Primary Tumor Resection in Leiomyosarcoma Patients With Synchronous Isolated Lung Metastases: A National Cancer Database Study.

INTRODUCTION: Up to half of patients with leiomyosarcoma (LMS) present with distant metastases, most commonly in the lungs. Despite guidelines around managing metachronous oligometastatic disease, limited evidence exists for synchronous isolated lung metastases (SILMs). Our histology-specific study describes management patterns and outcomes for patients with LMS and SILM across disease sites. METHODS: We used the National Cancer Database to analyze patients with LMS of the retroperitoneum, extremity, trunk/chest/abdominal wall, and pelvis with SILM. Patients with extra-pulmonary metastases were excluded. We identified factors associated with primary tumor resection and receipt of metastasectomy. Outcomes included median, 1-year, and 5-year overall survival (OS) across treatment approaches using log-rank tests, Kaplan-Meier curves, and Cox proportional hazard models. RESULTS: We identified 629 LMS patients with SILM from 2004 to 2017. Patients were more likely to have resection of their primary tumor or lung metastases if treated at an academic center compared to a community cancer center. Five year OS for patients undergoing both primary tumor resection and metastasectomy was 20.9% versus 9.2% for primary tumor resection alone, and 2.6% for nonsurgical patients. Median OS for all-comers was 15.5 mo. Community treatment site, comorbidity score, and larger primary tumors were associated with worse survival. Chemotherapy, primary resection, and curative intent surgery predicted improved survival on multivariate Cox regression. CONCLUSIONS: An aggressive surgical approach to primary LMS with SILM was undertaken for select patients in our population and found to be associated with improved OS. This approach should be considered for suitable patients at high-volume centers.

Surgical resection and survival outcomes in metastatic young adult colorectal cancer patients.

BACKGROUND: The incidence of colorectal cancer in adults younger than age 50 has increased with rates expected to continue to increase over the next decade. The objective of this study is to examine the survival benefit of surgical resection (primary and/or metastatic) versus palliative therapy in this patient population. METHODS: We identified 6708 young adults aged 18-45 years diagnosed with metastatic colorectal cancer (mCRC) from 2004 to 2015 from the SEER database. Overall survival (OS) was analyzed using Kaplan-Meier estimation, log rank test, and multivariate Cox proportional hazards model. RESULTS: Sixty-three percent of patients in our study underwent primary tumor resection (PTR), with 40% undergoing PTR alone and 23% undergoing both resection of primary disease and metastasectomy. The median OS for patients who underwent both PTR and metastasectomy was 36 months, compared to 13 months for those who did not receive any surgical intervention. The multivariate analysis showed significant OS benefit of receiving both PTR and metastasectomy (HR 0.34, 95% CI: 0.31-0.37, p < 0.001) compared to palliative therapy. Undergoing PTR only and metastasectomy only were also associated with improved OS (HR 0.46, 95% CI: 0.43-0.49, p < 0.001 and HR 0.64, 95% CI: 0.55-0.76, p < 0.001, respectively). CONCLUSION: This is the largest observational study to evaluate survival outcomes in young-onset mCRC patients and the role of surgical intervention of the primary and/or metastatic site. Our study provides evidence of statistically significant increase in OS for young mCRC patients who undergo surgical intervention of the primary and/or metastatic site.

Metastasectomy and BRAF mutation; an analysis of survival outcome in metastatic colorectal cancer.

