Distinct Differences in Gastroesophageal Junction and Gastric Adenocarcinoma in 2194 Patients: In Memory of Rebecca A. Carr, February 24, 1988-January 19, 2021.

OBJECTIVE: We sought to compare gastroesophageal junction (GEJ) cancer and gastric cancer (GC) and identify clinicopathological and oncological differences. SUMMARY BACKGROUND DATA: GEJ cancer and GC are frequently studied together. Although the treatment approach for each often differs, clinico-pathological and oncological differences between the 2 have not been fully evaluated. METHODS: We retrospectively identified patients with GEJ cancer or GC who underwent R0 resection at our center between January 2000 and December 2016. Clinicopathological characteristics, disease-specific survival (DSS), and site of first recurrence were compared. RESULTS: In total, 2194 patients were analyzed: 1060 (48.3%) with GEJ cancer and 1134 (51.7%) with GC. Patients with GEJ cancer were younger (64 vs 66 years; P < 0.001), more often received neoadjuvant treatment (70.9% vs 30.2%; P < 0.001), and had lower pathological T and N status. Five-year DSS was 62.2% in patients with GEJ cancer and 74.6% in patients with GC ( P < 0.001). After adjustment for clinicopathological factors, DSS remained worse in patients with GEJ cancer (hazard ratio, 1.78; 95% confidence interval, 1.40-2.26; P < 0.001). The cumulative incidence of recurrence was approximately 10% higher in patients with GEJ cancer ( P < 0.001). The site of first recurrence was more likely to be hematogenous in patients with GEJ cancer (60.1% vs 31.4%; P < 0.001) and peritoneal in patients with GC (52.9% vs 12.5%; P < 0.001). CONCLUSIONS: GEJ adenocarcinoma is more aggressive, with a higher incidence of recurrence and worse DSS, compared with gastric adenocarcinoma. Distinct differences between GEJ cancer and GC, especially in patterns of recurrence, may affect evaluation of optimal treatment strategies.

Risk of Lymph Node Metastasis in T1b Gastric Cancer: An International Comprehensive Analysis from the Global Gastric Group (G3) Alliance.

OBJECTIVE: We sought to define criteria associated with low lymph node metastasis risk in patients with submucosal (pT1b) gastric cancer from 3 Western and 3 Eastern countries. SUMMARY BACKGROUND DATA: Accurate prediction of lymph node metastasis risk is essential when determining the need for gastrectomy with lymph node dissection following endoscopic resection. Under present guidelines, endoscopic resection is considered definitive treatment if submucosal invasion is only superficial, but this is not routinely assessed. METHODS: Lymph node metastasis rates were determined for patient groups defined according to tumor pathological characteristics. Clinicopathological predictors of lymph node metastasis were determined by multivariable logistic regression and used to develop a nomogram in a randomly selected subset that was validated in the remainder. Overall survival was compared between Eastern and Western countries. RESULTS: Lymph node metastasis was found in 701 of 3166 (22.1%) Eastern and 153 of 560 (27.3%) Western patients. Independent predictors of lymph node metastasis were female sex, tumor size, distal stomach location, lymphovascular invasion, and moderate or poor differentiation. Patients fulfilling the National Comprehensive Cancer Network guideline criteria, excluding the requirement that invasion not extend beyond the superficial submucosa, had a lymph node metastasis rate of 8.9% (53/594). Excluding moderately differentiated tumors lowered the rate to 3.4% (10/296). The nomogram's area under the curve was 0.690. Regardless of lymph node status, overall survival was better in Eastern patients. CONCLUSIONS: The lymph node metastasis rate was lowest in patients with well differentiated tumors that were ≤3 cm and lacked lymphovascular invasion. These criteria may be useful in decisions regarding endoscopic resection as definitive treatment for pT1b gastric cancer.

Survival of Locally Advanced MSI-high Gastric Cancer Patients Treated With Perioperative Chemotherapy: A Retrospective Cohort Study.

