The impact of statins on melanoma survival: a systematic review and meta-analysis.

Statin use may decrease recurrence and improve survival in patients with melanoma. In this systematic review and meta-analysis, we examine the current body of literature concerning the use of statins as an adjunctive therapy in melanoma, Medline, EMBASE, CENTRAL, and PubMed were systematically searched from inception through to April 2023. Studies were included if they compared patients with melanoma receiving and not receiving statin therapy concurrently with their oncologic treatment in terms of long-term oncologic outcomes. The primary outcome was 5-year overall survival (OS). Meta-analyses was performed with DerSimonian and Laird random effects. Risk of bias was assessed with the ROBINS-I and GRADE was used to assess certainty of evidence. From 952 citations, eight non-randomized studies were identified. Included studies were conducted between 2007 and 2022. Random effects meta-analysis of adjusted hazard ratios from three studies suggested an improvement in 5-year OS with statin use with wide 95% confidence intervals (CIs) crossing the line of no effect (hazard ratio 0.87, 95% CI: 0.73-1.04, P = 0.12, I2 = 95%, very-low certainty). Outcome reporting was heterogeneous across all other oncologic outcomes such that pooling of data was not possible. Risk of bias was serious for seven studies and moderate for one study. This systematic review of studies evaluating the impact of statin use on survival in patients with melanoma found a 13% reduction in risk of death at 5 years from diagnosis - a point estimate suggesting benefit. However, the wide 95% CIs and resultant type II error risk create significant uncertainty.

Concurrent Use of Statins in Patients Undergoing Curative Intent Treatment for Triple Negative Breast Cancer: A Systematic Review and Meta-Analysis.

Pre-clinical studies in triple negative breast cancer (TNBC) suggest that statins may inhibit cell proliferation, promote cell-cycle arrest, induce apoptosis, change the tumor microenvironment, and improve effectiveness of other therapies. Observational studies have demonstrated variable effects from statin therapy on oncologic outcomes in these patients. As such, we aimed to pool previous data via a systematic review and meta-analysis to elucidate the impact of concurrent statin use on oncologic outcomes for patients with TNBC. Medline, EMBASE, CENTRAL, and PubMed were systematically searched from inception through to June 2022. Studies were included if they compared patients with TNBC receiving and not receiving statin therapy concurrently with oncologic treatment for curative intent in terms of recurrence and survival in a non-metastatic setting. The primary outcomes were 5-year disease-free survival (DFS) and 5-year overall survival (OS). A pairwise meta-analyses was performed using inverse variance random effects. Risk of bias was assessed with the ROBINS-I and the GRADE approach was conducted to assess quality of evidence. From 4014 citations, 5 studies with 625 patients on statin therapy and 2707 patients not on statin therapy were included. There was a significant increase in 5-year DFS for patients on statin therapy compared to patients not on statin therapy (OR 1.44, 95% CI 1.04-1.98, P = .03). No significant difference was noted in 5-year OS between the 2 groups (OR 1.12, 95% CI 0.86-1.47, P = .40). Included studies were at moderate-to-high risk of bias. The GRADE quality of evidence was very low. This review presents very low-quality evidence that concurrent use of statins with oncologic treatment may potentially improve long-term DFS for patients with TNBC undergoing curative intent therapy. Future research by way of large, prospective study is required to further clarify the clinical utility of statins on patients undergoing treatment for TNBC.

Patient reported symptom burden amongst immigrant and Canadian long-term resident women undergoing breast cancer surgery.

PURPOSE: Immigrants are susceptible to marginalization due to social isolation, economic disadvantage and systemic bias. Our goal was to compare symptom burden between immigrant and long-term resident women undergoing breast cancer surgery in Ontario, Canada. METHODS: A population-level retrospective cohort-study using administrative databases was conducted. Women who underwent surgery for newly diagnosed breast cancer and were treated at regional cancer centers between 2010 and 2016 were included. The primary outcome was a moderate or severe (≥ 4) symptom score on the Edmonton Symptom Assessment System Scale (ESAS). RESULTS: There were 12,250 (87.2%) long-term Canadian residents and 1,806(12.8%) immigrants. Immigrants were younger (mean age 53 vs. 61 years); had a higher proportion residing in a lowest income quintile neighbourhood (22.2% vs 15.4%); were less often on a primary-care physician roster (83.7% vs. 90.4%); and were less often diagnosed with Stage I/II disease (80.9% vs. 84.6%) (all p < 0.01). The proportion of women with scores ≥ 4 was significantly higher amongst immigrant women for 7/9 symptom categories; with the largest differences for depression (24.9% vs. 20.2%, p < 0.01) and pain (28.0% vs. 22.4%, p < 0.01). On multivariable regression analysis, immigration status was associated with scores ≥ 4 for pain (OR 1.13, 95% CI 1.02-1.23). There was an association between moderate/severe pain and region of origin, but not length of stay in Canada or immigration class. CONCLUSIONS: This is the first study comparing symptom burden amongst immigrant and non-immigrant women with breast cancer at a population-level. Immigrant women with breast cancer undergoing surgery were found to have a higher burden of pain.

