Nomograms for the Prediction of Local Control, Distant Metastases ...

Proceedings of the 52nd Annual ASTRO Meeting

215

Nomograms for the Prediction of Local Control, Distant Metastases, and Survival for Pancreas Cancer Patients

G. Mattiucci1, V. Valentini1, R. G. P. M. van Stiphout2,3, F. Calvo4, M. Reni5, R. C. Miller6, G. B. Doglietto7, S. Alfieri7, G. Lammering2, P. Lambin2 1 Department of Radiotherapy, Universita` Cattolica S. Cuore, Rome, Italy, 2Department of Radiation Oncology (MAASTRO), GROW, University Medical Centre Maastricht, Maastricht, Netherlands, 3Department of Knowledge Engineering, Faculty of Humanities and Sciences, Maastricht University, Maastricht, Netherlands, 4Department of Radiotherapy, Hospital Gregorio Maranon, Madrid, Spain, 5Medical Oncology, Ospedale San Raffaele, Milan, Italy, 6Department of Radiation Oncology, Mayo Clinic, Rochester, MN, 7Department of Surgery, Universita` Cattolica del Sacro Cuore, Rome, Italy

Purpose/Objective(s): Selection of pancreas cancer patients based on accurate prediction of follow-up outcome would allow intensive follow-up, treatment changes and trial arm selection. Therefore, we developed nomograms to predict local recurrence (LR), distant metastases (DM) and overall survival (OS) within 5 years of follow-up. Materials/Methods: A large pooled Italian database with clinical and surgery data of 798 pancreas cancer patients was analyzed. These data were captured between 1985 and 2008 and patients were treated with preoperative radiotherapy (40-50 Gy) and optionally concurrent and adjuvant chemotherapy. Treatment options were allowed to vary to induce robustness of the model. The variables included in the analysis: age and gender of the patient, the tumor site (head, body, tail), the surgical procedure (DCP, distal procedure, total procedure), macroscopic and microscopic residual disease, pathological tumor grade, tumor diameter at surgery, pathological T- and N-stage and several treatment options [yes/no]: pilors preserving technique, lymphadenectomy, vascular resection, adjuvant chemotherapy. The prediction models were based on multivariate analysis with a support vector machine. Performance of the model was expressed as the Area-Under-the-Curve (AUC) of the Receiver Operating Characteristic (ROC) curves. Nomograms were developed based on a 100-fold randomized selection of train and validation sets, with an optimal training set size of 60%. Weights were assigned to each selected predictor and converted to a probability for a 5-year outcome using logistic regression. Results: In the pooled database the occurrences of events were 37% LR, 56% DM, 23% OS. The accuracy of the developed nomograms was consistent for the validation sets for all outcomes; AUCLR = 0.57+/ 0.05, AUCMD = 0.62 +/ 0.05, AUCOS = 0.59+/ 0.04. The selected predictors were all linked to surgery, except for age (OS) and adjuvant chemotherapy (DM+OS). Conclusions: The provided nomograms have been validated and are able to accurately predict long-term outcome for pancreas cancer patients after treatment with (chemo)radiation. These nomograms should allow proper stratification in future trials, generation of new hypotheses and selection of patients who may benefit most from postoperative (alternative) adjuvant chemotherapy and intensive follow-up. Author Disclosure: G. Mattiucci, None; V. Valentini, None; R.G.P.M. van Stiphout, None; F. Calvo, None; M. Reni, None; R.C. Miller, None; G.B. Doglietto, None; S. Alfieri, None; G. Lammering, None; P. Lambin, None.

216

Adjuvant Radiotherapy and Lymph Node Status for Pancreatic Cancer: Results of a Study from the Surveillance, Epidemiology, and End Results (SEER) Registry Data

K. J. Opfermann, A. H. Wahlquist, E. Garrett-Mayer, L. Cannick, D. T. Marshall Medical University of South Carolina, Charleston, SC Purpose/Objective(s): The role of adjuvant radiotherapy (RT) after surgical resection in pancreatic cancer remains controversial. RT has been found to be beneficial in some studies in the presence of extensive disease or involved regional lymph nodes (LNs). The lymph node ratio (LNR), the ratio of involved nodes to nodes resected, has been correlated with outcome in surgical series. Our current study explores the relationship of the LNR to outcomes in patients receiving adjuvant RT. Materials/Methods: The SEER database was reviewed and records of 3,586 patients (1998 - 2006) were selected. All patients had a diagnosis of carcinoma of the pancreas, had received surgical resection, pathologic examination performed of the regional LNs, and had a survival of $ 2 months. of these, 1,698 patients also received RT. Survival curves were calculated by the Kaplan-Meier method and Cox proportional hazards regression models were used to determine if specific variables were related to the cause-specific survival (CSS) and OS. Significance of covariates was assessed using Cox proportional hazards regression and the log-rank test. Results: Median OS was 17 months for all patients. Median OS for patients having surgery alone was 15 months (1-yr survival 55.8%, 2-yr survival 31.6%) and for those receiving adjuvant RT was 20 months (1-yr survival 72.2%, 2-yr survival 40.4%). Statistically significant (SS) univariant relationships for shorter CSS and OS were found for the following variables: fewer LNs resected, increasing number of positive LNs, increasing LNR, earlier year of diagnosis, increasing t-stage, stage, and extent of disease, and lack of adjuvant RT. In analyzing CSS for patients treated with surgery only, the hazard ratio (HR) for the number of positive LNs (per increase of 5) = 1.05 (p \ 0.001) and the LNR HR = 3.15 (p \ 0.001). Among patients treated with RT the HR for the number of positive LNs (per increase of 5) = 1.31 (p \ 0.001), and the LNR HR = 2.61 (p \ 0.001). Analyzing OS in patients treated with surgery only, the HR for the number of positive LNs (per increase of 5) = 1.46 (p \ 0.001), and LNR = 2.96 (p \ 0.001). In analyzing OS in patients receiving RT the HR for the number of positive LNs (per increase of 5) = 1.29 (p \ 0.001), and LNR = 2.47 (p \ 0.001). Further stratifying the LNR into discrete cutpoints also revealed a statistically significant HR for the cutpoints of #20%, 20%-40%, and $40% in both groups with respect to the CSS and OS. Conclusions: A greater number of positive LNs and a higher LNR were SS indicators of worse CSS and OS in all patients, including those who received adjuvant RT and those who did not. Adjuvant RT was strongly associated with improvements in CSS and OS. Author Disclosure: K.J. Opfermann, None; A.H. Wahlquist, None; E. Garrett-Mayer, None; L. Cannick, None; D.T. Marshall, None.

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