Cancer最新文献

Background: Although trastuzumab deruxtecan (T-DXd) demonstrated unprecedented intracranial efficacy in HER2-positive breast cancer brain metastases (BCBM), its association with interstitial lung disease (ILD)/pneumonitis posed a critical safety concern in this high-risk population. Previous safety assessments lacked BCBM-specific analysis of ILD.

Methods: This systematic review and meta-analysis (PROSPERO identifier CRD420251130832) followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The authors searched the PubMed, Embase, Web of Science, and Cochrane databases and major oncology conferences through July 2025 for studies that reported T-DXd-related, treatment-emergent adverse events (TEAEs) in patients with HER2-positive BCBM, focusing on ILD/pneumonitis incidence and severity. Pooled rates were calculated using random effects models.

Results: In total, nine studies involving 684 patients with BCBM were included. The pooled incidence rates for all-grade and grade ≥3 ILD/pneumonitis were 10% (95% confidence interval [CI], 5%-16%) and 2% (95% CI, 1%-4%), respectively. ILD/pneumonitis led to discontinuation in 11% (95% CI, 0%-24%) of patients with BCBM. No fatal ILD events were reported. Overall, any-grade TEAEs occurred in 97% of patients, with grade ≥3 TEAEs occurring in 48%. Fatigue and nausea were the most prevalent all-grade TEAEs, with incidences of 67% and 60%, respectively.

Conclusions: In patients with BCBM, T-DXd-associated ILD/pneumonitis occurred in 10% of patient and frequently necessitated treatment modification. Although no fatal ILD was observed, the high discontinuation rate underscored the imperative for vigilant monitoring and protocol-guided management to mitigate pulmonary toxicity while preserving intracranial efficacy.

Background: Depression in older adults with cancer (OACs) is poorly captured by patient-reported outcomes (PROs) because traditional criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM) may overlook unique symptoms in OACs. By using US Food and Drug Administration Guidance for Industry on PRO development, the authors conceptualized depression in OACs and created the Older Adults with Cancer-Depression Scale (OAC-D). This study evaluates the psychometric properties of this novel measure.

Methods: Based on a refined conceptual model informed by literature reviews and qualitative work with patients and experts in geriatric oncology, a 35-item draft PRO was developed. The draft was administered, alongside legacy measures, to OACs aged >70 years and older at a comprehensive cancer center and across the United States. Exploratory graph analysis was used to identify items and factors.

Results: The mean ± standard deviation age of the 155 participants was 76 ± 5 years, and 56% were women. Exploratory graph analysis yielded an 18-item measure with five domains: (1) interest and enjoyment, (2) purpose and meaning, (3) loneliness, (4) social withdrawal, and (5) regret and guilt. Internal consistency (Cronbach alpha, .85-.95) and test-retest reliability (intraclass correlation coefficient = 0.61-0.80) were strong. Convergent validity was supported by correlations with the Patient Health Questionnaire-9 (r = 0.75), the Patient-Reported Outcomes Measurement Information System anxiety score (r = 0.69), and the Patient-Reported Outcomes Measurement Information System physical score (r = -0.39). Known groups analysis demonstrated higher OAC-D scores for those with a history of depression (p < .001).

Conclusions: The OAC-D identified five unique domains of depression, only one of which overlapped with DSM criteria. It demonstrated robust psychometric properties, providing a nuanced alternative to DSM-based measures and addressing the distinctive psychological challenges of cancer and aging.

Background: Germline pathogenic variants can inform targeted therapy for metastatic prostate cancer (mPC), and improve cancer early detection and risk reduction for family members. Guidelines recommend germline genetic testing be offered to all men with mPC, yet uptake of testing is only 10%-12%.

Methods: This prospective study enrolled veterans participating in the VA Million Veteran Program (MVP) with a diagnosis of mPC. Veterans were contacted by mail with option to opt-out of future contact. Eligible veterans who did not opt-out were mailed study information and received a follow-up phone call to establish interest in germline testing. Participants provided verbal consent and were mailed a saliva collection kit for a CLIA-level multigene cancer predisposition gene panel test. Results were disclosed to the patient and oncology provider. All steps were performed with genetic counseling support.

Results: Of 2104 eligible patients, 1952 veterans with mPC did not opt out. Of these, 681 (35%) provided consent and 459 (24%) completed testing. Of those who were approached 63% were White and 25% were Black. Fifty-nine (13%) of those completing testing carried a germline pathogenic variant in a cancer risk gene. Of the 37 eligible for targeted therapy, 14 received targeted therapy, 18 did not yet have an indication for that therapy, and five were deceased without having received targeted therapy.

Conclusions: Participant completion of remote germline testing was facilitated at rates higher than the 10% previously reported. Remote genetic testing can augment uptake of testing in large, integrated health care systems.

Minimal residual disease (MRD) refers to the presence of residual cancer cells or tumor-derived fragments that persist after treatment and remain undetectable by conventional imaging or protein-based assays. Circulating tumor DNA (ctDNA) has emerged as a dynamic biomarker for MRD detection. It enables real-time disease monitoring, prognostication, and often therapeutic decision-making. Two major ctDNA approaches exist, tumor-informed and tumor-agnostic, and they differ in sensitivity, specificity, and clinical feasibility. Recent clinical trials have supported a prognostic and predictive utility of ctDNA MRD in gastrointestinal, lung, breast, and other malignancies, with positive postoperative or post-treatment MRD status correlating with higher recurrence risk and inferior survival outcomes. However, integration into clinical practice remains limited by challenges, including tumor heterogeneity, variable ctDNA shedding across tumor stage, location and timing, lack of standardized assay interpretation, and cost-effectiveness concerns. Emerging technologies such as methylation-based sequencing, ultra-deep next-generation sequencing, and machine learning-driven risk models hold promise for improving detection accuracy and clinical applicability. Ongoing clinical trials are expected to determine the impact of earlier MRD detection and intervention on patient outcomes, potentially supporting the broader adoption of ctDNA MRD. In this article, the authors reviewed the recent clinical applications, limitations and future directions of MRD in solid tumors.