Neil Saunders

Prognostic Performance of Different Lymph Node Staging Systems After Curative Intent Resection for Gastric Adenocarcinoma

Objective: To compare the prognostic performance of American Joint Committee on Cancer/International Union Against Cancer seventh N stage relative to lymph node ratio (LNR), log odds of metastatic lymph nodes (LODDS), and N score in gastric adenocarcinoma. Background: Metastatic disease to the regional LN basin is a strong predictor of worse long-term outcome following curative intent resection of gastric adenocarcinoma. Methods: A total of 804 patients who underwent surgical resection of gastric adenocarcinoma were identified from a multi-institutional database. The relative discriminative abilities of the different LN staging/scoring systems were assessed using the Akaikes Information Criterion (AIC) and the Harrells concordance index (c statistic). Results: Of the 804 patients, 333 (41.4%) had no lymph node metastasis, whereas 471 (58.6%) had lymph node metastasis. Patients with ≥N1 disease had an increased risk of death (hazards ratio = 2.09, 95% confidence interval: 1.68–2.61; P < 0.001]. When assessed using categorical cutoff values, LNR had a somewhat better prognostic performance (C index: 0.630; AIC: 4321.9) than the American Joint Committee on Cancer seventh edition (C index: 0.615; AIC: 4341.9), LODDS (C index: 0.615; AIC: 4323.4), or N score (C index: 0.620; AIC: 4324.6). When LN status was modeled as a continuous variable, the LODDS staging system (C index: 0.636; AIC: 4304.0) outperformed other staging/scoring systems including the N score (C index: 0.632; AIC: 4308.4) and LNR (C index: 0.631; AIC: 4225.8). Among patients with LNR scores of 0 or 1, there was a residual heterogeneity of outcomes that was better stratified and characterized by the LODDS. Conclusions: When assessed as a categorical variable, LNR was the most powerful manner to stratify patients on the basis of LN status. LODDS was a better predicator of survival when LN status was modeled as a continuous variable, especially among those patients with either very low or high LNR.

Effect of Perioperative Transfusion on Recurrence and Survival after Gastric Cancer Resection: A 7-Institution Analysis of 765 Patients from the US Gastric Cancer Collaborative

BACKGROUND The prognostic effect of perioperative blood transfusion on recurrence and survival in patients undergoing resection of gastric adenocarcinoma (GAC) remains controversial. STUDY DESIGN All patients who underwent resection for GAC from 2000 to 2012 at the 7 institutions of the US Gastric Cancer Collaborative were identified. The effect of transfusion on recurrence-free (RFS) and overall survival (OS) in the context of adverse clinicopathologic variables was examined by univariate and multivariate regression analyses. RESULTS Of 965 patients, 765 underwent curative intent R0 resection. Median follow-up was 44 months; 30-day mortalities were excluded. Median estimated blood loss (EBL) was 200 mL, and 168 patients (22%) received perioperative allogeneic blood transfusions. Transfused patients were less likely to receive adjuvant therapy (44% vs 56%; p = 0.01). Transfusion was associated with significantly decreased median RFS (13.5 vs 37.2 months, p < 0.001). Median OS was similarly decreased in patients receiving transfusions (18.6 vs 49.8 months, p < 0.001). On multivariate analysis, transfusion remained an independent risk factor for decreased RFS (hazard ratio [HR] 1.63; 95% CI 1.13 to 2.37; p = 0.010) and decreased OS (HR 1.79; 95% CI 1.21 to 2.67; p = 0.004), regardless of EBL or need for splenectomy. Timing (intraoperative vs postoperative) and volume of transfusion did not alter the negative prognostic effect of transfusion on survival. CONCLUSIONS Perioperative allogeneic blood transfusion is associated with decreased RFS and OS after resection of gastric cancer, independent of adverse clinicopathologic factors. This supports the judicious use of perioperative transfusion during resection of gastric cancer.

A nomogram to predict overall survival and disease-free survival after curative resection of gastric adenocarcinoma.

AbstractBackgroundThe American Cancer Society projects there will be over 22,000 new cases, resulting in nearly 11,000 deaths, related to gastric adenocarcinoma in the US in 2014. The aim of the current study was to find clinicopathologic variables associated with disease-free survival (DFS) and overall survival (OS) following curative resection of gastric adenocarcinoma, and create a nomogram for individual risk prediction.Methods A nomogram to predict DFS and OS following surgical resection of gastric adenocarcinoma was constructed using a multi-institutional cohort of patients who underwent surgery for primary gastric adenocarcinoma at seven major institutions in the US between January 2000 and August 2013. Discrimination and calibration of the nomogram were tested by C-statistic, Kaplan–Meier curves, and calibration plots.ResultsA total of 719 patients who underwent surgery for primary gastric adenocarcinoma were included in the study. Using the backward selection of clinically relevant variables with Akaike information criteria, age, sex, tumor site, depth of invasion, and lymph node ratio (LNR) were selected as factors predictive of OS, while age, tumor site, depth of invasion, and LNR were incorporated in the prediction of DFS. A nomogram was constructed to predict OS and DFS using these variables. Discrimination and calibration of the nomogram revealed good predictive abilities (C-index, DFS 0.711; OS 0.702).Conclusion Independent predictors of recurrence and death following surgery for primary gastric adenocarcinoma were used to create a nomogram to predict DFS and OS. The nomogram was able to stratify patients into prognostic groups, and performed well on internal validation.

