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Background: Proton pump inhibitors (PPIs) negatively impact fluoropyrimidine-based chemotherapy efficacy in colorectal cancer. This study assessed PPI impact on major pathologic response (mPR) rates of pancreatic adenocarcinoma (PDAC) patients receiving fluoropyrimidine-based chemotherapy., Methods: An institutional retrospective review of resected PDAC patients receiving neoadjuvant fluoropyrimidine-based chemotherapy (98% FOLFIRINOX) from 2011 to 2021 was conducted. Outcomes were stratified by use or nonuse of PPIs within 6 months of neoadjuvant chemotherapy initiation. Primary outcome was mPR defined as complete or near complete response., Results: Among 540 patients included, the median age was 64 (IQR: 60-70) years, 297 (55%) were male, and 202 (37%) were PPI users. 170 (31%) patients had mPR with similar rates among PPI users and nonusers (29% vs. 33%, p = 0.38). No difference in mPR was seen between PPI users and nonusers receiving chemoradiation (35% vs. 36%, p = 0.89) or ≥8 cycles of NAC (33% vs. 36%, p = 0.55). Median OS for PPI users was 30.9 versus 31.7 months for nonusers (p = 0.62). On multivariable analysis, PPI therapy was not associated with decreased survival., Conclusion: PPI usage did not significantly influence mPR or OS following neoadjuvant fluoropyrimidine-based chemotherapy in resected PDAC patients. Further analysis of all patients, not just those who underwent resection, is required., (© 2024 Wiley Periodicals LLC.)

Background: The COVID-19 pandemic has severely affected healthcare systems globally, resulting in significant delays and challenges in various medical treatments, particularly in cancer care. This study aims to investigate the repercussions of the pandemic on surgical interventions for colorectal cancer (CRC) in the US, using data from the National Cancer Database., Study Design: We conducted a retrospective analysis of the National Cancer Database, encompassing adult patients who underwent surgical procedures for colon and rectal cancer in 2019 (pre-COVID) and 2020 (COVID). We examined various demographic and clinical variables, including patient characteristics, tumor staging, surgical approaches, and socioeconomic factors., Results: The analysis included 105,517 patients, revealing a 17.3% reduction in surgical cases during the initial year of the pandemic. Patients who underwent surgery in 2020 displayed more advanced clinical and pathological tumor stages compared to those treated in 2019. After diagnosis, no delay was reported in the treatment. Patients operated during the pandemic, Black patients, uninsured, and Medicaid beneficiaries had worse stage colon and rectal cancer, and individuals with lower incomes bore the burden of advanced colon cancer., Conclusions: The impact of the COVID-19 pandemic on CRC surgery transcends a mere decline in case numbers, resulting in a higher prevalence of patients with advanced disease. This study underscores the exacerbated disparities in cancer care, particularly affecting vulnerable populations. The COVID-19 pandemic has left a significant and enduring imprint on CRC surgery, intensifying the challenges faced by patients and healthcare systems. Comprehensive studies are imperative to comprehend the long-term consequences of delayed screenings, diagnoses, and treatments as healthcare planning for the future must consider the unintended repercussions of pandemic-related disruptions., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Bronchial carcinoids are rare in children and the treatment is based on tumor behavior in adults. The purpose of this study was to determine factors and management strategies associated with long-term survival in the pediatric population using a national cohort., Methods: Patients aged ≤20 years with bronchial carcinoid tumors were identified in the 2004-2020 National Cancer Database using ICD-O-3 codes. Tumor characteristics and management were compared among typical (TC) and atypical (AC) histological subtypes using Chi-square and Fisher's exact tests. Kaplan-Meier and univariate Cox proportional hazards analyses were used to assess survival., Results: Of 273 patients, 251 (92%) had TCs, and 22(8%) had ACs. The median (IQR) age was 18 (16,19) years. Most patients underwent lobectomy or bilobectomy (67%), followed by sublobar resection (17%), no resection or bronchoscopic excision or ablation (8%), and pneumonectomy (7.7%). Margins were negative in 96%. Lymph node (LN) assessment was performed in 216 patients (84%) with a median (IQR) of 7(3,13) LNs, and 50 (23%) had ≥1 positive LN. There was no difference in age, resection, margin status, LN assessment, or positivity between TC and AC (all p > 00.05). Detection of nodal metastasis did not increase beyond the resection of 1-3 LNs (p = 0.72). Ten-year survival was worse for AC than TC (79% (41, 100) vs 98% (95, 100), HR = 6.9 (95% CI: 1.2-38.3, p = 0.03). Ten-year survival among those with and without LN assessment was 97% (94, 100) vs 91% (81, 100), HR = 4.0, 95% CI: 0.8-19.9, p = 0.09). There were no deaths in those with negative LN while 10-year survival was 89% (72, 100) in those with ≥1 positive LN., Conclusion: Among children with bronchial carcinoids, survival is excellent with TC or negative LN. Atypical histology and positive LN have poor survival and should prompt close monitoring. These risk factors may be missed in the absence of surgical resection and lymph node sampling., Level of Evidence: III., Type of Study: Retrospective Study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Implementing perioperative interventions such as enhanced recovery pathways (ERPs) has improved short-term outcomes and minimized length of stay. Preliminary evidence suggests that adherence to the enhanced recovery after surgery protocol may also enhance 5-year cancer-specific survival (CSS) in colorectal cancer surgery. This retrospective study presents long-term survival outcomes and disease recurrence from a high-volume, single-center practice., Methods: All patients over 18 years of age diagnosed with rectal adenocarcinoma and undergoing elective minimally invasive surgery (MIS) were retrospectively reviewed between February 2005 and April 2018. Relevant data were extracted from Mayo electronic records and securely stored in a database. Short-term morbidity and long-term oncological outcomes were compared between patients enrolled in ERP and those who received non-enhanced care., Results: Overall, 600 rectal cancer patients underwent MIS, of whom 320 (53.3%) were treated according to the ERP and 280 (46.7%) received non-enhanced care. ERP was associated with a decrease in length of stay (3 vs. 5 days; p < 0.001) and less overall complications (34.7 vs. 54.3%; p < 0.001). The ERP group did not show an improvement in overall survival (OS) or disease-free survival (DFS) compared with non-enhanced care on multivariable (non-ERP vs. ERP OS: hazard ratio [HR] 1.268, 95% confidence interval [CI] 0.852-1.887; DFS: HR 1.050, 95% CI 0.674-1.635) analysis., Conclusion: ERP was found to be associated with a reduction in short-term morbidity, with no impact on long-term oncological outcomes, such as OS, CSS, and DFS., (© 2024. Society of Surgical Oncology.)

Background: Prolonged survival of patients with metastatic disease has furthered interest in metastasis-directed therapy (MDT)., Research Question: There is a paucity of data comparing lung MDT modalities. Do outcomes among sublobar resection (SLR), stereotactic body radiation therapy (SBRT), and percutaneous ablation (PA) for lung metastases vary in terms of local control and survival?, Study Design and Methods: Medical records of patients undergoing lung MDT at a single cancer center between January 2015 and December 2020 were reviewed. Overall survival, local progression, and toxicity outcomes were collected. Patient and lesion characteristics were used to generate multivariable models with propensity weighted analysis., Results: Lung MDT courses (644 total: 243 SLR, 274 SBRT, 127 PA) delivered to 511 patients were included with a median follow-up of 22 months. There were 47 local progression events in 45 patients, and 159 patients died. Two-year overall survival and local progression were 80.3% and 63.3%, 83.8% and 9.6%, and 4.1% and 11.7% for SLR, SBRT, and PA, respectively. Lesion size per 1 cm was associated with worse overall survival (hazard ratio, 1.24; P = .003) and LP (hazard ratio, 1.50; P < .001). There was no difference in overall survival by modality. Relative to SLR, there was no difference in risk of local progression with PA; however, SBRT was associated with a decreased risk (hazard ratio, 0.26; P = .023). Rates of severe toxicity were low (2.1%-2.6%) and not different among groups., Interpretation: This study performs a propensity weighted analysis of SLR, SBRT, and PA and shows no impact of lung MDT modality on overall survival. Given excellent local control across MDT options, a multidisciplinary approach is beneficial for patient triage and longitudinal management., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the completeness and reliability of recurrence data from an institutional cancer registry for patients with head and neck cancer., Patients and Methods: Recurrence information was collected by radiation oncology and otolaryngology researchers. This was compared with the institutional cancer registry for continuous patients treated with radiation therapy for head and neck cancer at a tertiary cancer center. The sensitivity and specificity of institutional cancer registry data was calculated using manual review as the gold standard. False negative recurrences were compared to true positive recurrences to assess for differences in patient characteristics., Results: A total of 1338 patients who were treated from January 1, 2010, through December 31, 2017, were included in a cancer registry and underwent review. Of them, 375 (30%) had confirmed cancer recurrences, 45 (3%) had concern for recurrence without radiologic or pathologic confirmation, and 31 (2%) had persistent disease. Most confirmed recurrences were distant (37%) or distant plus locoregional (29%), whereas few were local (11%), regional (9%), or locoregional (14%) alone. The cancer registry accuracy was 89.4%, sensitivity 61%, and specificity 99%. Time to recurrence was associated with registry accuracy. True positives had recurrences at a median of 414 days vs 1007 days for false negatives., Conclusion: Currently, institutional cancer registry recurrence data lacks the required accuracy for implementation into studies without manual confirmation. Longer follow-up of cancer status will likely improve sensitivity. No identified differences in patients accounted for differences in sensitivity. New, ideally automated, data abstraction tools are needed to improve detection of cancer recurrences and minimize manual chart review., Competing Interests: The spouse of author Roman Kowalchuk, MD, was previously employed by GE Healthcare., (© 2024 The Authors.)

