Quality of life of women with a screen-detected versus clinically detected breast cancer in the Netherlands: a prospective cohort study.

PURPOSE: Breast cancer (BC) screening enables early detection of BC, which may lead to improved quality of life (QoL). We aim to compare QoL between women with a screen-detected and clinically detected BC in the Netherlands. METHODS: We used data from the 'Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaluation' (UMBRELLA) between October 2013 and March 2022. Patients were categorized as screen-detected or clinically detected. We analysed three questionnaires, namely EORTC QLQ C-30, BR23, and HADS (Hospital Anxiety and Depression Scale) completed by BC patients shortly after diagnosis (T1) and one-year after treatment (T2). Independent t-tests were performed to compare QoL average differences between the two groups. Bonferroni-corrected p-value significance threshold of 0.00057 was used. The magnitude of differences was calculated using Cohen's d. The clinical relevance of QLQ-C30 differences was assessed based on interpretation guideline of EORTC-QLQ-C30 results. RESULTS: After applying inclusion and exclusion criteria, there were 691 women with screen-detected BC and 480 with clinically detected BC. Generally, screen-detected BC patients reported a better QoL. At T1, their average QLQ-C30 summary score was higher (86.1) than clinically detected BC patients (83.0) (p < 0.0001). Cohen's d for all items ranged between 0.00 and 0.39. A few QLQ-C30 score differences were clinically relevant, indicating better outcomes in emotional functioning, general health, constipation, and fatigue for women with screen-detected BC. CONCLUSIONS: In the Netherlands, women with screen-detected BC reported statistically significant and better QoL than women with clinically detected BC. However, clinical relevance of the differences is limited.

This study compares the quality of life (QoL) of women with breast cancer (BC) detected through screening versus through clinical detection in the Netherlands. BC screening aims to detect cancer early, potentially improving QoL. We analysed data from the UMBRELLA cohort, focusing on QoL questionnaires filled out shortly after diagnosis and one year after treatment. Results showed that women with screen-detected BC generally reported better QoL than those with clinically detected BC. For example, they had higher QLQ-C30 summary scores and several other QLQ-C30 scales and items, indicating better emotional functioning, better general health, less constipation, and less fatigue symptom. We also found that the differences in QoL are larger at one year after treatment. However, while statistically significant, the differences in QoL between the two groups were either trivial or small and may have limited clinical relevance. This study sheds light on the potential impact of mode of detection on the QoL of women with BC.

Preoperative Magnetic Resonance Guided Single-Dose Partial Breast Irradiation: 5-Year Results of the Prospective Single-Arm ABLATIVE Trial.

PURPOSE: Preoperative partial breast irradiation (PBI) can increase accuracy of target volume definition and decrease irradiated volumes compared with postoperative PBI. In the ABLATIVE trial (NCT02316561), 15 of 36 patients achieved pathologic complete response 6 to 8 months after preoperative PBI and breast-conserving surgery (BCS). We now present the 5-year results. METHODS AND MATERIALS: The ABLATIVE trial is a Dutch prospective cohort study conducted in 4 hospitals. Women aged ≥50 years with unifocal, nonlobular breast cancer, estrogen receptor-positive, HER2-negative, and a tumor negative sentinel node were treated between 2015 and 2018 with preoperative single-dose PBI followed by BCS after 6 or 8 months. The primary endpoint was pathologic complete response. Secondary endpoints were annually evaluated oncological outcomes, toxicity, cosmetic outcome (assessed by patients and physicians), and quality of life. RESULTS: Thirty-six patients were treated with BCS 6 (n = 15) and 8 (n = 21) months following PBI. Median tumor size was 13 mm (IQR 9-16 mm). After a median follow-up of 5.5 years (IQR, 5.1-6.0), 2 (6%) patients had ipsilateral breast events and 2 (6%) distant metastases. The 5-year overall survival was 94% (95% CI, 87-100). The 5-year cumulative incidence of clinician-reported grade 1/2 breast fibrosis and breast discomfort/pain were 94%/6% and 75%/6%, respectively. The proportion of patients (very) satisfied with the cosmetic results was 89% at baseline and 78% at 5 years. Cosmetic results evaluated using the BCCT.core software were excellent or good in all patients. The 4-year median global quality of life score was 83 (IQR, 67-92), similar to baseline (83; IQR, 75-83; P = .42). CONCLUSIONS: Preoperative single-dose PBI and BCS may be an oncologically safe treatment with mild late toxicity and no decline in cosmetic results and quality of life during 5 years of follow-up. This means that preoperative instead of standard postoperative irradiation has the potential to challenge the current clinical practice.

On Patient Experience and Anxiety During Treatment With Magnetic Resonance-Guided Radiation Therapy.

