To Örebro University

External comparator cohort (ECC) studies with real-world data (RWD) may provide more reliable estimates of treatment differences compared to single-arm trials (SAT), yet they face limitations such as selection bias and data heterogeneity. This study assessed the perceived strength of evidence of ECC studies compared to SAT and randomized controlled studies (RCT). The study included healthcare professionals (HCP) from the European Hematology Association (EHA), the European Society for Medical Oncology (ESMO), and assessors from international regulatory agencies (RA). A conjoint analysis evaluated strength of evidence ratings for establishing an effect on OS for different hypothetical scenarios, based on different designs, RWD quality, and observed OS improvement, for a new cancer treatment for advanced disease and no effective treatments. Participants from HCP organizations rated RWD studies favorably (advantages outweigh disadvantages) more frequently (47.6%; n = 103) compared to RA participants (12.9%; n = 116). Compared to a SAT, a high-quality RWD ECC study showing a 1.5-month and 3-month OS improvement had 2.7 (95% CI: 1.9-3.8) and 14.7 (95% CI: 10.0-21.5) times higher odds of receiving a higher strength of evidence rating, respectively. The OR for RCT v. SAT was 36.4 (95% CI: 24.0-55.2) and 358.4 (95% CI: 217.3-591.3), respectively. Strength of evidence ratings were associated with maximum acceptable risk of severe or symptomatic toxicity. In conclusion, when evaluating the OS of new therapies, ECC studies with RWD, especially when based on high-quality RWD or demonstrating a larger OS benefit, were rated as more convincing than SAT without a formal control.

Background: The secondary use of electronic health records (EHRs) poses legal challenges, particularly when the responsibility for managing EHRs lies with local or regional authorities. This article presents a case-based analysis of the secondary use of EHR data in contexts where data privacy responsibilities are managed regionally in Sweden.

Methods and results: Using two distinct purposes for the secondary use of the digital tool Patient Overview Breast Cancer: (i) assessing the uptake of new treatment strategies in a real-world setting for quality assurance, and (ii) evaluating the effectiveness of these strategies in specific patient subgroups with limited evidence for research purposes, the study explored the distinctions between research and quality assurance, the legal implications of each framework, and the potential role of federated learning as a privacy-preserving technological solution.

Conclusions: Federated learning offers a promising approach to overcome legal and organizational barriers to secondary use of regional EHRs in Sweden, enabling scalable, clinically meaningful insights for cancer care. However, its effective implementation requires a unified national framework that balances personal integrity with patient safety, supported by regulatory sandboxes.

PURPOSE: Patients with cancer receiving immune checkpoint inhibitors (CPIs) may experience immune-related adverse events (IRAEs) due to immune system overactivation. Concurrently, infections such as seasonal influenza can be more severe in cancer patients because of their compromised immune function, making influenza vaccination particularly important. In this multicenter retrospective study, we investigated whether influenza vaccination during CPI treatment influences CPI effectiveness and rates of IRAEs.

PATIENTS AND METHODS: We conducted a retrospective cohort study across three Swedish centers involving patients with metastatic cancer treated with CPIs-either PD-1/PD-L1 inhibitors or combination immunotherapy-between January 1, 2016, and December 31, 2021. To address immortal time bias in time-to-event outcomes, different statistical strategies were employed including time-dependent Cox regression and landmark analyses.

RESULTS: In total, 587 patients treated with CPIs during the study period were identified. The most common malignancy was non-small cell lung cancer (NSCLC; 34.4%), followed by cutaneous malignant melanoma (CMM; 32.5%). Time-dependent Cox regression analysis showed that real-world progression-free survival was significantly longer in influenza-vaccinated patients compared with unvaccinated in overall cohort (hazard ratio [HR], 0.59 [95% CI, 0.44 to 0.79]). No statistically significant differences in the occurrence of any grade IRAEs (48.4% v 51.2%, P = .455) or multiple IRAEs (15.1% v 19.2%, P = .297) between the vaccinated and unvaccinated groups were observed. The survival benefit was more pronounced in patients with CMM, whereas no statistically significant effect was observed in patients with NSCLC.

