Shi-Yi Wang

Network Meta-analysis of Margin Threshold for Women With Ductal Carcinoma In Situ

BACKGROUND Negative margins are associated with reduced risk of ipsilateral breast tumor recurrence (IBTR) for women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS). However, there is no consensus about the best minimum margin width. METHODS We searched the PubMed database for studies of DCIS published in English between January 1970 and July 2010 and examined the relationship between IBTR and margin status after BCS for DCIS. Women with DCIS were stratified into two groups, BCS with or without radiotherapy. We used frequentist and Bayesian approaches to estimate the odds ratios (OR) of IBTR for groups with negative margins and positive margins. We further examined specific margin thresholds using mixed treatment comparisons and meta-regression techniques. All statistical tests were two-sided. RESULTS We identified 21 studies published in 24 articles. A total of 1066 IBTR events occurred in 7564 patients, including BCS alone (565 IBTR events in 3098 patients) and BCS with radiotherapy (501 IBTR events in 4466 patients). Compared with positive margins, negative margins were associated with reduced risk of IBTR in patients with radiotherapy (OR = 0.46, 95% credible interval [CrI] = 0.35 to 0.59), and in patients without radiotherapy (OR = 0.34, 95% CrI = 0.24 to 0.47). Compared with patients with positive margins, the risk of IBTR for patients with negative margins was smaller (negative margin >0 mm, OR = 0.45, 95% CrI = 0.38 to 0.53; >2 mm, OR = 0.38, 95% CrI = 0.28 to 0.51; >5 mm, OR = 0.55, 95% CrI = 0.15 to 1.30; and >10 mm, OR = 0.17, 95% CrI = 0.12 to 0.24). Compared with a negative margin greater than 2 mm, a negative margin of at least 10 mm was associated with a lower risk of IBTR (OR = 0.46, 95% CrI = 0.29 to 0.69). We found a probability of .96 that a negative margin threshold greater than 10 mm is the best option compared with other margin thresholds. CONCLUSIONS Negative surgical margins should be obtained for DCIS patients after BCS regardless of radiotherapy. Within cosmetic constraint, surgeons should attempt to achieve negative margins as wide as possible in their first attempt. More studies are needed to understand whether margin thresholds greater than 10 mm are warranted.

Tumor characteristics as predictors of local recurrence after treatment of ductal carcinoma in situ: a meta-analysis

While ductal carcinoma in situ (DCIS) is seldom life threatening, the management of DCIS remains a dilemma for patients and their physicians. Aggressive treatment reduces the risk of ipsilateral breast tumor recurrence (IBTR), but has never been proven to improve survival. There is interest in identifying the prognostic factors for determining low-risk DCIS patients, but a comprehensive review of high-quality evidence on tumor characteristics in predicting local recurrence has never been carried out. We examined the following tumor characteristics: biomarkers, comedonecrosis, focality, surgical margin, method of detection, tumor grade, and tumor size. For this systematic review we restricted the analyses to the results of subgroup analyses from randomized controlled trials (RCTs) and multivariate analyses from RCTs and observational studies. We identified 44 eligible articles. The pooled random-effects risk estimates for IBTR are comedonecrosis 1.71(95% CI, 1.36–2.16), focality 1.95(95% CI, 1.59–2.40), margin 2.25(95% CI, 1.77–2.86), method of detection 1.35(95% CI, 1.12–1.62), tumor grade 1.81(95% CI, 1.53–2.13), and tumor size 1.63(95% CI, 1.30–2.06). Limited evidence indicated that women whose DCIS is ER-negative, PR-negative, or HER2/neu receptor positive have an IBTR higher than those whose DCIS is ER-positive, PR-positive, and HER2/neu receptor negative. A variety of tumor characteristics are significant predictors for IBTR. These results are important for both clinicians and patients to interpret the risk of local recurrence and to decide on a course of treatment.