Purpose: The role of neoadjuvant chemotherapy (NAC) in node-positive (N+) ER+/HER2- breast cancer (BC) is debated, given low total pathologic complete response (pCR) rates. However, the rate and impact of nodal pCR is unknown. We sought to evaluate nodal pCR rates and the impact on overall survival (OS). Further, we sought to validate the association between nodal pCR with age and Ki67., Methods: We queried the National Cancer Database for cN + ER+/HER2- BC patients treated with NAC and surgery. Data from 2010 to 2018 were used to evaluate nodal pCR and OS, with multivariable Cox proportional hazards modeling for OS, as well as Ki67 for the years 2018-2019., Results: From 2010 to 2018, we identified 19,611 cN + ER+/HER2- BC patients treated with NAC. While total pCR occurred in only 7.4%, nodal pCR rates were nearly double (14.3%). Nodal pCR (+/- breast pCR) was seen in 21.7% and associated with 5-year OS rate of 86.1% (95% CI: 84.9-87.4%) versus 77.1% (95% CI: 76.3-77.9%) in patients without nodal pCR (p < 0.001). On multivariable analysis, nodal pCR had better OS (adjusted HR 0.57, 95% CI 0.52-0.63, p < 0.001) across all age groups. Of 2,444 patients with available Ki67, those with age < 50 and Ki67 ≥ 20% had the highest nodal pCR at 31.6%., Conclusion: In cN + ER+/HER2- BC treated with NAC, nodal pCR is common, associated with age and Ki67, and prognostic for OS. These data strongly suggest that for cN + patients, eradication of nodal disease is critical for OS, and total pCR may not be the optimal measure of NAC benefit., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Mixed invasive ductolobular breast cancer (MIDLC) is a rare breast cancer with varying lobular and ductal components. Characteristics, management, and outcomes of MIDLC are not well understood due to the rarity of the cancer and the lack of uniform diagnostic criteria and reporting. There is a need for better understanding and individualized management of this heterogeneous spectrum of breast cancers., (© 2023. Society of Surgical Oncology.)

Background: Mixed invasive ductolobular breast cancer (MIDLC) is a rare histological subtype of breast cancer (BC), with components of both invasive ductal cancer (IDC) and invasive lobular cancer (ILC). Its clinicopathological features and outcomes have not been well characterized., Method: The National Cancer Database 2010-2017 was reviewed to identify women with stage I-III BCs. Univariate analysis was performed using Chi-square or Wilcoxon rank-sum tests and multivariable analysis with logistic regression to predict surgical decisions. Survival was assessed using multivariable Cox proportional hazards regression analysis., Results: We identified 955,828 women with stage I-III BCs (5.7% MIDLC, 10.3% ILC, and 84.0% IDC). MIDLC was more like ILC than IDC in terms of multicentricity (14.2% MIDLC, 13.0% ILC, 10.0% IDC), hormone receptor positivity (96.6% MIDLC, 98.2% ILC, 81.2% IDC), and use of neoadjuvant chemotherapy (NAC; 5.8% MIDLC, 5.2% ILC, 10.8% IDC). 744,607 women underwent upfront surgery. The mastectomy rates were 42.3% for MIDLC, 46.5% for ILC, and 33.3% for IDC (all p < 0.001). With 5.5 years of median follow-up, the adjusted overall survival in the upfront surgery hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) biological subgroup was better in MIDLC (hazard ratio 0.88, p < 0.001) and ILC (hazard ratio 0.91, p < 0.001) than in IDC. Like ILC, MIDLC also had a lower pathological complete response to NAC than IDC (12.3% MIDLC, 7.3% ILC, 28.6% IDC)., Conclusions: MIDLC displays a mixed pattern of characteristics favoring features of ILC compared with IDC, with favorable 5-year overall survival compared with IDC within the HR+/HER2- subtype who underwent upfront surgery., (© 2023. Society of Surgical Oncology.)

Background: Ileal pouch-anal anastomosis (IPAA) is the standard restorative procedure following proctocolectomy in patients with inflammatory bowel disease (IBD) who require colectomy. However, removal of the diseased colon does not eliminate the risk of pouch neoplasia. We aimed to assess the incidence of pouch neoplasia in IBD patients following IPAA., Methods: All patients at a large tertiary center with International Classification of Diseases-Ninth Revision/International Classification of Diseases-Tenth Revision codes for IBD who underwent IPAA and had subsequent pouchoscopy were identified using a clinical notes search from January 1981 to February 2020. Relevant demographic, clinical, endoscopic, and histologic data were abstracted., Results: In total, 1319 patients were included (43.9% women). Most had ulcerative colitis (95.2%). Out of 1319 patients, 10 (0.8%) developed neoplasia following IPAA. Neoplasia of the pouch was seen in 4 cases with neoplasia of the cuff or rectum seen in 5 cases. One patient had neoplasia of the prepouch, pouch, and cuff. Types of neoplasia included low-grade dysplasia (n = 7), high-grade dysplasia (n = 1), colorectal cancer (n = 1), and mucosa-associated lymphoid tissue lymphoma (n = 1). Presence of extensive colitis, primary sclerosing cholangitis, backwash ileitis, and rectal dysplasia at the time of IPAA were significantly associated with increased risk of pouch neoplasia., Conclusions: The incidence of pouch neoplasia in IBD patients who have undergone IPAA is relatively low. Extensive colitis, primary sclerosing cholangitis, and backwash ileitis prior to IPAA and rectal dysplasia at the time of IPAA raise the risk of pouch neoplasia significantly. A limited surveillance program might be appropriate for patients with IPAA even with a history of colorectal neoplasia., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Estrogen receptor (ER) and progesterone receptor (PR) guide management and impact outcomes of breast cancer (BC). This study compares ER-low (1-10%) with ER-negative (< 1%) and ER-positive (>10%) BC and investigates the significance of PR expression within ER-low disease., Patients and Methods: All patients with HER2-negative invasive BC were identified from the National Cancer Database 2018-2019. Treatment and outcomes were compared using chi-squared tests and multivariable logistic regression., Results: Of 232,762 patients, ER expression was: negative (13.8%), low (2.0%), and > 10% (84.2%). Chemotherapy was given in 83.9% of ER- disease, 82.4% of ER-low/PR- disease, 58.9% of ER-low/PR+ disease, and only in 22.9% of ER+ disease. Within the ER-low subgroup, adjuvant endocrine therapy, recurrence score, and Ki67 varied by PR status (all < 0.01). Patients with ER-low disease selected for neoadjuvant chemotherapy (NAC) were younger and had higher T and N category, tumor grade, and Ki67. With NAC, pathological complete response (pCR) rates were similar between ER-low/PR- and ER-low/PR+ (39.5% and 38.1%, respectively, p = 0.67), and were closer to the ER- group (39.7%) than the ER+ group (8.4%). On multivariable analysis, the adjusted effect of ER status (1-10% versus > 10%) on chemotherapy administration was odds ratio (OR) 8.2 (95% CI 7.3-9.2, p < 0.001) for PR-negative, and OR 3.3 (95% CI 7.3-9.2, p < 0.001) for PR-positive., Conclusions: This study suggests that the tumor features and clinical management of ER-low tumors vary significantly by PR expression. Within ER-low tumors, PR- tumors more closely resemble ER- BC, while PR+ tumors exhibit less aggressive characteristics. In ER-low disease selected for treatment with NAC, response is similar to ER- regardless of PR status., (© 2023. Society of Surgical Oncology.)

Background: Left ventricular outflow tract obstruction is common among symptomatic patients with hypertrophic cardiomyopathy, yet septal reduction by surgical myectomy (septal myectomy [SM]) is performed infrequently in many centers. This study examined the possible relationship between institutional case volume and early outcomes of SM., Methods: The Society of Thoracic Surgeons Adult Cardiac Surgery Database was queried for patients with hypertrophic cardiomyopathy who underwent SM from January 2012 to December 2019. The study defined center case volume categories as <1, 1 to 4.99, 5 to 9.99, and ≥10 cases performed on average per year., Results: The study population included 5935 patients at 481 centers with 933 surgeons. The range of average center volume was <1 to 138 cases per year. Overall early mortality was 2.6%, ventricular septal defect (VSD) occurred in 1.9%, and complete heart block occurred in 9.0%. Concomitant mitral valve (MV) repair was performed in 28.7%, and MV replacement was performed in 17.1%. In multivariable analysis, the lowest annual case volume (average <1 case/y) was consistently associated with greater early mortality (odds ratio [OR], 5.4; CI, 3.0-9.9; P < .001), greater risk of VSD (OR, 9.3; CI ,4.2-20.4; P < .001), increased incidence of complete heart block (OR, 2.0; CI, 1.5-2.7; P < .001), and a higher likelihood of MV replacement (OR, 9.4; CI, 7.5-11.8; P < .001)., Conclusions: Volume of SM cases varies widely among institutions reporting to the Society of Thoracic Surgeons Adult Cardiac Surgery Database. There appears to be an important association between surgical experience, as reflected by institutional case volume, and early outcomes, including mortality, as well as the occurrence of VSD, heart block, and MV replacement., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: We aim to explore the prognostic role of absolute lymphocyte count (ALC) before, during, and after treatment on oncologic outcomes in human papillomavirus associated oropharyngeal cancer (HPV(+)OPSCC)., Methods: Retrospective cohort at a tertiary center, 2006-2018. Multivariable Cox regressions were used to determine the effect of ALC on risk of progression. Univariate linear regression was performed to determine clinical factors associated with lower ALC., Results: All 197 patients underwent primary surgery. Mean (SD) ALC nadirs (×10 9  cells/L) were: baseline (N = 149): 1.69 (0.56); postoperative (N = 126): 1.58 (0.59); post-RT (N = 141): 0.68 (0.35) and long-term (N = 105): 0.88 (0.37). Lower baseline ALC nadir was associated with worse overall survival (HR 3.85, 95%CI: 1.03-14.29, p = 0.04). Lower postoperative ALC nadir was associated with higher risk of progression (HR 2.63, 95%CI: 1.04-6.67, p = 0.04)., Conclusions: Lower baseline ALC is associated with worse survival, whereas lower postoperative ALC is associated with increased risk of progression in surgically treated HPV(+)OPSCC., (© 2022 Wiley Periodicals LLC.)

