NCCN Guidelines® Insights: Merkel Cell Carcinoma, Version 1.2024.

The NCCN Guidelines for Merkel Cell Carcinoma (MCC) provide recommendations for diagnostic workup, clinical stage, and treatment options for patients. The panel meets annually to discuss updates to the guidelines based on comments from expert review from panel members, institutional review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new page for locally advanced disease in the setting of clinical node negative status, entitled "Clinical N0 Disease, Locally Advanced MCC." This new algorithm page addresses locally advanced disease, and the panel clarifies the meaning behind the term "nonsurgical" by further defining locally advanced disease. In addition, the guideline includes the management of in-transit disease and updates to the systemic therapy options.

Basal Cell Skin Cancer, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States. Due to the high frequency, BCC occurrences are not typically recorded, and annual rates of incidence can only be estimated. Current estimated rates are 2 million Americans affected annually, and this continues to rise. Exposure to radiation, from either sunlight or previous medical therapy, is a key player in BCC development. BCC is not as aggressive as other skin cancers because it is less likely to metastasize. However, surgery and radiation are prevalent treatment options, therefore disfigurement and limitation of function are significant considerations. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) outline an updated risk stratification and treatment options available for BCC.

NCCN Guidelines® Insights: Squamous Cell Skin Cancer, Version 1.2022.

The NCCN Guidelines for Squamous Cell Skin Cancer provide recommendations for diagnostic workup, clinical stage, and treatment options for patients with cutaneous squamous cell carcinoma. The NCCN panel meets annually to discuss updates to the guidelines based on comments from panel members and the Institutional Review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new surgical recommendation terminology (peripheral and deep en face margin assessment), as well as recent updates on topical prophylaxis, immunotherapy for regional and metastatic disease, and radiation therapy.

Overall health at diagnosis predicts the risk of complications within the first year after breast cancer diagnosis.

PURPOSE: Breast cancer patients with overall poor health are at a greater risk of both complications during treatment and mortality from competing causes. We sought to determine the association of pre-existing comorbidities on treatment-related complications and overall survival. METHODS: We identified women ages 40-90 years old from our institutional registry with stage I-II invasive breast cancer from 2005 to 2014. Recursive partitioning was used to stratify women based on pre-existing comorbidities as low, moderate, or high risk of treatment-associated complications. Cox proportional hazards model was constructed to estimate the association of risk with overall survival. RESULTS: 2077 women were studied. Mean age was 60 (IQR 51-68). Over half (54%) had ≥ 1 comorbid condition, and 29% experienced at least one adverse medical event within 1 year of diagnosis. Risk categories included low (no comorbidities or hypertension), moderate (combinations of comorbidities excluding congestive heart failure), and high (congestive heart failure in isolation or in combination with other conditions). High-risk women had a lower 10-year OS compared to moderate- or low-risk women (89% vs 90% vs 96%, log-rank p < 0.001). After adjustment, being at moderate (HR 2.20, 95% CI 1.30-3.72, p = 0.003) or high risk (HR 5.07, 95% CI 1.66-15.52, p = 0.004) of adverse sequelae was associated with reduced OS compared to those at low risk of these adverse medical events. CONCLUSIONS: Following breast cancer diagnosis, overall poor health was associated with a greater risk of mortality and complications within the first year of treatment, which was driven by a pre-existing diagnosis of congestive heart failure.

Surgical Resection of the Primary Tumor in Women With De Novo Stage IV Breast Cancer: Contemporary Practice Patterns and Survival Analysis.