CONCLUSION: Our findings suggest a potential association between influenza vaccination and improved survival in CPI-treated patients, without a corresponding increase in IRAEs, supporting current vaccination recommendations. The observed association in patients with CMM may reflect underlying biological mechanisms and is hypothesis-generating for further investigation.

PURPOSE: Metaplastic breast cancer (metBC) is a rare subtype of breast cancer known for its challenging management. The impact of this histological subtype on prognosis remains unclear.

METHODS: Data were collected from the Swedish Cancer Registry between 2008 and 2018. Patients with metBC were matched 2:1 with breast cancer cases of no special type (NST). Survival outcomes were analyzed using cause-specific hazard models for breast cancer specific survival (BCSS) and Cox proportional-hazards models for overall survival (OS).

RESULTS: In total, 127 metBC patients were matched 2:1 with 245 NST patients, with a median follow-up period of 54 months. When adjusted for matching variables and treatment-related characteristics, metBC was not significantly associated with either BCSS (cause-specific Hazard Ratio (HR): 1.13; 95% Confidence Interval (CI): 0.66-1.92) or OS (HR: 1.23; 95% CI: 0.83-1.82).

CONCLUSION: With appropriate treatment, metBC may have survival outcomes comparable to NST. Larger studies with longer follow-up are needed to provide further insights.

Accurate information about locoregional breast cancer treatments following neoadjuvant systemic therapy (NST) is essential for meaningful interpretation of oncological outcomes but reporting is currently poor. We developed a core outcome set (COS) to improve the quality and consistency of locoregional outcome reporting in breast cancer NST trials. The COS was developed in three phases according to COS-STAD guidance, with the generation of a list of relevant outcome domains, prioritisation of outcomes through two rounds of an international online multi-stakeholder Delphi survey and a consensus meeting. 159 unique locoregional outcomes were classified into 101 outcome domains for inclusion in the Delphi survey, which was completed by 470 international professionals. The final 15-item COS, which included the pre-NST surgical plan, details of surgery performed following completion of treatment and details of radiation therapy, was agreed at an in-person consensus meeting. Widespread COS implementation will improve the quality and value of future NST trials.

PURPOSE: Hypofractionated radiation therapy requires high accuracy in dose delivery to enable reduced treatment margins and minimize the dose to organs-at-risk. The purpose of this study was to evaluate whether accelerated (delivered 5 times per week) hypofractionated external beam radiation therapy (EBRT) can be performed without increased acute toxicity using a real-time tracking system. We also aimed to investigate patterns of intrafractional prostate movements.

METHODS AND MATERIALS: Patients with prostate cancer planned for combined high dose rate brachytherapy (14.5 Gy × 1) and EBRT (3 Gy × 14) were included in this randomized trial to receive the EBRT part of the treatment either 3 or 5 times per week. EBRT was delivered using small margins (3 mm) using the Raypilot system for real-time tracking of intrafractional prostate movements. Movements were continuously monitored in 3 dimensions. Primary endpoint was toxicity that was assessed using patient-reported outcome measures through european organisation for research and treatment of cancer (EORTC) quality of life questionnaires QLQ-C30 and QLQ-PR25.

RESULTS: During June 2018 to January 2020, 34 patients (median age 70 years) were included in the study of which 17 were randomized to each group. No statistically significant differences in toxicity were found between the study groups. Target displacement was <2 mm during 97.0% of the time and <3 mm during 99.9% of the active treatment time.

CONCLUSIONS: We found no evidence of increased acute toxicity in patients who received accelerated treatment schedule. Provided that the target is properly delineated, a 3 mm margin seems to be feasible and safe when using a real-time tracking system.

BACKGROUND: Multiple trials have evaluated escalation strategies of endocrine therapy for early breast cancer, including ovarian function suppression (OFS) and aromatase inhibitors (AI) in premenopausal patients and extended endocrine therapy. However, several aspects remain controversial due to the heterogeneity of study designs and lack of statistical power in relevant subgroups. We aimed to investigate the optimal endocrine therapy strategy.

