Invasive recurrence after breast conserving treatment of ductal carcinoma in situ of the breast in the Netherlands: time trends and the association with tumour grade.

BACKGROUND: The first aim of this study was to examine trends in the risk of ipsilateral invasive breast cancer (iIBC) after breast-conserving surgery (BCS) of ductal carcinoma in situ (DCIS). A second aim was to analyse the association between DCIS grade and the risk of iIBC following BCS. PATIENTS AND METHODS: In this population-based, retrospective cohort study, the Netherlands Cancer Registry collected information on 25,719 women with DCIS diagnosed in the period 1989-2021 who underwent BCS. Of these 19,034 received adjuvant radiotherapy (RT). Kaplan-Meier analyses and Cox regression models were used. RESULTS: A total of 1135 patients experienced iIBC. Ten-year cumulative incidence rates of iIBC for patients diagnosed in the periods 1989-1998, 1999-2008 and 2009-2021 undergoing BCS without RT, were 12.6%, 9.0% and 5.0% (P < 0.001), respectively. For those undergoing BCS with RT these figures were 5.7%, 3.7% and 2.2%, respectively (P < 0.001). In the multivariable analyses, DCIS grade was not associated with the risk of iIBC. CONCLUSION: Since 1989 the risk of iIBC has decreased substantially and has become even lower than the risk of invasive contralateral breast cancer. No significant association of DCIS grade with iIBC was found, stressing the need for more powerful prognostic factors to guide the treatment of DCIS.

A BRILLIANT-BRCA study: residual breast tissue after mastectomy and reconstruction.

INTRODUCTION: Different types of mastectomies leave different amounts of residual breast tissue. The significance of the residual breast volume (RBV) is not clear. Therefore, we developed an MRI tool that allows to easily assess the RBV. In this study we evaluated factors associated with RBV after skin or nipple sparing mastectomy (SSM/NSM) in breast cancer BRCA pathogenic variant (PV) carriers who underwent both therapeutic and risk reducing SSM/NSM and its relation to breast cancer outcomes using an innovative MRI-based tool. METHODS: Data of breast cancer BRCA PV who were treated between 2006 and 2020 were retrieved from of the oncogenetics unit databases. Only patients who underwent SSM/NSM and had a postoperative breast MRI available for analysis were included. Data collected included demographics, clinicopathological features, and outcomes. The MRI tool was developed by a breast cancer imaging laboratory. A logistic regression test and 95% confidence interval (CI) were used to assess the associated risk of increased RBV. A forward stepwise linear regression was used to correlate tumour-patient specific factors and RBV, and a Kaplan-Meier curve to show the probability of locoregional relapse. RESULTS: A total of 84 patients undergoing 89 mastectomies were included. At a median follow-up of 98 months, 5 local, 2 regional, and 4 distant recurrences were observed. RBV was not significantly related with breast cancer outcomes (p value = NS). A higher body mass index (BMI) was associated with a higher RBV (p < 0.0001). A larger number of involved axillary nodes was associated with a smaller RBV (p = 0.025). The RBV on the risk-reducing mastectomy side was significantly higher compared to the breast cancer side (p value = 0.007). Local recurrences occurred in the vicinity of the primary tumour.

De-escalation of axillary treatment in the event of a positive sentinel lymph node biopsy in cT1-2 N0 breast cancer treated with mastectomy: nationwide registry study (BOOG 2013-07).

