Natural history of undifferentiated pleomorphic sarcoma: Experience from the US Sarcoma Collaborative.

BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS) is a relatively rare but aggressive neoplasm. We sought to utilize a multi-institutional US cohort of sarcoma patients to examine predictors of survival and recurrence patterns after resection of UPS. METHODS: From 2000 to 2016, patients with primary UPS undergoing curative-intent surgical resection at seven academic institutions were retrospectively reviewed. Epidemiologic and clinicopathologic factors were reviewed by site of origin. Overall survival (OS), recurrence-free survival (RFS), time-to-locoregional (TTLR), time-to-distant recurrence (TTDR), and patterns of recurrence were analyzed. RESULTS: Of the 534 UPS patients identified, 53% were female, with a median age of 60 and median tumor size of 8.5 cm. The median OS, RFS, TTLR, and TTDR for the entire cohort were 109, 49, 86, and 46 months, respectively. There were no differences in these survival outcomes between extremity and truncal UPS. Compared with truncal, extremity UPS were more commonly amenable to R0 resection (87% vs. 75%, p = 0.017) and less commonly associated with lymph node metastasis (1% vs. 6%, p = 0.031). R0 resection and radiation treatment, but not site of origin (extremity vs. trunk) were independent predictors of OS and RFS. TTLR recurrence was shorter for UPS resected with a positive margin and for tumors not treated with radiation. CONCLUSION: For patients with resected extremity and truncal UPS, tumor size >5 cm and positive resection margin are associated with worse survival OS and RFS, irrespectively the site of origin. R0 surgical resection and radiation treatment may help improve these survival outcomes.

Calcifications and Cystic Morphology on Preoperative Imaging Predict Survival After Resection of Pancreatic Neuroendocrine Tumors.

BACKGROUND: Radiographic calcifications and cystic morphology are associated with higher and lower tumor grade, respectively, in pancreatic neuroendocrine tumors (PNETs). Whether calcifications and/or cystic morphology could be used preoperatively to predict post-resection survival in patients with PNETs remains elusive. METHODS: Patients undergoing curative-intent resection of well-differentiated PNETs from 2000 to 2017 at eight academic institutions participating in the US Neuroendocrine Tumor Study Group were identified. Preoperative cross-sectional imaging reports were reviewed to identify the presence of calcifications and of a cystic component occupying >50% of the total tumor area. Clinicopathologic characteristics and recurrence-free survival (RFS) were compared. RESULTS: Of 981 patients studied, 18% had calcifications and 17% had cystic tumors. Tumors with calcifications were more commonly associated with Ki-67 ≥3% (47% vs. 33%; p = 0.029), lymph node metastasis (36% vs. 24%; p = 0.011), and distant metastasis (13% vs. 4%; p < 0.001). In contrast, cystic tumors were less commonly associated with lymph node metastasis (12% vs. 30%; p < 0.001). Five-year RFS after resection was most favorable for cystic tumors without calcifications (91%), intermediate for solid tumors without calcifications (77%), and least favorable for any calcified PNET (solid 69%, cystic 67%; p = 0.043). Calcifications remained an independent predictor of RFS on multivariable analysis (p = 0.043) controlling for nodal (p < 0.001) and distant metastasis (p = 0.001). CONCLUSIONS: Easily detectable radiographic features, such as calcifications and cystic morphology, can be used preoperatively to stratify prognosis in patients with PNETs and possibly inform the decision to operate or not, as well as guide the extent of resection and potential use of neoadjuvant therapy.

Development and Validation of a Modified Eighth AJCC Staging System for Primary Pancreatic Neuroendocrine Tumors.

