Breast cancer screening is essential for reducing mortality, yet current modalities face significant barriers, including high costs, limited accessibly, and reliance on ionizing radiation, which leads many women to forego regular screenings. Magnetic resonance imaging (MRI) offers a radiation-free alternative, but its adoption for screening is constrained by cost, availability, and the need for IV contrast administration. In this study, we demonstrate the feasibility of ultra-low field (ULF) unilateral breast MRI for screening applications. ULF MRI was performed on 11 healthy women in a prone position. These participants were healthy women without a history of breast cancer. Three breast radiologists could reliably delineate breast outlines and distinguish fibroglandular tissue (FGT) from adipose tissue. Tissue patterns (fatty, scattered, heterogeneous, and extreme FGT) were consistently identified. In two additional patients with prior breast cancer, ULF MRI effectively eliminated magnetic susceptibility artifacts from surgical biopsy clips and in one of these patients revealed post-surgical changes following lumpectomy. Additionally, in another patient, a > 3 cm cyst, previously confirmed on standard clinical ultrasound, was feasible to visualize with ULF MRI. These findings establish the technical feasibility of ULF breast MRI. While preliminary, they motivate further technical development and evaluation to clarify its capabilities and limitations.

Chimeric antigen receptor (CAR) therapies have expanded beyond T-cells with addition of natural killer (NK) cells. In ovarian cancer, long-term survival remains poor with the rising need for new therapies. Therefore, this meta-analysis evaluated the pre-clinical efficacy of emerging CAR-NK therapies in ovarian cancer models. Following PRISMA-guidelines and registered protocol (PROSPERO, CRD420251131530), literature from PubMed, Web of Science, and Scopus was retrieved till 30-06-2025 for pre-clinical in-vivo studies of CAR-NK therapy in ovarian cancer. Studies without in-vivo components or human CAR-NK were excluded. Primary outcomes were ratio of means (ROM) for tumor burden and median survival ratio (MSR). Data was analyzed in JASP™ and risk of bias (RoB) was determined using SYRCLE's RoB tool for animal studies. Fourteen experiments (21 CAR-NK groups) were included. CAR-NK significantly reduced tumor burden versus untreated controls (ROM 0.09 [0.03-0.32], p < 0.001) and unmodified/mock NK-cells (ROM 0.18 [0.08-0.42], p < 0.001). Survival was significantly prolonged (MSR 1.67 [1.31-2.14] vs. control; 1.40 [1.08-1.83] vs. unmodified/mock NK, both p < 0.05). Subgroup analyses revealed no significant modifiers, though trends favored mesothelin-targeted and NK-92-based CARs. Limited safety data indicated no cytokine release syndrome or graft-versus-host disease. Small sample size in subgroup analyses and unclear RoB in certain areas are some limitations of this study. However, the pooled estimates were robust to sensitivity analyses and relatively insignificant heterogeneity in survival outcomes could be important for poor long-term survival in ovarian cancers. CAR-NK demonstrates potential pre-clinical efficacy in ovarian cancer models, outperforming naive NK-cells with a consistent survival benefit.

Compared to younger patients, older patients report differences in the occurrence, severity, and distress of common symptoms associated with cancer and its treatment.

Identify subgroups of younger and older patients with distinct symptom burden profiles and evaluate for risk factors associated with these profiles.

Oncology outpatients (n = 1329) were dichotomized into younger (< 60 years) and older (≥ 60 years) groups. Data included demographic and clinical questionnaires and measures of global, cancer-specific, and cumulative life stress, resilience, and coping. Memorial Symptom Assessment Scale evaluated the occurrence of 38 common symptoms. Separate latent class analyses were done within each age group to identify distinct symptom profiles. Differences among latent classes in demographic and clinical characteristics, stress, resilience, and coping were evaluated.

In younger group (n = 730), four profiles were identified (i.e., All Low (28.8%), Moderate Physical and Lower Psychological (21.9%), Moderate Physical and Higher Psychological (34.6%), All High (14.7%)). Compared to All Low class, All High class was younger, more likely to be female, had a higher comorbidity burden, and a lower functional status, as well as higher stress and lower resilience scores. In the older group (n = 599), three profiles were identified (i.e., Low (34.4%), Moderate (47.9%), High (17.7%)). Compared to Low class, High class was more likely to be female, had a higher comorbidity burden and lower functional status, and received a more toxic chemotherapy regimen, as well as higher stress and lower resilience scores.