OBJECTIVE: To evaluate the efficacy of chemotherapy in patients with microsatellite instability (MSI)-high gastric cancer. BACKGROUND: Although MSI-high gastric cancer is associated with a superior prognosis, recent studies question the benefit of perioperative chemotherapy in this population. METHODS: Locally advanced gastric adenocarcinoma patients who either underwent surgery alone or also received neoadjuvant, perioperative, or adjuvant chemotherapy between 2000 and 2018 were eligible. MSI status, determined by next-generation sequencing or mismatch repair protein immunohistochemistry, was determined in 535 patients. Associations among MSI status, chemotherapy administration, overall survival (OS), disease-specific survival, and disease-free survival were assessed. RESULTS: In 535 patients, 82 (15.3%) had an MSI-high tumor and ∼20% better OS, disease-specific survival, and disease-free survival. Grade 1 (90%-100%) pathological response to neoadjuvant chemotherapy was found in 0 of 40 (0%) MSI-high tumors versus 43 of 274 (16%) MSS. In the MSI-high group, the 3-year OS rate was 79% with chemotherapy versus 88% with surgery alone ( P =0.48). In the MSS group, this was 61% versus 59%, respectively ( P =0.96). After multivariable interaction analyses, patients with MSI-high tumors had superior survival compared with patients with MSS tumors whether given chemotherapy (hazard ratio=0.53, 95% confidence interval: 0.28-0.99) or treated with surgery alone (hazard ratio=0.15, 95% confidence interval: 0.02-1.17). CONCLUSIONS: MSI-high locally advanced gastric cancer was associated with superior survival compared with MSS overall, despite worse pathological chemotherapy response. In patients with MSI-high gastric cancer who received chemotherapy, the survival rate was ∼9% worse compared with surgery alone, but chemotherapy was not significantly associated with survival.

Phase II Trial Evaluating Esophageal Anastomotic Reinforcement with a Biologic, Degradable, Extracellular Matrix after Total Gastrectomy and Esophagectomy.

BACKGROUND: A biologic, degradable extracellular matrix (ECM) has been shown to support esophageal tissue remodeling, which could reduce the risk of anastomotic leak following total gastrectomy and esophagectomy. We evaluated the safety and efficacy of reinforcing the anastomosis with ECM in reducing anastomotic leak as compared to a matched cohort. STUDY DESIGN: In this single-center, nonrandomized phase II trial, gastric or esophageal adenocarcinoma patients undergoing total gastrectomy or esophagectomy were recruited from November 2013 through December 2018. ECM was surgically wrapped circumferentially around the anastomosis. Anastomotic leak was assessed clinically and by contrast study and defined as clinically significant if requiring invasive treatment (grade 3 or higher). Anastomotic stenosis, other adverse events, symptoms, and dysphagia score were collected by standardized forms at regular follow-up visits at approximately postoperative days (POD) 21 and 90. Patients receiving ECM were compared to a cohort matched for surgery type and age. RESULTS: ECM placement was not feasible in 9 of 75 patients (12%), resulting in 66 patients receiving ECM. Total gastrectomy was performed in 50 patients (76%) and esophagectomy in 16 (24%). Clinically significant anastomotic leak was diagnosed in 6 of 66 patients (9.1%) (3/50 [6.0%] after gastrectomy, 3/16 [18.8%] after esophagectomy); this rate did not differ from that in the matched cohort (p = 0.57). Stenosis requiring invasive treatment occurred in 8 patients (12.5%), and 10 patients (15.6%) reported not being able to eat a normal diet at POD 90. No adverse events related to ECM were reported. CONCLUSIONS: Esophageal anastomotic reinforcement after total gastrectomy or esophagectomy with a biologic, degradable ECM was mostly feasible and safe, but was not associated with a statistically significant decrease in anastomotic leak.

Enhanced PAtient Clinical Streamlining (EPACS): Quality Initiative to Improve Healthcare for New Surgical Outpatient Visits.

PURPOSE: For patients who select a specialty hospital for cancer treatment, the wait time until the initial consultation leaves patients anxious and delays treatment. To improve quality of care, we implemented an enhanced patient clinical streamlining (EPACS) process that establishes an early connection and coordinates care before the first surgical outpatient visit at our specialty cancer center. METHODS: During a pre-visit EPACS phone call to new patients, an advanced practice provider (APP) collected medical history and ordered work-up tests or consultations if feasible. First visit cancellation rate, number of patients who started treatment, time to start of treatment, and satisfaction by the care team and patient were compared between patients treated with versus without EPACS. RESULTS: Among 5062 consecutive new patients, 720 (14%) received an EPACS call and 4342 did not (86%); work-up was ordered pre-visit in 34% and 16%, respectively. Fewer EPACS patients cancelled the first visit (4.6% vs. 12%, p < 0.001), more started treatment (55% vs. 50%, p = 0.037), and their time to treatment was shorter, but not significantly (median 17 vs. 19 days, p = 0.086). Patient interaction was considered to be improved by EPACS by 17 of 17 APPs and 14 of 16 surgeons, and outpatient clinic efficiency by 14 of 17 APPs and 13 of 16 surgeons. EPACS reduced anxiety and increased preparedness for the first visit in 29 of 31 patients. CONCLUSIONS: EPACS improved effectiveness, timeliness, and physician and patient satisfaction with health care at our cancer center.

