Extremity Soft Tissue Sarcoma: A Multi-Institutional Validation of Prognostic Nomograms.

BACKGROUND: Prognostic nomograms for patients with resected extremity soft tissue sarcoma (STS) include the Sarculator and Memorial Sloan Kettering (MSKCC) nomograms. We sought to validate these two nomograms within a large, modern, multi-institutional cohort of resected primary extremity STS patients. METHODS: Resected primary extremity STS patients from 2000 to 2017 were identified across nine high-volume U.S. institutions. Predicted 5- and 10-year overall survival (OS) and distant metastases cumulative incidence (DMCI), and 4-, 8-, and 12-year disease-specific survival (DSS) were calculated with Sarculator and MSKCC nomograms, respectively. Predicted survival probabilities stratified in quintiles were compared in calibration plots to observed survival assessed by Kaplan-Meier estimates. Cumulative incidence was estimated for DMCI. Harrell's concordance index (C-index) assessed discriminative ability of nomograms. RESULTS: A total of 1326 patients underwent resection of primary extremity STS. Common histologies included: undifferentiated pleomorphic sarcoma (35%), fibrosarcoma (13%), and leiomyosarcoma (9%). Median tumor size was 8.0 cm (IQR 4.5-13.0). Tumor grade distribution was: Grade 1 (13%), Grade 2 (9%), Grade 3 (78%). Median OS was 172 months, with estimated 5- and 10-year OS of 70% and 58%. C-indices for 5- and 10-year OS (Sarculator) were 0.72 (95% CI 0.70-0.75) and 0.73 (95% CI 0.70-0.75), and 0.72 (95% CI 0.69-0.75) for 5- and 10-year DMCI. C-indices for 4-, 8-, and 12-year DSS (MSKCC) were 0.71 (95% CI 0.68-0.75). Calibration plots showed good prognostication across all outcomes. CONCLUSIONS: Sarculator and MSKCC nomograms demonstrated good prognostic ability for survival and recurrence outcomes in a modern, multi-institutional validation cohort of resected primary extremity STS patients. External validation of these nomograms supports their ongoing incorporation into clinical practice.

Interaction of Postoperative Morbidity and Receipt of Adjuvant Therapy on Long-Term Survival After Resection for Gastric Adenocarcinoma: Results From the U.S. Gastric Cancer Collaborative.

BACKGROUND: Postoperative complications (POCs) can negatively impact survival after oncologic resection. POCs may also decrease the rate of adjuvant therapy completion. We evaluated the impact of complications on gastric cancer survival and analyzed the combined effect of complications and adjuvant therapy on survival. METHODS: We analyzed 824 patients from 7 institutions of the U.S. Gastric Cancer Collaborative who underwent curative resection for gastric adenocarcinoma between 2000 and 2012. POC were graded using the modified Clavien-Dindo system. Survival probabilities were estimated using the method of Kaplan and Meier and analyzed using multivariate Cox regression. RESULTS: Median follow-up was 35 months. The overall complication rate was 41 %. The 5-year overall survival (OS) and recurrence-free survival (RFS) of patients who experienced complications were 27 and 23 %, respectively, compared with 43 and 40 % in patients who did not have complications (p < 0.0001 for OS and RFS). On multivariate analysis, POC remained an independent predictor for decreased OS and RFS (HR 1.3, 95 % CI 1.1-1.6, p = 0.03 for OS; HR 1.3, 95 % CI 1.01-1.6, p = 0.03 for RFS). Patients who experienced POC were less likely to receive adjuvant therapy (OR 0.5, 95 % CI 0.3-0.7, p < 0.001). The interaction of complications and failure to receive adjuvant therapy significantly increased the hazard of death compared with patients who had neither complications nor adjuvant therapy (HR 2.3, 95 % CI 1.6-3.2, p < 0.001). CONCLUSIONS: Postoperative complications adversely affect long-term outcomes after gastrectomy for gastric cancer. Not receiving adjuvant therapy in the face of POC portends an especially poor prognosis following gastrectomy for gastric cancer.

Multivisceral Resection for Gastric Cancer: Results from the US Gastric Cancer Collaborative.