BACKGROUND: Resection of oligometastases improves survival in metastatic colorectal cancer (mCRC). It is unclear whether the benefit is consistent for BRAF V600E mutant (MT) and wild type (WT) mCRC. This retrospective analysis explores the influence of BRAF MT on survival after metastasectomy. METHODS: Overall survival (OS) and recurrence-free survival (RFS) for BRAF MT and WT mCRC were evaluated. Survival was also analyzed in the cohort of BRAF MT with or without metastasectomy. RESULTS: Five hundred and thirteen patients who had undergone metastasectomy were identified, 6% were BRAF-MT. Median age 63. Median OS in BRAF MT vs WT: 25.7 vs 48.5 months (hazard ratio [HR] 1.95; 1.18-3.22). However, difference was not significant in a multivariate model. Right primary tumor, intact primary, >1 metastatic site, non-R0 resection, peritoneal metastasis, and synchronous metastasis were independent predictors of worse OS. Among 364 patients with RFS data there was no difference between BRAF MT and WT (16 vs 19 months, p=0.09). In another cohort of 158 BRAF-MT patients, OS was significantly better after metastasectomy compared to "no metastasectomy" (HR 0.34; 0.18-0.65, P= 0.001). Proficient mismatch repair status showed a trend toward worse survival after metastasectomy in BRAF MT (HR 1.71, P = 0.08). CONCLUSION: OS did not differ after metastasectomy between BRAF MT and WT in a multivariate model. Median OS was >2 years in this study after metastasectomy among BRAFV600E MT patients suggesting a survival benefit of metastasectomy in this group where systemic therapeutic options are limited. Metastasectomy may be considered in carefully selected BRAF-MT patients.

Outcomes of complete metastasectomy in metastatic renal cell carcinoma patients: The Canadian Kidney Cancer information system experience.

BACKGROUND: Surgical resection of metastasis can be integrated in the management of metastatic renal cell carcinoma (mRCC) as it can contribute to delay disease progression and improve survival. OBJECTIVE: This study assessed the impact of complete metastasectomy in mRCC patients using real-world pan-Canadian data. DESIGN, SETTING AND PARTICIPANTS: The Canadian Kidney Cancer information system (CKCis) database was used to select patients who were diagnosed with mRCC between January 2011 and April 2019. To minimize selection bias, each patient having received a complete metastasectomy was matched with up to 4 patients not treated with metastasectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) was calculated from the date of metastasectomy or selection, to death from any cause. A Cox proportional hazards model was used to assess the impact of the metastasectomy while adjusting for potential confounding variables. RESULTS: A total of 229 patients undergoing complete metastasectomy were matched with 803 patients not treated with metastasectomy. After matching, baseline characteristics were well balanced between groups. After 12 months, the proportion of patients that were still alive was 96.0% and 89.8% in the complete metastasectomy and its matched group, respectively; the 5-year OS were 63.2% and 51.4%, respectively. Multivariate analysis performed in the matched cohort revealed that patients who underwent complete metastasectomy had a lower risk of mortality compared to patients who did not undergo metastasectomy (hazard ratio: 0.41, 95% confidence interval:0.27-0.63). CONCLUSION: Our study found that patients who underwent complete metastasectomy have a longer overall survival and a longer time to initiation of targeted therapy compared to patients not receiving metastasectomy. These findings should support aggressive resection of metastasis in selected patients.

FOLFOXIRI Versus Doublet Regimens in Right-Sided Metastatic Colorectal Cancer: Focus on Subsequent Therapies and Impact on Overall Survival.

INTRODUCTION: It has been determined that right-sided metastatic colorectal cancer (mCRC) has a worse prognosis for overall survival (OS). Currently, there is no consensus on the best systemic regimen for treatment-naive right-sided tumors. We compared the impact of subsequent therapies on OS of patients treated with FOLFOXIRI (leucovorin, 5-fluorouracil, oxaliplatin, irinotecan) versus doublet regimens. PATIENTS AND METHODS: Data of patients with treatment-naive right-sided mCRC who received FOLFOXIRI or doublet regimens between January 2001 to December 2018 were retrospectively analyzed. OS was compared between the two groups, and prognostic factors were assessed by multivariate analysis. RESULTS: A total of 196 patients were selected; 33 patients received FOLFOXIRI and 163 patients doublet therapy. Median follow-up was 82.3 months. The FOLFOXIRI cohort received fewer subsequent lines of therapies (61% vs. 78%, P = .043). The greater the number of subsequent lines of therapy, the lower the risk of death (hazard ratio [95% confidence interval] 0.67 [0.46-0.99], 0.62 [0.45-0.86], and 0.56 [0.39-0.81] for > 1, > 2, and > 3 lines, respectively). By multivariate analysis, metastasectomy and bevacizumab with subsequent lines of therapy were the variables with greatest positive impact on OS (respectively, hazard ratio [95% confidence interval] 0.54 [0.38-0.78] and 0.61 [0.44-0.84]). CONCLUSION: Patients with treatment-naive right-sided mCRC who received front-line FOLFOXIRI had a lower number of subsequent therapies than patients who received doublet regimens. Our findings highlight the relevance of the continuum of care in mCRC, regardless of the first-line regimen, and the importance of careful selection of patients for the FOLFOXIRI regimen.

