Articles
Development and validation of nomograms to provide individualised predictions of seizure outcomes after epilepsy surgery: a retrospective analysis Lara Jehi, Ruta Yardi, Kevin Chagin, Laura Tassi, Giorgio Lo Russo, Gregory Worrell, Wei Hu, Fernando Cendes, Marcia Morita, Fabrice Bartolomei, Patrick Chauvel, Imad Najm, Jorge Gonzalez-Martinez, William Bingaman, Michael W Kattan
Summary Background Half of patients who have resective brain surgery for drug-resistant epilepsy have recurrent postoperative seizures. Although several single predictors of seizure outcome have been identified, no validated method incorporates a patient’s complex clinical characteristics into an instrument to predict an individual’s post-surgery seizure outcome. Methods We developed nomograms to predict complete freedom from seizures and Engel score of 1 (eventual freedom from seizures allowing for some initial postoperative seizures, or seizures occurring only with physiological stress such as drug withdrawal) at 2 years and 5 years after surgery on the basis of sex, seizure frequency, secondary seizure generalisation, type of surgery, pathological cause, age at epilepsy onset, age at surgery, epilepsy duration at time of surgery, and surgical side. We designed the models from a development cohort of patients who had resective surgery at the Cleveland Clinic (Cleveland, OH, USA) between 1996 and 2011. We then tested the nomograms in an external validation cohort operated on over a similar period in four epilepsy surgery centres, in Brazil, France, Italy, and the USA. We assessed performance of the nomogram by calculating concordance statistics and assessing the calibration of predicted freedom from seizures with the reported freedom from seizures and Engel score of 1. Findings The development cohort included 846 patients and the validation cohort included 604 patients. Variables included in the nomograms were sex, seizure frequency, secondary seizure generalisation, type of surgery, and pathological cause. In the development cohort, the baseline risk of complete freedom from seizures was 0·57 at 2 years and 0·40 at 5 years. The baseline risk of Engel score of 1 was 0·69 at 2 years and 0·62 at 5 years. In the validation cohort, the models had a concordance statistic of 0·60 for complete freedom from seizures and 0·61 for Engel score of 1. Calibration curves showed adequate calibration (judged by eye) of predicted and reported freedom from seizures, throughout the range of seizure outcomes. Interpretation If validated in prospective cohorts, these nomograms could be used to predict seizure outcomes in patients who have been judged eligible for epilepsy surgery. Funding Cleveland Clinic Epilepsy Center.
Introduction Every year, thousands of patients with medically intractable focal epilepsy undergo resective brain surgery to stop their seizures.1 Thousands more could probably benefit from the procedure, but are not referred for a surgical assessment.2–4 Both groups of patients face difficulties because seizure outcomes after epilepsy surgery cannot be accurately predicted. Surgery has been shown to be better than drug treatment for intractable epilepsy in two randomised clinical trials,5,6 a practice guideline,7 and hundreds of surgical cohort studies quantifying postoperative seizure outcomes:8–21 40–80% of patients with drug-resistant focal epilepsy become seizure-free after epilepsy surgery, as opposed to 3–8% when drug treatment alone is continued. However, for any individual patient considering surgery for epilepsy, the crucial question for deciding the best treatment is the individual’s odds of postoperative freedom from seizures. To date, the answer has been complicated and variable, as it is highly dependent on a subjective synthesis of the
published work on surgical outcomes. With half of patients, on average, continuing to have seizures after surgery, better outcome prediction and patient selection are needed. Most studies have focused on the identification of isolated outcome predictors, and a few have correlated various combinations of outcome predictors with postoperative seizure control.22,23 However, an instrument to combine a patient’s complex clinical characteristics and often multiple contradictory outcome predictors objectively into a single comprehensive validated risk assessment measure does not exist, to our knowledge. This absence leads to uncertainty during presurgical counselling because most candidates for surgery do not fall into clear categories with all negative or all positive outcome predictors. In an era when health-care costs are increasing for brain surgery, both patients and physicians would benefit from a prediction of the probability of success on a case by case basis. A nomogram is a statistical instrument that accounts for numerous variables to predict an outcome of interest
