Acta Oncologica最新文献

Background: Evidence of treatment of patients with relapse following multimodal treatment for oesophageal, gastro-oesophageal junctional and gastric adenocarcinoma is almost absent.

Methods: In a nationwide consecutive cohort of 202 patients, radically resected after perioperative chemotherapy (CTx) and followed-up without scheduled imaging, we identified 89 patients with recurrence within 12 years. We registered prior clinico-pathological and treatment characteristics, alarming symptoms, work-up, recurrence patterns, treatment of recurrence, and outcome.

Results: Median time to recurrence was 15.2 months, 91% of relapses occurred within 3 years. Frequent alarming symptoms were pain, weight loss and loss of appetite. Fifty-four percent recurred at multiple sites, 36% at a single anatomic site, and 10% were solitary. Recurrence was a 99% fatal event with a median overall survival (OS) of only 4.6 months. Older age, ypN3 at surgery, poor performance status, weight loss, non-solitary recurrence, no postoperative CTx, and no palliative CTx, were associated with short OS. Three patients had initial surgery, but all progressed; one additional patient was cured by salvage surgery after palliative CTx. Sixty percent (53 patients) were treated with CTx yielding a median progression-free survival and OS of 4.0 and 5.8 months, respectively; the overall response rate was 35%. Pleuroperitoneal metastases predicted poor prognosis. Non-platinum-based, first-line palliative CTx was used in 38%, mostly in patients with short treatment-free interval.

Interpretation: In this national cohort, recurrence was a 99% fatal event and only 60% of patients received palliative CTx. Efficacy of palliative CTx at relapse after multi-modal treatment is poor and needs further investigations.

Background and purpose: As more interventional clinical trials in Precision Cancer Medicine (PCM) are introduced, molecular descriptions of tumours have led to multiple subtypes, even within common tumour types. Therefore, the main limitation of these trials is the small number of eligible patients to assess the clinical benefit. The PRIME-ROSE project addresses this limitation by pooling data from multiple European Drug Rediscovery Protocol (DRUP)-like clinical trials, such that slowly accruing cohorts are accelerated. To achieve this task, a well-documented commonly approved procedure for data merging needs to be established. Patient/material and methods: Data sharing is achievable when there is an organisation that includes people from different disciplines who can navigate institutional and country-specific information and governance requirements. Furthermore, alignment of all the study procedures are needed before data are shared. Next, the process of merging data requires harmonisation and standardisation. Implementation of the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) facilitates future data aggregation.

Results: By aggregating data from European DRUP-like clinical trials, cohorts are completed that were unable to do so in stand-alone studies. Since initiation, the PRIME-ROSE project monitors over 300 cohorts across more than 20 treatments encompassing over 1,000 patients. At least 20 cohorts have progressed after interim analysis.

Interpretation: Data sharing across European trials is feasible and enhances the advancements of PCM studies. The methodologies developed in the PRIME-ROSE project provide a foundation for future data integration efforts in PCM clinical trials, underscoring the viability of conducting robust trials in a global context.

Background and purpose: Tobacco smoking was prognostic in B-cell lymphomas in the pre-rituximab era, but the association with modern treatment, stage, subtypes, and survival outcomes remains unclear. Patient/material and methods: All patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) from Turku and Tampere University Hospitals 2009-2019 were identified. Population-based data from electronic medical records included demographics, tumour histology, Ann Arbor staging, and treatments. Smoking status was extracted with a deep learning-based natural language processing algorithm. Kaplan-Meier overall survival (OS) estimates and adjusted hazard ratios (HRs) were calculated.

Results: With a median follow-up of 96 months, 1,258 patients with DLBCL and 529 with FL were included. In DLBCL, the 5-year OS rate was 61%, 53%, and 45% among never, former, and persistent smokers, respectively. Persistent smoking remained an independent prognostic factor for shorter OS, HR 1.27 (95% confidence interval 1.10-1.60) after adjustment for comorbidities and completed treatment. The prognosis of FL was indolent with no difference in OS regardless of smoking status, with 5-year OS rates of 79%, 75%, and 74% among never, former, and persistent smokers, respectively. Smokers were younger at diagnosis, while other baseline demographics were similar. No differences in the systemic therapy use were observed between the different smoking categories in both FL and DLBCL.

Interpretation: Overall and lymphoma-specific mortality is increased in persistent smokers with DLBCL compared with never smokers. Smoking prevention and cessation support remains of utmost importance.

