To evaluate the association of age with PSA kinetics and biochemical control after low-dose-rate brachytherapy (LDR-BT).

We retrospectively analyzed 347 patients treated with LDR-BT alone without androgen deprivation therapy between 2004 and 2015. Longitudinal PSA changes were evaluated using linear mixed-effects models with natural cubic splines for time. Age was modeled as a continuous fixed effect, including interactions with the spline terms for time. Time to PSA nadir < 0.2 ng/mL was evaluated using Cox proportional hazards models, whereas biochemical recurrence was evaluated using Fine-Gray competing-risk regression with death treated as a competing event.

Younger age was significantly associated with slower PSA decline over 5 years (p < 0.001). Each 1-year increase in age was associated with model-estimated PSA levels relative to baseline that were 4.6%, 6.4%, and 4.3% lower at 1, 3, and 5 years, respectively. This association remained significant after adjustment for Gleason grade group and treatment era and after excluding patients with PSA bounce (both p < 0.001). Median time to PSA nadir < 0.2 ng/mL was 54 months in patients aged < 65 years and 36 months in those aged ≥ 75 years. Increasing age was associated with earlier achievement of PSA nadir < 0.2 ng/mL (HR 1.04 per year, 95% CI 1.02-1.06) but was not significantly associated with biochemical recurrence.

Age was significantly associated with PSA kinetics following LDR-BT, with younger patients showing slower PSA decline and a delayed achievement of PSA nadir < 0.2 ng/mL. However, these age-related differences were not associated with biochemical recurrence.

To evaluate treatment-effect heterogeneity associated with local therapy in nonmetastatic advanced prostate cancer and develop a simple hypothesis-generating framework to estimate the expected absolute survival benefit associated with local therapy.

This multicentre retrospective cohort study included 1198 patients with clinical T3-4N0M0 or cN1M0 prostate cancer from the Kaga Million Uro-Oncology Network (KAMU-ON). Multivariable Cox models evaluated the association between local therapy and overall survival. Treatment-effect heterogeneity was assessed using interaction analyses. Adjusted 5 year overall survival and absolute survival benefit were estimated by g-computation. A simple clinical framework based on clinicopathological variables was derived from the subgroup analyses.

Local therapy was independently associated with improved overall survival (adjusted hazard ratio 0.32, 95% confidence interval 0.21-0.48; p < 0.001). Significant treatment-effect heterogeneity was observed according to clinical T stage (p for interaction = 0.030). The greatest absolute survival benefits were observed in patients with clinical T3b/T4 disease (20.3 percentage points) and Grade Group 4-5 disease (17.2 percentage points). The framework stratified the estimated absolute survival benefit from 0.1 to 19.5 percentage points across score groups (p for interaction = 0.041; p for trend = 0.023).

The survival benefit associated with local therapy varied substantially across patients with nonmetastatic advanced prostate cancer. This hypothesis-generating framework may provide estimates of expected treatment benefit and support individualized treatment discussions.

To evaluate the effect of neoadjuvant chemotherapy (NAC) on pathological response and oncologic outcomes in patients with high-risk upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU) in a real-world multicenter setting.

We retrospectively analyzed data from 184 patients with high-risk UTUC who underwent RNU across six institutions and were divided into NAC and non-NAC groups. The primary endpoint was pathological downstaging. Secondary endpoints were non-urinary-tract recurrence-free survival (NUT-RFS) and overall survival (OS). We also compared the NAC group with the combined non-NAC and adjuvant chemotherapy (AC) group. Propensity score matching (PSM) was performed to adjust for baseline differences.

34.2% and 14.1% of 184 patients (median age, 75 years; men, 70.7%) received NAC and AC, respectively. NAC was not significantly associated with pathological downstaging. On multivariable analysis, positive urine cytology (bladder) was independently associated with a lower likelihood of downstaging, whereas a higher baseline eGFR was independently associated with a higher likelihood of downstaging. Neither NUT-RFS nor OS differed significantly between the NAC and non-NAC groups or between the NAC and non-NAC plus AC groups, either in the overall cohort or after PSM.

