Sebaceous carcinoma of the trunk and extremities: Epidemiology and treatment patterns in the United States.

Background: Sebaceous carcinoma is a rare cancer, and little is known about its current epidemiology and treatment. This is particularly true for sebaceous carcinomas of the trunk and extremities. Objective: We present a database analysis of sebaceous carcinoma cases to further delineate demographics, location, tumor characteristics, and treatment modalities among patients diagnosed with these tumors. Methods: The National Cancer Database was queried for cases of sebaceous carcinoma between 2004 and 2016. 3211 cases were analyzed for descriptive and comparative statistics. Results: Twenty-six percent of sebaceous carcinomas were found on the trunk and extremities. Tumors on the trunk and extremities were more likely to be larger than tumors on the head and neck, with 8% being greater than 50 mm (P < .001). Tumors on the trunk and extremities were more likely to be well differentiated (P < .001) and have fewer lymph node metastases (P < .001). Surgery was the primary treatment modality for tumors, followed by radiotherapy and rarely chemotherapy. Conclusions: Sebaceous cancer is a poorly understood entity. We demonstrated that trunk and extremity tumors tend to be larger and more differentiated than those of the head and neck. Treatment practices are varied at this time, but surgery is the primary modality.

Trends of medicare reimbursement for breast cancer and reconstructive surgery.

This study evaluated trends in Medicare reimbursement for commonly performed breast oncologic and reconstructive procedures. Average national relative value units (RVUs) for physician-based work, facilities, and malpractice were collected along with the corresponding conversion factors for each year. From 2010 to 2021, there was an overall average decrease of 15% in Medicare reimbursement for both breast oncology (-11%) and reconstructive procedures (-16%). Based on these findings, breast and reconstructive surgeons should advocate for reimbursement that better reflects the costs of their practice.

Pigmented Epithelioid Melanocytoma of the Penis: A Case Report.

Pigmented epithelioid melanocytoma is rare cutaneous melanocytic proliferation, characterized by heavily pigmented melanocytes, with a potential for regional node metastasis, but with an overall favorable clinical course. Here, we describe an uncommon case of pigmented epithelioid melanocytoma involving the penis in an adolescent patient.

United States insurance coverage of immediate lymphatic reconstruction.

INTRODUCTION: Immediate Lymphatic Reconstruction (ILR) is a prophylactic microsurgical lymphovenous bypass technique developed to prevent breast cancer related lymphedema (BCRL). We investigated current coverage policies for ILR among the top insurance providers in the United States and compared it to our institutional experience with obtaining coverage for ILR. METHODS: The study analyzed the publicly available ILR coverage statements for American insurers with the largest market share and enrollment per state to assess coverage status. Institutional ILR coverage was retrospectively analyzed using deidentified claims data and categorizing denials based on payer reason codes. RESULTS: Of the 63 insurance companies queried, 42.9% did not have any publicly available policies regarding ILR coverage. Of the companies with a public policy, 75.0% deny coverage for ILR. In our institutional experience, $170,071.80 was charged for ILR and $166 118.99 (97.7%) was denied by insurance. CONCLUSIONS: Over half of America's major insurance providers currently deny coverage for ILR, which is consistent with our institutional experience. Randomized trials to evaluate the efficacy of ILR are underway and focus should be shifted towards sharing high level evidence to increase insurance coverage for BCRL prevention.

Efficacy of Targeted Axillary Dissection With Radar Reflector Localization Before Neoadjuvant Chemotherapy.

