European Journal of Cancer最新文献

Background: Targeting modifiable factors offers significant potential for primary cancer prevention. For public health strategies, it is essential to quantify the contribution from each factor on a national level. We estimated the contribution of 12 modifiable factors on cancer incidence in the Norwegian population.

Methods: Nationally representative data (1990-2015) on the prevalence of tobacco smoking, over-exposure to ultraviolet radiation (UVR), alcohol consumption, physical inactivity, overweight and obesity, intake of processed and red meat, fibre and calcium, menopausal hormone therapy (MHT), human papilloma virus (HPV) infection and insufficient breastfeeding were collected from health surveys. Using these prevalences, cancer risk estimates for for the exposures, and average annual cancer incidence rates for 2016-2020, we estimated annual population-attributable fractions (PAFs) and numbers of preventable cases.

Results: Of the average 24,608 annual cases of cancers related to our included modifiable factors, 12,12,250 (6240 in women and 6009 in men) (41 %) were attributed to these factors. Tobacco smoking caused the highest proportion of cancers cases, 20 % in men and 13 % in women. Sunburn and indoor tanning caused 13 % and 10 % of cancers in men and women, respectively, and overweight and obesity caused 4.5 % of the cases. Cancers of skin, lung, colon and female breast had the highest number of preventable cases.

Conclusion: Over a third of the annual cancer cases in Norway were attributed to 12 modifiable factors. Based on this study, efforts to reduce tobacco smoking, UVR over-exposure, and overweight and obesity could be the most effective in primary prevention of cancer.

Aim: Cemiplimab has demonstrated significantly longer survival than physician's choice of chemotherapy in patients with recurrent cervical cancer after first-line platinum-containing chemotherapy. We report the final survival analysis from the phase III randomized study (EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9).

Methods: Cemiplimab (n = 304) or chemotherapy (n = 304) were administered every 3 weeks. The primary endpoint was overall survival (OS). Patients were included regardless of programmed cell death-ligand 1 (PD-L1) status.

Results: At a median follow-up of 47.3 months (data cut-off: April 20, 2023), median OS was 11.7 versus 8.5 months for patients treated with cemiplimab and chemotherapy, respectively (hazard ratio 0.67, 95 % confidence interval 0.56-0.80, p < .00001). OS benefit was seen in PD-L1 positive and negative populations, even though more patients with PD-L1 < 1 % (n = 92), had poor performance status in the cemiplimab arm than the chemotherapy arm (61.4 % vs 47.9 %).

Conclusion: This final analysis confirms that cemiplimab maintains survival benefit compared with chemotherapy in recurrent cervical cancer after progression on first-line platinum therapy, regardless of PD-L1 expression. The safety profile was consistent with published data; incidences of adverse events were similar between cemiplimab and chemotherapy groups. These results support the use of second-line cemiplimab for patients with recurrent cervical cancer.

Background: Ossifying fibromyxoid tumour is a rare mesenchymal soft tissue sarcoma with uncertain differentiation and variable metastatic potential.

Patients and methods: This study offers a retrospective analysis of 23 patients diagnosed with OFMT between 1993 and 2024.

Results: The tumours most commonly arose in the extremities and trunk, with all patients undergoing surgical resection of the primary tumour. Immunohistochemical analysis frequently revealed the expression of S100 protein and desmin, while next-generation sequencing identified PHF1 rearrangements in 83 % of patients with available NGS, notably PHF1::EP400 and PHF1::TFE3 fusions. Five patients experienced local recurrence, and four developed metastatic disease. There is no prospective data to guide decision making with regards to systemic therapy, and doxorubicin-based regimens demonstrate limited efficacy. However, the potential role of epigenetic dysregulation in OFMT tumorigenesis opens exciting avenues for treatment. In this cohort, one patient exhibited a remarkably durable response to a combination of gemcitabine, which inhibits DNA methylation, and dacarbazine, following rapid tumour progression on doxorubicin.

Conclusions: Given the limited clinical experience with OFMT, multidisciplinary tumour boards are crucial for tailoring individualized treatment strategies. This study contributes to the growing body of literature on OFMT, providing a foundation for future research.

Background: Cabazitaxel and ¹⁷⁷Lu-PSMA-617 have been shown to improve survival in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and androgen receptor pathway inhibitors (ARPI). we aimed to evaluate the impact of sequencing cabazitaxel and ¹⁷⁷Lu-PSMA-617 on survival outcomes in patients with mCRPC.

