Designing clinical trials based on modern imaging and metastasis-directed treatments in patients with oligometastatic breast cancer: a consensus recommendation from the EORTC Imaging and Breast Cancer Groups.

Breast cancer remains the most common cause of cancer death among women. Despite its considerable histological and molecular heterogeneity, those characteristics are not distinguished in most definitions of oligometastatic disease and clinical trials of oligometastatic breast cancer. After an exhaustive review of the literature covering all aspects of oligometastatic breast cancer, 35 experts from the European Organisation for Research and Treatment of Cancer Imaging and Breast Cancer Groups elaborated a Delphi questionnaire aimed at offering consensus recommendations, including oligometastatic breast cancer definition, optimal diagnostic pathways, and clinical trials required to evaluate the effect of diagnostic imaging strategies and metastasis-directed therapies. The main recommendations are the introduction of modern imaging methods in metastatic screening for an earlier diagnosis of oligometastatic breast cancer and the development of prospective trials also considering the histological and molecular complexity of breast cancer. Strategies for the randomisation of imaging methods and therapeutic approaches in different subsets of patients are also addressed.

Current clinical practice in the management of phyllodes tumors of the breast: an international cross-sectional study among surgeons and oncologists.

PURPOSE: Phyllodes tumors of the breast are rare fibroepithelial lesions that are classified as benign, borderline or malignant. There is little consensus on best practice for the work-up, management, and follow-up of patients with phyllodes tumors of the breast, and evidence-based guidelines are lacking. METHODS: We conducted a cross-sectional survey of surgeons and oncologists with the aim to describe current clinical practice in the management of phyllodes tumors. The survey was constructed in REDCap and distributed between July 2021 and February 2022 through international collaborators in sixteen countries across four continents. RESULTS: A total of 419 responses were collected and analyzed. The majority of respondents were experienced and worked in a university hospital. Most agreed to recommend a tumor-free excision margin for benign tumors, increasing margins for borderline and malignant tumors. The multidisciplinary team meeting plays a major role in the treatment plan and follow-up. The vast majority did not consider axillary surgery. There were mixed opinions on adjuvant treatment, with a trend towards more liberal regiments in patients with locally advanced tumors. Most respondents preferred a five-year follow-up period for all phyllodes tumor types. CONCLUSIONS: This study shows considerable variation in clinical practice managing phyllodes tumors. This suggests the potential for overtreatment of many patients and the need for education and further research targeting appropriate surgical margins, follow-up time and a multidisciplinary approach. There is a need to develop guidelines that recognize the heterogeneity of phyllodes tumors.

Completeness of Reporting Oligometastatic Disease Characteristics in the Literature and Influence on Oligometastatic Disease Classification Using the ESTRO/EORTC Nomenclature.

PURPOSE: There is increasing evidence for the integration of locally ablative therapy into multimodality treatment of oligometastatic disease (OMD). To support standardised data collection, analysis, and comparison, a consensus OMD classification based on fundamental disease and treatment characteristics has previously been established. This study investigated the completeness of reporting the proposed OMD characteristics in literature and evaluated whether the proposed OMD classification system can be applied to the historical data. METHODS AND MATERIALS: A systematic literature review was performed in Medline, Embase, and Cochrane, searching for prospective and retrospective studies, where stereotactic body radiation therapy was a treatment component of OMD. Reporting of the OMD characteristics as described in the European Organisation for Research and Treatment of Cancer/European Society for Radiotherapy and Oncology classification was analyzed, feasibility to retrospectively classify the proposed OMD states was investigated, and the effect of the categorization on overall survival (OS) was evaluated. RESULTS: Our study shows incomplete reporting of the proposed OMD characteristics. The most fully reported characteristic was type of involved organs (88/95 studies); history of cancer progression was the least reported (not mentioned in 50/95 studies). Retrospective OMD classification of existing literature was only possible for 7 of the 95 studies. With respect to categorization as de novo, repeat, or induced OMD, homogeneous patient cohorts were observed in 21 of the 95 studies, most frequently de novo OMD in 20 studies. Differences in OS at 2, 3, or 5 years were not statistically significant between the different states. OS was significantly influenced by primary tumor histology, with superior OS observed for prostate cancer and worst OS observed for non-small cell lung cancer. CONCLUSIONS: The largely incomplete reporting of the proposed OMD characteristics hampers a retrospective classification of existing literature. To facilitate future comparison of individual studies, as well as validation of the OMD classification, comprehensive reporting of OMD characteristics using standardised terminology is recommended, as proposed by the European Organisation for Research and Treatment of Cancer/European Society for Radiotherapy and Oncology classification system and following the European Society for Radiotherapy and Oncology/American Society for Radiation Oncology consensus.