BACKGROUND: Trials have demonstrated the safety of omitting completion axillary lymph node dissection in patients with cT1-2 N0 breast cancer operated with breast-conserving surgery who have limited metastatic burden in the sentinel lymph node. The aim of this registry study was to provide insight into the oncological safety of omitting completion axillary treatment in patients operated with mastectomy who have limited-volume sentinel lymph node metastasis. METHODS: Women diagnosed in 2013-2014 with unilateral cT1-2 N0 breast cancer treated with mastectomy, with one to three sentinel lymph node metastases (pN1mi-pN1a), were identified from the Netherlands Cancer Registry, and classified by axillary treatment: no completion axillary treatment, completion axillary lymph node dissection, regional radiotherapy, or completion axillary lymph node dissection followed by regional radiotherapy. The primary endpoint was 5-year regional recurrence rate. Secondary endpoints included recurrence-free interval and overall survival, among others. RESULTS: In total, 1090 patients were included (no completion axillary treatment, 219 (20.1%); completion axillary lymph node dissection, 437 (40.1%); regional radiotherapy, 327 (30.0%); completion axillary lymph node dissection and regional radiotherapy, 107 (9.8%)). Patients in the group without completion axillary treatment had more favourable tumour characteristics and were older. The overall 5-year regional recurrence rate was 1.3%, and did not differ significantly between the groups. The recurrence-free interval was also comparable among groups. The group of patients who did not undergo completion axillary treatment had statistically significantly worse 5-year overall survival, owing to a higher percentage of non-cancer deaths. CONCLUSION: In this registry study of patients with cT1-2 N0 breast cancer treated with mastectomy, with low-volume sentinel lymph node metastasis, the 5-year regional recurrence rate was low and comparable between patients with and without completion axillary treatment.

De-ESCAlating RadioTherapy in breast cancer patients with pathologic complete response to neoadjuvant systemic therapy: DESCARTES study.

PURPOSE: Neoadjuvant systemic therapy (NST) is increasingly used in breast cancer patients and depending on subtype, 10-89% of patients will attain pathologic complete response (pCR). In patients with pCR, risk of local recurrence (LR) after breast conserving therapy is low. Although adjuvant radiotherapy after breast conserving surgery (BCS) reduces LR further in these patients, it may not contribute to overall survival. However, radiotherapy may cause early and late toxicity. The aim of this study is to show that omission of adjuvant radiotherapy in patients with a pCR after NST will result in acceptable low LR rates and good quality of life. METHODS: The DESCARTES study is a prospective, multicenter, single arm study. Radiotherapy will be omitted in cT1-2N0 patients (all subtypes) who achieve a pCR of the breast and lymph nodes after NST followed by BCS plus sentinel node procedure. A pCR is defined as ypT0N0 (i.e. no residual tumor cells detected). Primary endpoint is the 5-year LR rate, which is expected to be 4% and deemed acceptable if less than 6%. In total, 595 patients are needed to achieve a power of 80% (one-side alpha of 0.05). Secondary outcomes include quality of life, Cancer Worry Scale, disease specific and overall survival. Projected accrual is five years. CONCLUSION: This study bridges the knowledge gap regarding LR rates when adjuvant radiotherapy is omitted in cT1-2N0 patients achieving pCR after NST. If the results are positive, radiotherapy may be safely omitted in selected breast cancer patients with a pCR after NST. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov on June 13th 2022 (NCT05416164). Protocol version 5.1 (15-03-2022).

De-escalation of radiotherapy after primary chemotherapy in cT1-2N1 breast cancer (RAPCHEM; BOOG 2010-03): 5-year follow-up results of a Dutch, prospective, registry study.

BACKGROUND: Primary chemotherapy in breast cancer poses a dilemma with regard to adjuvant locoregional radiotherapy, as guidelines for locoregional radiotherapy were originally based on pathology results of primary surgery. We aimed to evaluate the oncological safety of de-escalated locoregional radiotherapy in patients with cT1-2N1 breast cancer treated with primary chemotherapy, according to a predefined, consensus-based study guideline. METHODS: In this prospective registry study (RAPCHEM, BOOG 2010-03), patients referred to one of 17 participating radiation oncology centres in the Netherlands between Jan 1, 2011, and Jan 1, 2015, with cT1-2N1 breast cancer (one to three suspicious nodes on imaging before primary chemotherapy, of which at least one had been pathologically confirmed), and who were treated with primary chemotherapy and surgery of the breast and axilla were included in the study. The study guideline comprised three risk groups for locoregional recurrence, with corresponding locoregional radiotherapy recommendations: no chest wall radiotherapy and no regional radiotherapy in the low-risk group, only local radiotherapy in the intermediate-risk group, and locoregional radiotherapy in the high-risk group. Radiotherapy consisted of a biologically equivalent dose of 25 fractions of 2 Gy, with or without a boost. During the study period, the generally applied radiotherapy technique in the Netherlands was forward-planned or inverse-planned intensity modulated radiotherapy. 5-year follow-up was assessed, taking into account adherence to the study guideline, with locoregional recurrence rate as primary endpoint. We hypothesised that 5-year locoregional recurrence rate would be less than 4% (upper-limit 95% CI 7·8%). This study was registered at ClinicalTrials.gov, NCT01279304, and is completed. FINDINGS: 838 patients were eligible for 5-year follow-up analyses: 291 in the low-risk group, 370 in the intermediate-risk group, and 177 in the high-risk group. The 5-year locoregional recurrence rate in all patients was 2·2% (95% CI 1·4-3·4). The 5-year locoregional recurrence rate was 2·1% (0·9-4·3) in the low-risk group, 2·2% (1·0-4·1) in the intermediate-risk group, and 2·3% (0·8-5·5) in the high-risk group. If the study guideline was followed, the locoregional recurrence rate was 2·3% (0·8-5·3) for the low-risk group, 1·0% (0·2-3·4) for the intermediate-risk group, and 1·4% (0·3-4·5) for the high-risk group. INTERPRETATION: In this study, the 5-year locoregional recurrence rate was less than 4%, which supports our hypothesis that it is oncologically safe to de-escalate locoregional radiotherapy based on locoregional recurrence risk, in selected patients with cT1-2N1 breast cancer treated with primary chemotherapy, according to this predefined, consensus-based study guideline. FUNDING: Dutch Cancer Society. TRANSLATION: For the Dutch translation of the abstract see Supplementary Materials section.