INTRODUCTION: For clinically node positive breast cancer patients treated with neoadjuvant chemotherapy (NAC), targeted axillary dissection (TAD) can be used to stage the axilla. TAD removes the sentinel lymph node (SLN) and tagged positive nodes, which can be identified via radar reflector localization (RRL). As it can be challenging to localize a previously positive node after NAC, we evaluated RRL prior to NAC. METHODS: We performed a retrospective chart review of breast cancer patients with node positive disease treated with NAC who underwent TAD with RRL. We compared retrieval of radar reflector and clip, timing of localization, and, if a node was positive, whether the radar reflector node or SLN was positive. RESULTS: Seventy-nine patients fulfilled inclusion criteria; 32 were placed pre-NAC (mean 187 d before surgery) and 47 were placed post-NAC (mean 7 d before surgery). For pre-NAC placement, 31 of 32 radar reflectors and 31 of 32 clips were retrieved. For post-NAC placement, 47 of 47 radar reflectors and 46 of 47 clips were retrieved. There was no significant difference in radar reflector or clip retrieval rates between pre-NAC and post-NAC groups (P = 0.41, P = 1, respectively). Thirty of 32 patients with pathologic complete response avoided an axillary lymph node dissection. Of 47 patients with a positive lymph node, 32 were both the SLN and radar reflector node, 11 were radar reflector alone, and four were the SLN. CONCLUSIONS: RRL systems are an effective way to guide TAD, and RRL makers can be safely placed prior to NAC.

The First Cold Atmospheric Plasma Phase I Clinical Trial for the Treatment of Advanced Solid Tumors: A Novel Treatment Arm for Cancer.

Local regional recurrence (LRR) remains the primary cause of treatment failure in solid tumors despite advancements in cancer therapies. Canady Helios Cold Plasma (CHCP) is a novel Cold Atmospheric Plasma device that generates an Electromagnetic Field and Reactive Oxygen and Nitrogen Species to induce cancer cell death. In the first FDA-approved Phase I trial (March 2020-April 2021), 20 patients with stage IV or recurrent solid tumors underwent surgical resection combined with intra-operative CHCP treatment. Safety was the primary endpoint; secondary endpoints were non-LRR, survival, cancer cell death, and the preservation of surrounding healthy tissue. CHCP did not impact intraoperative physiological data (p > 0.05) or cause any related adverse events. Overall response rates at 26 months for R0 and R0 with microscopic positive margin (R0-MPM) patients were 69% (95% CI, 19-40%) and 100% (95% CI, 100-100.0%), respectively. Survival rates for R0 (n = 7), R0-MPM (n = 5), R1 (n = 6), and R2 (n = 2) patients at 28 months were 86%, 40%, 67%, and 0%, respectively. The cumulative overall survival rate was 24% at 31 months (n = 20, 95% CI, 5.3-100.0). CHCP treatment combined with surgery is safe, selective towards cancer, and demonstrates exceptional LRR control in R0 and R0-MPM patients. (Clinical Trials identifier: NCT04267575).

Screening Practices for Breast and Nonbreast Cancers in High-Risk Mutation Carriers.

INTRODUCTION: Women with breast cancer often undergo genetic testing and may have a pathogenic variant associated with multiple cancers. This study examines the current screening practices for breast and nonbreast cancers in mutation carriers. METHODS: An institutional retrospective chart review of patients with BRCA1, BRCA2, ATM, CHEK2, BARD1, BRIP1, PALB2, and TP53 mutations were identified. Adherence to recommended screening based on National Comprehensive Cancer Network guidelines was analyzed. RESULTS: Six hundred sixty-two patients met inclusion criteria: 220 patients with BRCA1, 256 patients with BRCA2, 58 patients with PALB2, 51 patients with ATM, 48 patients with CHEK2, 14 patients with BRIP1, 10 patients with BARD1, and 5 patients with TP53. Overall, 214 (46%) of eligible patients completed recommended breast imaging. Of 106 patients eligible for pancreatic cancer screening, 20 (19%) received a magnetic resonance cholangiopancreatography and 16 (15%) received an endoscopic ultrasound. On multivariable analysis, age was associated with improved breast imaging adherence: patients in age groups 40-55 (adjusted odds ratio 2.05, 95% confidence interval 1.18-3.55) and age 56-70 (adjusted odds ratio 2.16, 95% confidence interval 1.18-3.95, P = 0.012) had better adherence than younger patients. CONCLUSIONS: Increases in genetic testing and updates to National Comprehensive Cancer Network guidelines provide an opportunity for improved cancer screening. While recommended breast cancer screenings are being completed at higher rates, there is a need for clear protocols in this high-risk population.