Validation of a prognostic scoring system for postmastectomy locoregional recurrence in breast cancer.

BACKGROUND: To date, it remains unclear which patients with breast cancer (BC) benefit from post-mastectomy radiotherapy (PMRT). Cheng et al. developed and validated a scoring system based on 4 prognostic factors for locoregional recurrence (LRR) to identify patients in need for PMRT. These factors include age, estrogen receptor status, lymphovascular status and number of affected axillary lymph nodes. PURPOSE: To validate the scoring system for LRR in BC developed by Cheng et al. by using an independent BC database. METHODS AND MATERIALS: We retrospectively identified 1989 BC cases, treated with mastectomy (ME) with or without PMRT at the University Hospitals Leuven between 2000 and 2007. The primary endpoint was 5-year locoregional control rate with and without PMRT, according to the LRR score. RESULTS: Median follow-up time was 11.4 years. After excluding patients with missing variables 1103 patients were classified using the LRR scoring system: 688 (62.38%) patients were at low risk of recurrence (LRR score 0-1), 335 (30.37%) patients were at intermediate risk of recurrence (LRR score 2-3) and 80 (7.25%) patients were at high risk of recurrence (LRR score ≥4). 5-year locoregional control rates with and without PMRT were 99.20% versus 99.21% (p = 0.43) in the low-risk group; 98.24% versus 85.74% (p < 0.0001) in the intermediate-risk group and 96.87% versus 85.71% (p = 0.10) in the high-risk group respectively. CONCLUSION: Our validation of the LRR scoring system suggests it can be used to point out patients that would benefit from PMRT. We recommend further validation of this scoring system by other independent institutions before application in clinical practice.

Defining oligometastatic disease from a radiation oncology perspective: An ESTRO-ASTRO consensus document.

BACKGROUND: Recognizing the rapidly increasing interest and evidence in using metastasis-directed radiotherapy (MDRT) for oligometastatic disease (OMD), ESTRO and ASTRO convened a committee to establish consensus regarding definitions of OMD and define gaps in current evidence. METHODS: A systematic literature review focused on curative intent MDRT was performed in Medline, Embase and Cochrane. Subsequent consensus opinion, using a Delphi process, highlighted the current state of evidence and the limitations in the available literature. RESULTS: Available evidence regarding the use of MDRT for OMD mostly derives from retrospective, single-centre series, with significant heterogeneity in patient inclusion criteria, definition of OMD, and outcomes reported. Consensus was reached that OMD is largely independent of primary tumour, metastatic location and the presence or length of a disease-free interval, supporting both synchronous and metachronous OMD. In the absence of clinical data supporting a maximum number of metastases and organs to define OMD, and of validated molecular biomarkers, consensus supported the ability to deliver safe and clinically meaningful radiotherapy with curative intent to all metastatic sites as a minimum requirement for defining OMD in the context of radiotherapy. Systemic therapy induced OMD was identified as a distinct state of OMD. High-resolution imaging to assess and confirm OMD is crucial, including brain imaging when indicated. Minimum common endpoints such as progression-free and overall survival, local control, toxicity and quality-of-life should be reported; uncommon endpoints as deferral of systemic therapy and cost were endorsed. CONCLUSION: While significant heterogeneity exists in the current OMD definitions in the literature, consensus was reached on multiple key questions. Based on available data, OMD can to date be defined as 1-5 metastatic lesions, a controlled primary tumor being optional, but where all metastatic sites must be safely treatable. Consistent definitions and reporting are warranted and encouraged in ongoing trials and reports generating further evidence to optimize patient benefits.