Metastasis directed treatment of brain metastases from colorectal cancer - a Danish population-based cohort study.

Background: Brain metastases (BMs) are an uncommon presentation of metastatic colorectal cancer (mCRC) with reported incidence of about 2-4%. Today, there is an increased awareness towards a metastasis directed treatment approach with either surgical resection, stereotactic radiotherapy (SRT) or both. We examined patient characteristics and survival for patients treated with a localized modality for BM from CRC in a nationwide population-based study.Methods: A registry-based cohort study of all patients with a resected primary colorectal cancer and localized treatment of BM during 2000-2013. We computed descriptive statistics and analysed overall survival by the Kaplan-Meier method and Cox regression.Results: A total of 38131 patients had surgery for a primary CRC and 235 patients were recorded with a metastasis directed treatment for BM, comprising resection alone (n = 158), SRT alone (n = 51) and combined resection and SRT (n = 26). Rectal primary tumor (48.9% vs. 36.2%, p < .001) and lung metastasectomy (11.9 vs 2.8%, p < .001) were more frequent in the BM group. The median survival of patients receiving localized treatment for BM was 9.6 months (95% confidence interval (CI) 7.2-10.8). The 1- and 5-year overall survival were 41.7% (95% CI 35-48%) and 11.2% (95% CI 6.9-16.3%). In multivariate analysis, nodal stage was associated with increased mortality with a hazard ratio of 1.63 (95% CI 1.07-2.60, p = .03) for N2 stage with reference to N0.Conclusion: We report a median overall survival of 9.6 months for patients receiving localized treatment for BM from CRC. Lung metastases and rectal primary tumor are more common in the population treated for BM.

Curative-intent pancreas resection for pancreatic metastases: surgical and oncological results.

BACKGROUND: Pancreatic metastasis is a rare cause for pancreas surgery and often a sign of advanced disease no chance of curative-intent treatment. However, surgery for metastasis might be a promising approach to improve patients' survival. The aim of this study was to analyze the surgical and oncological outcome after pancreatic resection of pancreatic metastasis. METHODS: This is a retrospective cohort analysis of a prospectively-managed database of patients undergoing pancreatic resection at the University of Freiburg Pancreatic Center from 2005 to 2017. RESULTS: In total, 29 of 1297 (2%) patients underwent pancreatic resection due to pancreatic metastasis. 20 (69%) patients showed metastasis of renal cell carcinoma (mRCC), followed by metastasis of melanoma (n = 5, 17%), colon cancer (n = 2, 7%), ovarian cancer (n = 1, 3%) and neuroendocrine tumor of small intestine (n = 1, 3%). Two (7%) patients died perioperatively. Median follow-up was 76.4 (range 21-132) months. 5-year and overall survival rates were 82% (mRCC 89% vs. non-mRCC 67%) and 70% (mRCC 78% vs. non-mRCC 57%), respectively. Patients with mRCC had shorter disease-free survival (14 vs. 22 months) than patients with other primary tumor entities. CONCLUSION: Despite malignant disease, overall survival of patients after metastasectomy for pancreatic metastasis is acceptable. Better survival appears to be associated with the primary tumor entity. Further research should focus on molecular markers to elucidate the mechanisms of pancreatic metastasis to choose the suitable therapeutic approach for the individual patient.