www.thelancet.com/neurology Published online January 29, 2015 http://dx.doi.org/10.1016/S1474-4422(14)70325-4
Lancet Neurol 2015 Published Online January 29, 2015 http://dx.doi.org/10.1016/ S1474-4422(14)70325-4 See Online/Comment http://dx.doi.org/10.1016/ S1474-4422(15)70011-6 Epilepsy Center, Cleveland Clinic, Cleveland, OH, USA (L Jehi MD, R Yardi MD, I Najm MD, J Gonzalez-Martinez MD, W Bingaman MD); Quantitative Health Sciences, Cleveland, OH, USA (K Chagin, M W Kattan PhD); Epilepsy Surgery Center, Ospedale Niguarda, Milan, Italy (L Tassi MD, G Lo Russo MD); Division of Epilepsy, Department of Neurology, Mayo Clinic, Rochester, MN, USA (G Worrell MD, W Hu MD); University of Campinas, Campinas, Campinas, Brazil (F Cendes MD, M Morita MD); Epileptology Department, and Clinical Neurophysiology Department, Assistance Publique des Hôpitaux de Marseille, Marseille, France (F Bartolomei MD, P Chauvel MD); and Institut de Neurosciences des Systèmes, UMR INSERM-AMU 1106, Marseille, France (F Bartolomei, P Chauvel) Correspondence to: Lara Jehi, Cleveland Clinic Epilepsy Center, 9500 Euclid Avenue, S51, Cleveland Clinic, OH 44195, USA [email protected]
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for an individual patient.24 They are routinely used to aid decision making in cancer,25,26 trauma,27 joint replacement surgery,28 neurocritical care,29 and other specialties. We present here the development and validation of two nomograms to predict seizure outcomes after epilepsy surgery for individual patients.
Methods Study design, participants, and procedures We developed the two nomograms from a patient cohort from the Cleveland Clinic Epilepsy Center (Cleveland, OH, USA). We did a retrospective cohort study of patients Development cohort (n=846)
Validation cohort (n=604)
Sex Female
424 (50%)
316 (52%)
Male
422 (50%)
288 (48%)
Age at seizure onset (years) Median (IQR)
8·3 (3·0–18·0)
7·0 (2·4–15·0)
Data missing
2 (
Development and validation of nomograms to provide individualised predictions of seizure outcomes after epilepsy surgery: a retrospective analysis Lara Jehi, Ruta Yardi, Kevin Chagin, Laura Tassi, Giorgio Lo Russo, Gregory Worrell, Wei Hu, Fernando Cendes, Marcia Morita, Fabrice Bartolomei, Patrick Chauvel, Imad Najm, Jorge Gonzalez-Martinez, William Bingaman, Michael W Kattan
Summary Background Half of patients who have resective brain surgery for drug-resistant epilepsy have recurrent postoperative seizures. Although several single predictors of seizure outcome have been identified, no validated method incorporates a patient’s complex clinical characteristics into an instrument to predict an individual’s post-surgery seizure outcome. Methods We developed nomograms to predict complete freedom from seizures and Engel score of 1 (eventual freedom from seizures allowing for some initial postoperative seizures, or seizures occurring only with physiological stress such as drug withdrawal) at 2 years and 5 years after surgery on the basis of sex, seizure frequency, secondary seizure generalisation, type of surgery, pathological cause, age at epilepsy onset, age at surgery, epilepsy duration at time of surgery, and surgical side. We designed the models from a development cohort of patients who had resective surgery at the Cleveland Clinic (Cleveland, OH, USA) between 1996 and 2011. We then tested the nomograms in an external validation cohort operated on over a similar period in four epilepsy surgery centres, in Brazil, France, Italy, and the USA. We assessed performance of the nomogram by calculating concordance statistics and assessing the calibration of predicted freedom from seizures with the reported freedom from seizures and Engel score of 1. Findings The development cohort included 846 patients and the validation cohort included 604 patients. Variables included in the nomograms were sex, seizure frequency, secondary seizure generalisation, type of surgery, and pathological cause. In the development cohort, the baseline risk of complete freedom from seizures was 0·57 at 2 years and 0·40 at 5 years. The baseline risk of Engel score of 1 was 0·69 at 2 years and 0·62 at 5 years. In the validation cohort, the models had a concordance statistic of 0·60 for complete freedom from seizures and 0·61 for Engel score of 1. Calibration curves showed adequate calibration (judged by eye) of predicted and reported freedom from seizures, throughout the range of seizure outcomes. Interpretation If validated in prospective cohorts, these nomograms could be used to predict seizure outcomes in patients who have been judged eligible for epilepsy surgery. Funding Cleveland Clinic Epilepsy Center.
