Triple-negative breast cancer (TNBC), an aggressive subtype lacking oestrogen and progesterone receptors and amplification of HER2 receptors, accounts for 12% to 17% of breast cancers. Adjuvant and neoadjuvant chemotherapy improve survival; however, 30% to 40% of early-stage TNBC cases progress to metastatic disease. Recent evidence suggests that combining immune checkpoint inhibitors (PD-1/PD-L1 inhibitors) with chemotherapy may improve pathological complete response and event-free survival.

To assess the benefits and harms of immune checkpoint inhibitors (PD-1 or PD-L1 inhibitors) plus chemotherapy compared with chemotherapy for people with early TNBC.

We searched the Cochrane Breast Cancer Group Specialised Register, CENTRAL, MEDLINE, Embase, the WHO ICTRP, and ClinicalTrials.gov up to 6 November 2024. We also searched the reference lists of identified relevant trials or reviews for potentially eligible studies.

Randomised controlled trials (RCTs) comparing PD-1 or PD-L1 inhibitors plus chemotherapy with chemotherapy alone in participants with early TNBC.

Pairs of review authors independently identified studies for inclusion and performed data extraction and risk of bias assessment. Outcomes were pathological complete response, event-free survival (EFS), overall survival (OS), health-related quality of life (HRQoL), and overall rates of any adverse events and serious adverse events (SAEs). We calculated hazard ratios (HRs) for time-to-event data, risk ratios (RRs), odds ratios (ORs), or risk differences (RDs) for dichotomous outcomes, and mean differences (MDs) for continuous outcomes with corresponding 95% confidence intervals (CIs). We performed random-effects meta-analyses to summarise the evidence and evaluated the certainty of evidence using the GRADE approach.

We included seven RCTs with a total of 4341 participants. Two trials investigated PD-1 inhibitors (i.e. pembrolizumab), and five investigated PD-L1 inhibitors (i.e. durvalumab, atezolizumab) in the intervention group. Six studies used neoadjuvant chemotherapy (NACT), and one study used adjuvant chemotherapy (ACT) in the control group. The studies cover a five-year follow-up period. Two studies were at low risk of bias for all reported outcomes. The main limitation of the other trials was lack of blinding. PD-1 or PD-L1 inhibitors plus chemotherapy versus chemotherapy alone beforebreast cancer surgery PD-1 or PD-L1 inhibitors plus chemotherapy probably increase pathological complete response rate (RR 1.47, 95% CI 1.15 to 1.86; 6 studies, 1564 participants; moderate-certainty evidence); improve EFS (HR 0.64, 95% CI 0.52 to 0.79; 4 studies, 1789 participants; high-certainty evidence); and probably improve OS (HR 0.56, 95% CI 0.34 to 0.93; 3 studies, 1681 participants; moderate-certainty evidence) compared with chemotherapy alone. There may be little or no difference between PD-1 or PD-L1 inhibitors plus chemotherapy and chemotherapy alone in HRQoL (MD -1.49, 95% CI -3.88 to 0.91; 2 studies, 1395 participants; low-certainty evidence). PD-1 or PD-L1 inhibitors plus chemotherapy probably have little or no effect on any adverse events (OR 0.26, 95% CI 0.05 to 1.24; 3 studies, 1781 participants; moderate-certainty evidence) and treatment-related deaths (RD 0.2%, 95% CI -0.4% to 0.8%; 4 studies, 1761 participants; moderate-certainty evidence) compared with chemotherapy alone. PD-1 or PD-L1 inhibitors plus chemotherapy probably increase immune-related SAEs (OR 1.75, 95% CI 1.15 to 2.67; 5 studies, 2016 participants; moderate-certainty evidence) compared with chemotherapy alone. PD-1 or PD-L1 inhibitors plus chemotherapy versus chemotherapy alone afterbreast cancer surgery There may be little or no difference between PD-1 or PD-L1 inhibitors plus chemotherapy and chemotherapy alone in EFS (HR 1.11, 95% CI 0.87 to 1.42; 1 study, 2199 participants; low-certainty evidence), OS (HR 1.23, 95% CI 0.87 to 1.73; 1 study, 2199 participants; low-certainty evidence), HRQoL (MD -1.02, 95% CI -2.71 to 0.67; 1 study, 2168 participants; low-certainty evidence), any adverse events (OR 3.38, 95% CI 0.93 to 12.33; 1 study, 2177 participants; low-certainty evidence), and treatment-related deaths (RD -0.1%, 95% CI -0.4% to 0.2%; 1 study, 2177 participants; low-certainty evidence). PD-1 or PD-L1 inhibitors plus chemotherapy probably increase immune-related SAEs (OR 1.81, 95% CI 1.47 to 2.24; 1 study, 2177 participants; moderate-certainty evidence) compared to chemotherapy alone.

