Faculty Bibliography

BACKGROUND:Neoadjuvant chemotherapy (NAC) is standard management for localized gastric cancer (GC). Attrition during NAC due to treatment-related toxicity or functional decline is considered a surrogate for worse biologic outcomes; however, data supporting this paradigm are lacking. We investigated factors predicting attrition and its association with overall survival (OS) in GC. METHODS:Patients with nonmetastatic GC initiating NAC were identified from the US Safety-Net Collaborative (2012-2014). Patient/treatment-related characteristics were compared between attrition/nonattrition cohorts. Cox models determined factors associated with OS. RESULTS:Of 116 patients initiating NAC, attrition during prescribed NAC occurred in 24%. No differences were observed in performance status, comorbidities, treatment at safety-net hospital, or clinicopathologic factors between cohorts. Despite absence of distinguishing factors, attrition was associated with worse OS (median: 11 vs. 37 months; p = 0.01) and was an independent predictor of mortality (hazard ratio [HR]: 4.7, 95% confidence interval [CI]: 1.5-15.2; p = 0.02). Fewer patients with attrition underwent curative-intent surgery (39% vs. 89%; p < 0.001). Even in patients undergoing surgical exploration (n = 89), NAC attrition remained an independent predictor of worse OS (HR: 50.8, 95% CI: 3.6-717.8; p = 0.004) despite similar receipt of adjuvant chemotherapy. CONCLUSION/CONCLUSIONS:Attrition during NAC for nonmetastatic GC is independently associated with worse OS, even in patients undergoing surgery. Attrition during NAC may reflect unfavorable tumor biology not captured by conventional staging metrics.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Perioperative therapy is a favored treatment strategy for gastric cancer. We sought to assess utilization of this approach at safety net hospitals (SNH) and tertiary referral centers (TRC). MATERIALS AND METHODS/METHODS:Patients in the US Safety Net Collaborative (2012-2014) with resectable gastric cancer across five SNH and their sister TRC were included. Primary outcomes were receipt of neoadjuvant chemotherapy (NAC) and perioperative therapy. RESULTS:Of 284 patients, 36% and 64% received care at SNH and TRC. The distribution of Stage II/III resectable disease was similar across facilities. Receipt of NAC at SNH and TRC was similar (56% vs. 46%, p = 0.27). Compared with overall clinical stage, 38% and 36% were pathologically downstaged at SNH and TRC, respectively. Among patients who received NAC, those who also received adjuvant chemotherapy at SNH and TRC were similar (66% vs. 60%, p = 0.50). Asian race and higher clinical stage were associated with receipt of perioperative therapy (both p < 0.05) while treatment facility type was not. CONCLUSIONS:There was no difference in utilization of a perioperative treatment strategy between facility types for patients with gastric cancer. Pathologic downstaging from NAC was similar across treatment facilities, suggesting similar quality and duration of therapy. Treatment at an SNH is not a barrier to receiving standard-of-care perioperative therapy for gastric cancer.

BACKGROUND:Hispanic patients have a higher incidence of gastric cancer when compared to non-Hispanics. Outlining clinicodemographic characteristics and assessing the impact of ethnicity on stage-specific survival may identify opportunities to improve gastric cancer care for this population. METHODS:Patients with gastric cancer in the US Safety Net Collaborative (2012-2014) were retrospectively reviewed. Demographics, clinicopathologic characteristics, operative details, and outcomes were compared between Hispanic and non-Hispanic patients. Early onset gastric cancer was defined as age <50 years. Kaplan-Meier and Cox proportional-hazards models were used to identify the impact of ethnicity on disease-specific survival (DSS). RESULTS:Seven hundred and ninety-seven patients were included, of which 219 (28%) were Hispanic. Hispanic patients were more likely to seek care at safety-net hospitals (66 vs 39%) and be uninsured (36 vs 17%), and less likely to have a primary care provider (PCP) (46 vs 75%; all P<0.05). Hispanic patients were twice as likely to present with early onset gastric cancer (28 vs 15%) and were more frequently diagnosed in the emergency room (54 vs 37%) with both abdominal pain and weight loss (44 vs 31%; all P <0.05). Treatment paradigms, operative outcomes, and DSS were similar between Hispanic and non-Hispanic patients when accounting for cancer stage. Cancer stage, pathologically positive nodes, and negative surgical margins were independently associated with DSS. CONCLUSIONS:A diagnosis of gastric cancer must be considered in previously healthy Hispanic patients who present to the emergency room with both abdominal pain and weight loss. Fewer than 50% of Hispanic patients have a PCP, indicating poor outpatient support. Efforts to improve outpatient support and screening may improve gastric cancer outcomes in this vulnerable population.

