Neoadjuvant therapy for resectable melanoma.

The standard of care for patients with resectable stage III/IV melanoma classically included upfront resection with adjuvant therapy. However, in more recent years, the amount of systemic therapies available for neoadjuvant use for these patients has increased. This article reviewed clinical trials investigating neoadjuvant therapy for patients with resectable stage III/IV melanoma. The outcomes of these trials have identified optimal treatment regimens to maximise patient response and minimize toxicities. Additionally, the date demonstrate advantages to neoadjuvant treatment compared to adjuvant therapy alone. Further research is needed to utilize a patient's response to neoadjuvant treatment for prognostication and creation of an individualized treatment plan.

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.

Delayed time to radiation and overall survival in Merkel cell carcinoma.

BACKGROUND: Clinically localized Merkel cell carcinoma (MCC) is commonly treated with surgical excision and radiotherapy. The relationship between time to adjuvant radiotherapy and overall survival (OS) remains understudied. METHODS: This retrospective study used data from the National Cancer Database (2006-2019). Patients with clinically localized MCC who received surgical excision and adjuvant radiotherapy were included. Multivariate regressions were used to account for various patient and tumor factors. The primary outcome was 5-year OS, and the secondary outcome was time from diagnosis to adjuvant radiation (TTR). RESULTS: Of the 1965 patients included, most were male (n = 1242, 63.2%) and white (n = 1915, 97.5%), and the median age was 74 years (interquartile range [IQR]: 66-81). The median TTR was 83 days (IQR: 65-106). A total of 83.6% of patients received radiotherapy to the primary site, 21.3% to the draining nodal basin, 17.1% to both, and 12.2% whose target location of radiotherapy was not recorded in the data. TTR of ≥79 days (the 45th percentile) was associated with worse OS on both univariate and multivariate analyses (log-rank p = 0.0014; hazard ratio [HR]: 1.258, 95% confidence interval [CI]: 1.055-1.500, p = 0.010). This persisted on sub-analyses of patients <80 years old (n = 1407; HR: 1.380, 95% CI: 1.080-1.764, p = 0.010) and of patients with Charlson comorbidity index (CCI) of 0 (n = 1411; HR: 1.284, 95% CI: 1.034-1.595, p = 0.024). Factors associated with delayed TTR included greater age (p = 0.039), male sex (p = 0.04), CCI > 1 (p = 0.036), academic facility (p < 0.001), rural county (p = 0.034), AJCC T2 stage (p = 0.010), negative margins (p = 0.017), 2+ pathologically positive regional nodes (p = 0.011), and margin size >2 cm (p = 0.015). CONCLUSIONS: Delayed radiotherapy (≥79 days) was associated with worse OS of MCC patients. Further study in controlled cohorts is needed to ascertain this relationship.

Neoadjuvant Chemotherapy in Retroperitoneal Sarcoma: A National Cohort Study.

INTRODUCTION: Management of retroperitoneal sarcoma (RPS) remains controversial, with the mainstay of treatment being surgery. While neoadjuvant radiation demonstrated no improvement in recurrence-free survival in a prospective randomized trial (STRASS), the role of neoadjuvant chemotherapy (NCT) remains unknown and is the subject of ongoing study (STRASS2). METHODS: Patients who underwent surgical resection of high-grade RP leiomyosarcoma (LMS) or dedifferentiated liposarcoma (DDLS) were identified from the National Cancer Database (2006-2019). Predictors of NCT were analyzed using univariate and multivariate logistic regression analyses. Differences in 5-year survival were examined using the Kaplan-Meier (KM) method and by Cox proportional hazard modeling. RESULTS: A total of 2656 patients met inclusion criteria. Fifty-seven percent of patients had DDLS and 43.5% had LMS. Six percent of patients underwent NCT. Patients who received NCT were younger (median age 60 vs 64 years, p < 0.001) and more likely to have LMS (OR 1.4, p = 0.04). In comparing NCT with no-NCT patients, there was no difference in 5-year overall survival (OS) on KM analysis (57.3% vs 52.8%, p = 0.38), nor was any difference seen after propensity matching (54.9% vs 49.1%, p = 0.48, N = 144 per group). When stratified by histology, there was no difference in OS based on receipt of NCT (LMS: 59.8% for NCT group, 56.6% for no-NCT, p = 0.34; DDLS: 54.2% for NCT group, 50.1% for no-NCT, p = 0.99). CONCLUSION: In patients undergoing surgical resection of RP LMS or DDLS, NCT does not appear to confer an OS advantage. Prospective randomized data from STRASS2 will confirm or refute these retrospective data.

Neoadjuvant chemotherapy in patients undergoing neoadjuvant radiation for trunk and extremity soft tissue sarcoma.

INTRODUCTION: Many patients with high-risk soft tissue sarcoma (STS) develop distant metastases. Meta-analyses suggest that chemotherapy confers a small survival benefit, though few studies focus on neoadjuvant chemotherapy (NCT). There has been more frequent use of neoadjuvant radiation therapy (NRT) in STS, but the utility of NCT for these patients remains unclear. METHODS: Patients with stage II-III trunk/extremity STS who underwent NRT and resection were identified using the National Cancer Database (2006-2019). Predictors of NCT were analyzed using logistic regression. Change in rate of NCT use over time was assessed using log-linear regression modeling. Survival was examined using Kaplan-Meier (KM) and Cox proportional hazard modeling. RESULTS: Of 5740 patients, 25% underwent NCT. The overall median age was 62, 55% of patients were male, and 67% had stage III disease. The most common histological subtypes were fibrosarcoma/myxofibrosarcoma (39%) and liposarcoma (16%). Use of NCT decreased by 4.0% per year throughout the study period (p < 0.01). Predictors of NCT included younger age (median 54, IQR 42-64 vs. median 65, IQR 53-75, p < 0.01), treatment at an academic center (odds ratio [OR] 1.5, p < 0.01), and stage III disease (OR 2.2, p < 0.01). Histologic predictors of NCT included synovial sarcoma (52%) and angiosarcoma (45%). With a median follow-up time of 77 months, NCT was associated with improved 5-year survival compared to NRT alone on KM analysis (70% vs. 63%, p < 0.01). This difference persisted on multivariate analysis (hazard ratio 0.86, p = 0.027) and after propensity matching (70% vs. 65%, p = 0.0064). CONCLUSION: Despite risk of distant failure in high-risk STS, use of NCT has decreased over time in patients receiving NRT. In this retrospective analysis, NCT was associated with a modestly improved overall survival.

