JNCI Journal of the National Cancer Institute最新文献

Background: Despite HPV vaccines' availability for over a decade, coverage across the US varies. While some states have tried to increase HPV vaccination coverage, most model-based analyses focus on national impacts. We evaluated hypothetical changes in HPV vaccination coverage at the national and state levels for California, New York, and Texas using a mathematical model.

Methods: We developed a new mathematical model of HPV transmission and cervical cancer, creating US and state-level models, incorporating country- and state-specific vaccination coverage and cervical cancer incidence and mortality. We quantified the national and state-level impact of increasing HPV vaccination coverage to 80% by 2025 or 2030 on cervical cancer outcomes and the time to elimination defined as < 4 per 100k women.

Results: Increasing vaccination coverage to 80% in Texas over ten years could reduce cervical cancer incidence by 50.9% (95% credible interval [CrI]: 46.6-56.1%) by 2100, from 1.58 (CrI : 1.19-2.09) to 0.78 (CrI : 0.57-1.02) per 100,000 women. Similarly, New York could see a 27.3% (CrI : 23.9-31.5%) reduction, from 1.43 (CrI : 0.93-2.07) to 1.04 (Crl : 0.66-1.53) per 100,000 women, and California a 24.4% (CrI : 20.0-30.0%) reduction, from 1.01 (Crl : 0.66-1.44) to 0.76 (Crl : 0.50-1.09) per 100,000 women. Achieving 80% coverage in five years will provide slightly larger and sooner reductions. If the vaccination coverage levels in 2019 continue, cervical cancer elimination could occur nationally by 2051 (Crl : 2034-2064), but state timelines may vary by decades.

Conclusion: Targeting an HPV vaccination coverage of 80% by 2030 will disproportionately benefit states with low coverage and higher cervical cancer incidence. Geographically focused analyses can better inform priorities.

Background: Pre-clinical cancer studies ascribe promising anticancer properties to metformin. Yet, clinical findings vary, casting uncertainty on its therapeutic value for non-small cell lung cancer (NSCLC) patients. We hypothesized that metformin could benefit obese and overweight patients with NSCLC.

Methods: We retrospectively analyzed two clinical cohorts and employed complementary mouse models to test our hypothesis. One cohort included NSCLC patients with overweight BMI (≥25, n = 511) and non-overweight BMI (<25, n = 232) who underwent lobectomy, evaluating metformin's impact on clinical outcomes. Another cohort examined metformin's effect on progression-free survival (PFS) after immune checkpoint inhibitors (ICI) in overweight (n = 284) vs non-overweight (n = 184) NSCLC patients. Metformin's effects on tumor progression, antitumor immunity, and ICI response in obese and normal-weight mice were assessed with lung cancer models.

Results: Metformin is associated with increased recurrence-free survival in overweight patients (HR = 0.47 [95%CI = 0.24-0.94], p = .035) after lobectomy. It also corrected accelerated tumor growth in diet-induced obese mouse models in a lymphocyte-specific manner while reversing several mechanisms of immune suppression potentiated by obesity. PD-1 blockade coupled with metformin was more effective at limiting tumor burden in obese mice and correlated with PFS only in overweight patients on immunotherapy (HR = 0.60, [95%CI = 0.39-0.93], p = .024).

Conclusions: Metformin may improve lung cancer-specific clinical outcomes in obese and overweight lung cancer patients and enhance immunotherapy efficacy in this growing population as well. This work identifies obesity as a potential predictive biomarker of metformin's anticancer and immunotherapy-enhancing properties in lung cancer while shedding light on the underlying immunological phenomena.

Introduction: Prognostic markers for overall survival (OS) in resected pancreatic ductal adenocarcinoma (PDAC) are well-established but remain unclear following neoadjuvant therapy (NAT). This systematic review and meta-analysis aimed to determine factors associated with OS following NAT in resected PDAC.

Methods: The PubMed, Embase, Scopus, Web of Science, and Cochrane CENTRAL databases were systematically searched from inception till May 2024. Studies that reported univariable and multivariable hazard ratios (HRs) were included if patients underwent NAT and resection for localized PDAC. Study quality assessment was performed using the Newcastle-Ottawa scale. Meta-analysis was performed using generic inverse-variance random-effects models.