OBJECTIVE: We evaluated patterns of surgical care and their association with overall survival among a contemporary cohort of women with stage IV breast cancer. BACKGROUND: Surgical resection of the primary tumor remains controversial among women with stage IV breast cancer. METHODS: Women diagnosed with clinical stage IV breast cancer from 2003 to 2012 were identified from the American College of Surgeons National Cancer Database. Those with intact primary tumors who were alive 12 months after diagnosis were categorized by treatment sequence: (1) surgery before systemic therapy, (2) systemic therapy before surgery, and (3) systemic therapy alone. Multivariate logistic regression was used to estimate the association of treatment sequence with surgery type. Overall survival was estimated using multivariate Cox proportional hazards models. RESULTS: Among 24,015 women, 56.2% (13,505) underwent systemic therapy alone and 43.8% (10,510) underwent surgical resection. Rates of surgery decreased slightly over time (43.1% in 2003 to 41.9% in 2011). Treatment with systemic therapy before surgery was associated with larger tumor size (median 4.5 vs 3.1 cm, P < 0.001) and receipt of mastectomy (81.4% vs 52.2%, P < 0.001) when compared to those who underwent surgery first. Receipt of surgery, whether before or after systemic therapy (Hazard Ratio, 0.68; 95% confidence interval, 0.62-0.73; Hazard Ratio, 0.56; 95% confidence interval, 0.52-0.61; P < 0.001), was independently associated with improved adjusted overall survival when compared to systemic therapy alone. CONCLUSIONS: Surgical resection of the primary tumor occurs in almost half of women with stage IV breast cancer alive 1 year after diagnosis, and is increasingly occurring after systemic therapy. Coordinated multidisciplinary care remains highly relevant in the setting of metastatic breast cancer, where surgical decisions should be made on an individual basis and may affect survival in select women.

The Effect of Hospital Volume on Breast Cancer Mortality.

OBJECTIVE: The aim of this study was to determine whether hospital volume was associated with mortality in breast cancer, and what thresholds of case volume impacted survival. BACKGROUND: Prior literature has demonstrated improved survival with treatment at high volume centers among less common cancers requiring technically complex surgery. METHODS: All adults (18 to 90 years) with stages 0-III unilateral breast cancer diagnosed from 2004 to 2012 were identified from the American College of Surgeons National Cancer Data Base (NCDB). A multivariable Cox proportional hazards model with restricted cubic splines was used to examine the association of annual hospital volume and overall survival, after adjusting for measured covariates. Intergroup comparisons of patient and treatment characteristics were conducted with X and analysis of variance (ANOVA). The log-rank test was used to test survival differences between groups. A multivariable Cox proportional hazards model was used to estimate hazard ratios (HRs) associated with each volume group. RESULTS: One million sixty-four thousand two hundred and fifty-one patients met inclusion criteria. The median age of the sample was 60 (interquartile range 50 to 70). Hospitals were categorized into 3 groups using restricted cubic spline analysis: low-volume (<148 cases/year), moderate-volume (148 to 298 cases/year), and high-volume (>298 cases/year). Treatment at high volume centers was associated with an 11% reduction in overall mortality for all patients (HR 0.89); those with stage 0-I, ER+/PR+ or ER+/PR- breast cancers derived the greatest benefit. CONCLUSIONS: Treatment at high volume centers is associated with improved survival for breast cancer patients regardless of stage. High case volume could serve as a proxy for the institutional infrastructure required to deliver complex multidisciplinary breast cancer treatment.

The Association of Extent of Axillary Surgery and Survival in Women with N2-3 Invasive Breast Cancer.

BACKGROUND: Although surgical management of the axilla for breast cancer continues to evolve, axillary lymphadenectomy remains the standard of care for women with advanced nodal disease. We sought to evaluate national patterns of care in axillary surgery, and its association with overall survival (OS) among women with N2-3 invasive breast cancer. METHODS: Women (18-90 years) with clinical N2-3 invasive breast cancer who underwent axillary surgery were identified from the National Cancer Data Base (NCDB) from 2004 to 2013. Axillary surgery was categorized as sentinel lymph node biopsy (SLNB, 1-5 nodes) or axillary lymph node dissection (ALND, ≥ 10 nodes). Patient and treatment characteristics, trends over time, and overall survival (OS) were compared by surgical treatment. RESULTS: Overall, 22,156 patients were identified. At diagnosis, 68.5% had cN2 and 31.5% had cN3 disease. Treatment included: lumpectomy (27%), mastectomy (73%), adjuvant chemotherapy (53.4%), neoadjuvant chemotherapy (NAC) (39.7%), radiation (74%), and endocrine therapy (54.4%). In total, 9.9% (n = 2190) underwent SLNB and 90.1% (n = 19,966) underwent ALND. Receipt of SLNB was associated with private insurance, grade 3 disease, invasive ductal cancer, NAC, and lumpectomy (all p < 0.001). After adjustment for known covariates, including chemotherapy use, ALND was associated with improved survival [hazard ratio (HR) 0.68, p < 0.001] and this effect was similar for N2 and N3 patients (axillary surgery × cN-stage interaction p = 0.29). CONCLUSIONS: Axillary lymphadenectomy was associated with improved survival in patients presenting with clinical N2-3 invasive breast cancer. Further studies, particularly in the neoadjuvant setting, are needed to identify breast cancer patients with advanced nodal disease who may safely avoid a lesser extent of axillary surgery.

