J.S. Wong

Is radiation alone adequate treatment to the axilla for patients with limited axillary surgery? implications for treatment after a positive sentinel node biopsy

PURPOSEnTo estimate the possible efficacy of axillary radiation therapy (AXRT) following a positive sentinel node biopsy (SNB), we evaluated the risk of regional nodal failure (RNF) for patients with clinical Stage I or II, clinically node-negative invasive breast cancer treated with either no dissection or a limited dissection (LD) defined as removal of 5 nodes or less followed by AXRT.nnnMATERIALS AND METHODSnFrom 1978 to 1987, 292 patients underwent AXRT in the absence of axillary dissection; 126 underwent AXRT following LD. The median dose to the axilla was 46 Gy. The median dose to the supraclavicular fossa was 45 Gy. Among patients found to have positive nodes on LD, adjuvant chemotherapy and tamoxifen were administered to 81% and 7% of subjects, respectively. All patients had potential 8-year follow-up.nnnRESULTSnSix of the 418 patients (1. 4%) developed RNF as a first site of failure within 8 years. Among these 6 patients (1.4%) with RNF as the first site of failure, 4 had simultaneous distant and regional recurrences; and 2 had isolated axillary failures. Three of the 292 patients (1%) with no axillary dissection, none of 84 patients with pathologically negative nodes and 3 of 42 patients (7%) with pathologically involved nodes had RNF as a first site of failure. Radiation pneumonitis developed in 5 patients (1.2%), brachial plexopathy in 5 (1.2%) and arm edema in 4 (1.2%). In all cases, radiation pneumonitis and brachial plexopathy were transient.nnnCONCLUSIONnThese results imply that AXRT may be an effective and safe alternative to completion dissection for treatment of the axilla following a positive SNB. Further studies comparing these two options in specific patient subgroups are needed.

Can Axillary Node Dissection Be Omitted in a Subset of Patients with Low Local and Regional Failure Rates

Abstract:u2002 Axillary node dissection (ALND) is the standard of care for patients who have a positive sentinel lymph node (SLN) on sentinel lymph node biopsy (SLNB). We sought to identify a low‐risk patient population with positive SLN that may not need cALND. We analyzed SLNB for breast cancer at our institutions between 1999 and 2007. We identified 130 patients who had a positive SLN but did not undergo completion ALND. We evaluated clinical data, adjuvant treatment patterns and intermediate locoregional and distant events. The median patient age was 50; 19% had N0(i+) disease, 53% had micrometastatic (N1mi) disease, and 28% had macrometastasis. Eighty‐eight percent of patients underwent radiation therapy; 66 patients (51%) had documented nodal radiation (of these 50 were treated with three fields and 14 with high tangents. Local recurrence in the breast occurred in two patients (2%) and nine patients (7%) developed distant metastases; there were no axillary/nodal recurrences. In this highly selected group of patients who had a positive SLNB but did not undergo cALND, we observed no axillary recurrences.

Optimal gantry angles and field sizes in kilovoltage cone-beam tomosynthesis for set-up of women with breast cancer undergoing radiotherapy treatment

Optimal beam geometry for kilovoltage cone-beam tomosynthesis (CB-TS) imaging for the set-up of 20 patients with breast cancer was analyzed and presented for prone and supine scenarios. Gantry angles and field sizes that allow maximum clearance and minimum dose to normal organs from kilovoltage imaging were determined for medial and lateral arcs. Optimal CB-TS arc span may vary depending on patient geometry, particularly on the separation between the cavity and the chest wall. CB-TS arc angles 40 degrees were found to be optimal for the cavity to chest wall separation d>3 cm for supine set-up and d>7 cm for prone set-up. Maximum required jaw openings were 20 x 14 cm(2). Recommendations are provided for clinical implementation of CB-TS imaging for breast cancer patients.

