JNCI Journal of the National Cancer Institute最新文献

Background: Hematologic malignancies, including leukemias and lymphomas, remain life‑threatening diseases for which preventive strategies have not yet been established. Recent studies have suggested that sodium-glucose cotransporter 2 (SGLT2) inhibitors have cancer-suppressive properties. This study investigated whether SGLT2 inhibitors are associated with reduced risk of hematologic malignancies in patients with diabetes, using a large-scale medical database.

Methods: Data of patients with diabetes prescribed diabetes medications were extracted from the JMDC Payer database (January 2005 to November 2023). After exclusions, patients were categorized into SGLT2 inhibitor (N = 158,877) and non-SGLT2 inhibitor (N = 118,678) groups. Propensity score matching, accounting for patient characteristics, resulted in 102,478 matched patients per group. The primary endpoint was time to hematologic malignancy; secondary endpoints were time to lymphoma, leukemia, and their subcategories.

Results: The incidence of hematologic malignancies was lower in the SGLT2 inhibitor group than in the non-SGLT2 inhibitor group (P<.001, hazard ratio (HR)=0.73[0.62-0.86], risk difference at 5 years (RD)=-0.16%). Lymphoma incidence was also lower in the SGLT2 inhibitor group (P=.003, HR = 0.71[0.57-0.89], RD=-0.12%), whereas no clear evidence of difference was observed for leukemia (P=.06, HR = 0.76[0.57-1.01], RD=-0.02%). Lymphocytic leukemia was associated with lower incidence compared to the non-SGLT2 inhibitor group (P=.04, HR = 0.44[0.19-0.99], RD=-0.02%), whereas no clear evidence of difference was observed for myeloid leukemia (P=.12, HR = 0.76[0.54-1.08], RD=-0.01%). Regarding acute myeloid leukemia (AML), the incidence was low in the SGLT2 inhibitor group (P=.001, HR = 0.34[0.19-0.62], RD=-0.05%).

Conclusion: SGLT2 inhibitor use may be associated with lower risk of hematologic malignancies in adults with diabetes.

Testicular cancer survivors (TCS) experience excess cardiovascular disease (CVD) incidence and mortality. To address the urgent need for new risk prediction tools, we evaluated the AHA's 2024 PREVENT-equation among 1,759 TC survivors (TCS; median baseline age = 37 years). Baseline median 10- and 30-year CVD risks were 1.3% and 9.1%. Among evaluated survivors with follow-up (N = 737; median age = 45), each 5% increase in 10-year PREVENT risk conferred 2.94-fold odds (95%CI = 1.99-4.35, P < .001) of incident CVD. Those with 10-year PREVENT absolute risk defined as intermediate-high (≥7.5% per AHA) had 12.11-fold higher odds (P < .001). Associations were strongest after four cycles of etoposide/cisplatin (EPX4) (OR = 4.93, P < .001), possibly driven by lower eGFR and slightly older age (P < .001 each), and among TCS without vigorous baseline physical-activity (OR = 4.25, P < .001). EPX4 patients were among those less engaged in activity (P = .005). PREVENT equations, utilizing routine measures, can identify high-risk TCS, highlighting physical-activity as a key modifiable factor for early intervention.

Surveillance, Epidemiology, and End Results (SEER) multiple myeloma (MM) survival statistics (https://seer.cancer.gov/statfacts/html/mulmy.html) that have been used to guide MM management and control have been systematically overestimated due to the inclusion of smoldering multiple myeloma (SMM), a premalignant condition of MM. Using the latest SEER release, we estimated the extent of such overestimation in the survival statistics. In 2016, 77.9% out of 5,495 patients reported as overall MM were symptomatic MM and 10.9% were SMM. Median survival was 65.8 months for overall MM versus 56.8 months for symptomatic MM (p < .001). Inclusion of SMM overestimated MM survival by 9 months. Five-year relative survival estimates from 2015-2021 were 61.6% for overall MM, 57.9% for symptomatic MM, and 88.3% for SMM, versus SEER's reported 62.4%. Survival statistics for symptomatic MM and SMM should be reported separately to guide MM management and prevention at the population level.

The National Cancer Policy Forum (NCPF) of the National Academies of Sciences, Engineering, and Medicine was founded in 2006 to serve as a trusted venue for identifying and addressing high-priority policy issues in cancer research and care. NPCF takes a comprehensive, multisectoral, and multidisciplinary approach to strategically consider the entire continuum of cancer research and cancer care. Over the past two decades, the Forum has served a uniquely important role in examining both long-standing and emerging policy issues that are relevant to reducing the burden of cancer, both through prevention and by improving the care and outcomes for those diagnosed with cancer, and exploring solutions from multiple perspectives. The Forum has fostered actionable dialogue among a broad range of participants, including patient advocacy organizations, federal agencies, academia, professional organizations, nonprofits, and industry. NCPF activities inform the cancer community and the general public about a wide range of scientific, clinical, and policy issues through workshops, webinars, and the proceedings published after these convenings. Forum activities have influenced policy through the resulting publications and by providing input to National Academies consensus studies, which provide consensus recommendations. This commentary summarizes the breadth of topics addressed by the Forum over the years and examples of the impact of the Forum activities on policies and procedures, programs and practices, and participants and people around the globe.

Background: Men with suspected prostate cancer (PCa) undergo MRI before biopsy. However, about 30-50% of MRIs are negative (Prostate Imaging-Reporting and Data System (PI-RADS) score 1-2), representing a challenge for MRI resource utilization. This study evaluates PCa-polygenic risk scores (PRS) and clinical markers to optimize MRI utilization.

Methods: In this prospective study, 500 cancer-suspected men of Western European descent scheduled for MRI (09/2017-12/2022) were enrolled. Exclusions included prior PCa diagnosis, missing serum prostate-specific antigen (PSA) or PSA levels ≥25 ng/mL/cc. Patient-specific PCa-PRS were calculated using genotype data obtained from saliva-derived DNA samples. Participants were grouped as MRI-negative and -positive (PI-RADS score 3-5). Logistic regression was used to calculate odds ratios (OR) and to build multivariable risk models, including age, PSA, and PRS for MRI-positivity. Clinical utility was tested in a hold-out test set using decision curve analysis.

Results: 386 men (median age: 65, interquartile range: 53-77) were eligible for analysis, which showed highly significant associations between PCa-PRS (OR 1.56 (95% CI: 1.23-1.98); p<.001) with MRI-positivity, while PSA alone did not (OR 1.17 (0.93-1.46); p=.18). The highest net benefit was shown using a multivariable age and PCa-PRS model, increasing the proportion of MRI-positive men by 14% compared to PSA alone (60%/46%; p=.011).

Conclusions: Genotype-informed risk stratification using PCa-PRS could increase the proportion of cancer-suspicious findings at MRI, while identifying those who could safely avoid unnecessary MRI.

Head and neck cancers represent a diverse group of malignancies with significant heterogeneity in biology and prognosis, for which management of advanced-stage disease remains a formidable challenge. While the incorporation of immune checkpoint inhibitors has led the way to a new era of treatment possibilities, the current state-of-the-science calls for further innovation and a nuanced approach to clinical trial design to address a number of unmet needs. This white paper from the NRG Oncology Recurrent/Metastatic Head and Neck Working Group aims to critically identify gaps in clinical practice and the scientific literature and to propose actionable recommendations for future research in the framework of recurrent/metastatic squamous cell carcinoma of the head and neck.