Acta Oncologica最新文献

Background and purpose: The poor delivery of drugs to infiltrating tumor cells contributes to therapeutic failure in glioblastoma. During the early phase of an anti-angiogenic treatment, a remodeling of the tumor vasculature could occur, leading to a more functional vessel network that could enhance drug delivery. However, the restructuration of blood vessels could increase the proportion of normal endothelial cells that could be a barrier for the free diffusion of drugs. The net balance, in favor or not, of a better delivery of compounds during the course of an antiangiogenic treatment remains to be established. This study explored whether cediranib and thalidomide could modulate perfusion and vessel permeability in the brain U87 tumor mouse model.

Methods: The dynamic evolution of the diffusion of agents outside the tumor core using the fluorescent dye Evans Blue in histology and Gd-DOTA using dynamic contrast-enhanced (DCE)-MRI. CD31 labelling of endothelial cells was used to measure the vascular density.

Results and interpretation: Cediranib and thalidomide effectively reduced tumor size over time. The accessibility of Evans Blue outside the tumor core continuously decreased over time. The vascular density was significantly decreased after treatment while the proportion of normal vessels remained unchanged over time. In contrast to histological studies, DCE-MRI did not tackle any significant change in hemodynamic parameters, in the core or margins of the tumor, whatever the parameter used or the pharmacokinetic model used. While cediranib and thalidomide were effective in decreasing the tumor size, they were ineffective in transiently increasing the delivery of agents in the core and the margins of the tumor.

Background and purpose: Although the diagnostic accuracy of 18F-fluorodeoxyglucose - positron emission tomography/computed tomography (18F-FDG-PET/CT) for breast cancer (BC) has been well studied, few studies have evaluated the impact of 18F-FDG-PET/CT on BC patient care. This study aimed to investigate restaging and 18F-FDG-PET/CT-induced changes in clinical decision-making in patients with BC.

Material and methods: We retrospectively evaluated 18F-FDG-PET/CT-scans performed for BC-related indications in a prospectively collected consecutive cohort of adult patients at Skane University Hospital, Sweden. Patients with all BC stages were included and divided into three groups based on the indication for 18F-FDG-PET/CT: Group A (primary staging), Group B (response evaluation), and Group C (recurrence). The impact of 18F-FDG-PET/CT-scans on clinical management was categorized as no change, minor change (e.g. modification of treatment plans), or major change (e.g. shift from curative to palliative treatment intention).

Results: A total of 376 scans (151 patients) were included: Group A 9.3% (35 of 376 scans), Group B 77.4% (291 of 376 scans), and Group C 13.3% (50 of 376 scans). Significant stage migration, predominantly upstaging, occurred in Group A (45.7%) and Group C (28.0%). Changes in clinical management were observed in 120 scans (31.9%), of which 66 were major and 54 were minor. The largest proportion of 18F-FDG-PET/CT-induced management changes were observed in Group A (57.1%), most commonly a shift from curative to palliative treatment intention due to upstaging.

Interpretation: Our study indicates the clinical utility of 18F-FDG-PET/CT in BC restaging and changes in clinical management; the latter observed in approximately one-third of all cases.

Background and purpose: This study aims to evaluate neutrophil-to-eosinophil ratio (NER) as a prognostic and/or predictive biomarker in metastatic clear cell renal cell carcinoma (m-ccRCC) treated with nivolumab or ipilimumab/nivolumab.

Patients/materials and methods: We performed a retrospective study on m-ccRCC patients treated with nivolumab or ipilimumab/nivolumab (2012-2022). Baseline NER was calculated and correlated with clinical outcomes: response rate (RR), progression free survival (PFS) and overall survival (OS). Corresponding transcriptomic data were analysed.