BACKGROUND: Resection of an adjacent organ during gastrectomy for gastric cancer is occasionally necessary to achieve margin clearance. The short- and long-term outcomes of this approach remain unclear. METHODS: Patients who underwent gastric cancer resection in seven U.S. academic institutions from 2000 to 2012 were evaluated to compare perioperative morbidity, mortality, and survival outcomes, stratified by the need for and type of multivisceral resection (MVR). RESULTS: Of 835 patients undergoing curative-intent gastrectomy, 159 (19 %) had MVR. The most common adjacent organs resected were the spleen (48 %), pancreas (27 %), liver segments 2/3 (14 %), and colon (13 %). As extent of resection increased (gastrectomy only, n = 676; MVR without pancreatectomy, n = 116; and MVR with pancreatectomy, n = 43), perioperative morbidity was higher: any complication (45, 60, 59 %, p = 0.012), major complication (17, 31, 33 %, p = 0.001), anastomotic leak (5, 11, 19 %, p < 0.001), and respiratory failure (9, 15, 22 %, p = 0.012). However, perioperative mortality did not significantly increase (30-day: 3, 4, 2 %, p = 0.74; 90-day: 6, 8, 9 %, p = 0.61). Overall survival after resection decreased as extent of resection increased (5-year: 42, 28, 6 %). After controlling for age, race, T stage, N stage, grade, margin status, perineural invasion, adjuvant therapy, and blood transfusion, MVR with pancreatectomy (HR 1.67, p = 0.044), but not MVR without pancreatectomy (HR 0.97, p = 0.759), remained an independent predictor of poor survival. CONCLUSION: In this modern, multi-institutional cohort of gastric cancer patients, multivisceral resection was associated with higher perioperative morbidity but not significantly higher perioperative mortality. If concomitant pancreatectomy is anticipated, patients should be selected with extreme caution because long-term survival remains poor.

Gastric remnant cancer: A distinct entity or simply another proximal gastric cancer?

BACKGROUND: The purpose of this study was to compare outcomes following resection of gastric remnant (GRC) and conventional gastric cancer. METHODS: Patients who underwent resection for gastric cancer in 8 academic institutions from 2000-2012 were evaluated to compare morbidity, mortality, and survival based on history of prior gastrectomy. RESULTS: Of the 979 patients who underwent gastrectomy with curative-intent during the 12-year study period, 55 patients (5.8%) presented with GRC and 924 patients (94.4%) presented with conventional gastric cancer. Patients with GRC were slightly older (median 69 vs. 66 years). GRC was associated with higher rates of complication (56% vs. 41%, P = 0.028), longer operative times (301 vs. 237 min, P < 0.001), higher intraoperative blood loss (300 vs. 200 ml, P = 0.012), and greater need for blood transfusion (43% vs. 23%, P = 0.001). There were no significant differences in 30-day (3.6% vs. 4%) or 90-day mortality (9% vs. 8%) between the two groups. Overall survival rates were similar between GRC and conventional gastric cancer (5-year 20.3% vs. 38.6%, P = 0.446). Multivariate analysis revealed that history of gastrectomy was not predictive of survival while established predictors (older age, advanced T-stage, nodal involvement, blood transfusion, multivisceral resection, and any complication) were associated with poor survival. CONCLUSIONS: Despite higher morbidity, prognosis after resection of gastric remnant cancer is similar to conventional gastric cancer.

Current treatment of locoregional recurrence of melanoma.

Surgical resection is the mainstay of therapy for locoregional recurrence of melanoma and the best chance for long-term cure in patients with locoregional recurrence of melanoma. In addition to true local recurrence at the site of the primary lesion, locoregional relapse can occur as regional nodal disease or as satellite or in-transit metastases, which may be unresectable and can present significant treatment challenges. Options for unresectable locoregional recurrence include regional hyperthermic isolated limb perfusion or isolated limb infusion, topical therapies, intralesional injection therapies, laser ablation, radiation therapy, and systemic therapy. Given the risk of further relapse and the negative impact on prognosis and overall survival after locoregional recurrence of melanoma, most patients should be considered for aggressive locoregional therapy.

Predictors and Prognostic Implications of Perioperative Chemotherapy Completion in Gastric Cancer.

