Alvin J. Siteman Cancer Center: Cancer Prevention Perspective.

We summarize Siteman Cancer Center catchment that covers 82 counties in southern Illinois and eastern Missouri. We note both the high poverty and cancer rates in many rural counties. Siteman Community Outreach and Engagement has developed a number of strategies to move towards achieving health equity. These include NCI-funded research projects in rural clinics and outreach to improve access to cancer prevention services. To increase capacity for community-engaged research, we have developed and refined a Community Research Fellows Training Program.

Impact of Prehabilitation on Postoperative Mortality and the Need for Non-Home Discharge in High-Risk Surgical Patients.

BACKGROUND: The preoperative period is an important target for interventions (eg Surgical Prehabilitation and Readiness [SPAR]) that can improve postoperative outcomes for older patients with comorbidities. STUDY DESIGN: To determine whether a preoperative multidisciplinary prehabilitation program (SPAR) reduces postoperative 30-day mortality and the need for non-home discharge in high-risk surgical patients, surgical patients enrolled in a prehabilitation program targeting physical activity, pulmonary function, nutrition, and mindfulness were compared with historical control patients from 1 institution's American College of Surgeons (ACS) NSQIP database. SPAR patients were propensity score-matched 1:3 to pre-SPAR NSQIP patients, and their outcomes were compared. The ACS NSQIP Surgical Risk Calculator was used to compare observed-to-expected ratios for postoperative outcomes. RESULTS: A total of 246 patients were enrolled in SPAR. A 6-month compliance audit revealed that overall patient adherence to the SPAR program was 89%. At the time of analysis, 118 SPAR patients underwent surgery with 30 days of follow-up. Compared with pre-SPAR NSQIP patients (n = 4,028), SPAR patients were significantly older with worse functional status and more comorbidities. Compared with propensity score-matched pre-SPAR NSQIP patients, SPAR patients had significantly decreased 30-day mortality (0% vs 4.1%, p = 0.036) and decreased need for discharge to postacute care facilities (6.5% vs 15.9%, p = 0.014). Similarly, SPAR patients exhibited decreased observed 30-day mortality (observed-to-expected ratio 0.41) and need for discharge to a facility (observed-to-expected ratio 0.56) compared with their expected outcomes using the ACS NSQIP Surgical Risk Calculator. CONCLUSIONS: The SPAR program is safe and feasible and may reduce postoperative mortality and the need for discharge to postacute care facilities in high-risk surgical patients.

Impact of the COVID-19 Pandemic on Surgical Training and Learner Well-Being: Report of a Survey of General Surgery and Other Surgical Specialty Educators.

BACKGROUND: The COVID-19 pandemic disrupted the delivery of surgical services. The purpose of this communication was to report the impact of the pandemic on surgical training and learner well-being and to document adaptations made by surgery departments. STUDY DESIGN: A 37-item survey was distributed to educational leaders in general surgery and other surgical specialty training programs. It included both closed- and open-ended questions and the self-reported stages of GME during the COVID-19 pandemic, as defined by the ACGME. Statistical associations for items with stage were assessed using categorical analysis. RESULTS: The response rate was 21% (472 of 2,196). US stage distribution (n = 447) was as follows: stage 1, 22%; stage 2, 48%; and stage 3, 30%. Impact on clinical education significantly increased by stage, with severe reductions in nonemergency operations (73% and 86% vs 98%) and emergency operations (8% and 16% vs 34%). Variable effects were reported on minimal expected case numbers across all stages. Reductions were reported in outpatient experience (83%), in-hospital experience (70%), and outside rotations (57%). Increases in ICU rotations were reported with advancing stage (7% and 13% vs 37%). Severity of impact on didactic education increased with stage (14% and 30% vs 46%). Virtual conferences were adopted by 97% across all stages. Severity of impact on learner well-being increased by stage-physical safety (6% and 9% vs 31%), physical health (0% and 7% vs 17%), and emotional health (11% and 24% vs 42%). Regardless of stage, most but not all made adaptations to support trainees' well-being. CONCLUSIONS: The pandemic adversely impacted surgical training and the well-being of learners across all surgical specialties proportional to increasing ACGME stage. There is a need to develop education disaster plans to support technical competency and learner well-being. Careful assessment for program advancement will also be necessary. The experience during this pandemic shows that virtual learning and telemedicine will have a considerable impact on the future of surgical education.