Results: We included 201 m-ccRCC patients, 76 treated with ipilimumab/nivolumab and 125 with nivolumab. Baseline NER was statistically significantly associated with International Metastatic RCC Database Consortium (IMDC) risk groups. Increased NER was associated with shorter PFS and OS in the total patient series and nivolumab-treated patients. In patients treated with ipilimumab/nivolumab, increased NER was only statistically significantly associated with shorter OS. The impact of baseline NER on PFS and OS was independent of IMDC risk stratification. No clear correlation was found between baseline NER and RECIST response or maximal tumour shrinkage. In two additional databases, NER was also associated with PFS and OS in first-line vascular-endothelial-growth-factor-receptor tyrosine-kinase-inhibitors (VEGFR-TKIs), but not to disease-free survival in the post-nephrectomy setting. Lower NER was associated with intratumoural molecular features possibly associated with better outcome on immune checkpoint inhibitors.

Interpretation: Lower baseline NER is associated with better PFS and OS, independent of IMDC risk score, in m-ccRCC patients treated with ipilimumab/nivolumab or nivolumab. It correlates with intratumoural molecular features possibly associated with better outcome on immune checkpoint inhibitors. The predictive power of this biomarker is probably limited and insufficient for patient selection.

Background and purpose: Multi-disciplinary Team (MDT) meetings are widely regarded as the 'gold standard' of lung cancer care. MDTs improve adherence to clinical guidelines for lung cancer patients. In this study, we describe and compare lung cancer MDTs in Denmark and Norway by combining national surveys and the MDT-Metric for the Observation of Decision-making (MDT-MODe) instrument.

Materials and method: Identical surveys were sent out to all lung cancer MDT centers in Denmark and Norway by the Danish Lung Cancer Group and the Norwegian Lung Cancer Group. Six MDT centers, three in Denmark and three in Norway, were observed using the MDT-MODe instrument.

Results and interpretation: We found similar organization of MDT meetings in both countries, with the main difference being more local MDT meetings in Norway. All lung cancer MDTs were chaired by respiratory physicians and attended by a radiologist. Other members included oncologists, pathologists, thoracic surgeons, specialist nurses, nuclear medicine specialists and junior doctors. Overall, members reported that they had sufficient time for preparation and attending MDT meetings. With the MDT-MODe instrument it was found that the MDT chairs, surgeons, oncologists, radiologists all contributed positively to case discussion. Comorbidities were included in the discussion of most patients while the patient's view and psychosocial issues were less often discussed. A treatment decision was reached in 79.7% of cases discussed. In conclusion, we found similar settings and overall good quality concerning lung cancer MDT meetings in Denmark and Norway.

Purpose and objective: Squamous cell carcinoma of the anal margin (SCCAM) is an uncommon lesion that comprises one-third to a quarter of all anal squamous cell carcinoma. Treatment involves surgery or exclusive radiotherapy for small tumours, whereas the preferred treatment for larger tumours is chemoradiotherapy. In our department, selected patients with SCCAM are treated with electron beam radiotherapy using one perineal field. The present study evaluates this strategy.

Material and methods: All consecutive patients with SCCAM and treated with electron beam radiotherapy from 2012 to 2022 were included. Data were retrospectively extracted from the medical records and analysed descriptively. Local control (LC) and overall survival (OS) were analysed using Kaplan-Meier statistics.

Results: Forty patients were evaluated. Primary radiotherapy was delivered in 35 (87.5%) patients. Five (12.5%) patients had postoperative radiotherapy. Median prescription dose was 60.0 (range 45.0-60.2) Gy in 28 (range 10-30) fractions delivered with 8 (range 4-18) MeV using a standard circular aperture and bolus. At a median follow-up of 73 (range 9-135) months, 7 (17.5%) patients were diagnosed with local recurrences. The 5-year LC rate was 84.3% (95% CI: 71.4%-97.2%). Analysis of LC according to T-stage revealed a 5-year LC of 100% (95% CI: 100%-100%) in T1 tumours compared to 57.0% (95% CI: 27.4%-86.6%) in T2 tumours (p < 0.001). 5-year OS was 91.6% (95% CI: 83.0%-100%). Late grade 3 toxicity included ulceration in the skin and subcutis in 2 (5.0%) patients.