Physical Therapy Interventions for Knee Pain Secondary to Osteoarthritis: A Systematic Review

BACKGROUND Osteoarthritis is a leading cause of disability. Nonsurgical treatment is a key first step. PURPOSE Systematic literature review of physical therapy (PT) interventions for community-dwelling adults with knee osteoarthritis. DATA SOURCES MEDLINE, the Cochrane Library, the Physiotherapy Evidence Database, Scirus, Allied and Complementary Medicine, and the Health and Psychosocial Instruments bibliography database. STUDY SELECTION 193 randomized, controlled trials (RCTs) published in English from 1970 to 29 February 2012. DATA EXTRACTION Means of outcomes, PT interventions, and risk of bias were extracted to pool standardized mean differences. Disagreements between reviewers abstracting and checking data were resolved through discussion. DATA SYNTHESIS Meta-analyses of 84 RCTs provided evidence for 13 PT interventions on pain (58 RCTs), physical function (36 RCTs), and disability (29 RCTs). Meta-analyses provided low-strength evidence that aerobic (11 RCTs) and aquatic (3 RCTs) exercise improved disability and that aerobic exercise (19 RCTs), strengthening exercise (17 RCTs), and ultrasonography (6 RCTs) reduced pain and improved function. Several individual RCTs demonstrated clinically important improvements in pain and disability with aerobic exercise. Other PT interventions demonstrated no sustained benefit. Individual RCTs showed similar benefits with aerobic, aquatic, and strengthening exercise. Adverse events were uncommon and did not deter participants from continuing treatment. LIMITATION Variability in PT interventions and outcomes measures hampered synthesis of evidence. CONCLUSION Low-strength evidence suggested that only a few PT interventions were effective. Future studies should compare combined PT interventions (which is how PT is generally administered for pain associated with knee osteoarthritis). PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Not just specific diseases: Systematic review of the association of geriatric syndromes with hospitalization or nursing home admission

To examine the association between geriatric syndromes with hospitalization or nursing home admission, we reviewed studies that examined hospitalization and nursing home admission in community-dwelling older adults with multiple morbidities, cognitive impairment, frailty, disability, sarcopenia, malnutrition, impaired homeostasis, and chronic inflammation. Studies published in English language were identified through MEDLINE (1990 through April 2010), Cochrane databases, the Centers for Disease Control and Prevention website and manual searches of reference lists from relevant publications. The study had to include general (non-disease specific) populations of adults aged 65 years or older. Using a standardized protocol, two investigators independently abstracted information on participant characteristics and adjusted measures of the association. Studies that controlled for the presence of specific diseases were further identified and analyzed. When the syndrome examined was similar from different studies, we computed the pooled risk estimates using a random-effects model. We assessed the strength of evidence following the recommended guidelines. We identified 47 eligible articles from 6 countries. Multiple morbidity, frailty, and disabilities were associated with hospitalization and nursing home admission (moderate evidence). Cognitive impairment was associated with hospitalization (low evidence) and nursing home admission (moderate evidence). Among these studies, 20 articles controlled for specific diseases. Limited evidence suggested that these geriatric syndromes are associated with hospitalization and institutionalization after controlling for the presence of specific diseases. We conclude that geriatric syndromes are associated with risk of hospitalization or nursing home admission. Efforts to prevent hospitalization or nursing home admission should target strategies to prevent and manage these syndromes.

Association between patient and tumor characteristics with clinical outcomes in women with ductal carcinoma in situ.

We synthesized the evidence of the association between patient and tumor characteristics with clinical outcomes in women with ductal carcinoma in situ of the breast. We identified five randomized controlled clinical trials and 64 observational studies that were published in English from January 1970 to January 2009. Younger women with clinically presented ductal carcinoma in situ had higher risk of ipsilateral recurrent cancer. African Americans had higher mortality and greater rates of advanced recurrent cancer. Women with larger tumor size, comedo necrosis, worse pathological grading, positive surgical margins, and at a higher risk category, using a composite prognostic index, had worse outcomes. Inconsistent evidence suggested that positive HER2 receptor and negative estrogen receptor status were associated with worse outcomes. Synthesis of evidence was hampered by low statistical power to detect significant differences in predictor categories and inconsistent adjustment practices across the studies. Future research should address composite prediction indices among race groups for all outcomes.

