Outcomes for Patients with Residual Stage II/III Breast Cancer Following Neoadjuvant Chemotherapy (AFT-01).

INTRODUCTION: Pathologic complete response (pCR) after neoadjuvant chemotherapy has a demonstrated survival advantage; however, outcomes for non-pCR by receptor status are less understood. We sought to evaluate survival and distant recurrence by receptor status for patients with residual stage II/III breast cancer. METHODS: A stage-stratified random sample of 11,366 patients with stage II-III breast cancer in 2006-2007 was selected from 1217 facilities in the National Cancer Database for a Commission on Cancer Special Study. We identified patients with residual pathologic stage II/III cancer who received standard of care therapy based on receptor status. Distant recurrence and 5-year survival were abstracted and Kaplan-Meier curves were generated by receptor status. Multivariable Cox regression was used to estimate hazard ratios for death and distant recurrence. RESULTS: A total of 734 patients had residual disease; 58%, 28%, and 14% were ER or PR+/Her2neu-, ER and PR-/Her2neu-, and Her2neu+ (any ER/PR), respectively. ER and PR-/Her2neu- cancers had the poorest 5-year overall (52% vs. 82% for Her2neu+ and ER or PR+/Her2neu-, p < 0.0001) and distant recurrence-free survival (57% vs. 72% Her2neu+ and 77% ER or PR+/Her2neu, p < 0.0001). Cox regression models demonstrated a higher likelihood of distant recurrence and death for patients with ER and PR-/Her2neu- disease (HR 2.25, 95% CI 1.56-3.24 and HR 3.19, 95% CI 2.20-4.64 respectively) compared with ER or PR+/Her2neu-. CONCLUSIONS: Patients with residual ER and PR-/Her2neu- cancer have a significant risk of distant recurrence and mortality compared with other breast cancer types, supporting the consideration for additional adjuvant therapy and novel clinical trials in this cohort. Trial registry number ClinicalTrials.gov identifier NCT02171078.

Multidisciplinary Intraoperative Assessment of Breast Specimens Reduces Number of Positive Margins.

BACKGROUND: Successful breast-conserving surgery requires achieving negative margins. At our institution, the whole surgical specimen is imaged and then serially sectioned with repeat imaging. A multidisciplinary discussion then determines need for excision of additional margins. The goal of this study was to determine the benefit of each component of this approach in reducing the number of positive margin. METHODS: This single-institution, prospective study included ten breast surgical oncologists who were surveyed to ascertain whether they would have taken additional margins based their review of whole specimen images (WSI) and review of serially sectioned images (SSI). These results were compared with the multidisciplinary decisions (MDD) and pathology results. Margin status was defined using consensus guidelines. RESULTS: One hundred surveys were completed. Margins on the original specimen were positive or close in 21%. After WSI, surgeons reported that they would have taken additional margins in 26 cases, reducing the number of positive/close margins from 21 to 13% (p < 0.001). After SSI, 52 would have taken additional margins; however, the number of positive/close margins remained 13%. MDD resulted in additional margins taken in 56 cases, reducing the number of positive/close margins to 7% (p < 0.001 compared with SSI). CONCLUSIONS: While surgeon review of specimen radiographs can decrease the number of positive or close margins from 21 to 13%, more rigorous multidisciplinary, intraoperative margin assessment reduces the number of close or positive margins to 7%.

Risk-reducing surgery in FAP: role for surgeons beyond the incision.

BACKGROUND: Although primary therapy in familial adenomatous polyposis (FAP) is surgical, little is known about patients' surgical decision-making experience. The objective was to explore the decision-making process surrounding risk-reducing surgery in FAP using qualitative methodology. METHODS: In-depth, semi-structured interviews with 14 FAP patients and 11 healthcare providers with experience caring for FAP patients were conducted. Using grounded theory, line-by-line content analysis identified categories from which themes describing patients' experiences emerged; analysis continued until data saturation. RESULTS: Median age at surgery was 23 (7-37) years; at interview 41 (19-74) years. Two patients underwent surgery secondary to cancer, the remainder for risk-reduction. Content experts included colorectal surgeons (3), geneticists (2), gastroenterologists (3), nurses (3).Three themes emerged: Information: Family was the primary information source, and patients' level of information varied. The importance of up-front information was emphasized. Influences on decision-making: Influential factors included family experiences, youth, emotional state, support, and decision-making role. Although patients often sought opinions, most (12/14) wanted an active/shared role in decision-making. Life after surgery: Patients described surgery as the "easy part," emphasizing the need for long-term relationships with care providers. CONCLUSIONS: Decisions surrounding risk-reducing surgery in FAP are unique. A decision support tool may facilitate decision-making, better preparing patients for life after surgery.