Study is the first to use latent class analysis to identify distinct symptom burden profiles in younger versus older oncology patients. In the younger group, differences in the occurrence of psychological symptoms differentiated among the symptom burden profiles. While some of the risk factors were similar, within the older group, patients in the High symptom burden class used a higher number of disengagement coping strategies.

Spontaneous cancers in client-owned dogs often closely recapitulate their human counterparts with respect to clinical presentation, histological features, molecular profiles, response and resistance to therapy, and the evolution of drug-resistant metastases. In several instances, the incorporation of dogs with cancer into the preclinical development path of cancer therapeutics has influenced outcomes by helping to establish pharmacokinetic/pharmacodynamics relationships, dose/regimen, expected clinical toxicities, and ultimately the potential for biologic activity. As our understanding regarding the molecular drivers and immune landscape of canine cancers has improved, unique opportunities have emerged to leverage this spontaneous model as a mechanism to better guide cancer drug development so that therapies likely to fail are eliminated earlier, whereas those with true potential are optimized prior to human trials. Both pets and people benefit from this approach, because it provides dogs with access to cutting-edge cancer treatments and helps to insure that people are given treatments with a greater probability of success.

In Study 309/KEYNOTE-775 (NCT03517449), lenvatinib+pembrolizumab versus chemotherapy significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) in advanced endometrial cancer (EC). We report 5-year follow-up results.

Participants had advanced/recurrent/metastatic EC with progressive disease after one prior platinum-based chemotherapy regimen, measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), and no prior receipt of anti-programmed cell death protein 1 or anti-programmed cell death ligand 1 agents. Participants were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks or chemotherapy (doxorubicin or paclitaxel). Pembrolizumab was given for ≤35 cycles. Primary endpoints were OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included ORR per RECIST v1.1 by BICR and safety. Efficacy endpoints were analyzed using Cox regression, Kaplan-Meier, and Miettinen and Nurminen methodology.

827 participants were randomized. At data cut-off (February 26, 2025), overall median follow-up was 68.8 months; 139 participants were alive (lenvatinib+pembrolizumab, n=86; chemotherapy, n=53), and all had ended their treatment in this study. Five-year OS rate was 16.7% with lenvatinib+pembrolizumab versus 7.3% with chemotherapy in mismatch repair-proficient EC, 36.5% versus 9.8% in mismatch repair-deficient EC, and 19.9% versus 7.7% in all-comers. Five-year PFS rates were 6.3% versus 2.1%, 26.4% versus 10.8%, and 9.8% versus 3.2%, respectively. In all-comers, treatment-related adverse events led to any treatment discontinuation in 32.3% versus 5.9%. Subsequent systemic anticancer therapy was used by 44.8% versus 51.2% (lenvatinib+pembrolizumab by 2.4% vs 10.1%).

Results were consistent with the primary analysis despite increased use of subsequent systemic anticancer therapy and crossover to lenvatinib+pembrolizumab in the chemotherapy group. The continued durable benefit, including OS, with lenvatinib+pembrolizumab and no new safety signals lend further support for this regimen as a standard of care therapy for EC.

Aging induces senescence-related immune changes that affect antitumor immunity and treatment efficacy. Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) are approved for recurrent and metastatic head and neck squamous cell carcinoma (SCC). We aimed to investigate how aging alters the tumor immune microenvironment and modulates ICI efficacy in a murine SCC model.

We analyzed SCCVII tumor growth and phenotypes of tumor-draining lymph node (TDLN) cells and tumor-infiltrating leukocytes in young, middle-aged, and aged mice. We examined the effects of antibodies against PD-1 ligand-1 (PD-L1) in young and aged mice.