Change in Neutrophil-to-Lymphocyte Ratio During Neoadjuvant Treatment Does Not Predict Pathological Response and Survival in Resectable Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been reported as prognostic in pancreatic ductal adenocarcinoma (PDAC). Data about NLR changes during neoadjuvant therapy (NAT) and its relationship with pathological tumor response and survival are lacking. METHODS: Pancreatic ductal adenocarcinoma patients with NAT followed by resection between 2009 and 2015 were identified from a prospective database. Neutrophil-to-lymphocyte ratio was collected prior to NAT (baseline), on chemotherapy (prior to cycle 3), and prior to surgery. Baseline NLR, and changes in NLR between baseline and on chemotherapy (delta 1) and between baseline and surgery (delta 2) were compared with pathologic response (<90% and ≥90% defined as poor and good), overall (OS), and disease-free survival (DFS) using Wilcoxon rank-sum and Cox proportional hazard models. RESULTS: Of 93 patients, 17% had good pathological response. Median (interquartile range) NLR at baseline, third cycle, and surgery were 2.7 (2.0-3.7), 2.5 (1.9-4.1), and 3.1 (2.1-5.3), respectively. Median change in NLR from baseline to third cycle was .06 (P = .72), and .6 from baseline to surgery (P < .01). Baseline NLR, delta 1, and delta 2 were not associated with pathological response, OS, or DFS. DISCUSSION: Neutrophil-to-lymphocyte ratio increased after NAT, but a significant association between NLR and pathological response, OS, and DFS in resected PDAC patients was not observed.

Association of Obesity with Worse Operative and Oncologic Outcomes for Patients Undergoing Gastric Cancer Resection.

BACKGROUND: How obesity has an impact on operative and oncologic outcomes for gastric cancer patients is unclear, and the influence of obesity on response to neoadjuvant chemotherapy (NAC) has not been evaluated. METHODS: Patients who underwent curative gastrectomy for primary gastric cancer between 2000 and 2018 were retrospectively identified. After stratification for NAC, operative morbidity, mortality, overall survival (OS), and disease-specific survival (DSS) were compared among three body mass index (BMI) categories: normal BMI (< 25 kg/m2), mild obesity (25-35 kg/m2), and severe obesity (≥ 35 kg/m2). RESULTS: During the study period, 984 patients underwent upfront surgery, and 484 patients received NAC. Tumor stage did not differ among the BMI groups. However, the rates of pathologic response to NAC were significantly lower for the patients with severe obesity (10% vs 40%; p < 0.001). Overall complications were more frequent among the obese patients (44.3% for obese vs 24.9% for normal BMI, p < 0.001). Intraabdominal infections were also more frequent in obese patients (13.9% for obese vs 4.7% for normal BMI, p = 0.001). In the upfront surgery cohort, according to the BMI, OS and DSS did not differ, whereas in the NAC cohort, severe obesity was independently associated with worse OS [hazard ratio (HR) 1.87; 95% confidence interval (CI) 1.01-3.48; p = 0.047] and disease-specific survival (DSS) (HR 2.08; 95% CI 1.07-4.05; p = 0.031). CONCLUSION: For the gastric cancer patients undergoing curative gastrectomy, obesity was associated with significantly lower rates of pathologic response to NAC and more postoperative complications, as well as shorter OS and DSS for the patients receiving NAC.

Longitudinal Analysis of Quality-of-Life Recovery After Gastrectomy for Cancer.

OBJECTIVE: The purpose of this study was to identify factors associated with quality-of-life recovery after gastrectomy. METHODS: Patients anticipated to undergo gastric cancer resection were invited to complete the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and STO22 surveys in the preoperative setting and at 0-1.5 months (early), > 1.5-6 months (intermediate), and > 6-18 months (late) following resection. Quality-of-life recovery was measured as paired differences between pre- and postoperative results. Multivariable linear regression identified factors associated with preoperative quality of life and degree of change following resection. RESULTS: Across 393 participants, response rates at the intermediate and late postoperative time points were 58% (n = 228) and 71% (n = 277), respectively. Relative to baseline, median global health scale decreased in the early (- 15.1 pts, p < 0.001) and intermediate (- 3.6 pts, p = 0.02) time points, but recovered by the late time point (+ 1.2 pts, p = 0.411). Relative to distal/subtotal gastrectomy, proximal/total gastrectomy was associated with worse recovery in both the early and late time points. Surgical complications were associated with worse early recovery. Patients who presented with locally advanced tumors (T3-T4) had lower preoperative quality-of-life scores, and more readily recovered to baseline after surgery. A minimally invasive approach was not associated with postoperative recovery. CONCLUSIONS: Most patients recover to baseline within 1 year following major gastrectomy, and recovery is easier with more limited resections. Patients with locally advanced tumors tend to have poorer baseline quality of life, which may improve following resection.