Purpose: To assess patient experience and anxiety during magnetic resonance (MR)-guided radiation therapy (MRgRT) using a hybrid 1.5Tesla (T) MR-guided linear accelerator (MR-Linac) when offered calming video content. Methods and Materials: A single-center study was conducted within the Multi-Outcome Evaluation of Radiation Therapy Using the MR-Linac (MOMENTUM) cohort. Patients were offered to watch calming video content on a video monitor during treatment. Questionnaires were used to assess patient experience (MR-Linac patient-reported experience) and anxiety (State-Trait Anxiety Inventory, STAI) at first treatment fraction (M1) and at third, fourth, or fifth treatment fraction (M2). Paired t tests were used to test for significant differences, and effect sizes (ESs) were used to estimate the magnitude of the difference. Results: Between November 2021 and November 2022, 66 patients were included. The majority were men (n = 59, 89%). MRgRT was most frequently delivered to prostate cancer (n = 45, 68%) followed by a lesion in the pancreas (n = 8, 12%). At M1 and M2, 24 of 59 patients (41%) preferred to watch calming video content. One patient was not able to look at the video monitor comfortably at M1. Patient experience was generally favorable or neutral; tingling sensations were reported by 17% of patients. Anxiety levels were high (16%), moderate (18%), or low to none (67%) prior to M1. STAI scores were 33 (SD, 9) prior to M1 and 29 (SD, 7) after M1 (ES, 0.7; P < .001). STAI scores were 32 (SD, 9) prior to M2 and 31 (SD, 8) after M2 (ES, 0.4; P = .009). Conclusions: Patients were able to comfortably view the video monitor during MRgRT. Consequently, this setup could be used for future applications, such as biofeedback. A sizable minority of patients preferred to watch calming videos that distracted them during treatment. Although the patients' experience was overall excellent, anxiety was reported. Anxiety levels were highest prior to treatment and decreased after treatment.

Characteristics, consent patterns, and challenges of randomized trials using the Trials within Cohorts (TwiCs) design - A scoping review.

OBJECTIVES: Trials within Cohorts (TwiCs) is a pragmatic design approach that may overcome frequent challenges of traditional randomized trials such as slow recruitment, burdensome consent procedures, or limited external validity. This scoping review aims to identify all randomized controlled trials using the TwiCs design and to summarize their design characteristics, ways to obtain informed consent, output, reported challenges and mitigation strategies. STUDY DESIGN AND SETTING: Systematic search of Medline, Embase, Cochrane, trial registries and citation tracking up to December 2022. TwiCs were defined as randomized trials embedded in a cohort with postrandomization consent for the intervention group and no specific postrandomization consent for the usual care control group. Information from identified TwiCs was extracted in duplicate from protocols, publications, and registry entries. We analyzed the information descriptively and qualitatively to highlight methodological challenges and solutions related to nonuptake of interventions and informed consent procedure. RESULTS: We identified a total of 46 TwiCs conducted between 2005 and 2022 in 14 different countries by a handful of research groups. The most common medical fields were oncology (11/46; 24%), infectious diseases (8/46; 17%), and mental health (7/46; 15%). A typical TwiCs was investigator-initiated (46/46; 100%), publicly funded (36/46; 78%), and recruited outpatients (27/46; 59%). Excluding eight pilot trials, only 16/38 (42%) TwiCs adjusted their calculated sample size for nonuptake of the intervention, anticipating a median nonuptake of 25% (interquartile range 10%-32%) in the experimental arm. Seventeen TwiCs (45%) planned analyses to adjust effect estimates for nonuptake. Regarding informed consent, we observed three patterns: 1) three separate consents for cohort participation, randomization, and intervention (17/46; 37%); 2) combined consent for cohort participation and randomization and a separate intervention consent (10/46; 22%); and 3) consent only for cohort participation and intervention (randomization consent not mentioned; 19/46; 41%). CONCLUSION: Existing TwiCs are globally scattered across a few research groups covering a wide range of medical fields and interventions. Despite the potential advantages, the number of TwiCs remains small. The variability in consent procedures and the possibility of substantial nonuptake of the intervention warrants further research to guide the planning, implementation, and analysis of TwiCs.

Patient-Reported Outcomes Following Magnetic Resonance-Guided Radiation Therapy for Prostate Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: This systematic review provides an overview of literature on the impact of magnetic resonance-guided radiation therapy (MRgRT) on patient-reported outcomes (PROs) in patients with prostate cancer (PC). METHODS AND MATERIALS: A systematic search was performed in October 2023 in PubMed, EMBASE, and Cochrane Library. The Patient, Intervention, Comparison, Outcomes, and Study design (PICOS) framework was used to determine eligibility criteria. Included were studies assessing PROs following MRgRT for PC with a sample size >10. Methodological quality was assessed using the Cochrane's Risk of Bias in Nonrandomized Studies - of Interventions and Cochrane's risk of bias tool for randomized trials. Relevant mean differences (MDs) compared with pre-RT were interpreted using minimal important differences. Meta-analyses were performed using random-effects models. Between-study heterogeneity was assessed using the I2 statistic. RESULTS: Eleven observational studies and 1 randomized controlled trial (n = 897) were included. Nine studies included patients with primary PC with MRgRT as first-line treatment (n = 813) and 3 with MRgRT as second-line treatment (n = 84). Substantial risk of bias was found in 5 studies. European Organization for Research and Treatment Quality of Life Questionnaire (EORTC QLQ) core 30 (C30) and EORTC QLQ prostate cancer module (PR25) scores were pooled from 3 studies, and Expanded Prostate Cancer Index Composite (EPIC)-26 scores were pooled from 4 studies. Relevant MDs for the urinary domain were found with the EPIC-26 (MD, -10.0; 95% CI, -12.0 to -8.1; I2 = 0%) and the EORTC QLQ-PR25 (MD, 8.6; 95% CI, -4.7 to 22.0; I2 = 97%), both at end-RT to 1-month follow-up. Relevant MDs for the bowel domain were found with the EPIC-26 (MD, -4.7; 95% CI, -9.2 to -0.2; I2 = 82%) at end-RT or 1-month follow-up, but not with the EORTC QLQ-PR25. For both domains, no relevant MDs were found after 3 months of follow-up. No relevant MDs were found in the general quality of life domains of the EORTC QLQ C30. CONCLUSIONS: MRgRT for PC results in a temporary worsening of patient-reported urinary and bowel symptoms during the first month after treatment compared with pre-RT, resolving at 3 months. No clinically relevant changes were found for general quality of life domains. These results provide important information for patient counseling and can serve as a benchmark for future studies.

