Impact of travel burden on the treatment of stage I and II breast cancer: A National Cancer Database analysis.

BACKGROUND: Although historic studies of state registries have demonstrated decreased radiation therapy use for patients with breast cancer living further away from radiation facilities, the association between travel distance and breast cancer treatment in a modern national cohort remains unknown. METHODS: Female patients with estrogen receptor/progesterone receptor positive and human epidermal growth factor receptor 2 negative pathologic stages I to II breast cancer were identified from the National Cancer Database (2018-2020) and dichotomized by distance ≤20 miles or >20 miles (75th percentile) from the treatment facility. The association between travel distance and type of surgery and treatment administered was analyzed by univariate and multivariate logistic regression and after 1:1 propensity matching. RESULTS: Of the 293,318 patients identified for inclusion, the median age was 63 years, and most patients (n = 190,567, 65%) lived ≤20 miles of the treatment facility. Patients with a travel burden >20 miles were more likely to receive a mastectomy (≤20 miles 30.4% vs >20 miles 34.0%, P < .001; odds ratio 1.14, P = .016), and less likely to receive radiation (≤20 miles 63.3% vs >20% miles 60.1%, P < .001; odds ratio 0.81, P < .001). These findings persisted after propensity score matching (n = 33,544 per cohort), with patients living further being more likely to undergo a mastectomy (≤20 miles 30.3% vs >20 miles 35.3%, P < .001) and less likely to receive radiation (≤ 20 miles 65.4% vs. >20 miles 58.5%, P < .001). CONCLUSION: Patients with hormone receptor-positive stage I to II breast cancer with a larger travel burden are more likely to receive a mastectomy and less likely to undergo radiation therapy to treat their disease.

Timing of Adjuvant Immunotherapy in Stage III Melanoma, Does it Matter?

BACKGROUND: The optimal time to initiate adjuvant immune checkpoint inhibitors (ICI) following resection remains undefined. Herein, we investigated the impact of time to adjuvant ICI on survival in patients with stage III melanoma. METHODS: Patients with resected stage III melanoma receiving adjuvant immune therapy were identified within a multi-institutional retrospective cohort. Patients were stratified by time to adjuvant ICI: within 6 weeks, 6-12 weeks, and greater than 12 weeks from surgery. Recurrence-free survival (RFS) was compared among time strata with Kaplan-Meier and Cox proportional hazards methods in the multi-institutional cohort. RESULTS: Altogether, 626 patients were identified within the multi-institutional cohort: 39% of patients initiated adjuvant ICI within 6 weeks, 42.2% within 6-12 weeks, and 18.8% greater than 12 weeks from surgery. In a multivariate Cox model, adjusting for histology, nodal tumor burden, and pathologic stage, we found that increased time to adjuvant ICI was associated with improved RFS. Patients who initiated adjuvant ICI within 6 weeks of surgery had worse RFS. These findings were preserved in a conditional landmark analysis and separate subgroups of patients with (1) new melanoma diagnoses, (2) occult stage III disease, and (3) those receiving anti-PD-1 monotherapy. CONCLUSIONS: Outcomes for patients with stage III melanoma are not compromised when adjuvant ICI is initiated beyond 6 weeks from resection. Additional work is needed to better understand the underlying mechanisms and implications of timing of adjuvant ICI on long-term outcomes.

Sentinel lymph node biopsy status improves adjuvant therapy decision-making in patients with clinical stage IIB/C melanoma: A population-based analysis.

BACKGROUND: Given the results of the recent KEYNOTE-716 trial, the performance of sentinel lymph node (SLN) biopsy for patients with clinical stage IIB/C melanoma has been questioned. OBJECTIVE: Determine the utility of SLN status in guiding the recommendations for adjuvant therapy. METHODS: Patients with clinical stage IIB/C cutaneous melanoma who underwent wide local excision and SLN biopsy between 2004 and 2011 were identified from the Surveillance, Epidemiology, and End Results database. Two prognostic models, with and without SLN status, were developed predicting risk of melanoma-specific death (MSD). The primary outcome was net benefit at treatment thresholds of 20% to 40% risk of 5-year MSD. RESULTS: For the 4391 patients included, the 5-year MSD rate was 46%. The model estimating 5-year MSD risk that included SLN status provided greater net benefit at treatment thresholds from 30% to 78% compared to the model without SLN status. The added net benefit for the SLN biopsy-containing model persisted in subgroup analysis of patients in different age groups and with various T stages. LIMITATIONS: Retrospective study. CONCLUSIONS: A prognostic model with SLN status estimating patient risk for 5-year MSD provides superior net benefit compared to a model with primary tumor staging factors alone for threshold mortality rates ≥30%.

