Clinical Utility of the 12-Gene DCIS Score Assay: Impact on Radiotherapy Recommendations for Patients with Ductal Carcinoma In Situ.

OBJECTIVE: The aim of this study was to determine the impact of the results of the 12-gene DCIS Score assay on (i) radiotherapy recommendations for patients with pure ductal carcinoma in situ (DCIS) following breast-conserving surgery (BCS), and (ii) patient decisional conflict and state anxiety. METHODS: Thirteen sites across the US enrolled patients (March 2014-August 2015) with pure DCIS undergoing BCS. Prospectively collected data included clinicopathologic factors, physician estimates of local recurrence risk, DCIS Score results, and pre-/post-assay radiotherapy recommendations for each patient made by a surgeon and a radiation oncologist. Patients completed pre-/post-assay decisional conflict scale and state-trait anxiety inventory instruments. RESULTS: The analysis cohort included 127 patients: median age 60 years, 80 % postmenopausal, median size 8 mm (39 % ≤5 mm), 70 % grade 1/2, 88 % estrogen receptor-positive, 75 % progesterone receptor-positive, 54 % with comedo necrosis, and 18 % multifocal. Sixty-six percent of patients had low DCIS Score results, 20 % had intermediate DCIS Score results, and 14 % had high DCIS Score results; the median result was 21 (range 0-84). Pre-assay, surgeons and radiation oncologists recommended radiotherapy for 70.9 and 72.4 % of patients, respectively. Post-assay, 26.4 % of overall recommendations changed, including 30.7 and 22.0 % of recommendations by surgeons and radiation oncologists, respectively. Among patients with confirmed completed questionnaires (n = 32), decision conflict (p = 0.004) and state anxiety (p = 0.042) decreased significantly from pre- to post-assay. CONCLUSIONS: Individualized risk estimates from the DCIS Score assay provide valuable information to physicians and patients. Post-assay, in response to DCIS Score results, surgeons changed treatment recommendations more often than radiation oncologists. Further investigation is needed to better understand how such treatment changes may affect clinical outcomes.

The current clinical value of the DCIS Score.

The management of ductal carcinoma in situ (DCIS) can be controversial. Widespread adoption of mammographic screening has made DCIS a more frequent diagnosis, and increasingly smaller, lower-grade lesions are being detected. DCIS is commonly treated with breast-conserving surgery and radiation. However, there is greater recognition that acceptable cancer control outcomes can be achieved for some patients with breast-conserving surgery alone, with radiotherapy reserved for those at higher risk of in-breast recurrence. The primary clinical dilemma is that there are currently no reliable clinicopathologic features that accurately predict which patients will have a recurrence, but risk stratification is an area of active research. Molecular profiling has the potential to assess recurrence risk based on the individual patient's tumor biology and guide treatment decisions. The DCIS Score is a 12-gene assay intended to support personalized treatment planning for patients with DCIS following local excision. It provides information on local failure risk independent of traditional clinicopathologic features. Our group of expert breast surgeons and radiation oncologists met in December 2013 at the San Antonio Breast Cancer Symposium to discuss current controversies in DCIS management and determine the potential value of the DCIS Score in managing these situations. We concluded that the DCIS Score provides clinically relevant information about personal risk that can guide patient discussions and facilitate shared decision making.

Clinical evaluation of interfractional variations for whole breast radiotherapy using 3-dimensional surface imaging.

PURPOSE: To evaluate the impact of 3-dimensional (3D) surface imaging on daily patient setup for breast radiotherapy. MATERIALS AND METHODS: Fifty patients undergoing treatment for whole breast radiotherapy were setup daily using an AlignRT system (VisionRT, London, UK) for 3D surface-based alignment. Daily alignments were performed against a reference surface topogram and shifts from skin marks were recorded daily. This investigation evaluated the following: (1) the performance of the surface-based imaging system for daily breast alignment; (2) the absolute displacements between setup with skin marks and setup with the surface-based imaging system; and (3) the dosimetric effect of daily alignments with skin marks versus surface-based alignments. RESULTS: Displacements from 1258 treatment fractions were analyzed. Sixty percent of those fractions (749) were reviewed against MV portal imaging in order to assess the performance of the AlignRT system. Daily setup errors were given as absolute displacements, comparing setup marks against shifts determined using the surface-based imaging system. Averaged over all patients, the mean displacements were 4.1 ± 2.6 mm, 2.7 ± 1.4 mm, and 2.6 ± 1.2 mm in the anteroposterior (AP), superoinferior (S/I), and left-right (L/R) directions, respectively. Furthermore, the standard deviation of the random error (σ) was 3.2 mm, 2.2 mm, and 2.2 mm in the A/P, S/I, and L/R directions, respectively. CONCLUSIONS: Daily alignment with 3D surface imaging was found to be valuable for reducing setup errors when comparing with patient alignment from skin marks. The result of the surface-based alignments specifically showed that alignment with skin marks was noticeably poor in the anteroposterior directions. The overall dosimetric effect of the interfractional variations was small, but these variations showed a potential for increased dose deposition to both the heart and lung tissues. Although these interfractional variations would not negatively affect the quality of patient care for whole breast radiotherapy, it may require an increase in PTV margin, especially in cases of partial breast irradiation.