Lung Metastasectomy Improves Survival in Patients Affected by Grade 2 and 3 Chondrosarcoma.

AIMS: The aim of this retrospective study is to evaluate the role of pulmonary metastasectomy (PM) in patients affected by lung metastasis (LM) of grade 2 and 3 chondrosarcoma (CS). PATIENTS AND METHODS: The study included 61 patients affected by LM. Patients unfit for PM were treated with chemotherapy and radiotherapy. RESULTS: The patients' mean age was 51 years, ranging from 17 to 84 years; 44 (66.7%) patients had grade 2 CS, while 17 (25.8%) patients had grade 3 CS. Fifty-one patients presented multiple nodules: 44 of those cases were bilateral LM (72.1%). Twenty-nine (47.5%) patients underwent PM, whereas 32 (52.5%) patients underwent chemotherapy and stereotactic radiotherapy alone. At the final follow-up (average of 83 months, range 13-298), 47 (77.0%) patients had died of the disease. A better post-relapse survival rate was observed in patients who underwent PM (55.1 vs. 13.1% at 5-year follow-up, p < 0.001) and in patients with unilateral LM (60.4 vs. 25.6% at 5-year follow-up, p = 0.016). The number of LM also played a prognostic role. CONCLUSIONS: Until significant improvements in chemotherapy can be made, PM can be a valid option in the attempt to improve post-metastatic survival.

Facilities that service economically advantaged neighborhoods perform surgical metastasectomy more often for patients with colorectal liver metastases.

BACKGROUND: Metastasectomy of isolated colorectal liver metastases (CRLM) requires significant clinical expertise and may not be readily available or offered. The authors hypothesized that hospitals that treat a greater percentage of patients from higher income catchment areas are more likely to perform metastasectomies regardless of patient or tumor characteristics. METHODS: Using the National Cancer Data Base, the authors classified facilities into facility income quartiles (FIQs) based on the percentage of patients from the wealthiest neighborhoods (by zip code). Quartile 1 included facilities with <2.1% of the patients residing within the highest income zip codes, quartile 2 included facilities with 2.2% to 15.6% of patients residing within the highest income zip codes, quartile 3 included facilities with 15.7% to 40.2% of patients residing within the highest income zip codes, and quartile 4 included facilities with 40.3% to 90.5% of patients residing within the highest income ZIP codes. Patient, tumor, and facility characteristics were analyzed using a multivariate logistic regression to identify associations between metastasectomy and FIQ. RESULTS: Patients with CRLM were more likely to undergo metastasectomy at facilities in the highest FIQ compared with the lowest FIQ (18% vs 11% in FIQ4; P = .001). This trend was not observed in the resection of primary tumors for nonmetastatic CRLM (rates of 95% vs 93%; P = .94). After adjusting for individual insurance status, distance traveled, zip code-level individual income, tumor, and host, patients who were treated at the highest FIQ facilities were found to be more likely to undergo metastasectomy (odds ratio, 1.29; 95% CI, 1.02-1.72 [P = .03]). CONCLUSIONS: Metastasectomy for CRLM is more likely to occur at facilities that serve a greater percentage of patients from high-income catchment areas, regardless of individual patient characteristics. This disparity uniquely affects those patients with advanced cancers for which specialized expertise for therapy is necessary.

Racial and Socioeconomic Disparities in Access and Utilization of Adrenal Metastasectomy.