Sentinel lymph node biopsy in patients with T1a cutaneous malignant melanoma: A multicenter cohort study.

BACKGROUND: Sentinel lymph node biopsy is not routinely recommended for T1a cutaneous melanoma due to the overall low risk of positivity. Prognostic factors for positive sentinel lymph node (SLN+) in this population are poorly characterized. OBJECTIVE: To determine factors associated with SLN+ in patients with T1a melanoma. METHODS: Patients with pathologic T1a (<0.80 mm, nonulcerated) cutaneous melanoma from 5 high-volume melanoma centers from 2001 to 2020 who underwent wide local excision with sentinel lymph node biopsy were included in the study. Patient and tumor characteristics associated with SLN+ were analyzed by univariate and multivariable logistic regression analyses. Age was dichotomized into ≤42 (25% quartile cutoff) and >42 years. RESULTS: Of the 965 patients identified, the overall SLN+ was 4.4% (N = 43). Factors associated with SLN+ were age ≤42 years (7.5% vs 3.7%; odds ratio [OR], 2.14; P = .03), head/neck primary tumor location (9.2% vs 4%; OR, 2.75; P = .04), lymphovascular invasion (21.4% vs 4.2%; OR, 5.64; P = .01), and ≥2 mitoses/mm2 (8.2% vs 3.4%; OR, 2.31; P = .03). Patients <42 years with ≥2 mitoses/mm2 (N = 38) had a SLN+ rate of 18.4%. LIMITATIONS: Retrospective study. CONCLUSION: SLN+ is low in patients with T1a melanomas, but younger age, lymphovascular invasion, mitogenicity, and head/neck primary site appear to confer a higher risk of SLN+.

The Role of Imaging in Soft Tissue Sarcoma Diagnosis and Management.

The differential diagnosis of a soft tissue mass is broad, and an appropriate imaging workup is crucial to accurate identification. Additionally, imaging plays a critical role in soft tissue sarcoma (STS) staging and monitoring for disease progression. In this article, we discuss the different imaging modalities and their utility in the workup and surveillance of STS.

National Practice Patterns in the Management of the Regional Lymph Node Basin After Positive Sentinel Lymph Node Biopsy for Cutaneous Melanoma.

BACKGROUND: Immediate completion lymph node dissection (CLND) for patients with sentinel lymph node (SLN) metastasis from cutaneous melanoma has been replaced largely by ultrasound nodal surveillance since the publication of two landmark trials in 2016 and 2017. National practice patterns of CLND remain poorly characterized. METHODS: Patients with a diagnosis of cutaneous melanoma in 2016 and 2018 without clinical nodal disease who underwent sentinel lymph node biopsy (SLNB) were identified from the National Cancer Database (NCDB). Characteristics associated with CLND were analyzed by uni- and multivariate logistic regression. Overall survival (OS) was estimated using Kaplan-Meier and Cox proportional hazards regression analyses. RESULTS: Of the 3517 patients included in the study, 1405 had disease diagnosed in 2016. The patients with cutaneous melanoma diagnosed in 2016 had a median age of 60 years and a tumor thickness of 2.3 mm compared to 62 years and 2.4 mm, respectively, for the patients with cutaneous melanoma diagnosed in 2018. According to the NCDB, 40 % (n = 559) of the patients underwent CLND in 2016 compared with 6 % (n = 132) in 2018. The factors associated with receipt of CLND in 2018 included younger age (odds ratio [OR], 0.97; 95 % confidence interval [CI], 0.95-0.99; p = 0.001), rural residence (OR, 3.96; 95 % CI, 1.50-10.49; p = 0.006), head/neck tumor location (OR, 1.88; 95 % CI, 1.10-3.23; p = 0.021), and more than one positive SLN (OR, 1.80; 95 % CI, 1.17-2.76; p = 0.007). The 5-year OS did not differ between the patients who received SLNB only and those who underwent CLND (hazard ratio [HR], 0.93; p = 0.54). CONCLUSION: The rates of CLND have decreased nationally. However, patients with head/neck primary tumors who live in rural locations are more likely to undergo CLND, highlighting populations for which treatment may be non-uniform with national practice patterns.