Background: Ductal carcinoma in situ (DCIS) is noninvasive breast cancer and therefore nodal staging is not routinely recommended. We evaluated the use of and factors associated with axillary surgery in DCIS in the National Cancer Database (NCDB)., Methods: DCIS cases were identified from the NCDB 2012-2018. Use of axillary surgery was evaluated over time, and factors associated with axillary surgery were assessed for breast-conserving surgery (BCS) and mastectomy groups., Results: We identified 178,762 patients, median age of 60 years. Majority of DCIS (87%) was ER-positive, and 14% low, 43% intermediate, and 44% high grade. Median DCIS size was 1.1 cm. BCS was performed in 72%, whereas 28% had mastectomy. Overall axillary surgery was performed in 38% and was higher in patients undergoing mastectomy compared with patients undergoing BCS (88% vs. 19%, p < 0.001). At axillary surgery, the vast majority (92%) had 1-5 nodes examined, whereas 8% had >5 nodes examined. Over time, axillary surgery decreased in BCS patients (21% in 2012 to 17% in 2018, p < 0.001) but increased slightly in mastectomy patients (86% in 2012 to 90% in 2018, p < 0.001). On multivariable analysis, factors significantly associated with axillary surgery were younger patient age, larger tumor size, higher grade, and ER-negative status., Conclusions: Factors associated with axillary surgery reflect higher risk disease for upstage to invasive cancer, indicating surgeon judgment. However, despite axillary surgery being overtreatment of DCIS, it is common in mastectomy and is performed for one in five patients undergoing BCS. This provides opportunity for improvement in breast cancer care delivery., (© 2022. Society of Surgical Oncology.)

Background: Fine needle aspiration (FNA) of sonographically suspicious axillary lymph nodes is helpful to clinically stage patients and guide consideration of neoadjuvant therapy in breast cancer. However, data are limited for suspicious nodes that are FNA negative. Our goal is to compare the frequency of node positivity between patients with negative axillary ultrasound (AUSneg) versus suspicious AUS with negative FNA (FNAneg)., Methods: With IRB approval, we identified all clinically node-negative (cN0) patients with invasive breast cancer treated with upfront surgery at our tertiary care center between 2016 and 2021. AUS is routinely performed with FNA of suspicious lymph node(s). We compared clinicopathologic characteristics and nodal positivity rates between AUSneg and FNAneg groups., Results: A total of 1580 cN0 patients with invasive breast cancer were analyzed, including 1240 AUSneg and 340 FNAneg patients. The FNAneg group was younger (median age 59.7 years versus 63.5 years, p < 0.001) and had higher clinical T (cT) category (29.1% versus 21.7% with cT2-cT4 disease, p = 0.005). Final axillary pathologic node positivity did not differ significantly between the AUSneg and FNAneg groups (16.5% versus 19.1%, p = 0.25). Among FNAneg patients, 58/340 (17.1%) had a clip placed, with retrieval confirmed in 28/58 (48.3%). Of the 28 retrieved clipped nodes, 27 were sentinel nodes. Final pathologic nodal status (pN+%) did not differ between patients in whom retrieval of the clipped node was confirmed versus not confirmed (28.6% versus 16.7%, p = 0.28)., Conclusions: Both patients with sonographically suspicious node(s) and negative FNA and patients with negative AUS have a similarly low chance of positive nodes. Additionally, routine targeted excision of FNA-negative clipped nodes is not warranted., (© 2022. Society of Surgical Oncology.)

Background: Although an advantage of neoadjuvant chemotherapy (NAC) is eradication of axillary disease, nodal pCR rates are much lower for ER+/HER2- breast cancer than other subtypes. We sought to evaluate the association of genomic risk with nodal pCR in ER+/HER2- disease., Methods: Patients with ER+/HER2- clinically-node-positive (cT0-cT4d/cN1-cN3/cM0) breast cancer treated with NAC and surgery 2010-2018 in the National Cancer Database were identified. Low genomic risk was classified as Oncotype Dx Recurrence Score (RS) 0-25, or Mammaprint 70-gene or RS coded as "Low." High genomic risk included RS >25, or 70-gene or RS coded as "High." Nodal pCR was compared between patients with high versus low genomic risk by using chi-square tests and multivariable logistic regression., Results: Of 15,698 patients, genomic risk was available for 692 of 15,698 (4.4%). High genomic risk was similar between patients aged <50 years versus 50+ (50.8% vs. 57.3%, p = 0.10). Nodal pCR was higher in high genomic risk (25.0%) than low genomic risk (10.4%, p < 0.001). This difference was observed both for patients aged <50 years (29.9% vs. 9.8%) and aged ≥50 years (22.7% vs. 10.8%). On multivariable analysis adjusted for potential confounding variables, including age, grade, and PR status, genomic risk was independently associated with decreased odds of residual nodal disease (odds ratio 0.49, p = 0.002)., Conclusions: For patients with node-positive ER+/HER2- breast cancer treated with NAC, nodal pCR was highest in patients aged <50 years with high genomic risk tumors. In contrast, nodal pCR rates were low in patients with low genomic risk tumors, regardless of age. This information may help when counseling patients regarding axillary management., (© 2022. Society of Surgical Oncology.)

Background: Management of the axilla in patients with cT1-2N0 breast cancer with one or two positive (+) sentinel lymph nodes (SLNs) is often debated, especially in patients undergoing mastectomy. In 2018, the National Cancer Database (NCDB) began collecting the number of +SLNs, enabling identification of patients with one or two +SLNs for the first time., Methods: From the 2018 NCDB participant user file (PUF), all cT1-2N0M0 patients with one or two +SLNs were identified. The rates of completion axillary lymph node dissection (cALND) after breast-conserving surgery (BCS) and mastectomy were determined, and logistic regression was used to assess factors associated with cALND., Results: Of 10,531 patients with one or two +SLNs, cALND was performed in 807/6498 (12.4%) BCS patients and 1845/4033 (45.7%) mastectomy patients (p < 0.001). Factors associated with cALND in BCS were cT2 versus cT1 (16.0% versus 11.1%, p < 0.001), two versus one positive SLN (20.7% versus 10.8%, p < 0.001), and higher tumor grade (grade 3: 15.4% versus grade 1-2: 11.7%, p = 0.002). Factors associated with cALND among mastectomy were cT2 versus cT1 (48.2% versus 43.7%, p = 0.004), two versus one positive SLN (56.6% versus 42.8%, p < 0.001), younger age (age < 50 years: 49.0%, age 50+ years: 44.1%, p = 0.004), and Hispanic ethnicity (55.7% versus 45.1%, p = 0.001). After adjusting for pN category, adjuvant radiation was significantly less likely after mastectomy if cALND was performed (odds ratio (OR) 0.51, p < 0.001)., Conclusions: Omission of cALND with one or two +SLNs in BCS is common. Deescalation of axillary therapy in mastectomy is slower, with a cALND rate of 45.7% in 2018. With the recent updates to the National Cancer Care Network (NCCN) guidelines, we anticipate continued deescalation of axillary therapy in mastectomy patients., (© 2022. Society of Surgical Oncology.)

Objectives: The incidence and predictors of pneumonitis for patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) in the era of consolidation durvalumab have yet to be fully elucidated. In this large single institution analysis, we report the incidence of and factors associated with grade 2 + pneumonitis in NSCLC patients treated with the PACIFIC regimen., Materials and Methods: We identified all patients treated at our institution with definitive CRT followed by durvalumab from 2018 to 2021. Clinical documentation and imaging studies were reviewed to determine grade 2 + pneumonitis events, which required the following: 1) pulmonary symptoms warranting prolonged steroid taper, oxygen dependence, and/or hospital admission and 2) radiographic findings consistent with pneumonitis., Results: One-hundred ninety patients were included. The majority received 60 Gray (Gy) in 30 fractions with concurrent carboplatin and paclitaxel. Median number of durvalumab cycles received was 12 (IQR: 4-22). At a median follow-up of 14.8 months, 50 (26.3%) patients experienced grade 2 + pneumonitis with a 1-year cumulative incidence of 27.8% (95% CI: 21.9-35.4). Seventeen (8.9%) patients experienced grade 3 + pneumonitis and 4 grade 5 (2.1%). Dosimetric predictors of pneumonitis included ipsilateral and total lung volume receiving 5 Gy or greater (V5Gy), V10Gy, V20Gy, V40Gy, and mean dose and contralateral V40Gy. Heart V5Gy, V10Gy, and mean dose were also significant variables. Overall survival estimates at 1 and 3 years were 87.4% (95% CI: 82.4-92.8) and 60.3% (95% CI: 47.9-74.4), respectively., Conclusion: We report a risk of pneumonitis higher than that seen on RTOG 0617 and comparable to the PACIFIC study. Multiple lung and heart dosimetric factors were predictive of pneumonitis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: The primary aim of this study was to evaluate patient-reported outcome measures in patients undergoing mastectomy with and without breast reconstruction (immediate or delayed) with and without nipple preservation., Methods: All female patients undergoing mastectomy between 2011 and 2015 at Mayo Clinic Rochester were identified and were mailed the BREAST-Q survey. Breast satisfaction, psychosocial well-being, and sexual well-being were evaluated and compared by surgery type using Wilcoxon rank-sum tests for univariate analysis and linear regression for multivariable analysis adjusting for potential confounders., Results: Of 1547 patients, 771 completed the BREAST-Q survey (response rate 50%). Of these 771 respondents, 237 (31%) did not have reconstruction, 198 (26%) had nipple-sparing mastectomy with reconstruction (NSM), and 336 (44%) had skin-sparing mastectomy with reconstruction (SSM) ± nipple-areolar complex (NAC) reconstruction (via surgery ± tattoo). Patients with breast reconstruction had consistently higher BREAST-Q scores versus those without. Comparing NSM with all SSMs, there was no difference in satisfaction with breasts (mean 71.8 vs. 70.2, p = 0.21) or psychosocial well-being (mean 81.9 vs. 81.3, p = 0.47); however, sexual well-being was significantly higher in the NSM group on univariate (mean 64.5 vs. 58.0, p = 0.002) and multivariable (β = -4.69, p = 0.03) analysis. Sexual well-being scores were similar for NSM and the SSM subgroups with any type of NAC reconstruction., Conclusions: This study demonstrates that NSM positively impacts patient sexual well-being after breast reconstruction compared with SSM, particularly SSM without nipple reconstruction or tattoo. SSM with any type of NAC reconstruction achieved similar satisfaction and sexual well-being to those undergoing NSM., (© 2022. Society of Surgical Oncology.)