Impact of Patient Comorbidities on Presentation Stage of Breast and Colon Cancers.

BACKGROUND: While patients with multiple comorbidities may have frequent contact with medical providers, it is unclear whether their healthcare visits translate into earlier detection of cancers, specifically breast and colon cancers. METHODS: Patients diagnosed with stage I-IV breast ductal carcinoma and colon adenocarcinoma were identified from the National Cancer Database and stratified by comorbidity burden, dichotomized as a Charlson Comorbidity Index (CCI) Score of <2 or ≥2. Characteristics associated with comorbidities were analyzed by univariate and multivariate logistic regression. Propensity-score matching was performed to determine the impact of CCI on stage at cancer diagnosis, dichotomized as early (I-II) or late (III-IV). RESULTS: A total of 672,032 patients with colon adenocarcinoma and 2,132,889 with breast ductal carcinoma were included. Patients with colon adenocarcinoma who had a CCI ≥ 2 (11%, n = 72,620) were more likely to be diagnosed with early-stage disease (53% vs. 47%; odds ratio [OR] 1.02, p = 0.017), and this finding persisted after propensity matching (CCI ≥ 2 55% vs. CCI < 2 53%, p < 0.001). Patients with breast ductal carcinoma who had a CCI ≥ 2 (4%, n = 85,069) were more likely to be diagnosed with late-stage disease (15% vs. 12%; OR 1.35, p < 0.001). This finding also persisted after propensity matching (CCI ≥ 2 14% vs. CCI < 2 10%, p < 0.001). CONCLUSIONS: Patients with more comorbidities are more likely to present with early-stage colon cancers but late-stage breast cancers. This finding may reflect differences in practice patterns for routine screening in these patients. Providers should continue guideline directed screenings to detect cancers at an earlier stage and optimize outcomes.

Frailty Assessment and Prehabilitation as Part of a PeRioperative Evaluation and Planning (PREP) Program for Patients Undergoing Colorectal Surgery.

Frailty assessment and prehabilitation can be incrementally implemented in a multidisciplinary, multiphase pathway to improve patient care. To start, modifications can be made to a surgeon's practice with existing resources while adapting standard pathways for frail patients. Frailty screening can identify patients in need of additional assessment and optimization. Personalized utilization of frailty data for optimization through prehabilitation can improve postoperative outcomes and identify patients who would benefit from adapted care. Additional utilization of the multidisciplinary team can lead to improved outcomes and a strong business case to add additional members of the team.

Radiation, Lymph Node Dissection, or Both: Management of Lymph Node Micrometastases from Merkel Cell Carcinoma.

BACKGROUND: Regional lymph node micrometastases from Merkel cell carcinoma (MCC) can be treated with completion lymph node dissection (CLND) and/or radiation therapy (RT). It is unclear how these options compare in terms of survival benefits for patients. PATIENTS AND METHODS: This retrospective cohort study used data from years 2012-2019 of the National Cancer Database. Patients with MCC and clinically negative, but pathologically positive, lymph node metastases who received RT to and/or CLND of the regional lymph node basin were included. Inverse probability weight balancing was performed using covariates followed by Cox proportional hazards modeling for survival analysis. RESULTS: A total of 962 patients were included [median (interquartile range) age, 74 (67-80) years, 662 (68.8%) male patients, 926 (96.3%) white patients]. The majority (63%, n = 606) had a CLND only, while 18% (n = 173) had RT only, and 19% (n = 183) had both CLND and RT. From 2016 to 2019, usage of RT only increased from 10% to 31.8%. Multivariate analysis demonstrated that treatment modality was not associated with survival [RT versus CLND, hazard ratio (HR) 0.842, 95% confidence interval (CI) 0.621-1.142, p = 0.269, RT+CLND versus CLND, HR 1.029, 95% CI 0.775-1.367, p = 0.844]. This persisted after balancing weights (RT versus CLND, HR 0.837, 95% CI 0.614-1.142, p = 0.262, RT+CLND versus CLND, HR 1.085, 95% CI 0.801-1.470, p = 0.599). CONCLUSIONS: The usage of RT for nodal micrometastasis in MCC is increasing as compared with CLND. This strategy appears to be safe, with no significant difference in survival outcomes.

Clinical Trials in Melanoma: Margins, Lymph Nodes, Targeted and Immunotherapy.

Multiple randomized controlled trials have influenced the current standard of care for patients with cutaneous melanoma. Since the development of targeted and immune therapy, studies of adjuvant therapy for patients with resected stage III/IV melanoma have led to the approval of combined B-raf proto-oncogene (BRAF) and mitogen-activated protein kinase kinase inhibitors for patients with a BRAF mutation, and cytotoxic T-lymphocyte associated protein-4 or antiprogrammed cell death-1 therapy for patients without a BRAF mutation. This article discusses the details of the trials that have influenced these treatment decisions, in addition to discussing ongoing trials and possible future directions.

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.