Safety and Accuracy of Sentinel Lymph Node Biopsy Alone in Clinically Node-Positive Patients Undergoing Upfront Surgery for Invasive Breast Cancer: A Systematic Review.

Landmark trials (Z0011 and AMAROS) have demonstrated that axillary lymph node dissection (ALND) can be safely omitted in patients with breast cancer and 1-2 positive sentinel nodes. Extrapolating from these and other cardinal studies such as NSABP B-04, guidelines state that patients with 1-2 needle biopsy-proven positive lymph nodes undergoing upfront surgery can have sentinel lymph node biopsy (SLNB) alone. The purpose of this study is to systematically review the literature to identify studies examining the direct application of SLNB in such patients. EMBASE and Ovid MEDLINE were searched from inception to 3 May 2022. Studies including patients with nodal involvement confirmed on pre-operative biopsy and undergoing SLNB were identified. Studies with neoadjuvant chemotherapy were excluded. Search resulted in 2518 records, of which 68 full-text studies were reviewed, ultimately yielding only 2 studies meeting inclusion criteria. Both studies used targeted axillary surgery (TAS) with pre-operative localization of the biopsy-proven positive node in addition to standard SLNB techniques. In a non-randomized single-center prospective study, Lee et al. report no regional recurrences in patients undergoing TAS or ALND, and no difference in distant recurrence or mortality at 5 years. In the prospective multicenter TAXIS trial by Webber et al., the median number of positive nodes retrieved with TAS in patients undergoing upfront surgery was 2 (1, 4 IQR). Within the subset of patients who underwent subsequent ALND, 61 (70.9%) had additional positive nodes, with 26 (30.2%) patients having ≥4 additional positive nodes. Our review demonstrates that there is limited direct evidence for SLNB alone in clinically node-positive patients undergoing upfront surgery. Available data suggest a high proportion of patients with residual disease in this setting. While the totality of the data, mostly indirect evidence, suggests SLNB alone may be safe, we call on clinicians and researchers to prospectively collect data on this patient population to better inform decision-making.

Multicenter Adoption and Outcomes of Nodal Observation for Patients with Melanoma and Sentinel Lymph Node Metastases.

BACKGROUND: Following publication of the MSLT-II trial showing no survival benefit of completion lymphadenectomy (CLND) in patients with melanoma sentinel lymph node (SLN) metastases, it is expected that practice patterns have changed. The purpose of this study is to understand real-world practices and outcomes after publication of this landmark trial. PATIENTS AND METHODS: Patients with truncal/extremity melanoma SLN metastases diagnosed between 2013 and 2019 at four academic cancer centers were included in this retrospective cohort study. Descriptive statistics, Cox proportional hazards model, and multivariable regression were used to characterize the cohort and identify predictors of CLND, harboring non-SLN (NSLN) metastases, and survival. RESULTS: Results of 1176 patients undergoing SLN biopsy, 183 had SLN metastases. The number of patients who underwent CLND before versus after trial publication was 75.7.% versus 20.5% (HR 0.16, 95% CI 0.09-0.28). Of those undergoing nodal observation (NO), 92% had a first nodal-basin ultrasound, while 63% of patients had a fourth. In exploratory multivariable analyses, age ≥ 50 years was associated with lower rate of CLND (HR 0.58, 95% CI 0.36-0.92) and larger SLN deposit (> 1.0 mm) with increased rate of CLND (HR 1.87, 95% CI 1.17-3.00) in the complete cohort. Extracapsular extension was associated with increased risk of NSLN metastases (HR 12.43, 95% CI 2.48-62.31). Adjusted survival analysis demonstrated no difference in recurrence or mortality between patients treated with CLND versus NO at median 2.2-year follow-up. CONCLUSION: Nodal observation was rapidly adopted into practice in patients with melanoma SLN metastases at four centers in Canada. Younger age and higher nodal burden were associated with increased use of CLND after trial publication. Ultrasound (US) surveillance decreased with time from SLNB. In our study, CLND was not associated with a decreased risk of recurrence or mortality.

Surgical and Oncologic Outcomes of Nipple-Sparing Mastectomy for a Cohort of Breast Cancer Patients, Including Cases with High-Risk Features.

