Adherence Disparities and Utilization Trends of Oncotype Dx Assay: A National Cancer Database Study.

INTRODUCTION: Oncotype Dx (ODX) is a genetic assay that analyzes tumor recurrence risk and provides chemotherapy recommendations for T1-T2 stage, hormone receptor-positive, human epidermal growth factor receptor-negative, and nodal-negative breast cancer patients. Despite its established validity, the utilization of this assay is suboptimal. The study aims to evaluate factors that are associated with adherence rate with the testing guidelines and examine changes in utilization trends. METHODS: This is a retrospective study, utilizing data from the National Cancer Database from 2010 to 2017. Patients who met the ODX testing guidelines were first evaluated for testing adherence. Secondly, all patients who underwent ODX testing were assessed to evaluate the trend in ODX utilization. RESULTS: A total of 429,648 patients met the criteria for ODX, and 43.4% of this population underwent testing. Advanced age, racial minorities, low-income status, well-differentiated tumor grade, uninsured status, and treatment at community cancer centers were associated with a decreased likelihood of receiving ODX in eligible patients. Additionally, a notable amount of testing was performed on patients who did not meet the ODX testing criteria. Among the 295,326 patients that underwent ODX testing, 16.6% of patients were node-positive and 1.8% had T3 or T4 stage tumors. CONCLUSIONS: A considerable number of patients who were eligible for ODX did not receive it, indicating potential barriers to care and disparities in breast cancer treatment. ODX usage has been expanded to broader patient populations, indicating more research is needed to validate the effectiveness of the assay in these patient groups.

Clinical T2N0M0 Esophageal Cancer-Is Treatment Pathway Associated With Overall Survival?

INTRODUCTION: Esophageal cancer therapy is commonly multimodal. The CROSS trial demonstrated a survival benefit of neoadjuvant chemoradiation versus surgery alone in T1N1 or T2-3N0-1 patients. Theoretically, chemoradiation should be most beneficial to patients with advanced disease. Treating the intermediary stage, T2N0M0, is challenging as national guidelines offer multiple options. This study aims to compare survival outcomes and associated factors in clinical T2N0M0 esophageal cancer via treatment modality and compare clinical to pathological stage. The authors conclude that neoadjuvant therapy use has increased; however, there is no associated survival benefit, which may be due to over- or under-staging. METHODS: A retrospective study was performed using the National Cancer Database (2006-2016). Patients who underwent neoadjuvant chemoradiation followed by surgery (NCRT + ESOPH) were compared to patients who underwent esophagectomy first (ESOPH). Multivariable logistic regression was used to determine factors associated with treatment pathway. Overall survival was compared using Kaplan-Meier estimates and log-rank tests at 1-, 3-, and 5-y post-treatment. Additionally, a multiple logistic regression analysis was conducted to identify factors associated with adjuvant therapy in ESOPH patients. RESULTS: There were 1662 patients (NCRT + ESOPH: 904 [54.4%], ESOPH: 758 [45.6%]). There was no difference in 5-y survival between NCRT + ESOPH and ESOPH patients. Despite this, NCRT + ESOPH treatment rates rose from 33% to 74% between 2006 and 2016. Patients who received NCRT + ESOPH were younger and more commonly had no Charlson-Deyo comorbidities. Notably, 41% of patients were over-staged (T1 or lower), and 32.8% were under-staged (N ≥ 1). CONCLUSIONS: T2N0M0 remains difficult to characterize, and pathological staging corresponds poorly to clinical staging. Neoadjuvant therapy use has increased; however, the lack of a significant survival benefit to correlate with such may be secondary to over- or under-staging.

Quality Improvement for Surgical Resection of Pancreatic Head Adenocarcinoma : Hospital and Surgeon Predictors of Higher Than Expected R1 Resection Using the National Cancer Database.

BACKGROUND: The mainstay of treatment for pancreatic cancer is surgical resection; however, positive surgical margins remain commonplace. We identified hospitals with higher than predicted rates of positive margins and isolated factors that caused this discordance. METHODS: This is a retrospective review of patients with head of the pancreas adenocarcinoma in the National Cancer Database between 2004 and 2015. A nomogram was used to calculate the observed to expected positive margin rates (O/E) for facilities. If the O/E differed significantly (P < .05), it was considered an outlier. RESULTS: Among a total of 19 968 patients, 24.3% had positive margins. Among hospitals with lower than expected positive margin rates, 73.6% were academic or research programs, 17% were comprehensive community cancer programs, and none were community cancer programs (P = .0002). Within the group with higher than expected positive margin rates, 47% were comprehensive community cancer programs and 38.6% were academic or research programs (P = .0002). The mean hospital volume was higher in the low positive margin group (110.4 vs 48.8, P < .0001). CONCLUSIONS: Facility type and hospital volume can predict improvement in the O/E ratio for margin positivity in pancreatic adenocarcinoma resection. Surgeons should consider referral to academic or research facilities with higher case volumes for improved surgical resection.