Background and purpose: The study aims to assess the occupational variation of sinonasal cancer (SNC) incidence in the Nordic population. SNC is an aggressive disease with poor prognosis and a strong connection with occupational exposure, hence, assessing occupational risk for SNC is an essential aspect in the efforts of cancer prevention.

Patients/material and methods: Standardized incidence ratios (SIR) with 95% confidence intervals (CI) for SNC were calculated for 54 occupational categories from data based on population censuses and cancer registries in the five Nordic countries Denmark, Finland, Iceland, Norway, and Sweden.

Results: During 1961-2005, 5,799 SNC cases were registered, 61% men and 39% women. Male woodworkers had an SIR of 1.84 for SNC (95% CI 1.66-2.04) with 355 cases, a finding consistent across all Nordic countries. The SIR for the histological subgroup sinonasal adenocarcinoma (SNAC) among male woodworkers was 5.50 (95% CI 4.56-6.56) with 122 cases. Female woodworkers also had an elevated SIR for SNC of 1.88 (95% CI 0.90-3.46), but based on only 10 cases. Country-specific elevated SIRs for SNC in men were noted in Denmark for shoe and leather workers (SIR 3.62, 95% CI 1.33-7.87), and in Norway for smelting workers (SIR 2.24, 95% CI 1.41-3.39). Reduced SIRs were observed for male military personnel, teachers, gardeners and farmers, and female religious workers.

Interpretation: According to these Nordic registry data, woodworking, which is normally based on soft wood in the Nordic countries, is a high-risk occupation for SNC and particularly for SNAC.

Background: Significant progress has been made in the management of metastatic NSCLC (mNSCLC). Our study investigated characteristics, treatment patterns, and outcomes in this patient population and subgroups based on histology and PD-L1 status.

Methods: We conducted a retrospective analysis of electronic health records of patients with mNSCLC 1/2019-8/2023 at HUS, Helsinki University Hospital, Finland. Patient characteristics, treatment, and outcomes were analyzed.

Results: We identified 646 patients with mNSCLC, including those metastatic at diagnosis and whose cancer later progressed to metastatic, who received systemic therapy. Median age was 70 years (interquartile range [IQR]: 62-75). Squamous cell carcinoma (SqC) presented 19% of patients, adenocarcinoma 68%, and other non-SqC 13%. Amongst the non-SqC patients 53% were female, whereas only 32% of SqC patients were female. Treatment evolved considerably, with increased use of immuno-oncology (IO) and tyrosine kinase inhibitor (TKI) therapies. Median overall survival was 8 months (confidence interval [CI] 95%: 6-9) for those treated with chemotherapy alone, 12 months (CI 95%: 7-18) for those treated with IO therapy, 14 months (CI 95%: 11-15) for those treated with IO + chemotherapy, and 24 months (CI 95%: 16-38) for those treated with TKIs.

Interpretation: Our study reports real-world management of patients with mNSCLC and evolving treatment patterns in clinical practice from the first years of IO treatment availability. As we continue to monitor more recent data, the proportion receiving chemotherapy alone is anticipated to continue decreasing. It is crucial to assess current outcomes in NSCLC to target resources correctly and improve prognosis.

Background and purpose: The psychosocial needs of migrant families affected by a child's severe -illness are extensive. However, few family-centred interventions have been evaluated and even fewer have included families with migrant backgrounds. The aim of this study was, therefore, to explore migrant families' experiences of participating in a family-centred psychosocial intervention, the Family Talk Intervention (FTI), in a paediatric care setting.

Material and methods: In this study, semi-structured interviews were performed with 14 family members (six parents, one ill child, and seven siblings) after participating in FTI. The interviews were transcribed and analysed using thematic network analysis.

Results: After participating in FTI, the families experienced that, in their already exposed situation, their family stability had increased as they were supported in dealing with social and financial issues, encouraged to talk openly about difficulties, and thus became closer as a family. Both children and parents described the value of having someone professional, continuously available, to turn to for guidance and information.

Interpretation: Migrant families dealing with a child's severe illness live in an exposed situation, with a double burden of distress related to the child's illness and socioeconomic factors. By acknowledging the importance of these families' psychosocial needs, it could be recognised that psychosocial support, such as FTI, not only aids family adjustment but also contributes to reducing this double burden, increasing family stability.