Performance of the American College of Surgeons NSQIP Surgical Risk Calculator for Total Gastrectomy.

BACKGROUND: To encourage implementation of the American College of Surgeons (ACS) NSQIP Risk Calculator for total gastrectomy for gastric cancer, its predictive performance for this specific procedure should be validated. We assessed its discriminatory accuracy and goodness of fit for predicting 12 adverse outcomes. STUDY DESIGN: Data were collected on all patients with gastric cancer who underwent total gastrectomy with curative intent at Memorial Sloan Kettering Cancer Center between 2002 and 2017. Preoperative risk factors from the electronic medical record were manually inserted into the ACS-NSQIP Risk Calculator. Predictions for adverse outcomes were compared with observed outcomes by Brier scores, c-statistics, and Hosmer-Lemeshow p value. RESULTS: In a total of 452 patients, the predicted rate of all complications (29%) was lower than the observed rate (45%). Brier scores varied between 0.017 for death and 0.272 for any complication. C-statistics were moderate (0.7-0.8) for death and renal failure, good (0.8-0.9) for cardiac complication, and excellent (≥0.9) for discharge to nursing or rehabilitation facility. Hosmer-Lemeshow p value found poor goodness of fit for pneumonia only. CONCLUSIONS: For adverse outcomes after total gastrectomy with curative intent in gastric cancer patients, performance of the ACS-NSQIP Risk Calculator is variable. Its predictive performance is best for cardiac complications, renal failure, death, and discharge to nursing or rehabilitation facility.

Effect of Case-Mix and Random Variation on Breast Cancer Care Quality Indicators and Their Rankability.

OBJECTIVES: Hospital comparisons to improve quality of care require valid and reliable quality indicators. We aimed to test the validity and reliability of 6 breast cancer indicators by quantifying the influence of case-mix and random variation. METHODS: The nationwide population-based database included 79 690 patients with breast cancer from 91 Dutch hospitals between 2011 and 2016. The indicator-scores calculated were: (1) irradical breast-conserving surgery (BCS) for invasive disease, (2) irradical BCS for ductal carcinoma-in-situ, (3) breast contour-preserving treatment, (4) magnetic resonance imaging (MRI) before neo-adjuvant chemotherapy, (5) radiotherapy for locally advanced disease, and (6) surgery within 5 weeks from diagnosis. Case-mix and random variation adjustments were performed by multivariable fixed and random effect logistic regression models. Rankability quantified the between-hospital variation, representing unexplained differences that might be the result of the level of quality of care, as low (<50%), moderate (50%-75%), or high (>75%). RESULTS: All of the indicators showed between-hospital variation with wide (interquartile) ranges. Case-mix adjustment reduced variation in indicators 1 and 3 to 5. Random variation adjustment (further) reduced the variation for all indicators. Case-mix and random variation adjustments influenced the indicator-scores of individual hospitals and their ranking. Rankability was poor for indicator 1, 2, and 5, and moderate for 3, 4, and 6. CONCLUSIONS: The 6 indicators lacked validity and/or reliability to a certain extent. Although measuring quality indicators may stimulate quality improvement in general, comparisons and judgments of individual hospital performance should be made with caution if based on indicators that have not been tested or adjusted for validity and reliability, especially in benchmarking.

From Multiple Quality Indicators of Breast Cancer Care Toward Hospital Variation of a Summary Measure.