Examination of Unplanned 30-Day Readmissions to a Comprehensive Cancer Hospital

PURPOSE The Centers for Medicare and Medicaid Services (CMS), under the Hospitals Readmissions Reductions Program, may withhold regular reimbursements for excessive 30-day readmissions for select diagnoses. Such penalties imply that some readmissions reflect poor clinical decision making or care during the initial hospitalization. We examined factors related to potentially preventable readmissions in CMS patients at a tertiary cancer hospital. METHODS The medical records of all CMS patients with unplanned readmissions within 30 days of index admission were reviewed over 6 months (October 15, 2011-April 15, 2012). Each readmission was classified as not preventable or potentially preventable. Factors associated with potentially preventable readmissions were sought. RESULTS Of 2,531 inpatient admissions in CMS patients over 6 months, 185 patients experienced at least one readmission for 282 total readmissions (11%). Median time to readmission was 9 days (range, 0 to 30 days). The most common causes for first readmission were new diagnoses not present at first admission (n = 43, 23%), new or worsening symptoms due to cancer progression (n = 40, 21%) and complications of procedures (n = 25, 13%). There were 38 (21%) initial readmissions classified as potentially preventable. Use of total parenteral nutrition at the time of discharge was associated with potentially preventable readmission (P = .028). CONCLUSION Most unplanned readmissions to a tertiary cancer hospital are related to progression of disease, new diagnoses, and procedure complications. Minimizing readmissions in complex cancer patients is challenging. Larger multi-institutional datasets are needed to determine a reasonable standard for expected readmission rates.

Factors Associated With Recurrence and Survival in Lymph Node-negative Gastric Adenocarcinoma: A 7-Institution Study of the US Gastric Cancer Collaborative.

Objectives: To determine pathologic features associated with recurrence and survival in patients with lymph node–negative gastric adenocarcinoma. Study Design: Multi-institutional retrospective analysis. Background: Lymph node status is among the most important predictors of recurrence after gastrectomy for gastric adenocarcinoma. Pathologic features predictive of recurrence in patients with node-negative disease are less well established. Methods: Patients who underwent curative resection for gastric adenocarcinoma between 2000 and 2012 from 7 institutions of the US Gastric Cancer Collaborative were analyzed, excluding 30-day mortalities and stage IV disease. Competing risks regression and multivariate Cox regression were used to determine pathologic features associated with time to recurrence and overall survival. Differences in cumulative incidence of recurrence were assessed using the Gray method (for univariate nonparametric analyses) and the Fine and Gray method (for multivariate analyses) and shown as subhazard ratios (SHRs) and adjusted subhazard ratios (aSHRs), respectively. Results: Of 805 patients who met inclusion criteria, 317 (39%) had node-negative disease, of which 54 (17%) recurred. By 2 and 5 years, 66% and 88% of patients, respectively, experienced recurrence. On multivariate competing risks regression, only T-stage 3 or higher was associated with shorter time to recurrence [aSHR = 2.7; 95% confidence interval (CI), 1.5–5.2]. Multivariate Cox regression showed T-stage 3 or higher [hazard ratio (HR) = 1.8; 95% CI, 1.2–2.8], lymphovascular invasion (HR = 2.2; 95% CI, 1.4–3.4), and signet ring histology (HR = 2.1; 95% CI, 1.2–3.6) to be associated with decreased overall survival. Conclusions: Despite absence of lymph node involvement, patients with T-stage 3 or higher have a significantly shorter time to recurrence. These patients may benefit from more aggressive adjuvant therapy and postoperative surveillance regimens.

An assessment of feeding jejunostomy tube placement at the time of resection for gastric adenocarcinoma: A seven‐institution analysis of 837 patients from the U.S. gastric cancer collaborative

Jejunostomy feeding tubes (J‐tubes) are often placed during resection for gastric adenocarcinoma (GAC). Their effect on postoperative complications and receipt of adjuvant therapy is unclear.

The importance of the proximal resection margin distance for proximal gastric adenocarcinoma: A multi-institutional study of the US Gastric Cancer Collaborative

A 5 cm margin is advocated for distal gastric adenocarcinoma (GAC). The optimal proximal resection margin (PM) length for proximal GAC is not established.