Clinical application of Varian OBI CBCT system and dose reduction techniques in breast cancer patients setup

PURPOSEnTo characterize the standard modes of Varian on board imaging (OBI) v1.4 system and identify techniques to further optimize imaging parameters, in particular, for breast treatment setup.nnnMETHODSnA male anthropomorphic torso phantom was used for image quality assessment and a simpler thorax phantom for dose measurements. Both phantoms had artificial breasts attached. Doses were measured with an ion chamber in seven locations in the thorax and the breast. Evaluation of image quality was performed in terms of contrast-to-noise ratio (CNR) and in combination with the dose-to-contrast-to-noise (CNRD) parameter. The effect of kVp and mAs on the image quality, dose, and CNRD parameter was analyzed. In addition, image geometry with noncentral isocenter location with start and stop imaging angles adjusted for greater sparing of the contralateral breast was evaluated in terms of image quality and dose.nnnRESULTSnThe measurements showed doses between 0.02 and 1.6 cGy for the three full-fan modes and 0.6-3.2 cGy for half-fan modes. This is a reduction of over 80% and 30%-50% compared to OBI v.1.3 modes for full-fan and half-fan modes, respectively. The CNRD is the highest for both low dose modes (low dose thorax and low dose head). Optimal ranges for an averaged sized thorax are tube voltages not higher than 100 kVp and current-time products between 100 and 400 mAsu2009. For the contralateral breast and lung, a dose less than 0.03 cGy per scan was measured for the optimized image geometry with the noncentral isocenter location.nnnCONCLUSIONSnThe OBI v1.4 system allows for imaging with a larger variety of imaging parameters compared to previous OBI v1.3 systems. The largest doses (up to 4 cGy) were measured in a phantom when OBI v1.4 system was used for imaging with half-fan modes. Using full-fan modes resulted in the doses less than 1.6 cGy. Further decrease in dose may be achieved by reducing mAs while preserving acceptable image quality. Organ specific sparing (e.g., contralateral breast) may be achieved by proper selection of the start and stop angles. For thorax imaging, the use of Low Dose Thorax mode is recommended.

SU‐E‐J‐57: Clinical Protocol for DTS‐Based APBI Setup: Optimal Data Acquisition, Reconstruction and Registration Parameters Using Varian DTS Software

Purpose: Digital tomosynthesis (DTS) was evaluated as an alternative to CBCT for minimizing possibility of collisions and reducing imaging dose. While feasibility of DTS was demonstrated for APBI patient setup, clinical implementation has not been optimized for this technique. This work characterizes data acquisition/registration parameters and establishes clinical protocol for accurate setup using: Varian OBI system for data acquisition; and non‐clinical Varian DTS software for DTS reconstruction/registration for APBI patient setup. Methods: Backprojection‐and‐deblurring algorithms were used for DTS volume reconstructions. DTS volume registrations were done manually and automatically (cross‐correlation). Subsequent triangulation on two short DTS arcs was done to improve registration accuracy. Software performance was evaluated on a breast phantom and nine breast cancer patients, under an IRB‐approved protocol. Parameters investigated include arc lengths, arc orientations, number of arcs, reconstruction slice spacing and other limiting factors relevant to clinical practice. Shifts determined from the registration of DTS volumes were compared to the shifts based on registration between planning CT and CBCT. The difference between these shifts was used to evaluate the software performance and accuracy. The findings were quantified and optimal parameters for clinical use of DTS technique were determined. Results: At least two arcs were necessary for accurate setup evaluation. Registration accuracy of 2 mm was achieved when reconstruction arc length was > 5 deg for clips with HU>1000; larger arc length (> 8 deg) was required for low HU clips. Optimal arc separation was found to be > 20 deg. Optimal arc length was determined to be 8–10 deg. No dependence on DTS slice spacing was found. Time required for DTS reconstruction was 10s– 45 s and it was less than 20s for registration. Conclusions: Optimal data acquisition/registration parameters were determined for DTS imaging utilized for APBI patient setup, and performance of the software was objectively quantified. This study is supported by grant from Varian Medical Systems Inc. and Kayes grant

Multidisciplinary Management of the Axilla in Patients with cT1-T2 N0 Breast Cancer Undergoing Primary Mastectomy: Results from a Prospective Single-Institution Series