Results: Among 2,208 unique articles identified by the search, 92 were included in the meta-analysis. Eighty-five of these were of 'good' and 7 of 'poor' quality. The NAT regimen was described in 84 studies, of which 62 included patients treated with FOLFIRINOX (FFX). Margin status, nodal disease, AJCC T-stage, and normalization of CA19-9 after NAT were prognostic for OS, while age, sex, perineural invasion, baseline tumor size, and baseline CA19-9 were not. The test for subgroup differences between ypN-substages was not significant in the multivariable model. Neoadjuvant FFX was associated with better survival than other regimens.

Conclusions: This meta-analysis identified margin status, nodal disease, AJCC T-stage, and normalization of CA19-9 after NAT as prognostic factors for OS in patients with resected localized PDAC following NAT.

Many components of long-term cancer follow-up and survivorship care are managed in the primary care context. Given the important role that primary care has in survivorship care, it is critical to ensure that teams in these settings are prepared to address long-term needs. Evidence-based strategies to deliver survivorship care in primary care settings in the US remain limited. The National Cancer Institute (NCI) Office of Cancer Survivorship (OCS) conducted a day-long virtual event, Enhancing Capacity for Primary Care Research in Cancer Survivorship: A Workshop for Action, on February 28, 2024, to discuss research needs addressing the intersection between primary care and cancer survivorship. Topics discussed to advance this area of research included: system-level interventions, methods and measurement, and mentorship and research team building, especially for early career researchers. The purpose of this report is to provide a summary of the key findings. Gaps and opportunities include: (1) health systems-level research that investigates primary care practice-level capacity, (2) identification and characterization of the targeted cancer survivor populations for primary care research; (3) leveraging electronic medical records to track relevant patient outcomes throughout survivorship; and (4) development/creation of communities of practice to support and build research capacity. Team science approaches were identified as a core strategy to advance survivorship research. The meeting closed with a reflection and call to action focused on building collaborations that span different research areas, disciplines, and organizations and building a broad network of a primary care practice focused research.

The marked increase in incidence and mortality in endometrial cancer over the last two decades is driven in part by rising rates of higher grade, more aggressive endometrial cancers with mutations in TP53, uterine serous cancers and their dedifferentiated component, uterine carcinosarcomas (collectively USC). USC rates have been increasing among all racial and ethnic groups, with higher rates of this aggressive uterine cancer in Black women. The National Cancer Institute (NCI) hosted a workshop in June 2023 to examine the diverse aspects of USC across epidemiology, biology, and molecular genetics, and to advance knowledge from basic to preclinical and translational efforts. Key stakeholders came together including basic scientists, clinical investigators, and patient advocates to identify critical research gaps that, when addressed, would facilitate more comprehensive and rapid progress in understanding and ultimately treating USC across all patients. NCI released a supplemental funding opportunity (NOT-CA-24-044) in Spring 2024 to facilitate rapid translation of these recommendations.

Background: While female survivors of Hodgkin lymphoma (HL) have an increased risk of breast cancer (BC), no BC risk prediction model is available. We developed such models incorporating mean radiation dose to the breast or breast quadrant-specific radiation doses.

Methods: Relative risks and age-specific incidence for BC and competing events (mortality or other subsequent cancer) were estimated from 1194 Dutch five-year HL survivors, treated at ages 11-40 during 1965-2000. Predictors were doses to ten breast segments or mean breast radiation dose, BC family history, year of and age at HL diagnosis, ages at menopause and first live birth. Models were independently validated using U.S. Childhood Cancer Survivor Study cohort participants.

Results: Predicted absolute BC risks 25 years after HL diagnosis ranged from 1.0% for survivors diagnosed at ages 20-24, with <10 Gy mean breast radiation dose and menopausal 5 years after HL diagnosis, to 22.0% for survivors 25-29 years at diagnosis, ≥25 Gy mean breast dose, and no menopause within 5 years. In external validation, the observed/expected BC case ratio was 1.19 (95% confidence interval 0.97 to 1.47) for the breast segment-specific doses model, and 1.29 (1.05 to 1.60) for the mean breast dose model. The areas under the receiver operating characteristic curve were 0.68 (0.63 to 0.74) and 0.68 (0.62 to 0.73), respectively.

Conclusion: Breast segment-specific or mean breast radiation dose with personal and clinical characteristics predicted absolute BC risk in HL survivors with moderate discrimination but good calibration, rendering the models useful for clinical decision-making.