The financial impact of SBRT for oligometastatic disease: A population-level analysis in Belgium.

INTRODUCTION: There is a steady rise in Stereotactic Body RadioTherapy (SBRT) utilization in oligometastatic disease (OMD). This may generate important financial consequences for radiotherapy budgets. The National Institute for Health and Disability Insurance of Belgium (NIHDI) initiated a coverage with evidence development (CED) project for innovative radiotherapy, including SBRT, in 2011. A cost calculation and budget estimation for SBRT in the OMD setting was carried out. MATERIALS AND METHODS: Predictive growth scenarios for future uptake of SBRT for OMD in Belgium were developed using demographics and CED data. The provider cost of SBRT for OMD in Belgium was calculated using the Time-Driven Activity-Based Costing (TD-ABC) model developed by ESTRO-HERO, alimented with national data on resources, treatments and operational parameters, and compared to the new reimbursement. Combining these, the future financial impact of this novel treatment indication for healthcare providers and payers in Belgium was evaluated. RESULTS: The number of 428 OMDs treated with SBRT in Belgium in 2017 is expected to increase between 484 and 2073 courses annually by 2025. A provider cost of €4360 per SBRT was calculated (range: €3488-€5654), whereas the reimbursement covers between €4139 and €4654. Large variations in potential extra provider costs by 2025 ensue from the different scenarios, ranging between €1,765,993 and €9,038,754. Provider costs and reimbursement show good agreement. CONCLUSION: Although the financial impact of SBRT for OMD in Belgium is forecasted to remain acceptable, even in extreme scenarios, further clinical trials and real-life clinical and financial monitoring with prospective data gathering are necessary to refine the data.

Validation of a normal tissue complication probability model for late unfavourable aesthetic outcome after breast-conserving therapy.

PURPOSE: To validate a normal tissue complication probability (NTCP) model for late unfavourable aesthetic outcome (AO) after breast-conserving therapy. MATERIALS/METHODS: The BCCT.core software evaluated the AO using standardized photographs of patients treated at the University Hospitals Leuven between April 2015 and April 2016. Dose maps in 2 Gy equivalents were calculated assuming α/ß = 3.6 Gy. The discriminating ability of the model was described by the AUC of the receiver operating characteristic curve. A 95% confidence interval (CI) of AUC was calculated using 10,000 bootstrap replications. Calibration was evaluated with the calibration plot and Nagelkerke R2. Patients with unfavourable AO at baseline were excluded. Patient, tumour and treatment characteristics were compared between the development and the validation cohort. The prognostic value of the characteristics in the validation cohort was further evaluated in univariable and multivariable analysis. RESULTS: Out of 175 included patients, 166 were evaluated two years after RT and 44 (26.51%) had unfavourable AO. AUC was 0.66 (95% CI 0.56; 0.76). Calibration was moderate with small overestimations at higher risk. When applying all of the univariable significant clinicopathological and dosimetrical variables from the validation cohort in a multivariable model, the presence of a seroma and V45 were selected as significant risk factors for unfavourable AO (Odds Ratio 4.40 (95% CI 1.96; 9.86) and 1.14 (95% CI 1.03; 1.27), p-value <.001 and .01, respectively). CONCLUSIONS: The NTCP model for unfavourable AO shows a moderate discrimination and calibration in the present prospective validation cohort with a small overestimation in the high risk patients.

A comparison of a brachytherapy and an external beam radiotherapy boost in breast-conserving therapy for breast cancer: local and any recurrences.

