Hypofractionated vs Conventionally Fractionated Postmastectomy Radiation After Implant-Based Reconstruction: A Randomized Clinical Trial.

Importance: Postmastectomy radiation therapy (PMRT) improves local-regional disease control and patient survival. Hypofractionation (HF) regimens have comparable efficacy and complication rates with improved quality of life compared with conventional fractionation (CF) schedules. However, the use of HF after mastectomy in patients undergoing breast reconstruction has not been prospectively examined. Objective: To compare HF and CF PMRT outcomes after implant-based reconstruction. Design, Setting, and Participants: This randomized clinical trial assessed patients 18 years or older undergoing mastectomy and immediate expander or implant reconstruction for breast cancer (Tis, TX, or T1-3) and unilateral PMRT from March 8, 2018, to November 3, 2021 (median [range] follow-up, 40.4 [15.4-63.0] months), at 16 US cancer centers or hospitals. Analyses were conducted between September and December 2023. Interventions: Patients were randomized 1:1 to HF or CF PMRT. Chest wall doses were 4256 cGy for 16 fractions for HF and 5000 cGy for 25 fractions for CF. Chest wall toxic effects were defined as a grade 3 or higher adverse event. Main Outcomes and Measures: The primary outcome was the change in physical well-being (PWB) domain of the Functional Assessment of Cancer Therapy-Breast (FACT-B) quality-of-life assessment tool at 6 months after starting PMRT, controlling for age. Secondary outcomes included toxic effects and cancer recurrence. Results: Of 400 women (201 in the CF arm and 199 in the HF arm; median [range] age, 47 [23-79] years), 330 patients had PWB scores at baseline and at 6 months. There was no difference in the change in PWB between the study arms (estimate, 0.13; 95% CI, -0.86 to 1.11; P = .80), but there was a significant interaction between age group and study arm (P = .03 for interaction). Patients younger than 45 years had higher 6-month absolute PWB scores if treated with HF rather than CF regimens (23.6 [95% CI, 22.7-24.6] vs 22.0 [95% CI, 20.7-23.3]; P = .047) and reported being less bothered by adverse effects (mean [SD], 3.0 [0.9] in the HF arm and 2.6 [1.2] in the CF arm; P = .02) or nausea (mean [SD], 3.8 [0.4] in the HF arm and 3.6 [0.8] in the CF arm; P = .04). In the as-treated cohort, there were 23 distant (11 in the HF arm and 12 in the CF arm) and 2 local-regional (1 in the HF arm and 1 in the CF arm) recurrences. Chest wall toxic effects occurred in 39 patients (20 in the HF arm and 19 in the CF arm) at a median (IQR) of 7.2 (1.8-12.9) months. Fractionation was not associated with chest wall toxic effects on multivariate analysis (HF arm: hazard ratio, 1.02; 95% CI, 0.52-2.00; P = .95). Fewer patients undergoing HF vs CF regimens had a treatment break (5 [2.7%] vs 15 [7.7%]; P = .03) or required unpaid time off from work (17 [8.5%] vs 34 [16.9%]; P = .02). Conclusions and Relevance: In this randomized clinical trial, the HF regimen did not significantly improve change in PWB compared with the CF regimen. These data add to the increasing experience with HF PMRT in patients with implant-based reconstruction. Trial Registration: ClinicalTrials.gov Identifier: NCT03422003.

Secondary Breast Angiosarcoma After a Primary Diagnosis of Breast Cancer: A Retrospective Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database.

OBJECTIVES: Angiosarcoma is a rare complication of breast-conserving therapy. This study evaluated the change in incidence between 1992 and 2016 of secondary breast angiosarcoma (SBA) in patients with a history of breast cancer and the impact of management strategies for the original breast carcinoma on angiosarcoma treatment. METHODS: Breast cancer and angiosarcoma cases were abstracted from the Surveillance, Epidemiology, and End Result (SEER) database. SBAs were defined as angiosarcomas located in the breast occurring after a prior breast cancer diagnosis. Primary breast angiosarcomas (PBAs) were defined as an angiosarcoma diagnosis listed as "one primary only." Incidence rates were estimated using a proportion of the US total population. Survival was analyzed by the Kaplan-Meier method, and Cox proportional hazard models were used to assess the association of clinicopathologic characteristics on overall survival. RESULTS: Between 1992 and 2016, 193 cases of SBA were reported in the SEER dataset in patients with a prior history of breast cancer. The incidence of breast angiosarcoma in patients with a prior diagnosis of breast cancer increased 3-fold from about 10 cases per 100,000 person-years to about 30 cases per 100,000 person-years over this same period ( P =0.0037). For treatment of SBA (n=193), almost all (95%) had surgery. Nine percent received radiation (compared with 35% of patients with PBA, P <0.001) and 23% received chemotherapy (vs. 45% for PBA, P =0.11). CONCLUSIONS: We demonstrate an increasing incidence of SBA over the study period. These data can help inform shared decision-making for optimal management of locoregional breast cancer and raise awareness of secondary angiosarcoma.