Intepretation: Electron beam radiotherapy enables the delivery of 'eye-guided' radiotherapy directly to the tumour. LC is good in patients with T1 tumours. Patients with T2 tumours have less satisfactory LC and should be treated with chemoradiotherapy. Electron beam radiotherapy enables the delivery of "eye-guided" RT directly to the tumour. LC is excellent in patients with T1 tumours. Patients with T2 tumours have less satisfactory LC and should be treated with chemoradiotherapy.

Background: Malignant pleural mesothelioma (MPM) is a rare thoracic malignancy with poor prognosis and limited treatment options. Immunotherapy shows potential for improved outcomes; however, real-world evidence on its use will take time to accumulate. This study examined patient characteristics, treatment patterns, overall survival (OS), and predictors of mortality among patients diagnosed with MPM in Denmark prior to the introduction of newer treatments.

Methods: This historical cohort study based on routinely collected Danish National Registry data included adults newly diagnosed with MPM between 01 January 2011 and 31 May 2018. Summary statistics were used to describe patient characteristics and initial treatment. OS was estimated using Kaplan-Meier methods; Cox regression was used to compare patient mortality against the (age/sex-matched) general population and to investigate mortality predictors.

Results: Overall, 880 patients were included; 44% had advanced MPM, 37% had non-advanced MPM, and 19% had unknown MPM stage. Median age at diagnosis was 71.9 years, and 82% of the patients were male. Within 180 days of diagnosis, no treatment was recorded for 215 patients (54%) with advanced MPM and 150 (46%) with non-advanced MPM. Median time-to-initial treatment (interquartile range) was 47 days (31-111) overall, 40 days (28-77) in patients with advanced MPM, and 53 days (35-121) with non-advanced MPM. Median OS was 13.7 months overall (non-advanced MPM: 18.0 months vs. advanced MPM: 10.0 months). Predictors of higher mortality were older age at diagnosis, histology, and advanced MPM stage.

Interpretation: These findings provide a baseline upon which to evaluate MPM epidemiology as newer treatments are adopted in routine practice.

Background and purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is a troublesome side effect in patients exposed to taxanes in the treatment of cancer and may affect quality of life dramatically. Here we assessed whether serum levels of neurofilament light (NfL) and tau (two neuroaxonal injury biomarkers) and glial fibrillary acidic protein (GFAP, a biomarker for astrocytic activation) correlate with the development of CIPN in the adjuvant setting of early breast cancer.

Materials and methods: Using ultrasensitive single molecule array technology, serum levels of NfL, GFAP, and tau were measured before and every 3 weeks in 10 women receiving adjuvant EC (epirubicin 90 mg/m² and cyclophosphamide 600 mg/m²) every 3 weeks × 3, followed by weekly paclitaxel 80 mg/m² × 9-12 weeks after surgery due to early breast cancer. CIPN was graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0) and the questionnaire EORTC QLQ CIPN-20.

Results: Serum levels of GFAP increased successively during cycles of EC. NfL increased instead in response to the treatment of paclitaxel. NfL and GFAP continued to rise throughout exposure of cumulatively higher doses of paclitaxel and were reduced 3 months after the end of chemotherapy. Serums levels of tau were marginally affected by exposure to chemotherapy. Women with worse symptoms of CIPN had higher concentrations of NfL than women with mild symptoms of CIPN.

Interpretation: NfL and GFAP are promising biomarkers to identify women at risk of developing CIPN. Larger prospective studies are now needed.

Background: In recent years, there has been a change in the therapeutic landscape of desmoid-type fibromatosis (DF). Watchful waiting is now preferred over initial local treatments such as surgery and radiotherapy. Systemic treatment is considered for progressive or symptomatic disease. The aim of this study is to review real-life data on the use of sorafenib in DF.

Methods: We established a retrospective dataset of patients treated with sorafenib in our centre, Ghent University Hospital, for progressive DF. Patient demographics, disease characteristics, response to therapy using Response Evaluation Criteria in Solid Tumours 1.1 criteria and toxicity according to CTCAE v5.0 were assessed.