Impact of the affordable care act's medicaid expansion on presentation stage and perioperative outcomes of colorectal cancer.

BACKGROUND AND OBJECTIVES: Medicaid expansion has improved healthcare coverage and preventive health service use. To what extent this has resulted in earlier stage colorectal cancer diagnoses and impacted perioperative outcomes is unclear. METHODS: This was a retrospective difference-in-difference study using the National Cancer Database on adults (40-64) with Medicaid or no insurance, diagnosed with colorectal adenocarcinomas before (2010-2013) and after (2015-2018) expansion. The primary outcome was early-stage (American Joint Committee on Cancer Stage 0-1) diagnosis. The secondary outcomes were rate of local excision, emergency surgery, postoperative length of stay, rates of minimally invasive surgery, postoperative mortality, and overall survival (OS). RESULTS: Medicaid expansion was associated with an increase in early-stage diagnoses for patients with colorectal cancers (odds ratio [OR]: 1.28, 95% confidence interval [CI]: 1.15-1.43), an increase in local excision (OR: 1.39, 95% CI: 1.13-1.69), and a decreased rate of emergent surgery (OR: 0.85, 95% CI: 0.75-0.97) and 90-day mortality (OR: 0.75, 95% CI: 0.59-0.97). Additionally, patients in expansion states postexpansion had an improved 5-year OS (hazard ratio: 0.88, 95% CI: 0.83-0.94). CONCLUSIONS: Insurance coverage expansion may be particularly important for optimizing stage of diagnosis, subsequent survival, and perioperative outcomes for socioeconomically vulnerable patients.

Association of type II diabetes mellitus with characteristics and outcomes for patients undergoing sentinel lymph node biopsy for cutaneous melanoma.

BACKGROUND AND OBJECTIVES: Type II diabetes mellitus (T2DM) can lead to an immunosuppressed state, but whether T2DM is associated with worse outcomes for patients with melanoma has not been well studied. METHODS: Consecutive patients diagnosed with clinical stage I-II cutaneous melanoma who underwent sentinel lymph node biopsy at a single institution (2007-2016) were identified. Melanoma characteristics and recurrence/survival outcomes were compared between patients with and without T2DM at the time of melanoma diagnosis. RESULTS: Of 1128 patients evaluated, 111 (9.8%) had T2DM (n = 94 [84.7%] non-insulin dependent [NID-T2DM]; n = 17 [15.3%] insulin dependent [ID-T2DM]). T2DM patients were more likely to be older (odds ratio [OR] 1.04, p < 0.001), male (OR 2.15, p = 0.003), have tumors >1.0 mm (OR 1.88, p = 0.023), and have microsatellitosis (OR 2.29, p = 0.030). Five-year cumulative incidence of melanoma recurrence was significantly higher for patients with ID-T2DM (46.7% ID-T2DM vs. 25.7% NID-T2DM vs. 17.1% no T2DM, p < 0.001), and on multivariable analysis, ID-T2DM was independently associated with melanoma recurrence (hazard ratio 2.57, p = 0.015). No difference in 5-year disease-specific survival was observed between groups. CONCLUSIONS: ID-T2DM appears to be associated with more advanced melanoma and increased risk for melanoma recurrence. Further study as to whether this reflects differences in tumor biology or host factors is warranted.