The Radiologist's Role in a Breast Multidisciplinary Tumor Board.

Breast multidisciplinary tumor boards (MTBs) play an important role in determining treatment. This article serves as a guide for the radiologist participating in a breast MTB, as the information presented at MTB can significantly influence treatment plans and dictate future steps for further patient work-up. Multidisciplinary tumor board preparation involves a careful review of the patient's history while gathering all relevant imaging studies, and reinterpreting them when appropriate. Presented images should be carefully selected, annotated, and displayed clearly before providing final recommendations for localization and incompletely assessed findings. Anatomic staging factors from the AJCC Breast Cancer Staging System, such as tumor size and degree of suspected skin involvement, should be described. In addition, there are many other types of information that the treatment specialists want to know. The surgeon is interested in anatomic information that will help them decide whether breast conservation therapy is feasible or if local structures, such as the nipple, can be spared. The radiation oncologist may need to know whether accelerated partial breast irradiation is feasible or if postmastectomy radiation therapy is indicated. The medical oncologist is looking for factors that may provide an indication for neoadjuvant therapy and ensuring there is a reliable follow-up method for evaluating the response to treatment, such as comparative MRI. Additionally, all specialists need to know the extent of suspected nodal involvement. By clearly and comprehensively presenting this information to the rest of the MTB team, the radiologist provides a vital contribution that guides treatment and ensures adherence to clinical guidelines.

Predictors of cardiac and lung dose sparing in DIBH for left breast treatment.

This retrospective study of left breast radiation therapy (RT) investigates the correlation between anatomical parameters and dose to heart or/and left lung in deep inspiration breath-hold (DIBH) compared to free-breathing (FB) technique. Anatomical parameters of sixty-seven patients, treated with a step-and-shoot technique to 50 Gy or 50.4 Gy were included. They consisted of the cardiac contact distances in axial (CCDax) and parasagittal (CCDps) planes, and the lateral heart-to-chest distance (HCD). Correlation analysis was performed to identify predictors for heart and lung dose sparing. Paired t-test and linear regression were used for data analysis with significance level of p = 0.05. All dose metrics for heart and lung were significantly reduced with DIBH, however 21% of patients analyzed had less than 1.0 Gy mean heart dose reduction. Both FB-CCDpsdistance and FB-HCD correlated with FB mean heart dose and mean DIBH heart dose reduction. The strongest correlation was observed for the ratio of FB-CCDpsand FB-HCD with heart dose sparing. A FB-CCDps and FB-HCD model was developed to predict DIBH induced mean heart dose reduction, with 1.04 Gy per unit of FB-CCDps/FB-HCD. Variation between predicted and actual mean heart dose reduction ranged from -0.6 Gy to 0.6 Gy. In this study, FB-CCDps and FB-HCD distance served as predictors for heart dose reduction with DIBH equally, with FB-CCDps/FB-HCD as a stronger predictor. These parameters and the prediction model could be further investigated for use as a tool to better select patients who will benefit from DIBH.

Cardiac sparing characteristics of internal mammary chain radiotherapy using deep inspiration breath hold for left-sided breast cancer.

BACKGROUND: While breast radiotherapy typically includes regional nodal basins, the treatment of the internal mammary nodes (IMN) has been controversial due to concern for long-term cardiac toxicity. For high risk patients where IMN treatment is warranted, there is limited data with regards to the degree of heart sparing conferred by modern techniques. In this study, we sought to analyze the specific heart sparing metrics conferred by deep inspiration breath hold (DIBH) in the setting of IMN irradiation. METHODS: From 2012 to 2015, 168 consecutive patients were treated with adjuvant left-sided radiotherapy using DIBH. Retrospective review identified 49 patients who received nodal irradiation, either to a supraclavicular field (SCF) and IMN (16), or to the SCF alone (33). Cardiac mean dose and dose volumes were calculated from free breathing (FB) and DIBH treatment plans, and compared by Wilcoxon signed-rank and Mann-Whitney U tests. RESULTS: DIBH achieved significant reductions in mean heart dose (p < 0.001) in both the IMN treated group from 6.73 Gy to 2.79 Gy (- 56.4%) and the IMN untreated group from 4.77 Gy to 1.55 Gy (- 63.7%). There was a 7.3% difference in relative reduction that was not statistically significant (p = 0.216). Relative reductions in heart dose volume measures were all significantly lower for IMN-irradiated patients (p ≤ 0.012), with the greatest deficits at V5 that gradually diminish with increasing dose (V25). CONCLUSIONS: The relative heart sparing benefits of the DIBH technique are retained even with IMN inclusion. However, the addition of IMN irradiation is associated with an intrinsically greater heart dose, which translates to an estimated 9.2% proportional increase in the risk of a subsequent major coronary event. In the setting of effective cardiac sparing techniques, clinicians should take these considerations into account to guide when IMN treatment is warranted.

