To Örebro University

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.

INTRODUCTION: Treatment of older cancer patients can be complex due to frailty that comes with age, and the benefits of radiation therapy for frail older patients are unclear. Radiation therapy staff play a crucial role in identifying and monitoring frailty and tailoring treatment. Research on radiation therapy in frail older patients is limited, and frailty assessments are not widely used in routine care. Understanding staff experiences with clinical judgement and frailty assessment is important for effective treatment. This study explored the radiation therapy staff's experiences of clinical judgement, treatment decision-making, and managing frail older cancer patients.

METHODS: The study has an inductive design in which 12 specialist oncology nurses and four clinical oncologists working with cancer patients at four radiation therapy units across four counties in Sweden were interviewed. In total, 16 participants were interviewed for the study. Data were collected in semi-structured individual interviews and were analysed using reflexive thematic analysis.

RESULTS: Three themes were identified from the interview analysis: Putting the patient first, Care with integrity and humanity and Receiving support in treatment decisions, along with nine sub-themes. None of the participants was using any structured instrument for assessing frailty.

CONCLUSIONS: Radiation therapy staff face significant and complex challenges when treating frail older cancer patients, which can lead to feelings of doubt and powerlessness. Awareness and use of structured frailty assessment are limited. Integrating structured frailty assessment could address the complex challenges experienced by staff by improving decision-making, communication, and patient outcomes, contributing to more ethical and person-centred care.

BACKGROUND: Although precision oncology has rapidly been developed in recent years, its real-world impact and challenges in healthcare implementation remain underexplored. Through a meta-analysis of real-world evidence (RWE), we aimed at investigating the applicability and clinical impact of comprehensive cancer genome profiling (CGP) in cancer patients with metastatic solid tumors.

METHODS: We systematically searched Medline, Embase, and Web of Science for RWE studies on CGP and matched therapies in metastatic solid tumors (publication period: 2012-2023). Pooled proportions of actionable genomic alterations, patients treated with matched targeted therapies, treatment, and survival outcomes were calculated. Data from Swedish cancer registries were used as a case-study for nationwide CGP implementation.

RESULTS: Out of the 7218 identified studies, 144 were included in our analysis. 59.8% of CGP-tested patients had actionable genomic alterations, with 15.6% (95% Confidence Interval (CI) 13.4-18.2%) of them having received targeted therapy. Objective response was seen in 23.9% (95% CI 20.8-27.3%). Overall, CGP-guided treatment was correlated with prolonged progression-free survival (pooled Hazard Ratio (HR) = 0.63; 95% CI, 0.56-0.70; 18 studies) and overall survival (pooled HR = 0.60; 95% CI, 0.51-0.70; 21 studies) when compared to conventional treatment. Meta-regression time projections analyses showed that these rates will steadily increase by 2030.

CONCLUSIONS: Pooled analyses of RWE studies indicate that approximately one-fourth of the patients receiving CGP-matched treatment have an objective response. By utilizing meta-regression projections, our nationwide cancer registry case-study offers insights into the potential of precision oncology for patients with metastatic cancer and to inform future healthcare strategies.

BACKGROUND: Alcohol consumption has been associated with an increased risk of cancer-related mortality. It may also negatively impact oncological therapies, potentially leading to impaired effectiveness or an increased risk of treatment-related toxicities. The aim of this systematic review and meta-analysis was to examine the current evidence regarding the potential effects of alcohol consumption during cancer treatments on both treatment effectiveness and toxicity, irrespective of cancer type.

METHODS: A comprehensive literature search was performed across three electronic databases (Medline, Web of Science, Cochrane) covering studies from January 1990 to December 2023. Furthermore, a manual search based on the reference lists of the eligible studies was performed to identify additional potentially eligible studies. Studies were eligible if they involved cancer patients and provided data on alcohol consumption during specific oncological treatments, including its effect on treatment outcomes, or compared treatment effectiveness or toxicity between drinkers and non-drinkers. Studies were excluded if they did not meet these criteria, were duplicates, case reports, conference abstracts, or focused only on cancer-specific or overall survival. Only studies using multivariable analyses to examine the association between alcohol consumption and treatment effectiveness or toxicity were included in the pooled analyses. Pooled Hazard Ratios (HRs) or Odds Ratios (ORs) and their corresponding 95% Confidence Intervals (CIs) were calculated using random-effects models. Study quality was assessed by using the Newcastle-Ottawa scale whereas the GRADE approach was applied to rate the certainty of evidence for pooled analyses.