Ensuring Equity, Diversity, and Inclusion in Academic Surgery: An American Surgical Association White Paper.

OBJECTIVE: The leadership of the American Surgical Association (ASA) appointed a Task Force to objectively address issues related to equity, diversity, and inclusion with the discipline of academic surgery. SUMMARY OF BACKGROUND DATA: Surgeons and the discipline of surgery, particularly academic surgery, have a tradition of leadership both in medicine and society. Currently, we are being challenged to harness our innate curiosity, hard work, and perseverance to address the historically significant deficiencies within our field in the areas of diversity, equity, and inclusion. METHODS: The ASA leadership requested members to volunteer to serve on a Task Force to comprehensively address equity, diversity, and inclusion in academic surgery. Nine work groups reviewed the current literature, performed primary qualitative interviews, and distilled available guidelines and published primary source materials. A work product was created and published on the ASA Website and made available to the public. The full work product was summarized into this White Paper. RESULTS: The ASA has produced a handbook entitled: Ensuring Equity, Diversity, and Inclusion in Academic Surgery, which identifies issues and challenges, and develops a set of solutions and benchmarks to aid the academic surgical community in achieving these goals. CONCLUSION: Surgery must identify areas for improvement and work iteratively to address and correct past deficiencies. This requires honest and ongoing identification and correction of implicit and explicit biases. Increasing diversity in our departments, residencies, and universities will improve patient care, enhance productivity, augment community connections, and achieve our most fundamental ambition-doing good for our patients.

Interim Analysis of a Prospective Multi-Institutional Study of Surgery Resident Experience with Flexibility in Surgical Training.

BACKGROUND: The Flexibility in Surgical Training (FIST) consortium project was designed to evaluate the feasibility and resident outcomes of optional subspecialty-focused training within general surgery residency training. STUDY DESIGN: After approval by the American Board of Surgery, R4 and R5 residents were permitted to customize up to 12 of the final 24 months of residency for early tracking into 1 of 9 subspecialty tracks. A prospective IRB-approved study was designed across 7 institutions to evaluate the impact of this option on operative experience, in-service exam (American Board of Surgery In-Training Examination [ABSITE]) and ACGME milestone performance, and resident and program director (PD) perceptions. The FIST residents were compared with chief residents before FIST initiation (controls) as well as residents during the study period who did not participate in FIST (no specialization track, NonS). RESULTS: From 2013 to 2017, 122 of 214 chief residents (57%) completed a FIST subspecialty track. There were no differences in median ABSITE scores between FIST, NonS residents, and controls. The ACGME milestones at the end of the R5 year favored the FIST residents in 13 of 16 milestones compared with NonS. Case logs demonstrated an increase in track-specific cases compared with NonS residents. Resident and PD surveys reported a generally favorable experience with FIST. CONCLUSIONS: In this prospective study, FIST is a feasible option in participating institutions. All FIST residents, regardless of track, met requirements for ABS Board eligibility, despite modifications to rotations and case experience. Future studies will assess the impact of FIST on ABS exam results and fellowship success.

NeoPalAna: Neoadjuvant Palbociclib, a Cyclin-Dependent Kinase 4/6 Inhibitor, and Anastrozole for Clinical Stage 2 or 3 Estrogen Receptor-Positive Breast Cancer.

