Young Boost Trial Research Articles

A case-control study to identify molecular risk factors for local recurrence in young breast cancer patients

PurposeTo investigate risk factors for local recurrence (LR) after breast conserving therapy in young breast cancer patients randomized in the “Young Boost Trial”. Material & methodsIn the “Young Boost Trial” 2421 patients ≤50 years old were randomized between a 16 Gy and 26 Gy boost after breast conserving surgery and whole breast radiation (50 Gy). We performed a case-control study comparing patients who developed a LR (cases) and for each of them three control patients free of recurrence (controls). Clinicopathological factors, copy number- and gene expression profiles of primary tumors were compared between cases and controls, and between primary tumors and local recurrences. ResultsThe cumulative 5-year LR rate was 1.07% (95% CI 0.72-1.59%) and 10-year LR rate 2.56% (1.81–3.62%). Analysis of a subset of primary tumors and local recurrences showed similar histopathological characteristics (n = 15), copy number (n = 13) and gene expression profiles (n = 14). Basal subtype was strongly associated with LR in univariable and multivariable analysis. Gains of CCND1 were identified more frequently among controls, while more frequent gains of FGFR1 and IGF1R were observed among cases. Upregulation of genes involved in the p53-pathway was observed in recurring tumors compared to non-recurring tumors. We could not identify a genomic classifier for LR. ConclusionsAll investigated local recurrences were true genomic recurrences. Although differences in copy number variation and gene expression pathways were observed in recurring tumors compared to non-recurring tumors, no genomic classifier for LR could be identified.

Predictors for poor cosmetic outcome in patients with early stage breast cancer treated with breast conserving therapy: Results of the Young boost trial

PurposeIn the Young Boost trial (YBT), breast cancer patients ≤50 years of age, treated with breast conserving therapy (BCT) were randomized between a 26 Gy boost dose and a 16 Gy boost dose, with local recurrence as primary and cosmetic outcome (CO) as secondary endpoint. Data of the YBT was used to investigate which factors are related with worse cosmetic outcome after BCT. MethodsFrom 2004 to 2011, 2421 cT1-2N0-2a breast cancer patients were randomized. CO was scored subjectively by the patient and physician, and objectively using BCCT.core: at baseline, one and four years after treatment. Associations between potential risk factors for worse cosmetic outcome, based on the objective BCCT.core, were investigated using a proportional odds model. ResultsAt four years, CO was significantly better in the standard boost group for all three scoring methods (satisfied CO ±65% vs 55%). A photon boost, high boost dose, poor cosmesis before radiation therapy, large boost volume and adjuvant chemotherapy significantly deteriorated CO. ConclusionImportant risk factors for worse CO were the use of a photon boost instead of an electron boost, a high boost dose, cosmesis at baseline, adjuvant chemotherapy and boost volume. These results can be used to define strategies aimed at improving CO.

5 - The influence of the boost dose on cosmetic outcome after breast conserving therapy: Results of the Young Boost Trial

5 - The influence of the boost dose on cosmetic outcome after breast conserving therapy: Results of the Young Boost Trial

Factors associated with patient-reported cosmetic outcome in the Young Boost Breast Trial

PurposeTo investigate which factors are related to patient reported cosmetic outcome (PRCO) after breast conserving therapy. MethodsFrom 2004 to 2011, 2421 cT1-2N0-2a breast cancer patients were randomised in the Young Boost Trial between a 16 and a 26Gy boost to the tumour bed. Cosmesis was scored subjectively by the patient and physician, and objectively using BCCT.core, at baseline, one and four years after treatment. Presence of fibrosis, QoL and rib pain at four years were also scored. Data were complete for 864 patients. The relation between the separate components was investigated using a proportional odds model. ResultsOf the 7 BCCT.core parameters, the distance from nipple to inframammary fold and the length of the breast contour were significantly related to the overall PRCO at four years. Patients with more fibrosis and poorer QoL scored their cosmesis worse, while rib pain was not related. The agreement between the different scores was low (kappa 0.26–0.42). ConclusionThe distance from nipple to inframammary fold, the length of the breast contour and the severity of fibrosis were the main factors related to patient-reported cosmetic outcome. Patients with better QoL scored their cosmesis better.

PO-0674: Factors influencing patient reported cosmetic outcome: results of the Young Boost Trial

PO-0674: Factors influencing patient reported cosmetic outcome: results of the Young Boost Trial

Abstract P4-11-01: Factors influencing patient reported cosmetic outcome: Results of the Young Boost trial

