TY - JOUR
T1 - Can We Estimate Short- and Intermediate-term Survival in Patients Undergoing Surgery for Metastatic Bone Disease?
AU - Forsberg, Jonathan A.
AU - Wedin, Rikard
AU - Boland, Patrick J.
AU - Healey, John H.
N1 - Funding Information:
One of the authors (JHH) received funding from the Maynard Limb Preservation Fund. Research at Memorial Sloan Kettering Cancer Center is supported in part by a Cancer Center Support Grant from the U.S. National Institutes of Health/National Cancer Institute (#P30 CA008748). The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, the Department of Defense, nor the U.S. Government. Research activities leading to the development of this abstract were approved by the local Institutional Review Board (NMRC.2014.0009 and IRBNet 392350) in compliance with all applicable regulations governing the protection of human subjects. One of the authors (JAF) is a military service member. This work was supported/funded by work-unit number HU0001-14-1-0010 and was prepared as part of his official duties. Title 17 U.S.C. §105 provides that "Copyright protection under this title is not available for any work of the United States Government". Title 17 U.S.C. §101 defines a U.S. government work as a work prepared by a military service member or employee of the U.S. Government as part of that person's official duties. We certify that the document represents valid work; that if we used information derived from another source, we obtained all necessary approvals to use it and made appropriate acknowledgements in the document; and we take public responsibility for it.
Funding Information:
One of the authors (JHH) received funding from the Maynard Limb Preservation Fund. Research at Memorial Sloan Kettering Cancer Center is supported in part by a Cancer Center Support Grant from the U.S. National Institutes of Health/National Cancer Institute (#P30 CA008748). All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request. Clinical Orthopaedics and Related Research® neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDA-approval status, of any drug or device prior to clinical use. Each author certifies that his or her institution approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained. This work was performed at the Naval Medical Research Center, Silver Spring, MD, USA. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, the Department of Defense, nor the U.S. Government. Research activities leading to the development of this abstract were approved by the local Institutional Review Board (NMRC.2014.0009 and IRBNet 392350) in compliance with all applicable regulations governing the protection of human subjects. One of the authors (JAF) is a military service member. This work was supported/funded by work-unit number HU0001-14-1-0010 and was prepared as part of his official duties. Title 17 U.S.C. §105 provides that ‘‘Copyright protection under this title is not available for any work of the United States Government’’. Title 17 U.S.C. §101 defines a U.S. government
Publisher Copyright:
© 2016, The Association of Bone and Joint Surgeons®.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - Background: Objective means of estimating survival can be used to guide surgical decision-making and to risk-stratify patients for clinical trials. Although a free, online tool (www.pathfx.org) can estimate 3- and 12-month survival, recent work, including a survey of the Musculoskeletal Tumor Society, indicated that estimates at 1 and 6 months after surgery also would be helpful. Longer estimates help justify the need for more durable and expensive reconstructive options, and very short estimates could help identify those who will not survive 1 month and should not undergo surgery. Thereby, an important use of this tool would be to help avoid unsuccessful and expensive surgery during the last month of life. Questions/Purposes: We seek to provide a reliable, objective means of estimating survival in patients with metastatic bone disease. After generating models to derive 1- and 6-month survival estimates, we determined suitability for clinical use by applying receiver operator characteristic (ROC) (area under the curve [AUC] > 0.7) and decision curve analysis (DCA), which determines whether using PATHFx can improve outcomes, but also discerns in which kinds of patients PATHFx should not be used. Methods: We used two, existing, skeletal metastasis registries chosen for their quality and availability. Data from Memorial Sloan-Kettering Cancer Center (training set, n = 189) was used to develop two Bayesian Belief Networks trained to estimate the likelihood of survival at 1 and 6 months after surgery. Next, data from eight major referral centers across Scandinavia (n = 815) served as the external validation set—that is, as a means to test model performance in a different patient population. The diversity of the data between the training set from Memorial Sloan-Kettering Cancer Center and the Scandinavian external validation set is important to help ensure the models are applicable to patients in various settings with differing demographics and treatment philosophies. We considered disease-specific, laboratory, and demographic information, and the surgeon’s estimate of survival. For each model, we calculated the area under the ROC curve (AUC) as a metric of discriminatory ability and the Net Benefit using DCA to determine whether the models were suitable for clinical use. Results: On external validation, the AUC for the 1- and 6-month models were 0.76 (95% CI, 0.72–0.80) and 0.76 (95% CI, 0.73–0.79), respectively. The models conferred a positive net benefit on DCA, indicating each could be used rather than assume all patients or no patients would survive greater than 1 or 6 months, respectively. Conclusions: Decision analysis confirms that the 1- and 6-month Bayesian models are suitable for clinical use. Clinical Relevance: These data support upgrading www.pathfx.org with the algorithms described above, which is designed to guide surgical decision-making, and function as a risk stratification method in support of clinical trials. This updating has been done, so now surgeons may use any web browser to generate survival estimates at 1, 3, 6, and 12 months after surgery, at no cost. Just as short estimates of survival help justify palliative therapy or less-invasive approaches to stabilization, more favorable survival estimates at 6 or 12 months are used to justify more durable, complicated, and expensive reconstructive options.
