European Journal of Cancer最新文献

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.

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.

Background: Cancer immunotherapy has revolutionized melanoma treatment, but the high number of non-responders still emphasizes the need for improvement of therapy. One potential avenue for enhancing anti-tumor treatment is through the modulation of coagulation and platelet activity. Both have been found to play an important role in the tumor microenvironment, tumor growth and metastasis. Preclinical studies indicate a beneficial effect, clinical data has been inconsistent.

Methods: We examined a cohort of advanced, non-resectable melanoma patients (n = 2419) derived from the German prospective multicenter skin cancer registry ADOReg, who were treated with immune checkpoint inhibitors (ICI). The patients were classified based on whether it was documented that they received platelet aggregation inhibition (PAI) (n = 137) (acetylsalicylic acid (ASA) or clopidogrel), anticoagulation (AC) (n = 185) (direct oral anticoagulation (DOAC), phenprocoumon, heparins) at the start of ICI or no antithrombotic medication (n = 2097) at any point during ICI treatment. The study endpoints were best overall response (BOR), progression-free survival (PFS) and overall survival (OS).

Results: A significantly improved PFS was observed in patients documented to receive ASA (15.1 vs 6.4 months, HR 0.67, 95 % CI: 0.5 to 0.88, p = 0.0047) as well as in patients to receive AC (15.1 vs. 6.4 months, HR 0.7, 95 % CI: 0.53 to 0.91, p = 0.01) compared to patients for whom no antithrombotic medication was documented. Multivariate analysis of OS showed significant risk reduction in patients who received DOAC (HR 0.68, 95 % CI: 0.49 to 0.92, p = 0.0170) or phenprocoumon (HR: 0.44, 95 % CI: 0.19 to 0.85, p = 0.0301).

Conclusion: Our study indicates a positive prognostic effect of anticoagulant and antiplatelet concomitant medication in melanoma patients receiving ICI. Further studies are needed to confrim the cancer-related benefit of adding anticoagulation or platelet inhibition to ICI treatment.

Background: Rare cancers correspond to approximately 200 clinical entities, which can be grouped into 12 families. Updated data are available for childhood and haematological cancers, ie, for only two of the 12 families of rare cancer. We provide incidence and survival for the remaining ten families of rare adult solid cancers (RAC), across 29 EU Member States and over time. We also evaluate the association between resources invested in health and survival from RACs.

Methods: We used the EUROCARE-6 database, which includes data from 108 cancer registries from 29 countries. We calculated incidence rates (IR) and 5-year relative survival (RS) for cases diagnosed during 2006-2013. We calculated 5-year RS in the follow-up period 2010-2014 using the period approach (last follow-up: December 31, 2014). We estimated changes in 5-year RS and IR over the period 2000-2013. We used a forest plot to report the differences in RS among countries with the highest and lowest health spending.

Results: RACs are heterogeneous in terms of incidence, survival, sex, and age distribution. Several RACs (eg, those of the hypopharynx, small intestine, and trachea) still have a 5-year RS < 30 %, which is not improving. Survival differs among European countries and is higher in countries with the greatest investments in health. The incidence of smoking-related RACs is decreasing but rising in HPV-related RACs.

Conclusion: Investments in health and healthcare networks at national and European level can help increase the survival of RACs, especially those requiring centralisation of care (eg, bone sarcomas, penile cancer). These investments are critical considering that survival from RACs is not significantly improving. Our results unmask the heterogeneity of RACs, which needs to be considered in clinical trial design. Finally, our findings support the importance of prevention strategies for known risk factors such as smoking.

Background: Extranodal natural killer/T-cell lymphoma (ENKTCL) is almost always fatal after the failure of asparaginase. This phase II study aimed to investigate the efficacy and safety of tislelizumab combined with gemcitabine and oxaliplatin (Tisle-GemOx) in patients with ENKTCL failing asparaginase.

Methods: Eligible patients received Tisle-GemOx as initial induction for 6-8 cycles at 21-day intervals. Responders continued tislelizumab maintenance every two months for two years. The primary endpoint was the best complete response rate (CRR).

Results: As of September 2023, 32 patients were enrolled in our study. Among the 30 efficacy-evaluable patients, the best CRR was 60 %, meeting the primary efficacy endpoint. With a median follow-up of 22.6 months, the median progression-free survival (PFS) was 7.4 months and the 1-year PFS rate was 46.4 %. Subgroup analyses showed that shorter PFS was associated with previous lines of chemotherapy ≥ 2 (P = 0.034) and concomitant hemophagocytic lymphohistiocytosis (P = 0.040). Pseudo-progression was observed in three patients (10 %). The most common grade ≥ 3 toxicities were lymphopenia (25 %) and anemia (15.6 %).

Conclusions: Tisle-GemOx exhibits promising anti-tumor activity and manageable toxicities as a salvage therapy for ENKTCL failing asparaginase. Further long-term follow-up is necessary to evaluate the durability of the response with tislelizumab maintenance in this patient population.

Background: Metastatic uveal melanoma (mUM) is rare. Immune checkpoint inhibitors (ICIs) have shown modest efficacy in mUM. Tebentafusp prolonged overall survival (OS) in a phase 3 study. We aimed to investigate the efficacy and safety of the sequence of tebentafusp and ICIs.

Methods: Patients with HLA-A * 02:01 positive mUM, or metastatic GNA11/GNAQ mutant melanocytic tumors treated with tebentafusp followed by ICIs (group 1) or the inverse sequence (group 2) at any treatment line were retrospectively identified. The primary objective was OS rate at 2 years.

Results: 131 patients were included; 51 in group 1 and 80 in group 2. 30 % in group 1 % and 40 % in group 2 had normal baseline lactate dehydrogenase (LDH, p = 0.05). 94 % in group 1 % and 77 % in group 2 had multilobular liver disease (p = 0.02). Median OS was 22.4 months (95 % CI 19-24.8) in group 1 and 33.6 months (95 % CI 28.9-43) in group 2 (p = 0.004). Total median PFS was 12 months (95 % CI 10.7-18.8) in group 1 and 20.3 months (95 % CI 17.2-27.3) in group 2 (p = 0.04). The frequency of cytokine release syndrome was higher in group 2 (15 % vs 27 %). Other clinical factors were associated with short total PFS in the multivariable analysis.

Conclusions: Both treatment sequences are clinically feasible. A clinical benefit was noted in the sequential combination of ICIs followed by tebentafusp. This observation is limited by the retrospective nature of the study and merits further investigation in prospective clinical trials.