Enhanced Recovery After Surgery and Postoperative Nausea and Length of Stay in Mastectomy Patients With Reconstruction.

INTRODUCTION: Surgery is a mainstay of curative breast cancer treatment and is associated with postoperative nausea and vomiting (PONV) negatively impacting the patient experience. Enhanced recovery after surgery (ERAS) protocols are a combination of evidence-based strategies applied to traditional perioperative practices with the goal to reduce postoperative complications. ERAS protocols have been traditionally underutilized in breast surgery. We investigated if the implementation of an ERAS protocol was associated with decreased rates of PONV as well as length of stay (LOS) in patients undergoing mastectomy with breast reconstruction. METHODS: We conducted a retrospective chart review case-control study in which we compared PONV and LOS between ERAS cases and non-ERAS controls. Our data set consisted of 138 ERAS cases and 96 non-ERAS controls. All patients were >18 y old and underwent mastectomy with immediate implant or tissue expander-based reconstruction between 2018 and 2020. The non-ERAS group consisted of procedure-matched controls that were treated prior to implementation of the ERAS protocol. RESULTS: In univariate comparisons, patients who underwent the ERAS protocol had significantly decreased postoperative nausea (mean 37.5% of controls versus 18.1% of ERAS, P < 0.001) and shorter LOS (1.21 versus 1.49 d, P < 0.001). Using a multivariable regression to control for potential confounders, ERAS protocol was associated with less postoperative nausea (odds ratio [OR] = 0.26, 95% confidence interval [CI] = 0.13-0.5), LOS 1 d versus > 1 d (OR = 0.19, 95% CI = 0.1-0.35), and less postoperative ondansetron use (OR = 0.03, 95% CI = 0.01-0.07). CONCLUSIONS: Our results indicate that implementation of the ERAS protocol in women undergoing mastectomy with immediate reconstruction is associated with improved patient outcomes in postoperative nausea and LOS.

Lymphoscintigraphy Using Tilmanocept Detects Multiple Sentinel Lymph Nodes in Melanoma Patients.

BACKGROUND: Technetium-99m-labeled Tilmanocept, a multivalent mannose, is readily internalized by the CD206 surface receptor on macrophages and dendritic cells which are abundantly present in lymph nodes. We want to examine the drainage patterns of Technetium-99m-labeled Tilmanocept to sentinel lymph nodes (SLNs) in melanoma patients following the 10% rule. METHODS: Multi-center retrospective review of patients with cutaneous melanoma undergoing SLN biopsy using Technetium-99m-labeled Tilmanocept between 2008 and 2014 was conducted. Statistical methods were used for data analyses. RESULTS: Of the 564 patients (mean age of 60.3 and 62% male) with preoperative lymphoscintigraphy showing at least one SLN, several primary tumor sites were included: 27% head/neck, 33% trunk, 21% upper extremity and 19% lower extremity. For the head/neck primary site, 36.5% of patients had multiple draining basins; for the trunk site, 36.4% of patients; for the upper extremity site, 13% of patients; and for the lower extremity, 27.4% of patients. A median of 3 (range 1-18) SLNs were identified and resected. Overall, 78% of patients had >1 SLN identified by Technetium-99m-labeled Tilmanocept. In a multivariate model, patients with >1 SLN were significantly associated with age, Breslow depth, tumor location and higher AJCC tumor stage. A total of 17.7% of patients (100/564) had a positive SLN identified. A total of 145 positive SLNs were identified out of 1,812 SLNs with a positive SLN rate of 8%. Positive SLN status was significantly associated with younger age, greater Breslow depth, mitosis rate, higher AJCC tumor stage, presence of ulceration and angiolymphatic invasion. CONCLUSIONS: Using the 10% rule, Technetium-99m-labeled Tilmanocept detects multiple SLNs in most melanoma patients.

Therapeutic Value of Sentinel Lymph Node Biopsy in Patients With Melanoma: A Randomized Clinical Trial.