MAGIC versus MacDonald treatment regimens for gastric cancer: Trends and predictors of multimodal therapy for gastric cancer using the National Cancer Database.

BACKGROUND: Multimodal therapy is beneficial in gastric cancer, however this practice is not universal. This study examines trends, identifies associative factors, and examines overall survival (OS) benefit from multimodal therapy in gastric cancer. METHODS: Gastric cancer patients staged IB-III from 2005 to 2014, identified using the National Cancer Database, were categorized by treatment: surgery alone, perioperative chemotherapy, and adjuvant chemoradiation. Groups were analyzed to identify associative factors of perioperative therapy. RESULTS: We examined 9243 patients, with the majority receiving multimodal therapy (57%). The proportion of those receiving perioperative chemotherapy rose dramatically from 7.5% in 2006 to 46% in 2013. Academic center treatment was strongly associated with perioperative over adjuvant therapy (p < 0.0001). An OS advantage was clearly seen in those receiving multimodal therapy versus surgery alone (p < 0.0001), with no difference between perioperative and adjuvant therapies. CONCLUSIONS: Treatment of gastric cancer with multimodal therapy has risen significantly since 2005, largely due to increasing use of perioperative chemotherapy. As perioperative therapy becomes more prevalent, more patients will have the opportunity for the improved survival benefit of multimodal therapy.

Disparities in Care: Impact of Socioeconomic Factors on Pancreatic Surgery: Exploring the National Cancer Database.

Studies have shown high-volume institutions have decreased mortality and increased survival for pancreatectomy. However, not all patients can travel to high-volume centers. Socioeconomic factors may influence treatment decisions. The goal of this study is to examine socioeconomic factors that determine where a patient is treated and how that location affects outcome. This is a retrospective study of the National Cancer Database of patients diagnosed with pancreatic cancer from 2004 to 2014. The primary outcome was to examine socioeconomic factors that predicted where a patient underwent their pancreatectomy. Patients treated at academic programs (APs) had to travel a mean distance of 80.9 miles, whereas patients treated at community programs (CPs) had to travel 31.7 miles (P < 0.0001). Spanish and Hispanic patients were less likely to travel to an AP (69% had surgery at an AP versus 76% of non-Hispanic patients, P < 0.001). Patients with higher comorbidities were also more likely to have care at CPs. Patients who had pancreatic cancer surgery at CPs were more likely to be Hispanic or with higher medical comorbidities. Those who had surgery at AP traveled further distances but had better perioperative outcomes and had an improvement in overall survival.

Lymph Node Harvest as a Measure of Quality and Effect on Overall Survival in Esophageal Cancer: A National Cancer Database Assessment.

Surgical therapy for esophageal cancer is the cornerstone of treatment, and the highest quality operation should lead to the highest cure rate. Evaluated lymph node (ELN) count is one quality measure that has been championed. The objective of this study was to explore ELN in esophagectomy, examine predictors of harvesting ≥12 nodes, and determine whether higher ELN improves overall survival (OS). ELN was examined in patients with resected esophageal cancer using the National Cancer Database from 2004 to 2013. In this study, 41,746 patients met the inclusion criteria. Fifty-two per cent of patients had 12 or more nodes harvested. Academic programs were most likely to harvest ≥12 nodes (58% of cases) compared with other programs (43-56% of cases). Seventy per cent of cases with ≥12 nodes harvested were performed at high-volume centers. Preoperative radiation or preoperative chemoradiation led to lower ELN (46% and 48%) versus preoperative chemotherapy alone (66%). Multivariate analysis showed that patients who had ≥12 nodes removed had better OS (Hazard Ratio 0.843 [95 confidence interval 0.820-0.867]). In addition, care at a high-volume facility, care at an academic facility, private insurance, and income ≥$63,000 were all associated with improved OS. Higher ELN count is associated with OS in patients with esophageal cancer. Patients who receive care at high-volume centers and academic centers are more likely to undergo more extensive lymphadenectomy. All centers should strive to examine at least 12 nodes to provide a quality esophagectomy.