OBJECTIVES: To improve quality in breast cancer care, large numbers of quality indicators are collected per hospital, but benchmarking remains complex. We aimed to assess the validity of indicators, develop a textbook outcome summary measure, and compare case-mix adjusted hospital performance. METHODS: From a nationwide population-based registry, all 79 690 nonmetastatic breast cancer patients surgically treated between 2011 and 2016 in 91 hospitals in The Netherlands were included. Twenty-one indicators were calculated and their construct validity tested by Spearman's rho. Between-hospital variation was expressed by interquartile range (IQR), and all valid indicators were included in the summary measure. Standardized scores (observed/expected based on case mix) were calculated as above (>100) or below (<100) expected. The textbook outcome was presented as a continuous and all-or-none score. RESULTS: The size of between-hospital variation varied between indicators. Sixteen (76%) of 21 quality indicators showed construct validity, and 13 were included in the summary measure after excluding redundant indicators that showed collinearity with others owing to strong construct validity. The median all-or-none textbook outcome score was 49% (IQR 42%-54%) before and 49% (IQR 48%-51%) after case-mix adjustment. From the total of 91 hospitals, 3 hospitals were positive (3%) and 9 (10%) were negative outliers. CONCLUSIONS: The textbook outcome summary measure showed discriminative ability when hospital performance was presented as an all-or-none score. Although indicator scores and outlier hospitals should always be interpreted cautiously, the summary measure presented here has the potential to improve Dutch breast cancer quality indicator efforts and could be implemented to further test its validity, feasibility, and usefulness.

Predicting malignancy in patients with adrenal tumors using 18 F-FDG-PET/CT SUVmax.

BACKGROUND AND OBJECTIVES: 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG-PET/CT) parameters may help distinguish malignant from benign adrenal tumors, but few have been externally validated or determined based on definitive pathological confirmation. We determined and validated a threshold for 18 F-FDG-PET/CT maximum standard uptake value (SUVmax) in patients who underwent adrenalectomy for a nonfunctional tumor. METHODS: Database review identified patients with 18 F-FDG-PET/CT images available (training cohort), or only SUVmax values (validation cohort). Discriminative accuracy was assessed by area under the curve (AUC), and the optimal cutoff value estimated by maximally selected Wilcoxon rank statistics. RESULTS: Of identified patients (n = 171), 86 had adrenal metastases, 20 adrenal cortical carcinoma, and 27 adrenal cortical adenoma. In the training cohort (n = 96), SUVmax was significantly higher in malignant versus benign tumors (median 8.3 vs. 3.0, p < .001), with an AUC of 0.857. Tumor size did not differ. The optimal cutoff SUVmax was 4.6 (p < .01). In the validation cohort (n = 75), this cutoff had a sensitivity of 75% and specificity 55%. CONCLUSIONS: 18 F-FDG-PET/CT SUVmax was associated with malignancy. Validation indicated that SUVmax ≥ 4.6 was suggestive of malignancy, while lower values did not reliably predict benign tumor.

Indications for Total Gastrectomy in CDH1 Mutation Carriers and Outcomes of Risk-Reducing Minimally Invasive and Open Gastrectomies.

Importance: CDH1 variants are increasingly identified on commercially available multigene panel tests, calling for data to inform counseling of individuals without a family history of gastric cancer. Objectives: To assess association between CDH1 variant pathogenicity or family history of gastric or lobular breast cancer and identification of signet ring cell cancer and to describe outcomes of risk-reducing minimally invasive and open total gastrectomy. Design, Setting, and Participants: This cohort study was performed from January 1, 2006, to January 1, 2020, in 181 patients with CDH1 germline variants from a single institution. Interventions: Genetic counseling, esophagogastroduodenoscopy, and possible total gastrectomy. Main Outcomes and Measures: CDH1 variant classification, family cancer history, findings of signet ring cell carcinoma at esophagogastroduodenoscopy and surgery, postoperative events and weight changes, and follow-up. Results: Of 181 individuals with CDH1 germline variants (mean [SD] age at time of testing, 44 [15] years; 126 [70%] female), 165 harbored a pathogenic or likely pathogenic variant. Of these patients, 101 underwent open (n = 58) or minimally invasive (n = 43) total gastrectomy. Anastomotic leaks that required drainage were infrequent (n = 3), and median long-term weight loss was 20% (interquartile range [IQR], 10%-23%). In those undergoing minimally invasive operations, more lymph nodes were retrieved (median, 28 [IQR, 20-34] vs 15 [IQR, 9-19]; P < .001) and the hospital stay was 1 day shorter (median, 6 [IQR, 5-7] vs 7 [IQR, 6-7] days; P = .04). Signet ring cell cancer was identified in the surgical specimens of 85 of 95 patients (89%) with a family history of gastric cancer and 4 of 6 patients (67%) who lacked a family history. Among the latter 6 patients, 4 had a personal or family history of lobular breast cancer, including 2 with signet ring cell cancer. Of the 16 patients with pathogenic or likely pathogenic CDH1 variants who presented with locally advanced or metastatic gastric cancer, 3 (19%) had no family history of gastric cancer or personal or family history of lobular breast cancer. Conclusions and Relevance: Total gastrectomy may be warranted for patients with pathogenic or likely pathogenic CDH1 variants and a family history of gastric or lobular breast cancer and may be appropriate for those without a family history. A minimally invasive approach is feasible and may be preferred for selected patients.