Importance: Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery. Objective: To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases. Design, Setting, and Participants: The second Multicenter Selective Lymphadenectomy Trial (MSLT-II), a prospective multicenter randomized clinical trial, randomized participants with SLN metastases to either CLND or nodal observation. The current analysis examines observation patients with regard to regional nodal recurrence. Trial patients were aged 18 to 75 years with melanoma metastatic to SLN(s). Data were collected from December 2004 to April 2019, and data were analyzed from July 2020 to January 2022. Interventions: Nodal observation with ultrasonography rather than CLND. Main Outcomes and Measures: In-basin nodal recurrence. Results: Of 823 included patients, 479 (58.2%) were male, and the mean (SD) age was 52.8 (13.8) years. Among 855 observed basins, at 10 years, 80.2% (actuarial; 95% CI, 77-83) of basins were free of nodal recurrence. By univariable analysis, freedom from regional nodal recurrence was associated with age younger than 50 years (hazard ratio [HR], 0.49; 95% CI, 0.34-0.70; P < .001), nonulcerated melanoma (HR, 0.36; 95% CI, 0.36-0.49; P < .001), thinner primary melanoma (less than 1.5 mm; HR, 0.46; 95% CI, 0.27-0.78; P = .004), axillary basin (HR, 0.61; 95% CI, 0.44-0.86; P = .005), fewer positive SLNs (1 vs 3 or more; HR, 0.32; 95% CI, 0.14-0.75; P = .008), and SLN tumor burden (measured by diameter less than 1 mm [HR, 0.39; 95% CI, 0.26-0.60; P = .001] or less than 5% area [HR, 0.36; 95% CI, 0.24-0.54; P < .001]). By multivariable analysis, younger age (HR, 0.57; 95% CI, 0.39-0.84; P = .004), thinner primary melanoma (HR, 0.40; 95% CI, 0.22-0.70; P = .002), axillary basin (HR, 0.55; 95% CI, 0.31-0.96; P = .03), SLN metastasis diameter less than 1 mm (HR, 0.52; 95% CI, 0.33-0.81; P = .007), and area less than 5% (HR, 0.58; 95% CI, 0.38-0.88; P = .01) were associated with basin control. When looking at the identified risk factors of age (50 years or older), ulceration, Breslow thickness greater than 3.5 mm, nonaxillary basin, and tumor burden of maximum diameter of 1 mm or greater and/or metastasis area of 5% or greater and excluding missing value cases, basin disease-free rates at 5 years were 96% (95% CI, 88-100) for patients with 0 risk factors, 89% (95% CI, 82-96) for 1 risk factor, 86% (95% CI, 80-93) for 2 risk factors, 80% (95% CI, 71-89) for 3 risk factors, 61% (95% CI, 48-74) for 4 risk factors, and 54% (95% CI, 36-72) for 5 or 6 risk factors. Conclusions and Relevance: This randomized clinical trial was the largest prospective evaluation of long-term regional basin control in patients with melanoma who had nodal observation after removal of a positive SLN. SLN biopsy without CLND cleared disease in the affected nodal basin in most patients, even those with multiple risk factors for in-basin recurrence. In addition to its well-validated value in staging, SLN biopsy may also be regarded as therapeutic in some patients. Trial Registration: ClinicalTrials.gov Identifier: NCT00297895.

Factors Mediating Racial/Ethnic Disparities in Delayed Treatment of Breast Cancer.