Introduction: The COVID-19 pandemic caused delays in breast cancer management forcing clinicians to potentially alter treatment recommendations. This study compared breast cancer stage at diagnosis and rates of neoadjuvant therapy among women presenting to our institution before and during COVID-19., Methods: Retrospective chart review of patients with a new breast cancer diagnosis from March 2020-August 2020 (during-COVID-19) were compared with March 2019-August 2019 (pre-COVID-19). We compared stage at diagnosis, clinical/demographic features, and neoadjuvant therapy use between the time periods., Results: A total of 573 patients included: 376 pre-COVID-19, 197 during-COVID-19. Method of cancer detection was by imaging in 66% versus 63% and by physical findings/symptoms in 34% versus 37% of patients comparing pre-COVID-19 to during-COVID-19, p = 0.47. Overall clinical prognostic stage did not differ significantly (p = 0.39) between the time periods, nor did cM1 disease (2% in each period); 23% pre-COVID-19 and 27% during-COVID-19 presented with cN+ disease (p = 0.38). Neoadjuvant therapy use was significantly higher during-COVID-19 (39%) versus pre-COVID-19 (29%, p = 0.02) driven by increased neoadjuvant endocrine therapy (NET) use (7% to 16%, p = 0.002), whereas neoadjuvant chemotherapy use did not change (22% vs. 23%, p = 0.72). In HR+/HER2- disease, NET use increased from 10% pre-COVID-19 to 23% during-COVID-19 (p = 0.001) with a significant increase in stage I patients (7 to 22%, p < 0.001) and nonsignificant increases in stage II (18 to 23%, p = 0.63) and stage III (9 to 29%, p = 0.29)., Conclusions: Breast cancer stage at diagnosis did not differ significantly during-COVID-19 compared with pre-COVID-19. More patients during-COVID-19 were treated with NET, which was significantly increased in stage I HR+/HER2- disease., (© 2021. Society of Surgical Oncology.)

The survival benefits of pulmonary thromboendarterectomy (PTE) for the treatment of chronic thromboembolic pulmonary hypertension have been well described. However, the significance of right heart hemodynamic changes and their impact on survival remains poorly understood. We sought to characterize the effects of these changes. We conducted a single center, retrospective review of 159 patients who underwent PTE between 1993 and 2015. Echocardiographic and right heart catheterization data were compared longitudinally before and after PTE in order to establish the extent of hemodynamic response to surgery. Kaplan Meier estimates were used to characterize patient survival over time. Univariable and multivariable Cox proportional hazards regression models were used to assess factors associated with long-term mortality. Among the 159 patients studied, 74 (46.5%) were male with a median age of 55 (IQR: 42-66). One-, 5-, 10-, and 15-year survival was 91.0% (95% CI: 86.6-95.6), 79.6% (73.5-86.3), 66.5% (59.2-74.7), and 56.2% (48.1-65.8). Of the 9 candidate risk factors that were evaluated, only advanced age and increased cardiopulmonary bypass time were found to be significantly associated with increased risk of mortality. Pre- and postsurgical echocardiographic imaging data, when available, revealed a median reduction in right ventricular systolic pressure of 29.0 mm Hg (P < 0.0001) and improvement of tricuspid regurgitation (P < 0.0001), both of which appeared to be sustained across long-term follow-up. Improvements in right heart hemodynamics and tricuspid valvular regurgitation persist on long term surveillance following PTE. While patient selection is often driven by the distribution of disease, close postoperative follow up may improve outcomes., (Copyright © 2021. Published by Elsevier Inc.)

Background: Avoiding unnecessary inpatient stay may decrease hospital-acquired complications and costs while increasing patient satisfaction. This study aimed to develop and validate a score to identify patients eligible for safe same-day discharge after colorectal resections., Methods: This bi-institutional retrospective cohort study included consecutive patients undergoing elective colon and rectal resections (2011-2018) for benign and malignant indications. Two multivariable logistic models were developed based on demographic and surgical risk factors to predict a combined endpoint (ileus, anastomotic leak, intra-abdominal abscess, and readmission). Development and validation datasets were randomly sampled from the entire cohort. Areas under the receiver operating characteristic curves (AUC) were evaluated, and Hosmer-Lemeshow goodness-of-fit tests were used to assess validation model fit., Results: Of 5,389 patients, 1,182 (21.9%) experienced at least one complication of the combined endpoint. Male gender, open surgery, ASA ≥3, wound class ≥3, ileostomy, surgical duration >3 hours, and perioperative IV fluids >3 L all had significantly greater odds of the combined endpoint in the parsimonious multivariable model (all P < .05). The reduced model considering only the 4 variables with the highest OR (>1.5) contained open surgery, ASA ≥3, wound class ≥3, and surgical duration ≥3 hours as predictors (all P < .05, AUC of 0.65; 95% CI 0.63, 0.68). Both the parsimonious model and the reduced model demonstrated no lack of fit in the validation cohort., Conclusion: The suggested score composed of preand intraoperative items may help physicians decide on patients' same-day discharge after colorectal resection., (Copyright © 2021. Published by Elsevier Inc.)

Objective: Substituting lymphadenectomy with sentinel lymph node biopsy for staging purposes in endometrial cancer has raised concerns about incomplete nodal resection and detrimental oncological outcomes. Therefore, this study aimed to investigate the association between the type of lymph node assessment and overall survival in endometrial cancer accounting for node status and histology., Methods: Women with stage I-III endometrial cancer who underwent hysterectomy and lymph node assessment from January 2012 to December 2015 were identified in the National Cancer Database. Patients who underwent neoadjuvant therapy, had previous cancer, and whose follow-up was less than 90 days were excluded. Multivariable Cox proportional hazards regression analyses were performed to assess factors associated with overall survival., Results: Of 68 614 patients, 64 796 (94.4%) underwent lymphadenectomy, 1777 (2.6%) underwent sentinel node biopsy only, and 2041 (3.0%) underwent both procedures. On multivariable analysis, neither sentinel lymph node biopsy alone nor sentinel node biopsy followed by lymphadenectomy was associated with significantly different overall survival compared with lymphadenectomy alone (HR 0.92, 95% CI 0.73 to 1.17, and HR 0.91, 95% CI 0.77 to 1.08, respectively). When stratified by lymph node status, sentinel node biopsy alone or followed by lymphadenectomy was not associated with different overall survival, both in patients with negative (HR 0.95, 95% CI 0.73 to 1.24, and HR 1.04, 95% CI 0.85 to 1.27, respectively) or positive (HR 0.91, 95% CI 0.54 to 1.52, and HR 0.77, 95% CI 0.57 to 1.04, respectively) lymph nodes. These findings held true when sentinel node biopsy alone and sentinel node biopsy plus lymphadenectomy groups were merged, and on stratification by histotype (type one vs type 2) or inclusion of only complete lymphadenectomy (at least 10 pelvic nodes and at least one para-aortic node removed). In all analyses, age, Charlson-Deyo score, black race, AJCC pathological T stage, grade, lymphovascular invasion, brachytherapy, and adjuvant chemotherapy were independently associated with overall survival., Discussion: No difference in overall survival was found in patients with endometrial cancer who underwent sentinel node biopsy alone, sentinel node biopsy followed by lymphadenectomy, or lymphadenectomy alone. This observation remained regardless of node status, histotype, and lymphadenectomy extent., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Given reports of low response rates to neoadjuvant chemotherapy (NAC) in invasive lobular carcinoma (ILC), we evaluated whether use of alternative strategies such as neoadjuvant endocrine therapy (NET) is increasing. Additionally, we investigated whether NET is associated with more breast conservation surgery (BCS) and less extensive axillary surgery in those with ILC., Patients and Methods: We queried the NCDB from 2010 to 2016 and identified all women with stage I-III hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) ILC who underwent surgery. We used Cochrane-Armitage tests to evaluate trends in utilization of the following treatment strategies: NAC, short-course NET, long-course NET, and primary surgery. We compared rates of BCS and extent of axillary surgery stratified by clinical stage and tumor receptor subtype for each treatment strategy., Results: Among 69,312 cases of HR+/HER2- ILC, NAC use decreased slightly (from 4.7 to 4.2%, p = 0.007), while there was a small but significant increase in long-course NET (from 1.6 to 2.7%, p < 0.001). Long-course NET was significantly associated with increased BCS in patients with cT2-cT4 disease and less extensive axillary surgery in clinically node positive patients with HR+/HER2- tumors., Conclusions: Primary surgery remains the most common treatment strategy in patients with ILC. However, NAC use decreased slightly over the study period, while the use of long-course NET had a small increase and was associated with more BCS and less extensive axillary surgery., (© 2021. Society of Surgical Oncology.)