OBJECTIVE: To improve the prognostic accuracy of the eighth edition of AJCC staging system for pNETs with establishment and validation of a new staging system. BACKGROUND: Validation of the updated eighth AJCC staging system for pNETs has been limited and controversial. METHODS: Data from the SEER registry (1975-2016) (n = 3303) and a multi-institutional database (2000-2016) (n = 825) was used as development and validation cohorts, respectively. A mTNM was proposed by maintaining the eighth AJCC T and M definitions, and the recently proposed N status as N0 (no LNM), N1 (1-3 LNM), and N2 (≥4 LNM), but adopting a new stage classification. RESULTS: The eighth TNM staging system failed to stratify patients with stage I versus IIA, stage IIB versus IIIA, and overall stage I versus II relative to long-term OS in both database. There was a monotonic decrement in survival based on the proposed mTNM staging classification among patients derived from both the SEER (5-year OS, stage I 87.0% vs stage II 80.3% vs stage III 72.9% vs stage IV 57.2%, all P < 0.001), and multi-institutional (5-year OS, stage I 97.6% vs stage II 82.7% vs stage III 78.4% vs stage IV 50.0%, all P < 0.05) datasets. On multivariable analysis, mTNM staging remained strongly associated with prognosis, as the hazard of death incrementally increased with each stage among patients in the 2 cohorts. CONCLUSION: A mTNM pNETs clinical staging system using N0, N1, N2 nodal categories was better at stratifying patients relative to long-term OS than the eighth AJCC staging.

New Nodal Staging for Primary Pancreatic Neuroendocrine Tumors: A Multi-institutional and National Data Analysis.

OBJECTIVE: To determine the prognostic role of metastatic lymph node (LN) number and the minimal number of LNs for optimal staging of patients with pancreatic neuroendocrine tumors (pNETs). BACKGROUND: Prognosis relative to number of LN metastasis (LNM), and minimal number of LNs needed to evaluate for accurate staging, have been poorly defined for pNETs. METHODS: Number of LNM and total number of LN evaluated (TNLE) were assessed relative to recurrence-free survival (RFS) and overall survival (OS) in a multi-institutional database. External validation was performed using Surveillance, Epidemiology and End Results (SEER) registry. RESULTS: Among 854 patients who underwent resection, 233 (27.3%) had at least 1 LNM. Patients with 1, 2, or 3 LNM had a comparable worse RFS versus patients with no nodal metastasis (5-year RFS, 1 LNM 65.6%, 2 LNM 68.2%, 3 LNM 63.2% vs 0 LNM 82.6%; all P < 0.001). In contrast, patients with ≥4 LNM (proposed N2) had a worse RFS versus patients who either had 1 to 3 LNM (proposed N1) or node-negative disease (5-year RFS, ≥4 LNM 43.5% vs 1-3 LNM 66.3%, 0 LNM 82.6%; all P < 0.05) [C-statistics area under the curve (AUC) 0.650]. TNLE ≥8 had the highest discriminatory power relative to RFS (AUC 0.713) and OS (AUC 0.726) among patients who had 1 to 3 LNM, and patients who had ≥4 LNM in the multi-institutional and SEER database (n = 2764). CONCLUSIONS: Regional lymphadenectomy of at least 8 lymph nodes was necessary to stage patients accurately. The proposed nodal staging of N0, N1, and N2 optimally staged patients.

Long-Term Outcomes after Spleen-Preserving Distal Pancreatectomy for Pancreatic Neuroendocrine Tumors: Results from the US Neuroendocrine Study Group.

BACKGROUND: The adoption of spleen-preserving distal pancreatectomy (SPDP) for malignant disease such as pancreatic neuroendocrine tumors (pNETs) has been controversial. The objective of the current study was to assess the impact of SPDP on outcomes of patients with pNETs. METHODS: Patients undergoing a distal pancreatectomy for pNET between 2002 and 2016 were identified in the US Neuroendocrine Tumor Study Group database. Propensity score matching (PSM) was used to compare short- and long-term outcomes of patients undergoing SPDP versus distal pancreatectomy with splenectomy (DPS). RESULTS: Among 621 patients, 103 patients (16.6%) underwent an SPDP. Patients who underwent SPDP were more likely to have lower BMI (median, 27.5 [IQR 24.0-31.2] vs. 28.7 [IQR 25.7-33.6]; p = 0.005) and have undergone minimally invasive surgery (n = 56, 54.4% vs. n = 185, 35.7%; p < 0.001). After PSM, while the median total number of lymph nodes examined among patients who underwent an SPDP was lower compared with DPS (3 [IQR 1-8] vs. 9 [5-13]; p < 0.001), 5-year overall survival (OS) and recurrence-free survival (RFS) were comparable (OS: 96.8 vs. 92.0%, log-rank p = 0.21, RFS: 91.1 vs. 84.7%, log-rank p = 0.93). In addition, patients undergoing SPDP had less intraoperative blood loss (median, 100 mL [IQR 10-250] vs. 150 mL [IQR 100-400]; p = 0.001), lower incidence of serious complications (n = 13, 12.8% vs. n = 28, 27.5%; p = 0.014), and shorter length of stay (median: 5 days [IQR 4-7] vs. 6 days [IQR 5-13]; p = 0.049) compared with patients undergoing DPS. CONCLUSION: SPDP for pNET was associated with acceptable perioperative and long-term outcomes that were comparable to DPS. SPDP should be considered for patients with pNET.

