The influence of socioeconomic determinants of health on early gastric adenocarcinoma (GAC) remains understudied. We evaluated the association between median household income (MHI), treatment patterns, and survival in T1aN0M0 GAC.

Using the SEER-17 Research Plus database (2004-2021), we identified 3,792 patients with T1aN0M0 GAC. MHI was stratified into tertiles. Overall survival (OS), cancer-specific mortality (CSM), and non-cancer-specific mortality (NCSM) were assessed with Kaplan-Meier methods. Independent predictors of CSM were identified using multivariable Fine-Gray competing-risk regression.

Patients in the lowest MHI tertile were younger, more likely to be Black, unemployed, and to receive no definitive treatment (surgery or endoscopic therapy (ET)) despite similar tumor size (all P < 0.001) vs higher tertiles. Treatment patterns varied by income: highest MHI patients were more likely to undergo ET, while lowest MHI patients more often received chemotherapy/radiation and no definitive therapy. Compared with the highest MHI group, the lowest MHI group had worse outcomes, with lower 5-year OS (82.3% vs. 86.0%) and higher 5-year CSM (17.6% vs. 13.6%; both P < 0.001). NCSM did not differ across income tertiles. Compared with the lowest MHI tertile, the middle (sHR 0.68, 95% CI 0.55-0.83; P < 0.001) and highest MHI tertiles (sHR 0.72, 95% CI 0.56-0.93; P = 0.011) were associated with significantly lower CSM. Older age ( ≥ 65 years), tumor size ≥ 2 cm, poor tumor differentiation, no definitive treatment, and receipt of radiation therapy were independently associated with higher CSM, whereas Asian or Pacific Islander race, residence in the Northern region and diagnosis during 2019-2021 were associated with lower CSM.

Lower MHI was independently associated with poorer survival in early GAC, highlighting persistent socioeconomic disparities in access to definitive treatment. Strategies to improve equitable access to curative therapy are warranted.

RET gene fusion is one of the key oncogenic drivers in papillary thyroid cancer (PTC). However, the impact of different RET fusion subtypes on clinicopathological features and radioiodine (RAI) avidity in metastatic PTC remains unclear.

We retrospectively analyzed clinicopathological data, RAI avidity, and progression-free survival (PFS) in RET-driven metastatic PTC. Initial RAI avidity status was classified as initially RAI-avid (all or partial lesions showing uptake in the first therapy) or initially RAI-non-avid (all lesions with no uptake in the first therapy). The definition of RAI refractory (RAIR) was based on the 2025 ATA guidelines.

Among 65 enrolled patients, 25 (38.5%) harbored CCDC6-RET, 24 (36.9%) NCOA4-RET, and 16 (24.6%) other RET fusions. Older age was associated with the other RET fusion group (P = 0.011). NCOA4-RET patients were more likely to be initially RAI-avid (P = 0.017). Overall, 46.8% (29/62) of evaluable patients were classified as RAIR (CCDC6: 56.0%, NCOA4: 27.3%, other RET fusions: 60.0%; P = 0.072). TERT promoter mutation (18.2%, 8/44) in RET-fusion PTC was associated with older age (P < 0.001), larger metastatic lesions (P = 0.012) and metastatic sites beyond lungs (P = 0.002). RAIA patients demonstrated a longer median PFS compared with RAIR patients (86 vs. 33 months), but this association was not statistically significant (P = 0.402).

In this metastatic RET-driven PTC cohort, 46.8% of evaluable patients eventually develop RAIR status. While the specific RET subtypes are associated with initial RAI avidity status, no significant differences in RAIR status or PFS were observed across distinct RET subtypes, warranting further exploration in larger sample sizes.

Breast cancer (BC) patients with pathogenic germline BRCA1/2 mutations (gBRCA1/2mut) have a substantially increased risk of ovarian cancer (OC). Risk-reducing bilateral salpingo-oophorectomy (RRSO) remains the only effective preventive strategy. However, data on the utilization and time to RRSO in gBRCAmut BC patients are limited.

This retrospective study included 148 patients with gBRCA1/2mut BC treated at the Hereditary Breast and Ovarian Cancer Center, University Hospital Erlangen, between 2012 and 2024. Clinical, pathological, treatment-related, and genetic data were collected and analyzed from electronic records. Time to RRSO at date of BC surgery was calculated for all patients, and stratified according guideline recommendations for RRSO, using the Kaplan-Meier method.