AB - Background: Objective means of estimating survival can be used to guide surgical decision-making and to risk-stratify patients for clinical trials. Although a free, online tool (www.pathfx.org) can estimate 3- and 12-month survival, recent work, including a survey of the Musculoskeletal Tumor Society, indicated that estimates at 1 and 6 months after surgery also would be helpful. Longer estimates help justify the need for more durable and expensive reconstructive options, and very short estimates could help identify those who will not survive 1 month and should not undergo surgery. Thereby, an important use of this tool would be to help avoid unsuccessful and expensive surgery during the last month of life. Questions/Purposes: We seek to provide a reliable, objective means of estimating survival in patients with metastatic bone disease. After generating models to derive 1- and 6-month survival estimates, we determined suitability for clinical use by applying receiver operator characteristic (ROC) (area under the curve [AUC] > 0.7) and decision curve analysis (DCA), which determines whether using PATHFx can improve outcomes, but also discerns in which kinds of patients PATHFx should not be used. Methods: We used two, existing, skeletal metastasis registries chosen for their quality and availability. Data from Memorial Sloan-Kettering Cancer Center (training set, n = 189) was used to develop two Bayesian Belief Networks trained to estimate the likelihood of survival at 1 and 6 months after surgery. Next, data from eight major referral centers across Scandinavia (n = 815) served as the external validation set—that is, as a means to test model performance in a different patient population. The diversity of the data between the training set from Memorial Sloan-Kettering Cancer Center and the Scandinavian external validation set is important to help ensure the models are applicable to patients in various settings with differing demographics and treatment philosophies. We considered disease-specific, laboratory, and demographic information, and the surgeon’s estimate of survival. For each model, we calculated the area under the ROC curve (AUC) as a metric of discriminatory ability and the Net Benefit using DCA to determine whether the models were suitable for clinical use. Results: On external validation, the AUC for the 1- and 6-month models were 0.76 (95% CI, 0.72–0.80) and 0.76 (95% CI, 0.73–0.79), respectively. The models conferred a positive net benefit on DCA, indicating each could be used rather than assume all patients or no patients would survive greater than 1 or 6 months, respectively. Conclusions: Decision analysis confirms that the 1- and 6-month Bayesian models are suitable for clinical use. Clinical Relevance: These data support upgrading www.pathfx.org with the algorithms described above, which is designed to guide surgical decision-making, and function as a risk stratification method in support of clinical trials. This updating has been done, so now surgeons may use any web browser to generate survival estimates at 1, 3, 6, and 12 months after surgery, at no cost. Just as short estimates of survival help justify palliative therapy or less-invasive approaches to stabilization, more favorable survival estimates at 6 or 12 months are used to justify more durable, complicated, and expensive reconstructive options.
UR - http://www.scopus.com/inward/record.url?scp=85000978545&partnerID=8YFLogxK
U2 - 10.1007/s11999-016-5187-3
DO - 10.1007/s11999-016-5187-3
M3 - Article
C2 - 27909972
AN - SCOPUS:85000978545
SN - 0009-921X
VL - 475
SP - 1252
EP - 1261
JO - Clinical Orthopaedics and Related Research
JF - Clinical Orthopaedics and Related Research
IS - 4
ER -