European Society for Radiotherapy and Oncology Advisory Committee in Radiation Oncology Practice consensus recommendations on patient selection and dose and fractionation for external beam radiotherapy in early breast cancer.

High-quality randomised clinical trials testing moderately fractionated breast radiotherapy have clearly shown that local control and survival is at least as effective as with 2 Gy daily fractions with similar or reduced normal tissue toxicity. Fewer treatment visits are welcomed by patients and their families, and reduced fractions produce substantial savings for health-care systems. Implementation of hypofractionation, however, has moved at a slow pace. The oncology community have now reached an inflection point created by new evidence from the FAST-Forward five-fraction randomised trial and catalysed by the need for the global radiation oncology community to unite during the COVID-19 pandemic and rapidly rethink hypofractionation implementation. The aim of this paper is to support equity of access for all patients to receive evidence-based breast external beam radiotherapy and to facilitate the translation of new evidence into routine daily practice. The results from this European Society for Radiotherapy and Oncology Advisory Committee in Radiation Oncology Practice consensus state that moderately hypofractionated radiotherapy can be offered to any patient for whole breast, chest wall (with or without reconstruction), and nodal volumes. Ultrafractionation (five fractions) can also be offered for non-nodal breast or chest wall (without reconstruction) radiotherapy either as standard of care or within a randomised trial or prospective cohort. The consensus is timely; not only is it a pragmatic framework for radiation oncologists, but it provides a measured proposal for the path forward to influence policy makers and empower patients to ensure equity of access to evidence-based radiotherapy.

Implementing a breast cancer patient decision aid: Process evaluation using medical files and the patients' perspective.

OBJECTIVE: Although patient decision aids (PtDAs) have been shown to improve shared decision-making, integration into clinical care pathways remains limited. This study investigated, among other outcomes, the uptake of the PtDA by professionals and the uptake as perceived by patients. METHODS: We performed a process evaluation among four breast cancer care teams that had been exposed to a multifaceted implementation strategy. Data were gathered by auditing patient files using a standardised data extraction sheet and conducting telephone interviews with patients using a structured interview guide. We analysed the data by using descriptive statistics. RESULTS: We found that the implementation strategies, including advice on how and when to present the PtDA to the patient, were followed for 14% of the included patients (N = 84); 92% of the patients reported to have received a login code for the web-based PtDA, while 67% logged in and used the PtDA at home. An important factor influencing the use was the clinician promoting it when delivering the PtDA (OR 9.95 95% CI 3.03-37.72). DISCUSSION: The implementation strategies were followed in 14% of the patients, and a high delivery of the PtDA was achieved. Redesigning the care pathway and providing personal instruction on using PtDAs seem crucial.

Evaluating the Age-Based Recommendations for Long-Term Follow-Up in Breast Cancer.

