Deep Learning-Aided Automatic Contouring of Clinical Target Volumes for Radiotherapy in Breast Cancer After Modified Radical Mastectomy

Purpose: The aim of this study is to develop a practicable automatic clinical target volume (CTV) delineation method for radiotherapy of breast cancer after modified radical mastectomy.Methods: Unlike breast conserving surgery, the radiotherapy CTV for modified radical mastectomy involves several regions, including CTV in the chest wall (CTVcw), supra- and infra-clavicular region (CTVsc), and internal mammary lymphatic region (CTVim). For accurate and efficient segmentation of the CTVs in radiotherapy of breast cancer after modified radical mastectomy, a multi-scale convolutional neural network with an orientation attention mechanism is proposed to capture the corresponding features in different perception fields. A channel-specific local Dice loss, alongside several data augmentation methods, is also designed specifically to stabilize the model training and improve the generalization performance of the model. The segmentation performance is quantitatively evaluated by statistical metrics and qualitatively evaluated by clinicians in terms of consistency and time efficiency.Results: The proposed method is trained and evaluated on the self-collected dataset, which contains 110 computed tomography scans from patients with breast cancer who underwent modified mastectomy. The experimental results show that the proposed segmentation method achieved superior performance in terms of Dice similarity coefficient (DSC), Hausdorff distance (HD) and Average symmetric surface distance (ASSD) compared with baseline approaches.Conclusion: Both quantitative and qualitative evaluation results demonstrated that the specifically designed method is practical and effective in automatic contouring of CTVs for radiotherapy of breast cancer after modified radical mastectomy. Clinicians can significantly save time on manual delineation while obtaining contouring results with high consistency by employing this method.

Racial and Ethnic Disparities in the Refusal of Surgical Treatment in Women 40 Years and Older With Breast Cancer in the United States Between 2010 and 2017

Purpose Although surgical resection is the main modality of treatment for breast cancer, some patients elect to refuse the recommended surgery. We assessed racial and ethnic differences in women 40 years and older who received or refused to receive surgical treatment for breast cancer in the United States and whether racial disparities in mortality were affected by their differences in the prevalence of refusal for surgical treatmentMethods We studied 277,127 women with breast cancer using the Surveillance, Epidemiology, and End Results (SEER) data and performed multivariable logistic regressions to investigate the association between surgery status of breast cancer and race/ethnicity. Additionally, we performed Cox logistic regression analyses to determine the predictors of mortality outcomes. Results Of 277,127 patients with breast cancer, 1,468 (0.53%) refused to receive the recommended surgical treatment in our cohort. Non-Hispanic Black women were 112% more likely to refuse recommended surgical treatment for breast cancer compared to their non-Hispanic White counterparts [adjusted odds ratio: 2.12, 95% confidence interval (CI)=1.82-2.47]. Women who underwent breast conserving surgery [hazards ratio (HR): 0.15, 95% CI: 0.13-0.16] and mastectomy (HR:0.21, 95% CI: 0.18-0.23) had lower hazard ratios of mortality as compared to women who refused the recommended treatment after adjusting for covariates. Conclusion Race/ethnicity was associated with refusal for recommended surgery, especially among non-Hispanic Black women. Also, surgery refusal was associated with a higher risk of all-cause and breast cancer-related mortality. These disparities stress the need to tailor interventions aimed at raising awareness of the importance of following physician recommendations among minorities.

Neoadjuvant Therapy with Doxorubicin-Cyclophosphamide Followed by Weekly Paclitaxel in Early Breast Cancer: A Retrospective Analysis of 200 Consecutive Patients Treated in A Single Center with A Median Follow-Up of 9.5 Years.