Second Uterine Curettage and the Number of Chemotherapy Courses in Postmolar Gestational Trophoblastic Neoplasia: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effect of second uterine curettage on the number of chemotherapy courses and relapse rate in low-risk postmolar gestational trophoblastic neoplasia. METHODS: In a phase III trial, patients with low risk gestational trophoblastic neoplasia were randomised (1:1) to a second curettage or no curettage group before methotrexate treatment. Eligibility criteria were serum human chorionic gonadotropin (hCG) level 5,000 international units/L or less and fit for treatment with methotrexate. Exclusion criteria were previous uterine perforation and life-threatening bleeding. With a two-sided 5% significance level and a power of 99%, a sample size of 44 patients per group was necessary to detect a mean reduction in 2.3 chemotherapy courses. The primary outcome was the number of chemotherapy courses required for hCG normalization. Secondary outcomes were needed for second-line treatment, toxicity, relapse rates, and variables associated with number of chemotherapy courses. RESULTS: From October 2011 through February 2016, 89 patients entered the study at the Mansoura Trophoblastic Clinic; in each group, 43 patients were included in the intention-to-treat analyses. Surgical complications did not occur. The mean number of chemotherapy courses required to reach hCG normalization was 4.4±2.2 SD in the control group vs 3.8±2.3 SD in the intervention group (P=.14). Groups were comparable in terms of second-line treatment needed to reach hCG normalization, and relapse within the first year. Only hCG levels related to the number of chemotherapy cycles required for hCG normalization. CONCLUSION: Second uterine curettage did not reduce the number of chemotherapy courses required or affect relapse rate in patients with low-risk postmolar gestational trophoblastic neoplasia. CLINICAL TRIALS REGISTRATION: Dutch Trial Registry, NTR3390.

Evaluation of cosmetic outcome following breast-conserving therapy in trials: panel versus digitalized analysis and the role of PROMs.

Cosmetic outcome is an important quality of life-related end point following breast-conserving therapy (BCT). To advise on a gold standard, we compare cosmetic outcome evaluated by panel and an objective evaluation (BCCT.core software). Second, patient-reported outcome measures (PROMs) are compared to cosmetic outcome evaluation by panel and BCCT.core. Sixty-eight breast cancer patients were included following BCT between 2007 and 2012. Two independent 6-member panels and two observers using the BCCT.core evaluated cosmetic outcome. First, reproducibility, repeatability, and relatedness of panel and BCCT.core were analyzed using the interclass correlation coefficient (ICC). Second, the association between panel/BCCT.core with PROMs (EORTC-QLQ-C30/BR23, EQ-5D-5L, and BREAST-Q) was analyzed with a linear regression and the goodness of fit by the R2 . Both panel and BCCT.core evaluations showed "excellent" intraobserver agreement (ICC 0.93 [95% CI: 0.83; 0.97] and 0.93 [95% CI: 0.84; 0.97]) for respectively panel 1 and BCCT.core 1 and "excellent" interobserver agreement (ICC 0.94 [95% CI: 0.90; 0.96] and 0.85 [95% CI: 0.77; 0.91]) respectively for panel and BCCT.core. Association between panel and BCCT.core varied, ICC 0.59-0.69. Only the PROM BREAST-Q showed a significant association with both panel evaluations and BCCT.core observers (panel 1 and BCCT.core 1; R2 of .157 [P = .002] and .178 [P = .001]). Both panel and BCCT.core showed comparable "excellent" intraobserver and interobserver agreement. For future trials evaluating cosmetic outcome following BCT, one of those can be chosen. Solely, the PROM BREAST-Q showed a significant association with panel and/or BCCT.core evaluation. To enable standardized cosmetic outcome evaluation and corresponding patient satisfaction in future trials, at least the BREAST-Q should be combined with a panel or BCCT.core evaluation.

Omitting re-excision for focally positive margins after breast-conserving surgery does not impair disease-free and overall survival.