Ductal Carcinoma In Situ: Risk Factors and Impact of Screening

BACKGROUND The National Institutes of Health Office of Medical Applications of Research commissioned a structured literature review on the incidence of ductal carcinoma in situ (DCIS) as a background paper for the State of the Science Conference on Diagnosis and Management of DCIS. METHODS Published studies were abstracted from MEDLINE and other sources. We include articles published through January 31, 2009; 92 publications were abstracted. RESULTS DCIS incidence rose from 1.87 per 100,000 in 1973-1975 to 32.5 per 100,000 in 2005. Increases in incidence were greatest in tumors without comedo necrosis. Incidence increased in all ages but more in women older than 50 years. Increased use of mammography explains some but not all of the increased incidence. Risk factors for incident DCIS include older age and positive family history. Whereas tamoxifen prevents both invasive breast cancer and DCIS, raloxifene is associated with decreased invasive breast cancer but not decreased DCIS. CONCLUSIONS Scientific questions deserving further investigation include the relationship between mammography use and DCIS incidence and the role of chemoprevention for reducing the incidence of DCIS and invasive breast cancer.

Transitions Between Healthcare Settings of Hospice Enrollees at the End of Life

To characterize the number and types of care transitions in the last 6 months of life of individuals who used hospice and to examine factors associated with having multiple transitions in care.

Are Small Breast Cancers Good because They Are Small or Small because They Are Good

Data from the Surveillance, Epidemiology, and End Results registry show that smaller breast cancers, like many of those detected by mammography, are disproportionately biologically favorable in natural history.

Racial Differences in the Use and Outcome of Neoadjuvant Chemotherapy for Breast Cancer: Results From the National Cancer Data Base

PURPOSE To explore racial differences in the use and outcome of neoadjuvant chemotherapy for breast cancer. METHODS The National Cancer Data Base was queried to identify women with stage 1 to 3 breast cancer diagnosed in 2010 and 2011. Chemotherapy use and rate of pathologic complete response (pCR) was determined for various racial/ethnic groups. RESULTS Of 278,815 patients with known race and ethnicity, 127,417 (46%) received chemotherapy, and of 121,446 where the timing of chemotherapy was known, 27,300 (23%) received neoadjuvant chemotherapy. Chemotherapy, and neoadjuvant chemotherapy in particular, was given more frequently to black, Hispanic, and Asian women than to white women (P < 0.001). This difference was largely explained by more advanced stage, higher grade tumors, and a greater proportion of triple-negative and human epidermal growth factor receptor 2 (HER2)-positive tumors in these women. Of 17,970 patients with known outcome, 5,944 (33%) had a pCR. No differences in response rate for estrogen receptor (ER)/progesterone receptor (PR)-positive tumors were found, but compared with white women, black but not Hispanic or Asian women had a lower rate of pCR for ER/PR-negative, HER2-positive (43% v 54%, P = 0.001) and triple-negative tumors (37% v 43%, P < 0.001). This difference persisted when adjusted for age, clinical T stage, clinical N stage, histology, grade, comorbidity index, facility type, geographic region, insurance status, and census-derived median income and education for the patients zip code (odds ratio, 0.84; 95% CI, 0.77 to 0.93). CONCLUSION Neoadjuvant chemotherapy is given more frequently to black, Hispanic, and Asian women than to white women. Black women have a lower likelihood of pCR for triple-negative and HER2-positive breast cancer. Whether this is due to biologic differences in chemosensitivity or to treatment or socioeconomic differences that could not be adjusted for is unknown.

Examining the Cost-Effectiveness of Radiation Therapy Among Older Women With Favorable-Risk Breast Cancer

BACKGROUND Little is known about the cost-effectiveness of external beam radiation therapy (EBRT) or newer radiation therapy (RT) modalities such as intensity modulated radiation (IMRT) or brachytherapy among older women with favorable-risk breast cancer. METHODS Using a Markov model, we estimated the cost-effectiveness of no RT, EBRT, and IMRT over 10 years. We estimated the incremental cost-effectiveness ratio (ICER) of IMRT compared with EBRT under different scenarios to determine the necessary improvement in effectiveness for newer modalities to be cost-effective. We estimated model inputs using women in the Surveillance, Epidemiology, and End Results-Medicare database fulfilling the Cancer and Leukemia Group B C9343 trial criteria. RESULTS The incremental cost of EBRT compared with no RT was