PURPOSE: Adding a tumour bed boost to whole-breast irradiation in breast-conserving therapy reduces local recurrence rates. The purpose of the present study was to investigate whether the boost technique influences the magnitude of the effect. METHODS: Patients treated with breast-conserving therapy for invasive breast cancer between 2000 and 2007 were included in the analysis. Three groups were considered according to the applied boost technique: electrons, brachytherapy or photons. The endpoints were local recurrence and any recurrence. Cox regression models were used and correction for the confounders in the association between boost technique and outcome was performed using multivariable models. RESULTS: 1879 tumours were included in the analysis. 1448 tumours (77.1%) were treated with an electron boost, 334 (17.8%) with a brachytherapy boost and 97 (5.2%) with a photon boost. Median follow-up was 13.1 years. The 10-year local recurrence rate was 2.2%. In multivariable analysis with correction for age, pathological Tumour or Node stage (pT, pN), chemotherapy and hormonal therapy, there was no significant difference between the three groups for the local recurrence risk (p = 0.89). 10-year any recurrence rate was 10.8%. In multivariable analysis with correction for age, pT, pN, resection margins, radiotherapy, year of diagnosis, chemotherapy and hormonal therapy, there was no significant difference between the brachytherapy group and the electron group or the photon group (p = 0.11 and p = 0.28, respectively). The photon group had more recurrences compared to the electron group (Hazard Ratio 1.81, 95% Confidence Interval 1.12; 2.92, p = 0.02). CONCLUSIONS: The local recurrence risk reduction of the tumour bed boost in breast-conserving therapy is not influenced by the applied boost technique.

Development of a normal tissue complication probability model for late unfavourable aesthetic outcome after breast-conserving therapy.

PURPOSE/OBJECTIVES: To develop a normal tissue complication probability (NTCP) model for late unfavourable aesthetic outcome (AO) after breast-conserving therapy. MATERIAL AND METHODS: The BCCT.core software evaluated the AO using standardized photographs of patients treated between 2009 and 2014. Dose maps in 2 Gy equivalents were calculated assuming α/ß = 3.6 Gy. Uni- and multivariable logistic regression analysis was performed to study the predictive value of clinicopathological and dosimetric variables for unfavourable AO. The Lyman Kutcher Burman (LKB) model was fit to the data with dose modifying factors (dmf). Model performance was assessed with the area under the curve (AUC) of the receiver operating characteristic curve and bootstrap sampling. RESULTS: Forty-four of the 121 analysed patients (36%) developed unfavourable AO. In the optimal multivariable logistic regression model, a larger breast volume receiving ≥55 Gy (V55), a seroma and an axillary lymph node dissection (ALND) were independently associated with an unfavourable AO, AUC = 0.75 (95%CI 0.64;0.85). Beta-estimates were -2.68 for ß0, 0.057 for V55, 1.55 for seroma and 1.20 for ALND. The optimal LKB model parameters were EUD3.6(50) = 63.3 Gy, n = 1.00, m = 0.23, dmf(seroma) = 0.83 and dmf(ALND) = 0.84, AUC = 0.74 (95%CI 0.61;0.83). CONCLUSIONS: An NTCP model for late unfavourable AO after breast-conserving therapy was developed including seroma, axillary lymphadenectomy and V55.

Feasibility study of individualized optimal positioning selection for left-sided whole breast radiotherapy: DIBH or prone.

