Spare the Nipple: A Systematic Review of Tumor Nipple-Distance and Oncologic Outcomes in Nipple-Sparing Mastectomy.

BACKGROUND: Preserving the nipple-areolar complex (NAC) in breast cancer surgery improves patient satisfaction and quality of life. The oncologic safety of NSM in tumors < 2 cm from the nipple remains in question. We conducted a systematic review to determine whether TND < 2 cm was associated with increased risk of LRR in patients undergoing NSM. METHODS: We included studies of invasive or in situ breast cancer < 2 cm from NAC undergoing NSM which reported LRR rates. LRR rates were stratified by TND and culminated across studies. Cohort study quality was assessed using Newcastle-Ottawa Criteria. Meta-analysis was not possible due to heterogeneity in reporting survival outcomes. RESULTS: We identified seven retrospective cohort studies with 2295 patients and 18 case series with 3507 patients. Direct tumor involvement of NAC was considered an absolute contraindication to NSM in all studies. In cohort studies, median follow-up was 31-112 (range 14-204) months. Cohorts with TND < 2 cm did not have a significantly higher rate of LRR. Amongst case series, 275 patients had TND < 2 cm. Combined LRR in case series was 2.6%, with median follow-up 10.4-71 (range 0-158) months. CONCLUSIONS: Our systematic review did not identify TND < 2 cm as a significant risk factor for LRR. NSM appears oncologically safe in select patients with TND < 2 cm. Given the improved quality of life associated with NSM compared to skin-sparing mastectomy, we suggest NSM as the procedure of choice in appropriately selected patients.

Skeletal muscle is prognostic in resected stage III malignant melanoma.

BACKGROUND: Sarcopenia (low skeletal muscle index, SMI) and myosteatosis (low skeletal muscle radiodensity, SMD) have been associated with worse survival in cancer. This study evaluated associations of body composition with survival in patients with resected stage III melanoma. METHODS: A retrospective review was performed of resected stage III melanoma patients in Alberta, Canada from 2007 to 2017. Preoperative CT scans were analyzed to determine SMI and SMD. Cohort-specific SMI and SMD cut-offs that optimally predicted overall survival (OS) were identified through stratification, in addition to testing cut-offs previously established in the literature. Overall (OS), melanoma-specific (MSS), and recurrence-free survival (RFS) were determined from date of surgery and analysed using multivariable Cox regressions with age, sex, BMI, stage subgroup, ECOG PS, and tumor location as covariates. RESULTS: We included 330 patients in the final analysis. Mean age was 56 years and 62.4% of patients were male. At time of censoring 150 patients (45.6%) had died. Sarcopenia based on literature cut-offs was associated with decreased OS (HR 1.55, 95% CI 1.00-2.21, p = 0.016). Using cohort-specific cut-offs, sarcopenic patients also had significantly decreased OS (HR 1.87, 95% CI 1.27-2.76, p = 0.002). Myosteatosis defined using cohort-specific cut-offs predicted worse OS (HR 2.15, 95% CI 1.42-3.25, p < 0.001), MSS (HR 2.29, 95% CI 1.40-3.75, p = 0.001) and RFS (HR 1.52, 95% CI 1.02-2.27, p = 0.041). Increased BMI ( ≥ 25) and visceral fat index were not significantly associated with survival. CONCLUSIONS: Sarcopenia and myosteatosis, defined using two sets of cut-offs, are associated with decreased OS and MSS in resected stage III melanoma.

CT-based assessment of body composition and skeletal muscle in melanoma: A systematic review.

BACKGROUND/OBJECTIVES: Sarcopenia (low skeletal muscle index) and myosteatosis (low skeletal radiodensity) have been associated with poor outcomes in melanoma. This systematic review was performed to summarize and critically evaluate current literature surrounding body composition in melanoma. METHODS: MEDLINE and Embase databases were searched for studies of melanoma patients with computed tomography (CT) based body composition analysis from 2000 to 2020. Outcomes of interest were survival, including overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS), as well as treatment-related adverse events (AEs). RESULTS: Nine studies of 914 patients were included in the final review. The majority of studies were of metastatic melanoma patients treated with immunotherapy. Studies demonstrated a variety of CT analysis techniques and cut-offs to define sarcopenia and myosteatosis. Associations of sarcopenia or myosteatosis with survival (OS, PFS, DFS) or risk of treatment-related AEs were conflicting. Multiple studies had low quality of evidence due to small sample sizes, use of non-validated CT measures, and lack of multivariable analyses. CONCLUSIONS: Due to methodologic heterogeneity and low quality of evidence, impacts of CT-derived body composition parameters on outcomes in melanoma are unclear. Further research should be conducted to elucidate impacts of body composition in melanoma.