Introduction: Controversy exists regarding optimal management of the axilla in clinically node-negative (cN0) mastectomy patients with one or two positive sentinel lymph nodes (+SLNs). We evaluated the influence of frozen-section pathology on axillary management and recurrence., Patients and Methods: We studied cN0 breast cancer patients treated from 2008 to 2018 with mastectomy and SLN surgery with one or two +SLNs. Patients with one or two +SLNs identified on frozen-section intraoperatively (FS+SLN) were compared to those with one or two +SLNs not detected by frozen section (FS-SLN). Recurrence rates were estimated using the Kaplan-Meier method., Results: Of 2295 cN0 mastectomy patients, 338 patients had one or two +SLNs: 108 (32%) FS-SLN and 230 (68%) FS+SLN. In the FS+SLN cases, completion axillary lymph node dissection (cALND) was more frequent (97% vs. 39%; P < .001), and median SLN metastasis size (5 vs. 1.3 mm; P < .001) and likelihood of positive non-SLNs (31% vs. 14%; P = .02) were greater compared with FS-SLN cases. Across all 338 patients, 40% had SLN surgery alone, and 47% of cALND patients received post-mastectomy radiation therapy (PMRT). At a median follow-up of 61 months, no axillary recurrences were observed among FS-SLN patients. Among FS+SLN patients, 97% proceeded to cALND but 49% avoided PMRT; three regional nodal recurrences were observed (all in patients treated with cALND, of whom two received PMRT)., Conclusion: Mastectomy patients with one or two FS+SLNs have a higher nodal disease burden than FS-SLN patients. The majority of FS+SLN patients underwent cALND, and 51% received PMRT with very low 5-year regional nodal recurrence rates. A substantial proportion of FS-SLN patients successfully avoided both cALND and PMRT. Frozen-section pathology analysis can guide de-escalation of axillary management., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Many neuro-oncology studies commonly assess the association between a prognostic factor (predictor) and disease or outcome, such as the association between age and glioma. Predictors can be continuous (eg, age) or categorical (eg, race/ethnicity). Effects of categorical predictors are frequently easier to visualize and interpret than effects of continuous variables. This makes it an attractive, and seemingly justifiable, option to subdivide the continuous predictors into categories (eg, age <50 years vs age ≥50 years). However, this approach results in loss of information (and power) compared to the continuous version. This review outlines the use cases for continuous and categorized predictors and provides tips and pitfalls for interpretation of these approaches., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Tumor genomic prognostic assays estimate 10-year local recurrence risk in ductal carcinoma in situ (DCIS) and can guide treatment decisions. This study aimed to evaluate which DCIS patients treated with breast-conserving surgery (BCS) underwent DCIS score genomic testing and the influence of the results on adjuvant treatment recommendations., Methods: The study identified patients from the National Cancer Database (NCDB) who had DCIS treated with BCS from 2010 to 2016., Results: Of 141,047 patients, 4255 (3%) had a DCIS score assessed, 0.3% in 2010 increasing to 5.8% in 2016 (p < 0.001). The patients most likely to undergo DCIS score assessment had more favorable tumor features in the multivariable analysis. The DCIS score result was documented for 91.4% of the tested patients (n = 3888): 70.5% of the low-risk, 14.9% of the intermediate-risk, and 14.6% of the high-risk patients. The patients with low-risk scores were less likely to have radiation than those with intermediate- or high-risk scores among the patients with either ER + (35.0% vs 71.0% or 81.1%) or ER- disease (48.1% vs 77.0% or 85.5%) (each p ≤ 0.001). The patients who had ER + disease with high- and intermediate-risk scores were most commonly treated with both radiation and hormone therapy (HT) (57.1% and 52.2%), whereas the most common treatment for those with a low-risk DCIS score was HT alone without radiation (37.1%). Comparison of genomic testing with clinicopathologic features showed an independent influence of genomic testing on treatment., Conclusions: Use of the DCIS score increased over time, predominantly for favorable DCIS. Patients with a low-risk score were significantly less likely to receive radiation, supporting an impact of the DCIS score on treatment de-escalation.

Background: Surgical treatment for transverse colon cancer involves either extended colectomy or segmental resection, depending on the location of the tumor and surgeon perspective. However, the oncological safety of segmental resection has not yet been established in large cohort studies., Objective: This study aims to compare segmental resection versus extended colectomy for transverse colon cancer in terms of oncological outcomes., Design: This was a retrospective cohort study., Settings: This study was conducted using a nationwide cohort., Patients: A total of 66,062 patients who underwent colectomy with curative intent for transverse stage I to III adenocarcinoma were identified in the National Cancer Database (2004-2015)., Main Outcome Measures: Patients were divided in 2 groups based on the type of surgery received (extended versus segmental resection). The primary outcome was overall survival. Secondary outcomes were 30- and 90-day mortality, length of hospital stay, and readmission rate within 30 days of surgical discharge., Results: Extended colectomy was performed in 44,417 (67.2%) patients, whereas 21,645 (32.8%) patients underwent segmental resection. Extended colectomy was associated with lower survival at multivariate analysis (HR, 1.07; 95% CI, 1.04-1.10; p < 0.001). The subgroup analysis showed that extended resection was independently associated with poorer survival in mid transverse colon cancers (HR, 1.08; 95% CI, 1.04-1.12; p < 0.001) and in stage III tumors (HR, 1.11; 95% CI, 1.04-1.18; p < 0.001). The number of at least 12 harvested lymph nodes was an independent predictor of improved survival in both overall and subgroup analyses., Limitations: This study was limited by its retrospective design., Conclusion: Extended colectomy was not associated with a survival advantage compared with segmental resection. On the contrary, extended colectomy was associated with slightly poorer survival in mid transverse cancers and locally advanced tumors. Segmental resection was found to be safe when appropriate margins and adequate lymph node harvest were achieved. See Video Abstract at http://links.lww.com/DCR/B454., Abordaje Quirrgico Del Cncer De Colon Transverso Anlisis De La Prctica Actual Y Los Resultados Oncolgicos Utilizando La Base De Datos Nacional De Cncer: ANTECEDENTES:El tratamiento quirúrgico para el cáncer de colon transverso implica colectomía extendida o resección segmentaria, según la ubicación del tumor y la perspectiva del cirujano. Sin embargo, la seguridad oncológica de la resección segmentaria aún no se ha establecido en estudios de cohortes grandes.OBJETIVO:Este estudio tiene como objetivo comparar la resección segmentaria versus la colectomía extendida para el cáncer de colon transverso en términos de resultados oncológicos.DISEÑO:Este fue un estudio de cohorte retrospectivo.ESCENARIO:Este estudio se realizó utilizando una cohorte a nivel nacional.PACIENTES:Un total de 66,062 pacientes que se sometieron a colectomía con intención curativa por adenocarcinoma de colon transverso en estadio I-III fueron identificados en la Base de Datos Nacional del Cáncer (2004-2015).PRINCIPALES MEDIDAS DE RESULTADO:Los pacientes se dividieron en dos grupos según el tipo de cirugía recibida (resección extendida versus resección segmentaria). El resultado primario fue la supervivencia global. Los resultados secundarios fueron la mortalidad a los 30 y 90 días, la duración de la estancia hospitalaria y la tasa de reingreso dentro de los 30 días posteriores al alta quirúrgica.RESULTADOS:Se realizó colectomía extendida en 44,417 (67.2%) casos, mientras que 21,645 (32.8%) pacientes fueron sometidos a resección segmentaria. La colectomía extendida se asoció con una menor supervivencia en el análisis multivariado (HR 1.07 IC 95% 1.04-1.10; p <0.001). El análisis de subgrupos mostró que la resección extendida se asoció de forma independiente con una menor supervivencia en los cánceres de colon transverso medio (HR 1.08 IC 95% 1.04-1.12; p <0.001) y en tumores en estadio III (HR 1.11 IC 95% 1.04-1.18; p <0.001). Un número de al menos 12 ganglios linfáticos cosechados fue un predictor independiente de una mejor supervivencia en los análisis general y de subgrupos.LIMITACIONES:Este estudio estuvo limitado por su diseño retrospectivo.CONCLUSIÓN:La colectomía extendida no se asoció con una ventaja de supervivencia en comparación con la resección segmentaria. Por el contrario, la colectomía extendida se asoció con una supervivencia levemente menor en cánceres de colon transverso medio y tumores localmente avanzados. Se encontró que la resección segmentaria es segura cuando se logran los márgenes apropiados y la cosecha adecuada de ganglios linfáticos. Consulte Video Resumen en http://links.lww.com/DCR/B454., (Copyright © The ASCRS 2021.)

Background: Aortic syndromes, including aortic dissection (AD), intramural hematoma (IMH), and penetrating aortic ulcer (PAU), carry significant morbidity and mortality; few data exist regarding burden and causes of related rehospitalizations following initial discharge., Methods: The study was conducted using the Rochester Epidemiology Project. All adult residents (age ≥18 years) with an incident diagnosis of AD, IMH, and PAU (1995-2015) were identified from the Rochester Epidemiology Project using the International Classification of Diseases, Ninth Revision and Tenth Revision codes and Hospital Adaptation of the International Classification of Diseases, second edition, codes. Assessment of any-cause (aortic and cardiovascular), aorta-related, or cardiovascular-related readmissions was determined following date of hospital discharge or diagnosis date (ie, the index event)., Results: A total of 117 patients of 130 cases of AD, IMH, and PAU included in the initial study population survived the index event and were evaluated. The median age of diagnosis was 74 years, and 70 (60%) were male. A total of 79 patients (68%) experienced at least one readmission. The median time to first any-cause, cardiovascular, and aortic readmission was 143, 861, and 171 days, respectively. The cumulative incidence of any-cause readmissions at 2, 4, and 10 years was 45%, 55%, and 69%, respectively. The cumulative incidence of cardiovascular readmissions at 2, 4, and 10 years was 15%, 20%, and 28%, respectively. The cumulative incidence of aortic readmissions at 2, 4, and 10 years was 38%, 46%, and 59%, respectively. Overall survival for the entire cohort at 2, 4, and 10 years was 84%, 75%, and 50%, respectively., Conclusions: Readmissions following initial discharge after diagnosis of aortic syndrome are common and not different across specific disease types. Whereas aorta-related rehospitalizations occur in more than half of patients but tend to be earlier, cardiovascular-related rehospitalizations tend to happen later in about one-third of patients. This may suggest the need for early follow-up focused on aortic complications, whereas later follow-up should address cardiovascular events., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: To report long-term efficacy and adverse events (AEs) associated with intensity modulated radiotherapy (IMRT) for patients with anal canal squamous cell carcinoma (ASCC)., Materials and Methods: This was a retrospective review of patients with ASCC who received curative-intent IMRT and concurrent chemotherapy (98%) between 2003 and 2019. Overall survival (OS), colostomy-free survival (CFS), and progression-free survival (PFS) were estimated using the Kaplan-Meier method. The cumulative incidence of local recurrence (LR), locoregional recurrence (LRR), and distant metastasis (DM) were reported. Acute and late AEs were recorded per National Cancer Institute Common Terminology Criteria for AEs., Results: 127 patients were included. The median patient age was 63 years (interquartile range [IQR] 55-69) and 79% of patients were female. 33% of patients had T3-4 disease and 68% had clinically involved pelvic or inguinal lymph nodes (LNs).The median patient follow-up was 47 months (IQR: 28-89 months). The estimated 4-year OS, CFS, and PFS were 81% (95% confidence interval [CI]: 73%-89%), 77% (95% CI: 68%-86%), and 78% (95% CI: 70%-86%), respectively. The 4-year cumulative incidences of LR, LRR, and DM were 3% (95% CI: 1%-9%), 9% (95% CI: 5%-17%), and 10% (95% CI: 6%-18%), respectively. Overall treatment duration greater than 39 days was associated with an increased risk of LRR (Hazard Ratio [HR]: 5.2, 95% CI: 1.4-19.5, p = 0.015). The most common grade 3+ acute AEs included hematologic (31%), gastrointestinal (GI) (17%), dermatologic (16%), and pain (15%). Grade 3+ late AEs included: GI (3%), genitourinary (GU) (2%), and pain (1%). Current smokers were more likely to experience grade 3+ acute dermatologic toxicity compared to former or never smokers (34% vs. 7%, p < 0.001)., Conclusions: IMRT was associated with favorable toxicity rates and long-term efficacy. These data support the continued utilization of IMRT as the preferred treatment technique for patients with ASCC., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Jethwa report honoraria from RadOncQuestions.com, LLC., (© 2021 The Author(s).)