BACKGROUND: Perioperative chemotherapy in gastric cancer is increasingly used since the "MAGIC" trial, while clinical practice data outside of trials remain limited. We sought to evaluate the predictors and prognostic implications of perioperative chemotherapy completion in patients undergoing curative-intent gastrectomy across multiple US institutions. METHODS: Patients who underwent curative-intent resection of gastric adenocarcinoma between 2000 and 2012 in eight institutions of the US Gastric Cancer Collaborative were identified. Patients who received preoperative chemotherapy were included, while those who died within 90 days or with unknown adjuvant chemotherapy status were excluded. Predictors of chemotherapy completion and survival were identified using multivariable logistic regression and Cox proportional hazards. RESULTS: One hundred sixty three patients were included (median age 63.3, 36.8% female). The postoperative component of perioperative chemotherapy was administered in 112 (68.7%) patients. Factors independently associated with receipt of adjuvant chemotherapy were younger age (odds ratio (OR) 2.73, P = 0.03), T3 tumors (OR 14.3, P = 0.04), lymph node metastasis (OR 5.82, P = 0.03), and D2 lymphadenectomy (OR 4.12, P = 0.007), and, inversely, postoperative complications (OR 0.25, P = 0.008). Median overall survival (OS) was 25.1 months and 5-year OS was 36.5%. Predictors of OS were preexisting cardiac disease (hazard ratio (HR) 2.7, 95% CI 1.13-6.46), concurrent splenectomy (HR 4.11, 95% CI 1.68-10.0), tumor stage (reference stage I; stage II HR 2.62; 95% CI 0.99-6.94; stage III HR 4.86, 95% CI 1.81-13.02), and D2 lymphadenectomy (HR 0.43, 95% CI 0.19-0.95). After accounting for these factors, adjuvant chemotherapy administration was associated with improved OS (HR 0.33, 95% CI 0.14-0.82). CONCLUSION: Completion of perioperative chemotherapy was successful in two thirds of patients with gastric cancer and was independently associated with improved survival.

Stage-Specific Prognostic Effect of Race in Patients with Resectable Gastric Adenocarcinoma: An 8-Institution Study of the US Gastric Cancer Collaborative.

BACKGROUND: Gastric cancer constitutes a major public health problem. This study sought to evaluate the relevance of race in gastric cancer and its prognostic effect in the overall outcomes of patients with gastric adenocarcinoma. STUDY DESIGN: Patients who underwent curative intent resection of gastric adenocarcinoma in 8 institutions of the US Gastric Cancer Collaborative were included, from 2000 to 2012. Nonparametric descriptive statistics were used to evaluate characteristics of standard demographic data. Multivariate Cox proportional hazards regression was used to identify factors associated with recurrence-free survival and overall survival. RESULTS: There were 1,077 patients included in the study, the majority of whom were of Caucasian race (n = 698, 68%), followed by African-American (n = 164, 15%), Asian (n = 132, 12%), Hispanic (n = 34, 3.2%), and other (n = 49, 4.5%). Clinicopathologic data were similarly distributed among the 5 groups. Mean follow-up was 27.1 months. By multivariate, stage-specific analysis, Asian race was a significant predictor of recurrence (all stages hazard ratio [HR] 0.45 95% CI [0.23, 0.97], p = 0.041) and of overall survival (all stages HR 0.35 95% CI [0.18, 0.68], p = 0.002). Recurrence-free survival was significantly increased in the Asian population compared with the non-Asian population (25th percentile: 38.6 vs 17.7 months, p = 0.0096), as was overall median survival (141 vs 38.8 months, p < 0.001). CONCLUSIONS: Patients of Asian race undergoing curative gastrectomy for gastric adenocarcinoma appear to have a better prognosis stage for stage. Further studies are required to elucidate the underlying etiology of this phenomenon.

Number of Lymph Nodes Removed and Survival after Gastric Cancer Resection: An Analysis from the US Gastric Cancer Collaborative.

BACKGROUND: Examination of at least 16 lymph nodes (LNs) has been traditionally recommended during gastric adenocarcinoma resection to optimize staging, but the impact of this strategy on survival is uncertain. Because recent randomized trials have demonstrated a therapeutic benefit from extended lymphadenectomy, we sought to investigate the impact of the number of LNs removed on prognosis after gastric adenocarcinoma resection. STUDY DESIGN: We analyzed patients who underwent gastrectomy for gastric adenocarcinoma from 2000 to 2012, at 7 US academic institutions. Patients with M1 disease or R2 resections were excluded. Disease-specific survival (DSS) was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses. RESULTS: Of 742 patients, 257 (35%) had 7 to 15 LNs removed and 485 (65%) had ≥16 LNs removed. Disease-specific survival was not significantly longer after removal of ≥16 vs 7 to 15 LNs (10-year survival, 55% vs 47%, respectively; p = 0.53) for the entire cohort, but was significantly improved in the subset of patients with stage IA to IIIA (10-year survival, 74% vs 57%, respectively; p = 0.018) or N0-2 disease (72% vs 55%, respectively; p = 0.023). Similarly, for patients who were classified to more likely be "true N0-2," based on frequentist analysis incorporating both the number of positive and of total LNs removed, the hazard ratio for disease-related death (adjusted for T stage, R status, grade, receipt of neoadjuvant and adjuvant therapy, and institution) significantly decreased as the number of LNs removed increased. CONCLUSIONS: The number of LNs removed during gastrectomy for adenocarcinoma appears itself to have prognostic implications for long-term survival.