Combining PD-1 or PD-L1 inhibitors with chemotherapy compared to chemotherapy alone before breast cancer surgery improves pathological response, EFS, and OS in early TNBC. In contrast, the combination of PD-1/PD-L1 inhibitors with chemotherapy after breast cancer surgery may have little to no effect on EFS and OS in early-stage TNBC when compared with chemotherapy alone. The addition of PD-1 or PD-L1 inhibitors probably increases immune-related SAEs.

Muscle and adipose tissue quantified on computed tomography (CT) are associated with overall survival (OS), toxicity, and quality of life (QOL) in solid tumor malignancies. This study sought to evaluate the association of body composition with outcomes in older adult aggressive non-Hodgkin lymphoma (aNHL).

The authors conducted a longitudinal study of 105 adults ≥65 years old with aNHL receiving chemoimmunotherapy. They performed body composition analysis on pretreatment CTs (third lumbar vertebral level using validated, fully automated pipeline and manual quality control). They derived skeletal muscle (SMI), subcutaneous and visceral adipose tissue indices (SATI and VATI) and calculated corresponding age-adjusted and sex-adjusted z scores. They conducted univariate and multivariable (controlling for International Prognostic Index) regression models evaluating the association of body composition with OS, grade 3+ nonhematologic toxicity (tox), unplanned hospitalization (UH), and QOL (FACT-Lym) decline (QOLD).

Eighty-seven patients had imaging available for analysis. In univariate analyses, higher SATI z score had numerically higher odds of tox (odds ratio [OR], 1.77; p < .01) and UH (OR, 1.67; p = .01), and numerically more QOLD (OR, 1.58; p = .06). No association was observed for VATI z score. Higher SMI z score had numerically better OS (hazard ratio [HR], 0.47; p = .04) and numerically lower odds of QOLD (OR, 0.52; p = .07). In multivariable analyses, higher SMI z score (HR, 0.50; p = .05) had numerically better OS, whereas higher SATI z score (OR, 1.89; p < .01) had numerically higher odds of tox.

In this exploratory analysis of older patients with aNHL, body composition on baseline CT was associated with OS and tox, underscoring imaging's potential for risk stratification.

To test the effectiveness of a surgical web-based decision aid (DA) in improving knowledge.

DAs support decision making by providing information about the options.

A stepped wedge trial was conducted in 10 National Cancer Institute Community Oncology Research Program clinics (Alliance for Clinical Trials in Oncology). Clinics were randomized to time of transition from usual care (UC) to delivery of a web-based DA. Patients with stage 0 through 3 breast cancer being considered for surgery were enrolled. Knowledge (primary outcome) was measured using the Breast Cancer Surgery Decision Quality Instrument and patients were asked, "How informed do you feel?" Intervention effects were tested with linear mixed-effects models, accounting for surgeon and clinic-level clustering, time, and enrollment after COVID. Additional models controlled for demographics.

A total of 44% of DA arm patients reviewed the DA and 58% in UC arm reported reviewing "any information." Being in the DA arm versus UC was not associated with knowledge. However, "review of information" was associated with higher knowledge. In addition, non-White race and lower education were associated with lower knowledge. The DA arm was associated with higher perceptions of feeling informed (parameter estimate 1.36; 95% CI, 0.18-2.55; p = .02); this persisted even when controlling for review of information or demographics.

Improved knowledge was not demonstrate with a web-based DA versus UC. Interestingly, the DA was associated with a higher likelihood of feeling informed. Future research will explore the discrepancy between patients feeling informed but having low knowledge, especially for disadvantaged patients.

ClinicalTrials.gov Identifier: NCT0376600.

Myasthenia gravis (MG) is an autoantibody-mediated neuromuscular disease often co-occurring with other autoimmune diseases (ADs). We aimed to determine the temporal relationship between other ADs and MG.

We conducted a nationwide, population-based case-control study of MG patients and 10 age-, sex-, and index date-matched controls from 1985 to 2020. We used conditional logistic regression to estimate odds ratios (ORs) for AD diagnoses preceding MG, and Cox regression to calculate hazard ratios (HRs) for ADs succeeding MG. Analyses were stratified by sex, age group (≤ 50 and > 50 years), baseline comorbidity, and time intervals (0-5 and 5-10 years) before and after MG.