Merkel Cell Carcinoma, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Merkel Cell Carcinoma (MCC) focuses on areas impacted by recently emerging data, including sections describing MCC risk factors, diagnosis, workup, follow-up, and management of advanced disease with radiation and systemic therapy. Included in these sections are discussion of the new recommendations for use of Merkel cell polyomavirus as a biomarker and new recommendations for use of checkpoint immunotherapies to treat metastatic or unresectable disease. The next update of the complete version of the NCCN Guidelines for MCC will include more detailed information about elements of pathology and addresses additional aspects of management of MCC, including surgical management of the primary tumor and draining nodal basin, radiation therapy as primary treatment, and management of recurrence.

Patient Age and Tumor Subtype Predict the Extent of Axillary Surgery Among Breast Cancer Patients Eligible for the American College of Surgeons Oncology Group Trial Z0011.

BACKGROUND: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial established the safety of omitting axillary lymph node dissection (ALND) for early-stage breast cancer patients with limited nodal disease undergoing lumpectomy. We examined the extent of axillary surgery among women eligible for Z0011 based on patient age and tumor subtype. METHODS: Patients with cT1-2, cN0 breast cancers and one or two positive nodes diagnosed from 2009 to 2014 and treated with lumpectomy were identified in the National Cancer Data Base. Sentinel lymph node biopsy (SLNB) was defined as the removal of 1-5 nodes and ALND as the removal of 10 nodes or more. Tumor subtype was categorized as luminal, human epidermal growth factor 2-positive (HER2+), or triple-negative. Logistic regression was used to estimate the odds of receiving SLNB alone versus ALND. RESULTS: The inclusion criteria were met by 28,631 patients (21,029 SLNB-alone and 7602 ALND patients). Patients 70 years of age or older were more likely to undergo SLNB alone than ALND (27.0% vs 20.1%; p < 0.001). The radiation therapy use rate was 89.4% after SLNB alone and 89.7% after ALND. In the multivariate analysis, the uptake of Z0011 recommendations increased over time (2014 vs 2009: odds ratio [OR] 13.02; p < 0.001). Younger patients were less likely to undergo SLNB alone than older patients (age <40 vs ≥70: OR 0.59; p < 0.001). Patients with HER2+ (OR 0.89) or triple-negative disease (OR 0.79) (p < 0.001) were less likely to undergo SLNB alone than those with luminal subtypes. CONCLUSIONS: Among women potentially eligible for ACOSOG Z0011, the use of SLNB alone increased over time in all groups, but the extent of axillary surgery differed by patient age and tumor subtype.

The use of adjuvant radiotherapy in elderly patients with early-stage breast cancer: changes in practice patterns after publication of Cancer and Leukemia Group B 9343.