Introduction Every year, thousands of patients with medically intractable focal epilepsy undergo resective brain surgery to stop their seizures.1 Thousands more could probably benefit from the procedure, but are not referred for a surgical assessment.2–4 Both groups of patients face difficulties because seizure outcomes after epilepsy surgery cannot be accurately predicted. Surgery has been shown to be better than drug treatment for intractable epilepsy in two randomised clinical trials,5,6 a practice guideline,7 and hundreds of surgical cohort studies quantifying postoperative seizure outcomes:8–21 40–80% of patients with drug-resistant focal epilepsy become seizure-free after epilepsy surgery, as opposed to 3–8% when drug treatment alone is continued. However, for any individual patient considering surgery for epilepsy, the crucial question for deciding the best treatment is the individual’s odds of postoperative freedom from seizures. To date, the answer has been complicated and variable, as it is highly dependent on a subjective synthesis of the
published work on surgical outcomes. With half of patients, on average, continuing to have seizures after surgery, better outcome prediction and patient selection are needed. Most studies have focused on the identification of isolated outcome predictors, and a few have correlated various combinations of outcome predictors with postoperative seizure control.22,23 However, an instrument to combine a patient’s complex clinical characteristics and often multiple contradictory outcome predictors objectively into a single comprehensive validated risk assessment measure does not exist, to our knowledge. This absence leads to uncertainty during presurgical counselling because most candidates for surgery do not fall into clear categories with all negative or all positive outcome predictors. In an era when health-care costs are increasing for brain surgery, both patients and physicians would benefit from a prediction of the probability of success on a case by case basis. A nomogram is a statistical instrument that accounts for numerous variables to predict an outcome of interest
www.thelancet.com/neurology Published online January 29, 2015 http://dx.doi.org/10.1016/S1474-4422(14)70325-4
Lancet Neurol 2015 Published Online January 29, 2015 http://dx.doi.org/10.1016/ S1474-4422(14)70325-4 See Online/Comment http://dx.doi.org/10.1016/ S1474-4422(15)70011-6 Epilepsy Center, Cleveland Clinic, Cleveland, OH, USA (L Jehi MD, R Yardi MD, I Najm MD, J Gonzalez-Martinez MD, W Bingaman MD); Quantitative Health Sciences, Cleveland, OH, USA (K Chagin, M W Kattan PhD); Epilepsy Surgery Center, Ospedale Niguarda, Milan, Italy (L Tassi MD, G Lo Russo MD); Division of Epilepsy, Department of Neurology, Mayo Clinic, Rochester, MN, USA (G Worrell MD, W Hu MD); University of Campinas, Campinas, Campinas, Brazil (F Cendes MD, M Morita MD); Epileptology Department, and Clinical Neurophysiology Department, Assistance Publique des Hôpitaux de Marseille, Marseille, France (F Bartolomei MD, P Chauvel MD); and Institut de Neurosciences des Systèmes, UMR INSERM-AMU 1106, Marseille, France (F Bartolomei, P Chauvel) Correspondence to: Lara Jehi, Cleveland Clinic Epilepsy Center, 9500 Euclid Avenue, S51, Cleveland Clinic, OH 44195, USA [email protected]
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for an individual patient.24 They are routinely used to aid decision making in cancer,25,26 trauma,27 joint replacement surgery,28 neurocritical care,29 and other specialties. We present here the development and validation of two nomograms to predict seizure outcomes after epilepsy surgery for individual patients.
Methods Study design, participants, and procedures We developed the two nomograms from a patient cohort from the Cleveland Clinic Epilepsy Center (Cleveland, OH, USA). We did a retrospective cohort study of patients Development cohort (n=846)
Validation cohort (n=604)
Sex Female
424 (50%)
316 (52%)
Male
422 (50%)
288 (48%)
Age at seizure onset (years) Median (IQR)
8·3 (3·0–18·0)
7·0 (2·4–15·0)
Data missing
2 (