BACKGROUND: After 5 years of annual follow-up following breast cancer, Dutch guidelines are age based: annual follow-up for women <60 years, 60-75 years biennial, and none for >75 years. We determined how the risk of recurrence corresponds to these consensus-based recommendations and to the risk of primary breast cancer in the general screening population. SUBJECTS, MATERIALS, AND METHODS: Women with early-stage breast cancer in 2003/2005 were selected from the Netherlands Cancer Registry (n = 18,568). Cumulative incidence functions were estimated for follow-up years 5-10 for locoregional recurrences (LRRs) and second primary tumors (SPs). Risks were compared with the screening population without history of breast cancer. Alternative cutoffs for age were determined by log-rank tests. RESULTS: The cumulative risk for LRR/SP was lower in women <60 years (5.9%, 95% confidence interval [CI] 5.3-6.6) who are under annual follow-up than for women 60-75 (6.3%, 95% CI 5.6-7.1) receiving biennial visits. All risks were higher than the 5-year risk of a primary tumor in the screening population (ranging from 1.4% to 1.9%). Age cutoffs <50, 50-69, and > 69 revealed better risk differentiation and would provide more risk-based schedules. Still, other factors, including systemic treatments, had an even greater impact on recurrence risks. CONCLUSION: The current consensus-based recommendations use suboptimal age cutoffs. The proposed alternative cutoffs will lead to a more balanced risk-based follow-up and thereby more efficient allocation of resources. However, more factors should be taken into account for truly individualizing follow-up based on risk for recurrence. IMPLICATIONS FOR PRACTICE: The current age-based recommendations for breast cancer follow-up after 5 years are suboptimal and do not reflect the actual risk of recurrent disease. This results in situations in which women with higher risks actually receive less follow-up than those with a lower risk of recurrence. Alternative cutoffs could be a start toward risk-based follow-up and thereby more efficient allocation of resources. However, age, or any single risk factor, is not able to capture the risk differences and therefore is not sufficient for determining follow-up. More risk factors should be taken into account for truly individualizing follow-up based on the risk for recurrence.

Spatial location of local recurrences after mastectomy: a systematic review.

PURPOSE: We performed a systematic review to document the spatial location of local recurrences (LR) after mastectomy. METHODS: A PubMed search was conducted in August 2019 for the following terms: breast [Title/Abstract] AND cancer [Title/Abstract] AND recurrence [Title/Abstract] AND mastectomy [Title/Abstract]. The search was filtered for English language. Exclusion criteria included studies that did not specify the LR location or studies reporting LR associated with inflammatory breast cancer, or other breast cancers such as phyllodes tumours, lymphoma or associated with sarcoma/angiosarcoma. RESULTS: A total of 3922 titles were identified, of which 21 publications were eligible for inclusion in the final analysis. A total of 6901 mastectomy patients were included (range 25-1694). The mean LR proportion was 3.5%. Among the total of 351 LR lesions, 81.8% were in the subcutaneous tissue and the skin, while 16% were pectoral muscle recurrences. CONCLUSION: Local recurrences are mostly located within the subcutaneous tissue and the skin, assumed to result from unrecognized/subclinical tumour foci left behind after mastectomy, surgical implantation of tumour cells in the wound/scar and/or tumour emboli within the subcutaneous lymphatics. Pectoral muscle recurrences are less frequent and may be attributed to residual disease along the posterior surgical margin and/or lymphatic involvement.

Residual Glandular Breast Tissue After Mastectomy: A Systematic Review.

BACKGROUND: The goal of mastectomy is remove all of the glandular breast tissue (BGT) without compromising skin flaps viability. The purpose of this systematic review was to localize and/or estimate the amount of residual BGT (rBGT) after mastectomy and to identify factors that could be related to rBGT and/or residual disease. METHODS: We conducted a PubMed search. The report was subdivided according to the method used to evaluate the presence of rBGT. A total of 16 publications were included in our final report. Two main methods for identifying rBGT included imaging (i.e., MRI scan) and histological evaluation at the time of mastectomy. RESULTS: The rate of rBGT was reported in up to 100% of the patients and was found to be associated mainly with the type of surgical resection, indication, and surgeon's expertise. Residual breast tissue can be found in all areas of the remaining chest wall, mostly in the skin-flaps, and more frequently underneath the nipple-areola complex.