BACKGROUND: The Cancer and Leukemia Group B (CALGB) 9343 randomized phase 3 trial established lumpectomy and adjuvant therapy with tamoxifen alone, rather than both radiotherapy and tamoxifen, as a reasonable treatment course for women aged >70 years with clinical stage I (AJCC 7th edition), estrogen receptor-positive breast cancer. An analysis of the Surveillance, Epidemiology, and End Results (SEER) registry was undertaken to assess practice patterns before and after the publication of this landmark study. METHODS: The SEER database from 2000 to 2009 was used to identify 40,583 women aged ≥70 years who were treated with breast-conserving surgery for clinical stage I, estrogen receptor-positive and/or progesterone receptor-positive breast cancer. The percentage of patients receiving radiotherapy and the type of radiotherapy delivered was assessed over time. Administration of radiotherapy was further assessed across age groups; SEER cohort; and tumor size, grade, and laterality. RESULTS: Approximately 68.6% of patients treated between 2000 and 2004 compared with 61.7% of patients who were treated between 2005 and 2009 received some form of adjuvant radiotherapy (P < .001). Coinciding with a decline in the use of external beam radiotherapy, there was an increase in the use of implant radiotherapy from 1.4% between 2000 and 2004 to 6.2% between 2005 to 2009 (P < .001). There were significant reductions in the frequency of radiotherapy delivery over time across age groups, tumor size, and tumor grade and regardless of laterality (P < .001 for all). CONCLUSIONS: Randomized phase 3 data support the omission of adjuvant radiotherapy in elderly women with early-stage breast cancer. Analysis of practice patterns before and after the publication of these data indicates a significant decline in radiotherapy use; however, nearly two-thirds of women continue to receive adjuvant radiotherapy.

Dosimetric comparison of preoperative single-fraction partial breast radiotherapy techniques: 3D CRT, noncoplanar IMRT, coplanar IMRT, and VMAT.

The purpose of this study was to compare dosimetric parameters of treatment plans among four techniques for preoperative single-fraction partial breast radiotherapy in order to select an optimal treatment technique. The techniques evaluated were noncoplanar 3D conformal radiation therapy (3D CRT), noncoplanar intensity-modulated radiation therapy (IMRTNC), coplanar IMRT (IMRTCO), and volumetric-modulated arc therapy (VMAT). The planning CT scans of 16 patients in the prone position were used in this study, with the single-fraction prescription doses of 15 Gy for the first eight patients and 18 Gy for the remaining eight patients. Six (6) MV photon beams were designed to avoid the heart and contralateral breast. Optimization for IMRT and VMAT was performed to reduce the dose to the skin and normal breast. All plans were normalized such that 100% of the prescribed dose covered greater than 95% of the clinical target volume (CTV) consisting of gross tumor volume (GTV) plus 1.5 cm margin. Mean homogeneity index (HI) was the lowest (1.05 ± 0.02) for 3D CRT and the highest (1.11 ± 0.04) for VMAT. Mean conformity index (CI) was the lowest (1.42 ± 0.32) for IMRTNC and the highest (1.60 ± 0.32) for VMAT. Mean of the maximum point dose to skin was the lowest (73.7 ± 11.5%) for IMRTNC and the highest (86.5 ± 6.68%) for 3D CRT. IMRTCO showed very similar HI, CI, and maximum skin dose to IMRTNC (differences <1%). The estimated mean treatment delivery time, excluding the time spent for patient positioning and imaging, was 7.0 ± 1.0, 8.3 ± 1.1, 9.7 ± 1.0, and 11.0 ± 1.5min for VMAT, IMRTCO, IMRTNC and 3D CRT, respectively. In comparison of all four techniques for preoperative single-fraction partial breast radiotherapy, we can conclude that noncoplanar or coplanar IMRT were optimal in this study as IMRT plans provided homogeneous and conformal target coverage, skin sparing, and relatively short treatment delivery time.

Early-stage Breast Cancer: Tailored External Beam Fractionation Approaches for Treatment of the Whole or Partial Breast.

Historically, radiotherapy fractionation for early-stage breast cancer primarily consisted of 1.8-2 Gy per fraction given once daily to a total dose of 45-66 Gy over 5-7 weeks for whole breast treatment. Partial breast treatment employed larger dose per fraction (3.4-3.85 Gy) in 10 fractions given twice daily over 1 week. Radiobiologically, breast cancer is increasingly appreciated as a low alpha-beta ratio malignancy that is best treated with larger dose per fraction. Over the past 10 years, there have been increasing data from multiple large randomized clinical trials that support the use of shorter treatment courses: first hypofractionated regimens consisting of 15-20 treatments, and more recently, ultra-hypofractionated regimens as short as 5 treatments. Simultaneously, data from modern partial breast irradiation (PBI) trials support once daily treatment regimens ranging from 1-5 treatments. Shorter treatment courses represent less treatment burden on patients, reduced financial impact, and potentially improved access to care for patients with transportation and/or socioeconomic barriers. Here we review the evolution of whole and partial breast treatment regimens for early-stage breast cancer.