Laparoscopic versus robotic adrenalectomy: a review of the national inpatient sample.

BACKGROUND: Laparoscopic adrenalectomy (LA) has become the standard treatment of adrenal lesions. Recently, robotic-assisted adrenalectomy (RA) has become an option, however, short-term outcomes for RA have not been well studied and benefits over LA are debatable. The aim of this study was to explore differences in short-term outcomes between LA and RA using the national inpatient sample (NIS) database. METHODS: Patient data were collected from the NIS. All patients undergoing LA or RA from January 2009 to December 2012 were included. Univariate analysis and propensity matching were performed to look for differences between the groups. RESULTS: A total of 1006 patients (66.4% in LA group and 33.6% in RA group) were identified. Patient age group, gender, race, risk of mortality, severity of illness or indication for adrenalectomy did not differ significantly between the LA or RA cohorts. Insurance type predicted procedure type (45% of medicare patients underwent RA versus 29% of patients with private insurance, p < 0.0001). Patients living in the highest income areas were more likely to receive the laparoscopic approach (31.7 versus 17.4%, p < 0.0001). Hospital volume, bed size and teaching status of the hospital were not significant factors in the decision of RA versus LA. There was no difference in complication and conversion rates between RA versus LA. The mean length of stay was shorter in the RA group (2.2 versus 1.9 days, p = 0.03). Total charges were higher in the RA group ($42,659 versus $33,748, p < 0.0001). There was a significant trend towards more adrenalectomies being performed robotic assisted by year. Only 22% of adrenalectomies were performed robotic-assisted in 2009 compared with 48% in 2012. CONCLUSIONS: The overall benefit for RA remains small and higher total charges for RA may currently outweigh the benefits. These findings may change as more cases are performed robotically assisted and robotic technology improves.

Neoadjuvant versus Adjuvant Chemotherapy for Resectable Pancreatic Adenocarcinoma: A National Cancer Database Analysis.

There is controversy regarding the role of neoadjuvant versus adjuvant chemotherapy for pancreatic cancer (PAC). Neoadjuvant therapy has been touted as a method to improve survival in PAC patients. This study's objective is to investigate predictors and potential benefits of neoadjuvant therapy in resectable PAC patients. The National Cancer Data Base was used to retrospectively analyze stage I and II surgically resected PAC patients receiving adjuvant or neoadjuvant therapy from 2004 to 2012. A total of 12,983 patients were identified. A significant increase in the rate of neoadjuvant therapy was observed over time with 5 per cent receiving neoadjuvant therapy in 2004 versus 17 per cent in 2012 (P < 0.0001). Multivariate analysis showed that patients were more likely to receive neoadjuvant therapy if they were treated at an academic facility. Private insurance was associated with higher odds of neoadjuvant chemotherapy (P < 0.0001). Pathological outcomes were improved in neoadjuvant patients compared with adjuvant patients on multivariate analysis with neoadjuvant patients having higher rates of negative surgical margins (OR: 1.273, 95% Confidence interval: 1.099-1.474) and negative lymph nodes (OR: 2.852, 95% Confidence interval: 2.547-3.194). Pathological outcomes are improved after neoadjuvant therapy compared with adjuvant therapy, with more patients achieving negative margins and negative lymph nodes. Prospective studies are needed to compare these two treatment modalities in a head to head comparison.

Outcomes of complicated appendicitis: Is conservative management as smooth as it seems?

BACKGROUND: This study characterized the failure rate of non-operative management (NOM) for complicated appendicitis (CA; perforation, abscess, phlegmon), and compared outcomes among patients undergoing acute appendectomy (AA), elective interval appendectomy (EIA), and unplanned appendectomy after failing to improve with NOM. METHODS: Adults treated at one facility between 2007 and 2014 were retrospectively studied. RESULTS: Ninety-five patients presented with CA. Sixty individuals underwent AA. The remaining 35 patients initially underwent NOM: 14 underwent EIA, nine (25.7%) failed NOM, 12 never underwent surgery. All patients failing NOM had an open operation with most (55.6%) requiring bowel resection. AA and EIA were comparable in surgical approach, bowel resection and post-operative readmission. However, AA demonstrated a lower incidence of bowel resection (3.3% vs 17.1%, P = 0.048) when compared to all patients initially undergoing NOM. CONCLUSIONS: Due to the high incidence of failed NOM and the morbidity associated with failure, AA may be appropriate for CA.