In this real-world cohort, NAC did not significantly improve pathological or survival outcomes in patients with high-risk UTUC. Oncological outcomes did not differ significantly between NAC and AC administered after pathological confirmation of risk, although this comparison is susceptible to selection and guarantee-time bias. Pathology-guided AC may be a reasonable perioperative strategy, but its relative benefit remains uncertain and warrants prospective validation.

Perioperative treatment with enfortumab vedotin (EV) plus pembrolizumab has demonstrated a high pathological complete response (pCR) rate in patients with cisplatin-ineligible muscle-invasive bladder cancer (MIBC). However, whether this therapeutic benefit reflects true pharmacologic synergy or can be explained by independent drug action (IDA) remains uncertain.

We analyzed data from EV-103 cohort H (EV monotherapy), the cisplatin-ineligible subset of PURE-01 (pembrolizumab monotherapy), and KEYNOTE-905/EV-303 (EV plus pembrolizumab). An IDA model incorporating a Gaussian copula was applied to estimate the predicted pCR rate of the combination therapy. The primary analysis assumed weak positive dependence between drug responses (correlation coefficient ρ = 0.24). Sensitivity analyses evaluated the observed-minus-IDA-predicted pCR difference across a continuous range of dependence assumptions (ρ = 0.00-0.99).

The predicted pCR rate for EV plus pembrolizumab was 53.5%, consisting of 21.4% EV-only responders, 17.1% pembrolizumab-only responders, and 15.0% dual responders. The observed pCR rate in the KEYNOTE-905/EV-303 trial was 57.1%, corresponding to an absolute difference of 3.6 percentage points compared with the model prediction. In sensitivity analyses, the posterior median observed-minus-predicted difference increased with stronger positive dependence, but the 95% credible intervals were wide and included zero across a broad range of dependence assumptions.

Although modest pharmacologic synergy cannot be excluded given the uncertainty in the available data, substantial population-level pharmacologic synergy is not required to explain the high pCR observed with the combination.

MRI-guided focused ultrasound (MRgFUS) thalamotomy is an effective ablative procedure for medication-refractory essential tremor (ET). However, limited data exist regarding its safety in patients with coexisting intracranial disease such as cerebral cavernous malformations. We present a man in his late 60s with medication-refractory ET who underwent staged bilateral MRgFUS thalamotomy. Preoperative MRI demonstrated heterogeneously T1-hyperintense and T2-hyperintense lesions in the left caudate head and basal ganglia consistent with cavernous malformations, with an associated developmental venous anomaly and no prior haemorrhage. After individualised counselling regarding unknown procedural risks, the patient underwent right-sided thalamotomy, followed 1 year later by left-sided thalamotomy. MRI after each procedure demonstrated expected treatment-related changes without acute intracranial haemorrhage around the cavernous malformations. This case demonstrates successful staged bilateral MRgFUS thalamotomy in a patient with cerebral cavernous malformations, suggesting they may not uniformly preclude MRgFUS in carefully selected patients. Preoperative planning, counselling and MRI surveillance remain essential.

Radiation therapy (RT) is central to curative treatment for oropharyngeal squamous cell carcinoma (OPSCC) but may cause late side effects that can adversely impact quality of life (QOL). As OPSCC treatment becomes more personalised, clinically meaningful QOL endpoints and their predictors are increasingly important.

To assess long-term QOL, treatment regret, and predictors of QOL after curative-intent RT for OPSCC.