Patients and methods: This is a retrospective, multicenter, cohort study which included patients with mCRPC who received sequential treatment with ¹⁷⁷Lu-PSMA-617 and cabazitaxel between January 2015 and December 2023. Primary outcome was progression-free survival-2 (PFS-2) RESULTS: A total of 68 patients with mCRPC who received sequential ¹⁷⁷Lu-PSMA-617 and cabazitaxel were included in the study. The primary outcome, progression-free survival-2 (PFS-2), was similar in patients treated with ¹⁷⁷Lu-PSMA-617 first (LU-CA) and those receiving cabazitaxel (CA-LU) first (10.8 and 11.7 months, respectively; p = 0.422). The median overall survival (OS) was also similar in the LU-CA and CA-LU groups (16.6 and 19.9 months, respectively; p = 0.917). The objective response rate (ORR) for ¹⁷⁷Lu-PSMA-617 was 23.1 % when used first and 16.1 % after cabazitaxel. ORR for cabazitaxel was 25.6 % and 31.3 % when used as the first agent and when used after ¹⁷⁷Lu-PSMA-617, respectively.

Conclusions: In conclusion, treatment sequencing between cabazitaxel and ¹⁷⁷Lu-PSMA-617 did not significantly affect survival outcomes in patients with mCRPC. These findings suggest that both drugs can be effectively integrated into the mCRPC treatment paradigm without concerns about the effect of sequencing. However, prospective data are needed to optimize sequencing strategies and explore their impact on specific patient subgroups for more personalized care.

Background: Ribociclib + endocrine therapy (ET) showed significant progression-free survival (PFS) and overall survival (OS) benefits in the MONALEESA trials in patients with HR+ /HER2 - advanced breast cancer (ABC). We report efficacy, safety, and patient-reported outcomes (PROs) across age groups, including older patients, in these trials.

Methods: Data from the MONALEESA-2, -3, and -7 trials for pre- and postmenopausal patients receiving first-line treatment for ABC were pooled and analyzed by age (<65y, 65-74y, and ≥75y). PFS, OS, time to first chemotherapy (TTC), and time to definitive deterioration (TTD) in PROs were evaluated using Kaplan-Meier methods; a Cox regression model stratified by study and liver/lung metastasis was used for hazard ratios.

Results: Among 1229 patients included, 63 % were < 65y, 27 % were 65-74y, and 10 % were ≥ 75y. Baseline characteristics were generally well balanced. Regardless of patient age, ribociclib+ET showed a consistent PFS and OS benefit and delayed TTC. With ribociclib+ET, the most common first subsequent treatment was ET. Safety results were consistent with those in the overall trial population; no new signals were identified. Rates of discontinuation due to AEs with ribociclib+ET were numerically higher in patients ≥ 75y. Among patients who discontinued treatment due to AEs, the percentage without prior dose reduction was higher in those ≥ 75y. A PRO benefit with ribociclib+ET was observed across all age groups for pain and fatigue scores.

Conclusions: This analysis demonstrated that ribociclib+ET is an effective and well-tolerated treatment for patients of all age groups with HR+ /HER2 - ABC, including older patients. (MONALEESA-2, NCT01958021; MONALEESA-3, NCT02422615; MONALEESA-7, NCT02278120).

Background: Inadequate tumour samples often hinder molecular testing in non-small cell lung cancer (NSCLC). Plasma-based cell-free DNA (cfDNA) sequencing has shown promise in bypassing these tissue limitations. Nevertheless, pleural effusion (PE) samples may offer a richer cfDNA source for mutation detection in patients with malignant PE.

Methods: This prospective study enrolled newly diagnosed advanced NSCLC patients with malignant PE. PE samples were collected for cfDNA NGS analysis. Meanwhile, PE cell pellet RNA was extracted for reverse transcription polymerase chain reaction (RT-PCR) for clinically relevant actionable mutations and then confirmed by Sanger sequencing. The concordance between PE cell pellet RT-PCR and PE cfDNA NGS analyses was analysed.

Results: Fifty patients were enrolled. The median age was 68.5 years, and the female-to-male ratio was 29:21. Most patients (74 %) were non-smokers. Notably, 45/50 patients (90 %) had actionable mutations, including EGFR exon 19 deletions (24 %), EGFR L858R mutations (36 %), HER2 exon20 insertions (10 %), ROS1 rearrangements (4 %), EGFR exon20 insertions (2 %), ALK rearrangements (4 %), RET rearrangements (2 %), KRAS G12C mutations (2 %), and CD74-NRG1 fusions (2 %). Among the 50 enrolled patients, actionable mutations were detected in 44 (88 %) by PE cfDNA NGS, 39 (78 %) by PE cell pellet Sanger sequencing, and 33 (66 %) by clinical tissue genetic testing (P = 0.031). The detection of actionable mutations from PE cfDNA NGS remained consistently high across M1a to M1c stages.