Abstract Purpose The Young Boost trial (YBT), a multicenter RCT (NCT00212121), investigates whether a higher boost dose leads to a lower recurrence rate in young patients treated with breast conserving therapy. Cosmetic outcome is the secondary objective. The aim of the current analysis is to investigate which factors influence the patients' opinion about cosmesis. Patients & methods From 2004-2011, 2421 breast cancer patients ≤ 50 yrs were included in The Netherlands, France, and Germany. All patients were treated with lumpectomy, followed by 50 Gy whole breast irradiation. Patients were randomized to receive a standard 16 Gy (n=1211) or a high 26 Gy boost (n=1210) to the tumour bed. Cosmesis was scored prior to radiation therapy, at 1 year and at 4 years follow-up according to the following three scoring systems: 1. BCCT.core: Digital photographs were analyzed using a software program to extract an overall cosmetic score: excellent, good, fair or poor. This score is based on symmetry, skin colour and scar visibility. The 7 features of symmetry in the BCCT.core program are:  pBRA (nipple position)  pLBC (level of lower breast contour)  pUNR (level of nipple)  pBCE (distance from nipple to inframammary fold)  pBCD (length of breast contour)  pBAD (area of the breast)  pBOD (non overlapping area between left and right breast) 2. Physician's score: excellent, good, fair or poor 3. Patients' score using a validated patient's questionnaire about the breast appearance, including an overall score: very satisfied, satisfied, not dissatisfied, dissatisfied or very dissatisfied. Very satisfied and satisfied were grouped as satisfactory. At the same time points fibrosis was scored by the physician on a 4-point scale. The presence of rib pain was scored as well. First, we analyzed the correlation between the 3 scoring methods. Secondly, we analyzed the 7 features of BCCT.core in a proportional odds model, to investigate which parameters are related to the patients' opinion about cosmesis at 4 years. Also, we analyzed whether fibrosis score or presence of rib pain are related to the patients' opinion on cosmetic outcome. Results At 4 years, the agreement between the different scoring methods was low. The agreement between the physician and the patient was the highest (kappa 0.42), compared to the agreement between the patient and BCCT.core (kappa 0.26) or between BCCT.core and physician (kappa 0.39). Of the 7 BCCT.core parameters, pBCE and pBCD are significantly related to patients' score at 4 years (table 1). Further, patients with any fibrosis interpret their cosmesis worse than patients without fibrosis, even when the objective score (i.e. BCCT.core) was similar. This effect was larger by increasing grade of fibrosis. The presence of rib pain had no influence. Conclusion The patients 'opinion on cosmetic outcome was significantly related to the score on pBCE and pBCD, and to the severity of fibrosis. The correlation between objective score and subjective scores (patient and physician) was low. oddsppBRA1.3190.150pLBC1.1420.477pUNR1.0560.779pBCE1.1770.040pBCD1.7180.041pBAD0.8560.505pBOD1.0380.812 Citation Format: Brouwers P, van Werkhoven E, van Loon J, Leer JW, Poortmans P, Bartelink H, Boersma L. Factors influencing patient reported cosmetic outcome: Results of the Young Boost trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-11-01.

OC-0389: The influence of the boost dose on cosmetic outcome after breast conserving therapy: results of the Young Boost Trial

OC-0389: The influence of the boost dose on cosmetic outcome after breast conserving therapy: results of the Young Boost Trial

Multiinstitutional study on target volume delineation variation in breast radiotherapy in the presence of guidelines

Purpose This study aims to determine magnitude, causes and consequences of post-operative breast tumour target volume delineation variation among radiation oncologists in the presence of guidelines. Materials and methods Excision cavities, CTVs and PTVs of eight breast cancer patients were delineated on CT scans by 13 Dutch radiation oncologists (observers) from 12 Dutch institutes participating in the international Young Boost Trial. Delineated volumes and conformity indices were determined. CTV delineation variation (SD) was determined for anatomically relevant regions. Non-parametric statistics were performed to establish effects of observers, patient characteristics and regions on delineation variation. Results Even in the presence of delineation guidelines considerable delineation variation is present (0.24 < SD < 1.22 cm). Presence of clips or seroma reduced interobserver variation (0.24 < SD < 0.62 cm). Region-specific analysis showed distinct regions of higher variability per patient. This could not always be ascribed to anatomical features, suggesting interobserver variation is not solely due to lack of image quality. Conclusions In this study, interobserver delineation variation in breast tumour target volume delineation is larger than, e.g. setup inaccuracies and results from limited reliable visual guidance as well as interpretation differences between observers, despite guidelines. Reduction of delineation variation is essential in view of current developments in planning techniques, particularly for External Partial Breast Irradiation.

The influence of the use of CT-planning on the irradiated boost volume in breast conserving treatment

Background and purpose The purpose of this study was to investigate the effect of CT-based delineation and planning on the irradiated boost volume. For this specific purpose we used the data as derived from 2 prospective phase III randomised trials. Patients and methods Data from 1331 patients (⩽50 years) were analyzed with a reported boost volume from a simulation-based treatment plan (EORTC boost vs no boost trial, n = 922), and a CT-scan-based treatment plan (Young Boost Trial, n = 409) group. Tumour diameter, irradiation technique (photons vs electrons), lumpectomy size, and age were used as covariates. Results Median V 95% in the conventional simulation-based treatment plans was 99 cc (range 9–628) for photons and was 98 cc (13–651) for electrons, whereas in the CT-planned patients, these figures were 178 cc (37–2699) and 150 cc (43–1272), respectively. Multivariable analysis showed an association of the irradiated boost volume with tumour size ( p < 0.0067), lumpectomy size ( p < 0.0002), and boost technique ( p < 0.0004). The use of a CT-scan for volume delineation and treatment planning remained significant ( p < 0.0001). Conclusions The use of a CT-scan for delineation and treatment planning led to a significant increase of the irradiated boost volume by a factor of 1.5–1.8, compared to conventional simulator-based plans.