Purpose: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor-positive (ER+) breast cancer. This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the antiproliferative activity of the CDK4/6 inhibitor palbociclib in primary breast cancer as a prelude to adjuvant studies.Experimental Design: Eligible patients with clinical stage II/III ER+/HER2- breast cancer received anastrozole 1 mg daily for 4 weeks (cycle 0; with goserelin if premenopausal), followed by adding palbociclib (125 mg daily on days 1-21) on cycle 1 day 1 (C1D1) for four 28-day cycles unless C1D15 Ki67 > 10%, in which case patients went off study due to inadequate response. Anastrozole was continued until surgery, which occurred 3 to 5 weeks after palbociclib exposure. Later patients received additional 10 to 12 days of palbociclib (Cycle 5) immediately before surgery. Serial biopsies at baseline, C1D1, C1D15, and surgery were analyzed for Ki67, gene expression, and mutation profiles. The primary endpoint was complete cell cycle arrest (CCCA: central Ki67 ≤ 2.7%).Results: Fifty patients enrolled. The CCCA rate was significantly higher after adding palbociclib to anastrozole (C1D15 87% vs. C1D1 26%, P < 0.001). Palbociclib enhanced cell-cycle control over anastrozole monotherapy regardless of luminal subtype (A vs. B) and PIK3CA status with activity observed across a broad range of clinicopathologic and mutation profiles. Ki67 recovery at surgery following palbociclib washout was suppressed by cycle 5 palbociclib. Resistance was associated with nonluminal subtypes and persistent E2F-target gene expression.Conclusions: Palbociclib is an active antiproliferative agent for early-stage breast cancer resistant to anastrozole; however, prolonged administration may be necessary to maintain its effect. Clin Cancer Res; 23(15); 4055-65. ©2017 AACR.

Successful Completion of the Pilot Phase of a Randomized Controlled Trial Comparing Sentinel Lymph Node Biopsy to No Further Axillary Staging in Patients with Clinical T1-T2 N0 Breast Cancer and Normal Axillary Ultrasound.

BACKGROUND: Axillary surgery is not considered therapeutic in patients with clinical T1-T2 N0 breast cancer. The importance of axillary staging is eroding in an era in which tumor biology, as defined by biomarker and gene expression profile, is increasingly important in medical decision making. We hypothesized that axillary ultrasound (AUS) is a noninvasive alternative to sentinel lymph node biopsy (SLNB), and AUS could replace SLNB without compromising patient care. STUDY DESIGN: Patients with clinical T1-T2 N0 breast cancer and normal AUS were eligible for enrollment. Subjects were randomized to no further axillary staging (arm 1) vs SLNB (arm 2). Descriptive statistics were used to describe the results of the pilot phase of the randomized controlled trial. RESULTS: Sixty-eight subjects were enrolled in the pilot phase of the trial (34 subjects in arm 1, no further staging; 32 subjects in arm 2, SLNB; and 2 subjects voluntarily withdrew from the trial). The median age was 61 years (range 40 to 80 years) in arm 1 and 59 years (range 31 to 81 years) in arm 2, and there were no significant clinical or pathologic differences between the arms. Median follow-up was 17 months (range 1 to 32 months). The negative predictive value (NPV) of AUS for identification of clinically significant axillary disease (>2.0 mm) was 96.9%. No axillary recurrences have been observed in either arm. CONCLUSIONS: Successful completion of the pilot phase of the randomized controlled trial confirms the feasibility of the study design, and provides prospective evidence supporting the ability of AUS to exclude clinically significant disease in the axilla. The results provide strong support for a phase 2 randomized controlled trial.

Key Tenets of Effective Surgery Leadership: Perspectives From the Society of Surgical Chairs Mentorship Sessions.