Safety and Tolerability of Online Adaptive High-Field Magnetic Resonance-Guided Radiotherapy.

Importance: In 2018, the first online adaptive magnetic resonance (MR)-guided radiotherapy (MRgRT) system using a 1.5-T MR-equipped linear accelerator (1.5-T MR-Linac) was clinically introduced. This system enables online adaptive radiotherapy, in which the radiation plan is adapted to size and shape changes of targets at each treatment session based on daily MR-visualized anatomy. Objective: To evaluate safety, tolerability, and technical feasibility of treatment with a 1.5-T MR-Linac, specifically focusing on the subset of patients treated with an online adaptive strategy (ie, the adapt-to-shape [ATS] approach). Design, Setting, and Participants: This cohort study included adults with solid tumors treated with a 1.5-T MR-Linac enrolled in Multi Outcome Evaluation for Radiation Therapy Using the MR-Linac (MOMENTUM), a large prospective international study of MRgRT between February 2019 and October 2021. Included were adults with solid tumors treated with a 1.5-T MR-Linac. Data were collected in Canada, Denmark, The Netherlands, United Kingdom, and the US. Data were analyzed in August 2023. Exposure: All patients underwent MRgRT using a 1.5-T MR-Linac. Radiation prescriptions were consistent with institutional standards of care. Main Outcomes and Measures: Patterns of care, tolerability, and technical feasibility (ie, treatment completed as planned). Acute high-grade radiotherapy-related toxic effects (ie, grade 3 or higher toxic effects according to Common Terminology Criteria for Adverse Events version 5.0) occurring within the first 3 months after treatment delivery. Results: In total, 1793 treatment courses (1772 patients) were included (median patient age, 69 years [range, 22-91 years]; 1384 male [77.2%]). Among 41 different treatment sites, common sites were prostate (745 [41.6%]), metastatic lymph nodes (233 [13.0%]), and brain (189 [10.5%]). ATS was used in 1050 courses (58.6%). MRgRT was completed as planned in 1720 treatment courses (95.9%). Patient withdrawal caused 5 patients (0.3%) to discontinue treatment. The incidence of radiotherapy-related grade 3 toxic effects was 1.4% (95% CI, 0.9%-2.0%) in the entire cohort and 0.4% (95% CI, 0.1%-1.0%) in the subset of patients treated with ATS. There were no radiotherapy-related grade 4 or 5 toxic effects. Conclusions and Relevance: In this cohort study of patients treated on a 1.5-T MR-Linac, radiotherapy was safe and well tolerated. Online adaptation of the radiation plan at each treatment session to account for anatomic variations was associated with a low risk of acute grade 3 toxic effects.

MRI-guided radiotherapy in twenty fractions for localised prostate cancer; results from the MOMENTUM study.

Background and purpose: MRI-guided radiotherapy (MRIgRT) offers multiple potential advantages over CT-guidance. This study examines the potential clinical benefits of MRIgRT for men with localised prostate cancer, in the setting of moderately hypofractionated radiotherapy. We evaluate two-year toxicity outcomes, early biochemical response and patient-reported outcomes (PRO), using data obtained from a multicentre international registry study, for the first group of patients with prostate cancer who underwent treatment on a 1.5 T MR-Linac. Materials and methods: Patients who were enrolled within the MOMENTUM study and received radical treatment with 60 Gy in 20 fractions were identified. PSA levels and CTCAE version 5.0 toxicity data were measured at follow-up visits. Those patients who consented to PRO data collection also completed EQ-5D-5L, EORTC QLQ-C30 and EORTC QLQ-PR25 questionnaires. Results: Between November 2018 and June 2022, 146 patients who had MRIgRT for localised prostate cancer on the 1.5 T MR-Linac were eligible for this study. Grade 2 and worse gastro-intestinal (GI) toxicity was reported in 3 % of patients at three months whilst grade 2 and worse genitourinary (GU) toxicity was 7 % at three months. There was a significant decrease in the median PSA at 12 months. The results from both the EQ-5D-5L data and EORTC global health status scale indicate a decline in the quality of life (QoL) during the first six months. The mean change in score for the EORTC scale showed a decrease of 11.4 points, which is considered clinically important. QoL improved back to baseline by 24 months. Worsening of hormonal symptoms in the first six months was reported with a return to baseline by 24 months and sexual activity in all men worsened in the first three months and returned to baseline at 12 months. Conclusion: This study establishes the feasibility of online-MRIgRT for localised prostate on a 1.5 T MR-Linac with low rates of toxicity, similar to that published in the literature. However, the clinical benefits of MRIgRT over conventional radiotherapy in the setting of moderate hypofractionation is not evident. Further research will focus on the delivery of ultrahypofractionated regimens, where the potential advantages of MRIgRT for prostate cancer may become more discernible.