The deep inspiration breath hold (DIBH) and prone (P) position are two common heart-sparing techniques for external-beam radiation treatment of left-sided breast cancer patients. Clinicians select the position that is deemed to be better for tissue sparing based on their experience. This approach, however, is not always optimum and consistent. In response to this, we develop a quantitative tool that predicts the optimal positioning for the sake of organs at risk (OAR) sparing. Sixteen left-sided breast cancer patients were considered in the study, each received CT scans in the supine free breathing, supine DIBH, and prone positions. Treatment plans were generated for all positions. A patient was classified as DIBH or P using two different criteria: if that position yielded (1) lower heart dose, or (2) lower weighted OAR dose. Ten anatomical features were extracted from each patient's data, followed by the principal component analysis. Sequential forward feature selection was implemented to identify features that give the best classification performance. Nine statistical models were then applied to predict the optimal positioning and were evaluated using stratified k-fold cross-validation, predictive accuracy and receiver operating characteristic (AUROC). For heart toxicity-based classification, the support vector machine with radial basis function kernel yielded the highest accuracy (0.88) and AUROC (0.80). For OAR overall toxicities-based classification, the quadratic discriminant analysis achieved the highest accuracy (0.90) and AUROC (0.84). For heart toxicity-based classification, Breast volume and the distance between Heart and Breast were the most frequently selected features. For OAR overall toxicities-based classification, Heart volume, Breast volume and the distance between ipsilateral lung and breast were frequently selected. Given the patient data considered in this study, the proposed statistical model is feasible to provide predictions for DIBH and prone position selection as well as indicate important clinical features that affect the position selection.

Tumour bed boost radiotherapy for women after breast-conserving surgery.

BACKGROUND: Breast-conserving therapy, involving breast-conserving surgery followed by whole-breast irradiation and optionally a boost to the tumour bed, is a standard therapeutic option for women with early-stage breast cancer. A boost to the tumour bed means that an extra dose of radiation is applied that covers the initial tumour site. The rationale for a boost of radiotherapy to the tumour bed is that (i) local recurrence occurs mostly at the site of the primary tumour because remaining microscopic tumour cells are most likely situated there; and (ii) radiation can eliminate these causative microscopic tumour cells. The boost continues to be used in women at high risk of local recurrence, but is less widely accepted for women at lower risk. Reasons for questioning the boost are twofold. Firstly, the boost brings higher treatment costs. Secondly, the potential adverse events are not negligible. In this Cochrane Review, we investigated the effect of the tumour bed boost on local control and side effects. OBJECTIVES: To assess the effects of tumour bed boost radiotherapy after breast-conserving surgery and whole-breast irradiation for the treatment of breast cancer. SEARCH METHODS: We searched the Cochrane Breast Cancer Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (January 1966 to 1 March 2017), Embase (1980 to 1 March 2017), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov on 1 March 2017. We also searched the European Society of Radiotherapy and Oncology Annual Meeting, the St Gallen Oncology Conferences, and the American Society for Radiation Oncology Annual Meeting for abstracts. SELECTION CRITERIA: Randomised controlled trials comparing the addition and the omission of breast cancer tumour bed boost radiotherapy. DATA COLLECTION AND ANALYSIS: Two review authors (IK and CW) performed data extraction and assessed risk of bias using Cochrane's 'Risk of bias' tool, resolving any disagreements through discussion. We entered data into Review Manager 5 for analysis and applied GRADE to assess the quality of the evidence. MAIN RESULTS: We included 5 randomised controlled trials analysing a total of 8325 women.Local control appeared to be better for women receiving a tumour bed boost compared to no tumour bed boost (hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.55 to 0.75; 5 studies, 8315 women, low-quality evidence). Overall survival did not differ with or without a tumour bed boost (HR 1.04, 95% CI 0.94 to 1.14; 2 studies, 6342 women, moderate-quality evidence). Disease-free survival did not differ with or without a tumour bed boost (HR 0.94, 95% CI 0.87 to 1.02; 3 studies, 6549 women, low-quality evidence). Late toxicity scored by means of percentage of breast retraction assessment did not differ with or without a tumour bed boost (mean difference 0.38, 95% CI -0.18 to 0.93; 2 studies, 1526 women, very low-quality evidence). Cosmesis scored by a panel was better (i.e. excellent or good compared to fair or poor) in the no-boost group (odds ratio (OR) 1.41, 95% CI 1.07 to 1.85; 2 studies, 1116 women, low-quality evidence). Cosmesis scored by a physician did not differ with or without a tumour bed boost (OR 1.58, 95% CI 0.93 to 2.69; 2 studies, 592 women, very low-quality evidence).We excluded two studies in a sensitivity analysis of local recurrence (because the biological equivalent dose (BED) to the tumour bed was lower, in situ tumours were included, or there was a high risk of selective reporting bias or blinding of outcome assessment bias), which resulted in a HR of 0.62 (95% CI 0.52 to 0.73; 3 studies, 6963 women, high-quality evidence). Subgroup analysis including women older than 40 years of age yielded a HR of 0.65 (95% CI 0.53 to 0.81; 2 studies, 5058 women, high-quality evidence).We found no data for the outcomes of acute toxicity, quality of life, or costs. AUTHORS' CONCLUSIONS: It appears that local control rates are increased with the boost to the tumour bed, but we found no evidence of a benefit for other oncological outcomes. Subgroup analysis including women older than 40 years of age yielded similarly significant results. Objective percentage of breast retraction assessment appears similar between groups. It appears that the cosmetic outcome is worse with the boost to the tumour bed, but only when measured by a panel, not when assessed by a physician.