Indications and outcomes of enucleation versus formal pancreatectomy for pancreatic neuroendocrine tumors.

BACKGROUND: Pancreatoduodenectomy (PD) or distal pancreatectomy (DP) are common procedures for patients with a pancreatic neuroendocrine tumor (pNET). Nevertheless, certain patients may benefit from a pancreas-preserving resection such as enucleation (EN). The aim of this study was to define the indications and differences in long-term outcomes among patients undergoing EN and PD/DP. METHODS: Patients undergoing resection of a pNET between 1992 and 2016 were identified. Indications and outcomes were evaluated, and propensity score matching (PSM) analysis was performed to compare long-term outcomes between patients who underwent EN versus PD/DP. RESULTS: Among 1034 patients, 143 (13.8%) underwent EN, 304 (29.4%) PD, and 587 (56.8%) DP. Indications for EN were small size (1.5 cm, IQR:1.0-1.9), functional tumors (58.0%) that were mainly insulinomas (51.7%). After PSM (n = 109 per group), incidence of postoperative pancreatic fistula (POPF) grade B/C was higher after EN (24.5%) compared with PD/DP (14.0%) (p = 0.049). Median recurrence-free survival (RFS) was comparable among patients who underwent EN (47 months, 95% CI:23-71) versus PD/DP (37 months, 95% CI: 33-47, p = 0.480). CONCLUSION: Comparable long-term outcomes were noted among patients who underwent EN versus PD/DP for pNET. The incidence of clinically significant POPF was higher after EN.

A Novel Machine-Learning Approach to Predict Recurrence After Resection of Colorectal Liver Metastases.

BACKGROUND: Surgical resection of hepatic metastases remains the only potentially curative treatment option for patients with colorectal liver metastases (CRLM). Widely adopted prognostic tools may oversimplify the impact of model parameters relative to long-term outcomes. METHODS: Patients with CRLM who underwent a hepatectomy between 2001 and 2018 were identified in an international, multi-institutional database. Bootstrap resampling methodology used in tandem with multivariable mixed-effects logistic regression analysis was applied to construct a prediction model that was validated and compared with scores proposed by Fong and Vauthey. RESULTS: Among 1406 patients who underwent hepatic resection of CRLM, 842 (59.9%) had recurrence. The full model (based on age, sex, primary tumor location, T stage, receipt of chemotherapy before hepatectomy, lymph node metastases, number of metastatic lesions in the liver, size of the largest hepatic metastases, carcinoembryonic antigen [CEA] level and KRAS status) had good discriminative ability to predict 1-year (area under the receiver operating curve [AUC], 0.693; 95% confidence interval [CI], 0.684-0.704), 3-year (AUC, 0.669; 95% CI, 0.661-0.677), and 5-year (AUC, 0.669; 95% CI, 0.661-0.679) risk of recurrence. Studies analyzing validation cohorts demonstrated similar model performance, with excellent model accuracy. In contrast, the AUCs for the Fong and Vauthey scores to predict 1-year recurrence were only 0.527 (95% CI, 0.514-0.538) and 0.525 (95% CI, 0.514-0.533), respectively. Similar trends were noted for 3- and 5-year recurrence. CONCLUSION: The proposed clinical score, derived via machine learning, which included clinical characteristics and morphologic data, as well as information on KRAS status, accurately predicted recurrence after CRLM resection with good discrimination and prognostic ability.

