title: Omission of adjuvant therapy after gastric cancer resection: development of a validated risk model.
abstract: NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Gastric Cancer recommend adjuvant chemotherapy with or without radiotherapy following after resection of gastric adenocarcinoma (GA) for patients who have not received neoadjuvant therapy. Despite frequent noncompliance with NCCN Guidelines nationally, risk factors underlying adjuvant therapy omission (ATom) have not been well characterized. We developed an internally validated preoperative instrument stratifying patients by incremental risk of ATom. The National Cancer Data Base was queried for patients with stage IB-III GA undergoing gastrectomy; those receiving neoadjuvant therapy were excluded. Multivariable models identified factors associated with ATom between 2006 and 2011. Internal validation was performed using bootstrap analysis; model discrimination and calibration were assessed using k-fold cross-validation and Hosmer-Lemeshow procedures, respectively. Using weighted β-coefficients, a simplified Omission Risk Score (ORS) was created to stratify ATom risk. The impact of ATom on overall survival (OS) was examined in ORS risk-stratified cohorts. In 4,728 patients (median age, 70 years; 64.8% male), 53.7% had ATom. The bootstrap-validated model identified advancing age, comorbidity, underinsured/uninsured status, proximal tumor location, and clinical T1/2 and N0 tumors as independent ATom predictors, demonstrating good discrimination. The simplified ORS, stratifying patients into low-, moderate-, and high-risk categories, predicted incremental risk of ATom (30% vs 53% vs 80%, respectively) and progressive delay to adjuvant therapy initiation (median time, 51 vs 55 vs 61 days, respectively). Patients at moderate/high-risk of ATom demonstrated worsening risk-adjusted mortality compared with low-risk patients (median OS, 26.4 vs 29.2 months). This ORS may aid in rational selection of multimodality treatment sequence in GA.
authors.affiliation: From the Department of Surgery; Division of Hematology/Oncology, Department of Medicine; and Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Jashodeep
authors.initials: J
authors.lastname: Datta
authors.affiliation: From the Department of Surgery; Division of Hematology/Oncology, Department of Medicine; and Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: McMillan
authors.affiliation: From the Department of Surgery; Division of Hematology/Oncology, Department of Medicine; and Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Eric K
authors.initials: EK
authors.lastname: Shang
authors.affiliation: From the Department of Surgery; Division of Hematology/Oncology, Department of Medicine; and Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Ronac
authors.initials: R
authors.lastname: Mamtani
authors.affiliation: From the Department of Surgery; Division of Hematology/Oncology, Department of Medicine; and Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Russell S
authors.initials: RS
authors.lastname: Lewis
authors.affiliation: From the Department of Surgery; Division of Hematology/Oncology, Department of Medicine; and Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Rachel R
authors.initials: RR
authors.lastname: Kelz
authors.affiliation: From the Department of Surgery; Division of Hematology/Oncology, Department of Medicine; and Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Ursina
authors.initials: U
authors.lastname: Teitelbaum
authors.affiliation: From the Department of Surgery; Division of Hematology/Oncology, Department of Medicine; and Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: John P
authors.initials: JP
authors.lastname: Plastaras
authors.affiliation: From the Department of Surgery; Division of Hematology/Oncology, Department of Medicine; and Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Drebin
authors.affiliation: From the Department of Surgery; Division of Hematology/Oncology, Department of Medicine; and Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Fraker
authors.affiliation: From the Department of Surgery; Division of Hematology/Oncology, Department of Medicine; and Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Giorgos C
authors.initials: GC
authors.lastname: Karakousis
authors.affiliation: From the Department of Surgery; Division of Hematology/Oncology, Department of Medicine; and Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Roses
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011182:Postoperative Care; D018714:Radiotherapy, Adjuvant; D015203:Reproducibility of Results; D013274:Stomach Neoplasms / Q000473:pathology / Q000628:therapy*; D047368:Tumor Burden