Randomised trials conducted using cohorts: a scoping review.

INTRODUCTION: Cohort studies generate and collect longitudinal data for a variety of research purposes. Randomised controlled trials (RCTs) increasingly use cohort studies as data infrastructures to help identify and recruit trial participants and assess outcomes. OBJECTIVE: To examine the extent, range and nature of research using cohorts for RCTs and describe the varied definitions and conceptual boundaries for RCTs using cohorts. DESIGN: Scoping review. DATA SOURCES: Searches were undertaken in January 2021 in MEDLINE (Ovid) and EBM Reviews-Cochrane Methodology Registry (Final issue, third Quarter 2012). ELIGIBILITY CRITERIA: Reports published between January 2007 and December 2021 of (a) cohorts used or planned to be used, to conduct RCTs, or (b) RCTs which use cohorts to recruit participants and/or collect trial outcomes, or (c) methodological studies discussing the use of cohorts for RCTs. DATA EXTRACTION AND SYNTHESIS: Data were extracted on the condition being studied, age group, setting, country/continent, intervention(s) and comparators planned or received, unit of randomisation, timing of randomisation, approach to informed consent, study design and terminology. RESULTS: A total of 175 full-text articles were assessed for eligibility. We identified 61 protocols, 9 descriptions of stand-alone cohorts intended to be used for future RCTs, 39 RCTs using cohorts and 34 methodological papers.The use and scope of this approach is growing. The thematics of study are far-ranging, including population health, oncology, mental and behavioural disorders, and musculoskeletal conditions.Authors reported that this approach can lead to more efficient recruitment, more representative samples, and lessen disappointment bias and crossovers. CONCLUSION: This review outlines the development of cohorts to conduct RCTs including the range of use and innovative changes and adaptations. Inconsistencies in the use of terminology and concepts are highlighted. Guidance now needs to be developed to support the design and reporting of RCTs conducted using cohorts.

Stereotactic Body and Conventional Radiotherapy for Painful Bone Metastases: A Systematic Review and Meta-Analysis.

Importance: Conventional external beam radiotherapy (cEBRT) and stereotactic body radiotherapy (SBRT) are commonly used treatment options for relieving metastatic bone pain. The effectiveness of SBRT compared with cEBRT in pain relief has been a subject of debate, and conflicting results have been reported. Objective: To compare the effectiveness associated with SBRT vs cEBRT for relieving metastatic bone pain. Data Sources: A structured search was performed in the PubMed, Embase, and Cochrane databases on June 5, 2023. Additionally, results were added from a new randomized clinical trial (RCT) and additional unpublished data from an already published RCT. Study Selection: Comparative studies reporting pain response after SBRT vs cEBRT in patients with painful bone metastases. Data Extraction and Synthesis: Two independent reviewers extracted data from eligible studies. Data were extracted for the intention-to-treat (ITT) and per-protocol (PP) populations. The study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: Overall and complete pain response at 1, 3, and 6 months after radiotherapy, according to the study's definition. Relative risk ratios (RRs) with 95% CIs were calculated for each study. A random-effects model using a restricted maximum likelihood estimator was applied for meta-analysis. Results: There were 18 studies with 1685 patients included in the systematic review and 8 RCTs with 1090 patients were included in the meta-analysis. In 7 RCTs, overall pain response was defined according to the International Consensus on Palliative Radiotherapy Endpoints in clinical trials (ICPRE). The complete pain response was reported in 6 RCTs, all defined according to the ICPRE. The ITT meta-analyses showed that the overall pain response rates did not differ between cEBRT and SBRT at 1 (RR, 1.14; 95% CI, 0.99-1.30), 3 (RR, 1.19; 95% CI, 0.96-1.47), or 6 (RR, 1.22; 95% CI, 0.96-1.54) months. However, SBRT was associated with a higher complete pain response at 1 (RR, 1.43; 95% CI, 1.02-2.01), 3 (RR, 1.80; 95% CI, 1.16-2.78), and 6 (RR, 2.47; 95% CI, 1.24-4.91) months after radiotherapy. The PP meta-analyses showed comparable results. Conclusions and Relevance: In this systematic review and meta-analysis, patients with painful bone metastases experienced similar overall pain response after SBRT compared with cEBRT. More patients had complete pain alleviation after SBRT, suggesting that selected subgroups will benefit from SBRT.

The Value of Biological and Conditional Factors for Staging of Patients with Resectable Pancreatic Cancer Undergoing Upfront Resection: A Nationwide Analysis.