Optimizing Adjuvant Treatment Recommendations for Older Women with Biologically Favorable Breast Cancer: Short-Course Radiation or Long-Course Endocrine Therapy?

Omission of radiotherapy among older women taking 5 years of adjuvant endocrine therapy following breast conserving surgery for early-stage, hormone sensitive breast cancers is well-studied. However, endocrine therapy toxicities are significant, and many women have difficulty tolerating endocrine therapy, particularly elderly patients with comorbidities. Omission of endocrine therapy among women receiving adjuvant radiation is less well-studied, but available randomized and non-randomized data suggest that this approach may confer equivalent local control and survival for select patients. Herein we review available randomized and non-randomized outcome data for women treated with radiation monotherapy and emphasize the need for future prospective, randomized studies of endocrine therapy omission.

Dosimetric variation in preoperative partial breast radiosurgery assessed by deformable image registrations.

Objective: To assess dosimetric variation caused by breast deformation in breast radiosurgery based on deformable image registration. Methods: This study included 30 patients who were treated in the prone position for preoperative partial breast radiosurgery. The biopsy clip in CBCT was aligned to the one from the planning CT. Deformable image registration (DIR) was performed to deform the planning CT into the CBCT, focusing on the breast shape. The treated plan (PTx) was recalculated based on the deformed CT. Thus, PTx represented the actual treatment delivered to the patient and was compared to the original plan (POrg). Results: The mean differences of target volumes covered by 95% and 100% of the prescribed dose between POrg and PTx were less than 0.5%. The mean differences ± standard division for skin maximum dose (Dmax), dose to 1cc (D1cc) and D10cc were 0.3 ± 0.7 Gy, 0.3 ± 0.6 Gy and 0.6 ± 0.6Gy between POrg and PTx, respectively. Conclusion: The treated plan was accurately recalculated based on the deformed CT. Despite slight variance in breast deformation, the dosimetric variation was very small, ensuring that adequate target coverage and skin dose were maintained during treatment as planned originally.

Utilization of neoadjuvant chemotherapy in high-risk, node-negative early breast cancer.

BACKGROUND: Controversy exists regarding the optimal sequence of chemotherapy among women with operable node-negative breast cancers with high-risk tumor biology. We evaluated national patterns of neoadjuvant chemotherapy (NACT) use among women with early-stage HER2+, triple-negative (TNBC), and high-risk hormone receptor-positive (HR+) invasive breast cancers. METHODS: Women ≥18 years with cT1-2/cN0 HER2+, TNBC, or high recurrence risk score (≥31) HR+ invasive breast cancers who received chemotherapy were identified in the National Cancer Database (2010-2016). Cochran-Armitage and logistic regression examined temporal trends and likelihood of undergoing NACT versus adjuvant chemotherapy based on patient age and molecular subtype. RESULTS: Overall, 96,622 patients met study criteria; 25% received NACT and 75% underwent surgery first, with comparable 5-year estimates of overall survival (0.90, 95% CI 0.892-0.905 vs 0.91, 95% CI 0.907-0.913). During the study period, utilization of NACT increased from 14% to 36% and varied according to molecular subtype (year*molecular subtype p < 0.001, p-corrected < 0.001). Women with HER2+ (OR 4.17, 95% CI 3.70-4.60, p < 0.001, p-corrected < 0.001) and TNBC (OR 3.81, 95% CI 3.38-4.31, p < 0.001, p-corrected < 0.001) were more likely to receive NACT over time, without a change in use among those with HR+ disease (OR 1.58, 95% CI 0.88-2.87, p = 0.13, p-corrected = 0.17). CONCLUSION: Among women with early-stage triple-negative and HER2+ breast cancers, utilization of NACT increased over time, a trend that correlates with previously reported improved rates of pCR and options post-neoadjuvant treatment with residual disease. Future research is needed to better understand multidisciplinary decisions for NACT and implications for breast cancer patients.