Background: The maximum number of sentinel lymph nodes (SLN) to be resected to accurately stage the axilla in patients undergoing neoadjuvant chemotherapy (NAC) for the treatment of clinically node-negative (cN0) breast cancer has not been determined. We sought to determine the sequence of removal of the positive SLNs in this patient population., Methods: All patients aged ≥ 18 years diagnosed with cN0 invasive breast cancer who received NAC and underwent SLN surgery at Mayo Clinic Rochester between September 2008 and September 2018 were identified. Univariate analysis was performed to compare factors associated with positive nodes and where the first positive node was in the sequence of removal of the SLNs., Results: We identified 446 cancers among 440 patients with a median age of 51 (IQR: 43, 61) years. At surgery, 381 (85.4%) cancers were pathologically node (ypN) negative and 65 (14.6%) were pN + . The number of nodes removed was similar for both patients with ypN0 and ypN + disease, with a median number of SLNs removed of 2.0 (IQR: 2.0, 3.0). Of all patients with a positive node, the first positive node was most commonly the 1st node removed (75.4%), and was identified by the 3rd SLN removed in all cases., Conclusions: Among cN0 patients treated with NAC, if a positive SLN is present, it is most commonly identified as the 1st sentinel node removed by the surgeon, and was identified by the 3rd sentinel node in our series. This suggests that once 3 SLNs have been resected, removal of additional sentinel lymph nodes does not add diagnostic value.

Utility of adjuvant chemotherapy for stage II cancer remains a matter of debate. Clinical guidelines suggest adjuvant chemotherapy for stage II tumors with high-risk features, in particular T4 tumors. However, limited consensus exists regarding the importance of other high-risk features (lymphovascular or perineural invasion, microsatellite instability). Our study aimed to investigate the impact of adjuvant chemotherapy for stage IIA (T3N0) colon cancer patients. Patients who underwent colectomy for stage IIA colon adenocarcinoma (2010-2015) were identified in the National Cancer Database (NCDB) and divided in two groups based on receipt of adjuvant chemotherapy vs observation. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier and Cox proportional hazards regression analyses were performed to compare overall survival between the two groups. Subgroup analysis of patients with specific high-risk features LVI, PNI and MSI was performed. Among 46 688 surgical patients with stage IIA colon adenocarcinoma 5937 (12.7%) received adjuvant chemotherapy, while 40 751 (87.3%) were observed. Five-year IPTW-adjusted survival was higher in the adjuvant chemotherapy group (79.7% [95% CI 79.1, 80.2]) compared to the observation group (70.3% [95% CI 69.7, 70.9]). Patients with high-risk pathological features showed an estimated 5-year survival benefit of 11.3% (78.2% [95% CI 77.4, 79.1] vs 66.9% [95% CI 65.9, 67.8]) when treated with adjuvant chemotherapy. This NCDB analysis revealed a survival benefit for patients with stage IIA colon adenocarcinoma and high-risk features that were treated with adjuvant chemotherapy., (© 2020 Union for International Cancer Control.)

Background: Acute encephalopathy (AE) is a common complication of critical illness and is associated with increased short and long-term mortality. In this study, we evaluated the role of cefepime in causing AE., Methods: Retrospective case-control study involving consecutive patients enrolled in the intensive care units (ICUs) of Mayo Clinic Rochester, MN between July 1, 2004 and December 31, 2015. AE was defined by the presence of delirium or depressed level of consciousness in the absence of deep sedation. Controls were identified as patients not developing AE and were matched by propensity score for age, Charlson Comorbidity Index, 24-h Apache III score and invasive ventilation use., Results: The total number of eligible ICU admissions during our study period was 152,999. AE was present in 57,726 (37.7%) with a median AE duration of 17 (interquartile range [IQR] 4.0-51.8) hours. We matched 14,645 cases with AE with the same number of controls. Cefepime was used in 1241 (4.2%) patients and its use was associated with greater incidence of AE [713 (4.9%) vs 528 (3.6%), p < 0.001] and duration [unit estimate 0.73; (95% CI 0.542-0.918)]. On multivariate analysis, cefepime was associated with an increased likelihood of AE after controlling for shock, midazolam infusion and acute kidney injury [OR 1.24 (95% CI 1.10-1.27)]. These associations were also present after controlling for prior chronic kidney disease., Conclusion: The use of cefepime is associated with increased likelihood and duration of AE. These associations are stronger among patients with impaired renal function, but can also occur in patients without renal impairment.

Background: Sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) has been well studied. However, outcomes data addressing the oncologic safety of this technique are sparse. This study aimed to evaluate use of SLN surgery versus axillary lymph node dissection (ALND) for clinically node-positive patients treated with NAC and to report outcomes., Methods: The study identified patients at the authors' institution with biopsy proven clinically node-positive (cN1-cN3) breast cancer undergoing axillary surgery after NAC from 2009 to 2019. Practice patterns and outcomes were evaluated., Results: Of 602 patients, 52.3% underwent SLN surgery. Use of SLN surgery increased significantly over time, reaching 75.3% during 2015-2019. For 52.5% of the patients who had an SLN identified, ALND was not used. Use of ALND (± SLN surgery) decreased from 100% in 2009 to 57.2% in 2015-2019. The nodal positivity rate of patients who proceeded directly to ALND was 64.5% (185/287), increasing significantly over time. Factors significantly associated with performing SLN surgery on multivariable analysis were lower presenting clinical T category, lower presenting clinical N category (cN1 vs cN2-3) and HER2-positive status. During the median 34-month follow-up period, 17 regional recurrences were observed (16/443 with ALND; 1/159 with SLN surgery alone), for a 2-year freedom-from-regional-recurrence rate of 99.1% among the SLN surgery patients and 96.4% among the ALND patients (p = 0.10)., Conclusions: For cN1-3 breast cancer treated with NAC, SLN surgery has been incorporated into clinical practice at the authors' institution. In this study, selection for SLN surgery was based on clinical factors and tumor biology. More than half of the patients who were selected for SLN surgery were spared ALND, with a low nodal failure rate and no recurrence-free survival disadvantage at 2 years.

Introduction: Prediction models are useful to guide decision making. Our goal was to compare three published nomograms predicting axillary response to neoadjuvant chemotherapy (NAC), clinically node-positive breast cancer., Methods: Patients with cT1-T4, cN1-N3 breast cancer treated with NAC and surgery from 2008 to 2019 were reviewed. The predicted probability of pathologic node-negative (ypN0) status was estimated for each nomogram. Area under the curve (AUC) was compared across models, overall and by biologic subtype., Results: Of 581 patients, 253 (43.5%) were ypN0. ypN0 status varied by subtype: 23.9% for estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-), 68.9% for HER2-positive (HER2+), and 47.2% for ER-negative (ER-)/HER2-. The three nomograms had similar AUC values (0.761-0.769; p = 0.80). The Mayo model-predicted probability was significantly lower (p < 0.001) than the observed probability of ypN0 status, while the MD Anderson Cancer Center (MDACC) 1- and 2-predicted probabilities were similar to the observed probability. At a predicted probability threshold of 50%, the Mayo model had the highest sensitivity (89.6%) for detecting ypN+ patients compared with MDACC models 1 and 2 (76.5%; p < 0.001). However, both MDACC models had higher specificity in identifying ypN0 status among HER2+ (81.7%) and ER-/HER2- (75.9-77.6%) patients compared with the Mayo model (59.5% and 43.1%; each p < 0.001). None of the models identified the ER+/HER2- patients with ypN0 status well at the ≥ 50% threshold (specificity 0-9.4%)., Conclusion: All three models predicting nodal response to NAC performed well overall with respect to discrimination, but differed with respect to calibration and performance at a 50% probability threshold. However, none of the models performed well at the 50% threshold for ER+/HER2- patients.