BACKGROUND: Novel definitions suggest that resectability status for pancreatic ductal adenocarcinoma (PDAC) should be assessed beyond anatomical criteria, considering both biological and conditional factors. This has, however, yet to be validated on a nationwide scale. This study evaluated the prognostic value of biological and conditional factors for staging of patients with resectable PDAC. PATIENTS AND METHODS: A nationwide observational cohort study was performed, including all consecutive patients who underwent upfront resection of National Comprehensive Cancer Network resectable PDAC in the Netherlands (2014-2019) with complete information on preoperative carbohydrate antigen (CA) 19-9 and Eastern Cooperative Oncology Group (ECOG) performance status. PDAC was considered biologically unfavorable (RB+) if CA19-9 ≥ 500 U/mL and favorable (RB-) otherwise. ECOG ≥ 2 was considered conditionally unfavorable (RC+) and favorable otherwise (RC-). Overall survival (OS) was assessed using Kaplan-Meier and Cox-proportional hazard analysis, presented as hazard ratios (HRs) with 95% confidence interval (CI). RESULTS: Overall, 688 patients were analyzed with a median overall survival (OS) of 20 months (95% CI 19-23). OS was 14 months (95% CI 10 months-median not reached) in 20 RB+C+ patients (3%; HR 1.61, 95% CI 0.86-2.70), 13 months (95% CI 11-15) in 156 RB+C- patients (23%; HR 1.86, 95% CI 1.50-2.31), and 21 months (95% CI 12-41) in 47 RB-C+ patients (7%; HR 1.14, 95% CI 0.80-1.62) compared with 24 months (95% CI 22-27) in 465 patients with RB-C- PDAC (68%; reference). CONCLUSIONS: Survival after upfront resection of anatomically resectable PDAC is worse in patients with CA19-9 ≥ 500 U/mL, while performance status had no impact. This supports consideration of CA19-9 in preoperative staging of resectable PDAC.

Hyperbaric Oxygen Therapy and Late Local Toxic Effects in Patients With Irradiated Breast Cancer: A Randomized Clinical Trial.

Importance: Hyperbaric oxygen therapy (HBOT) is proposed as treatment for late local toxic effects after breast irradiation. Strong evidence of effectiveness is lacking. Objective: To assess effectiveness of HBOT for late local toxic effects in women who received adjuvant radiotherapy for breast cancer. Design, Setting, and Participants: This was a hospital-based, pragmatic, 2-arm, randomized clinical trial nested within the prospective UMBRELLA cohort following the trials within cohorts design in the Netherlands. Participants included 189 women with patient-reported moderate or severe breast, chest wall, and/or shoulder pain in combination with mild, moderate, or severe edema, fibrosis, or movement restriction 12 months or longer after breast irradiation. Data analysis was performed from May to September 2023. Intervention: Receipt of 30 to 40 HBOT sessions over a period of 6 to 8 consecutive weeks. Main Outcomes and Measures: Breast, chest wall, and/or shoulder pain 6 months postrandomization measured by the European Organization for Research and Treatment of Cancer QLQ-BR23 questionnaire. Secondary end points were patient-reported fibrosis, edema, movement restriction, and overall quality of life. Data were analyzed according to intention-to-treat (ITT) and complier average causal effect (CACE) principles. Results: Between November 2019 and August 2022, 125 women (median [range] age at randomization, 56 [37-85] years) with late local toxic effects were offered to undergo HBOT (intervention arm), and 61 women (median [range] age at randomization, 60 [36-80] years) were randomized to the control arm. Of those offered HBOT, 31 (25%) accepted and completed treatment. The most common reason for not accepting HBOT was high treatment intensity. In ITT, moderate or severe pain at follow-up was reported by 58 of 115 women (50%) in the intervention arm and 32 of 52 women (62%) in the control arm (odds ratio [OR], 0.63; 95% CI, 0.32-1.23; P = .18). In CACE, the proportion of women reporting moderate or severe pain at follow-up was 32% (10 of 31) among those completing HBOT and 75% (9.7 of 12.9) among control participants expected to complete HBOT if offered (adjusted OR, 0.34; 95% CI, 0.15-0.80; P = .01). In ITT, moderate or severe fibrosis was reported by 35 of 107 (33%) in the intervention arm and 25 of 49 (51%) in the control arm (OR, 0.36; 95% CI, 0.15-0.81; P = .02). There were no significant differences in breast edema, movement restriction, and quality of life between groups in ITT and CACE. Conclusions and Relevance: In this randomized clinical trial, offering HBOT to women with late local toxic effects was not effective for reducing pain, but was effective for reducing fibrosis. In the subgroup of women who completed HBOT, a significant reduction in pain and fibrosis was observed. A smaller than anticipated proportion of women with late local toxic effects was prepared to undergo HBOT. Trial Registration: ClinicalTrials.gov Identifier: NCT04193722.

Competing risk analysis of cardiovascular disease risk in breast cancer patients receiving a radiation boost.

