George Papadatos

Prediction of Local Recurrence, Distant Metastases, and Death After Breast-Conserving Therapy in Early-Stage Invasive Breast Cancer Using a Five-Biomarker Panel

PURPOSEnTo determine the clinical utility of intrinsic molecular phenotype after breast-conserving therapy (BCT) with lumpectomy and whole-breast irradiation with or without a cavity boost.nnnPATIENTS AND METHODSnFour hundred ninety-eight patients with invasive breast cancer were enrolled into a randomized trial of BCT with or without a tumor bed radiation boost. Tumors were classified by intrinsic molecular phenotype as luminal A or B, HER-2, basal-like, or unclassified using a five-biomarker panel: estrogen receptor, progesterone receptor, HER-2, CK5/6, and epidermal growth factor receptor. Kaplan-Meier and Cox proportional hazards methodology were used to ascertain relationships to ipsilateral breast tumor recurrence (IBTR), locoregional recurrence (LRR), distant disease-free survival (DDFS), and death from breast cancer.nnnRESULTSnMedian follow-up was 84 months. Three hundred ninety-four patients were classified as luminal A, 23 were luminal B, 52 were basal, 13 were HER-2, and 16 were unclassified. There were 24 IBTR (4.8%), 35 LRR (7%), 47 distant metastases (9.4%), and 37 breast cancer deaths (7.4%). The overall 5-year disease-free rates for the whole cohort were: IBTR 97.4%, LRR 95.6%, DDFS 92.9%, and breast cancer-specific death 96.3%. A significant difference was observed for survival between subtypes for LRR (P = .012), DDFS (P = .0035), and breast cancer-specific death (P = .0482), but not for IBTR (P = .346).nnnCONCLUSIONnThe 5-year and 10-year survival rates varied according to molecular subtype. Although this approach provides additional information to predict time to IBTR, LRR, DDFS, and death from breast cancer, its predictive power is less than that of traditional pathologic indices. This information may be useful in discussing outcomes and planning management with patients after BCT.

Prediction of outcome of early ER+ breast cancer is improved using a biomarker panel, which includes Ki-67 and p53

Background:The aim of this study is to determine whether immunohistochemical (IHC) assessment of Ki67 and p53 improves prognostication of oestrogen receptor-positive (ER+) breast cancer after breast-conserving therapy (BCT). In all, 498 patients with invasive breast cancer from a randomised trial of BCT with or without tumour bed radiation boost were assessed using IHC.Methods:The ER+ tumours were classified as ‘luminal A’ (LA): ER+ and/or PR+, Ki-67 low, p53−, HER2− or ‘luminal B’ (LB): ER+ and/or PR+and/or Ki-67 high and/or p53+ and/or HER2+. Kaplan–Meier and Cox proportional hazards methodology were used to ascertain relationships to ispilateral breast tumour recurrence (IBTR), locoregional recurrence (LRR), distant metastasis-free survival (DMFS) and breast cancer-specific survival (BCSS).Results:In all, 73 patients previously LA were re-classified as LB: a greater than four-fold increase (4.6–19.3%) compared with ER, PR, HER2 alone. In multivariate analysis, the LB signature independently predicted LRR (hazard ratio (HR) 3.612, 95% CI 1.555–8.340, P=0.003), DMFS (HR 3.023, 95% CI 1.501–6.087, P=0.002) and BCSS (HR 3.617, 95% CI 1.629–8.031, P=0.002) but not IBTR.Conclusion:The prognostic evaluation of ER+ breast cancer is improved using a marker panel, which includes Ki-67 and p53. This may help better define a group of poor prognosis ER+ patients with a greater probability of failure with endocrine therapy.

The impact of breast cosmetic and functional outcomes on quality of life: long-term results from the St. George and Wollongong randomized breast boost trial

The aims of this study were to evaluate the impact of cosmetic and functional outcomes after breast-conserving surgery (BCS) and radiation on quality of life (QOL). In this exploratory analysis; baseline, 5 and 10xa0years data of patient’s assessment of breast cosmesis, arm swelling/pain, limitation of movement, loss of feeling in fingers and breast sensitivity/tenderness were dichotomized and their impact on QOL (QLQ-C30) were assessed. Multivariable modelling was also performed to assess associations with QOL. The St. George and Wollongong randomized trial randomized 688 patients into the boost and no boost arms. 609, 580, and 428 patients had baseline, 5 and 10xa0years cosmetic data available, respectively. Similar numbers had the various functional assessments in the corresponding period. By univariate analysis, cosmesis and a number of functional outcomes were highly associated with QOL. Adjusted multivariate modelling showed that cosmesis remained associated with QOL at 5 and 10xa0years. Breast sensitivity, arm pain, breast separation, age and any distant cancer event were also associated with QOL on multivariate modelling at 10xa0years. This study highlights the importance of maintaining favorable cosmetic and functional outcomes following BCS. In addition, the clinically and statistically significant relationship between functional outcomes and QOL shows the importance for clinicians and allied health professionals in identifying, discussing, managing, and limiting these effects in women with breast cancer in order to maintain QOL.