Clinical Experience With Machine Learning-Based Automated Treatment Planning for Whole Breast Radiation Therapy.

PURPOSE: The machine learning-based automated treatment planning (MLAP) tool has been developed and evaluated for breast radiation therapy planning at our institution. We implemented MLAP for patient treatment and assessed our clinical experience for its performance. METHODS AND MATERIALS: A total of 102 patients of breast or chest wall treatment plans were prospectively evaluated with institutional review board approval. A human planner executed MLAP to create an auto-plan via automation of fluence maps generation. If judged necessary, a planner further fine-tuned the fluence maps to reach a final plan. Planners recorded the time required for auto-planning and manual modification. Target (ie, breast or chest wall and nodes) coverage and dose homogeneity were compared between the auto-plan and final plan. RESULTS: Cases without nodes (n = 71) showed negligible (<1%) differences for target coverage and dose homogeneity between the auto-plan and final plan. Cases with nodes (n = 31) also showed negligible difference for target coverage. However, mean ± standard deviation of volume receiving 105% of the prescribed dose and maximum dose were reduced from 43.0% ± 26.3% to 39.4% ± 23.7% and 119.7% ± 9.5% to 114.4% ± 8.8% from auto-plan to final plan, respectively, all with P ≤ .01 for cases with nodes (n = 31). Mean ± standard deviation time spent for auto-plans and additional fluence modification for final plans were 12.1 ± 9.3 and 13.1 ± 12.9 minutes, respectively, for cases without nodes, and 16.4 ± 9.7 and 26.4 ± 16.4 minutes, respectively, for cases with nodes. CONCLUSIONS: The MLAP tool has been successfully implemented for routine clinical practice and has significantly improved planning efficiency. Clinical experience indicates that auto-plans are sufficient for target coverage, but improvement is warranted to reduce high dose volume for cases with nodal irradiation. This study demonstrates the clinical implementation of auto-planning for patient treatment and the significant importance of integrating human experience and feedback to improve MLAP for better clinical translation.

Accuracy and efficiency of image-guided radiation therapy (IGRT) for preoperative partial breast radiosurgery.

OBJECTIVE: To analyze and evaluate accuracy and efficiency of IGRT process for preoperative partial breast radiosurgery. METHODS: Patients were initially setup with skin marks and 5 steps were performed: (1) Initial orthogonal 2D kV images, (2) pre-treatment 3D CBCT images, (3) verification orthogonal 2D kV images, (4) treatment including mid-treatment 2D kV images (for the final 15 patients only), and (5) post-treatment orthogonal 2D kV or 3D CBCT images. Patient position was corrected at each step to align the biopsy clip and to verify surrounding soft tissue positioning. RESULTS: The mean combined vector magnitude shifts and standard deviations at the 5 imaging steps were (1) 0.96 ± 0.69, (2) 0.33 ± 0.40, (3) 0.05 ± 0.12, (4) 0.15 ± 0.17, and (5) 0.27 ± 0.24 in cm. The mean total IGRT time was 40.2 ± 13.2 minutes. Each step was shortened by 2 to 5 minutes with improvements implemented. Overall, improvements in the IGRT process reduced the mean total IGRT time by approximately 20 minutes. Clip visibility was improved by implementing oblique orthogonal images. CONCLUSION: Multiple imaging steps confirmed accurate patient positioning. Appropriate planning and imaging strategies improved the effectiveness and efficiency of the IGRT process for preoperative partial breast radiosurgery.

Optimizing Radiation Therapy to Boost Systemic Immune Responses in Breast Cancer: A Critical Review for Breast Radiation Oncologists.