Minimally Invasive Versus Open Liver Resection for Hepatocellular Carcinoma in the Setting of Portal Vein Hypertension: Results of an International Multi-institutional Analysis.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) and portal vein hypertension assessed with platelet count (PVH-PLT; platelet count < 100,000/mL) are often denied surgery even when the disease is technically resectable. Short- and long-term outcomes of patients undergoing minimally invasive surgery (MIS) versus open resection for HCC and PVH-PLT were compared. METHODS: Propensity score matching (PSM) was used to balance the clinicopathological differences between MIS and non-MIS patents. Univariate comparison and standard survival analyses were utilized. RESULTS: Among 1974 patients who underwent surgery for HCC, 13% had a PVH-PLT and 33% underwent MIS. After 1:1 PSM, 407 MIS and 407 non-MIS patients were analyzed. Incidence of complications and length-of-stay (LoS) were higher among non-MIS versus MIS patients (both p ≤ 0.002). After PSM, among 178 PVH-PLT patients (89 MIS and 89 non-MIS), patients who underwent a non-MIS approach had longer LoS (> 7 days; non-MIS: 55% vs. MIS: 29%), as well as higher morbidity (non-MIS: 42% vs. MIS: 29%) [p <0.001]. In contrast, long-term oncological outcomes were comparable, including 3-year overall survival (non-MIS: 66.2% vs. MIS: 72.9%) and disease-free survival (non-MIS: 47.3% vs. MIS: 50.2%) [both p ≥ 0.08]. CONCLUSION: An MIS approach was associated with improved short-term outcomes, but similar long-term outcomes, compared with open liver resection for patients with HCC and PVH-PLT. An MIS approach for liver resection should be considered for patients with HCC, even those individuals with PVH-PLT.

Correction to: Trends in the Number of Lymph Nodes Evaluated Among Patients with Pancreatic Neuroendocrine Tumors in the United States: A Multi-Institutional and National Database Analysis.

In the original article, Ryan C. Fields' middle initial is missing.

Trends in the Number of Lymph Nodes Evaluated Among Patients with Pancreatic Neuroendocrine Tumors in the United States: A Multi-Institutional and National Database Analysis.

BACKGROUND: The role of routine lymphadenectomy in the surgical treatment of pancreatic neuroendocrine tumors (pNET) remains poorly defined. The objective of the current study was to investigate trends in the number of lymph nodes (LN) evaluated for pNET treatment at a nationwide level. METHODS: Patients undergoing surgery for pNET between 2000 and 2016 were identified in the U.S. Neuroendocrine Tumor Study Group (US-NETSG) database as well as the Surveillance, Epidemiology, and End Results (SEER) database. The number of LNs examined was evaluated over time. RESULTS: The median number of evaluated LNs increased roughly fourfold over the study period (US-NETSG, 2000: 3 LNs vs. 2016: 13 LNs; SEER, 2000: 3 LNs vs. 2016: 11 LNs, both p < 0.001). While no difference in 5-year OS and RFS was noted among patients who had 1-3 lymph node metastases (LNM) vs. ≥ 4 LNM between 2000-2007 (OS 73.5% vs. 69.9%, p = 0.12; RFS: 64.9% vs. 40.1%, p = 0.39), patients who underwent resection and LN evaluation during the period 2008-2016 had an incrementally worse survival if the patient had node negative disease, 1-3 LNM and ≥ 4 LNM (OS 86.8% vs. 82.7% vs. 74.9%, p < 0.001; RFS: 86.3% vs. 64.7% vs. 50.4%, p < 0.001). On multivariable analysis, a more recent year of diagnosis, pancreatic head tumor location, and tumor size > 2 cm were associated with 12 or more LNs evaluated in both US-NETSG and SEER databases. CONCLUSION: The number of LNs examined nearly quadrupled over the last decade. The increased number of LNs examined suggested a growing adoption of the AJCC staging manual recommendations regarding LN evaluation in the treatment of pNET.

Specific Growth Rate as a Predictor of Survival in Pancreatic Neuroendocrine Tumors: A Multi-institutional Study from the United States Neuroendocrine Study Group.

