Tag Archive | giant cell tumor of bone

Giant-Cell Tumor Treatment: Curettage Without Denosumab Is Better

GCTB for OBuzzDenosumab is an FDA-approved drug for osteoporosis. It works by binding RANKL, thus inhibiting osteoclastic activity. Denosumab  has also been shown to have a favorable impact on tumor response in relatively small, short-term studies among patients with giant-cell tumor of bone (GCTB).

In the March 21, 2018 issue of The Journal, Errani et al. report on a longer-term follow up (minimum 24 months, median 85.6 months) in two cohorts of patients with GCTB who were treated with joint-preserving curettage: those treated with curettage plus denosumab and those treated with curettage alone. The study found that denosumab administration was significantly associated with unfavorable outcomes in patients treated with curettage. Specifically, the local GCTB recurrence rate was nearly 4 times higher (60% vs 16%) in patients treated with denosumab plus curettage, compared to those treated with curettage alone.

Recent in vitro studies have shown that denosumab only slows giant-cell multiplication to some degree. The authors point out that patients treated with denosumab in this cohort study had more severe GCTB disease, which would seem to further confirm that cellular proliferation of giant cells is ineffectively slowed by this RANKL-binding drug. What’s most important about the Errani et al. study is that it’s the first one to look at the longer-term outcomes of denosumab usage before and after curettage for GCTB.

The authors emphasize that while their study shows a strong and independent association between denosumab administration and a high level of local recurrence, “causation could not be evaluated.” Still, at a time when clinicians, payers, and patients are critically evaluating every facet of treatment, it seems difficult to recommend the use of denosumab in addition to curettage for GCTB. The data in this study should encourage the musculoskeletal oncology community to continue to investigate other adjunctive treatments to be used with curettage for this disease process.

Marc Swiontkowski, MD
JBJS Editor-in-Chief

What’s New in Orthopaedic Oncology

Every month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Here is a summary of selected findings from studies cited in the December 16, 2015 Specialty Update on orthopaedic oncology:

Malignant Primary Bone Tumors

  • A study comparing the efficacy of surgery versus radiation in 465 patients with Ewing sarcoma managed with standardized chemotherapy found lower local failure rates with surgery, but no significant differences in event-free survival, overall survival, or distant metastasis.1
  • A study of 30 long-term survivors of Ewing sarcoma after limb salvage found that, at a mean follow-up of 16 years, 83% of patients were performing athletic activity regularly. Those with pelvic and femoral resections with no reconstruction exercised more hours per week than those with endoprosthetic pelvic reconstruction.2
  • A survival and relapse analysis of 45 locally recurrent osteosarcomas identified a recurrent tumor that was ≥5 cm and metastatic disease at presentation as independent risk factors. Most recurrences were in soft tissues. Early detection and resection with wide negative margins are crucial for optimal outcomes.3
  • A long-term outcome study of 30 patients with recurrent sacral chordoma treated surgically found survival of 89% at two years, 56% at five years, and 19% at ten years. Wide resection gave the best chance of long-term survival, and complete resection of local recurrence gave the best chance of disease control.4

Benign Bone Tumors

  • A study investigating pulmonary metastasis risk factors in 167 patients with giant cell tumor of bone identified local recurrence as the strongest independent predictor of metastasis. Younger patients also had higher metastatic rates.
  • A multicenter study of clinical presentation and outcomes in 126 operatively treated patients with chondroblastoma of the extremities found a local recurrence rate of 4.8% over a minimum two-year follow-up. Findings suggested that local recurrence may be more common in patients with open physes.
  • An investigation of 195 patients with multiple hereditary exostosis found that seven (3.6%) had intraosseous chondroid lesions. Five of those patients developed chondrosarcomas.
  • Curettage, high-speed burring, and bone grafting without other adjuvants in 31 patients with an aneurysmal bone cyst resulted in only one recurrence (3.2%).5

Bone Metastasis and Reconstruction

  • In a study of 125 patients, CT-based structural rigidity analysis of femora to detect impending pathologic fractures had higher sensitivity, specificity, and predictive values than the Mirels classification.6
  • In 111 patients who underwent hemicortical allograft reconstruction of a remaining defect after hemicortical resection of a bone tumor, all of the host bone fractures healed without surgeons having to remove the allograft. The authors recommended hemicortical resections with allograft reconstructions for low- to intermediate-grade tumors.
  • Five-year revision-free survival of conventional total femoral replacements in 40 patients with primary malignant bone tumors was 48%. The most common mechanism of failure was soft-tissue insufficiency.7

References

  1. DuBois SG, Krailo MD, Gebhardt MC, Donaldson SS, Marcus KJ, Dormans J, Shamberger RC, Sailer S, Nicholas RW, Healey JH, Tarbell NJ, Randall RL, Devidas M, Meyer JS, Granowetter L, Womer RB, Bernstein M, Marina N, Grier HE. Comparative evaluation of local control strategies in localized Ewing sarcoma of bone: a report from the Children’s Oncology Group. Cancer. 2015 Feb1;121(3):467-75. Epub 2014 Sep 23.
  2. Hobusch GM, Lang N, Schuh R, Windhager R, Hofstaetter JG. Do patients with Ewing’s sarcoma continue with sports activities after limb salvage surgery of the lower extremity? Clin Orthop Relat Res. 2015 Mar;473(3):839-46.
  3. Takeuchi A, Lewis VO, Satcher RL, Moon BS, Lin PP. What are the factors that affect survival and relapse after local recurrence of osteosarcoma? Clin Orthop Relat Res. 2014 Oct;472(10):3188-95. Epub 2014 Jul 1.
  4. Xie C, Whalley N, Adasonla K, Grimer R, Jeys L. Can local recurrence of a sacral chordoma be treated by further surgery? Bone Joint J. 2015 May;97-B(5):711-5.
  5. Wang EH, Marfori ML, Serrano MV, Rubio DA. Is curettage and high-speed burring sufficient treatment for aneurysmal bone cysts? Clin Orthop Relat Res. 2014Nov;472(11):3483-8. Epub 2014 Jul 22.
  6. Damron TA, Nazarian A, Entezari V, Brown C, Grant W, Calderon N, Zurakowski D,Terek RM, Anderson ME, Cheng EY, Aboulafia AJ, Gebhardt MC, Snyder BD. CT-based structural rigidity analysis is more accurate than Mirels scoring for fracture prediction in metastatic femoral lesions. Clin Orthop Relat Res. 2015 Jul 14.
  7. Sevelda F, Schuh R, Hofstaetter JG, Schinhan M, Windhager R, Funovics PT. Total femur replacement after tumor resection: limb salvage usually achieved but complications and failures are common. Clin Orthop Relat Res. 2015Jun;473(6):2079-87. Epub 2015 Apr 2.