Purpose We analyzed outcomes of doxorubicin-cyclophosphamide(AC) followed by weekly paclitaxel as neoadjuvant chemotherapy(NAC) for breast cancer(BC), in an everyday practice with long-term follow-up of patients. Methods All patients (n=200) who received the AC-paclitaxel combination as NAC for BC at the Soroka University Medical Center from 2003 to 2012 were included in this retrospective cohort study. AC was administered on an every 3-week schedule (standard dose) until May, 2007(n=99); and subsequently every 2 weeks (dose dense)(dd)(n=101). Clinical pathologic features, treatment course and outcome information were recorded. Complete pathologic response(pCR) was analyzed according to BC subtype, dose regimen and stage. Results Median age was 49 years; 55.5% and 44.5% of patients were clinically stage 2 and 3, respectively. Standard dose patients had more T3 tumors. Subtypes were human-epidermal-growth-factor receptor(HER 2)-positive 32.5% (of whom 82% received trastuzumab), hormone-receptor positive/HER2 negative 53%, triple negative 14.5%. Breast conserving surgery(BCS) was performed in 48.5% of patients; only 9.5% were deemed suitable for BCS prior to NAC. Toxicity was acceptable. The overall pCR rate was 26.0% and was significantly higher in the dd group and HER2-positive patients. With a median follow-up of 9.51 years median event-free survival(EFS), and overall survival(OS) is 10.85 years and 12.61 years, respectively. Patients achieving pCR had significantly longer EFS and OS. Conclusions- NAC for BC with AC-paclitaxel can be safely administered in the “real-world’ setting with high efficacy. Current efforts are aimed at Increasing rates of pCR and identifying patients who may benefit from additional therapy or conversely, de-escalated treatment.

Intensification of radiation therapy for localized breast cancer in the settings of the COVID-19 pandemic: A literature review

Relevance: Since 2004, breast cancer steadily ranks first in the structure of the incidence of malignant neoplasms in the Republic of Kazakhstan in both sexes. In 2020, its share was 14.5% (vs. 15.2% in 2019). Breast cancer also constantly ranks first in the structure of female cancer incidence, with 44.3‰ in 2020 (vs. 51.6‰in 2019). In the early 1980s, radiation therapy was a standard specialized treatment for breast cancer. The current realities of the COVID-19 pandemic require a reorganization of healthcare facilities to determine the priorities. It is also important to balance the economic and clinical efficacy of radiotherapy methods applied. The study aimed to analyze the results of large randomized trials and compare breast cancer outcomes after hypofractionated and standard fractionation radiation treatment. Methods: We reviewed the results of large randomized trials of hypofractionated radiation therapy, emphasizing adequate patient selection according to the American Society of Therapeutic Radiology and Oncology (ASTRO) guidelines. Radiobiological aspects of hypofractionation were considered due to its implementation in clinical practice. The research materials were obtained from the “PubMed” database of evidence-based medicine by the keywords “radiotherapy,” “breast cancer,” “hypofractionation dose” for the period 2000-2021. Large randomized trials involving patients of any age diagnosed with stages T1-3, N0-1 breast cancer, who underwent beam therapy in standard or hypofractionated mode, met the criteria for inclusion in this study. Results: According to the results of large randomized trials, the hypofractionated regimen is similar to the standard regimen in terms of late effects on normal tissues and ensures good control over the oncological process. Conclusions: Hypofractionation has proven effectiveness and safety and has lower late and/or acute radiation toxicity when treating early breast cancer. Hypofractionation can become a new standard of radiation therapy at early stages after breast-conserving surgery.

De-Escalating Breast Cancer Surgery: Should We Apply Quality Indicators from Other Jurisdictions in Canada?

Quality Indicators (QIs), including the breast-conserving surgery (BCS) rate, were published by the European and American Breast Cancer Societies and this study assesses these in a Canadian population to look for opportunities to de-escalate surgery. A total of 2311 patients having surgery for unilateral, unifocal breast cancer between 2013 and 2017 were identified and BCS QIs calculated. Reasons for mastectomy had been prospectively collected with synoptic operative reporting. Our BCS rate for invasive cancer < 3 cm was 77.1%, invasive cancer < 2 cm was 84.1%, and DCIS < 2 cm was 84.9%. There was no statistically significant change in BCS rates over a five-year period, but there was a reduction in contralateral prophylactic mastectomies (CPM) from 28% in 2013 to 16% in 2017 (p < 0.001). Trend analysis looking at tumour size and medical need for mastectomy indicated that 80% of patients at our centre would be eligible for BCS with tumour cut off of 2.5 cm. Our institution met American but not European QI standards for BCS rates, potentially indicating a difference in patient demographics compared to Europe. Our results support the understanding that BCS rates are influenced by multiple factors and are challenging to compare across jurisdictions. CPM rates may offer a more actionable opportunity to de-escalate surgery for breast cancer.