METHODS: A systematic literature search was performed and last updated in August 2024 to identify randomized controlled trials (RCT) evaluating endocrine treatment strategies for hormone receptor positive breast cancer. A network meta-analysis with a frequentist framework using random-effects model was used to pool direct and indirect evidence. In addition, an extracted individual patient data meta-analysis was conducted to estimate the absolute differences between treatments. Study endpoints were disease-free survival (DFS), overall survival (OS), and safety. PROSPERO: CRD42023447979.

FINDINGS: A total of 37 RCT that had enrolled 107,684 patients were included in the study. During the first five years, OFS + AI was the most effective strategy in premenopausal women, while AI or switch strategy showed the better efficacy results in postmenopausal ones. Following five years of tamoxifen, continuation with five additional years of AI was associated with improved 8-year DFS (85.8%) compared to no extended therapy (78.1%) or five additional years of tamoxifen (81.0%). Following five years of AI or switch strategy, extended treatment with AI improved DFS (Hazard Ratio = 0.81, 95% Confidence Interval 0.73-0.90).

INTERPRETATION: This study provides information regarding the optimal endocrine treatment strategies for patients with resected hormone receptor positive early breast cancer. FUNDING: None.

Sarcopenia is characterised by low grip strength, muscle quantity or quality, and physical performance. This study investigated the associations of sarcopenia and its components with cancer incidence. A prospective cohort study was conducted utilising data from the UK Biobank. Sarcopenia and its components were defined according to the European Working Group on Sarcopenia in Older People criteria (EWGSOP2 2019). Cox proportional hazard models adjusted for sociodemographic, lifestyle, and health-related factors were performed. Overall, 63,379 out of 414,094 study participants had an incident diagnosis of cancer during a median follow-up of 11.7 years. In total, 32,286 participants had probable sarcopenia and 934 confirmed/severe sarcopenia at recruitment. Combined probable, confirmed, and severe sarcopenia was associated with a higher risk of liver (hazard ratio [HR] = 1.65, 95% confidence interval [CI]: 1.17-2.33), haematological (HR = 1.22, 95% CI: 1.01-1.46), and colorectal cancer (HR = 1.21, 95% CI: 1.04-1.41) in males, but not in females. The components of sarcopenia were associated with a higher risk of several cancers, including low grip strength (with liver, haematological and colorectal cancer in males), low muscle mass index (oesophageal in females and oral cancer in males), and slow walking pace (liver and lung in males, lung and overall cancer in females). Compared to participants with non-sarcopenic obesity, those with sarcopenic obesity had a higher risk of colorectal cancer in males (HR = 1.31, 95% CI: 1.03-1.68). Our study suggests that sarcopenia, sarcopenia components, and sarcopenic obesity can be associated with risk for several cancers, mainly of the gastrointestinal tract and in males. Thus, early identification of sarcopenia components may benefit cancer prevention.

INTRODUCTION: Treating localized high-risk prostate cancer with a combination of external beam radiation therapy (EBRT) and high-dose-rate brachytherapy (HDR-BT) is a common approach. Moderately hypofractionated EBRT and a single HDR-BT boost simplifies the treatment. We aim to present our five-year results.

METHODS: In this study, 355 patients treated with moderately hypofractionated EBRT (42 Gy in 14 fractions) and a single HDR-BT boost (14.5 Gy) at Örebro University Hospital between 2008 and 2018 were included. They were followed with regular PSA tests.

RESULTS: The median age of the cohort was 70 years (range: 51-81) and the median follow-up duration was 56 months (range: 6-150). Among them, 45% were classified as very high-risk, 38% as high-risk and 17% as intermediate-risk. Adjuvant androgen deprivation therapy (ADT) with a median duration of 24 months was given to 75% of the patient cohort. The estimated 5-year failure free survival rates were 79% (whole cohort), 66% (very high-risk), 90% (high-risk) and 85% (intermediate-risk), respectively. Initial PSA > 10 ng/mL, Gleason score 9-10 and tumor stage T3 were significantly associated with biochemical failure (BF). A PSA bounce occurred in 53 (15%) cases and was inversely associated with BF (p = 0.001) for patients receiving ADT.

CONCLUSIONS: Moderately hypofractionated EBRT and a single HDR-BT boost seems to be an effective treatment against intermediate- and high-risk localized prostate cancer. Treatment escalation strategies should be investigated for very high-risk patients where the risk of recurrence remains high.