Interobserver Variability in Clinical Target Volume Delineation in Tangential Breast Irradiation: a Comparison between Radiation Oncologists and Radiation Therapists

AIMSnThe delineation of target volumes has been radiation oncologist led. If radiation therapists were to undertake this task, work processes may be more efficient and the skills set of radiation therapy staff broadened. This study was undertaken to quantify interobserver variability of breast target volumes between radiation oncologists and radiation therapists.nnnMATERIALS AND METHODSnThe planning computed tomography datasets of 30 patients undergoing tangential breast radiotherapy were utilised. Four radiation oncologists and four radiation therapists independently contoured the clinical target volume (CTV) of the breast on planning computed tomography using a written protocol. The mean CTV volumes and the mean distance between centres of volume (COV) were determined for both groups to determine intergroup variation. Each of the radiation oncologists readings in turn has been used as the gold standard and compared with that of the radiation therapists. The concordance index for each patients CTV was determined relative to the gold standard for each group. A paired t-test was used for statistical comparison between the groups. An intraclass correlation coefficient was calculated to measure the agreement between the radiation oncologist and radiation therapist groups.nnnRESULTSnThe mean concordance index was 0.81 for radiation oncologists and 0.84 for radiation therapists. The intraclass correlation coefficient for the mean volume was 0.995 (95% confidence interval 0.981-0.998) between radiation oncologist- and radiation therapist-contoured volumes. The intraclass correlation for the mean difference between radiation oncologists and radiation therapists COV was 0.999 (95% confidence interval 0.999-1.000).nnnCONCLUSIONSnInterobserver variability between radiation oncologists and radiation therapists was found to be low. Radiation therapists could potentially assume the role of CTV voluming for breast radiotherapy provided a standardised contouring protocol is in place.

Women’s choice between sentinel lymph node biopsy and axillary clearance

Purpose: To determine whether women would choose sentinel lymph node biopsy (SLNB) or axillary clearance (AC) for breast cancer treatment when they are given a single choice based on clear information about morbidity and mortality.

Hypofractionated versus conventionally fractionated radiotherapy for ductal carcinoma in situ (DCIS) of the breast

Hypofractionated radiotherapy (RT) in the setting of early invasive breast cancer has been shown to have similar local control rates and cosmetic outcomes as conventionally fractionated RT. This study compares ipsilateral recurrence rates between hypofractionated and conventional RT, with and without a boost. The effect of hypofractionated RT and chest wall separation (CWS) on cosmetic outcome was also assessed.

The impact of imaging modality (CT vs MRI) and patient position (supine vs prone) on tangential whole breast radiation therapy planning

PURPOSEnThe purpose of this study was to evaluate the impact of magnetic resonance imaging (MRI) versus computed tomography (CT)-derived planning target volumes (PTVs), in both supine and prone positions, for whole breast (WB) radiation therapy.nnnMETHODS AND MATERIALSnFour WB radiation therapy plans were generated for 28 patients in which PTVs were generated based on CT or MRI data alone in both supine and prone positions. A 6-MV tangential intensity modulated radiation therapy technique was used, with plans designated as ideal, acceptable, or noncompliant. Dose metrics for PTVs and organs at risk were compared to analyze any differences based on imaging modality (CT vs MRI) or patient position (supine vs prone).nnnRESULTSnWith respect to imaging modality 2/11 whole breast planning target volume (WB_PTV) dose metrics (percentage of PTV receiving 90% and 110% of prescribed dose) displayed statistically significant differences; however, these differences did not alter the average plan compliance rank. With respect to patient positioning, the odds of having an ideal plan versus a noncompliant plan were higher for the supine position compared with the prone position (P = .026). The minimum distance between the seroma cavity planning target volume (SC_PTV) and the chest wall was increased with prone positioning (P < .001, supine and prone values 1.1 mm and 8.7 mm, respectively). Heart volume was greater in the supine position (P = .005). Heart doses were lower in the supine position than prone (P < .01, mean doses 3.4 ± 1.55 Gy vs 4.4 ± 1.13 Gy for supine vs prone, respectively). Mean lung doses met ideal dose constraints in both positions, but were best spared in the prone position. The contralateral breast maximum dose to 1cc (D1cc) showed significantly lower doses in the supine position (P < .001, 4.64 Gy vs 9.51 Gy).nnnCONCLUSIONSnPlanning with PTVs generated from MRI data showed no clinically significant differences from planning with PTVs generated from CT with respect to PTV and doses to organs at risk. Prone positioning within this study reduced mean lung dose and whole heart volumes but increased mean heart and contralateral breast doses compared with supine.

