Acta Oncologica最新文献

Background and purpose: This study aimed to evaluate the efficacy and safety of argon-helium cryoablation combined with Programmed Death-1 (PD-1) inhibitors versus PD-1 inhibitors plus chemotherapy in treating non-small cell lung cancer (NSCLC). Patient/material and methods: In this single-center, open-label, randomized controlled trial, 60 NSCLC patients treated between December 2020 and December 2023 were enrolled. Patients were randomly assigned (1:1) to either a study group (argon-helium cryoablation + PD-1 inhibitor, n = 30) or a control group (PD-1 inhibitor + chemotherapy, n = 30). Allocation was concealed using sequentially numbered, opaque, sealed envelopes (SNOSE). Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included short-term efficacy - objective response rate (ORR), disease control rate (DCR) - immune function changes (CD4+, CD8+, CD4+/CD8+), and adverse reactions, assessed after four cycles and during a 1-year follow-up.

Results: ORR and DCR were higher in the study group (ORR: 73.33% vs. 53.33%; DCR: 90.00% vs. 83.33%), though not statistically significant (P > 0.05). Baseline immune parameters were similar. After four cycles, the study group showed statistically significantly higher CD4+ and CD4+/CD8+ ratios, and lower CD8+ levels (all P < 0.001). Adverse reactions were comparable between groups (P > 0.05). At 1-year follow-up, the PFS rate was 63.3% vs. 43.3%. The study group had a statistically significantly better OS (median not reached vs. 10.3 months, P = 0.003) and longer median PFS (9.6 vs. 8.3 months, P = 0.005).

Interpretation: Argon-helium cryoablation combined with PD-1 inhibitors statistically significantly improved OS, PFS and immune function in NSCLC patients, offering a promising alternative to standard therapy.

Background: While adjuvant CDK4/6 inhibitors (abemaciclib and ribociclib) have improved invasive disease-free survival (iDFS) in ER-positive, HER2-negative early breast cancer (EBC) in the MonarchE and NATALEE trials, their real-world applicability in Denmark remains unclear. This study evaluates Danish patients meeting comparable high-risk criteria and their outcomes, hypothesizing that a substantial proportion could benefit from additional adjuvant treatment options.

Methods: Patients with ER-positive, HER2-negative EBC, diagnosed 2014-2019, who met MonarchE and/or NATALEE eligibility, were included and categorized as intermediate or high risk corresponding to trial definitions. Outcomes were overall survival (OS), iDFS, cumulative incidence of distant recurrence-free survival (DRFS) events and endocrine therapy adherence.

Results: Of all new cases of EBC, approximately 31% were included. Of 5,788 patients, 59.1% were intermediate risk and 40.9% high risk. Five-year OS and iDFS were lower in high-risk than intermediate-risk patients (84.5% vs. 91.9% and 76.2% vs. 85.7%, respectively), and cumulative DRFS event rates were higher (18.5% vs. 8.9%). High-risk patients more often received chemotherapy, yet nonchemotherapy subgroups in both risk categories had worse outcomes. Endocrine therapy adherence at 5 years was 77%.

Interpretation: A considerable proportion of Danish EBC patients meet high-risk criteria similar to CDK4/6 inhibitor trial populations and experience inferior outcomes despite standard therapy of antihormone treatment +/- chemotherapy. Our real-world data underscore the need for more effective and less toxic adjuvant therapies such as CDK4/6 inhibitors.

Background and purpose: Radioligand therapy targeting prostate-specific membrane antigen (PSMA) with lutetium-177 PSMA (¹⁷⁷Lu-PSMA) compounds has emerged as an effective treatment for metastatic castration-resistant prostate cancer (mCRPC). The KuPSMALu trial evaluated the real-world efficacy and safety of in-house produced ¹⁷⁷Lu-PSMA imaging & therapy (I&T) for mCRPC patients in a public healthcare setting and assessed whether selection based on ¹⁸F-PSMA-PET and contrast-enhanced CT - without FDG-PET - provides favourable oncological outcomes.