BACKGROUND:For patients with sentinel lymph node (SLN)-positive cutaneous melanoma, the Second Multicenter Selective Lymphadenectomy trial demonstrated equivalent disease-specific survival (DSS) with active surveillance using nodal ultrasound versus completion lymph node dissection (CLND). Adoption and outcomes of active surveillance in clinical practice and in adjuvant therapy recipients are unknown. METHODS:In a retrospective cohort of SLN-positive adults treated at 21 institutions in Australia, Europe, and the United States from June 2017 to November 2019, the authors evaluated the impact of active surveillance and adjuvant therapy on all-site recurrence-free survival (RFS), isolated nodal RFS, distant metastasis-free survival (DMFS), and DSS using Kaplan-Meier curves and Cox proportional hazard models. RESULTS:Among 6347 SLN biopsies, 1154 (18%) were positive and had initial negative distant staging. In total, 965 patients (84%) received active surveillance, 189 (16%) underwent CLND. Four hundred thirty-nine patients received adjuvant therapy (surveillance, 38%; CLND, 39%), with the majority (83%) receiving anti-PD-1 immunotherapy. After a median follow-up of 11 months, 220 patients developed recurrent disease (surveillance, 19%; CLND, 22%), and 24 died of melanoma (surveillance, 2%; CLND, 4%). Sixty-eight patients had an isolated nodal recurrence (surveillance, 6%; CLND, 4%). In patients who received adjuvant treatment without undergoing prior CLND, all isolated nodal recurrences were resectable. On risk-adjusted multivariable analyses, CLND was associated with improved isolated nodal RFS (hazard ratio [HR], 0.36; 95% CI, 0.15-0.88), but not all-site RFS (HR, 0.68; 95% CI, 0.45-1.02). Adjuvant therapy improved all-site RFS (HR, 0.52; 95% CI, 0.47-0.57). DSS and DMFS did not differ by nodal management or adjuvant treatment. CONCLUSIONS:Active surveillance has been adopted for most SLN-positive patients. At initial assessment, real-world outcomes align with randomized trial findings, including in adjuvant therapy recipients. LAY SUMMARY/UNASSIGNED:For patients with melanoma of the skin and microscopic spread to lymph nodes, monitoring with ultrasound is an alternative to surgically removing the remaining lymph nodes. The authors studied adoption and real-world outcomes of ultrasound monitoring in over 1000 patients treated at 21 centers worldwide, finding that most patients now have ultrasounds instead of surgery. Although slightly more patients have cancer return in the lymph nodes with this strategy, typically, it can be removed with delayed surgery. Compared with up-front surgery, ultrasound monitoring results in the same overall risk of melanoma coming back at any location or of dying from melanoma.

BACKGROUND:Access to health insurance and curative interventions [surgery/liver-directed-therapy (LDT)] affects survival for early-stage hepatocellular carcinoma (HCC). The aim of this multi-institutional study of high-volume safety-net hospitals (SNHs) and their tertiary-academic-centers (AC) was to identify the impact of type/lack of insurance on survival disparities across hospitals, particularly SNHs whose mission is to minimize insurance related access-to-care barriers for vulnerable populations. METHODS:Early-stage HCC patients (2012-2014) from the US Safety-Net Collaborative were propensity-score matched by treatment at SNH/AC. Overall survival (OS) was the primary outcome. Multivariable Cox proportional-hazard analysis was performed accounting for sociodemographic/clinical parameters. RESULTS:Among 925 patients, those with no insurance (NI) had decreased curative surgery, compared to those with government insurance (GI) and private insurance [PI, (PI-SNH:60.5% vs. GI-SNH:33.1% vs. NI-SNH:13.6%, p < 0.001)], and decreased median OS (PI-SNH:32.1 vs. GI-SNH:22.8 vs. NI-SNH:9.4 months, p = 0.002). On multivariable regression controlling for sociodemographic/clinical parameters, NI-SNH (HR:2.5, 95% CI:1.3-4.9, p = 0.007) was the only insurance type/hospital system combination with significantly worse OS. CONCLUSION/CONCLUSIONS:NI-SNH patients received less curative treatment than other insurance/hospitals types suggesting that treatment barriers, beyond access-to-care, need to be identified and addressed to achieve survival equity in early-stage HCC for vulnerable populations (NI-SNH).