Results: Eleven patients with DF were treated with sorafenib between 2020 and 2024. Median treatment duration was 20.4 months (95% confidence interval [CI], 10.0-NR). 36.4% achieved partial response, 54.5% stable disease and 9.1% progressive disease. For three patients, the treatment is ongoing. The median time to objective response rate is 15.0 months (95% CI, 8.8-NR). The majority (81.8%) experienced grade 2 toxicity, and one third of patients grade 3 toxicity (36.4%). The most common all-grade adverse event was skin toxicity (hand-foot syndrome, pruritus and rash) (90.9%). Nine patients (81.8%) needed dose reduction with a median time to first reduction of 1.1 months (95% CI, 0.5-NR). One patient stopped treatment due to toxicity.

Interpretation: Real-life data on the use of sorafenib in the treatment of DF is consistent with published data in clinical trial setting. Sorafenib is an effective treatment option for progressive DF although associated with significant toxicity and the need for rapid dose reduction.

Background and purpose: There are few studies of personality traits in long-term Hodgkin lymphoma survivors (HLSs) treated according to contemporary stage-and risk-adapted approaches. The Distressed Personality (DP) Scale covers negative affectivity and social inhibition. We examined differences in self-reported late adverse effects (LAEs) between HLSs with and without DP and other explanatory variables.

Material and methods: This cross-sectional questionnaire-based study included a population-based cohort of HLSs treated from 1997 to 2006, aged 8-49 years at diagnosis, and alive in 2016. Among 518 eligible HLSs, 303 responded (58%), and 294 completed the DP scale. DP was defined by scores above cut-off on both the negative affectivity and social inhibition subscales. LAEs studied were major depression, posttraumatic stress disorder, sleep problems, obesity, neuropathy, fatigue, memory problems, and general health. DP and 10 other explanatory variables were tested against LAEs as dependent variables in multivariable regression analyses.

Results: The mean age at survey was 45.9 years (standard deviation [SD] 4.6), mean follow-up time 16.7 years (SD 3.0), and 48% were females. Eighty-two HLSs had DP (28%, 95% confidence interval 23% - 33%). All LAEs except obesity were significantly more common/had higher mean score in HLSs with DP. In multivariable analyses, presence of DP was significantly associated with all LAEs except obesity.

Interpretation: The presence of DP is common among HLSs. The presence of DP was associated with most self-report LAEs examined. Including assessment of personality traits in the survivorship care plans of HLSs should be considered. Prospective studies assessing the influence of pretreatment DP on LAEs are warranted.

Background and purpose: Metaplastic breast carcinoma (BC-Mp) is an uncommon subtype that poses unique challenges. The limited information on patient prognosis and therapeutic strategies motivated our research initiative. We aimed to assess disease-free survival (DFS), overall survival (OS), and influential factors in patients with nonmetastatic BC-Mp.

Materials and methods: In this multicenter retrospective cohort study, clinicopathological data for nonmetastatic BC-Mp patients treated at four oncology units in Poland (2012-2022) were gathered.

Results: Among 115 women (median age 61, range: 28-91), the median tumor size was 40 mm (range 20-130); 30% of patients exhibited positive local lymph nodes. The majority of patients presented with stage II (46%) and triple-negative breast cancer (TNBC) (84%). Radiotherapy was administered to 61% of patients. Surgical procedures included breast-conserving surgery in 31% of patients and mastectomy in 68%. Eighty-three per cent of patients received chemotherapy. The median estimated DFS and OS were 59 and 68 months, respectively. Multivariable analysis revealed that tumor size influenced DFS and OS (Hazard ratios [HR] = 1.02, 95%CI 0.01-0.03 for both endpoints) and taxanes application improved DFS (HR = 0.47, 95%CI 0.24-0.93), but other factors did not. For patients receiving neoadjuvant systemic therapy (N = 51), taxanes improved DFS and OS according to univariable analysis.

Interpretation: Our findings highlight poor DFS and OS regardless of receiving optimal treatment, emphasizing the need for tailored therapeutic strategies for BC-Mp patients. Taxanes appear promising in a neoadjuvant setting, particularly within the current standard of care for the TNBC subtype.