BackgroundThe after mapping of the axilla: radiotherapy or surgery (AMAROS) trial concluded that for patients with cT1-2 N0 breast cancer and one or two positive sentinel lymph nodes (SLNs), axillary radiotherapy (AxRT) provides equivalent locoregional control and a lower incidence of lymphedema compared with axillary lymph node dissection (ALND). The study prospectively assessed how often ALND could be replaced by AxRT in a consecutive cohort of patients undergoing mastectomy for cT1-2 N0 breast cancer.MethodsIn November 2015, our multidisciplinary group agreed to omit routine intraoperative SLN evaluation for cT1-2 N0 patients undergoing upfront mastectomy and potentially eligible for postmastectomy radiation therapy (PMRT), including those 60xa0years of age or younger and those older than 60xa0years with high-risk features. Patients with one or two positive SLNs on final pathology were reviewed to determine whether PMRT including the full axilla was an appropriate alternative to ALND.ResultsFrom November 2015 to December 2016, 154 patients met the study criteria, and 114 (74%) formed the final study cohort. Intraoperative SLN evaluation was omitted for 76 patients (67%). Of these patients, 20 (26%) had one or two positive SLNs, and 14 of these patients received PMRTu2009+u2009AxRT as an alternative to ALND. Three patients returned for ALND, and three patients were observed. On univariate analysis, tumor size, LVI, number of positive lymph nodes, and receipt of chemotherapy were associated with receipt of PMRT.ConclusionsFor the majority of patients with one or two positive SLNs, ALND was avoided in favor of PMRTu2009+u2009AxRT. With appropriate multidisciplinary strategies, intraoperative evaluation of the SLN and immediate ALND can be avoided for patients meeting the AMAROS criteria and eligible for PMRT.

Poster Viewing AbstractProspective Assessment of Deep Inspiration Breath Hold Using 3-Dimensional Surface Tracking for Irradiation of Left-Sided Breast Cancer

Purpose: Deep inspiration breath hold (DIBH) is used to decrease cardiac irradiation during radiation therapy (RT) for breast cancer. The patients most likely to benefit and the impact on treatment time remain largely unknown. We sought to identify predictors for the use of DIBH and to quantify differences in dosimetry and treatment time using a prospective registry. Methods and materials: A total of 150 patients with left breast cancer were enrolled. All patients were simulated with both free breathing (FB) and DIBH. RT was delivered by either modality. Alternate scans were planned with useof deformable registration toinclude identical RTvolumes.DIBHpatientswere monitored by a real-time surface tracking system, AlignRT (Vision RT, Ltd, London, United Kingdom). Baseline characteristics and treatment times were compared by Fisher exact test and Wilcoxon rank sum test. Dosimetric endpoints were analyzed by Wilcoxon signed rank test, and linear regression identified predictors for change in mean heart dose (ΔMHD). Results: We treated 38 patients with FB and 110 with DIBH. FB patients were older, more likely to have heart and lung disease, and less likely to receive chemotherapy or immediate reconstruction (all Pb .05). Treatment times were not significantly different, but DIBH patients had greater variability in times (P = .0002). Of 146 evaluable patients,DIBH resulted inN20 cGy improvement in MHD in 107 patients but a N20 cGy increase in MHD in 14. Both MHD and lung V20 were significantly lower in DIBH than in paired FB plans. On multivariate analysis, younger age (4.18 cGy per year; P b .0001), higher body mass index (6.06 cGy/kg/m 2 ; P = .0018), and greater change in lung volumes (130 cGy/L; P = .003) were associated with greater ΔMHD.

Surgical margins and the risk of local-regional recurrence (LRR) following mastectomy for early-stage breast cancer.

95 Background: We sought to clarify the influence of a positive or close superficial or deep mastectomy margin on the risk of LRR. Methods: We reviewed the charts of 561 consecutive women who underwent mastectomy without radiation for newly diagnosed in situ or invasive breast cancer between 1998 and 2005. The study cohort consists of 167 of these women who had a positive or close (≤2 mm) superficial or deep surgical margin. LRR as the site of first recurrence (+/− simultaneous distant disease) and distant metastasis (DM) rates were calculated using the Kaplan-Meier method. The median age was 50 years. Forty-five (27%) had ductal carcinoma in situ (DCIS) only. Of the 122 women with invasive disease, 79% had T1, 18% T2, and 3% T3 tumors, and 25% had positive axillary nodes (range, 1-4; 68% 1 positive node). Twenty-nine (24%) of those with invasive disease had lymphovascular invasion. The superficial margin was positive in 61 (37%) and close in 69 (41%). The deep margin was positive in 28 (17%) and close in...