125I brachytherapy in younger prostate cancer patients : Outcomes in low- and intermediate-risk disease.

PURPOSE: To evaluate local recurrence in younger men treated with low-dose-rate (LDR) 125I brachytherapy (BT) for localized prostate cancer. PATIENTS AND METHODS: A total of 192 patients (≤65-years-old) were treated with LDR 125I-BT ± hormone therapy. Local failure was defined as any prostate-specific antigen (PSA) rise leading to salvage treatment or biochemical failure according to the Phoenix definition. A bounce was defined as a rise in the nadir of ≥0.2 ng/mL followed by spontaneous return. Proportions were compared using Fisher's exact tests; continuous variables using the unpaired t-test or its non-parametric equivalent. Cox proportional hazards models were applied for multivariable survival analysis. RESULTS: Median follow-up was 66 months. The 5­year local recurrence-free survival was 96.1%. Biopsy-proven local recurrence developed in 13 patients, 4 had a Phoenix-defined recurrence at the last follow-up. Androgen deprivation therapy was started in 1 patient without proven recurrence. Univariable risk factors for local recurrence were: at least 50% positive biopsies, intermediate risk, treatment with neoadjuvant hormone therapy, low preimplantation volume receiving 100% of the prescribed dose, and no bounce development. Hormone-naïve patients not attaining a PSA value <0.5 ng/mL during follow-up also had a higher risk of local recurrences. Cox regression demonstrated that the variables "at least 50% positive biopsies" and "bounce" significantly impacted local failure (hazard ratio, HR 1.02 and 11.59, respectively). A bounce developed in 70 patients (36%). Younger patients and those treated with a lower activity per volume had a higher chance of developing a bounce in the Cox model (HR 0.99 and 0.04, respectively). CONCLUSION: For younger men, LDR BT is a valid primary curative treatment option in low-risk and is to consider in intermediate-risk localized prostate cancer.

Boost delineation in breast radiation therapy: Isotropic versus anisotropic margin expansion.

PURPOSE: The purpose of this article is to compare isotropic and anisotropic margin expansion with regard to the size of the clinical target volume boost (CTVboost) and the interobserver variability (IOV). METHODS AND MATERIALS: Lumpectomy cavities marked with 3 or more surgical clips were delineated by 6 radiation oncologists who specialized in breast radiation therapy. CTVboost anisotropic was created by manually expanding the tumor bed with an anisotropic margin of 15 mm (20 mm in case of extensive intraductal component) minus the surgical free margins in 6 directions (anteroposterior, craniocaudal, and superoinferior). For the CTVboost isotropic, the tumor bed was enlarged with an isotropic margin of 15 mm (20 mm in case of extensive intraductal component) minus the minimal surgical free margin. The volumes of the delineated CTVboost (cm3) were measured. To assess the IOV, the Jaccard index (JI), defined as the intersection divided by the size of the union of the sample sets, was used (ideal value = 1). The JI was calculated for each case and each observer pair. Linear mixed models were used for all analyses. RESULTS: A total of 444 delineated tumor beds were evaluated. The mean volume of the CTVboost almost doubled by expanding the tumor bed with an isotropic margin compared with anisotropic margins (CTVboost isotropic 94 mL [12.5-331.0] vs CTVboost anisotropic 50 mL [3.2-332.7]; P = .0006). The IOV, assessed by the JI, significantly decreased by using isotropic versus anisotropic margin expansion (JICTV boost isotropic 0.73 [0.02-0.92] vs JICTV boost anisotropic 0.51 [0.0-0.8]; P< .0001). Because of the known positive correlation of the IOV and larger volumes, we corrected for CTVboost volumes. With this correction, the difference in IOV remains highly significant (P < .0001) in favor of isotropic margin expansion. CONCLUSIONS: The use of anisotropic margin expansion from tumorbed to CTVboost isotropic significantly reduced the volume of the delineated CTVboost with a factor of 1.9 compared with isotropic margin expansion, but it substantially increased the interobserver variability.