RESULTS: Out of 6734 studies identified through searching, 38 met the inclusion criteria for pooled analyses. Alcohol consumption during radiotherapy, with or without concomitant chemotherapy, was associated with worse disease-free survival (pooled HR: 2.05; 95% CI: 1.09 - 3.89), although the numerically increased risk for locoregional recurrence did not reach statistically significance (pooled HR: 2.01; 95% CI: 0.76 - 5.36). The potential impact of alcohol consumption on chemotherapy-induced neurotoxicity and acute / delayed nausea was not statistically significant. However, alcohol consumption was associated with a lower risk of overall chemotherapy-induced nausea (OR: 0.69; 95% CI: 0.57, 0.84).

CONCLUSION: Our findings suggest that alcohol consumption may have a negative impact on radiotherapy, whereas its potential impact on the effectiveness of systemic oncological therapies (chemotherapy, molecular targeted therapy, immunotherapy, endocrine therapy) has not been adequately studied. Similarly, the current evidence on the potential association between alcohol consumption and treatment-related toxicities is weak, highlighting the need for well-designed prospective studies on this topic.

Introduction: Wound-related complications following breast surgery are common and may delay adjuvant treatment, prolong healing time ,and increase morbidity. Incisional negative pressure wound therapy (iNPWT) has been proposed as a strategy to reduce postoperative complications across various surgical procedures. However, its effectiveness in breast surgery remains uncertain.

Method: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Studies comparing iNPWT with standard dressings in closed breast surgery incisions were included if they reported at least one wound-related outcome. Comprehensive searches were conducted in MEDLINE, EMBASE, and CENTRAL up to March 2025. A random-effects model using the Hartung-Knapp-Sidik-Jonkman method was applied. Heterogeneity, publication bias, and study quality were assessed using the RoB2 and ROBINS-I tools. The certainty of evidence was evaluated according to the GRADE approach.

Result: Twenty-nine studies involving 4,904 patients were included. iNPWT had a modest but significant effect in reducing the risk o fwound dehiscence (RR: 1.07; 95% CI: 1.03–1.12; p < 0.001; I² = 81.6%) and surgical site infection (RR: 1.05; 95% CI: 1.01–1.09; p = 0.02; I² = 84.13%), despite the substantial heterogeneity. Prediction intervals highlighted the substantial between-study variability. Findings for seroma, skin necrosis, heamatoma, and nipple-areolar complex necrosis were inconclusive. Meta-regression identified low BMI and younger age as potential protective factors for skin necrosis, although no predictors were found for other complications.

Discussion: iNPWT may reduce specific wound complications in breast surgery, but heterogeneity and methodological limitations constrain conclusions. Further high-quality randomized trials with standardized outcomes are needed.

PURPOSE: The aim of this retrospective, single-center cohort study was to evaluate the effectiveness and safety of two-fraction high-dose-rate brachytherapy (HDR-BT) as monotherapy in a consecutive cohort of prostate cancer patients.

METHODS: We included consecutive patients who received 28 Gy HDR-BT in two fractions (14 Gy × 2) as monotherapy during 2005 to 2021 at our institution. Eligible patients were derived from an institutional database consisting of prospectively collected data. Primary endpoint was biochemical recurrence (BCR) and secondary endpoints included toxicity (assessed through both healthcare provider and patient-reported outcomes) and quality-of-life (QoL) assessment.

RESULTS: In total, 175 patients with prostate cancer (94 % classified as low- or intermediate-risk) were treated with HDR-BT during the study period with a median age of 68 years (range: 51-80), and a median follow-up of 60 months (range: 0-174). The estimated five-year cumulative BCR rate was 3.0 % (95 % Confidence Interval (CI): 0 %-13.3 %) for low-risk patients and 9.6 % (95 % CI: 4.7 %-16.7 %) for intermediate-risk patients. PSA exceeding 10 ng/mL at diagnosis was a significant risk factor for BCR (Odds Ratio (OR) = 3.29, 95 % CI: 1.01-10.67) whereas PSA of ≤0.1 ng/ml as nadir was a significant positive prognostic factor, associated with lower risk of BCR (OR = 0.11, 95 % CI: 0.03-0.33). At 12 months, 22 % of the patients had grade 2 and 3 % grade 3 urinary toxicity whereas 2 % of patients had grade 2 and none grade 3 bowel toxicity. At 12 months, 49 % of the patients with at least some erectile function before the treatment, had an impaired function.

CONCLUSION: We found that two-fraction HDR-BT as monotherapy among patients with mainly low- and intermediate-risk prostate cancer appears to be safe in terms of biochemical recurrence, with a low proportion of severe urinary and bowel toxicity.