This Special Communication summarizes the key points raised at the Society of Surgical Chairs mentorship panel sessions held at the 2014 and 2015 annual meetings of the society. Highlights of these expert panel discussions include senior chairs' insights into successfully dealing with increasingly complex academic medical organizations and horizontal department management expectations in the context of the arrival of the Millennial Generation into the work force. Three key tenets of effective surgery leadership that arose from these sessions deal with the importance of (1) collaboration and cooperativity, (2) humanized relationships and mentorship, and (3) operational efficiency. Overall, the panel consensus for the future of surgery leadership was optimistic while recognizing that the demands of chairmanship are considerable.

Surgical Training and the Early Specialization Program: Analysis of a National Program.

BACKGROUND: The Early Specialization Program (ESP) in surgery was designed by the American Board of Surgery, the American Board of Thoracic Surgery, and the Residency Review Committees for Surgery and Thoracic Surgery to allow surgical trainees dual certification in general surgery (GS) and either vascular surgery (VS) or cardiothoracic surgery (CTS) after 6 to 7 years of training. After more than 10 years' experience, this analysis was undertaken to evaluate efficacy. STUDY DESIGN: American Board of Surgery and American Board of Thoracic Surgery records of VS and CTS ESP trainees were queried to evaluate qualifying exam and certifying exam performance. Case logs were examined and compared with contemporaneous non-ESP trainees. Opinions of programs directors of GS, VS, and CTS and ESP participants were solicited via survey. RESULTS: Twenty-six CTS ESP residents have completed training at 10 programs and 16 VS ESP at 6 programs. First-time pass rates on American Board of Surgery qualifying and certifying exams were superior to time-matched peers; greater success in specialty specific examinations was also found. Trainees met required case minimums for GS despite shortened time in GS. By survey, 85% of programs directors endorsed satisfaction with ESP, and 90% endorsed graduate readiness for independent practice. Early Specialization Program participants report increased mentorship and independence, greater competence for practice, and overall satisfaction with ESP. CONCLUSIONS: Individuals in ESP programs in VS and CTS were successful in passing GS and specialty exams and achieving required operative cases, despite an accelerated training track. Programs directors and participants report satisfaction with the training and confidence that ESP graduates are prepared for independent practice. This documented success supports ESP training in any surgical subspecialty, including comprehensive GS.

Lymphovascular space invasion and lack of downstaging after neoadjuvant chemotherapy are strong predictors of adverse outcome in young women with locally advanced breast cancer.

Younger age diagnosis of breast cancer is a predictor of adverse outcome. Here, we evaluate prognostic factors in young women with locally advanced breast cancer (LABC). We present a retrospective review of 104 patients younger than 40 years with LABC treated with surgery, radiotherapy (RT), and chemotherapy from 2003 to 2014. Patient-, tumor-, and treatment-related factors important for overall survival (OS), local/regional recurrence (LRR), distant metastasis (DM), and recurrence-free survival (RFS) were evaluated. Mean age at diagnosis was 34 years (23-39 years) with a median follow-up of 47 months (8-138 months). Breast-conserving surgery was performed in 27%. Axillary lymph node dissection was performed in 85%. Sixty percent of patients received neoadjuvant chemotherapy with 19% achieving pathologic complete response (pCR), and 61% downstaged. Lymph node positivity was present in 91% and lymphovascular space invasion (LVSI) in 35%. Thirty-two percent of patients had triple negative tumors (TN, ER-/PR-/HER2 nonamplified). Four-year OS and RFS was 84% and 71%, respectively. Factors associated with worse OS on multivariate analysis include TN status, LVSI, and number of positive lymph nodes. LVSI was also associated with DM and LRR, as well as worse RFS. Downstaging was associated with improved 4 year RFS in patients receiving neoadjuvant chemotherapy (74% vs. 38%, P = 0.002). With high risks of recurrence and inferior OS compared to older women, breast cancer in young women can be difficult to treat. Among additional factors, presence of LVSI and lack of downstaging portends a particularly worse prognosis.

Delivering High-Quality Cancer Care: The Critical Role of Quality Measurement.