BACKGROUND: There is substantial evidence that resecting adrenal metastases can be safely accomplished and extend overall survival in select patients. However, patient access to this operation has not been studied at the population level. The purpose of this study was to determine differences in utilization rates of adrenal metastasectomy (ADMX) across patient populations. METHODS: The Healthcare Utilization Project National Inpatient Sample was used to identify patients who had adrenal metastases (ADM) and who underwent ADMX from 2007 to 2011. Patients were identified by ICD-9-CM diagnosis and procedure codes. Predictor variables included sex, race, median household income, and primary insurance payer. Primary outcomes included receiving an ADMX and same hospitalization mortality. Secondary outcomes included length of stay, infection, cardiac, pulmonary, and renal complications. Univariable and multivariable logistic regression models were used to identify statistical associations. RESULTS: 32,331 ADM and 1070 ADMX patients identified in the database. Despite similar comorbidities, Black patients had 0.30 (95% CI 0.21-0.41) lower odds to receive an ADMX compared to White patients. Medicaid patients had 0.38 (0.28-0.52) less odds and Private Insurance patients 1.18 (1.00-1.39) more odds to receive an ADMX compared to Medicare patients. Women had a 1.39 (1.22-1.58) higher odds ratio of undergoing ADMX compared to men. Of the ADMX cohort, there was no difference in same hospitalization mortality or surgical complications. CONCLUSIONS: Black and Medicaid patients underwent fewer adrenal metastasectomies despite similar comorbidities and postoperative outcomes. This suggests a potential disparity in access to this treatment that disproportionately affects Black and low-income patients, and prompts further study, outreach attempts, as well as, research into improving access.

Novel Predictive Models of Early Death Less Than 1 Year in Patients With Metastatic Renal Cell Carcinoma After Treatment With First-line Tyrosine Kinase Inhibitors.

BACKGROUND: We aimed to develop a modified International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model that can predict early death less than 1 year in patients with metastatic renal cell carcinoma (mRCC) after receiving first-line tyrosine kinase inhibitors (TKIs). PATIENTS AND METHODS: We retrospectively reviewed records of patients with mRCC treated with first-line TKIs at our institution between 2007 and 2012. The primary endpoint was the rate of early death within 1 year after first-line TKI administration. We determined statistically significant factors predicting early death by performing multiple logistic regression. The modified IMDC model 1 was developed using new variables in addition to the risk criteria of the IMDC model, and model 2 was developed using new variables irrespective of the risk classification of IMDC model. RESULTS: Early mortality within 1 year of first-line TKI treatment was 19.7% (n = 98) in 462 patients. Although the C-index of the IMDC model for early death was 0.655, the C-index of model 1, which includes 5 variables (previous nephrectomy, body mass index, multiple metastases, previous metastasectomy, and serum albumin level) in addition to the Heng criteria, was 0.823. The C-index of model 2, which includes 7 variables (hemoglobin, neutrophil level, and the 5 variables of model 1) was 0.822. Of note, there was no significant difference in net reclassification index between the 2 models. CONCLUSION: This is the first study suggesting novel prediction models for early death less than 1 year in patients with mRCC treated with first-line TKI.

Unmarried status is a barrier for access to treatment in patients with metastatic renal cell carcinoma.

PURPOSE: We tested the effect of marital status on cytoreductive nephrectomy, metastasectomy, and systemic therapy rates, as well as on cancer-specific mortality (CSM) in patients with metastatic clear cell renal carcinoma (mccRCC). METHODS: Within the Surveillance, Epidemiology and End Results database (2004-2015), we identified 6975 patients (4806 men and 2169 women) with metastatic clear cell renal carcinoma. Temporal trend analyses, logistic regression models, cumulative incidence plots, and competing-risk regression models were used. RESULTS: Overall, 1450 men and 1018 women were unmarried (30.2% and 47.0%, respectively). In men, unmarried status was an independent predictor of lower cytoreductive nephrectomy rate (OR: 0.54), lower metastasectomy rate (OR: 0.70), and lower systemic therapy rate (OR: 0.70). Conversely, in women, unmarried status was an independent predictor of lower cytoreductive nephrectomy rate (OR: 0.63) and of lower systemic therapy rate (OR: 0.80), but not of lower metastasectomy rate (OR: 0.83; p = 0.12). In multivariable competing-risk regression analyses, unmarried status was an independent predictor of higher CSM in men (HR: 1.15), but not in women (HR 0.97, p = 0.6). CONCLUSIONS: Unmarried men are at higher risk of not benefiting of cytoreductive nephrectomy, metastasectomy, or systemic therapy than their married counterparts. Unmarried women are at higher risk of not benefiting of cytoreductive nephrectomy or systemic therapy. These gender-related differences cumulate in higher CSM in unmarried men, but not in unmarried women.