Quantifying the Mitigating Effects of Whole-Breast Radiotherapy and Systemic Treatments on Regional Recurrence Incidence Among Breast Cancer Patients.

BACKGROUND: Despite the potential for residual lymph node metastases after a negative or positive sentinel lymph node biopsy (SLNB), breast cancer patients rarely experience regional recurrences (RRs). This study aimed to quantify the effects of nonsurgical treatments on RR incidence among SLNB-negative (SLNB N0) breast cancer patients. METHODS: All primary SLNB N0-staged breast cancer patients with a diagnosis between 2005 and 2008 and 5-year follow-up data on recurrences were selected from the Netherlands Cancer Registry. The cumulative incidence function (CIF) for RR was calculated as the first event at 5 years, taking into account any other first-event (local or distant recurrence, contralateral breast cancer, or death) as competing risk. Cox regression analysis was used to model the cause-specific hazard of RR developing as the first event to quantify the effect of adjuvant systemic therapy and whole-breast radiotherapy (RT) on RR incidence at 5 years. RESULTS: The study included 13,512 patients. Of these patients, 162 experienced an RR. The CIF of RR at 5 years was 1.3% (95% confidence interval [CI], 1.1-1.5%), whereas the CIFs for death and other events were 4.4% and 9.5%, respectively. Cox regression analysis showed hazard ratios (HRs) of 0.46 (95% CI 0.33-0.64), 0.31 (95% CI 0.18-0.55), and 0.40 (95% CI 0.24-0.67) respectively for patients treated by RT as a routine part of breast-conserving therapy (BCT), chemotherapy, and hormonal therapy. CONCLUSION: RT as routine part of BCT, chemotherapy, and hormonal therapy independently exerted a mitigating effect on the risk for the development of RR. The three methods at least halved the risk.

Applying Risk-Based Follow-Up Strategies on the Dutch Breast Cancer Population: Consequences for Care and Costs.

OBJECTIVES: An important aim of follow-up after primary breast cancer treatment is early detection of locoregional recurrences (LRR). This study compares 2 personalized follow-up scheme simulations based on LRR risk predictions provided by a time-dependent prognostic model for breast cancer LRR and quantifies their possible follow-up efficiency. METHODS: Surgically treated early patients with breast cancer between 2003 and 2008 were selected from the Netherlands Cancer Registry. The INFLUENCE nomogram was used to estimate the 5-year annual LRR. Applying 2 thresholds, they were defined according to Youden's J-statistic and a predefined follow-up sensitivity of 95%, respectively. These patient's risk estimations served as the basis for scheduling follow-up visits; 2 personalized follow-up schemes were simulated. The number of potentially saved follow-up visits and corresponding cost savings for each follow-up scheme were compared with the current Dutch breast cancer guideline recommendation and the observed utilization of follow-up on a training and testing cohort. RESULTS: Using LRR risk-predictions for 30 379 Dutch patients with breast cancer from 2003 to 2006 (training cohort), 2 thresholds were calculated. The threshold according to Youden's approach yielded a follow-up sensitivity of 62.5% and a potential saving of 62.1% of follow-up visits and €24.8 million in 5 years. When the threshold corresponding to 95% follow-up sensitivity was used, 17% of follow-up visits and €7 million were saved compared with the guidelines. Similar results were obtained by applying these thresholds to the testing cohort of 11 462 patients from 2007 to 2008. Compared with the observed utilization of follow-up, the potential cost-savings decline moderately. CONCLUSIONS: Personalized follow-up schemes based on the INFLUENCE nomogram's individual risk estimations for breast cancer LRR could decrease the number of follow-up visits if one accepts a limited risk of delayed LRR detection.

Developing an aftercare decision aid; assessing health professionals' and patients' preferences.

Personalising aftercare for curatively treated breast cancer patients is expected to improve patient satisfaction with care. A patient decision aid can support women in making decisions about their aftercare trajectory, but is currently not available. The aim of this study was to assess the needs of patients and health professionals with regard to an aftercare decision aid to systematically develop such a decision aid. Focus groups with patients and individual interviews with health professionals were digitally recorded and coded using the Framework analysis. Although most patients felt few aftercare options were available to them, health professionals reported to provide various options on the patients' request. Patients reported difficulty in expressing their need for options to their health professional. Although most patients were unfamiliar with decision aids, the majority preferred a paper-based patient decision aid, while most health professionals preferred an online tool. The practical implications for the intended patient decision aid are: that a digital tool with paper-based element should be developed, the patient decision aid should facilitate both rational and intuitive processes and should provide insight in patients' preferences concerning aftercare to discuss these explicitly.