In 1999, the Institute of Medicine (IOM) published Ensuring Quality Cancer Care, an influential report that described an ideal cancer care system and issued ten recommendations to address pervasive gaps in the understanding and delivery of quality cancer care. Despite generating much fervor, the report's recommendations-including two recommendations related to quality measurement-remain largely unfulfilled. Amidst continuing concerns regarding increasing costs and questionable quality of care, the IOM charged a new committee with revisiting the 1999 report and with reassessing national cancer care, with a focus on the aging US population. The committee identified high-quality patient-clinician relationships and interactions as central drivers of quality and attributed existing quality gaps, in part, to the nation's inability to measure and improve cancer care delivery in a systematic way. In 2013, the committee published its findings in Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis, which included two recommendations that emphasize coordinated, patient-centered quality measurement and information technology enhancements: Develop a national quality reporting program for cancer care as part of a learning health care system; and,Develop an ethically sound learning health care information technology system for cancer that enables real-time analysis of data from cancer patients in a variety of care settings. These recommendations underscore the need for independent national oversight, public-private collaboration, and substantial funding to create robust, patient-centered quality measurement and learning enterprises to improve the quality, accessibility, and affordability of cancer care in America.

An institutional strategy to increase minority recruitment to therapeutic trials.

PURPOSE: Participation in therapeutic clinical trials rarely reflects the race and ethnic composition of the patient population. To meet National Institutes of Health-mandated goals, strategies to increase participation are required. We present a framework for institutional enhancement of minority clinical trial accrual. METHODS: We implemented structural changes on four levels to induce and sustain minority accrual to clinical trials: (1) leadership support; (2) center-wide policy change; (3) infrastructural process control, data analysis, and reporting; and (4) follow-up with clinical investigators. A Protocol Review and Monitoring Committee reviews studies and monitors accrual, and the Program for the Elimination Cancer Disparities leads efforts for proportional accrual, supporting the system through data tracking, Web tools, and feedback to investigators. RESULTS: Following implementation in 2005, minority accrual to therapeutic trials increased from 12.0 % in 2005 to 14.0 % in 2010. The "rolling average" minority cancer incidence at the institution during this timeframe was 17.5 %. In addition to therapeutic trial accrual rates, we note significant increase in the number of minorities participating in all trials (therapeutic and nontherapeutic) from 2005 to 2010 (346-552, 60 % increase, p < 0.05) compared to a 52 % increase for Caucasians. CONCLUSIONS: Implementing a system to aid investigators in planning and establishing targets for accrual, while requiring this component as a part of annual protocol review and monitoring of accrual, offers a successful strategy that can be replicated in other cancer centers, an approach that may extend to other clinical and translational research centers.

Inflammatory monocyte mobilization decreases patient survival in pancreatic cancer: a role for targeting the CCL2/CCR2 axis.

PURPOSE: To determine the role of the CCL2/CCR2 axis and inflammatory monocytes (CCR2(+)/CD14(+)) as immunotherapeutic targets in the treatment of pancreatic cancer. EXPERIMENTAL DESIGN: Survival analysis was conducted to determine if the prevalence of preoperative blood monocytes correlates with survival in patients with pancreatic cancer following tumor resection. Inflammatory monocyte prevalence in the blood and bone marrow of patients with pancreatic cancer and controls was compared. The immunosuppressive properties of inflammatory monocytes and macrophages in the blood and tumors, respectively, of patients with pancreatic cancer were assessed. CCL2 expression by human pancreatic cancer tumors was compared with normal pancreas. A novel CCR2 inhibitor (PF-04136309) was tested in an orthotopic model of murine pancreatic cancer. RESULTS: Monocyte prevalence in the peripheral blood correlates inversely with survival, and low monocyte prevalence is an independent predictor of increased survival in patients with pancreatic cancer with resected tumors. Inflammatory monocytes are increased in the blood and decreased in the bone marrow of patients with pancreatic cancer compared with controls. An increased ratio of inflammatory monocytes in the blood versus the bone marrow is a novel predictor of decreased patient survival following tumor resection. Human pancreatic cancer produces CCL2, and immunosuppressive CCR2(+) macrophages infiltrate these tumors. Patients with tumors that exhibit high CCL2 expression/low CD8 T-cell infiltrate have significantly decreased survival. In mice, CCR2 blockade depletes inflammatory monocytes and macrophages from the primary tumor and premetastatic liver resulting in enhanced antitumor immunity, decreased tumor growth, and reduced metastasis. CONCLUSIONS: Inflammatory monocyte recruitment is critical to pancreatic cancer progression, and targeting CCR2 may be an effective immunotherapeutic strategy in this disease.