Characterizing the Relationship Between Surgical Resident and Faculty Perceptions of Autonomy in the Operating Room.

OBJECTIVE: Characterize the concordance among faculty and resident perceptions of surgical case complexity, resident technical performance, and autonomy in a diverse sample of general surgery procedures using case-specific evaluations. DESIGN: A prospective study was conducted in which a faculty surgeon and surgical resident independently completed a postoperative assessment examining case complexity, resident operative performance (Milestone assessment) and autonomy (Zwisch model). Pearson correlation coefficients (r) reaching statistical significance (p < 0.05) were further classified as moderate (r ≥ 0.40), strong (r ≥ 0.60), or very strong (r ≥ 0.80). SETTING: This study was conducted in the General Surgery Residency Program at an academic tertiary care facility (Geisinger Medical Center, Danville, PA). PARTICIPANTS: Participants included 6 faculty surgeons, in addition to 5 postgraduate year (PGY) 1, 6 midlevel (PGY 2-3), and 4 chief (PGY 4-5) residents. RESULTS: In total, 75 surgical cases were analyzed. Midlevel residents accounted for the highest number of cases (35, 46.6%). Overall, faculty and resident perceptions of case complexity demonstrated a strong correlation (r = 0.76, p < 0.0001). Technical performance scores were also strongly correlated (r = 0.66, p < 0.0001), whereas perceptions of autonomy demonstrated a moderate correlation (r = 0.56, p < 0.0001). Subgroup analysis revealed very strong correlations among faculty perceptions of case complexity and the perceptions of PGY 1 (r = 0.80, p < 0.0001) and chief residents (r = 0.82, p < 0.0001). All other intergroup correlations were strong with 2 notable exceptions as follows: midlevel and chief residents failed to correlate with faculty perceptions of autonomy and operative performance, respectively. CONCLUSIONS: General surgery residents generally demonstrated high correlations with faculty perceptions of case complexity, technical performance, and operative autonomy. This generalized accord supports the use of the Milestone and Zwisch assessments in residency programs. However, discordance among perceptions of midlevel resident autonomy and chief resident operative performance suggests that these trainees may need more direct communication from the faculty.

External Validation of a Survival Nomogram for Non-Small Cell Lung Cancer Using the National Cancer Database.

PURPOSE: Survival nomograms offer individualized predictions using a more diverse set of factors than traditional staging measures, including the American Joint Committee on Cancer Tumor Node Metastasis (AJCC TNM) Staging System. A nomogram predicting overall survival (OS) for resected, non-metastatic non-small cell lung cancer (NSCLC) has been previously derived from Asian patients. The present study aims to determine the nomogram's predictive capability in the US using the National Cancer Database (NCDB). METHODS: This was a retrospective review of adults with resected, non-metastatic NSCLC entered into the NCDB between 2004 and 2012. Concordance indices and calibration plots analyzed discrimination and calibration, respectively. Multivariate analysis was also used. RESULTS: A total of 57,313 patients were included in this study. The predominant histologies were adenocarcinoma (48.2%) and squamous cell carcinoma (31.3%), and patients were diagnosed with stage I-A (38.3%), stage I-B (22.7%), stage II-A (14.2%), stage II-B (11.5%), and stage III-A (13.3%). Median OS was 74 months. 1-, 3- and 5-year OS rates were 89.8% [95% confidence interval (CI) 89.5-90.0%], 71.1% (95% CI 70.7-71.6%), and 55.7% (95% CI 54.7-56.6%), respectively. The nomogram's concordance index (C-index) was 0.804 (95% CI 0.792-0.817). AJCC TNM staging demonstrated higher discrimination (C-index 0.833, 95% CI 0.821-0.840). CONCLUSIONS: The nomogram's individualized estimates accurately predicted survival in this patient collective, demonstrating higher discrimination in this population than in the developer's cohorts. However, the generalized survival estimates provided by traditional staging demonstrated superior predictive capability; therefore, AJCC TNM staging should remain the gold standard for the prognostication of resected NSCLC in the US.

Esophagectomy: Comparison of Short-Term Outcomes between Single-versus Two-Team Approach.