Breast MRI increases the number of mastectomies for ductal cancers, but decreases them for lobular cancers.

PURPOSE: In this retrospective population-based cohort study, we analyzed breast MRI use and its impact on type of surgery, surgical margin involvement, and the diagnosis of contralateral breast cancer. METHODS: All Dutch patients with cT1-4N0-3M0 breast cancer diagnosed in 2011-2013 and treated with primary surgery were eligible for inclusion. Using multivariable analyses, we analyzed in different categories whether MRI use was related to surgery type, margin involvement, and diagnosis of contralateral breast cancer (CBC). RESULTS: MRI was performed in 10,740 out of 36,050 patients (29.8%). Patients with invasive ductal cancer undergoing MRI were more likely to undergo primary mastectomy than those without MRI (OR 1.30, 95% confidence interval (CI) 1.22-1.39, p < 0.0001). Patients with invasive lobular cancer undergoing MRI were less likely to undergo primary mastectomy than those without MRI (OR 0.86, 95% CI 0.76-0.99, p = 0.0303). A significantly lower risk of positive surgical margins after breast-conserving surgery was only seen in patients with lobular cancer who had undergone MRI as compared to those without MRI (OR 0.59, 95% CI 0.44-0.79, p = 0.0003) and, consequently, a lower risk of secondary mastectomy (OR 0.61, 95% CI 0.42-0.88, p = 0.0088). Patients who underwent MRI were almost four times more likely to be diagnosed with CBC (OR 3.55, 95% CI 3.01-4.17, p < 0.0001). CONCLUSIONS: Breast MRI use was associated with a reduced number of mastectomies and less positive surgical margins in invasive lobular cancer, but with an increased number of mastectomies in ductal cancers. Breast MRI use was associated with a fourfold higher incidence of CBC.

Three-dimensional dose evaluation in breast cancer patients to define decision criteria for adaptive radiotherapy.

BACKGROUND: Dose-guided adaptive radiation therapy (DGART) is the systematic evaluation and adaptation of the dose delivery during treatment for an individual patient. The aim of this study is to define quantitative action levels for DGART by evaluating changes in 3D dose metrics in breast cancer and correlate them with clinical expert evaluation. MATERIAL AND METHODS: Twenty-three breast cancer treatment plans were evaluated, that were clinically adapted based on institutional IGRT guidelines. Reasons for adaptation were variation in seroma, hematoma, edema, positioning or problems using voluntary deep inspiration breath hold. Sixteen patients received a uniform dose to the breast (clinical target volume 1; CTV1). Six patients were treated with a simultaneous integrated boost to CTV2. The original plan was copied to the CT during treatment (re-CT) or to the stitched cone-beam CT (CBCT). Clinical expert evaluation of the re-calculated dose distribution and extraction of dose-volume histogram (DVH) parameters were performed. The extreme scenarios were evaluated, assuming all treatment fractions were given to the original planning CT (pCT), re-CT or CBCT. Reported results are mean ± SD. RESULTS: DVH results showed a mean dose (Dmean) difference between pCT and re-CT of -0.4 ± 1.4% (CTV1) and -1.4 ± 2.1% (CTV2). The difference in V95% was -2.6 ± 4.4% (CTV1) and -9.8 ± 8.3% (CTV2). Clinical evaluation and DVH evaluation resulted in a recommended adaptation in 17/23 or 16/23 plans, respectively. Applying thresholds on the DVH parameters: Dmean CTV, V95% CTV, Dmax, mean lung dose, volume exceeding 107% (uniform dose) or 90% (SIB) of the prescribed dose enabled the identification of patients with an assumed clinically relevant dose difference, with a sensitivity of 0.89 and specificity of 1.0. Re-calculation on CBCT imaging identified the same plans for adaptation as re-CT imaging. CONCLUSIONS: Clinical expert evaluation can be related to quantitative DVH parameters on re-CT or CBCT imaging to select patients for DGART.