BACKGROUND: Despite improvements, disparities in breast cancer care have led to an inequitable distribution of treatment delays and worse outcomes among patients with breast cancer. This study aimed to quantify the contribution of mediators that may explain racial/ethnic disparities in breast cancer treatment delays. PATIENTS AND METHODS: We conducted a retrospective analysis of patients from the National Cancer Database with stage I-III breast cancer who underwent surgical resection. Mediation analyses estimated the extent to which racial/ethnic disparities in the distribution of patient characteristics account for racial/ethnic disparities in delayed treatment. RESULTS: Of the 1,349,715 patients with breast cancer included, 10%, 5%, and 4% were Black, Hispanic, and other non-white race/ethnicity, respectively. Multivariable models showed that patients in these racial/ethnic groups had 73%, 81%, and 24% increased odds of having a treatment delay relative to white patients. Mediation analyses suggested that 15%, 19%, and 15% of the treatment delays among Black, Hispanic, and other non-white race/ethnicity patients, respectively, are explained by disparities in education, comorbidities, insurance, and facility type. Therefore, if these mediators had been distributed equally among all races/ethnicities, a reduction of 15-19% in the delayed treatment disparities experienced by minority patients would have been observed. Academic facility type was the factor that could yield the largest reduction in time to treatment disparities, contributing to 8-13% of racial/ethnic disparities. CONCLUSIONS: Patients with breast cancer who identified as Black, Hispanic, and other non-white races/ethnicities are exposed to longer treatment delays relative to white patients. Efforts to equalize mediators could remove substantial portions of racial/ethnic disparities in delayed treatment.

Trends in Skin Melanoma Burden: Findings From the Global Burden of Disease Study.

Background: Melanoma is the third most common skin cancer and the leading cause of skin cancer mortality. This study sought to investigate trends in melanoma incidence, mortality, and burden of disease. Methods: The authors assessed the records of the Global Burden of Disease Study 2017 to extract information about the incidence, mortality, and disability adjusted life years (DALY) related to melanoma during 1990-2017 in the US and other countries based on their socio-demographic index (SDI). Results: Melanoma incidence in the US increased 1.6 times, although the difference was not statistically significant. For patients over the age of 60, the incidence was significantly increased by 1.72 to 164.6 times. Mortality was relatively stable during the study period; however, it was increased for patients over 65 years of age (range: 1.03 to 70 times), although not statistically significant. Mortality-to-incidence ratio was decreased, but the difference was not statistically significant. For patients over 75 years of age, DALYs were statistically significantly increased by 1.34 to 1.71 times. Conclusions: This study highlights differences in melanoma incidence and mortality from 1990-2017. Physicians involved in melanoma care should be aware of these changes in order to anticipate care needs.

100 Disruptive Publications in Breast Cancer Research.

BACKGROUND: Breast cancer has a rich history of research over the past 75 years. Many studies have had disruptive influences on the field itself. Our study employs a new, validated measurement to determine the most disruptive publications within the field of breast cancer. MATERIALS AND METHODS: PubMed® database was queried for articles between 1954-2014 related to breast cancer with in 21 different journals deemed important to the field. Articles were then scored for disruption and citation count. The top 100 most disruptive and cited publications were compiled and analyzed. RESULTS: Disruption score was a distinct measurement from citation count and had low level of correlation. Disruptive publications tended to skew older with the median year of publication in 1977. The score identified a variety of study designs and publication types within multiple journals. CONCLUSIONS: Measurement of the disruptive quality of a publication is a new way to describe academic impact of a publication and is distinct from citation count. Used in conjunction with citation count in may give a more descriptive bibliometric assessment of the literature. Further exploration within the field of oncology is warranted.
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Impact of Inequities on Delay in Breast Cancer Management in Women Undergoing Second Opinions.

BACKGROUND: Inequities in breast cancer treatment lead to delay in therapy, decreased survival and lower quality of life. This study aimed to examine demographics and clinical factors impacting time to treatment for second-opinion breast cancer patients. MATERIALS AND METHODS: We performed a retrospective chart review to analyze patients presenting to one academic institution for second opinion of breast imaging, diagnosis, or breast-related treatment. Data from women with stage I-III breast cancer who received treatment at this institution were evaluated to determine the impact of patient demographics and clinical characteristics on time to first treatment. RESULTS: Of the 1006 charts reviewed, 307 met inclusion criteria. Low-income patients averaged 58 days from diagnosis to surgery compared to 35 days for high-income patients (incidence rate ratio [IRR] 0.64, P<0.01). Black patients averaged 56 days from diagnosis to surgery compared to 42 days for White patients (IRR 1.37, P<0.01). Latina patients averaged 38 days from initial encounter to neoadjuvant chemotherapy compared to 20 days for White patients (IRR 1.69, P<0.05). CONCLUSION: Patients with low-income, of Black race and Latina ethnicity experienced increased time to treatment. Additionally, time to mastectomy with and without reconstruction was longer than time to partial mastectomy. Further exploration is needed to determine why certain factors lead to treatment delay and how inequities can be eliminated.