Validation of the Web-Based IBTR! 2.0 Nomogram to Predict for Ipsilateral Breast Tumor Recurrence After Breast-Conserving Therapy.

PURPOSE: To evaluate the IBTR! 2.0 nomogram, which predicts 10-year ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy with and without radiation therapy for breast cancer, by using a large, external, and independent cancer center database. METHODS AND MATERIALS: We retrospectively identified 1898 breast cancer cases, treated with breast-conserving therapy and radiation therapy at the University Hospital Leuven from 2000 to 2007, with requisite data for the nomogram variables. Clinicopathologic factors were assessed. Two definitions of IBTR were considered where simultaneous regional or distant recurrence were either censored (conform IBTR! 2.0) or included as event. Validity of the prediction algorithm was tested in terms of discrimination and calibration. Discrimination was assessed by the concordance probability estimate and Harrell's concordance index. The mean predicted and observed 10-year estimates were compared for the entire cohort and for 4 risk groups predefined by nomogram-predicted IBTR risks, and a calibration plot was drawn. RESULTS: Median follow-up was 10.9 years. The 10-year IBTR rates were 1.3% and 2.1%, according to the 2 definitions of IBTR. The validation cohort differed from the development cohort with respect to the administration of hormonal therapy, surgical section margins, lymphovascular invasion, and tumor size. In univariable analysis, younger age (P=.002) and a positive nodal status (P=.048) were significantly associated with IBTR, with a trend for the omission of hormonal therapy (P=.061). The concordance probability estimate and concordance index varied between 0.57 and 0.67 for the 2 definitions of IBTR. In all 4 risk groups the model overestimated the IBTR risk. In particular, between the lowest-risk groups a limited differentiation was suggested by the calibration plot. CONCLUSIONS: The IBTR! 2.0 predictive model for IBTR in breast cancer patients shows substandard discriminative ability, with an overestimation of the risk in all subgroups.

Is the use of a preoperative computed tomography beneficial to reduce the interobserver variability of the CTVboost delineation for breast radiation therapy?

PURPOSE: To determine whether the use of a preoperative (preop) computed tomography (CT) reduces (1) the clinical target volume boost (CTVboost) and (2) the interobserver variability (IOV) of the delineated CTVboost in breast radiation therapy. METHODS AND MATERIALS: In patients treated with breast-conserving therapy, 3 CT scans in treatment position were performed: (1) preop; (2) after surgery, prechemotherapy (postop); and (3) postchemotherapy (postchemo). Six radiation-oncologists delineated the tumor bed and CTVboost before and after fusion of the preop CT. To assess the IOV, the Jaccard index was used. Linear mixed models were performedfor all analyses. RESULTS: Eighty-two lumpectomy cavities were evaluated in 22 patients. No difference in CTVboost using the fusion of the preop CT (50.0 cm3; 95% confidence interval [CI], 35.6-64.4) compared with no fusion (49.0 cm3; 95% CI, 34.6-63.4) (P = .6) was observed. A significant increase in IOV was shown with the fusion of the preop CT; the mean Jaccard index of the CTVboost delineation of postop and postchemo CT together without the fusion of the preop CT was 0.53 (95% CI, 0.49-0.57) versus 0.50 (95% CI, 0.46-0.53) with fusion (P < .0001). CONCLUSIONS: There is no benefit of using a preop CT to reduce the volume or the interobserver variability of the delineated CTVboost for breast radiation therapy.

