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Should the Use of Biologic Agents in Patients With Renal and Lung Cancer Affect Our Surgical Management of Femoral Metastases?

Gutowski, Christina J., MD, MPH; Zmistowski, Benjamin, MD; Fabbri, Nicola, MD; Boland, Patrick J., MD; Healey, John H., MD

Clinical Orthopaedics and Related Research®: April 2019 - Volume 477 - Issue 4 - p 707–714
doi: 10.1097/CORR.0000000000000434
2017 MUSCULOSKELETAL TUMOR SOCIETY PROCEEDINGS
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Background Biologic agents may prolong survival of patients with certain kidney and lung adenocarcinomas that have metastasized to bone, and patient response to these agents should be considered when choosing between an endoprosthesis and internal fixation for surgical treatment of femoral metastases.

Questions/purposes Among patients undergoing surgery for femoral metastases of lung or renal cell carcinoma, (1) Does survival differ between patients who receive only cytotoxic chemotherapy and those who either respond or do not respond to biologic therapy? (2) Does postsurgical incidence of local disease progression differ between groups stratified by systemic treatment and response? (3) Does implant survival differ among groups stratified by systemic treatment and response?

Methods From our institutional longitudinally maintained orthopaedic database, patients were identified by a query initially identifying all patients who carried a diagnosis of renal cell carcinoma or lung carcinoma. Patients who underwent internal fixation or prosthetic reconstruction between 2000 and 2016 for pathologic fracture of the femur and who survived ≥ 1 year after surgery were studied. Patients who received either traditional cytotoxic chemotherapy or a biologic agent were included. Patients were classified as responders or nonresponders to biologic agents based on whether they had clinical and imaging evidence of a response recorded on two consecutive office visits over ≥ 6 months. Endpoints were overall survival from the time of diagnosis, survival after the femoral operation, evidence of disease progression in the femoral operative site, and symptomatic local disease progression for which revision surgery was necessary. Our analysis included 148 patients with renal (n = 26) and lung (n = 122) adenocarcinoma. Fifty-one patients received traditional chemotherapy only. Of 97 patients who received a biologic agent, 41 achieved a response (stabilization/regression of visceral metastases), whereas 56 developed disease progression. We analyzed overall patient survival with the Kaplan-Meier method and used the log-rank test to identify significant differences (p < 0.05) between groups.

Results One-year survival after surgery among patients responsive to biologic therapy was 61% compared with 20% among patients nonresponsive to biologics (p < 0.001) and 10% among those who received chemotherapy only (p < 0.009). With the number of patients we had to study, we could not detect any difference in local progression of femoral disease associated with systemic treatment and response. Radiologic evidence of periimplant local disease progression developed in three (7%) of 41 patients who responded to biologic treatment, two (3%) of 56 patients nonresponsive to biologics, and one (2%) of 51 patients treated with traditional chemotherapy. With the numbers of patients we had, we could not detect a difference in patients who underwent revision. All three patients responsive to biologics who developed local recurrence underwent revision, whereas the two without a response to biologics did not.

Conclusions Biologic therapy improves the overall longevity of some patients with lung and renal metastases to the femur in whom a visceral disease response occurred. In our limited cohort, we could not demonstrate an implant survival difference between such patients and those with shorter survival who may have had more aggressive disease. However, an increased life expectancy beyond 1 year among patients responsive to biologics may increase risk of mechanical failure of fixation constructs.

Level of Evidence Level III, therapeutic study.

C. J. Gutowski, MD Anderson Cancer Center at Cooper, Department of Orthopaedic Surgery, Cooper University Hospital, Camden, NJ, USA

C. J. Gutowski, N. Fabbri, P. J. Boland, J. H. Healey, Orthopaedic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

B. Zmistowski, Department of Orthopaedic Surgery, Thomas Jefferson University Hospital, Philadelphia, PA, USA

N. Fabbri, P. J. Boland, J. H. Healey, Department of Surgery, Weill Cornell Medical College, New York, NY, USA

J. H. Healey, Orthopaedic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA, email: healeyj@mskcc.org

All research at Memorial Sloan Kettering is supported in part by a grant from the National Institutes of Health/National Cancer Institute (#P30 CA008748) (CJG, NF, PJB, JHH). One of the authors (CJG) was supported by an unrestricted educational fellowship from the Major Family Fellowship Fund at Memorial Sloan Kettering Cancer Center. In addition, the MSK Musculoskeletal Oncology Fellowship program acknowledges the Omega Medical Grants Association and the support of Genentech for its generous 2016-2017 Orthopaedic Oncology Fellowship grant.

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 before clinical use.

Each author certifies that his or her institution approved the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

This work was performed at Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Received December 17, 2017

Accepted July 17, 2018

© 2019 Lippincott Williams & Wilkins LWW
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