiles of modern-day MPLC patients, and can these features be used to identify a subset of patients classified as MPLC that may warrant additional investigation as intrapulmonary metastasis (IPM)? Study Design and Methods: We conducted a retrospective cohort study using electronic medical record data from patients who underwent multiple lung cancer resections at Mount Sinai Hospital. Patient demographics, tumor characteristics, and surgical treatments were compared with those reported in the original Martini and Melamed series. We then proposed a reclassification framework incorporating a CT-based assessment of synchronous versus metachronous tumors and contemporary clinicopathologic features documented in imaging and pathology reports. Results: Ninety-one patients underwent successive lung cancer resections. Among first nodules treated with surgical resection, 46% exhibited pathologic features suggestive of metastasis within the lung, including visceral pleural invasion (18%), vascular invasion (24%), lymphatic invasion (36%), and/or lymph node positivity (3%). In contrast, among second nodules (second temporal surgery), 45% demonstrated ground-glass opacity (GGO) supportive of a diagnosis of MPLC. Using the original criteria, 83 patients (91%) were classified as having MPLC; this proportion decreased to 53 patients (58%) under the reclassification criteria. Regardless of the criteria applied, contemporary MPLCs were more likely to occur in older patients, women, those with adenocarcinoma histology, and treated with sublobar resections compared with MPLCs described in the Martini and Melamed era. Conclusions: MPLCs are increasingly recognized, and their clinical presentation has changed substantially over time. Modern imaging and pathologic assessment may be useful tools for diagnosing MPLCs, but this requires future validation. This has important implications for staging and treatment decision-making, as patients may be undertreated by not being offered multimodal treatments or over-treated with systemic therapy when surgery alone may be sufficient. Full article

Background/Objectives: Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) has undergone rapid therapeutic evolution. However, heterogeneous outcomes persist, driven by mutations, central nervous system (CNS) involvement, and dynamic tumor burden reflected in part by circulating tumor DNA (ctDNA). As such, this review aims to summarize the most recent risk stratification frameworks in treating EGFR-mutant NSCLC, evaluate evidence supporting treatment intensification strategies and managing adverse effects, and explore the evolving role of ctDNA in guiding personalized therapy. Methods: A comprehensive literature search was conducted using major medical databases with a focus on key relevant studies on the workup and management of EGFR-mutant NSCLC. All authors reviewed the literature, assessed study quality, and interpreted the results from each study. Results: Molecular co-alterations, such as TP53 and RB1, as well as central nervous system (CNS) involvement, are consistently associated with inferior outcomes, supporting consideration of upfront treatment intensification. Combination strategies, including osimertinib plus chemotherapy or amivantamab-based regimens, demonstrate improved progression-free survival and delayed CNS progression when compared against osimertinib monotherapy. Intensification, however, is associated with a higher risk of increased toxicity, including dermatologic adverse events and infusion-related reactions. Finally, the utilization of circulating tumor DNA (ctDNA) has emerged as a strong prognostic marker, with ongoing trials investigating its predictive role for both escalation and de-escalation of therapy. Conclusions: The treatment paradigm for EGFR-mutant NSCLC is gradually evolving beyond first-line osimertinib to include a more integrated approach that considers molecular features, CNS involvement, and early ctDNA response. Although intensified regimens offer meaningful efficacy gains for high-risk patients, proactive toxicity management is essential to preserving quality of life. ctDNA-guided strategies represent a new and promising frontier for escalation and de-escalation of therapy, with results from ongoing trials poised to further refine personalized treatment algorithms. Full article

Primary liver malignancies, including hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma, remain major causes of cancer-related morbidity and mortality worldwide. Although systemic therapies have advanced substantially, intrahepatic tumor progression, liver failure, and portal hypertension continue to drive adverse outcomes in many patients. Interventional radiology plays a central and expanding role in the multidisciplinary management of these tumors by providing image-guided locoregional therapies for local tumor control, downstaging, bridging transplantation or resection, palliation, and potential survival benefit. This narrative review summarizes current evidence and technical considerations for major locoregional approaches, including radiofrequency ablation, microwave ablation, cryoablation, transarterial chemoembolization, transarterial radioembolization, endobiliary therapies, stereotactic body radiation therapy, irreversible electroporation, histotripsy, high-intensity focused ultrasound, hepatic arterial infusion, and brachytherapy. Interventional radiology also contributes to preoperative liver optimization through portal vein embolization, liver venous deprivation, lobar radioembolization to induce contralateral hypertrophy, and, in some patients, portal decompression before hepatic resection. For hepatocellular carcinoma, ablation and transarterial therapies are integrated into stage-based treatment algorithms and may provide curative-intent treatment in some patients. In intrahepatic cholangiocarcinoma, locoregional therapies provide meaningful disease control and may prolong survival, particularly when combined with systemic therapy. In combined hepatocellular cholangiocarcinoma, treatment remains individualized because of limited prospective data and heterogeneous tumor biology. Beyond cytoreduction, locoregional therapies can modulate the tumor immune microenvironment through immunogenic cell death, antigen release, cytokine signaling, and vascular remodeling, providing a rationale for combination strategies with immune checkpoint inhibitors, anti-angiogenic agents, and targeted therapies. As treatment paradigms evolve, the future of interventional radiology in primary liver cancer will depend on appropriate patient selection, optimized dosimetry and technique, integration with molecular and immunologic biomarkers, and coordinated multidisciplinary care. Full article