A Population-based Analysis of Lymph Node Metastasis in Extremity Soft Tissue Sarcoma: An Update.

BACKGROUND: Soft tissue sarcomas (STSs) are mesenchymal tumors that may rarely metastasize to lymph nodes. This investigation sought to evaluate regional lymph node metastasis (RLNM) in extremity STS using a national cohort. MATERIALS AND METHODS: This study was a retrospective review of the Surveillance, Epidemiology, and End Results database from 1975 to 2016. A Cox proportional hazards model was used to identify prognostic factors associated with disease-specific survival (DSS). RESULTS: RLNM was present in 3.7% (n = 547) of extremity STS. The rate of RLNM was highest in rhabdomyosarcoma (26.7%), clear cell sarcoma (18.8%), epithelioid sarcoma (14.5%), angiosarcoma (8.1%), spindle cell sarcoma (5.0%), and synovial sarcoma (3.2%). The 5-year DSS probability without RLNM was 69% (standard error: 1.3%) compared to 26% (standard error: 3.6%) with RLNM (P < 0.001). For the historically high-risk extremity STS, advanced age (hazard ratio (HR), 1.036; 95% confidence interval (CI), 1.0-1.04; P < 0.001), higher grade tumors (HR, 1.979; 95% CI, 1.3-3.0; P < 0.001), tumor size greater than 10 cm (HR, 1.892; 95% CI, 1.3-2.7; P < 0.001), primary site surgery (HR, 0.529; 95% CI, 0.3-0.8; P = 0.006), distant metastasis (HR, 4.585; 95% CI, 3.0-6.8; P < 0.001), and RLNM (HR, 2.153; 95% CI, 1.3-3.5; P = 0.003) were each independent disease-specific prognostic factors. CONCLUSIONS: The prognosis of RLNM in historically high-risk extremity STS is poor with a 5-year DSS of 26%. These data support a staging system of STS inclusive of nodal involvement and contribute to the growing body of evidence that characterizes the rates of RLNM in STS.

Microsatellitosis in Patients with Melanoma.

BACKGROUND: Microsatellitosis (mS) in melanoma has been considered a marker of unfavorable tumor biology, leading to the current American Joint Committee on Cancer staging of IIIB/C/D disease, despite few investigative studies of this entity limited by the small sample sizes and incomplete nodal microstaging. We sought to better characterize outcomes and prognostic factors in a multi-institutional cohort of patients with mS and nodal microstaging. METHODS: The Sentinel Lymph Node Working Group cohort included 414 mS patients who underwent sentinel lymph node (SLN) biopsy. Cox regression analysis was used to evaluate the prognostic significance of established clinicopathologic characteristics. Melanoma-specific survival (MSS) of patients with mS was compared with 3002 similarly staged patients from the Surveillance, Epidemiology, and End Results (SEER) Program registry. RESULTS: The median age of the mS cohort was 64.9 years; 39.6% were female. Median thickness was 3 mm, 40.6% of cases were ulcerated, and the SLN positivity rate was 46.7%. Increasing thickness, male sex, and SLN positivity were significantly associated with poorer MSS. Stage IIIB/C/D 5-year MSS rates were 86.3% (95% confidence interval [CI] 79.4-93.3%), 54.1% (95% CI 45.4-59.7%), and 44.2% (95% CI 25.4-63.0%), respectively. MSS survival for the stage IIIB mS cohort was significantly better than a similarly staged SEER cohort (5-year MSS of 70.1%, 95% CI 66.0-74.2%), while no significant difference was observed for the stage IIIC or D cohorts. CONCLUSIONS: SLN metastases are common and are a significant prognostic factor in patients with mS. Survival in stage IIIB patients with mS was considerably more favorable than their stage would otherwise suggest, which has important implications for decisions regarding adjuvant therapy for patients with mS.