Patients/material and methods: This prospective, single-centre observational study included 40 patients with PSMA-positive mCRPC who had progressed after chemotherapy and at least one androgen receptor pathway inhibitor. Patients received 3-6 cycles of ¹⁷⁷Lu-PSMA-I&T at 6-8-week intervals. Imaging, blood-based markers and patient-reported outcomes were collected longitudinally. Dosimetry, adverse events (AEs) and quality-of-life metrics were systematically assessed.

Results: The median overall survival (mOS) was 16.0 months. ECOG 0-1 patients had significantly longer mOS than ECOG 2 patients (20.0 vs. 4.7 months, p < 0.01). A PSA decrease ≥ 50% was observed in 40% of patients and correlated with improved mOS (23.7 vs. 9.1 months, p < 0.01). PSA doubling time (dt) > 4 months predicted superior survival (23.8 vs. 12.6 months, p = 0.040). Grade ≥ 3 AEs occurred in only 12.3% of patients.

Interpretation: In-house ¹⁷⁷Lu-PSMA-I&T production combined with pragmatic imaging-based patient selection provides a safe, cost-effective therapy for mCRPC in public healthcare. PSA kinetics, particularly PSA dt, are strong predictors of therapeutic benefit. The findings align with VISION and TheraP trials and highlight the feasibility of integrating radioligand therapy into routine clinical care.

Background and purpose: Little is known about how pulmonary nodules are managed in routine clinical care. We examined their occurrence, the use of computed tomography (CT) scans, referrals to cancer pathways, and the risk of lung cancer and death post-diagnosis.

Patients/material and methods: We conducted a population-based cohort study using Danish health registry data. We identified all adults with a first-time pulmonary nodule diagnosis from 2018 to 2022. We examined the incidence of pulmonary nodules using age- and sex-standardized incidence rates (SIRs). We used the Aalen-Johansen estimator to calculate the probability of receiving a chest CT scan, a cancer patient pathway referral, the risk of lung cancer, and mortality within 12 months after a nodule diagnosis.

Results: We identified 43,209 patients with a pulmonary nodule diagnosis. The age- and sex-SIR of pulmonary nodules was 197 per 100,000 person-years in 2018, declining to 186 per 100,000 person-years in 2022. Within 12 months after a nodule diagnosis, 68.3% of the cohort underwent at least one chest CT scan, with 51.0% receiving a low-dose chest CT scan and 7.2% receiving a referral to a lung cancer patient pathway. The 12-month lung cancer risk was 3.6% (95% CI, 3.4 to 3.8%), with the highest risk for stage I lung cancer, and the mortality was 7.0% (95% CI, 6.8 to 7.3%).

Interpretation: The incidence of pulmonary nodules remained relatively stable from 2018 to 2022. More than 30% of patients with nodules lacked a chest CT scan within 12 months after a pulmonary nodule diagnosis.

Background and purpose: Successful clinical integration of pMBRT requires comprehensive investigations of the relationship between various pMBRT parameters and their associated biological effects. Such investigations are critically dependent on small animal models. Therefore, a state-of-the-art small animal irradiation platform like SIRMIO (Small Animal Proton Irradiator for Research in Molecular Image-guided Radiation-Oncology), capable of delivering precisely controlled spatially fractionated doses, is highly desirable for advancing preclinical pMBRT research.

Material and methods: This in silico study evaluates the SIRMIO beamline's capability to deliver beams essential for pMBRT experiments. We used Geant4-based Monte Carlo simulations to investigate two configurations: one without a collimator, and one using a 30 mm thick brass multislit collimator (MSC). For both configurations, we examined center-to-center (CTC) of 3, 4, and 5 mm, with a constant 1 mm slit width when MSC is used.

Results: The SIRMIO beamline can effectively generate spatially fractionated dose profiles with varying CTC. Without a collimator, sufficient dose contrast for pMBRT can be achieved with CTC of 4 mm and above, as evidenced by peak-to-valley dose ratios (PVDR) of 3.44 and 6.57 for 4 and 5 mm CTC, respectively. MSC further enhances dose contrast, achieving PVDR of 11.3, 20.7, and 28.7 for 3, 4, and 5 mm CTC, respectively. Furthermore, we explored interlacing beams as a means of achieving a uniform target dose while preserving dose contrast in normal tissue, demonstrating the potential of this approach using the SIRMIO beamline.