In this cohort of 148 patients with gBRCAmut BC, 60.8% harbored a gBRCA1 and 39.2% a gBRCA2 mutation. BC was diagnosed at the mean age of 47.1 years, 73.6% presenting at UICC stage I-II. 47.9% of patients presented with triple-negative BC, 38.4% of patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative BC and 8.9% with HER2-positive BC. 101 patients (68.2%) additionally underwent RRSOs. The 12-month RRSO-free probability was 0.58 (95% CI 0.50-0.68) and the 24-month RRSO-free probability 0.39 (95% CI 0.31-0.49). Occult OC was detected in three patients at the time of RRSO during BC follow-up, four patients without RRSO were diagnosed with OC after BC.

In real-world setting, RRSO is a common prevention in gBRCAmut BC follow-up. The majority of patients undergo surgery within the first two years following a BC diagnosis. Survival outcomes among patients with BC have improved substantially in recent years. Consequently, developing OC in gBRCAmut BC individuals still remains a risk. RRSO should therefore continue to be offered and discussed in accordance with current guidelines, even in the context of a BC diagnosis.

Testicular adrenal rest tumors (TARTs) are among the most important long-term complications in males with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The aim of this study was to evaluate the prevalence, clinical characteristics, and hormonal profile associated with TARTs in adult men with CAH.

This retrospective cohort study included 23 adult male patients with CAH due to 21-hydroxylase deficiency. Clinical, biochemical, genetic and radiological data, including treatment and treatment response, were retrospectively collected, and CYP21A2 genotypes were classified into severity groups. Clinical, laboratory and genetic characteristics were compared between patients with and without TARTs.

Among 23 patients, TARTs were detected in 11 (48%). Patients with TARTs had significantly higher concentrations of ACTH (384 ng/L) and 17-OHP (96 ng/mL) (both p < 0.001). Of the patients with TARTs, 82% had the salt-wasting phenotype, while 18% had the simple-virilizing phenotype. Group Null genotypes were more frequent in patients with TARTs (90% vs. 20%, p = 0.005). Bilateral testicular involvement was observed in 9/11 patients (82%). Median age at diagnosis of CAH was significantly lower in patients with TARTs [0 (0-44) years] than in those without TARTs [7 (0-63) years] (p = 0.021). No consistent pattern was observed between changes in glucocorticoid therapy and TART regression.

TARTs are a common complication in adult men with CAH and are associated with impaired testicular function. TARTs were more frequent among patients with severe genotypes and/or inadequate disease control. Early and regular testicular ultrasound screening may facilitate timely diagnosis and help preserve fertility potential.

Treatment strategies for advanced breast cancer (ABC) are rapidly evolving, but treatment decisions and monitoring remain dependent on imaging-based assessments. Circulating tumour DNA (ctDNA) has emerged as a minimally invasive biomarker with potential to provide real-time assessments, yet its clinical relevance in ABC has not been established. This systematic review and meta-analysis evaluates the prognostic value of ctDNA in ABC.

Medline, Embase, and Cochrane databases were systematically searched up to 07/02/2025. Eligible studies analysed associations between ctDNA and progression free survival (PFS) and/or overall survival (OS) in patient with ABC. Study quality was assessed using the Quality in Prognosis Studies Tool. Hazard ratios (HR) with 95% confidence intervals (CI) were extracted, and meta-analyses were performed using random-effects models.

Sixty-four studies were included and divided into subgroups. Elevated ctDNA levels at baseline were significantly associated with shorter PFS (n = 2,586, pooled HR = 2.0; 95% CI: 1.8-2.3) and OS (n = 2,454, pooled HR = 2.6; 95% CI: 2.1-3.3). Unfavourable changes in ctDNA levels were associated with reduced PFS (n = 710, pooled HR = 2.5; 95% CI: 1.9-3.4) and OS (n = 154, pooled HR = 2.4; 95% CI: 1.5-3.8). Additionally, analyses on specific genetic alterations in ctDNA and survival outcomes indicated a less favourable prognosis when detected at baseline. However, results were not consistent.

This review supports an association between baseline ctDNA levels, on-treatment changes in ctDNA levels, and survival outcomes in ABC. Furthermore, specific genetic alterations in ctDNA add prognostic information and may support treatment tailoring.

Registered in PROSPERO (CRD42024534851).

Sacituzumab govitecan (SG) is an antibody-drug conjugate approved across multiple metastatic breast cancer settings. Although hematologic and gastrointestinal toxicities dominate its safety profile, dermatologic adverse events (dAEs) remain poorly characterized, despite the physiological expression of Trop-2 in epidermal keratinocytes. We aimed to comprehensively characterize the spectrum, severity, time to onset, and oncologic impact of SG-associated dAEs across real-world and pharmacovigilance data sources.