A retrospective chart review study describing metastatic melanoma patients profile and treatment patterns in Spain.

PURPOSE: To describe patient characteristics by disease stage, resectability status and current treatment management after first diagnosis of IIIB to IV1c advanced (AM)/metastatic melanoma (MM). METHODS/PATIENTS: Multicentre, retrospective study based on data from medical charts of patients > 18 years at MM first diagnosis, visited by oncologists at 4 reference centres in Spain: Hospital Universitario Gregorio Marañón (Madrid), Hospital General de Valencia (Valencia), Clínica Universidad de Navarra (Pamplona), and Hospital Clínic (Barcelona). RESULTS: Metastatic non-visceral melanoma (IIIB, IIIC, IV M1a) was reported in 139 (48.6%) patients and 40.9% (n = 117) were diagnosed with IV-M1c disease. 160 (55.9%) metastases were resectable. Available therapies under clinical practice were used in 210 patients; 74 were treated under clinical trials (CT). Intention-to-cure surgery (47.6%) was the most common treatment at time of MM diagnosis. Systemic (45.1% overall) therapy included chemo-, targeted- and immunotherapy (19.6%, 14.3%, 8.4%, respectively). At time of data collection, 26 patients were still alive and 120 had progressed to IV-M1c. Median overall survival (OS) was significantly larger in IIIB patients, 28.9 m (25.2-32.7); the shortest for IV-M1c patients, 11.0 m (8.7-13.3). CONCLUSIONS: Novel treatments are undoubtedly a major step forward in AM/MM, however these are often only available in the CT setting because early stages of development or country-specific regulations. Further prospective studies and multifactorial analysis should be performed to clearly identify possible clinical associations for outcome in Spanish patients with AM/MM.

Prognostic factors for pulmonary metastasectomy in malignant melanoma: size matters.

OBJECTIVES: Pulmonary metastasectomy for malignant melanoma requires an individualized therapeutic decision. Due to recently developed novel treatment options, the prognosis of patients with melanoma has improved significantly. Validated prognostic factors that identify patients who are most likely to benefit from metastasectomy are urgently needed. METHODS: We retrospectively reviewed all consecutive patients with melanoma undergoing complete pulmonary metastasectomy between January 2010 and December 2016. The impact of age, sex, extrapulmonary metastases, preoperative systemic therapy, number of metastases, laterality and largest diameter of metastasis on survival after metastasectomy was analysed. RESULTS: A total of 29 male and 32 female patients were included in the study. The median follow-up time was 25.6 months. The mean number of resected metastases was 1.7 ± 1.1 (range 1-5). Ten patients had repetitive pulmonary metastasectomies. The median survival time was 31.3 months with a 2-year survival rate of 54%. Bilateral metastases or multiple nodules were not associated with a significantly decreased overall survival rate after metastasectomy. Shorter overall survival times were observed in male patients [hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.42-5.92; P = 0.0035] and in patients with nodules larger than 2 cm (HR 3.18, 95% CI 1.45-6.98; P = 0.004). In multivariable analysis, both gender and tumour size remained significant independent prognostic factors. CONCLUSIONS: Excellent overall survival rates after pulmonary metastasectomy for melanoma metastases were observed in patients with a metastatic diameter less than 2 cm and in female patients. In view of improved long-term outcome due to novel treatment options, the selection of patients for pulmonary metastasectomy based on prognostic factors will become increasingly important.

[Is surgical treatment of pulmonary metastases justified?] / Resectie van longmetastasen gerechtvaardigd?