Myosteatosis is prognostic in metastatic melanoma treated with nivolumab.

BACKGROUND: While immunotherapy agents have improved outcomes in metastatic melanoma (MM), predictive biomarkers in these patients are lacking. Parameters identified from body composition analysis, such as low SMD (also termed myosteatosis), may prognosticate MM patients on immunotherapy. METHODS: In this retrospective study, 44 MM patients received nivolumab, either as monotherapy or in combination with ipilimumab. Pre-treatment computed tomography (CT) scans were analyzed to determine skeletal muscle density (SMD) in Hounsfield units (HU) and muscle surface area (MSA) in cm2 at L3. MSA was used to determine nivolumab dosing in mg/cm2. RESULTS: Low SMD was associated with worse overall survival (OS) by log rank test (median 12.03 vs. 34.96 months, p = 0.001) and in multivariate analysis when accounting for age, sex, performance status, and number of prior lines of therapy (HR 4.40, 95% CI 1.44-13.42, p = 0.009). Lower nivolumab dosing by MSA was significantly associated with improved OS (median 42.9 vs. 12.3 months, p < 0.001). This association remained significant in multivariate analysis with age, sex, performance status, and number of prior lines of therapy (HR 0.05, 95% CI 0.01-0.30, p = 0.001). Neither SMD nor higher nivolumab dose per MSA were associated with increased incidence of treatment toxicity. CONCLUSIONS: Low SMD is prognostic in MM treated with nivolumab immunotherapy. Presence of myosteatosis or higher nivolumab dose based on body composition did not predict treatment toxicity.

An exploratory study of body composition as a predictor of dose-limiting toxicity in metastatic pancreatic cancer treated with gemcitabine plus nab-paclitaxel.

BACKGROUND: Body composition is increasingly being studied as a method of predicting chemotherapy toxicity. Our study aimed to evaluate associations of body composition with treatment toxicity in a group of pancreatic cancer patients treated with gemcitabine plus nab-paclitaxel. METHODS: A retrospective review was performed for all patients who received first-line gemcitabine plus nab-paclitaxel for metastatic pancreatic cancer at a northern Alberta cancer institute (Canada) from 2014 to 2017. Total lean body mass (LBM) was derived from measurements of muscle surface area at L3 on baseline computed tomography (CT) scans. Optimal stratification, or minimal p-value analysis, was used to assess for a threshold of nab-paclitaxel dose per LBM (mg/kg) associated with a higher risk of dose-limiting toxicity (DLT). RESULTS: 152 patients were included in the study, of whom 62 (40.8%) experienced DLT. nab-Paclitaxel dose/LBM ranged from 0.98 to 8.76 mg/kg. A threshold for nab-paclitaxel dose/LBM that optimally predicted risk of DLT was identified at 5.83 mg/kg. Above this cut-off, 18/31 (58.1%) patients experienced DLT, compared to 44/121 (36.4%) patients below (p = 0.028). Patients above this cut-off had a higher incidence of peripheral neuropathy compared to those below, though this was not statistically significant based on an adjusted p-value threshold (48.4 vs. 29.8% respectively, p = 0.050). Body mass index, body surface area, and absolute initial doses of nab-paclitaxel or gemcitabine did not significantly impact likelihood of DLT. CONCLUSIONS: nab-Paclitaxel dose normalized to LBM, based on CT-derived measures of skeletal muscle, has potential to predict risk of chemotherapy toxicity. Chemotherapy dosing based on body composition, rather than conventional anthropometric measures, may be effective in reducing treatment toxicity.