An international retrospective cohort study was conducted within the EADV Task Force "Dermatology for Cancer Patients" (n = 56 breast cancer patients). Findings were triangulated with disproportionality analyses of the WHO Global Pharmacovigilance database (VigiBase^®; n = 696 cases) and the French Pharmacovigilance Database (FPVD; n = 46 cases), alongside a literature review of SG clinical trials reporting dAEs.

Across all data sources, alopecia was the most frequently reported dAE (EADV cohort: 41.1%; FPVD: 52.2%; VigiBase^®: 67.6%), followed by stomatitis/mucositis, pruritus, xerosis, and maculopapular rash. In the EADV cohort, 13 distinct dAE types were identified; median time to first dAE was 56 days, and 96.4% of events were grade 1-2. Treatment discontinuation attributable to dAEs occurred in only 3.6% of patients. VigiBase^® disproportionality analysis identified significant reporting signals for alopecia (IC 3.3 [3.09; 3.53]), infusion-related reactions (IC 1.9 [1.07; 2.55]), and stomatitis (IC 1.6 [0.86; 2.30]). Preliminary signals of cutaneous infections were observed but did not consistently meet the threshold for statistical significance.

SG-associated dAEs are predominantly low-grade and infrequently precipitate treatment discontinuation. Pharmacovigilance data raises a potential signal for cutaneous infections that warrants further investigation. As SG increasingly enters combination regimens, structured dermatologic monitoring and prospective characterization of dAEs are essential to guide oncodermatologic management and protect oncological outcomes.

Not applicable.

Assessment of HER2 status change in HER2-positive breast carcinoma (BC) prior to and after HER2-targeted neoadjuvant therapy (NAT) may potentially impact adjuvant HER2-targeted therapy. Reported rates of HER2 status change vary widely (< 10-56%), underscoring the need for further study. This study evaluated the frequency of HER2 status change and its clinicopathologic correlations in HER2-positive BC cases.

Residual breast carcinomas were retrospectively assessed at a single institution after HER2-targeted NAT. HER2 status on residual tumor was evaluated by immunohistochemistry (IHC) and, for IHC 2 + cases, confirmed by fluorescence in situ hybridization (FISH). Tumors were categorized as HER2-retained (IHC 3 + or 2+/FISH amplified) or HER2-change (IHC 0/1 + or 2+/FISH non-amplified). Clinicopathologic features were correlated with post-treatment HER2 status.

Among 161 HER2-positive BC patients treated with HER2-targeted NAT between 2016 and 2025, 65 had adequate residual invasive tumor for HER2 assessment. Invasive ductal carcinoma was the predominant histologic type. Retained HER2 overexpression was observed in 28/65 (43%) cases, while 37/65 (57%) showed HER2 status change. Pre-NAT hormone receptor positivity was present in 23 (82.1%) HER2-retained and 33 (89.2%) HER2- status changed cases. Clinicopathologic parameters were comparable between the groups.

HER2 status change from HER2 overexpression to loss of overexpression occurred in more than half of residual breast carcinomas following HER2-targeted NAT. The current national and international guidelines recommend adjuvant HER2-targeted therapy regardless of post-treatment HER2. Prospective randomized phase II/III trials are needed to determine the benefit of adjuvant HER2-targeted therapy in this subgroup of patients with HER2-positive BC.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, and available treatments remain limited. Plant-derived exosome-like nanoparticles (PELNs) are promising natural nanocarriers due to their low toxicity and ability to cross biological barriers. Brassica oleracea (kale) contains bioactive compounds, including glucosinolates and sulforaphane, with known antiproliferative, pro-apoptotic, and antioxidant properties.

This study investigated the effects of kale-derived exosome-like nanovesicles (K-Exo) and dactolisib (Dacto), a dual PI3K/mTOR inhibitor, alone and in combination in Hep3B cells. Cell viability, apoptosis, intracellular reactive oxygen species (ROS), ferrous iron (Fe²⁺) levels, and the expression of genes associated with PI3K/AKT/mTOR signaling and apoptosis were evaluated. Cleaved caspase-3 and NRF2 protein expression were also assessed by immunofluorescence staining.