Tumor growth accelerated with age and was accompanied with increased CD206⁺ M2-like tumor-associated macrophage (TAM) accumulation. In intact LNs and TDLNs, CD8⁺ T cells (CD8T), interferon (IFN)-γ, and PD-1 expression increased with age. The CD8T phenotype in the tumor microenvironment (TME) differed between young and aged mice; however, CD8T and regulatory T cells preferentially recruited to the TME across all age groups. PD-1 expression was significantly impaired in TME of aged mice. PD-1^-IFN-γ^- CD8T predominated in aged mice, whereas PD-1⁺IFN-γ^- CD8T predominated in young mice. Anti-PD-L1 treatment in aged mice enhanced antitumor immunity, but preferentially increased PD-1⁺ CD8T in both TDLNs and TME.

In the SCCVII model, aging impaired the antitumor immune responses, associated with early recruitment of M2-like TAMs. PD-1 expression in aged TME CD8T was impaired, but the PD-L1 blockade increased PD-1 expression, suggesting that the site of action for PD-L1 blockade differs between young and aged mice.

International guidelines on breast cancer (BC) screening have differing recommendations leading to uncertainty on best practices for primary care providers. The purpose of this study was to create a Canadian best practices document on BC health and screening for primary healthcare providers through multidisciplinary consensus using Nominal Group Technique and Delphi method.

A 9-member multidisciplinary expert group and a patient advocate participated in the consensus methods and voting. Experts included those involved in BC management and two primary care physicians. Twenty-nine experts across BC disciplines participated in external review.

Two study objectives included (1) building consensus on key 'best practice' behaviours related to BC-related health and screening and (2) building consensus on specific definitions related to BC screening.

The final consensus document consists of 65 statements grouped in five categories with companion resources to support uptake of all best practices. Categories include identification and work-up for diagnostic imaging, risk factors and identifying individuals eligible for high-risk screening, shared decision-making, decisions and referrals for BC screening and screening outcomes. Special areas of focus were shared decision-making, age to initiate screening, and BC screening in special populations.

We created a comprehensive consensus document distilling the latest evidence to provide practical Canadian consensus-based advice on specific 'best practice behaviours' related to BC health and screening to serve as a resource for providers.

Global disparities exist in cancer incidence, mortality, and survival. We aimed to provide estimates of avoidable deaths among people diagnosed with cancer to inform the prioritisation of interventions and narrow cancer inequalities.

National incidence estimates for 35 cancer sites in 2022 for 185 countries were extracted from the GLOBOCAN database. We estimated numbers of avoidable deaths within 5 years of diagnosis for patients diagnosed with cancer in 2022, consisting of those deaths avoidable through primary prevention (preventable deaths) and those avoidable through early detection and improved access to treatment (treatable deaths) by cancer site, country, region, and human development index (HDI) group. Preventable deaths were estimated using population attributable fractions for tobacco use, alcohol consumption, excess body weight, infectious agents, and ultraviolet radiation obtained from the literature. Treatable deaths were estimated by eliminating survival differences using 5-year net survival from the SURVCAN-3 project and additional sources. Preventable, treatable, and overall avoidable deaths as proportions of the total expected deaths within 5 years of cancer diagnosis were also calculated.

5 years after cancer diagnosis, 4·5 million (47·6% [95% uncertainty interval 47·5-47·8]) of the 9·4 million expected deaths were avoidable. Of these avoidable deaths, 3·1 million (3·1-3·1; 33·2% [33·1-33·3] of total expected deaths) were preventable and 1·4 million (1·4-1·4; 14·4% [14·4-14·5]) were treatable. Lung, liver, stomach, colorectal, and cervical cancers contributed the greatest burden, collectively accounting for 59·1% of all avoidable deaths. Lung cancer was responsible for the most preventable deaths (1·1 million; 34·6% of all preventable deaths), while female breast cancer was responsible for the most treatable deaths (0·2 million; 14·8% of all treatable deaths). Disproportionately large proportions of avoidable deaths from cervical and breast cancer were observed in countries with a low or medium HDI.

Nearly half of deaths among people diagnosed with cancer globally could be avoided through primary prevention and improvements in early detection and curative cancer treatment. Global efforts are needed to tailor prevention, early diagnosis, and treatment of cancer to address inequities in avoidable deaths, especially in low and medium HDI countries.