BACKGROUND: Nipple-sparing mastectomy (NSM) remains controversial in patients with high-risk breast cancer. The objective of this study was to assess surgical and oncologic outcomes of NSM and to evaluate associations of outcomes with high-risk features. METHODS: A retrospective review was conducted of all NSM cases performed for breast cancer at 2 academic cancer centers between January 2013 and August 2018. RESULTS: Of the 175 patients who underwent NSM, 13 (7.4%) had locally advanced breast cancer (LABC), 52 (29.2%) had previous neoadjuvant chemotherapy, 21 (12.0%) had previous radiation therapy, 40 (22.8%) received postmastectomy radiation, 27 (15.4%) had de-epithelialized skin reduction, and 13 (7.4%) had free nipple grafting. The median duration of follow-up was 24 months. Nipple necrosis (4 cases; 2.2%) was associated with previous radiation (9.5%; P = .018), skin reduction (11.1%; P = .001), and nipple grafting (15.4%; P = .001). The nipple-areolar complex margin (NAC) was involved with invasive disease in 1 case. Local recurrence occurred in 8 cases (4.6%), with 1 in-NAC recurrence. Overall survival was 98.3%, and disease-free survival (DFS) was 88.6%. LABC was associated with worse DFS (hazard ratio, 4.28; P = .011), with all 4 recurrences being distant. CONCLUSIONS: Previous radiation, skin reduction, and nipple grafting are associated with an increased risk of NAC necrosis. None of these should be considered absolute contraindications, but patients should be counseled appropriately. Although LABC is associated with worse DFS, relapses are systemic. Longer follow-up is needed to establish oncologic safety in unselected breast cancer patients.

Axillary Lymph Node Ultrasound Following Neoadjuvant Chemotherapy in Biopsy-Proven Node-Positive Breast Cancer: Results from the SN FNAC Study.

BACKGROUND: The sentinel node biopsy following neoadjuvant chemotherapy (SN FNAC) study has shown that in node-positive (N+) breast cancer, sentinel node biopsy (SNB) can be performed following neoadjuvant chemotherapy (NAC), with a low false negative rate (FNR = 8.4%). A secondary endpoint of the SN FNAC study was to determine whether axillary ultrasound (AxUS) could predict axillary pathological complete response (ypN0) and increase the accuracy of SNB. METHODS: The SN FNAC trial is a study of patients with biopsy-proven N+ breast cancer who underwent SNB followed by completion node dissection. All patients had AxUS following NAC and the axillary nodes were classified as either positive (AxUS+) or negative (AxUS-). AxUS was compared with the final axillary pathology results. RESULTS: There was no statistical difference in the baseline characteristics of patients with AxUS+ versus those with AxUS-. Overall, 82.5% (47/57) of AxUS+ patients had residual positive lymph nodes (ypN+) at surgery and 53.8% (42/78) of AxUS- patients had ypN+. Post NAC AxUS sensitivity was 52.8%, specificity 78.3%, and negative predictive value 46.2%. AxUS FNR was 47.2%, versus 8.4% for SNB. If post-NAC AxUS- was used to select patients for SNB, FNR would decrease from 8.4 to 2.7%. However, using post-NAC AxUS in addition to SNB as an indication for ALND would have led to unnecessary ALND in 7.8% of all patients. CONCLUSION: AxUS is not appropriate as a standalone staging procedure, and SNB itself is sufficient to assess the axilla post NAC in patients who present with N+ breast cancer.

Adoption and outcomes of radioguided seed localization for non-palpable invasive and in-situ breast cancer at three academic tertiary care centers.

INTRODUCTION: Radioguided seed localization (RSL) is an alternative technique to wire-guided localization (WL) for localizing non-palpable breast lesions for breast conserving surgery. The purpose of this study was to assess adoption and outcomes of RSL at 3 academic hospitals in our city. METHODS: Data for consecutive invasive and in-situ breast cancer cases localized with RSL or WL at 3 hospitals between January 2012 and February 2016 were abstracted. Data analysis was conducted using the Student's t-test, ANOVA with Tukey's HSD test for post-hoc multiple comparisons, and chi-squared test. RESULTS: There were 803 consecutive cases. Hospital 1 exclusively used RSL (247 cases), whereas H2 adopted RSL (109 cases), but continued to use WL (347 cases). Hospital 3 exclusively used WL (100 cases). There was no difference between RSL and WL groups in positive margin rate (p = 0.337), re-operation (p = 0.413), or mean specimen volume (p = 0.190). DISCUSSION: There has been variable adoption of RSL in our city. Despite this, relevant surgical outcomes have been similar across groups. The causes of variable adoption of this novel technique merit further investigation.

A cosmesis outcome substudy in a prospective, randomized trial comparing radioguided seed localization with standard wire localization for nonpalpable, invasive, and in situ breast carcinomas.