Our study population included 2110 MG cases (1060 females) and 21,100 matched controls, with 27.4% ≤ 50 years old. Before the index date, 5.2% of MG patients and 2.7% of controls were diagnosed with another AD, yielding an OR of 1.9 (95% CI 1.5-2.3). After MG diagnosis, 5.0% of MG patients and 2.7% of controls received an AD diagnosis (HR 2.1, 95% CI 1.2-2.6), with an overrepresentation of patients ≤ 50 years or younger, females, and patients with a low comorbidity level. Most diagnoses occurred within 5 years before MG onset. The strongest associations were observed for autoimmune thyroiditis, systemic lupus erythematosus, and pernicious anemia.

MG patients are twofold more likely to be diagnosed with another AD, especially MG patients ≤ 50 years and women, suggesting a shared autoimmune predisposition. Understanding the AD spectrum associated with MG could improve diagnostic accuracy and treatment strategies.

Intussusception is the telescoping of one part of the bowel into an adjacent part, and it is most common in the pediatric population. In the adult population, intussusception is rare; however, it is likely secondary to a pathological lead point, such as a neoplasm. Intussusception has been described secondary to Meckel's diverticulum, but ileocolic intussusceptions from an inverted Meckel's diverticulum are rare. We describe here a rare case of a 33-year-old male with no past medical or surgical history presenting with an acute abdomen and imaging findings of ileocolic intussusception with bowel ischaemia. He underwent an emergency laparoscopy, where reduction was attempted but unsuccessful and an ileocolic resection was performed. Histological findings were consistent with ileocolic intussusception containing an inverted Meckel's diverticulum as a lead point. Surgical reduction and/or resection remain the mainstay of treatment when they present hemodynamically unstable and/or concerns for bowel ischaemia/perforation.

Dysembryoplastic neuroepithelial tumor (DNET) is a benign central nervous system neoplasm, usually diagnosed in pediatric patients with epilepsy. We describe a case of a 57-year-old man presenting with a first episode of generalized tonic-clonic seizure and subacute cognitive decline, in whom a multicystic right temporal lobe lesion was detected. Further workup led to a new diagnosis of human immunodeficiency virus (HIV) infection. Comprehensive investigations excluded infectious and malignant etiologies. Review of prior imaging, combined with multidisciplinary input, led to a diagnosis of DNET. Two-year follow-up confirmed radiological stability, and the patient remained seizure-free under antiepileptic treatment. This case highlights the importance of expanding the differential diagnosis of cerebral lesions in HIV-positive adults and utilizing prior imaging to guide clinical decision-making.

Basal cell carcinoma with matrical differentiation (BCCMD) is a rare subtype of basal cell carcinoma (BCC), with only about 43 cases described in the literature. It is characterized by typical BCC morphology, including basaloid cell aggregates with peripheral palisading, along with areas of matrical differentiation containing shadow cells, trichohyalin granules, and corneocytes. Immunohistochemically, the basaloid component expresses BerEP4, while the matrical component often shows diminished BerEP4 and positive β-catenin and epithelial membrane antigen staining. BerEP4 represents an immunohistochemical marker that highlights basaloid cells and is commonly used to aid in identifying basal cell carcinoma and distinguishing it from other skin tumors. A 79-year-old man presented with a new 9-mm pearly papule on the right forehead, which was diagnosed as BCCMD following histopathologic and immunohistochemical evaluation. The lesion was successfully treated with one stage of Mohs micrographic surgery, and the patient remained disease-free after nine months of follow-up. Due to overlapping histologic features with other follicular neoplasms, diagnosis is critical, and management strategies are not well established. While most cases have been treated with standard excision, Mohs surgery may offer superior margin control, especially for tumors in cosmetically sensitive regions. Rare reports of metastasis suggest a potentially more aggressive clinical course than typical BCC. Comprehensive excision and long-term surveillance are recommended to optimize outcomes and further characterize this rare variant.

Chronic obstructive pulmonary disease (COPD) is a recognized risk factor for lung adenocarcinoma (LUAD), but the molecular mechanisms behind this association are still unclear. This study aims to reveal shared key genes and pathways involved in both COPD and LUAD, and identify potential biomarkers and therapeutic targets.

Two-sample Mendelian randomization (MR) analysis using Genome-Wide Association Study (GWAS) data was performed to evaluate genetic causality. Differential expression analysis was performed on GSE76925 (COPD) and GSE116959 (LUAD), followed by LASSO regression, enrichment analysis, immune cell infiltration analysis, RNA modification analysis, competing endogenous RNA (ceRNA) network construction, and drug sensitivity prediction. Single-cell RNA sequencing data (GSE270667, GSE189357) were used to explore cell-type-specific expression, and qPCR was performed to validate gene expression in patient blood samples.