Conclusions: PE cfDNA genotyping has clinical applicability for NSCLC patients and can serve as an additional source for molecular testing. Incorporating PE NGS cfDNA analysis into genetic testing enhances diagnostic yield and aids in identifying actionable mutations in clinical practice.

Background: Multiple studies have suggested that gut microbiome may influence immune checkpoint inhibitor (ICI) efficacy, but its association with immune-related adverse events (irAEs) is less well studied. In this prospective cohort study, we assessed whether gut microbiome composition at start, or changes during ICI, are associated with severe irAEs.

Methods: Stool samples of cancer patients treated with anti-PD-1 ± anti-CTLA-4 were analyzed using 16S rRNA gene sequencing and metagenomic shotgun sequencing. Differences in alpha and beta diversity between patients with and without severe irAE were assessed, as well as differential relative abundance (RA) of taxa, MetaCyc pathways, and seven prespecified literature-based bacterial groups including pathobionts and Ruminococcaceae.

Findings: We analyzed 497 samples of 195 patients before and soon after starting ICI, at severe irAE onset and after starting immunosuppression. Mean RA of the pathobionts group was significantly higher in patients who developed a severe irAE (8.2 %) compared to those who did not (4.8 %; odds ratio 1.40; 95 %CI 1.07-1.87) at baseline, and also early during ICI treatment and at severe irAE onset. A significantly stronger decrease in RA of Ruminococcaceae after starting ICI was observed in patients who developed a severe irAE compared to those who did not. RAs of Ruminococcaceae, the genus Ruminococcus, and the species R. bromii and R. callidus were significantly lower at severe irAE onset compared to other time points.

Interpretation: Gut microbiome dysbiosis signaled by higher RA of pathobionts and decrease in RA of Ruminococcaceae may predispose to severe irAEs.

Most breast cancer screening programs rely only on demographic data without considering individual risk factors of the population, which might limit their effectiveness by over- and underscreening specific subgroups. Therefore, the aim of this study is to highlight health and economic disparities in outcomes from such a uniform screening strategy. With the microsimulation model MISCAN, we simulated outcomes of the Dutch screening program considering 16 subgroups varying by their 5-year breast cancer risk and breast density. All outcomes showed significant disparities across risk-density subgroups. Notably, women with extremely dense breasts showed a mortality reduction from the current screening of 16-17 % compared to 25-29 % in other groups. Absolute benefits (breast cancer deaths averted, and life-years gained) increased with risk and varied independently by density. The range of false-positive rates varied almost twofold across the span of subgroups and nearly a ninefold difference in the medical costs incurred with lifelong follow-up. These findings emphasize the potential for stratified screening strategies to improve equity in health outcomes and reduce the burden of breast cancer.

Introduction: The prognostic value of PAM50 intrinsic subtypes (IS), cell cycle, and immune-related gene expression in HR+ /HER2- advanced breast cancer (BC) treated with CDK4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) in a first-line metastatic setting is unclear. This study evaluates these biomarkers in metastatic biopsies from patients diagnosed with HR+ /HER2- advanced BC.

Methods: CDK-PREDICT study is a multicentric, ambispective observational cohort study conducted in six Spanish hospitals. It included patients diagnosed with HR+ /HER2- advanced BC treated in the first-line setting with CDK4/6i and ET. Baseline biopsies were obtained prior to treatment to determine research-based PAM50 IS, cell cycle and immune-related gene expression. The primary objective was to evaluate progression-free survival (PFS) differences among PAM50 IS using uni- and multivariable Cox regression models. Secondary objectives included overall survival (OS), overall response rate (ORR), and correlating cell cycle and immune response gene expression with PFS.

Results: A total of 185 patients were included, with a median follow-up of 38.5 months. PAM50 luminal subtypes were predominant (82.7 %). Non-luminal subtypes showed significantly shorter median PFS (10.2 vs. 25.7 months; HR, 2.50; p < 0.001) and OS (32.3 vs. 58.1 months; HR, 2.54; p < 0.001) than luminal subtypes. Higher cell cycle and immune-related genes expression, such as CCNE1 and PDCD1, as well as tumor infiltrating lymphocytes were associated with poorer outcomes.

Conclusions: This study confirms the independent prognostic value of PAM50 IS in HR+ /HER2- advanced BC treated with CDK4/6i and ET. Non-luminal subtypes exhibited the worst prognosis, underscoring the need for novel therapeutic strategies in this population.