BACKGROUND: Thoracic radiotherapy may damage the myocardium and arteries, increasing cardiovascular disease (CVD) risk. Women with a high local breast cancer (BC) recurrence risk may receive an additional radiation boost to the tumor bed. OBJECTIVE: We aimed to evaluate the CVD risk and specifically ischemic heart disease (IHD) in BC patients treated with a radiation boost, and investigated whether this was modified by age. METHODS: We identified 5260 BC patients receiving radiotherapy between 2005 and 2016 without a history of CVD. Boost data were derived from hospital records and the national cancer registry. Follow-up data on CVD events were obtained from Statistics Netherlands until December 31, 2018. The relation between CVD and boost was evaluated with competing risk survival analysis. RESULTS: 1917 (36.4%) received a boost. Mean follow-up was 80.3 months (SD37.1) and the mean age 57.8 years (SD10.7). Interaction between boost and age was observed for IHD: a boost was significantly associated with IHD incidence in patients younger than 40 years but not in patients over 40 years. The subdistribution hazard ratio (sHR) was calculated for ages from 25 to 75 years, showing a sHR range from 5.1 (95%CI 1.2-22.6) for 25-year old patients to sHR 0.5 (95%CI 0.2-1.02) for 75-year old patients. CONCLUSION: In patients younger than 40, a radiation boost is significantly associated with an increased risk of CVD. In absolute terms, the increased risk was low. In older patients, there was no association between boost and CVD risk, which is likely a reflection of appropriate patient selection.

Clinical outcomes after online adaptive MR-guided stereotactic body radiotherapy for pancreatic tumors on a 1.5 T MR-linac.

Introduction: Online adaptive magnetic resonance-guided radiotherapy (MRgRT) is a promising treatment modality for pancreatic cancer and is being employed by an increasing number of centers worldwide. However, clinical outcomes have only been reported on a small scale, often from single institutes and in the context of clinical trials, in which strict patient selection might limit generalizability of outcomes. This study presents clinical outcomes of a large, international cohort of patients with (peri)pancreatic tumors treated with online adaptive MRgRT. Methods: We evaluated clinical outcomes and treatment details of patients with (peri)pancreatic tumors treated on a 1.5 Tesla (T) MR-linac in two large-volume treatment centers participating in the prospective MOMENTUM cohort (NCT04075305). Treatments were evaluated through schematics, dosage, delivery strategies, and success rates. Acute toxicity was assessed until 3 months after MRgRT started, and late toxicity from 3-12 months of follow-up (FU). The EORTC QLQ-C30 questionnaire was used to evaluate the quality of life (QoL) at baseline and 3 months of FU. Furthermore, we used the Kaplan-Meier analysis to calculate the cumulative overall survival. Results: A total of 80 patients were assessed with a median FU of 8 months (range 1-39 months). There were 34 patients who had an unresectable primary tumor or were medically inoperable, 29 who had an isolated local recurrence, and 17 who had an oligometastasis. A total of 357 of the 358 fractions from all hypofractionated schemes were delivered as planned. Grade 3-4 acute toxicity occurred in 3 of 59 patients (5%) with hypofractionated MRgRT and grade 3-4 late toxicity in 5 of 41 patients (12%). Six patients died within 3 months after MRgRT; in one of these patients, RT attribution could not be ruled out as cause of death. The QLQ-C30 global health status remained stable from baseline to 3 months FU (70.5 at baseline, median change of +2.7 [P = 0.5]). The 1-year cumulative overall survival for the entire cohort was 67%, and that for the primary tumor group was 66%. Conclusion: Online adaptive MRgRT for (peri)pancreatic tumors on a 1.5 T MR-Linac could be delivered as planned, with low numbers of missed fractions. In addition, treatments were associated with limited grade 3-4 toxicity and a stable QoL at 3 months of FU.

Breast cancer patients' needs and perspectives on a one-on-one peer support program: quantitative and qualitative analyses.

PURPOSE: Although peer support programs as a health resource have become increasingly popular, only limited studies evaluated the added value of one-on-one peer support for breast cancer patients. This study aims to bridge the knowledge gap by focusing on two related research topics. First, we evaluated emotional well-being and (unmet) needs regarding supportive care. Second, we evaluated patients' perspectives on their experiences after having one-on-one peer support. METHODS: A quantitative analysis was conducted to provide insight in patients' symptoms of anxiety and depression (HADS), quality of life (EORTC-QLQ-C30), and supportive care needs (CaSUN-questionnaire). Furthermore, approximately 1 year after the implementation of a one-on-one peer support program, focus groups were conducted to evaluate patients' perspectives regarding one-on-one peer support. RESULTS: Two hundred twenty-five of 537 patients diagnosed with breast cancer between 2019 and 2020 completed the questionnaires. Quantitative analysis showed increased symptoms of anxiety and depression among breast cancer patients and lower scores on all EORTC-QLQ-C30 domains compared to the Dutch normative population. Of all patients, 27.6% (95%CI = 0.22-0.34) reported to have unmet needs regarding emotional support and 23.1% (95%CI = 0.18-0.29) reported an unmet need to talk to someone who has experienced breast cancer. For the qualitative analysis, 19 breast cancer patients who were taking part in the one-on-one peer support program participated in three focus groups. Benefits, limitations, and wishes regarding the one-on-one peer support program were discussed. CONCLUSION: Breast cancer patients showed increased anxiety and depression and lower quality of life, physical, role, emotional, cognitive, and social functioning compared to the Dutch normative population. Almost one-third of breast cancer patients reported unmet needs regarding emotional support and a desire to talk to other breast cancer patients. These (unmet) needs can successfully be met by providing a low-threshold one-on-one peer support program.

Efficacy of indocyanine green fluorescence for the identification of non-palpable breast tumours: systematic review.