Interpretation: The SIRMIO platform can be a viable option for pMBRT experiments.

Background and purpose: Accurate dose plans in proton radiotherapy with consistent target in complex anatomical regions such as the brain are crucial. This study investigates a Swin Transformer-based deep learning model for voxel-wise dose prediction in brain cancer proton therapy, evaluating its spatial and dosimetric fidelity against clinically delivered plans. Patient/material and methods: A cohort of 206 patients with primary brain tumors were retrospectively analyzed. Dual-energy computed tomography (CT) scans, clinical contours, and corresponding proton dose plans were used to train and test a 3D Swin Transformer integrated within a UNet architecture. The model was evaluated on an independent test set (n = 20) using 3D gamma analysis (3%/3 mm), mean absolute error (MAE), and clinical target volume (CTV) coverage (V95%). Mean dose-volume histograms (DVHs) were compared across CTV.

Results: The model achieved a median gamma pass rate of 99.8% within the CTV (range: 78.6-100%), 83.2% outside the CTV (range: 52.3-99.8%), and a whole-volume median pass rate of 90.0% (range: 53.7-99.8%). The median MAE was 0.72 Gy (range: 0.2816-1.8966 Gy). Predicted dose distributions preserved high-dose conformity, with a median of V95% of 97.9% (range: 78.8-100%). DVH curves closely matched the clinical reference plans across all evaluated structures.

Interpretation: The proposed Swin Transformer-based model is a step toward accurate, anatomy-aware dose prediction for brain tumor proton therapy. Future work will address prospective validation and optimization for clinical deployment.

Background and purpose: The study aims to evaluate dosimetric properties of hypofractionated treatment plans integrating focal boost, using registered whole-mount histopathology (WMHP) as reference standard.

Methods: Fifteen men from the PAMP trial (EudraCT: 2015-005046-55) were included. Participants had ≥ 1 ISUP Grade group ≥ 4 lesion and underwent [68Ga]prostate-specific membrane antigen (PSMA) positron emission tomography/multiparametric magnetic resonance imaging (PET/mpMRI) and [11C]Acetate-PET/computed tomography before radical prostatectomy. Four radiation oncologists delineated gross tumor volumes (GTVs) on PSMA-PET/mpMRI. Sixty treatment plans were optimized, one per GTV and patient. Prostate planning target volumes were prescribed 42.7 Gy in seven fractions, with a simultaneous GTV boost up to 49.0 Gy, prioritizing organs at risk (OARs). Digital WMHP provided Gleason grading and was co-registered with in-vivo imaging. Target coverage for GTVs and voxels sharing Gleason patterns (GPs) was assessed via dose-volume histogram (DVH) analysis. Interobserver agreement in GTV-delineations was quantified with Fleiss' kappa.

Results: The median GTV dose per plan (D50) ranged from 48.3 to 49.1 Gy. For voxels with the highest GP, D50 was 42.9-49.2 Gy, exceeding 47.2 Gy in all except one plan. In lowest pattern voxels, D50 was 42.5-49.3 Gy, and below 43.4 Gy in over half the plans. Significant positive correlations between Fleiss' kappa and DVH parameters appeared only for GP 5 regions, specifically for Fleiss' kappa and D50 for two observers and the average D50 across observers.

Interpretation: The histologically confirmed tumor was only partially boosted. Regions with more aggressive disease received better coverage. These findings provide a rational for prioritizing OARs in treatment planning.

Background and purpose: Metastatic non-small cell lung cancer (mNSCLC) contributes to the economic burden. Over the past decade, treatment has evolved with the introduction of epidermal growth factor receptor (EGFR) anaplastic lymphoma kinase (ALK)-targeted, and immune-oncology (IO) drugs. However, limited evidence exists on the long-term costs of mNSCLC treatments in Sweden. Patient/material and methods: This population-based retrospective study used data from the National Board of Health and Welfare, identifying patients initially diagnosed with stage IV NSCLC between 2011 and 2020. Healthcare costs, including inpatient care, outpatient care, and drug expenses, were assessed using Diagnosis-Related Group (DRG) tariffs and prescription data. Drug expenses exceeding DRG tariff limits, such as IO drugs, were calculated separately based on retail list prices. Costs were analyzed over 5 years post-diagnosis and adjusted to 2023 values.