Impact of lymph node ratio in selecting patients with resected gastric cancer for adjuvant therapy

Background. The impact of adjuvant chemotherapy and chemo‐radiation therapy in the treatment of resectable gastric cancer remains varied. We sought to define the clinical impact of lymph node ratio on the relative benefit of adjuvant chemotherapy or chemo‐radiation therapy among patients having undergone curative‐intent resection for gastric cancer. Methods. Using the multi‐institutional US Gastric Cancer Collaborative database, 719 patients with gastric adenocarcinoma who underwent curative‐intent resection between 2000 and 2013 were identified. Patients with metastasis or an R2 margin were excluded. The impact of lymph node ratio on overall survival among patients who received chemotherapy or chemo‐radiation therapy was evaluated. Results. Median patient age was 65 years, and the majority of patients were male (56.2%). The majority of patients underwent either subtotal (40.6%) or total gastrectomy (41.0%), with the remainder undergoing distal gastrectomy or wedge resection (18.4%). On pathology, median tumor size was 4 cm; most patients had a T3 (33.0%) or T4 (27.9%) lesion with lymph node metastasis (59.7%). Margin status was R0 in 92.5% of patients. A total of 325 (45.2%) patients underwent resection alone, 253 (35.2%) patients received 5‐FU or capecitabine‐based chemo‐radiation therapy, whereas the remaining 141 (19.6%) received chemotherapy. Median overall survival was 40.9 months, and 5‐year overall survival was 40.3%. According to lymph node ratio categories, 5‐year overall survival for patients with a lymph node ratio of 0, 0.01–0.10, >0.10–0.25, >0.25 were 54.1%, 53.1 %, 49.1 % and 19.8 %, respectively. Factors associated with worse overall survival included involvement of the gastroesophageal junction (hazard ratio 1.8), T‐stage (3–4: hazard ratio 2.1), lymphovascular invasion (hazard ratio 1.4), and lymph node ratio (>0.25: hazard ratio 2.3; all P < .05). In contrast, receipt of adjuvant chemo‐radiation therapy was associated with an improved overall survival in the multivariable model (versus resection alone: hazard ratio 0.40; versus chemotherapy: hazard ratio 0.45, both P < .001). The benefit of chemo‐radiation therapy for resected gastric cancer was noted only among patients with lymph node ratio >0.25 (versus resection alone: hazard ratio R 0.34; versus chemotherapy: hazard ratio 0.45, both P < .001). In contrast, there was no noted overall survival benefit of chemotherapy or chemo‐radiation therapy among patients with lymph node ratio ≤0.25 (all P > .05). Conclusion. Adjuvant chemotherapy or chemo‐radiation therapy was utilized in more than one‐half of patients undergoing curative‐intent resection for gastric cancer. Lymph node ratio may be a useful tool to select patients for adjuvant chemo‐radiation therapy, because the benefit of chemo‐radiation therapy was isolated to patients with greater degrees of lymphatic spread (ie, lymph node ratio >0.25).

Is linitis plastica a contraindication for surgical resection? A 7-institution study of the U.S. Gastric Cancer Collaborative.

118 Background: Linitis plastica (LP) describes a diffusively infiltrative gastric adenocarcinoma that portends poor prognosis. Current treatment guidelines do not differentiate between LP and non-LP cancers and it is not known if the same staging system should be applied to both situations. Methods: Using the multi-institutional U.S. Gastric Cancer Collaborative database, 869 patients with gastric adenocarcinoma who underwent resection between 2000-2012 were identified. Clinicopathologic, perioperative and survival outcomes of the 58 patients with LP were compared to the 811 patients without LP. Results: Advanced disease (stage III/IV) at presentation was more common in patients with LP compared to non-LP patients (90 vs 44%, p<0.01). Despite the fact that most LP patients underwent total gastrectomy (88% vs 57%, p<0.01), positive margins were more common in LP patients (33 vs 7%, p<0.01). There was no difference in perioperative complications (48 vs 43%, p=0.45) or mortality (7 vs 3%, p=0.12) between LP...

Optimal extent of lymphadenectomy in gastric adenocarcinoma: A seven-institution study of the U.S. Gastric Cancer Collaborative.

115 Background: The optimal extent of lymphadenectomy in the treatment of gastric adenocarcinoma continues to be a subject of intense debate. We aimed to compare gastrectomy outcomes following limited (D1) or extended (D2) lymphadenectomy. Methods: Using the multi-institutional U.S. Gastric Cancer Collaborative database, we reviewed the morbidity, mortality, recurrence, and overall survival (OS) of 727 patients receiving D1 or D2 lymphadenectomies. Patients with stage IV disease, prior gastrectomy, and age 85 or greater were excluded. Multivariate analyses included variables with p values less than 0.1. Results: Between 2000 and 2014, 266 (36.6%) and 461 (63.4%) patients received a D1 and D2 lymphadenectomy, respectively. ASA class, mean number of comorbidities, grade, stage, and signet ring cell subtypes were similar between groups. Neoadjuvant and adjuvant chemotherapy was more common in the D2 group (p<0.001). The mean number of lymph nodes recovered was significantly higher in patients receiving a D2 ...