Immunotherapy using immune checkpoint blockade has revolutionized the treatment of many types of cancer. Radiation therapy (RT)-particularly when delivered at high doses using newer techniques-may be capable of generating systemic antitumor effects when combined with immunotherapy in breast cancer. These systemic effects might be due to the local immune-priming effects of RT resulting in the expansion and circulation of effector immune cells to distant sites. Although this concept merits further exploration, several challenges need to be overcome. One is an understanding of how the heterogeneity of breast cancers may relate to tumor immunogenicity. Another concerns the need to develop knowledge and expertise in delivery, sequencing, and timing of RT with immunotherapy. Clinical trials addressing these issues are under way. We here review and discuss the particular opportunities and issues regarding this topic, including the design of informative clinical and translational studies.

Immediate Breast Reconstruction Allows for the Timely Initiation of Postmastectomy Radiation Therapy.

BACKGROUND: Complications from breast reconstruction may delay postmastectomy radiation therapy and impact breast cancer outcomes. The authors hypothesized that immediate breast reconstruction may be associated with delays in the initiation of radiation, but that this delay would not significantly impact overall patient survival. METHODS: Using the National Cancer Database, the authors identified women with breast cancer who underwent mastectomy and received postmastectomy radiation therapy. Delayed radiation was defined as treatment initiated 6 months or more after surgery in patients who received adjuvant chemotherapy or 12 weeks or more after surgery in patients who received neoadjuvant or no chemotherapy. RESULTS: Women undergoing breast reconstruction had an increased time to postmastectomy radiation therapy, 154 days versus 132 days (p < 0.001), and were more likely to experience a delay in initiating radiation (OR, 1.25; 95 percent CI, 1.188 to 1.314). Other factors associated with delayed radiation included increased Charlson/Deyo scores, neoadjuvant chemotherapy, nonprivate insurance, and black race. Cox proportional hazards models revealed no evidence of a reduced adjusted overall survival in the immediate breast reconstruction group (hazard ratio, 0.836; 95 percent CI, 0.802 to 0.871; p < 0.001). Restricted cubic spline analysis identified the threshold number of days at which the start of radiation began to impact survival at 169 days (95 percent CI, 160 to 190 days), 75 days (95 percent CI, 42 to 90 days), and 71 days (95 percent CI, 41 to 90 days) in patients undergoing adjuvant, neoadjuvant, and no chemotherapy, respectively. CONCLUSION: Immediate breast reconstruction is associated with a modest delay in initiating postmastectomy radiation therapy but does not impact overall survival. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Automatic Planning of Whole Breast Radiation Therapy Using Machine Learning Models.

Purpose: To develop an automatic treatment planning system for whole breast radiation therapy (WBRT) based on two intensity-modulated tangential fields, enabling near-real-time planning. Methods and Materials: A total of 40 WBRT plans from a single institution were included in this study under IRB approval. Twenty WBRT plans, 10 with single energy (SE, 6MV) and 10 with mixed energy (ME, 6/15MV), were randomly selected as training dataset to develop the methodology for automatic planning. The rest 10 SE cases and 10 ME cases served as validation. The auto-planning process consists of three steps. First, an energy prediction model was developed to automate energy selection. This model establishes an anatomy-energy relationship based on principle component analysis (PCA) of the gray level histograms from training cases' digitally reconstructed radiographs (DRRs). Second, a random forest (RF) model generates an initial fluence map using the selected energies. Third, the balance of overall dose contribution throughout the breast tissue is realized by automatically selecting anchor points and applying centrality correction. The proposed method was tested on the validation dataset. Non-parametric equivalence test was performed for plan quality metrics using one-sided Wilcoxon Signed-Rank test. Results: For validation, the auto-planning system suggested same energy choices as clinical-plans in 19 out of 20 cases. The mean (standard deviation, SD) of percent target volume covered by 100% prescription dose was 82.5% (4.2%) for auto-plans, and 79.3% (4.8%) for clinical-plans (p > 0.999). Mean (SD) volume receiving 105% Rx were 95.2 cc (90.7 cc) for auto-plans and 83.9 cc (87.2 cc) for clinical-plans (p = 0.108). Optimization time for auto-plan was <20 s while clinical manual planning takes between 30 min and 4 h. Conclusions: We developed an automatic treatment planning system that generates WBRT plans with optimal energy selection, clinically comparable plan quality, and significant reduction in planning time, allowing for near-real-time planning.