Background: Although inflammatory breast cancer (IBC) is postulated to be a distinct biological entity, practice guidelines and previous data suggest that treatment and outcomes are influenced by standard approximated biological subtype. The aim of this study was validation in a large recent National Cancer Database (NCDB) patient cohort., Methods: Patients with non-metastatic IBC treated in 2010-2015 with neoadjuvant systemic therapy and surgery were identified from the NCDB. Approximated biological subtypes were categorized as oestrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-), ER-/HER2- and HER2+. Total pathological complete response (pCR) was defined as ypT0/ypTis, ypN0. χ 2 tests were used to compare pCR rates, and Kaplan-Meier curves and Cox proportional hazards regression to analyse overall survival., Results: Among 4068 patients with IBC (median age 56 years), the approximated biological subtype was ER+/HER2- in 1575 (38·7 per cent), HER2+ in 1323 (32·5 per cent) and ER-/HER2- in 1170 (28·8 per cent). A total of 3351 patients (84·0 per cent) were cN+ at presentation, with no differences across subtypes. Total pCR rates varied significantly by subtype: ER+/HER2- (6·2 per cent), HER2+ (38·8 per cent), ER-/HER2- (19·1 per cent) (P < 0·001), as did breast pCR rates (10·4, 44·5 and 25·2 per cent respectively) and nodal pCR rates (16·9, 56·9 and 33·1 per cent). The 5-year overall survival rate varied significantly across subtypes (ER+/HER2- 64·9 per cent, HER2+ 74·0 per cent, ER-/HER2- 44·0 per cent; P < 0·001) and by pCR within subtypes (all P < 0·001). In multivariable analysis, ER-/HER2- subtype (hazard ratio 2·89 versus HER2+ as reference; P < 0·001) and absence of total pCR (hazard ratio 3·23; P < 0·001) predicted worse survival., Conclusion: Both treatment response and survival in patients with IBC varied with approximated biological subtype, as among other invasive breast cancers. These data support continued tailoring of systemic treatment to approximated biological subtype and highlight the recent improved outcomes in patients with HER2+ disease., (© 2020 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Introduction: Mucinous appendiceal carcinoma is a rare malignancy that commonly spreads to the peritoneum leading to peritoneal metastases. Complete cytoreduction with perioperative intraperitoneal chemotherapy (PIC) is the mainstay of treatment, administered as either hyperthermic intra peritoneal chemotherapy (HIPEC) or early post-operative intraperitoneal chemotherapy (EPIC). Our goal was to assess the perioperative and long term survival outcomes associated with these two PIC methods., Materials and Methods: Patients with mucinous appendiceal carcinoma were identified in the US HIPEC Collaborative database from 12 academic institutions. Patient demographics, clinical characteristics, and survival outcomes were compared among patients who underwent HIPEC vs. EPIC with inverse probability weighting (IPW) used for adjustment., Results: Among 921 patients with mucinous appendiceal carcinoma, 9% underwent EPIC while 91% underwent HIPEC. There was no difference in Grade III-V complications between the two groups (18.5% for HIPEC vs. 15.0% for EPIC, p =.43) though patients who underwent HIPEC had higher rates of readmissions (21.2% vs. 8.8%, p <.01). Additionally, PIC method was not an independent predictor for overall survival (OS) or recurrence-free survival (RFS) after adjustment on multivariable analysis., Conclusions: Among patients with mucinous appendiceal carcinoma, both EPIC and HIPEC appear to be associated with similar perioperative and long-term outcomes.

Background: Little information exists regarding the use of arch operations for repair of acute type A aortic dissections (AADs) despite increasing interest in this strategy and its potential impact on outcomes. We aimed to determine the relationship between extent of aortic repair, US geographic regions, and outcome., Methods: We queried The Society of Thoracic Surgeons database for patients who underwent AAD repair from January 1, 2004 to December 31, 2016 and grouped patients by ascending-only operations and operations involving the arch., Results: We identified 25,462 patients (mean age, 59.8 ± 14.2; 66.7% men) who underwent AAD repair. Operations involving the ascending aorta only were performed in 54% of patients; 46% had repair additionally involving the arch. The 30-day mortality was 18.9% for patients who underwent ascending-only operations vs 19.8% for patients who underwent arch operations (P = .09). In multivariable analysis older age (P < .001), earlier year of operation (P < .001), diabetes mellitus (P < .001), severe chronic lung disease (P < .001), prior cerebrovascular disease (P < .001), and longer bypass time (P < .001) were independently associated with 30-day mortality. There was regional variation in 30-day mortality (P < .001), and incidence of arch repair varied from 38.6% to 52.6% in 9 geographic regions (P < .001)., Conclusions: In this analysis of cardiac surgical practice in the United States, repair of AADs included a portion of the aortic arch in 46% of patients. Early mortality remained high throughout the current era regardless of extent of aortic resection. Regional variation in perioperative mortality may signal an opportunity for practice improvement., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: Ileal Pouch-Anal Anastomosis (IPAA) is the standard of care for children requiring surgical treatment of severe colitis or polyposis syndromes. This study aims is to investigate the sexual function and fertility in women after undergoing childhood IPAA., Methods: A prospectively maintained colon and rectal database of consenting patients was queried from January 1980 to October 2015. We included all females that replied to at least 1 survey between the ages of 20 and 45 years that had undergone IPAA younger than 20 years of age., Results: Two hundred females met inclusion criteria, whereas 149 women replied to the sexual function questions. Ulcerative colitis was diagnosed in 122 (83%) patients, with the remainder having polyposis. Seven patients had a laparoscopic proctectomy. Only 2 patients had a pelvic infection, whereas 21 had intestinal obstruction postoperatively. A severely restricted sex life was reported in 6 (5%) patients. Of the 93 (62%) women who attempted pregnancy, 68 (73%) became pregnant. Median age of pregnancy and IPAA was 34 (range 22-45) and 17 years (range 9-20), respectively. Medical intervention to assist fertilization was required in 14/68. A total of 29 women reported problems during pregnancy with 58/68 (88%) giving birth to a live baby. Elective termination was reported in 2/68 surveys. Vaginal delivery occurred in 26/58 mothers with 27/58 planned and 9/58 unplanned cesarean sections. Age at IPAA, diagnosis, procedure type, pelvic infection, and obstruction were not associated with decreased fertility. All 7 patients operated laparoscopically have become pregnant. Change in pouch function after delivery was reported in 20/68 (32%, 5 missing) surveys., Conclusions: 73% of women who desired children become pregnant, and 88% had a successful delivery after pediatric IPAA. Only 5% reported severely restricted sexual function. Changes in pouch function occurred with pregnancy and persisted in 1/3 after delivery. Minimally invasive techniques may improve fertility rates but equire continued follow-up., Level of Evidence: Level IV., Type of Study: Observational study., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Adolescents and young adults (AYAs; age < 40 years) account for less than 2% of breast cancer patients. Therefore, little is known about the tumor characteristics and care provided to AYA patients. This study sought to describe demographic, tumor, and treatment variables among AYA patients., Methods: The study identified patients ages 15 to 49 years with breast cancer between 2010 and 2015 from the National Cancer Database. Patient and tumor factors were compared using Chi-square tests. Multivariable logistic regression was used to model the effect of age group on treatment while adjusting for confounding variables., Results: The study identified 46,265 AYA patients with stages 0 to 3 breast cancer and compared them with 169,423 breast cancer patients ages 40 to 49 years. A greater proportion of the AYA patients presented with clinical stage 2 or 3 disease than the adult patients 40 to 49 years old (stage 2 disease: 44.3% vs 29.9%, respectively; stage 3 disease: 14.0% vs 7.7%, respectively; both p < 0.001). A greater proportion of the AYA patients had triple-negative breast cancer (TNBC) or human epidermal growth factor receptor 2-positive (HER2+) cancer than the adult patients (TNBC: 21.2% vs 13.8%, respectively; HER2+: 26.0% vs 18.6%, respectively; both p < 0.001). Among the AYA patients, the very young (ages 15-29 years) had more advanced disease and TNBC or HER2+ disease than the older youth (ages 30 to 39 years). The multivariable analysis showed that the AYA patients were more likely to undergo mastectomy (odds ratio [OR] 2.1) and receive chemotherapy (OR 1.9) than patients in their forties (both p < 0.001)., Conclusion: A greater proportion of the AYA breast cancer patients had more advanced disease and TNBC and HER2+ disease. The AYA patients had higher rates of mastectomy and use of chemotherapy than the adult breast cancer patients, reflecting that more aggressive therapy is recommended or chosen for women in this age group.

Background: Timeliness of care is emerging as a quality indicator for breast cancer care. We sought to evaluate the impact of surgical treatment type on time to adjuvant chemotherapy and impact of treatment delay on survival., Methods: Patients with stage I-III breast cancer treated with both surgery and adjuvant chemotherapy from 2010 to 2014 were identified from the National Cancer Database (NCDB). Delay in treatment was defined as > 120 days from diagnosis to chemotherapy. Multivariable analysis was performed to assess factors associated with delay in treatment and the effect of treatment delay on overall survival., Results: Of 172,043 patients identified, 89.5% initiated chemotherapy within 120 days of diagnosis. Median time from diagnosis to surgery was shorter in patients undergoing breast conservation (25 days) than mastectomy (29 days, p < 0.001) and within mastectomy patients was shorter for mastectomy without reconstruction (26 versus 35 days, p < 0.001). Time from diagnosis to surgery showed larger differences between surgical groups than time from surgery to chemotherapy. On multivariable analysis of mastectomy patients, reconstruction remained significantly associated with delay to chemotherapy [odds ratio (OR) 1.7, p < 0.001]. For all patients regardless of type of surgery, after adjusting for patient, clinical, and treatment factors, delay of > 120 days from diagnosis to chemotherapy was associated with worse overall survival [hazard ratio (HR) 1.29, p < 0.001]., Conclusions: Initiation of chemotherapy greater than 120 days after diagnosis was associated with poorer overall survival. Time interval from diagnosis to surgery had the greatest impact on time from diagnosis to chemotherapy, with reconstruction resulting in the greatest delay.