Bacterial meningitis in childhood at the Children's Hospital of Pittsburgh: 1988-1998.

Bacterial meningitis is an important acute infectious disease of childhood that remains a source of substantial morbidity and mortality. The impact of the Haemophilus influenzae type b (HIB) conjugate vaccines on the epidemiology of the other bacterial causes of meningitis in childhood has received little attention. The objective of this study is to report the experience at a tertiary-care children's hospital with the occurrence of bacterial meningitis before and after the licensure of the HIB conjugate vaccine. With use of International Classification of Diseases diagnostic codes for bacterial meningitis, a list of all children admitted to Children's Hospital of Pittsburgh with a primary or secondary diagnosis of meningitis due to H. influenzae, Streptococcus pneumoniae, and Neisseria meningitidis from January 1, 1988, to December 31, 1998, was constructed. Medical records were examined for basic patient demographic information including age, gender, race, bacterial etiology of meningitis, receipt of vaccine for HIB, underlying conditions, and fatalities. Two hundred twenty-one cases of bacterial meningitis caused by H. influenzae, N. meningitidis, and S. pneumoniae were identified. The age of infected children ranged from 1 month to 18 years, with a mean and median age of 38.1 months and 13 months, respectively. Fifty-two percent of the children were female, 83% were Caucasian and 16% were African-American. Before the routine use of HIB conjugate vaccine, HIB was the bacterial species responsible for the greatest proportion of cases (average of 58%/year). The absolute number of cases of bacterial meningitis attributable to HIB declined after 1991 to an average of 2.5 cases/year. The number of cases of meningitis caused by S. pneumoniae and N. meningitidis have remained relatively stable between 1988 and 1998. The case fatality rates for children with meningitis caused by H. influenzae, S. pneumoniae, and N. meningitidis were 0.0%, 9.2%, and 7.5%, respectively. Most cases of meningitis due to HIB occurred in children who had not been immunized. Three children who received the polysaccharide vaccine developed meningitis due to HIB; there were no failures of the conjugate vaccine.

Colon Cancer Staging in Vulnerable Older Adults: Adherence to National Guidelines and Impact on Survival.

BACKGROUND: There is concern that elders are not adequately evaluated prior to colon cancer surgery. We sought to determine adherence with ACOVE-3 (Assessing Care of Vulnerable Elders) quality indicators for pre-operative staging prior to colectomy for colon cancer utilizing the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database (1992-2005). METHODS: We determined the proportion of patients aged 75 and older who had preoperative staging prior to colectomy for colon adenocarcinoma. Preoperative staging was defined as abdominopelvic computed tomography or magnetic resonance imaging scan (SCAN) and colonoscopy or flexible sigmoidoscopy (SCOPE). Multivariate logistic regression identified predictors of adherence. Odds ratios were adjusted for comorbidity, socioeconomic status, and disease severity. The association of adherence to ACOVE-3 and survival was quantified. RESULTS: Of the 37,862 patients, the majority were 75-84 years, 28% of the patients were ≥85 years. Regarding preoperative staging in the 6-month interval prior to surgical resection, 8% had neither SCAN nor SCOPE, 6% had only SCAN, 43% had only SCOPE, and 43% had both SCAN and SCOPE. Compared to patients who were not staged, those evaluated with either SCOPE alone or SCAN plus SCOPE had lower odds of 3-year mortality. Patients who were staged with SCAN alone had an increased odds of death compared to those who had neither SCAN or SCOPE. CONCLUSIONS: These data demonstrate that the majority of vulnerable elders with colon cancer did not receive appropriate preoperative staging prior to resection. The findings also confirm that adherence to ACOVE-3 guidelines is associated with improved long-term survival.