PURPOSE: In contrast to other countries, the Dutch breast cancer guideline does not recommend re-excision for focally positive margins after breast-conserving surgery (BCS) in invasive tumor and does recommend whole-breast irradiation including boost. We investigated whether omitting re-excision as compared to performing re-excision affects prognosis with a retrospective population-based cohort study. METHODS: The total cohort included 32,119 women with primary BCS for T1-T3 breast cancer diagnosed between 2003 and 2008 from the nationwide Netherlands cancer registry. The subcohort included 10,433 patients in whom the resection margins were registered. Outcome measures were 5-year ipsilateral breast tumor recurrence (IBTR) rate, 5-year disease-free survival (DFS) rate, and 10-year overall survival (OS) rate. RESULTS: In the total cohort, 25,878 (80.6%) did not have re-excision, 2368 (7.4%) had re-excision by BCS, and 3873 (12.1%) had re-excision by mastectomy. Five-year IBTR rates were 2.1, 2.8, and 2.9%, respectively (p = 0.001). In the subcohort, 7820 (75.0%) had negative margins without re-excision, 492 (4.7%) had focally positive margins without re-excision, 586 (5.6%) had focally positive margins and underwent re-excision, and 1535 (14.7%) had extensively positive margins and underwent re-excision. Five-year IBTR rate was 2.3, 2.9, 1.1, and 2.9%, respectively (p = 0.099). Compared to omitting re-excision, performing re-excision for focally positive margins was associated with lower risk of IBTR (adjusted HR 0.30, 95% CI 0.11-0.82), but not with DFS (adjusted HR 0.83 95% CI 0.59-1.17) nor with OS (adjusted HR 1.17 95% CI 0.87-1.59). CONCLUSION: Omitting re-excision in breast cancer patients for focally positive margins after BCS does not impair DFS and OS, provided that whole-breast irradiation including boost is given.

Patient Satisfaction and Nipple-Areola Sensitivity After Bilateral Prophylactic Mastectomy and Immediate Implant Breast Reconstruction in a High Breast Cancer Risk Population: Nipple-Sparing Mastectomy Versus Skin-Sparing Mastectomy.

BACKGROUND: Prophylactic skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) both are associated with major risk reduction in women with high breast cancer risk. Skin-sparing mastectomy followed by nipple-areola complex (NAC) reconstruction is standard of care, but NSM is increasingly being performed. Preservation of the NAC in NSM may increase patient satisfaction. Therefore, we measured NAC sensitivity after NSM and compared patient satisfaction as well as body image after SSM with NSM. METHODS: Women who underwent prophylactic bilateral SSM or NSM and immediate implant breast reconstruction between 2002 and 2012 were eligible. Patient satisfaction was assessed using the Breast-Q reconstruction questionnaire, body image using Hopwood's body image scale (BIS), and satisfaction with the (reconstructed) NAC using a study-specific questionnaire. In the NSM group, NAC sensitivity was assessed using Semmes Weinstein monofilaments with a 5-point scale and compared with NAC sensitivity in a nonoperated control group. RESULTS: The SSM group comprised 25 women (50 SSMs) and the NSM group 20 women (39 NSMs). Median follow-up was 65 months in the SSM group compared with 27 months in the NSM group (P < 0.01). In univariable analyses, Breast-Q scores were favorable in the SSM group compared with the NSM group with trends for higher "satisfaction with breasts" (66.2 vs 56.6; P = 0.06) and "satisfaction with outcome" (76.1 vs 61.5; P = 0.09). Mean BIS score of 7.1/30 in the SSM group and 9.3/30 in the NSM group (P = 0.35). Adjusted for follow-up, there were no significant differences in Breast-Q scores, nor in BIS scores. Interestingly, satisfaction with the (reconstructed) NAC was similar after SSM and NSM. Nipple-areola complex sensitivity was lower in the NSM group (mean score, 1.9; 95% confidence interval, 1.5-2.3) compared with the control group (mean score, 4.7; 95% confidence interval, 4.6-4.9; P < 0.01). CONCLUSIONS: Breast-Q scores regarding satisfaction with breasts and overall outcome were in favor of the SSM group. Residual NAC sensitivity after NSM was low. This suggests that SSM followed by NAC reconstruction is a balanced alternative to NSM. We observed no significant differences in body image and NAC-specific satisfaction between the NSM and SSM groups.

Overall survival in patients with a re-excision following breast conserving surgery compared to those without in a large population-based cohort.