Literature about combining expertise of two specialties in esophageal cancer surgery is limited. We present the experience at a single institute comparing single-team (ST) versus two-team (TT) approach combining thoracic and abdominal surgeons. This is a retrospective study from a single tertiary care center. Data were collected from electronic medical records. Patients undergoing esophagectomy for esophageal cancer from November 2006 until August 2014 were included. The primary outcome measured was 30-day postoperative morbidity, secondary outcomes measured were operative time, intraoperative blood loss, and 30-day mortality. Results are reported as mean with an interquartile range. Forty-nine patients underwent esophagectomy by an ST and 51 patients by TT. Patient demographics, tumor characteristics, stage, pathology, and use of neoadjuvant therapy were comparable between groups. Charlson comorbidity index was significantly higher in TT group [3 (2, 4) vs 2 (2, 3), P = 0.02]. The TT group had a significantly shorter operative time compared to the ST group [304 (252,376) minutes vs 438 (375, 494] minutes, P < 0.0001). Intraoperative blood loss was 300 (200, 550) mL for the TT group and 250 (200,400) mL for the ST group (P = 0.29). There was no difference in 30-day postoperative morbidity (68.6% for TT, 59.2% for ST, P = 0.32) and mortality (2% each, P = 1) between the two groups. In conclusion, the operative time by the TT approach was significantly shorter than the ST approach with comparable postoperative morbidity and mortality. Long-term follow-up is needed to study this approach's effect on long-term survival.

Increased complication rate in obese patients undergoing laparoscopic adrenalectomy.

OBJECTIVES: Laparoscopic adrenalectomy has become the standard of care for resection of adrenal masses, with extremely low morbidity and mortality. This study investigates the difference in outcomes in patients who underwent laparoscopic adrenalectomy, comparing obese with healthy weight patients. METHODS: A retrospective chart review was performed on patients undergoing laparoscopic adrenalectomy between January 2000 and February 2010. Intraoperative and postoperative complications in the patients were compared. A patient with a body mass index >30kg/m(2) was considered obese. RESULTS: Eighty patients underwent laparoscopic adrenalectomy between January 2000 and February 2010. Forty-nine patients (61%) were considered obese based on the body mass index criteria. Operative time, estimated blood loss, and length of stay did not differ significantly between the 2 cohort groups. There was no 30-day mortality in the population. There were 9 complications in the obese population and no complications in the healthy weight population (P<.011). Four obese patients had intraoperative complications, and 5 obese patients had postoperative morbidity. CONCLUSIONS: A significant increase occurred in intraoperative and postoperative complications for obese individuals undergoing laparoscopic adrenalectomy compared with healthy weight individuals. However, high body mass index should not preclude elective laparoscopic adrenalectomy.

Novel method of stump closure for distal pancreatectomy with a 75% reduction in pancreatic fistula rate.

BACKGROUND: Pancreatic fistula is a significant problem for patients undergoing distal pancreatectomy with fistula rates up to 61%. Fistulas lead to substantial morbidity. The study objective was to compare radiofrequency dissector closure with traditional stump closure for distal pancreatectomy. METHODS: Sixty-two patients underwent distal pancreatectomy at our institution between 2002 and 2011. Thirty-three patients had traditional stump closure compared with 29 patients who had radiofrequency closure. Fistula rates, operative times, and blood loss were compared. The control patients underwent open operation in 20 (60%) cases and laparoscopic operation in the remaining 13 (40%). Of the patients that underwent radiofrequency closure, 10 (35%) underwent open operation, and the remaining 19 (65%) patients underwent laparoscopic operation. RESULTS: Fistula occurred in 12 of 33 (36%) patients with traditional stump closure compared to 3 of 29 (10%) patients with radiofrequency closure (p<0.02). Operative time (307 vs. 231 min [p<0.002]) and blood loss (364-200 mL [p<0.02]) were decreased in the radiofrequency closure group. Length of stay decreased from 7.8 to 6.6 days; however, this was not statistically significant. CONCLUSIONS: The use of radiofrequency dissector in distal pancreatectomy is effective with low rates of fistula formation. Radiofrequency closure should be studied further in prospective trials.

Combining agents that target the tumor microenvironment improves the efficacy of anticancer therapy.