Until recently, patients with cancer and distant metastases were considered incurable. However, nowadays, some of these patients are eligible for curative-intent therapy. Surgery of metastases is becoming an increasingly important part of this ever-evolving therapy. The introduction of minimally invasive surgical techniques has resulted in more resections being performed of pulmonary metastases, even in elderly patients. Low postoperative morbidity and mortality rates have been observed after pulmonary metastasectomy. This is also true for elderly patients as age has not been linked to postoperative morbidity. Long-term survival is better for patients undergoing pulmonary metastasectomy compared to non-surgically treated patients. However, selection bias plays an important role as only relatively fit patients can tolerate surgery and their prognosis is therefore better from the onset. The question therefore remains whether pulmonary metastasectomy, a non-evidence-based treatment, is justified.

Long-term outcomes and prognostic factors of pulmonary metastasectomy for osteosarcoma and soft tissue sarcoma.

BACKGROUND: The prognostic factors of pulmonary metastasectomy in patients with osteosarcoma and soft tissue sarcoma remain controversial. The purpose of our analysis was to explore the prognostic factors and outcomes of patients with osteosarcoma and soft tissue sarcoma who underwent pulmonary metastasectomy at our institution. METHODS: We reviewed the data of 44 patients who underwent resection of pulmonary metastases from 1996 to 2016 at our institution. The Kaplan-Meier method, log-rank test and multivariate Cox hazard model were used for comparison and survival analyses. RESULTS: There was no perioperative mortality. The median post-metastasectomy overall survival was 24.8 months, and the 5-year overall survival rate of all patients was 43.5%. The 5-year survival rate of the patients who underwent repeat thoracotomies was 60.0%. Incomplete resection, a largest tumor size > 2 cm and a disease-free interval < 12 months were associated with poor survival in multivariate analyses. Among eight patients, who underwent repeat pulmonary resection, two remain alive with no evidence of disease. These patients had the longest DFI and DFI-2 (time from first pulmonary metastasectomy to the diagnosis of recurrent pulmonary metastasis), respectively. CONCLUSION: The survival of patients with a relatively long disease-free interval, small tumor size and complete resection was favorable following the treatment of osteosarcoma and soft tissue sarcoma with pulmonary metastasectomy. Repeat pulmonary metastasectomies also provide favorable prognosis in select patients.

Longitudinal patterns of recurrence in patients with adrenocortical carcinoma.

BACKGROUND: Patterns and prognostic implications of recurrent adrenocortical carcinoma are poorly understood. In this study, we aim to describe temporal and spatial patterns of adrenocortical carcinoma recurrence. METHODS: This is a retrospective review of 576 patients with adrenocortical carcinoma evaluated at a single institution. Clinicopathologic and follow-up data were collected longitudinally. RESULTS: A total of 354 patients underwent resection of stage I-III adrenocortical carcinoma. We found that 249 (70%) patients developed disease recurrence. The median recurrence-free interval after primary resection was 11 months. The most common sites of initial recurrence were lung and tumor bed. The shortest time to recurrence was associated with lung or multiple site metastases. We found that 142 of 249 patients developed one or more additional sites of recurrence (median 5 months), most commonly involving the lungs. A total of 20 patients developed a third site of recurrence. We found that 100 patients underwent one or more reoperations or metastasectomies and 79 recurred again after reoperation. Same organ or site recurrence was common after reoperation (67%). Although lung metastases occurred early, recurrences to the peritoneal cavity or to multiple sites were associated with worse survival. Metastasectomy beyond three total operations did not improve overall survival. CONCLUSION: Survival varies according to site of recurrence and other clinicopathologic factors. Knowledge of patterns of recurrence may assist in anticipating disease course and lead to better informed selection of treatment.

Pancreaticoduodenectomy and metastasectomy for metastatic pancreatic neuroendocrine tumors.