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are often indolent; however, identifying patients at risk for rapidly progressing variants is critical, particularly for those with small tumors who may be candidates for expectant management. Specific growth rate (SGR) has been predictive of survival in other malignancies but has not been examined in PNETs. METHODS: A retrospective cohort study of adult patients who underwent PNET resection from 2000 to 2016 was performed utilizing the multi-institutional United States Neuroendocrine Study Group database. Patients with ≥ 2 preoperative cross-sectional imaging studies at least 30 days apart were included in our analysis (N = 288). Patients were grouped as "high SGR" or "low SGR." Demographic and clinical factors were compared between the groups. Kaplan-Meier and log-rank analysis were used for survival analysis. Cox proportional hazard analysis was used to assess the impact of various clinical factors on overall survival (OS). RESULTS: High SGR was associated with higher T stage at resection, shorter doubling time, and elevated HbA1c (all P ≤ 0.01). Patients with high SGR had significantly decreased 5-year OS (63 vs 80%, P = 0.01) and disease-specific survival (72 vs 91%, P = 0.03) compared to those with low SGR. In patients with small (≤ 2 cm) tumors (N = 106), high SGR predicted lower 5-year OS (79 vs 96%, P = 0.01). On multivariate analysis, high SGR was independently associated with worse OS (hazard ratio 2.67, 95% confidence interval 1.05-6.84, P = 0.04). CONCLUSION: High SGR is associated with worse survival in PNET patients. Evaluating PNET SGR may enhance clinical decision-making, particularly when weighing expectant management versus surgery in patients with small tumors.

Resection of pancreatic neuroendocrine tumors: defining patterns and time course of recurrence.

BACKGROUND: To define recurrence patterns and time course, as well as risk factors associated with recurrence following curative resection of pNETs. METHOD: Patients who underwent curative-intent resection for pNET between 1997 and 2016 were identified from the US Neuroendocrine Tumor Study Group. Data on baseline and tumor-specific characteristics, overall survival (OS), timing and first-site of recurrence, predictors and recurrence management were analyzed. RESULTS: Among 1020 patients, 154 (15.1%) patients developed recurrence. Among patients who experienced recurrence, 76 (49.4%) had liver-only recurrence, while 35 (22.7%) had pancreas-only recurrence. The proportion of liver-only recurrence increased from 54.3% within one-year after surgery to 61.5% from four-to-six years after surgery; whereas the proportion of pancreas-only recurrence decreased from 26.1% to 7.7% over these time periods. While liver-only recurrence was associated with tumor characteristics, pancreas-only recurrence was only associated with surgical margin status. Patients undergoing curative resection of recurrence had comparable OS with patients who had no recurrence (median OS, pancreas-only recurrence, 133.9 months; liver-only recurrence, not attained; no recurrence, 143.0 months, p = 0.499) CONCLUSIONS: Different recurrence patterns and timing course, as well as risk factors suggest biological heterogeneity of pNET recurrence. A personalized approach to postoperative surveillance and treatment of recurrence disease should be considered.

Tumor burden score predicts tumor recurrence of non-functional pancreatic neuroendocrine tumors after curative resection.

BACKGROUND: To investigate the feasibility of Tumor Burden Score (TBS) to predict tumor recurrence following curative-intent resection of non-functional pancreatic neuroendocrine tumors (NF-pNETs). METHOD: The TBS cut-off values were determined by a statistical tool, X-tile. The influence of TBS on recurrence-free survival (RFS) was examined. RESULTS: Among 842 NF-pNETs patients, there was an incremental worsening of RFS as the TBS increased (5-year RFS, low, medium, and high TBS: 92.0%, 73.3%, and 59.3%, respectively; P < 0.001). TBS (AUC 0.74) out-performed both maximum tumor size (AUC 0.65) and number of tumors (AUC 0.5) to predict RFS (TBS vs. maximum tumor size, p = 0.05; TBS vs. number of tumors, p < 0.01). The impact of margin (low TBS: R0 80.4% vs. R1 71.9%, p = 0.01 vs. medium TBS: R0 55.8% vs. R1 37.5%, p = 0.67 vs. high TBS: R0 31.9% vs. R1 12.0%, p = 0.11) and nodal (5-year RFS, low TBS: N0 94.9% vs. N1 68.4%, p < 0.01 vs. medium TBS: N0 81.8% vs. N1 55.4%, p < 0.01 vs. high TBS: N0 58.0% vs. N1 54.2%, p = 0.15) status on 5-year RFS outcomes disappeared among patients who had higher TBS. CONCLUSIONS: TBS was strongly associated with risk of recurrence and outperformed both tumor size and number alone.

