Heather B. Neuman

Stage IV breast cancer in the era of targeted therapy: does surgery of the primary tumor matter?

Multiple studies have suggested that resection of the primary tumor improves survival in patients with stage IV breast cancer, yet in the era of targeted therapy, the relation between surgery and tumor molecular subtype is unknown. The objective of the current study was to identify subsets of patients who may benefit from primary tumor treatment and assess the frequency of local disease progression.

Desmoid Tumors (Fibromatoses) of the Breast: A 25-Year Experience

BackgroundBreast desmoid tumors are rare and often clinically mistaken for carcinoma. We reviewed our 25-year institutional experience with breast desmoid tumors.MethodsA search of pathology and sarcoma databases (1982–2006) identified 32 patients with pathologically confirmed breast desmoids. Records were retrospectively reviewed.ResultsMedian presentation age was 45 years (range, 22–76). Eight patients (25%) had prior history of breast cancer and 14 (44%) of breast surgery, with desmoids diagnosed a median of 24 months postoperatively. All presented with physical findings. Mammography visualized the mass in 6/16, ultrasound in 9/9, and magnetic resonance imaging (MRI) in 8/8 patients in whom it was performed. In 15 patients with attempted needle biopsy, fine needle aspiration was inconclusive (9/9 patients), and core biopsy demonstrated a spindle cell lesion (6/7 patients).Treatment was surgical, with median tumor size of 2.5 cm (range, 0.3–15). Eight patients (29%) had recurring tumors at a median 15 months. Patients with recurring tumors were younger (median age: 28 vs. 46 years, p = 0.03). A trend toward more frequent recurrences in patients with positive (5/9 patients) versus negative (3/19 patients) margins (p = 0.07) and larger tumors (p = 0.12) was observed.ConclusionsIn our series, breast desmoids presented as palpable masses suspicious for carcinoma clinically and radiographically. Therapy remains primarily surgical, and core biopsy aided in operative planning. Recurrences are common, with younger age and possibly positive margin status and larger tumor size associated with increased risk of recurrence. As 5/9 patients with positive and 3/19 patients with negative margins experienced recurrences, clinical judgment should be used prior to extensive and potentially deforming resections.

Stage-IV Melanoma and Pulmonary Metastases: Factors Predictive of Survival

BackgroundWe reviewed a contemporary, single-institution experience to evaluate the natural history of stage-IV melanoma metastatic to the lung and identify factors predictive of survival.MethodsA search of our prospective database was performed to identify patients with stage-IV melanoma and pulmonary metastases as the initial disease site; only patients seen at our institution prior to developing stage-IV disease and in whom treatment response was available were included. Patients’ demographic, clinical, and treatment variables were recorded. Cox regression was used to identify factors independently predictive of survival.ResultsThe study cohort was comprised of 122 patients. Median survival was 14 months (5-year survival of 8%). Clinical factors at time of diagnosis of stage IV independently predictive of survival were a solitary pulmonary metastasis (HR 2.7, CI 1.6–4.4, P<0.0005) and absence of extra-pulmonary disease (HR 1.9, CI 1.2–3.1, P = 0.01). Among treatment factors, only metastasectomy was independently predictive of survival (HR 0.42, CI 0.21–0.87, P = 0.02). Of the patients, 26 (21%) underwent metastasectomy, with a median survival of 40 months compared with 13 months in patients not selected for surgical treatment. Of these 26, 23 (88%) experienced recurrence at a median of 5 months after the procedure. No survival difference was seen between responders and non-responders to systemic therapy (P = 0.55).ConclusionsIn stage-IV melanoma with pulmonary metastases, a solitary metastasis and absence of extra-pulmonary disease are predictive of survival. While these factors are often present in patients selected for pulmonary metastasectomy, this independently predicts survival. However, response to systemic therapy does not correlate with a survival difference.

Optimizing Cancer Care Delivery through Implementation Science.

The 2013 Institute of Medicine report investigating cancer care concluded that the cancer care delivery system is in crisis due to an increased demand for care, increasing complexity of treatment, decreasing work force, and rising costs. Engaging patients and incorporating evidence-based care into routine clinical practice are essential components of a high-quality cancer delivery system. However, a gap currently exists between the identification of beneficial research findings and the application in clinical practice. Implementation research strives to address this gap. In this review, we discuss key components of high-quality implementation research. We then apply these concepts to a current cancer care delivery challenge in women’s health, specifically the implementation of a surgery decision aid for women newly diagnosed with breast cancer.

Impact of neoadjuvant chemotherapy on wound complications after breast surgery.

BACKGROUND Use of neoadjuvant chemotherapy for breast cancer is increasing. The objective was to examine risk of postoperative wound complications in patients receiving neoadjuvant chemotherapy for breast cancer. METHODS Patients undergoing breast surgery from 2005 to 2010 were selected from the American College of Surgeons National Surgical Quality Improvement Program database. Patients were included if preoperative diagnosis suggested malignancy and an axillary procedure was performed. We performed a stepwise multivariable regression analysis of predictors of postoperative wound complications, overall and stratified by type of breast surgery. Our primary variable of interest was receipt of neoadjuvant chemotherapy. RESULTS Of 44,533 patients, 4.5% received neoadjuvant chemotherapy. Wound complications were infrequent with or without neoadjuvant chemotherapy (3.4% vs. 3.1%; P = .4). Smoking, functional dependence, obesity, diabetes, hypertension, and mastectomy were associated with wound complications. No association with neoadjuvant chemotherapy was seen (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.78-1.32); however, a trend was observed toward increased complications in neoadjuvant patients undergoing mastectomy with immediate reconstruction (OR, 1.58; 95% CI, 0.98-2.58). CONCLUSION Postoperative wound complications after breast surgery are infrequent and not associated with neoadjuvant chemotherapy. Given the trend toward increased complications in patients undergoing mastectomy with immediate reconstruction, however, neoadjuvant chemotherapy should be among the many factors considered when making multidisciplinary treatment decisions.