BACKGROUND: The primary study objective was to compare the cosmetic result of radioguided seed localization (RSL) with wire localization (WL). METHODS: A subgroup of patients enrolled in a multicentered, randomized trial comparing WL with RSL participated. Frontal photographs were taken 1 and 3 years postsurgery. The European Organization for Research and Treatment of Cancer Cosmetic Rating System was used to evaluate cosmesis outcomes by the patient and a panel of 5 raters. RESULTS: The study enrolled 73 patients (WL, n = 38; RSL, n = 35). Most patients rated their overall cosmesis as "excellent" or "good" (76% WL, 80% RSL). Patient and panel ratings on all cosmetic outcomes were similar between groups. Multivariable regression for overall cosmesis found larger specimen volume and reoperation to be predictors of worse ratings. CONCLUSIONS: All cosmetic outcomes assessed were similar after WL and RSL. The comparable outcomes may reflect similar reoperation rates and volumes of excision between groups.

Survey of American and Canadian general surgeons' perceptions of margin status and practice patterns for breast conserving surgery.

Although breast conservation surgery (BCS) is commonly performed, several aspects of the procedure remain controversial. We undertook a cross-sectional survey to compare Canadian (CDN) and American (AM) general surgeons' reported BCS practice patterns to better understand the cross-border differences in early-stage breast cancer surgery care. A modified Dillman Method survey was mailed to 1,447 AM and 1,443 CDN surgeons. Factors evaluated included preoperative assessment, margin definition, surgical techniques, and re-excision practices. The response rate was 26% and 51% for AM and CDN surgeons, respectively. There was variation in use of preoperative core biopsies. American surgeons required wider margins for invasive cancer and ductal carcinoma in situ, and more often recommend re-excision for invasive cancer with 1 and 2 mm margins (p < 0.05). There was also variability in surgical techniques used for intraoperative margin assessment. Wide variation in BCS practice was observed, with some of this variability related to surgeon country.

Effect of liposomal lidocaine and sucrose alone and in combination for venipuncture pain in newborns.

OBJECTIVE: To determine the relative effectiveness of liposomal lidocaine, sucrose, and their combination for reducing pain in term newborns. METHODS: Ours was a double-blind, randomized, controlled, double-dummy trial of 330 healthy term newborns. Before venipuncture for the newborn screening test, neonates received (1) 1 g of liposomal lidocaine cream topically, (2) 2 mL of 24% sucrose solution orally, or (3) sucrose and liposomal lidocaine. The facial grimacing score (0-100) was used to assess pain. Adverse events and lidocaine levels were used to assess safety. RESULTS: Infant characteristics did not differ among groups. Facial grimacing scores were lower in the sucrose group compared with those in the liposomal lidocaine group (mean difference: -27 [95% confidence interval (CI): -36 to -19; P < .001) and for the sucrose plus liposomal lidocaine group compared with those in the liposomal lidocaine group (mean difference: -23 [95% CI: -31 to -14]; P < .001). The sucrose and sucrose plus liposomal lidocaine groups did not differ (mean difference: -5 [95% CI: -13 to 4]; P = .3). Local skin reactions were not observed, and the incidence of spitting up did not differ between sucrose-exposed and non-sucrose-exposed infants (1.4% vs 2.7%, respectively; P = .22). The mean (SD) plasma lidocaine level was 44.6 (55.3) ng/mL. CONCLUSIONS: Sucrose was more effective than liposomal lidocaine for reducing pain during venipuncture in newborns. The addition of liposomal lidocaine to sucrose did not confer any additional benefit to sucrose alone. There was no evidence of harm from liposomal lidocaine or sucrose.

Mothers' beliefs about analgesia during childhood immunization.

BACKGROUND: Immunization injections are the most common painful medical procedures experienced during childhood, yet there is a discrepancy between recommendations for the effective use of topical anesthetics to reduce vaccine injection pain and actual practice. OBJECTIVE: To improve our understanding of mothers' experiences and practices regarding their children's routine immunizations. METHOD: Adopting an interpretive, naturalistic paradigm, semi-structured interviews were conducted with 15 mothers to examine their perceptions and experiences of their children's immunization pain and pain management. RESULTS: The findings demonstrated three main themes: attitudes toward immunization pain, immunization pain management and physicians as sources of information. Participants described feeling distressed while their children were being immunized, but most managed these difficulties by focusing on the benefits of immunization and by minimizing or justifying the pain. All of the participants used non-pharmacological techniques to manage immunization injection pain. Few mothers were aware of the availability of topical anesthetics. When participants did use pharmacological analgesic approaches, oral analgesics were most likely to be used for prophylaxis and treatment of fever, and participants were unaware of evidence-based approaches to managing pain. Participants viewed their physicians as trusted sources of information, and the majority said that they would likely use a topical anesthetic in the future if recommended or approved by their physician. CONCLUSION: The present findings provide direction for future knowledge translation activities to enhance the knowledge of mothers and clinicians regarding pain during immunization injections and its effective management.