Three-Dimensional Breast Radiotherapy and the Elective Radiation Dose at the Sentinel Lymph Node Site in Breast Cancer.

BACKGROUND: Several trials are presently randomizing clinically node-negative breast cancer patients treated with breast-conserving therapy (BCT) to sentinel lymph node biopsy (SLNB) or watchful waiting. We aimed to investigate the elective radiation dose at the sentinel lymph node (SLN) site while evaluating two techniques for SLN localization, in breast cancer patients treated with lumpectomy and three-dimensional (3D) whole-breast radiotherapy. METHODS: The SLN site of consecutive Tis-2N0 breast cancer patients undergoing lumpectomy and forward intensity-modulated whole-breast radiotherapy was determined by the location of the hotspot on preoperative single-photon emission computed tomography (SPECT)/computed tomography (CT) and by a surgical clip placed at the removed SLN(s) during SLNB. The radiation dose at the SLN site was subsequently determined on the postoperative radiotherapy planning CT. An elective radiation dose to the SLN site was defined as at least 95 % of the breast dose. RESULTS: Of the 42 included patients, the mean percentage of the breast dose on the SLN site was 90 % (standard deviation 26, range 7-132, median 99), with a non-significant difference between the two techniques (surgical clip or SPECT/CT) (p = 0.608). In 32/42 patients (76 %) the SLN site received an elective radiation dose. CONCLUSIONS: A surgical clip placed at the removed SLN(s) during SLNB proved to be an adequate method of determining the radiation dose at the SLN site when compared with using SPECT/CT. With the use of 3D radiotherapy, the site of the SLN is treated with an elective radiation dose in the majority of patients who are treated with BCT.

Modern clinical research: How rapid learning health care and cohort multiple randomised clinical trials complement traditional evidence based medicine.

BACKGROUND: Trials are vital in informing routine clinical care; however, current designs have major deficiencies. An overview of the various challenges that face modern clinical research and the methods that can be exploited to solve these challenges, in the context of personalised cancer treatment in the 21st century is provided. AIM: The purpose of this manuscript, without intending to be comprehensive, is to spark thought whilst presenting and discussing two important and complementary alternatives to traditional evidence-based medicine, specifically rapid learning health care and cohort multiple randomised controlled trial design. Rapid learning health care is an approach that proposes to extract and apply knowledge from routine clinical care data rather than exclusively depending on clinical trial evidence, (please watch the animation: http://youtu.be/ZDJFOxpwqEA). The cohort multiple randomised controlled trial design is a pragmatic method which has been proposed to help overcome the weaknesses of conventional randomised trials, taking advantage of the standardised follow-up approaches more and more used in routine patient care. This approach is particularly useful when the new intervention is a priori attractive for the patient (i.e. proton therapy, patient decision aids or expensive medications), when the outcomes are easily collected, and when there is no need of a placebo arm. DISCUSSION: Truly personalised cancer treatment is the goal in modern radiotherapy. However, personalised cancer treatment is also an immense challenge. The vast variety of both cancer patients and treatment options makes it extremely difficult to determine which decisions are optimal for the individual patient. Nevertheless, rapid learning health care and cohort multiple randomised controlled trial design are two approaches (among others) that can help meet this challenge.

Innovative Education Method for a More Effective, Faster, and Valued Training in Radiation Therapy Treatment Planning.