BACKGROUND AND OBJECTIVES: Various treatment options exist for patients with metastatic pancreatic neuroendocrine tumors (PNETs). Surgical resection with pancreaticoduodenectomy (PD) typically reserved for patients with limited disease. Definitive data are lacking to support either the resection of primary PNET in the metastatic setting or for surgical debulking of metastatic lesions. METHODS: We conducted an analysis of the National Cancer Database (NCDB) using the pancreatic cancer Participant User File. Thirty- and 90-day mortality rates and survival rates were determined for patients undergoing PD for primary tumor resection and compared with patients who had no surgery or metastasectomy. The Kaplan-Meier method was used to compare survival time. Cox regression models were used to assess factors independently associated with overall survival time. RESULTS: Resection of the primary tumor or metastatic disease each significantly improved overall survival time compared with no resection. Adding metastasectomy to PD resulted in an incremental increase in overall survival time. Both PD and metastasectomy are independently associated with overall survival time. CONCLUSIONS: Our report highlights the potential for survival time benefit in appropriately selected patients who undergo PD in the setting of metastatic PNET.

Predictors, utilization patterns, and overall survival of patients undergoing metastasectomy for metastatic renal cell carcinoma in the era of targeted therapy.

INTRODUCTION: Metastasectomy (MSX) is considered a treatment option in patients with metastatic renal cell carcinoma (mRCC) at diagnosis, but its role in the targeted therapy era is unclear. We sought to describe the utilization trends of MSX and survival outcomes in a large US cohort. MATERIALS AND METHODS: Using the National Cancer Database, we identified patients undergoing MSX for mRCC at diagnosis between 2006 and 2013. Linear regression methods estimated utilization trends, and hierarchical models identified independent predictors of MSX after adjusting for hospital clustering. Kaplan-Meier survival estimates and Cox proportional hazard models were used to evaluate overall survival according to treatment after propensity-score matching. RESULTS: Of 6994 mRCC patients, 1976 underwent MSX (28.3%). Those treated at academic facilities were more likely to undergo a MSX (OR: 1.57, 95% CI 1.20-2.06, p = 0.001). In contrast, older patients (OR: 0.99, 95% CI: 0.98-1.00), black race (OR: 0.65, 95% CI: 0.51-0.82), higher pT stage (OR: 0.76, 95% CI: 0.65-0.89), and who received targeted therapy (OR: 0.72, 95% CI: 0.63-0.82, all p ≤ 0.008) were less likely to undergo MSX. Overall, MSX patients had an improved survival compared to non-MSX patients (HR: 0.83, 95% CI: 0.77-0.90, p < 0.001), as well as among patients treated with targeted therapy (HR: 0.77, 95% CI: 0.77-0.96, p = 0.008). CONCLUSIONS: Our findings indicate that MSX-treated patients may benefit from an improved overall survival compared to non-MSX treated patients. Good patient selection and a proper risk stratification strategy are still very important considerations.

Overall survival after stereotactic radiotherapy or surgical metastasectomy in oligometastatic renal cell carcinoma patients treated at two Swedish centres 2005-2014.

BACKGROUND AND PURPOSE: Investigate effects of stereotactic radiotherapy (SRT) or surgical metastasectomy (SM) on overall survival (OS) in metastatic renal cell carcinoma (mRCC) in the era of targeted agents (TA). MATERIAL AND METHODS: mRCC patients (n = 117) treated with SRT (n = 57), SM (n = 30) or both modalities sequentially (n = 30) at two oncological centres in Sweden in 2005-2014 were retrospectively included. Median follow-up (mFU) was 63 months. RESULTS: A majority had clear cell histology, 1-3 metastases, and ECOG performance status of 0 or 1. Two thirds had intermediate or poor risk and 44% synchronous metastases. 65% received TA. SRT patients were more likely to have adverse risk profiles. Median OS was 51 months without significant differences between SRT and SM. ECOG 1 vs 0 (HR 2.9; CI 1.6-5.2; p < 0.001), intracranial targets (HR 1.8; CI 1.1-3.2; p = 0.03) and watchful waiting >18 months prior to treatment (HR 0.3; CI 0.2-0.6; p = 0.001) were independently associated with OS. 15% of curatively treated patients (n = 60) were relapse-free with mFU of 87 months. CONCLUSIONS: OS after SRT was comparable to SM and longer than expected considering patients with adverse risk profiles were common. Fit patients with non-brain metastases treated after an initial period of watchful waiting had the best prognosis.