BACKGROUND:In sentinel lymph node (SLN)-positive melanoma, two randomized trials demonstrated equivalent melanoma-specific survival with nodal surveillance vs completion lymph node dissection (CLND). Patients with microsatellites, extranodal extension (ENE) in the SLN, or >3 positive SLNs constitute a high-risk group largely excluded from the randomized trials, for whom appropriate management remains unknown. STUDY DESIGN/METHODS:SLN-positive patients with any of the three high-risk features were identified from an international cohort. CLND patients were matched 1:1 with surveillance patients using propensity scores. Risk of any-site recurrence, SLN-basin-only recurrence, and melanoma-specific mortality were compared. RESULTS:Among 1,154 SLN-positive patients, 166 had ENE, microsatellites, and/or >3 positive SLN. At 18.5 months median follow-up, 49% had recurrence (vs 26% in patients without high-risk features, p < 0.01). Among high-risk patients, 52 (31%) underwent CLND and 114 (69%) received surveillance. Fifty-one CLND patients were matched to 51 surveillance patients. The matched cohort was balanced on tumor, nodal, and adjuvant treatment factors. There were no significant differences in any-site recurrence (CLND 49%, surveillance 45%, p = 0.99), SLN-basin-only recurrence (CLND 6%, surveillance 14%, p = 0.20), or melanoma-specific mortality (CLND 14%, surveillance 12%, p = 0.86). CONCLUSIONS:SLN-positive patients with microsatellites, ENE, or >3 positive SLN constitute a high-risk group with a 2-fold greater recurrence risk. For those managed with nodal surveillance, SLN-basin recurrences were more frequent, but all-site recurrence and melanoma-specific mortality were comparable to patients treated with CLND. Most recurrences were outside the SLN-basin, supporting use of nodal surveillance for SLN-positive patients with microsatellites, ENE, and/or >3 positive SLN.

BACKGROUND:While hepatocellular carcinoma (HCC) is ideally diagnosed outpatient by screening at-risk patients, many are diagnosed in Emergency Departments (ED) due to undiagnosed liver disease and/or limited access-to-healthcare. This study aims to identify sociodemographic/clinical factors associated with being diagnosed with HCC in the ED to identify patients who may benefit from improved access-to-care. METHODS:HCC patients diagnosed between 2012 and 2014 in the ED or an outpatient setting [Primary Care Physician (PCP) or hepatologist] were identified from the US Safety-Net Collaborative database and underwent retrospective chart-review. Multivariable regression identified predictors for an ED diagnosis. RESULTS:Among 1620 patients, median age was 60, 68% were diagnosed outpatient, and 32% were diagnosed in the ED. ED patients were more likely male, Black/Hispanic, uninsured, and presented with more decompensated liver disease, aggressive features, and advanced clinical stage. On multivariable regression, controlling for age, gender, race/ethnicity, poverty, insurance, and PCP/navigator access, predictors for ED diagnosis were male (odds ratio [OR] 1.6, 95% confidence interval [CI]: 1.1-2.2, p = 0.010), black (OR 1.7, 95% CI: 1.2-2.3, p = 0.002), Hispanic (OR 1.6, 95% CI: 1.1-2.6, p = 0.029), > 25% below poverty line (OR 1.4, 95% CI: 1.1-1.9, p = 0.019), uninsured (OR 3.9, 95% CI: 2.4-6.1, p < 0.001), and lack of PCP (OR 2.3, 95% CI: 1.5-3.6, p < 0.001) or navigator (OR 1.8, 95% CI: 1.3-2.5, p = 0.001). CONCLUSIONS:The sociodemographic/clinical profile of patients diagnosed with HCC in EDs differs significantly from those diagnosed outpatient. ED patients were more likely racial/ethnic minorities, uninsured, and had limited access to healthcare. This study highlights the importance of improved access-to-care in already vulnerable populations.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Surgical resection is indicated for hepatocellular carcinoma (HCC) patients with Child A cirrhosis. We hypothesize that surgical intervention and survival are limited by advanced HCC presentation at safety net hospitals (SNHs) versus academic medical centers (AMCs). METHODS:Patients with HCC and Child A cirrhosis in the US Safety Net Collaborative (2012-2014) were evaluated. Demographics, clinicopathologic features, operative characteristics, and outcomes were compared between SNHs and AMCs. Liver transplantation was excluded. Kaplan-Meier and Cox proportional-hazards models were used to identify the effect of surgery on overall (OS). RESULTS:A total of 689 Child A patients with HCC were identified. SNH patients frequently presented with T3/T4 stage (35% vs. 24%) and metastases (17% vs. 8%; p < .05). SNH patients were as likely to undergo surgery as AMC patients (17% vs. 18%); however, SNH patients were younger (56 vs. 64 years), underwent minor hepatectomy (65% vs. 38%), and frequently harbored well-differentiated tumors (23% vs. 2%; p < .05). On multivariate analysis, surgical resection and stage, but not hospital type, were associated with improved OS. CONCLUSIONS:Although SNH patients present with advanced HCC, survival outcomes for early stage HCC are similar at SNHs and AMCs. Identifying barriers to early diagnosis at SNH may increase surgical candidacy and improve outcomes.

Clinical trials have demonstrated the efficacy of immunotherapy, especially checkpoint blockade inhibitors, in the treatment of patients with metastatic melanoma. More recently, improvements in survival have been reported in patients with high-risk resectable melanoma when these agents are used in the adjuvant setting. Increasing interest in neoadjuvant immunotherapy for high-risk resectable melanoma has been fueled by early reports of significant efficacy. We review the rationale and data behind utilizing neoadjuvant immunotherapy.