Erasmus Mundus Exchange Programme and French National Cancer Institute (INCa).

To investigate the treatment effect of adjuvant chemotherapy for stage I ovarian clear cell carcinoma.

We searched Cochrane, PubMed, International Standard Randomised Controlled Trial Number registry, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and Ichushi-Web to January 22, 2025.

We included randomized controlled trials (RCTs) and non-RCTs that included more than 50 patients with stage I ovarian clear cell carcinoma. The primary and secondary outcomes were disease-free survival and overall survival, respectively. We performed a meta-analysis of the stage-adjusted hazard ratios (HRs) of adjuvant chemotherapy compared with placebo or no intervention. The substage-related heterogeneity of effects was also assessed. A meta-analysis of proportions was also conducted to assess 5-year disease-free survival and 5-year overall survival. Risk of bias was assessed with the Risk of Bias in Non-randomized Studies of Interventions tool.

Because no RCTs reported HRs for the ovarian clear cell carcinoma subgroup, data from nine non-RCTs were analyzed. The pooled substage-adjusted HR for disease-free survival associated with use of chemotherapy was 0.47 (95% CI, 0.29-0.74) and that for overall survival was 0.66 (95% CI,0.43-1.00). Heterogeneity in the effect by substage was not evident for either disease-free survival (P for subgroup difference=.91) or overall survival (P=.60). The pooled 5-year disease-free survival was 0.80 (95% CI, 0.65-0.89) for stage I overall, 0.95 (95% CI, 0.47-1.0) for stage IA, and 0.61 (95% CI, 0.47-0.74) for stage IC. The estimated number needed to treat was 10.2 (95% CI, 5.8-18.6) for stage I overall, 40.8 (95% CI, 3.9-infinity) for stage IA, and 5.2 (95% CI, 3.9-7.8) for stage IC.

Adjuvant chemotherapy improves disease-free survival and may prolong overall survival in patients with stage I ovarian clear cell carcinoma. Available evidence suggests that recurrence is reduced by approximately 50%. Treatment decisions should consider the baseline recurrence risks and absolute benefits.

PROSPERO, CRD42024562486.

Approximately one in three patients with appendiceal cancer (AC) is diagnosed before age 50 years. Early-onset appendiceal cancer (EOAC) exhibits distinct clinicopathologic and demographic features compared with late-onset disease, suggesting potential biological differences. However, the molecular differences remain poorly understood. This study aims to compare EOAC and late-onset AC (LOAC, ≥50 years) mutational profiles and evaluate their impact on overall survival (OS).

A retrospective analysis was conducted using the Memorial Sloan Kettering-Metastatic Events and Tropisms database. Patients were stratified by age at the time of surgery into EOAC and LOAC groups. Logistic regression was used to assess differences in mutational profiles between these two groups. Findings were validated using data from the American Association for Cancer Research Genomics Evidence Neoplasia Information Exchange project. Kaplan-Meier survival analysis and multivariable Cox proportional hazard models were used to evaluate associations with survival.

The study included 200 patients with appendiceal adenocarcinoma (median age: 55 years, IQR, 47-68), of whom 70 (35%) had EOAC and 130 (65%) had LOAC. Patients with EOAC had higher odds of harboring PIK3CA mutations compared with LOAC (17.1% v 7.7%; odd ratio, 2.65; P = .04), which was consistent when combined with the GENIE data set (12.3% v 5.9%; P < .01). PIK3CA mutations were exclusively observed in patients with metastatic disease (11.8%) and were more common in adenocarcinoma not otherwise specified (NOS) than mucinous tumors (63.6% v 36.4%; P = .04). In multivariable analysis, PIK3CA mutations were independently associated with worse OS (hazard ratio, 2.62 [95% CI, 1.32 to 5.20]; P < .01).

PIK3CA mutations are more common in EOAC and independently associated with worse OS. These findings suggest incorporating PIK3CA mutation status into prognostic assessments and warrant further investigation of PIK3CA inhibitors as a potential therapeutic strategy for appendiceal adenocarcinoma.