Disease recurrence in sentinel node-positive breast cancer patients forgoing axillary lymph node dissection.

BACKGROUND: Clinically node-negative breast cancer patients usually undergo sentinel lymph node (SLN) biopsy. When metastasis is identified, completion axillary lymph node dissection (CALND) is recommended. Newer data suggest that CALND may be omitted in some women as it does not improve local control or survival. METHODS: Women with a positive SLN diagnosed between 1999 and 2010 were included in this review and were stratified according to whether they did or did not undergo CALND. Primary endpoints included recurrence and breast cancer-specific mortality. Differences between the groups and in time to recurrence were compared and summarized. RESULTS: Overall, 276 women were included: 206 (79 %) women who underwent CALND (group 1) and 70 (21 %) women in whom CALND was omitted (group 2). Group 1 patients were younger, had more SLN disease, and received more chemotherapy (P < 0.05 for each). The groups did not vary by tumor characteristics (P > 0.05 for each). Median follow-up was 69 (range 6-147) and 73 (range 15-134) months for groups 1 and 2, respectively. Five (2 %) women in group 1 and three (4 %) women in group 2 died of breast cancer (P = 0.39). Local-regional or distant recurrence occurred in 20 (10 %) group 1 patients and in 10 (14 %) group 2 patients (P = 0.39). On multivariate analysis, only estrogen receptor negativity and lymphovascular invasion predicted for recurrence. CONCLUSIONS: Omission of CALND in women with SLN disease does not significantly impact in-breast, nodal, or distant recurrence or mortality. Longer-term follow-up is needed to verify that this remains true with time.

Positive margin rates following breast-conserving surgery for stage I-III breast cancer: palpable versus nonpalpable tumors.

BACKGROUND: Margin status is a significant risk factor for local recurrence. We sought to examine whether the method of tumor localization predicted the margin status and the need for re-excision for both nonpalpable and palpable breast cancer. METHODS: We identified 358 consecutive breast cancer patients who were treated with breast-conserving therapy (BCT) from 1999 to 2006. Data included patient and tumor characteristics, method of localization (needle versus palpation), and pathologic outcomes. Descriptive statistics were used for data summary and data were compared using χ(2). RESULTS: Of 358 patients undergoing BCT, 234 (65%) underwent needle localization for a nonpalpable tumor and 124 (35%) underwent a palpation-guided procedure. Patients undergoing palpation-guided procedures were younger and had larger tumors at a more advanced pathologic stage of disease than those undergoing needle localization procedures (P < 0.05 for each). Patient race, tumor grade, presence of lymphovascular invasion, biomarker profile, and nodal status were not significantly different between the two groups (P > 0.05). Overall, 137 patients (38%) had one or more positive margins: 90 of 234 (38%) who had a needle localization procedure and 47 of 124 (38%) who had a palpation-guided procedure (P > 0.05). The number of margins affected did not differ significantly between the two groups. CONCLUSION: Although patients with palpable breast cancer had larger tumors than those with nonpalpable breast cancer, the incidence and number of positive margins was similar to those who had needle localization for nonpalpable tumors. Improved methods of localization are needed to reduce the rate of positive margins and the need for re-excision.