Results: A total of 17,107 patients were included. IO drug use increased sharply after 2016, becoming the predominant therapy. EGFR- and ALK-targeted drug use steadily increased. Overall costs rose over time, especially in the first year after diagnosis. The first-year mean cost was highest among patients receiving IO drugs (€105,286), primarily due to drug acquisition, but declined in subsequent years. ALK- and EGFR-targeted therapies also had high initial costs but remained stable thereafter.

Interpretation: This study highlights the increasing economic burden of mNSCLC treatment in Sweden, driven by the targeted and IO drugs. While ALK-, EGFR-targeted, and IO drugs contribute to high first-year mean costs, IO drug costs decline significantly in subsequent years after diagnosis.

Background and purpose: Robust methods for analysis and prediction of local cell survival after spatially fractionated radiotherapy (SFRT) in vitro remain limited. We present a methodology integrating spatial dosimetry with colony formation assessment and modelling to improve prediction of SFRT-induced responses. Patient/material and methods: A549 lung cancer cells were irradiated with 220 kV X-rays in three field patterns: open, striped, and dotted. Colony centroid locations were mapped from scanned images of culture flasks. Dose distributions were measured using radiochromic film dosimetry. Digital images with colony locations and dose maps were divided into 1 mm² quadrats. A Poisson regression model was fitted to colony counts per quadrat, incorporating linear-quadratic (LQ) model parameters α and β. A modified LQ (MLQ) model included an additional interaction between dose and nearest distance to a peak region, with parameter δ.

Results: The methodology was successfully implemented. LQ fitting across all quadrats and patterns yielded α = 0.254 Gy-¹ and β = 0.039 Gy-², while the MLQ model gave α = 0.249 Gy-¹, β = 0.032 Gy-², and δ = -0.040 Gy-¹ cm-¹. Parameter uncertainty was below 0.5%. The MLQ model showed slightly lower fitting errors than the LQ model, indicating improved predictive accuracy.

Interpretation: We introduce a novel analysis pipeline for 2D localization of colonies and SFRT survival modelling in vitro. Findings suggest that distance to peak dose regions significantly influences local SFRT effects. Incorporating this spatial factor via an MLQ model may enhance understanding and prediction of SFRT-induced survival.

Background and purpose: Smoking status, health literacy challenges and chronic diseases may influence the diagnostic evaluation of patients presenting with lung cancer symptoms (LCSs) in general practice. This study aimed to (1) analyse associations between smoking status, health literacy, chronic disease and having completed diagnostic imaging amongst patients with LCSs in Danish general practice and (2) investigate how these factors interact in relation to the completion of diagnostic imaging, by examining effect modification and causal mediation. Patient/material and methods: In 2022, a random sample of 100,000 individuals aged ≥ 20 years from the Danish population was invited to participate in a survey about symptoms and healthcare seeking. This study included individuals aged ≥ 40 years who reported general practitioner (GP) contact with LCSs. Questionnaire data included health literacy, chronic disease and smoking status. Register data included socioeconomics, prescription drugs and diagnostic imaging. Descriptive statistics, multivariable logistic regression and causal mediation models were applied.

Results: Of the 2,252 patients who had contacted their GP with LCSs, 22% had completed diagnostic imaging. Formerly smoking increased odds of diagnostic imaging compared to never smoking, whereas current smoking had no influence. No associations or mediations were demonstrated between health literacy, chronic disease and diagnostic imaging. Effect modification was implied by varying impact of health literacy on diagnostic imaging depending on smoking status, yet the results were limited by power.

Interpretation: Initiatives targeting awareness of the risk of overlooking cancer symptoms amongst high-risk patients presenting in general practice may improve the chance of timely diagnosis of lung cancer.