Treatment for patients with rectal cancer and a clinical complete response to neoadjuvant therapy: a decision analysis.

PURPOSE: A clinical complete response to neoadjuvant therapy occurs in a subset of patients with rectal cancer. Management of these patients is controversial and tension exists between the recurrence risk with observation, and the impact of surgery on quality-of-life. Therefore, the objective was to develop a decision-analytic model to evaluate the relative benefits of surgery vs. observation in rectal cancer patients who achieve clinical complete response after neoadjuvant chemoradiation. METHODS: Clinically relevant inputs and events, including the ability to identify complete responders, likelihood of relapse and of salvage surgery after relapse, and utilities for each health state, were simulated by use of a Markov state-transition model. Transition probabilities and health-state utilities were derived from the literature and expert consensus. One-way and two-way sensitivity analyses were performed to assess the robustness of model results to assumptions. The primary outcome was quality-adjusted life expectancy. RESULTS: In the base-case analysis, the quality-adjusted life expectancy with surgery exceeded observation (5.63 vs. 5.34 quality-adjusted life-years). Sensitivity analysis demonstrated that observation was preferred to surgery if the ability to correctly identify patients with true complete responses exceeded 58 percent, if quality-of-life after surgery was poor (utility <0.81), or if the relative reduction in recurrence risk with surgery was <43 percent when compared with observation. CONCLUSIONS: Our model outlines the issues associated with surgery vs. observation, and suggests that surgery is beneficial for the average patient with rectal cancer with a clinical complete response after neoadjuvant therapy. Current limitations in the clinical assessment of patient response to chemoradiation constitute an important factor influencing our results, and therefore warrant further investigation.

Management of the axilla.

Status of the axillary lymph nodes is one of the most important factors impacting overall prognosis and treatment for breast cancer. The sentinel lymph node (SLN) concept for breast cancer has been validated and SLN biopsy should be considered standard of care for axillary staging in patients with clinically node-negative axilla given the decreased morbidity when compared with axillary lymph node dissection. Ongoing controversy includes use of SLN in patients with ductal carcinoma in situ, prior axillary surgery, multicentric breast cancer, and large breast cancers. Determining the optimal timing of SLN in patients undergoing neoadjuvant chemotherapy and the prognostic and clinical significance of micrometastases remain areas of research.

Impact of axillary ultrasound and core needle biopsy on the utility of intraoperative frozen section analysis and treatment decision making in women with invasive breast cancer

BACKGROUND Our objective was to evaluate the impact of preoperative axillary ultrasound and core needle biopsy (CNB) on breast cancer treatment decision making. A secondary aim was to evaluate the impact on the utility of intraoperative sentinel lymph node (SLN) frozen section. METHODS A review of 84 patients with clinically negative axilla who underwent axillary ultrasound was performed. Sensitivity, specificity, and positive/negative predictive value for axillary ultrasound with CNB was calculated. RESULTS Thirty-one (37%) had suspicious nodes. Of 27 amenable to CNB, 12 (14%) were malignant, changing treatment plans. The sensitivity of ultrasound and CNB was 54% and specificity 100%; the positive and negative predictive values were 100% and 80%, respectively. In 41 patients with normal ultrasounds who underwent SLN frozen section, 10 (24%) were positive. CONCLUSIONS Preoperative axillary ultrasound impacts treatment decision making in 14%. With a sensitivity of 54%, it is a useful adjunct to, but not replacement for, SLN biopsy. Frozen section remains of utility even after a negative axillary ultrasound.

Safety and Feasibility of Minimally Invasive Inguinal Lymph Node Dissection in Patients With Melanoma (SAFE-MILND): Report of a Prospective Multi-institutional Trial

Background: Minimally invasive inguinal lymph node dissection (MILND) is a novel approach to inguinal lymphadenectomy. SAFE-MILND (NCT01500304) is a multicenter, phase I/II clinical trial evaluating the safety and feasibility of MILND for patients with melanoma in a group of surgeons newly adopting the procedure. Methods: Twelve melanoma surgeons from 10 institutions without any previous MILND experience, enrolled patients into a prospective study after completing specialized training including didactic lectures, participating in a hands-on cadaveric laboratory, and being provided an instructional DVD of the procedure. Complications and adverse postoperative events were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 4.0. Results: Eighty-seven patients underwent a MILND. Seventy-seven cases (88.5%) were completed via a minimally invasive approach. The median total inguinal lymph nodes pathologically examined (SLN + MILND) was 12.0 (interquartile range 8.0, 14.0). Overall, 71% of patients suffered an adverse event (AE); the majority of these were grades 1 and 2, with 26% of patients experiencing a grade 3 AE. No grade 4 or 5 AEs were observed. Conclusions: After a structured training program, high-volume melanoma surgeons adopted a novel surgical technique with a lymph node retrieval rate that met or exceeded current oncologic guidelines and published benchmarks, and a favorable morbidity profile.

Quality of Online Information to Support Patient Decision-Making in Breast Cancer Surgery

Breast cancer patients commonly use the internet as an information resource. Our objective was to evaluate the quality of online information available to support patients facing a decision for breast surgery.