Minimally invasive versus open distal pancreatectomy for pancreatic neuroendocrine tumors: An analysis from the U.S. neuroendocrine tumor study group.

BACKGROUND: To determine short- and long-term oncologic outcomes after minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for the treatment of pancreatic neuroendocrine tumor (pNET). METHODS: The data of the patients who underwent curative MIDP or ODP for pNET between 2000 and 2016 were collected from a multi-institutional database. Propensity score matching (PSM) was used to generate 1:1 matched patients with MIDP and ODP. RESULTS: A total of 576 patients undergoing curative DP for pNET were included. Two hundred and fourteen (37.2%) patients underwent MIDP, whereas 362 (62.8%) underwent ODP. MIDP was increasingly performed over time (2000-2004: 9.3% vs 2013-2016: 54.8%; P < 0.01). In the matched cohort (n = 141 in each group), patients who underwent MIDP had less blood loss (median, 100 vs 200 mL, P < 0.001), lower incidence of Clavien-Dindo ≥ III complications (12.1% vs 24.8%, P = 0.026), and a shorter hospital stay versus ODP (median, 4 versus 7 days, P = 0.026). Patients who underwent MIDP had a lower incidence of recurrence (5-year cumulative recurrence, 10.1% vs 31.1%, P < 0.001), yet equivalent overall survival (OS) rate (5-year OS, 92.1% vs 90.9%, P = 0.550) compared with patients who underwent OPD. CONCLUSION: Patients undergoing MIDP over ODP in the treatment of pNET had comparable oncologic surgical metrics, as well as similar long-term OS.

Response to preoperative chemotherapy: impact of change in total burden score and mutational tumor status on prognosis of patients undergoing resection for colorectal liver metastases.

BACKGROUND: Progression of colorectal liver metastasis (CRLM) on preoperative chemotherapy has been associated with a worse prognosis compared with patients who have responsive disease. Defining response can be challenging as traditional criteria largely assess only tumor size. METHODS: Patients who underwent hepatectomy between 2010 and 2017 were identified using a multi-centric database. This study aimed to define the impact of preoperative chemotherapy response relative to initial tumor burden score (TBS) and determine impact of clinico-pathological variables on overall survival (OS). RESULTS: Among 784 patients who received preoperative chemotherapy, the regimen was oxaliplatin- (66%) or irinotecan-based (34%). Among patients with a TBS<6 at diagnosis, genetic status was the most important prognostic variable. Patients with a TBS<6, 5-year OS was 55%, 35%, and 0% for patients with KRAS/NRAS/BRAF wild-type, KRAS/NRAS, and BRAF mutations, respectively. Among patients who presented with CRLM with a TBS≥6, only Δ-TBS was prognostically important and patients with a Δ-TBS ≥ -10% had a 5-year OS of 27% compared with 49% for patients with a Δ-TBS < -10%. CONCLUSIONS: Prognostic stratification of patients with CRLM receiving preoperative chemotherapy should be multi-faceted and include consideration of initial tumor burden, change in tumor burden due to chemotherapy, and tumor genetic status.

Is hepatectomy safe following Yttrium-90 therapy? A multi-institutional international experience.