Background: Immediate breast reconstruction after mastectomy may confer more complication rates in the elderly. Therefore, granular analysis of postmastectomy complications in women aged ≥65 years may help formulate clinical guidelines to improve patient selection and outcomes., Methods: We identified patients undergoing mastectomy with or without immediate reconstruction from our breast surgery database (2014-2018). Complications requiring treatment were compared between patients aged ≥65 and <65 years., Results: A total of 1,721 mastectomies were performed in 1,698 patients; 85.8% had a 30-day follow-up. Of these patients, 968 (65.6%) had immediate breast reconstruction, of whom 95 (9.8%) were aged ≥65 years. Among patients aged ≥65 years, 27.6% underwent mastectomy with immediate breast reconstruction compared with 77.1% of women aged <65 years (P < .001). Overall complication rates were not greater for older compared with younger mastectomy patients but were for older versus younger patients who had mastectomy with immediate breast reconstruction (12.6% vs 6.8%; P = .04). Hematoma requiring reoperation was more frequent in patients aged ≥65 years (5.3% vs 0.9%; P = .006). Necrosis (5.3% vs 2.6%; P = .18) and 30-day unplanned readmissions (7.4% vs 4.0%; P = .18) were not greater., Conclusion: Despite low overall postoperative complication rates, we found some clinically relevant differences between older and younger patients after mastectomy with immediate breast reconstruction. Additional investigation of contributing factors may help further refine patient selection. In the interim, elderly patients should be counseled on their somewhat greater risk of postoperative complications to facilitate shared decision making., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The National Cancer Database (NCDB) is a valuable resource for studying national cancer treatment patterns. However, data abstraction rules from 2004 to 2007 resulted in missing clinical stage for a high percentage of cases. We investigated how this missingness can bias results in breast cancer studies including patients treated with neoadjuvant chemotherapy (NAC)., Methods: The impact of missing clinical stage on the estimated percentage of breast cancers treated with NAC versus adjuvant chemotherapy (AC) was examined from 2004 to 2013. Trends in NAC use were presented, excluding those cases with missing clinical stage, and compared with trends after multiple imputation, performed using the chained equations approach with predictive mean matching., Results: Clinical stage was missing for 56% of cases in 2004-2007, versus 12% in 2008-2013, and was missing more than twice as often for AC patients versus NAC patients (31% vs. 12% overall), with the largest difference occurring in 2004-2007 (60% vs. 27% missing). Because stage was more frequently missing in AC patients, excluding those missing clinical stage introduced bias when considering NAC versus AC trends. With multiple imputation, significant increases in NAC use were identified between 2004 and 2013 for each stage: use for stage I was 2% in 2004 and 5% in 2013, use for stage II was 11% in 2004 and 24% in 2013, use for stage III was 34% in 2004 and 46% in 2013, in contrast to an analysis excluding those missing stage, which suggested little or no increase within any stage., Conclusion: NCDB data abstraction rules from 2004 to 2007 resulted in missing clinical stage for > 50% of breast cancers, which may introduce substantial bias. Multiple imputation or exclusion of the years 2004-2007 should be considered to mitigate the problem of missing clinical stage in NCDB.

Purpose: Previous studies have shown that sphincter-preserving surgery is associated with better quality of life in postsurgical rectal cancer patients. However, the factors predicting the likelihood of undergoing sphincter-preserving surgery have not been well-described. The aim of this study was to report the factors that determined the likelihood of undergoing sphincter-preserving surgery., Methods: Characteristics of 24,018 rectal cancer patients undergoing sphincter-preserving surgery and abdominoperineal resection diagnosed from 2008 to 2012 from the National Cancer Database were investigated retrospectively for rate, pattern, and differences in mortality. Cox proportional hazards models were used to calculate hazard ratios for assessing mortality. Odds ratios were calculated using logistic regressions models for outcome sphincter-preserving surgery., Results: Eighteen thousand four hundred fifty-two (77%) patients had sphincter-preserving surgery. Majority of sphincter-preserving surgery patients were aged < 70 (74%), had private insurance (52%), and got treatment at a comprehensive community cancer program (54%). Multivariable analysis showed that patients with age ≥ 70 (OR 0.87, 95% CI 0.80-0.95), male gender (OR 0.90, 95% CI 0.84-0.96), having Medicare (OR 0.83, 95% CI 0.76-0.90), Medicaid (OR 0.72, 95% CI 0.63-0.81), and poorly differentiated grade (OR 0.78, 95% CI 0.71-0.85) were less likely to undergo sphincter-preserving surgery. Multivariable analysis showed that patients having abdominoperineal resection have higher likelihood of mortality than sphincter-preserving surgery (HR 1.26, 95% CI 1.16-1.36)., Conclusions: We were able to identify several patient and tumor-related factors impacting the likelihood of undergoing sphincter-preserving surgery. Patients undergoing non-sphincter sparing surgery had a higher mortality that sphincter preservation.

Purpose: Grade 4 lymphopenia (G4L) during radiation therapy (RT) is associated with higher rates of distant metastasis and decreased overall survival in a number of malignancies, including esophageal cancer (EC). Through a reduction in integral radiation dose, proton RT (PRT) may reduce G4L relative to photon RT (XRT). The purpose of this study was to compare G4L in patients with EC undergoing PRT versus XRT., Methods and Materials: Patients receiving curative-intent RT and concurrent chemotherapy for EC were identified. Lymphocyte nadir was defined as the lowest lymphocyte count during RT. G4L was defined as absolute lymphocyte count <200/mm 3 . Univariate and multivariable logistic regression analyses (MVA) were performed to assess patient and treatment factors associated with lymphopenia. A propensity-matched (PM) cohort was created using logistic regression, including baseline covariates., Results: A total of 144 patients met the inclusion criteria. The median age was 66 years (range, 32-85 years). Of these patients, 79 received XRT (27% 3-dimensional chemo-RT and 73% intensity modulated RT) and 65 received PRT (100% pencil-beam scanning). Chemotherapy consisted of weekly carboplatin and paclitaxel (99%). There were no significant differences in baseline characteristics between the groups, except for age (median 4 years older in the PRT cohort). G4L was significantly higher in patients who received XRT versus those who received PRT (56% vs 22%; P < .01). On MVA, XRT (odds ratio [OR]: 5.13; 95% confidence interval [CI], 2.35-11.18; P < .001) and stage III/IV (OR: 4.54; 95% CI, 1.87-11.00; P < .001) were associated with G4L. PM resulted in 50 PRT and 50 XRT patients. In the PM cohort, G4L occurred in 60% of patients who received XRT versus 24% of patients who received PRT. On MVA, XRT (OR: 5.28; 95% CI, 2.14-12.99; P < .001) and stage III/IV (OR: 3.77; 95% CI, 1.26-11.30; P = .02) were associated with G4L., Conclusions: XRT was associated with a significantly higher risk of G4L in comparison with PRT. Further work is needed to evaluate a potential association between RT modality and antitumor immunity as well as long-term outcomes.

Importance: A recent publication reported that of 527 patients with clinically node-negative (cN0) cT1/cT2 triple-negative breast cancer (TNBC) or ERBB2-positive disease treated with neoadjuvant chemotherapy (NAC), 100% of those who achieved a breast pathologic complete response (pCR) had pathologic node negativity (pN0). Eliminating axillary surgery in these patients has been suggested as safe based on these results., Objective: To evaluate nodal positivity rates in patients with cT1/cT2 N0 ERBB2-positive disease and TNBC with a breast pCR after NAC using the National Cancer Database (NCDB), which included academic and community settings., Design, Setting, and Participants: This retrospective study reviewed data from the NCDB from January 1, 2010, through December 31, 2015. Participants included patients with cN0/cN1 cT1/cT2 breast cancer who received NAC followed by surgery. Pathologic nodal positivity rates by breast pCR were compared in cN0 and cN1 disease, within each tumor subtype (ERBB2-positive, TNBC, and hormone receptor-positive/ERBB2-negative). Data were analyzed from September 13, 2017, through January 30, 2018., Exposures: Neoadjuvant chemotherapy followed by surgery., Main Outcomes and Measures: The pathologic nodal positivity rate after NAC (ypN) specifically in patients with cT1/cT2 cN0 ERBB2-positive disease or TNBC who achieve a breast pCR after NAC., Results: A total of 30 821 patients with cT1/cT2 cN0/cN1 breast cancer treated with NAC and surgical resection (99.6% female; mean [SD] age, 52.0 [11.5] years) were identified. Of 6802 patients with cN0 ERBB2-positive disease, 3062 (45.0%) achieved breast pCR and of those, 49 (1.6%; 95% CI, 1.2%-2.1%) were ypN positive. In 6222 patients with cN0 TNBC, 2315 (37.2%) achieved breast pCR, and of those, 36 (1.6%; 95% CI, 1.1%-2.1%) were pathologic node positive after NAC. Rates of ypN positivity were higher in patients with cN0 and residual disease in the breast; 632 of 3740 (16.9%) with ERBB2-positive disease and 492 of 3907 (12.6%) with TNBC with residual disease in the breast were node positive (P < .001). Among 4164 patients with cN1 ERBB2-positive disease, 1801 (43.3%) achieved breast pCR, with 223 of those (12.4%) being ypN positive. In 3293 patients with TNBC, 1229 (37.3%) achieved breast pCR, with 173 of these (14.1%) being ypN postive. Breast pCR rates were lower in hormone receptor-positive/ERBB2-negative disease (646 of 5069 [12.7%] for cN0; 711 of 5271 [13.5%] for cN1) and ypN positivity rates were 26 of 646 (4.0%) in cN0 vs 217 of 711 (30.5%) in cN1 disease with breast pCR and 1464 of 4423 (33.1%) in cN0 disease vs 3775 of 4560 (82.8%) in cN1 disease with residual disease in the breast., Conclusions and Relevance: In this study, the highest rates of breast pCR were seen in ERBB2-positive disease and TNBC. In patients with cN0 ERBB2-positive disease or TNBC with breast pCR, the nodal positivity rate was less than 2%, which supports consideration of omission of axillary surgery in this subset of patients.

Background: Variables such as tumor size, histology, and grade, tumor biology, presence of lymphovascular invasion, and patient age have been shown to impact likelihood of nodal positivity. The aim of this study is to determine whether primary location of invasive disease within the breast is associated with nodal positivity., Patients and Methods: Patients with invasive breast cancer undergoing axillary staging from 2010 to 2014 were identified from the National Cancer Data Base. Rates of axillary nodal positivity by primary tumor locations were compared, and multivariable analysis performed using logistic regression to control for factors known to impact nodal positivity., Results: A total of 599,722 patients met inclusion criteria. Likelihood of nodal positivity was greatest with primary tumors located in the nipple (43.8%), followed by multicentric disease (40.8%), central breast lesions (39.4%), and axillary tail lesions (38.4%). Tumor location remained independently associated with nodal positivity on multivariable analysis adjusting for variables known to affect nodal positivity with odds ratio 2.8 for tumors in the nipple [95% confidence interval (CI) 2.5-3.1], 2.2 for central breast (95% CI: 2.2-2.3), and 2.7 for axillary tail (95% CI: 2.4-2.9). When restricted to patients with clinically negative nodes (n = 430,949), a similar association was seen., Conclusion: Patients with invasive breast cancer located in the nipple, central breast, and axillary tail have the highest risk of positive axillary lymph nodes independent of patient age, tumor grade, biologic subtype, histology, and size. This should be considered along with other factors in preoperative counseling and decision-making regarding plans for axillary lymph node staging.