MR confirmed the genetic relationship between COPD and LUAD. Three key genes (FCRLA, GREM1, and MMP9) were significantly upregulated and involved in immune regulation, extracellular matrix (ECM) remodeling, and the PI3K-Akt signaling pathway. Single-cell analysis revealed that these genes were specifically expressed in B cells, T cells, and monocytes. Multiple omics analyses indicated epigenetic and RNA level regulation. Several candidate drugs have been identified.

FCRLA, GREM1, and MMP9 are inflammation-associated genes that may link the pathobiology of COPD and LUAD, and serve as valuable biomarkers with therapeutic potential in high-risk populations.

Evidence on the efficacy and safety of radioligand therapy (RLT) in lung neuroendocrine tumors (LNETs) remains scarce. The limited data available, derived mainly from retrospective analyses are based on small patient cohorts and heterogeneous treatment protocols. The objective of this study was to assess the efficacy and safety of RLT in patients with SSTR-positive LNETs treated with either [¹⁷⁷Lu]Lu-DOTA-TATE or tandem therapy with [⁹⁰Y]Y-DOTA-TATE/[¹⁷⁷Lu]Lu-DOTA-TATE at Polish ENETS Center of Excellence.

We conducted a retrospective analysis of 22 LNET patients who received RLT and had complete follow-up data. Treatment response and survival outcomes were evaluated. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Prognostic associations with PFS and OS were explored using univariate and multivariable Cox proportional hazards models, treatment-related AE were graded according to CTCAE.

A total of 22 patients with LNETs (Med. 61 years; 68.2% male) were included. Histology comprised 31.8% typical carcinoid, 54.5% atypical carcinoid, and 13.6% LNET G3. 14 patients received [¹⁷⁷Lu]Lu-DOTA-TATE and 8 tandem [⁹⁰Y]Y/[¹⁷⁷Lu]Lu-DOTA-TATE. At a median follow-up of 54 months, median PFS and OS were 16.0 months (95% CI: 11.2-20.8) and 62.0 months (95% CI: 30.7-93.3), respectively. PFS was longer in patients with high SSTR uptake (34vs16 months; p=0.021) and, in unadjusted exploratory analyses, in those treated with tandem therapy (34vs16 months; p=0.037). OS differed significantly by histology and by prior chemotherapy, while FDG-avid disease was associated with shorter PFS and OS. However, these subgroup comparisons are based on a very small sample and should be regarded as exploratory and interpreted with caution. Treatment was generally well tolerated, with hematologic toxicity being the most common.

RLT demonstrated signals of clinically meaningful activity and an acceptable safety profile in patients with advanced LNETs in this small retrospective cohort. Outcomes were numerically more favorable in individuals with high SSTR uptake and in those treated with tandem therapy, but the study was not designed to compare treatment regimens. These exploratory findings should be regarded as hypothesis-generating only and do not provide evidence of comparative efficacy.

Thymic neuroendocrine neoplasms (tNENs) are rare anterior mediastinal tumors with aggressive behavior and can be misdiagnosed as type A thymoma on small biopsies or intraoperative frozen sections, although accurate distinction is critical for prognosis and management. Type A thymoma, while generally considered a low-grade malignant tumor with a favorable prognosis, comprises a small subset that exhibits aggressive features and develops distant metastases after surgical resection; these tumors are classified as atypical type A thymomas. A 72-year-old woman had a history of resected atypical type A thymoma two years earlier. Surveillance computed tomography revealed a 15-mm mediastinal nodule located anterior to the superior vena cava with intense fluorodeoxyglucose uptake on positron emission tomography-computed tomography. Frozen sections showed a proliferation of small- to medium-sized polygonal and short spindle cells arranged in solid nests and trabeculae without a lymphocyte-rich background, and were interpreted as recurrent atypical type A thymoma. In contrast, imprint cytology demonstrated monomorphic small- to medium-sized tumor cells with round to oval nuclei, finely granular "salt-and-pepper" chromatin, inconspicuous nucleoli, loose cohesion, and scattered rosette-like structures, strongly suggesting a tNEN. Permanent sections revealed nests, trabeculae, and rosettes of small- to medium-sized polygonal cells with granular chromatin and approximately four mitoses per 10 high-power fields, without large confluent necrosis. Immunohistochemistry showed diffuse positivity for CD56, chromogranin A, synaptophysin, and insulinoma-associated protein 1; a Ki-67 index of about 20%; negativity for CD5, CD117 (c-KIT), p63 (TP63), CK5/6, and CD20; and the absence of TdT/CD99-positive immature T cells, supporting a diagnosis of thymic atypical carcinoid. This case highlights the complementary value of imprint cytology and an appropriate immunohistochemical panel, in addition to frozen sections, in avoiding misclassification of tNENs as type A thymoma.