BACKGROUND: Single institution reports demonstrate variable safety profiles when liver-directed therapy with Yttrium-90 (Y-90) is followed by hepatectomy. We hypothesized that in well-selected patients, hepatectomy after Y90 is feasible and safe. METHODS: Nine institutions contributed data for patients undergoing Y90 followed by hepatectomy (2008-2017). Clinicopathologic and perioperative data were analyzed, with 90-day morbidity and mortality as primary endpoints. RESULTS: Forty-seven patients were included. Median age was 59 (20-75) and 62% were male. Malignancies treated included hepatocellular cancer (n = 14; 30%), colorectal cancer (n = 11; 23%), cholangiocarcinoma (n = 8; 17%), neuroendocrine (n = 8; 17%) and other tumors (n = 6). The distribution of Y-90 treatment was: right (n = 30; 64%), bilobar (n = 14; 30%), and left (n = 3; 6%). Median future liver remnant (FLR) following Y90 was 44% (30-78). Resections were primarily right (n = 16; 34%) and extended right (n = 14; 30%) hepatectomies. The median time to resection from Y90 was 196 days (13-947). The 90-day complication rate was 43% and mortality was 2%. Risk factors for Clavien-Dindo Grade>3 complications included: number of Y-90-treated lobes (OR 4.5; 95% CI1.14-17.7; p = 0.03), extent of surgery (p = 0.04) and operative time (p = 0.009). CONCLUSIONS: These data demonstrate that hepatectomy following Y-90 is safe in well-selected populations. This multi-disciplinary treatment paradigm should be more widely studied, and potentially adopted, for patients with inadequate FLR.

Nomogram predicting the risk of recurrence after curative-intent resection of primary non-metastatic gastrointestinal neuroendocrine tumors: An analysis of the U.S. Neuroendocrine Tumor Study Group.

BACKGROUND: The risk of recurrence after resection of non-metastatic gastro-entero-pancreatic neuroendocrine tumors (GEP-NET) is poorly defined. We developed/validated a nomogram to predict risk of recurrence after curative-intent resection. METHODS: A training set to develop the nomogram and test set for validation were identified. The predictive ability of the nomogram was assessed using c-indices. RESULTS: Among 1477 patients, 673 (46%) were included in the training set and 804 (54%) in y the test set. On multivariable analysis, Ki-67, tumor size, nodal status, and invasion of adjacent organs were independent predictors of DFS. The risk of death increased by 8% for each percentage increase in the Ki-67 index (HR 1.08, 95% CI, 1.05-1.10; P < 0.001). GEP-NET invading adjacent organs had a HR of 1.65 (95% CI, 1.03-2.65; P = 0.038), similar to tumors ≥3 cm (HR 1.67, 95% CI, 1.11-2.51; P = 0.014). Patients with 1-3 positive nodes and patients with >3 positive nodes had a HR of 1.81 (95% CI, 1.12-2.87; P = 0.014) and 2.51 (95% CI, 1.50-4.24; P < 0.001), respectively. The nomogram demonstrated good ability to predict risk of recurrence (c-index: training set, 0.739; test set, 0.718). CONCLUSION: The nomogram was able to predict the risk of recurrence and can be easily applied in the clinical setting.

Surrogate End Points for Overall Survival in Metastatic, Locally Advanced, or Unresectable Pancreatic Cancer: A Systematic Review and Meta-Analysis of 24 Randomized Controlled Trials.

BACKGROUND: Overall survival (OS) has traditionally been the primary end point in studies evaluating the clinical benefit of first-line chemotherapy in metastatic, locally advanced, or unresectable pancreatic cancer (MLAUPC). Given the prolonged follow-up assessment required to obtain OS and its potential to be confounded by second-line treatments, this study sought to determine whether progression-free survival (PFS), response rate (RR), or disease control rate (DCR) can serve as a reliable surrogate for OS. METHODS: A systematic review and meta-analysis was performed including all phase 3 clinical trials for MLAUPC, with gemcitabine as the control arm of the trial. The hazard ratios (HRs) for OS and PFS and odds ratios (ORs) for RR and DCR were recorded. A weighted Pearson correlation coefficient was estimated for the association between OS and the other outcomes. The primary analysis used a random effects weighting model, whereas the secondary analyses used a fixed effects- or sample size-weighted approach. RESULTS: For the study, 24 randomized controlled trials were identified. The Pearson correlation coefficient between OS and PFS was 0.86 (95% confidence interval [CI] 0.67-0.94; p < 0.001). Sensitivity analysis of the studies with little to no crossover further showed a correlation coefficient of 0.91 (95% CI 0.76-0.97; p < 0.001). The correlation coefficient between OS and RR was 0.45 (95% CI 0.07-0.72; p = 0.02) and between OS and DCR was 0.74 (95% CI 0.38-0.90; p < 0.001). CONCLUSIONS: First-line chemotherapy trials for MLAUPC show a robust correlation between OS and PFS, affirming its role as a surrogate of OS.