Commentary on Eccles et al.: Familial breast cancer: an investigation into the outcome of treatment for early stage disease

The authors have presented results of a carefully performed retrospective analysis of the treatment outcome of early-stage breast cancer patients, with and without a family history of breast cancer. The patients were gathered from several sources over a reasonably lengthy period, and include both women selected because of younger age at breast cancer diagnosis and a subgroup of family history-positive (FH+) patients collected because they were known to harbor a germline BRCA1 mutation. The primary objective of the study was to assess whether these groups had different outcomes with respect to rates of local recurrence, contralateral breast cancer, relapse-free survival, and overall survival. Local therapy included breast-conservation and mastectomy, and a range of systemic therapies were used. The main findings include similar local and distant recurrence rates in patients with familial vs. sporadic breast cancer, and a substantial excess of contralateral breast cancers among patients with a positive family history. At a median follow-up of 7 years, there were ipsilateral recurrences in 22% of the FH+ and 24% of the FH– groups. Contralateral breast cancer occurred in 36% of the FH+ patients, in contrast to only 16% of the FH– patients. A non-significant trend towards worse relapsefree survival was seen in the FH+ patients, without a difference in overall survival. This study has several strengths. One is the large number of patients for whom family history data were available. Another is the presence of sufficient numbers of patients with known BRCA1 mutation status to permit detailed comparison to other subsets, although the lack of BRCA2 mutation data makes some misclassification likely. Concerns raised by the higher proportion of node status unknown patients in the FH+ group are clearly acknowledged by the authors. The data from Eccles et al. add to accumulating observations that are beginning to influence therapy recommendations for newly-diagnosed women with strong familial breast cancer history. Our experience assessing the outcome of 201 young (age 36 or younger) patients with a positive family history (defined as having a mother or sister with breast cancer before age 50 or ovarian cancer at any age) is similar to that of Eccles et al., providing further reassurance that individuals with potentially inherited forms of breast cancer can be safely managed with breast-conserving therapy [1]. Overall survival after BRCA1/2-associated ovarian cancer is clearly superior to survival in non-mutation carriers [2], but data on breast cancers are inconclusive [3, 4]. There is particular controversy surrounding the best local therapy for patients with a BRCA1/2-associated hereditary breast cancer predisposition. Concerns about the role of radiotherapy in BRCA1/2associated breast cancer come from both laboratory and clinical data. The complex formed by BRCA1/2 is involved in repair of DNA damage. As radiotherapy (RT) causes DNA damage, there has been concern that RT may yield unexpected toxicities in carriers of germline BRCA1/2 mutations. Both BRCA1and BRCA2-knock-out mice have been shown to be incompetent to repair radiation-induced DNA damage, though the mice hemizygous for either gene are able to repair this damage as well as wild type mice [5–7]. In a recent publication, Pierce et al. reported on 71 women with early stage breast cancer and a known BRCA1/2 mutation, matched to 213 women with sporadic breast cancer, all treated with breast-conserving surgery and RT [8]. No significant differences in acute or chronic toxicities were seen, nor were there significant differences in 5-year actuarial local control, relapse-free survival or overall survival between the mutation carriers and the sporadic cases. These data provide reassurance that radiation therapy is a safe and effective approach for this cohort. However, after correcting for patients who underwent prophylactic mastectomy, Pierce et al. also observed contralateral breast cancer (CBC) in 22% of the mutation carriers at 5 years, compared with 2% among the sporadic cases (hazard ratio, 8.58, p < 0.0001). They also observed second primary ovarian cancers among mutation carriers, not seen by Eccles et al. in this series. Other investigators have reported similar and conflicting findings [3, 9].