K-Exo alone did not significantly reduce cell viability, whereas Dacto + K-Exo decreased Hep3B cell viability. The combination downregulated genes involved in cell survival and drug resistance, including AKT, mTOR, and MDM2. Apoptosis was supported by significant increases in TP53 and CASP3 mRNA levels and confirmed by flow cytometry. Immunofluorescence showed increased cleaved caspase-3 and NRF2 fluorescence in the combination group. The combined treatment also affected iron homeostasis and oxidative stress regulation.

Decreased ROS and Fe²⁺ levels, together with increased expression of apoptosis-related genes, indicate that Dacto + K-Exo induces apoptosis rather than ferroptosis in Hep3B cells. These findings suggest that the combination may promote apoptosis and modulate cellular redox and iron balance in this HCC cell line. However, further studies using additional HCC models are required to evaluate the broader therapeutic potential of this approach.

Positive surgical margin (PSM) rates in robot-assisted radical prostatectomy (RARP) remain high and understanding their cause remains key to their elimination. We examined the prostate cancer pathway as a whole to systematically identify and quantify sourcescontributing to PSMs.

Using a prospectively maintained database at a high-volume centre, we retrospectively analysed 100 consecutive patients with positive surgical margins (PSMs) following robot-assisted radical prostatectomy between January and December 2022. For each patient, a pre-operative imaging-based surgical plan was available. Potential sources contributing to PSMs were identified by reviewing diagnostic and staging information, the recommended surgical plan, the executed surgical template, and final pathology. Sources were categorised into three pathway phases: Diagnostic and Staging, Surgical Planning, and Surgical Execution. Proportions were reported with 95% confidence intervals calculated using the exact binomial (Clopper-Pearson) method.

A total of 112 positive surgical margins (PSMs) were identified in 100 patients. One hundred and twenty-five contributing sources were identified, with a single source attributed to 102 PSMs, two sources to 7 PSMs, and three sources to 3 PSMs. Surgical execution accounted for the majority of identified sources (98/125, 78.4%; 95% CI 70.2-85.3%), followed by surgical planning (14/125, 11.2%; 95% CI 6.3-18.1%) and diagnostic and staging factors (13/125, 10.4%; 95% CI 5.7-17.1%). Within the surgical execution category, nerve-sparing was the most frequently implicated surgical step, being associated with 57/112 PSMs (50.9%; 95% CI 41.3-60.5%), followed by apical dissection (34/112, 30.4%; 95% CI 22.0-39.8%).

Despite high volume, the most common sourceis surgical execution. This represents an opportunity for intra-operative margin assessment to reduce PSM rates. Diagnostic and planning steps still contributed to one- fifth of PSMs and can also be improved. We emphasise how this novel systematic approach can be used as a framework in quality assurance and improvement processes.

To assess the rate of histological discordance between renal mass biopsy(RMB) and final surgical pathology in patients with localized renal tumors, and to identify risk factors of discordance.

The BIRD study is a retrospective multicenter analysis conducted within the prospective UroCCR database between February 2004 and January 2025. We included all patients who underwent a renal mass biopsy followed by surgical treatment(partial or radical nephrectomy). The primary endpoint was the histological discordance rate, defined as a mismatch in tumor type between the biopsy and the surgical specimen, or a non-diagnostic biopsy, and diagnostic accuracy. Univariate and multivariate logistic regression analyses were performed to identify factors associated with discordance.

A total of 1,301 patients from 19 centers were included, with 65% male and a median age of 63 years(51-71). Tumors were equally distributed between the right and left kidneys, with a median size of 3.7 cm(2.5-5.0). Final histology showed 8% benign and 92% malignant tumors. Tumor necrosis was found in 23% of cases. Among tumors assessed for nuclear grade, a 48% discordance was observed between low(ISUP1-2) and high grades(ISUP3-4). Overall, the histological discordance rate was 18%, including 3.7% for malignancy diagnosis, 8.4% for histological subtype, and 5.7% for non-diagnostic biopsies. On multivariable analysis after multiple imputation, cystic tumor(OR 2.18, 95%CI 1.23-3.85, p = 0.007) was independently associated with increased risk of histological discordance. Moderate and high R.E.N.A.L. score complexity were associated with reduced discordance risk(OR 0.67, 95%CI 0.47-0.96, p = 0.03 and OR 0.60, 95%CI 0.37-0.98, p = 0.04, respectively).

RMB provided a high diagnostic yield but was associated with an overall 18% discordance rate. Cystic tumors were the only independent factor associated with an increased risk of discordance, while tumor complexity and size influenced discordance subtypes. Regarding ISUP grade, RMB showed imperfect reliability, failing to reflect true tumor aggressiveness in nearly half of discordant cases.