This cross-sectional survey included patients with primary OPSCC treated with curative intent RT between 2007 and 2023 at a single tertiary institution. Patients completed validated EORTC QOL questionnaires and additional items assessing perceived health and treatment regret. Survival outcomes were estimated using Kaplan-Meier methods, and compared by p16 status using log-rank test. QOL scores were analysed as continuous variables using univariate and multivariable linear regression models, with prespecified dosimetric predictors tested against clinically corresponding EORTC QOL-HN43 symptom scales and adjusted for multiple comparisons. Of the 344 patients treated, 274 (80%) had p16-positive disease. At median follow of 7.7 years, 5-year overall survival was 90% for p16-positive versus 52% for p16-negative disease, and disease-free survival 89% versus 72%. Of 232 patients contacted, 186 (80%) completed the QOL survey at median 6.3 years after RT. 173 (93%) reported no treatment regret regarding RT. Mean global health status was 81.3/100, while dry mouth/sticky saliva was the most affected domain (mean 41.9/100). On multivariable analysis, older age was associated with worse global health status (-4.9 points per 10 years, p = 0.001) and higher contralateral mean parotoid dose with worse dry mouth/sticky saliva scores (10.1 points per 10 Gy, 95% CI: 3.7 to 16.5, p = 0.002). Chemotherapy and prior surgery were not associated with any domain.

Long-term survivors of OPSCC reported favourable global QOL and little treatment regret after RT. However, dry mouth/sticky saliva remained a substantial burden, and more likely with higher contralateral parotid mean dose. These findings support ongoing contralateral parotid sparing and consideration of unilateral neck irradiation when oncologically appropriate, while recognising the cross-sectional cohort and need for rigorous prospective studies in this area.

Localized laryngeal amyloidosis is a localized plasma cell-mediated process characterized by extracellular amyloid deposition confined to the larynx. Surgical excision has traditionally been the mainstay of treatment; however, complete resection may be anatomically difficult, and some patients experience persistent or progressive disease. Evidence supporting systemic therapy in localized disease remains limited. We report two adult female patients with biopsy-proven localized laryngeal amyloidosis without evidence of systemic involvement who were treated with plasma cell-directed immunochemotherapy in collaboration with ENT and head and neck surgery teams. Both patients presented with worsening dysphonia. One had persistent symptoms following partial surgical resection, while the other had multifocal unresectable supraglottic disease. Given limited surgical options, treatment with daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) was initiated. Therapy was well tolerated overall, with only mild neuropathy and mild leukopenia reported. After 6-14 cycles, both patients experienced marked improvement in voice quality and functional status, with no radiographic or clinical evidence of progression. Neither patient required additional surgical intervention, and both achieved durable symptom control during follow-up. These cases highlight a potential role for systemic plasma cell-targeted therapy in selected patients with localized laryngeal amyloidosis when surgery is noncurative or not feasible. Although local resection alone remains curative for many patients, multidisciplinary collaboration is essential in complex cases. Further study is needed to clarify patient selection, optimal treatment duration, and long-term outcomes of systemic immunochemotherapy in this rare disorder.

Breast cancer (BC) stands as a major medical concern for women because treatment hurdles include drug resistance combined with treatment failure and severe side effects and the intricate tumor microenvironment (TME). The treatment-resistant breast cancer subtype triple-negative breast cancer (TNBC) exhibits high aggressiveness through its failure to respond to targeted treatment yet maintains substantial metastatic potential. Hydrogels that react to stimuli have recently shown promise as solutions for solving these clinical issues. These hydrogels show response to precise stimuli which include pH, temperature and light and magnetic fields and biological elements including glutathione together with overexpressed enzymes MMP2 and MMP9 that appear within BC tumors. Hydrogel systems that respond to enzymes release drugs precisely at tumors thus minimizing drug side effects and optimizing their therapeutic effects. Hydrogel systems become more effective because of their ability to control drug delivery and combine various treatments when nanomaterials are incorporated as parts of their structure. Hydrogels must have adequate mechanical toughness because it enables them to withstand physical pressure without losing their drug release capabilities throughout the extended treatment period. This review has demonstrated that hydrogel-based drug delivery systems decrease tumor dimensions while inhibiting metastasis making them an advanced treatment strategy for BC management. The novel hydrogel platforms will lead to individualized treatment methods which show substantial promise to enhance breast cancer therapy results.

To investigate the clinical course of subsolid nodules (SSNs) in children and adolescents and explore risk factors associated with their progression.