Purpose: Because of the automation of radiation therapy, competencies of radiation technologists (RTTs) change, and training methods are challenged. This study aims to develop, and pilot test an innovative training method based on lean management principles. Methods and Materials: A new training method was developed for lung cancer treatment planning (TP). The novelty is summarized by including a stable environment and an increased focus on the how and why of key decision making. Trainees have to motivate their decisions during TP process, and to argue their choices with peers. Six students and 6 RTTs completed this training for lung cancer TP. Effects of the training were measured by (1) quality of TP, using doses in organs at risk and target volumes, (2) perceived experiences (survey), measured at baseline (T0); after peer session (T1); and 6 months later (T2). Finally, training throughput time was measured. Results: At T0, RTTs showed a larger intragroup interquartile range (IIR) (2.63Gy vs 1.51Gy), but lower mean doses to heart and esophagus than students (6.79Gy vs 8.49Gy; 20.87Gy vs 24.62Gy). At T1, quality of TPs was similar between RTTs and students (IIR: 1.39Gy vs 1.33Gy) and no significant differences in mean dose to heart and esophagus (4.48Gy vs 4.69Gy; 17.75Gy vs 18.47Gy). At T2, students still performed equal to RTTs (IIR: 1.07Gy vs 1.45Gy) and achieved lower maximum dose to esophagus (44.75Gy vs 46.45Gy). The training method and peer sessions were experienced positive: at baseline (T0): 8 score on a scale 1-10, directly after the peer sessions; (T1): 8 by the students and 7 by the RTTs, after 9 months; (T2): 9 by the students and 7 by the RTTs. Training throughput time decreased from 12 to 3 months. Conclusions: This training method based on lean management principles was successfully applied to training of RTTs for lung cancer TP. Training throughput time was reduced dramatically and TP quality sustained after 6 months. This method can potentially improve training efficiency in diverse situations with complex decision-making.

Residual breast tissue after mastectomy and reconstruction: A substudy of the Spatial location of breast cancer local rECurRence aftEr masTectomy (SECRET) project.

The current project is part of the Spatial location of breast cancer local rECurRence aftEr masTectomy (SECRET) study (NCT06130111). Herein we compared the chest wall thickness after non-skin sparing mastectomy (non-SSM) with the chest wall thickness after SSM, as a surrogate for residual breast tissue after mastectomy. METHODS: The study was approved by the ethics committee of relevant institutions. Data of patients with a local recurrence (LR) after non-SSM was collected from the Netherlands Cancer Registry (NCR); data of patients undergoing SSM were collected from Sheba Medical Center. Student's t-test was used to evaluate the difference between the cohorts. Chest wall thickness was measured on postoperative images. RESULTS: Out of 4949 patients who underwent mastectomy from the NCR cohort, a total of 173 (3.5 %) had a LR at 5 years, of these a total of 153 patients included in the non-SSM cohort. The median age was 59 years (age 33-92), LR occurred at a median of 23.6 months (2.5-60 months). The SSM cohort included 84 patients, with a median age of 38.4 years (28-63.5), overall, 5 LRs occurred at a median of 15 months (5-46 months). The SSM cohort had significantly thicker chest walls compared to non-SSM (p < 0.001). Most LRs in both groups occurred in the subcutis. CONCLUSION: The chest wall thickness differed according to mastectomy procedures. Most of the LR occurred at the subcutis. The role of residual breast tissue and residual cancer in relation to type of mastectomy should be further investigated.

A taskforce for national improvement of innovation implementation in radiotherapy.

BACKGROUND AND PURPOSE: Previous research among Dutch radiotherapy centres (RTCs) showed that 69% of innovations was simultaneously implemented in 7/19 centres, with a success rate of 51%. However, no structure to share lessons learned about the implementation process existed. Therefore, a national Taskforce Implementation (TTI) was raised to stimulate efficient implementation of innovations. The aim of the current study was to develop and pilot-evaluate a website for facilitating mutual learning on implementation issues. MATERIAL AND METHODS: First, we made an inventory in all Dutch RTCs on their 10 most valuable innovations between 2019 and 2022. In-depth interviews, structured according to the Consolidated Framework for Implementation Research, were performed on the four most mentioned topics. A website was built, and pilot evaluated 1 year after the launch, using a qualitative survey amongst the TTI members. RESULTS: In 13/18 centres, 19 interviews were conducted on 1) automation, 2) patient participation, 3) adaptive radiotherapy 4) surface guided radiotherapy and tracking. Most innovations (13/16) were implemented with a delay, with many comparable challenges: e.g. shortage of personnel (7/16) and prioritization of projects (9/16). The website allows users to upload and search for projects, including implementation experiences. After 1 year, 14 projects were uploaded. The qualitative evaluation was largely positive with room for improvement, i.e.75 % would recommend the website to others. CONCLUSION: This study showed that RTCs experience comparable challenges when implementing innovations, thereby underlining the need for a platform to share implementation-lessons learned. The first concept of this platform was evaluated positively.