An Internally Validated Prognostic Risk-Score Model for Disease-Specific Survival in Clinical Stage I and II Merkel Cell Carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy for which factors predictive of disease-specific survival (DSS) are poorly defined. METHODS: Patients from six centers (2005-2020) with clinical stage I-II MCC who underwent sentinel lymph node (SLN) biopsy were included. Factors associated with DSS were identified using competing-risks regression analysis. Risk-score modeling was established using competing-risks regression on a training dataset and internally validated by point assignment to variables. RESULTS: Of 604 patients, 474 (78.5%) and 128 (21.2%) patients had clinical stage I and II disease, respectively, and 189 (31.3%) had SLN metastases. The 5-year DSS rate was 81.8% with a median follow-up of 31 months. Prognostic factors associated with worse DSS included increasing age (hazard ratio [HR] 1.03, p = 0.046), male sex (HR 3.21, p = 0.021), immune compromise (HR 2.46, p = 0.013), presence of microsatellites (HR 2.65, p = 0.041), and regional nodal involvement (1 node: HR 2.48, p = 0.039; ≥2 nodes: HR 2.95, p = 0.026). An internally validated, risk-score model incorporating all of these factors was developed with good performance (AUC 0.738). Patients with ≤ 4.00 and > 4.00 points had 5-year DSS rates of 89.4% and 67.2%, respectively. Five-year DSS for pathologic stage I/II patients with > 4.00 points (n = 49) was 79.8% and for pathologic stage III patients with ≤ 4.00 points (n = 62) was 90.3%. CONCLUSIONS: A risk-score model, including patient and tumor factors, based on DSS improves prognostic assessment of patients with clinically localized MCC. This may inform surveillance strategies and patient selection for adjuvant therapy trials.

The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study.

PURPOSE: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. METHODS: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. RESULTS: A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4-12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. CONCLUSION: Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.

Postsplenectomy morbidity and mortality in patients with immune thrombocytopenic purpura: A national cohort study.

BACKGROUND: We sought to identify factors associated with 30-day morbidity, and their impact on 30-day mortality, among patients undergoing splenectomy for immune thrombocytopenic purpura (ITP). METHODS: Using the ACS-NSQIP database, patients undergoing splenectomy for ITP were identified (2005-2019), and those with and without postoperative complications within 30 days of surgery were compared. RESULTS: Of 2483 patients evaluated, 280 (11.3%) developed 30-day morbidity: infection (n= 145 [5.8%]), venous thromboembolism (n = 71 [2.9%]), acute renal failure (n = 7 [0.3%]), respiratory failure (n = 40 [1.6%]), cardiac arrest/myocardial infarction (n = 16 [0.6%]), cerebrovascular accident (n = 4 [0.2%]), or postoperative blood transfusion (n = 62 [2.5%]). Risk-factors for 30-day morbidity included age ≥50 years (odds ratio [OR] 1.50, p = 0.020), body mass index ≥30 kg/m2 (OR 1.45, p = 0.023), functional dependence (OR 2.90, p = 0.009), preoperative albumin <3.5 g/dL (OR 2.10, p < 0.001), preoperative platelets <30 000/µL (OR 1.54, p = 0.020), open surgical approach (OR 2.32, p < 0.001), and inpatient status before surgery (OR 1.85, p = 0.040). Among patients at low-risk for 30-day morbidity (no risk-factors present), the 30-day morbidity rate was 5.0% versus 41.5% for ≥5 risk-factors (p < 0.001). Thirty-day mortality was 1.2%. CONCLUSIONS: Thirty-day morbidity and mortality are low with splenectomy for ITP. Select patients have particularly low perioperative risk and may benefit from early splenectomy if initial medical therapy fails.

Fourteen years of pancreatic surgery for malignancy among ACS-NSQIP centers: Trends in major morbidity and mortality.

BACKGROUND: The American College of Surgeons National Surgical Quality Improvement Program was established to help participating hospitals track and report surgical complications with the goal of improving surgical care. We sought to determine whether this has led to improvements in surgical outcomes for pancreatic malignancies. METHODS: Patients with pancreatic malignancies who underwent surgical resection were identified from the American College of Surgeons National Surgical Quality Improvement Program database (2006-2019). Thirty-day postoperative major morbidity and mortality were analyzed by year. Major morbidity included organ and deep surgical site infection, venous thromboembolism, cardiac event, pneumonia, acute renal failure, sepsis, and respiratory failure. RESULTS: Of the 28,888 patients identified, 51% were male, the median age was 68, 74.3% underwent a pancreaticoduodenectomy, and 25.7% underwent a distal pancreatectomy. Among patients who underwent a pancreaticoduodenectomy, there was a significant increase in major morbidity (annual percent change 0.77, P = .012) driven by increases in organ space surgical site infection (annual percent change 3.52, P < .001) and venous thromboembolism (annual percent change 4.72, P = .005). However, there was a decrease in postoperative mortality (annual percent change -4.58, P = .001). For distal pancreatectomy patients, there was no change in rates of overall major morbidity (annual percent change -1.35, P = .08) or mortality (annual percent change -3.21, P = .25). CONCLUSION: Although major morbidity and mortality have not significantly changed for distal pancreatectomy patients, mortality has steadily decreased for patients undergoing pancreaticoduodenectomy, despite an increase in major morbidity. Whether this trend reflects a change in patient selection, an increase in detection of postoperative morbidities and/or an improvement in mitigation of these morbidities warrants further study.