This retrospective multicenter cohort investigation enrolled children and adolescents with incidental persistent SSNs between January 2010 and December 2024. The incidence of SSN progression, clinical characteristics, radiologic features, and survival status were assessed. Univariable and multivariable Cox regression analyses were used to identify potential risk factors for nodule growth and subsequent lung cancer diagnosis.

Overall, 333 incidental persistent SSNs in 241 patients (100 females; median age, 17 years; median follow-up period, 34 months) were included in the final analysis. 35 of the 333 (10.5%) SSNs showed interval growth, including 32 pure ground-glass nodules (PGGNs) and three part-solid nodules (PSNs). 22 PGGNs and two PSNs exhibited an increase in nodule size. One PSN demonstrated an increase in solid components, and ten PGGNs showed a new small solid component. Among 21 surgically resected nodules, approximately 95% (20/21) were early-stage lung adenocarcinoma. There were no deaths or metastases during the follow-up period. PSN was a significant predictor of growth. PSN and ≥ 10 mm were significant predictive risk factors for subsequent lung cancer diagnosis.

10.5% of incidental persistent SSNs exhibit subsequent growth. The identified risk factors were predominantly related to varying SSN characteristics. Our findings underscore that the individualized risk-stratified management strategies-long-interval follow-up (2 years or longer) for PGGNs and short-interval follow-up (annual or shorter) for PSNs-should be recommended to guide appropriate clinical decision-making.

QuestionDue to the lack of recommendations for SSNs in the pediatric population, clinicians and radiologists might inappropriately apply Fleischner guideline data to these patients. Findings10.5% of persistent SSNs in children and adolescents showed subsequent growth. PSNs are identified as an independent risk factor for predicting nodule growth. Clinical relevanceThe individualized risk-stratified management strategies should be recommended for the pediatric population with SSNs to guide appropriate clinical decision-making.

To assess the associations between imaging characteristics and histologic subtype in screen-detected lung cancers.

We retrospectively analyzed histologically confirmed lung cancers from the NELSON trial. Radiological features (location, margins, nodule type, size, volume, volume doubling time (VDT), pleural distance) were annotated using standardized protocols. Logistic regression adjusted for age, sex, smoking, and stage assessed associations with adenocarcinoma (ADC) versus non-ADC. Sensitivity analyses included models with VDT and were restricted to stage I-II disease.

Among 213 cancers, 67.5% were ADC and 32.5% non-ADC. Participants were predominantly male (82.4%), with a mean age of 64 years; 73.7% had stage I-II disease. ADCs were more often early stage (86.1% vs 47.8%), smaller (14.6 vs 17.3 mm), and more frequently located in the right upper lobe (49.3% vs 31.9%). In multivariable analysis, larger lesion size was associated with lower odds of ADC (odds ratio (OR) = 0.92, 95% CI 0.85-0.99), while pleural attachment increased the odds (OR = 6.67, 95% CI 1.20-33.33). Compared with the right upper lobe, lesions in the left lower (OR = 0.28), right lower (OR = 0.24), and right middle lobes (OR = 0.17) had lower odds. Model discrimination was acceptable (Area under the curve (AUC) = 0.75), with sensitivity 96% and specificity 29%. In sensitivity analyses, higher VDT was associated with ADC (OR = 5.65), with consistent findings in stage I-II disease.

In low-dose computed tomography screening, ADCs are smaller, slower-growing, and more often upper-lobe or pleural-based. These patterns may support improved diagnostic interpretation and personalized nodule management.

Question Radiological features guide malignancy risk, but their association with histologic subtype in screen-detected lung cancers remains unclear, limiting subtype-specific diagnostic interpretation. Findings Compared to non-adenocarcinomas, adenocarcinomas were smaller, more often pleural-based, and predominantly located in upper lobes, while lower and middle lobe lesions showed lower odds. Clinical relevance Recognizing imaging patterns associated with histologic subtype may improve understanding of tumor biology and inform future multimodal diagnostic approaches.