AIM: To investigate the overall survival of invasive breast cancer patients with primary breast conserving surgery (BCS) followed by re-excision compared to those with primary BCS only. The Dutch re-excision indications are less stringent compared to other European and Northern American countries (Society of Surgical Oncology-American Society for Radiation Oncology (SSO/ASTRO) guideline). METHODS: Retrospective analyses in women <75years with breast cancer stage pT1-T3 treated by BCS and radiotherapy between 1999 and 2012 from a population-based database. The national guideline recommends to reserve re-excision for invasive tumours showing 'more than focally positive' margin since 2002. Patients were divided into 'primary BCS only', 're-excision by BCS', and 're-excision by mastectomy'. Multivariable Cox regression analysis was adjusted for patient and systemic treatment characteristics. RESULTS: A total of 11,695 patients were included of which 2156 (18.4%) underwent re-excision. Median time of follow-up was 61months (interquartile range (IQR) 26-101). The 5-year overall survival rates in the 'primary BCS only', 're-excision by BCS' and 're-excision by mastectomy' group were 92%, 95% and 91%, respectively. The 10-year overall survival rates were 81%, 82% and 79%, respectively (P=0.20). After multivariable analyses no significant association was observed between use of and type of re-excision and overall survival. CONCLUSIONS: The overall survival of breast cancer patients with a re-excision did not significantly differ from the survival of women who underwent primary BCS only. Advising re-excision only for those tumours showing 'more than focally positive' resection margin appears safe, supposing the long-term safety of the recent SSO/ASTRO guideline that more cautiously recommended re-excision for tumours showing 'ink on tumour'.

Preoperative prediction of cosmetic results in breast conserving surgery.

BACKGROUND: Preoperative objective predictions of cosmetic result after breast conserving surgery (BCS) has the potential to aid in surgical treatment decision making. Our aim was to investigate the predictive value of tumor volume in relation to breast volume (TV/BV ratio) for cosmetic result. METHODS: Sixty-nine invasive breast cancer women with preoperative MRI and treated by BCS and radiotherapy in 2007-2012 were prospectively included. Simple excision or basic oncoplastic techniques were used, but no volume displacement. TV/BV ratio was measured in the MRI while 3D-projected in virtual reality environment (I-Space). Cosmetic result was assessed by patient questionnaire, panel evaluation, and breast retraction assessment (BRA). Quality-of-life was assessed by EORTC QLQ-C30 and BR23. RESULTS: Intraobserver and interobserver correlation coefficients for tumor and breast volume were all >0.95. Increasing TV/BV ratio correlated with decreasing cosmetic result as determined by patient, panel, and BRA. TV/BV ratio was a significant independent predictor for the panel evaluation (P=0.028), as was tumor location (P<0.05), and together they constituted a good prediction model (AUC 0.83). CONCLUSIONS: TV/BV ratio was a precise and independent predictor for cosmetic result determined by a panel and can be used as preoperative prediction tool to enable more informed surgical treatment decision making.

Intramucosal carcinoma of the rectum can be safely treated with transanal endoscopic microsurgery; clinical support of the revised Vienna classification.

AIM: The revised Vienna criteria were proposed for classifying rectal neoplasia and subsequent treatment strategies. Restaging intramucosal carcinoma to a non-invasive subgroup seems logical, but clinical support is lacking. In this study, we investigated whether distinction between intramucosal carcinomas (IMC) and rectal adenoma (RA) is of clinical relevance and whether these neoplasms can all be similarly and safely treated by transanal endoscopic microsurgery (TEM). METHODS: All consecutive patients with IMC and RA, treated with TEM between 1996 and 2010 in tertiary referral centre for TEM were included. Long-term outcome of 88 IMC was compared to 356 pure rectal adenomas (RA). Local recurrence (LR) rate was the primary endpoint. Risk factors for LR were analysed. RESULTS: LR was diagnosed in 7/88 patients (8.0 %) with IMC and in 33/356 patients with primary RA (9.3 %; p = 0.700) and LR-free survival did not differ (p = 0.438). Median time to recurrence was 10 months (IQR IMC 5-30; RA 6-16). Overall recurrence occurred mainly in the first 3 years (38/40; 95 %). None of the LR revealed malignancy on pathological evaluation. No differences could be found in complication rates (IMC 9 %; RA 13 %; p = 0.34). Metastases did not occur in either group. Independent risk factors for LR were irradical margins at final histopathology (HR 2.32; 95 % CI 1.17-4.59; p = 0.016) and more proximal tumours (HR 0.84; 95 % CI 0.77-0.92; P = <0.001). CONCLUSION: In this study, IMC of the rectum and RA have similar recurrence rates. This supports the revised Vienna classification. Both entities can be safely treated with TEM.