Sentinel lymph node biopsy in patients with clinical stage IIB/C cutaneous melanoma: A national cohort study.

BACKGROUND: Approval of adjuvant anti-programmed cell death protein 1 therapy for pathologic stage IIB/C cutaneous melanoma has led some to question the role of sentinel lymph node (SLN) biopsy in the clinical stage IIB/C disease. OBJECTIVE: To determine the prognostic significance of SLN staging on disease-specific survival (DSS) for clinical stage IIB/C primary cutaneous melanoma in the preimmunotherapy era. METHODS: A retrospective cohort study was performed evaluating patients who underwent excision of clinical stage IIB/C cutaneous melanoma using the Surveillance, Epidemiology, and End Results database (2004-2011). Patients who did and did not undergo SLN biopsy were compared using propensity matching, and among those who underwent SLN biopsy, matched patients were further stratified by SLN status (SLN positive [SLN+] or SLN negative [SLN-]). RESULTS: Of the 8562 patients evaluated, 6021 (70.3%) underwent SLN biopsy. SLN positivity was associated with significantly reduced 5-year DSS among matched patients who underwent SLN biopsy (47.1% SLN+ vs 75.5% SLN-; P < .001). Five-year DSS remained significantly different across matched T-stages: T3b (54.2% SLN+ vs 64.8% SLN-; P = .004), T4a (55.5% SLN+ vs 71.6% SLN-; P = .001), and T4b (38.6% SLN+ vs 60.9% SLN-; P < .001). LIMITATIONS: Retrospective study. CONCLUSION: For patients with clinical stage IIB/C cutaneous melanoma, SLN status provides essential prognostic information.

Validated Risk-Score Model Predicting Lymph Node Metastases in Patients with Non-Functional Gastroenteropancreatic Neuroendocrine Tumors.

BACKGROUND: The incidence of, and factors associated with, lymph node metastasis (LN+) in non-functional gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are not well characterized. METHODS: Patients were identified from the 2010-2015 National Cancer Database who underwent surgical resection with lymphadenectomy for clinical stage I-III non-functional GEP NETs. Among a randomly selected training subset of 75% of the study population, variables associated with LN+ were identified using multivariable logistic regression analysis, and these variables were used to create a risk-score model for LN+, which was internally validated among the remaining 25% of the cohort. RESULTS: Of 12,228 patients evaluated, 6,902 (56.4%) had LN+. Among the training set, variables associated with LN+ included age (70 years of age or older: odds ratio [OR] 1.12, 95% CI 1.00-1.24; ref: less than 70 years), tumor location (stomach: OR 3.72, 95% CI 2.94-4.71; small intestine: OR 19.60, 95% CI 17.31-22.19; ref: pancreas), tumor grade (moderately differentiated: OR 1.47, 95% CI 1.30-1.67; poorly differentiated/anaplastic: OR 1.53, 95% CI 1.21-1.95; ref: well-differentiated), tumor size (2-4 cm: OR 2.40, 95% CI 2.13-2.70; >4 cm: OR 5.25, 95% CI 4.47-6.17; ref: <2 cm), and lymphovascular invasion (OR 5.62, 95% CI 5.08-6.21; ref: no lymphovascular invasion). After internal validation, a risk-score model for LN+ using these variables was developed composed of low- (N = 2,779), intermediate- (N = 2,598), high- (N = 3,433), and very-high-risk (N = 3,418) groups; within each group the rate of LN+ was 8.7%, 48.6%, 64.9%, and 92.8%, respectively. CONCLUSIONS: This developed risk-score model, including both patient and tumor variables, can be used to calculate the risk for LN metastases in patients with GEP NETs.