PURPOSE: Over the past 60 years, cytotoxic chemotherapy has targeted the cancer cell. Despite this, there have been few cancer cures. A new approach to cancer therapy is to target the multicellular biological entity of the tumor microenvironment. EXPERIMENTAL DESIGN: Lenalidomide, an immunomodulatory drug, sunitinib, a tyrosine kinase inhibitor, and low-dose metronomic cyclophosphamide, were tested alone and in combination for their abilities to inhibit endothelial cell tube formation, rat aortic ring outgrowth, tumor growth, and metastatic development in mice. In addition, ectopic tumor lysates were evaluated for the presence of proangiogenic proteins. RESULTS: The three agents alone were shown to significantly inhibit endothelial cells' ability to form tubes and significantly inhibit the multicellular microenvironment in the rat aortic ring assay (P < 0.01 and P < 0.001). This effect was also significantly augmented when the agents were combined. Furthermore, the three-drug combination was able halt the progression of tumor growth almost completely in xenograft models of ocular melanoma, colon cancer, pancreatic cancer, and cutaneous melanoma. These agents significantly decrease the number of proliferating cells in tumors, significantly increase the number of cells undergoing active cell death in tumors, and significantly decrease the number of blood vessels in treated tumors (P < 0.05). Combination therapy shows a decrease in the compensatory up-regulation of proangiogenic proteins after treatment when compared with single-agent therapy. CONCLUSIONS: This combination of agents causes an inhospitable microenvironment for tumor cells and shows great promise for use in the clinic.

Clinical, genetic and radiographic analysis of 108 patients with von Hippel-Lindau disease (VHL) manifested by pancreatic neuroendocrine neoplasms (PNETs).

BACKGROUND: von Hippel-Lindau (vHL) disease is an autosomal dominant syndrome associated with neoplasms in multiple organs, which includes the pancreas. Here, we report the greatest single center experience in patients with vHL pancreatic endocrine neoplasm (PNETs). METHODS: Between December 1998 and November 2006, 633 patients with vHL were evaluated and those with PNETs were enrolled on a prospective protocol. RESULTS: Overall, 108 vHL patients had PNETs (17%). Nine patients had metastatic disease (8.3%) from their PNET. Patients with lesions greater than 3 cm (n = 25) were more likely to develop metastases than patients with lesions less than 3 cm (n = 83) (P < .005). Thirty-nine patients underwent resection. Germline sequencing showed that 78% of patients with metastases (7/9) had exon 3 mutations compared with 46% of patients without metastases (32/98; P < .01). Tumor doubling time was calculated for the largest PNET. The group with metastases had an average tumor doubling time of 337 days (range, 180-463 days) compared with 2630 days (range, 103-9614 days) for those without metastases (P < .0001). CONCLUSIONS: By implementing a system of selective operative resection based on defined criteria, vHL patients with PNETs can be managed safely. For patients with small primary lesions (<3 cm), without a mutation of exon 3 and slow tumor doubling time (>500 days), a nonoperative approach may be appropriate for these nonfunctional neoplasms.

Combination therapy targeting the tumor microenvironment is effective in a model of human ocular melanoma.

BACKGROUND: Ocular melanoma is the leading intraocular malignancy. There is no effective treatment for metastatic ocular melanoma. We sought a treatment targeting the tumor microenvironment as well as the tumor cells. METHODS: Migration of HUVEC cells, the ability of HUVEC cells to form tubes, and proliferative capacity of a human ocular melanoma cell line were tested in the presence of lenalidomide and sorafenib alone and in combination. The compounds were also tested in a rat aortic ring assay and were tested in a highly aggressive human ocular melanoma xenograft model. RESULTS: Lenalidomide and Sorafenib inhibit HUVEC ability to migrate and form tubes and when used in combination the inhibition is increased. The agents alone and in combination inhibit outgrowth in the rat aortic ring model. The combination of the agents improved the inhibition over either single agent. In a xenograft model, combination therapy inhibited tumor growth over inhibition by single agent alone in a significant fashion (p < 0.004: lenalidomide and p < 0.0035: sorafenib). Furthermore, spontaneous lung metastasis development was completely inhibited in the combination treated animals. Sixty percent of vehicle treated animals developed lung metastases compared to 50% of lenalidomide treated animals, and 33% of sorafenib treated animals. CONCLUSION: Lenalidomide and sorafenib are effective at targeting endothelial cells, inhibiting growth of ocular melanoma cells and can inhibit growth of tumors in a xenograft model as well as inhibit development of metastases. Combining these agents works in an additive to synergistic way to inhibit the growth of tumors and development of metastases.