Investigation of accelerated partial breast patient alignment and treatment with helical tomotherapy unit.

PURPOSE: To determine the precision of megavoltage computed tomography (MVCT)-based alignment of the seroma cavity for patients undergoing partial breast irradiation; and to determine whether accelerated partial breast irradiation (APBI) plans can be generated for TomoTherapy deliveries that meet the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 protocol guidelines for target coverage and normal tissue dose limitations. METHODS AND MATERIALS: We obtained 50 MVCT images from 10 patients. An interuser study was designed to assess the alignment precision. Using a standard helical and a fixed beam prototype ("topotherapy") optimizer, two APBI plans for each patient were developed. RESULTS: The precision of the MVCT-based seroma cavity alignment was better than 2 mm if averaged over the patient population. Both treatment techniques could be used to generate acceptable APBI plans for patients that fulfilled the recommended NSABP B-39/RTOG-0413 selection criteria. For plans of comparable treatment time, the conformation of the prescription dose to the target was greater for helical deliveries, while the ipsilateral lung dose was significantly reduced for the topotherapy plans. CONCLUSIONS: The inherent volumetric imaging capabilities of a TomoTherapy Hi-Art unit allow for alignment of patients undergoing partial breast irradiation that is determined from the visibility of the seroma cavity on the MVCT image. The precision of the MVCT-based alignment was better than 2 mm (+/-standard deviation) when averaged over the patient population. Using the NSABP B-39/RTOG-0413 guidelines, acceptable APBI treatment plans can be generated using helical- or topotherapy-based delivery techniques.

A prospective pilot study of curative-intent stereotactic body radiation therapy in patients with 5 or fewer oligometastatic lesions.

BACKGROUND: It is hypothesized that oligometastatic disease represents a state of potentially curable, limited metastases. Stereotactic body radiation therapy (SBRT) is an option for patients who are not amenable to or do not want resection. METHODS: From 2001 to 2006, 121 patients with < or =5 detectable metastases were enrolled in 2 prospective studies that used curative-intent SBRT. Most patients were treated with 10 fractions of 5 Gray. Stereotactic radiosurgery was offered to patients with brain metastases. RESULTS: The 2-year overall survival (OS), progression-free survival (PFS), local control (LC), and distant control (DC) rates were 50%, 26%, 67%, and 34%, respectively; and the respective 4-year rates values were 28%, 20%, 60%, and 25%. A greater net tumor volume predicted significantly worse OS, PFS, LC, and DC. Patients with breast cancer fared significantly better with respect to OS, PFS, LC, and DC; and patients with adrenal metastases had significantly worse OS, PFS, and DC despite the small number of such patients enrolled. Neither the number of metastatic lesions nor the number of organs involved was a significant predictor of outcome. Among 45 patients who remained alive at the last follow-up, 29 patients had no evidence of disease, including 23 patients with > or =2 years of follow-up. CONCLUSIONS: Oligometastatic disease is a potentially curable state of distant cancer spread. In this hypothesis-generating analysis, patients with less volume burden of their metastatic disease and those with primary breast cancer fared better. SBRT delivered with curative intent in patients with limited metastases should be investigated further. The Southwest Oncology Group is developing a prospective protocol to treat women who have limited breast cancer metastases with SBRT.

Evaluation of two tomotherapy-based techniques for the delivery of whole-breast intensity-modulated radiation therapy.

PURPOSE: To evaluate two different techniques for whole-breast treatments delivered using the Hi-ART II tomotherapy device. METHODS AND MATERIALS: Tomotherapy uses the standard rotational helical delivery. Topotherapy uses a stationary gantry while delivering intensity-modulated treatments. CT scans from 5 breast cancer patients were used. The prescription dose was 50.4 Gy. RESULTS: On average, 99% of the target volume received 95% of prescribed dose with either technique. If treatment times are restricted to less than 9 min, the average percentage ipsilateral lung receiving > or =20 Gy was 22% for tomotherapy vs. 10% for topotherapy. The ipsilateral lung receiving > or =50.4 Gy was 4 cc for tomotherapy vs. 27 cc for topotherapy. The percentage of left ventricle receiving > or =30 Gy was 14% with tomotherapy vs. 4% for topotherapy. The average doses to the contralateral breast and lung were 0.6 and 0.8 Gy, respectively, for tomotherapy vs. 0.4 and 0.3 Gy for topotherapy. CONCLUSIONS: Tomotherapy provides improved target dose homogeneity and conformality over topotherapy. If delivery times are restricted, topotherapy reduces the amount of heart and ipsilateral lung volumes receiving low doses. For whole-breast treatments, topotherapy is an efficient technique that achieves adequate target uniformity while maintaining low doses to sensitive structures.