BACKGROUND: Accurate tumour localization is crucial for precise surgical targeting and complete tumour removal. Indocyanine green fluorescence, an increasingly used technique in oncological surgery, has shown promise in localizing non-palpable breast tumours. The aim of this systematic review was to describe the efficacy of indocyanine green fluorescence for the identification of non-palpable breast tumours. METHODS: A systematic literature search was performed in PubMed, Embase, and the Cochrane Library, including studies from 2012 to 2023. Studies reporting the proportion of breast tumours identified using indocyanine green fluorescence were included. The quality of the studies and their risk of bias were appraised using the Methodological Index for Non-Randomized Studies ('MINORS') tool. The following outcomes were collected: identification rate, clear resection margins, specimen volume, operative time, re-operation rate, adverse events, and complications. RESULTS: In total, 2061 articles were screened for eligibility, resulting in 11 studies, with 366 patients included: two RCTs, three non-randomized comparative studies, four single-arm studies, and two case reports. All studies achieved a 100 per cent tumour identification rate with indocyanine green fluorescence, except for one study, with an identification rate of 87 per cent (13/15). Clear resection margins were found in 88-100 per cent of all patients. Reoperation rates ranged from 0.0 to 5.4 per cent and no complications or adverse events related to indocyanine green occurred. CONCLUSION: Indocyanine green fluorescence has substantial theoretical advantages compared with current routine localization methods. Although a limited number of studies were available, the current literature suggests that indocyanine green fluorescence is a useful, accurate, and safe technique for the intraoperative localization of non-palpable breast tumours, with equivalent efficacy compared with other localization techniques, potentially reducing tumour-positive margins.

Risk factors for unplanned reoperation during the expansion phase in two-stage breast reconstruction in the Dutch Breast Implant Registry.

BACKGROUND: The majority of postmastectomy breast reconstructions (PMBRs) are currently performed in two stages using a tissue expander (TE). However, complications during the expansion phase occur regularly, leading to unplanned reoperations and/or reconstruction failure. This study aimed to identify risk factors for unplanned reoperation after TE placement, assessed the time until unplanned and planned reoperation, and investigated indications for unplanned reoperation. METHODS: Patient and surgery-related characteristics of patients who underwent two-stage PMBR between 2017 and 2021 were collected from the Dutch Breast Implant Registry (DBIR). Unplanned reoperation was defined as TE explantation followed by either no replacement or replacement with the same or a different TE. Co-variate adjusted characteristics associated with unplanned reoperation were determined using backward stepwise selection and multivariable logistic regression analyses. RESULTS: In total, 2529 patients (mean age, 50.2 years) were included. Unplanned reoperation occurred in 19.4 percent of all registered TEs (n=3190). Independent factors associated with unplanned reoperation were BMI≥25 kg/m 2 (adjusted Odds Ratio [aOR]=1.63;99% Confidence Interval [99%CI]=1.20-2.57 for BMI 25-29.9 kg/m2, aOR=2.57;99%CI=1.74-3.78 for BMI≥30 kg/m 2), low institutional volume (aOR=1.51;99%CI=1.06-2.18), no drains (aOR=2.06;99%CI=1.15-3.60), subcutaneous TE placement (aOR=5.71;99%CI=3.59-9.10), and partial pectoralis major muscle coverage (aOR=1.35;99%CI=1.02-1.79). Age<40 years (aOR=0.49;99%CI=0.32-0.74) and delayed PMBR (aOR=0.35;99%CI=0.19-0.60) reduced the risk of unplanned reoperation. Median time until reoperation was 97 days for unplanned and 213 days for planned reoperation. Deep wound infections were most often registered as indication for unplanned reoperation (34.4 percent). CONCLUSION: This study identified several risk factors for unplanned reoperation which may be used to reduce complications in expander-based PMBR.

Introducing the New Patient Expectations in Spine Oncology Questionnaire.

BACKGROUND AND OBJECTIVES: It has been hypothesized that a discrepancy between pretreatment expectations and perceived outcomes is a significant source of patient dissatisfaction. Currently, there is lack in understanding and tools to assess patient expectations regarding the outcomes of treatment for spinal metastases. The objective of this study was therefore to develop a patient expectations questionnaire regarding the outcomes after surgery and/or radiotherapy for spinal metastases. METHODS: A multiphase international qualitative study was conducted. Phase 1 of the study included semistructured interviews with patients and relatives to understand their expectations of the outcomes of treatment. In addition, physicians were interviewed about their communication practices with patients regarding treatment and expected outcomes. In phase 2, items were developed based on the results of the interviews in phase 1. In phase 3, patients were interviewed to validate the content and language of the questionnaire. Selection of the final items was based on feedback from patients regarding content, language, and relevance. RESULTS: In phase 1, 24 patients and 22 physicians were included. A total of 34 items were developed for the preliminary questionnaire. After phase 3, a total of 22 items were retained for the final version of the questionnaire. The questionnaire is divided into 3 sections: (1) patient expectations regarding treatment outcomes, (2) prognosis, and (3) consultation with the physician. The items cover expectations related to pain, analgesia requirements, daily and physical function, overall quality of life, life expectancy, and information provided by the physician. CONCLUSION: The new Patient Expectations in Spine Oncology questionnaire was developed to evaluate patient expectations regarding the outcomes after treatment for spinal metastases. The Patient Expectations in Spine Oncology questionnaire will allow physicians to systematically assess patient expectations of planned treatment and thus help guide patients toward realistic expectations of treatment outcome.