Evaluation of a breast cancer nomogram to predict ipsilateral breast relapse after breast-conserving therapy.

BACKGROUND AND PURPOSE: A nomogram to predict for the 10-year ipsilateral breast relapse (IBR) after breast-conserving therapy (BCT) for breast cancer (BC) was developed based on the 'boost-no-boost'-trial with a concordance probability estimate (CPE) of 0.68. The aim of our study was to validate that algorithm. MATERIAL AND METHODS: We retrospectively identified 1787 BC cases, treated with BCT and radiotherapy at the University Hospitals Leuven from 2000 to 2007, without missing data of the nomogram variables. Clinicopathologic factors were assessed. Validity of the prediction model was tested in terms of discrimination and calibration. RESULTS: Median follow-up time was 10.75years. The validation cohort differed with respect to the administration of a radiation boost, chemo- or hormonal therapy, age, tumour diameter or grade, ductal carcinoma in situ and hormone receptor positivity. On multivariable analysis, the omission of the boost was a significant prognosticator of IBR (p<0.01). The 10-year IBR-rate was 1.4%. The nomogram demonstrated suboptimal discrimination (CPE 0.54) and calibration, with an overestimation of the IBR-risk in general. CONCLUSIONS: The predictive model for IBR in BC is imperfect in this more recent study population.

A comparison of three different radiotherapy boost techniques after breast conserving therapy for breast cancer.

PURPOSE: Compare different boost techniques after breast conserving therapy (BCT) in terms of local and loco-regional recurrences. MATERIALS AND METHODS: From 2000 to 2005, patients treated with BCT for invasive breast cancer (BC) were included. An electron boost (EB) was performed for a superficial boost-volume (less than 29 mm under the epidermis), in all other cases a brachytherapy boost (BTB) was proposed. When patients refused a BTB or it was not possible for technical reasons, a photon boost (PB) was given. The primary endpoints were local and loco-regional recurrences. Secondary endpoints were metastasis-free and overall survival. RESULTS: 1379 patients were eligible for analysis. Most patients (1052) received an EB, 225 a BTB and 76 a PB. At a median follow-up of 8.8 years, 35 (2.5%) patients developed a local or loco-regional recurrence. Ten years local relapse-free rate was 97.9%. No differences between boost techniques were observed in relapse risk, metastasis-free and overall survival after multivariate analyses. CONCLUSION: In women treated with BCT followed by a boost irradiation to the tumor bed, no difference in local and loco-regional recurrence, metastasis-free and overall survival was observed comparing three different boost techniques. Outcome was excellent regardless of the boost technique.

Case report of cold-weather-induced radiation recall dermatitis after chemoradiotherapy with cisplatin.

BACKGROUND: The radiation recall reaction (RRR) is an inflammatory reaction that occurs in previously irradiated areas. The phenomenon is probably due to an idiosyncratic hypersensitivity reaction, in which a second agent can recall the inflammatory reaction. CASE REPORT: This case report documents a cold-weather-induced radiation recall dermatitis (RRD). We observed a severe RRD in a patient after chemoradiotherapy treatment with cisplatin for a nasopharyngeal carcinoma, precipitated by cold temperatures, which developed 9 days after completion of therapy. In the medical literature, RRD following extreme cold temperatures seems to be a peculiar event. CONCLUSION: Until further information on the interaction is available, future studies on combined chemotherapy with cisplatin should be carefully monitored and any side effects clearly documented. This case suggests that environmental conditions may play a contributing role in the development of RRD. This case also implies that neither fraction size nor total radiation dose is a determining factor in the development of the dermatologic reaction.