Comparison of Magnetic Resonance Imaging and Computed Tomography for Breast Target Volume Delineation in Prone and Supine Positions

PURPOSEnToxa0determine whether T2-weighted MRI improves seroma cavity (SC) and whole breast (WB) interobserver conformity for radiation therapy purposes, compared with the gold standard of CT, both in the prone and supine positions.nnnMETHODS AND MATERIALSnEleven observers (2 radiologists and 9 radiation oncologists) delineated SC and WB clinical target volumes (CTVs) on T2-weighted MRI and CT supine and prone scans (4 scans per patient) for 33 patient datasets. Individual observers volumes were compared using the Dice similarity coefficient, volume overlap index, center of mass shift, and Hausdorff distances. An average cavity visualization score was also determined.nnnRESULTSnImaging modality did not affect interobserver variation for WB CTVs. Prone WB CTVs were larger in volume and more conformal than supine CTVs (on both MRI and CT). Seroma cavity volumes were larger on CT than on MRI. Seroma cavity volumes proved to be comparable in interobserver conformity in both modalities (volume overlap index of 0.57xa0(95% Confidence Interval (CI) 0.54-0.60) for CT supine and 0.52xa0(95% CI 0.48-0.56) for MRI supine, 0.56xa0(95% CI 0.53-0.59) for CT prone and 0.55xa0(95% CI 0.51-0.59) for MRI prone); however, after registering modalities together the intermodality variation (Dice similarity coefficient of 0.41xa0(95% CI 0.36-0.46) for supine and 0.38xa0(0.34-0.42) for prone) was larger than the interobserver variability for SC, despite the location typically remaining constant.nnnCONCLUSIONSnMagnetic resonance imaging interobserver variation was comparable to CT for the WB CTV and SC delineation, in both prone and supine positions. Although the cavity visualization score and interobserver concordance was not significantly higher for MRI than for CT, the SCs were smaller on MRI, potentially owing to clearer SC definition, especially on T2-weighted MR images.

Outcomes of Ethnic Minority Groups with Node-Positive, Non-Metastatic Breast Cancer in Two Tertiary Referral Canters in Sydney, Australia

Purpose There is a lack of information in ethnic minority groups with regard to presentation and treatment of early node-positive breast cancer. We carried out a retrospective study of patients referred to two tertiary cancer centers in South Western Sydney, both of which serve a high proportion of this ethnic minority population. Patients and methods Women who had pathologically node-positive non-metastatic breast cancer (T1-3, N1-3, M0) diagnosed between 2003 and 2006 were studied, with variables of interest being tumor size, number of positive nodes, histological grade, hormone receptor status, age at diagnosis, country of birth and treatment. We compared the Asian and Western subgroups with regard to tumor characteristics, treatment and clinical outcomes. Results A total of 652 eligible patients were identified, with a median follow-up of 6.1 years. Women with Asian backgrounds (nu200a=u200a125, 20%) were significantly younger at presentation (48 years versus 55 years, p-value <0.0001) and more likely to undergo mastectomy (53% versus 39%, p-value 0.0009) and chemotherapy (86% versus 72%, p-value 0.0063) than their non-Asian counterparts. Tumor stage, grade and receptor status were not statistically different between these two groups. There were also no differences in disease-free survival and overall survival, with medians of 12.7 and 14.8 years respectively. Conclusion Women of Asian background are younger at diagnosis, which may reflect population epidemiology and likely results in higher uptake of chemotherapy. Higher mastectomy rates may be influenced by cultural factors. Future research is warranted to investigate potential differences in tumor biology, psychosocial, economic and cultural factors.

SU‐E‐J‐175: Comparison of Prone and Supine MRI Sequences for the Purpose of Radiotherapy Treatment Planning for Breast Cancer

Purpose: The delineation of treatment volumes for breast cancer radiotherapy utilising standard CT images is associated with significant inter‐observer variability. It has been proposed that MRI with improved quality soft tissue definition may reduce this inter‐observer variability. The purpose of this study was to determine the optimum set‐up and sequence for MRI‐defined radiotherapy volume delineation. Methods: Six observers (2 radiologists, 4 radiation oncologists) were asked to score MRI quality for the purposes of radiotherapy delineation using the following scoring criteria where 0 — margin not recognisable (inability to discriminate) through to a score of 3, when margins were distinct (excellent discrimination). Supine breast MRI was achieved using a foam bridge to support a surface coil without touching the patient surface. T1 and T2 sequences were compared for both 1.5Tesla (1.5T) and 3T MRIs for a volunteer. Prone breast images were obtained using a 4 channel breast coil. Supine and prone breast MRIs were compared for T1 and T2 sequences for 3T for 2 volunteers. Results: Supine breast images were shown to be acceptable for the purpose of radiotherapy delineation with the 3T 2D T2 turbo spin echo sequences scoring 2s (fair discrimination) and 3s (excellent discrimination), most optimal. The prone 3D T1 gradient echo was the optimum of the supine and prone 3T images, however results were inconsistent with this sequence receiving a score of zero from one observer. Conclusion: Supine breast MRI scans can be achieved for the purpose of radiotherapy delineation. Scoring between observers was inconsistent when comparing scan sequences. This work has been supported by project grant 1033237 from Cancer Australia and The National Breast Cancer Foundation