Towards Response ADAptive Radiotherapy for organ preservation for intermediate-risk rectal cancer (preRADAR): protocol of a phase I dose-escalation trial.

INTRODUCTION: Organ preservation is associated with superior functional outcome and quality of life (QoL) compared with total mesorectal excision (TME) for rectal cancer. Only 10% of patients are eligible for organ preservation following short-course radiotherapy (SCRT, 25 Gy in five fractions) and a prolonged interval (4-8 weeks) to response evaluation. The organ preservation rate could potentially be increased by dose-escalated radiotherapy. Online adaptive magnetic resonance-guided radiotherapy (MRgRT) is anticipated to reduce radiation-induced toxicity and enable radiotherapy dose escalation. This trial aims to establish the maximum tolerated dose (MTD) of dose-escalated SCRT using online adaptive MRgRT. METHODS AND ANALYSIS: The preRADAR is a multicentre phase I trial with a 6+3 dose-escalation design. Patients with intermediate-risk rectal cancer (cT3c-d(MRF-)N1M0 or cT1-3(MRF-)N1M0) interested in organ preservation are eligible. Patients are treated with a radiotherapy boost of 2×5 Gy (level 0), 3×5 Gy (level 1), 4×5 Gy (level 2) or 5×5 Gy (level 3) on the gross tumour volume in the week following standard SCRT using online adaptive MRgRT. The trial starts on dose level 1. The primary endpoint is the MTD based on the incidence of dose-limiting toxicity (DLT) per dose level. DLT is a composite of maximum one in nine severe radiation-induced toxicities and maximum one in three severe postoperative complications, in patients treated with TME or local excision within 26 weeks following start of treatment. Secondary endpoints include the organ preservation rate, non-DLT, oncological outcomes, patient-reported QoL and functional outcomes up to 2 years following start of treatment. Imaging and laboratory biomarkers are explored for early response prediction. ETHICS AND DISSEMINATION: The trial protocol has been approved by the Medical Ethics Committee of the University Medical Centre Utrecht. The primary and secondary trial results will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: WHO International Clinical Trials Registry (NL8997; https://trialsearch.who.int).

Timing of rectal cancer surgery after short-course radiotherapy: national database study.

BACKGROUND: Previous randomized trials found that a prolonged interval between short-course radiotherapy (SCRT, 25 Gy in 5 fractions) and surgery for rectal cancer (4-8 weeks, SCRT-delay) results in a lower postoperative complication rate and a higher pCR rate than SCRT and surgery within a week (SCRT-direct surgery). This study sought to confirm these results in a Dutch national database. METHODS: Patients with intermediate-risk rectal cancer (T3(mesorectal fascia (MRF)-) N0 M0 and T1-3(MRF-) N1 M0) treated with either SCRT-delay (4-12 weeks) or SCRT-direct surgery in 2018-2021 were selected from a Dutch national colorectal cancer database. Confounders were adjusted for using inverse probability of treatment weighting (IPTW). The primary endpoint was the 90-day postoperative complication rate. Secondary endpoints included the pCR rate. Endpoints were compared using log-binomial and Poisson regression. RESULTS: Some 664 patients were included in the SCRT-direct surgery and 238 in the SCRT-delay group. After IPTW, the 90-day postoperative complication rate was comparable after SCRT-direct surgery and SCRT-delay (40.1 versus 42.3 per cent; risk ratio (RR) 1.1, 95 per cent c.i. 0.9 to 1.3). A pCR occurred more often after SCRT-delay than SCRT-direct surgery (10.7 versus 0.4 per cent; RR 39, 11 to 139). CONCLUSION: There was no difference in surgical complication rates between SCRT-delay and SCRT-direct, but SCRT-delay was associated with more patients having a pCR.

The use of red flags during the referral chain of patients surgically treated for symptomatic spinal metastases.

Background: The use of so-called "red flags" may be beneficial in identifying patients with metastatic spinal disease. This study examined the utility and efficacy of these red flags in the referral chain of patients surgically treated for spinal metastases. Methods: The referral chains from the onset of symptoms until surgical treatment for all patients receiving surgery for spinal metastases between March 2009 and December 2020 were reconstructed. The documentation of red flags, as defined by the Dutch National Guideline on Metastatic Spinal Disease, was assessed for each healthcare provider involved. Results: A total of 389 patients were included in the study. On average, 33.3% of red flags were documented as present, 3.6% were documented as absent, and 63.1% were undocumented. A higher rate of red flags documented as present was associated with a longer time to diagnosis, but a shorter time to definitive treatment by a spine surgeon. Moreover, red flags were documented as present more often in patients who developed neurological symptoms at any point during the referral chain than those who remained neurologically intact. Conclusions: The association of red flags with developing neurological deficits highlights their significance in clinical assessment. However, the presence of red flags was not found to decrease delays prior to referral to a spine surgeon, indicating that their relevance is currently not sufficiently recognized by healthcare providers. Raising awareness of symptoms indicative of spinal metastases may expedite timely (surgical) treatment and thus improve treatment outcome.