Specimen Mammography for Intraoperative Margin Assessment in Breast Conserving Surgery: A Meta-Analysis

Specimen mammography is one of the widely used intraoperative methods assessing margin status in breast conserving surgery. We performed a meta-analysis to evaluate the diagnostic accuracy of specimen mammography. Literature databases including Pubmed, Cochrane Library, Web of Science and EMBASE were searched prior to May 2020. 18 studies with a total of 1142 patients were included. Data was extracted to perform pooled analysis, heterogeneity testing, threshold effect testing, sensitivity analysis, publication bias analysis and subgroup analyses. The pooled weighted values were a sensitivity of 0.55 (95% CI, 0.45–0.64), a specificity of 0.85 (95% CI, 0.77–0.90), a DOR of 7 (95% CI, 4–11) and a pooled positive likelihood ratio of 3.6 (95% CI 2.4-5.3). The area under the receiver operator characteristic curve was 0.75 (95% CI 0.71-0.78). In the subgroup analysis, the pooled specificity in the positive margin defined as tumor at margin subgroup was lower than the other positive margin definition subgroup (0.79 [95% CI: 0.66, 0.91] vs. 0.88 [95% CI: 0.81, 0.95], p = 0.01). Our findings indicated specimen mammography to be an accurate and intraoperative imaging technique for margin assessment in breast conserving surgery.

Nomogram for Predicting Overall Survival in Patients With Invasive Micropapillary Carcinoma After Breast-Conserving Surgery: A Population‐Based Analysis

Background: Due to the rarity of invasive micropapillary carcinoma (IMPC) of the breast, no randomized trial has investigated the prediction of overall survival (OS) for patients with IMPC after breast-conserving surgery (BCS). This study aimed to construct a nomogram for predicting OS in IMPC patients after BCS. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, 481 eligible cases diagnosed with IMPC were collected. OS in IMPC patients after BCS were assessed through multivariable Cox analyses, Harrell’s concordance indexes (C-indexes), receiver operating characteristics (ROCs) curves, calibration curves, decision curve analyses (DCA), and survival analyses. Results: 336 patients were randomly assigned into training cohort and 145 cases in validation cohort. The multivariate Cox regression analyses revealed that age at diagnosis, American Joint Committee on Cancer (AJCC) stage, marital status, hormone receptor status and chemotherapy were significant prognostic factors for OS in conservatively operated IMPC patients. The nomogram had a good prediction performance with the C-indices 0.771 (95%CI, 0.712-0.830) and 0.715 (95%CI, 0.603-0.827) in training and validation cohorts, respectively, and good consistency between the predicted and observed probability, with calibration curves plotted and the slope was close to 1. Based on calculation of the model, participants in low-risk group had a better OS in comparison with those in high-risk group (P < 0.001). Conclusions: A nomogram was developed to predict individualized risk of OS for IMPC patients after BCS. By risk stratification, this model is expected to guide treatment decision making in improving long-term follow-up strategies for IMPC patients.

An absence of equipoise: Examining surgeons’ decision talk during encounters with women considering breast cancer surgery

Shared decision-making is recommended for decisions with multiple reasonable options, yet clinicians often subtly or explicitly guide choices. Using purposive sampling, we performed a secondary analysis of 142 audio-recorded encounters between 13 surgeons and women eligible for breast-conserving surgery with radiation or mastectomy. We trained 9 surgeons in shared decision-making and provided them one of two conversation aids; 4 surgeons practiced as usual. Based on a published taxonomy of treatment recommendations (pronouncements, suggestions, proposals, offers, assertions), we examined how surgeons framed choices with patients. Many surgeons made assertions providing information and advice (usual care 71% vs. intervention 66%; p = 0.54). Some made strong pronouncements (usual care 51% vs. intervention 36%; p = .09). Few made proposals and offers, leaving the door open for deliberation (proposals usual care 21% vs. intervention 26%; p = 0.51; offers usual care 40% vs. intervention 40%; p = 0.98). Surgeons were significantly more likely to describe options as comparable when using a conversation aid, mentioning this in all intervention group encounters (usual care 64% vs. intervention 100%; p<0.001). Conversation aids can facilitate offers of comparable options, but other conversational actions can inhibit aspects of shared decision-making.