Abstract Purpose: Neoadjuvant anti–PD-1 therapy in melanoma may increase tumor-infiltrating lymphocytes (TIL), and more TIL are associated with better treatment response. A major pathologic response (MPR) in melanoma after neoadjuvant anti–PD-1 therapy usually comprises tumor necrosis and fibrosis. The role of TIL in necrotic tumor necrosis (nTIL) has not been explored. Experimental Design: We performed CD3 and CD8 IHC stains on 41 melanomas with geographic necrosis. Of the 41, 14 were immunotherapy-naïve, and 27 had been treated with one dose of neoadjuvant anti–PD-1 in two clinical trials. CD3+ and CD8+ nTIL were graded as absent/minimal or moderate/brisk. The percentage of necrotic areas in the tumor bed before and after treatment was quantified. The endpoints were MPR and 5-year recurrence-free survival (RFS). Results: In the immunotherapy-naïve cohort, 3/14 (21%) specimens had moderate/brisk CD3+, and 2/14 (14%) had moderate/brisk CD8+ nTIL. In the treated cohort, 16/27 (59%) specimens had moderate/brisk CD3+, and 15/27 (56%) had moderate/brisk CD8+ nTIL, higher than those of the naïve cohort (CD3, P = 0.046; CD8, P = 0.018). Tumor necrosis was significantly increased after anti–PD-1 therapy (P = 0.007). In the treated cohort, moderate/brisk CD3+ and CD8+ nTIL correlated with MPR (P = 0.042; P = 0.019, respectively). Treated patients with moderate/brisk CD3+ nTIL had higher 5-year RFS than those with absent/minimal nTIL (69% vs. 0%; P = 0.006). This persisted on multivariate analysis (HR, 0.16; 95% confidence interval, 0.03–0.84; P = 0.03), adjusted for pathologic response, which was borderline significant (HR, 0.26; 95% confidence interval, 0.07–1.01; P = 0.051). Conclusions: CD3+ and CD8+ nTIL are associated with pathologic response and 5-year RFS in patients with melanoma after neoadjuvant anti–PD-1 therapy.

BackgroundMerkel cell carcinoma (MCC) is a radiosensitive aggressive skin cancer that spreads via the lymphatics. There is uncertainty regarding the optimal management of the nodal basin for patients with MCC with clinically positive nodes. We study the efficacy of single node excision (SNE) as an alternative to a therapeutic lymph node dissection (TLND) in patients with limited nodal disease.MethodsWe performed a retrospective cohort study of patients with MCC with clinical nodal disease who underwent resection in the form of either SNE or TLND using the National Cancer Database. The association between type of surgery and overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional hazards modeling.Results1835 patients met all inclusion criteria with 281 patients undergoing SNE and the remainder undergoing TLND. Patients receiving SNE and TLND were equally likely to receive radiation to the nodal basin (SNE 44.5% vs. TLND 48.5%, p = 0.22). There was no difference in 5-year OS between patients who received SNE versus TLND (SNE 43.9% vs. TLND 44.7%, p = 0.36). This persisted in a multivariable Cox proportional hazards model in which receipt of SNE remained not significantly associated with survival after adjusting for clinical and treatment factors including receipt of radiation (Hazard Ratio [HR] 1.17, 95% CI 0.96-1.42, p = 0.11). In patients undergoing SNE with radiation, 5-year OS was 54.4% (95% CI 44.1-63.6).ConclusionsTLND is not associated with a survival advantage over SNE. Further prospective study into patterns of recurrence and safety of SNE is needed.

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.

Introduction: Malignant bowel obstructions (MBO) are complex, heterogeneous disease processes which can be managed with surgical or endoscopic interventions. Patients with MBO often have advanced metastatic disease and poor functional status, which makes it difficult for providers to determine the best treatment strategy. Methods: Patients with urgent or emergent admissions and a primary or secondary ICD-9/ICD-10 diagnosis of bowel obstruction with an additional diagnosis of disseminated cancer were identified from the National Inpatient Sample (2000-2017). Patients were stratified into operative and non-operative intervention groups. Multivariate regression determined factors associated with surgical treatment of MBO based on significant factors on univariate analysis. Trends in treatment over time were calculated using log-linear regression to determine the annual percent change (APC). Results: Of 1118 patients, 18% underwent surgery and 7% underwent endoscopic intervention. From 2000 to 2017, a decreasing proportion of patients underwent surgery (APC -2.4, p = 0.023) with a commensurate increase in endoscopic interventions (APC 5.3, p = 0.042). There was also a decrease in the proportion of patients who died during hospitalization (APC -4.3, p = 0.029). Surgery was associated with longer mean lengths of stay (13 days vs. 7 days, p < 0.001) and higher rates of in-hospital mortality (13% vs. 6%, p = 0.001) compared to non-operative management. Conclusion: The proportion of patients receiving surgery for MBO is decreasing and that receiving endoscopic interventions is increasing. In-hospital mortality is also decreasing proportionately, suggesting an improvement in patient selection.

All supplemental data (Supp Figs S1-S4)

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.

Vision researchers have investigated the differences between global and local feature perception. No one has, however, examined the role of global and local feature discrimination in sustained attention tasks. In this experiment participants performed a sustained attention task requiring either global or local letter target discriminations or watched the same displays without any work imperative. Reaction time to targets was slower when global feature discriminations were required than when local feature discriminations were required. Tympanic membrane temperature (TMT) was utilized in this study as an index of cerebral activation. Participants in the global letter detection condition had elevated post-task right TMT, indicative of reduced cerebral activation in the right hemisphere, in comparison to participants in the local letter detection or no-work imperative conditions. Both the performance and physiological results of this study indicate increased cognitive fatigue when global feature discriminations are required.

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.

Straker, Richard III MD; Sharon, Cimarron MD; Wood, Christian BA; Kelly, Nicholas J BA; Ahmad, Nuzhat A MD; El Jack, Amr K MD, PhD; Miura, John T MD; DeMatteo, Ronald P MD, FACS; Karakousis, Giorgos C MD, FACS; Roses, Robert E MD, FACS Author Information

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.

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.

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.

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+.