Preoperative MRI improves prediction of extensive occult axillary lymph node metastases in breast cancer patients with a positive sentinel lymph node biopsy.

RATIONALE AND OBJECTIVES: To test the ability of quantitative measures from preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict, independently and/or with the Katz pathologic nomogram, which breast cancer patients with a positive sentinel lymph node biopsy will have four or more positive axillary lymph nodes on completion axillary dissection. MATERIALS AND METHODS: A retrospective review was conducted to identify clinically node-negative invasive breast cancer patients who underwent preoperative DCE-MRI, followed by sentinel node biopsy with positive findings and complete axillary dissection (June 2005-January 2010). Clinical/pathologic factors, primary lesion size, and quantitative DCE-MRI kinetics were collected from clinical records and prospective databases. DCE-MRI parameters with univariate significance (P < .05) to predict four or more positive axillary nodes were modeled with stepwise regression and compared to the Katz nomogram alone and to a combined MRI-Katz nomogram model. RESULTS: Ninety-eight patients with 99 positive sentinel biopsies met study criteria. Stepwise regression identified DCE-MRI total persistent enhancement and volume adjusted peak enhancement as significant predictors of four or more metastatic nodes. Receiver operating characteristic curves demonstrated an area under the curve of 0.78 for the Katz nomogram, 0.79 for the DCE-MRI multivariate model, and 0.87 for the combined MRI-Katz model. The combined model was significantly more predictive than the Katz nomogram alone (P = .003). CONCLUSIONS: Integration of DCE-MRI primary lesion kinetics significantly improved the Katz pathologic nomogram accuracy to predict the presence of metastases in four or more nodes. DCE-MRI may help identify sentinel node-positive patients requiring further local-regional therapy.

Dynamic contrast-enhanced magnetic resonance imaging and invasive breast cancer: primary lesion kinetics correlated with axillary lymph node extracapsular extension.

PURPOSE: To determine if dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) peak enhancement (PE) of primary breast cancer can predict the presence of lymph node extracapsular extension (LNECE) in patients with axillary metastatic disease. MATERIALS AND METHODS: In all, 167 patients treated with radiotherapy for invasive breast cancer from January 1, 2006 to November 1, 2007 were retrospectively identified. Patients with DCE-MRI and surgical axillary staging were included in this study. PE of primary tumors was compared according to axillary nodal status: negative, positive without LNECE, or positive with LNECE. A receiver operator characteristic curve (ROC) was plotted to determine accuracy of PE to predict LNECE. RESULTS: Forty-six patients met the study criteria. Thirty-two (70%) were node-negative, 9 (19%) were node-positive without LNECE, and 5 (11%) were node-positive with LNECE. PE was greater for patients with LNECE (mean 365%) compared to node-positive patients without LNECE (mean 183%) P = 0.05 and node-negative patients (mean 144%) P = 0.0012. Area under the ROC curve was 0.93. CONCLUSION: DCE-MRI PE may be a surrogate marker for LNECE. If validated, DCE-MRI may provide noninvasive kinetic information informing axillary nodal status for patients who receive chemotherapy prior to surgical axillary staging or forego axillary dissection after a positive sentinel node biopsy.

Dynamic contrast-enhanced MRI kinetics of invasive breast cancer: a potential prognostic marker for radiation therapy.

PURPOSE: Our goal was to determine the correlations between dynamic contrast-enhanced MRI (DCE-MRI) kinetics of breast cancers and axillary nodal status (ANS) which may have prognostic value in designing radiation therapy recommendations. METHODS AND MATERIALS: A retrospective review identified 167 consecutive patients treated with external beam radiotherapy for invasive breast cancer from Jan 1, 2006 to Nov 1, 2007. Patients with DCE-MRI kinetic data from our institution who underwent axillary surgical staging prior to chemotherapy were included. ANS was assessed as positive or negative by pathology record review. For each primary cancer, maximum tumor diameter and kinetic values for initial peak enhancement (PE), percent initial rapid enhancement (RE), and percent delayed washout enhancement (WE) were measured with a computer-aided evaluation program. Univariate, multivariate, and receiver operating characteristic curve analyses were performed according to the ANS. RESULTS: Forty-six patients met study criteria, with 32 (70%) node-negative and 14 (30%) node-positive patients. Median PE was significantly greater in node-positive patients (209%) than in node-negative patients (138%, p = 0.0027). Similarly, median RE was significantly greater in node-positive patients (57%) than in node-negative patients (27%, p = 0.0436). WE was not different between groups (p = 0.9524). Median maximum tumor diameter was greater in node-positive patients (26 mm) than in node-negative patients (15 mm, p = 0.015). Multivariate analysis showed that only PE trended toward significance (p = 0.18). CONCLUSIONS: DCE-MRI kinetics of primary breast cancers correlate with ANS. Multivariate analysis demonstrates the correlation is not due simply to underlying lesion size. If validated prospectively, DCE-MRI kinetics may aid as a tool in selecting patients or designing fields for radiation therapy.