Background: In patients with cancer, unintentional weight loss and cancer-associated cachexia (CAC) reduce overall survival and impair the quality of life. Because of insulin's anabolic effects, insulin resistance could contribute to CAC progression. However, the role of insulin resistance in CAC remains unclear, and this study aimed to investigate the association between insulin resistance and CAC. Addressing this knowledge gap may help identify treatable targets to improve patient outcomes.

Methods: We performed a systematic review and meta-analysis. By including studies reporting both fasting levels of circulating insulin and glucose in patients with cancer and CAC according to the internationally accepted CAC definition, we calculated the HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) index to estimate the level of insulin resistance (defined as HOMA-IR above 2.0) in patients with CAC. A subgroup analysis was conducted from studies reporting a HOMA-IR index both from a group of patients with CAC and a group without CAC (nonCAC).

Results: Seventeen studies were included, with a total of 197 patients. The mean HOMA-IR of all studies was 1.84 (95% confidence interval [CI]: 1.77-1.91). Twelve studies found HOMA-IR below 2.0. Five of the 17 studies also reported HOMA-IR from a group of patients with cancer without CAC. We observed a mean difference of -0.42 (95% CI: -2.24 to 1.40) in favour of a lower HOMA-IR in patients with CAC compared to nonCAC, and thus no statistically significant difference between the groups.

Interpretation: This systematic review suggests no clear association between insulin resistance and CAC. However, the limited sample sizes and study heterogeneity highlight the need for larger, longitudinal investigations.

Background and purpose: Despite being a critical treatment modality, radiotherapy effectiveness is often limited by tumor resistance. Therefore, there exists a need to identify molecular targeted drugs that enhance the therapeutic response to radiation. We hypothesize that a systematic comparison of targeted radiosensitizers across two-dimensional (2D) and three-dimensional (3D) spheroid cultures will reveal context-specific differences in radiosensitivity to guide preclinical prioritization of candidate radiosensitizers.

Material and methods: Radiosensitizing effects of DNA-PKcs (M3814), ATR (M6620), PARP (Olaparib), and IAP (Birinapant) inhibitors using a panel of lung cancer cell lines were studied. A 3D extracellular matrix (ECM) colony formation assay for single doses of 0-6 Gy, coupled with automated colony counting, was implemented alongside standard 2D colony formation assays. Dose Enhancement Factor (DEF0.1SF) was used to compare radiosensitizing effects, and drug-radiation interactions were assessed using the Synergyfinder tool.

Results: DNA-PKcs and ATR inhibitors induced moderate to strong dose-dependent radiosensitization (DEF0.1SF > 1.4 for at least one drug concentration) in most cell lines under both conditions (15/16 drug/cell line combinations). PARP inhibition showed similar effects in 3D and 2D (2/3 vs 3/5 combinations). Birinapant showed no relevant effect. The strongest synergy was at 2 Gy, particularly with the DNA-PK inhibitor in both culture models.

Interpretation: Integrating multiple culture models enhances the detection of cell line - and drug-specific radiosensitization. Although 2D and 3D cultures produced largely similar results, and 2D assays provide a practical alternative when 3D methods are not feasible, the 3D cultures reveal additional ECM-dependent responses. These results emphasize the utility of physiologically relevant platforms for robust screening and prioritization of candidate radiosensitizers.

Background and purpose: The objective of this systematic review was to establish an overview of changes in body composition as a result of early breast cancer treatment. Patient/material and methods: Five databases (PubMed, CINAHL, Embase, Web of Science and Cochrane Library) were used for identifying studies and papers. Selection criteria included: > 18 years, early breast cancer stage 0-III and measurement of body composition with either dual X-ray absorptiometry (DXA), magnetic resonance imaging (MRI) or computed tomography (CT). Studies using only bioelectrical impedance were excluded.

Results: A total of 734 studies were screened; 29 studies were full-text reviewed, and 10 studies were included in this systematic review, with a total of n = 1,062. Included studies were published from 2018 to 2024. This review found consistent increases in fat mass between 3.3 and 9.2% across the studies. Results for lean body mass were less consistent. Two studies examined visceral fat mass, yet both found statistically significant increases.

Interpretation: This systematic review identified consistent increases in total fat mass and visceral fat across the included studies, regardless of whether the treatment involved chemotherapy, endocrine therapy or a combination of both. In contrast, findings related to lean body mass were considerably less consistent. The results highlight the potential implications following breast cancer treatment and emphasise the importance of metabolic monitoring, diet and exercise to increase quality of life and prevent recurrence. This review also highlights the need for more research on the topic, as the included studies exhibit substantial heterogeneity, making it difficult to draw definitive conclusions.