Giant-Cell Tumor Treatment: Curettage Without Denosumab Is Better
Denosumab 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
In Spinal-Metastasis Surgery, High-Volume Yields Better Outcomes
In orthopaedics, the connection between a hospital/surgeon performing a surgical procedure many times and improved outcomes has been demonstrated compellingly with total joint replacement. In the October 18, 2017 edition of JBJS, Schoenfeld et al. show that this same volume-outcome relationship holds true in the surgical treatment of spinal metastases.
The study analyzed 3,135 patients treated by 1,488 surgeons at 162 hospitals throughout Florida. Using sophisticated statistics, the authors defined high-volume surgeons as those who had performed ≥49 procedures per year and high-volume hospitals as those at which ≥167 procedures per year had been performed.
Among the entire cohort, the 90-day complication rate was 26% and the readmission rate was 43%. (Rates that high are not unexpected with such risky spinal surgeries.) Here are the findings according to surgeon volume:
- 21% complication rate for patients treated by high-volume surgeons
- 30% complication rate for patients treated by low-volume surgeons
- 37% readmission rate for patients treated by high-volume surgeons
- 47% readmission rate for patients treated by low-volume surgeons
In other words, the relative odds of complications and readmissions following operations performed by low-volume surgeons were approximately 40% higher than those following operations done by high-volume surgeons. A similar percentage difference was found between the odds at low- and high-volume hospitals. In a secondary analysis, the authors found that African Americans and Hispanics were significantly less likely than white patients to receive care from a high-volume surgeon or at a high-volume hospital.
Schoenfeld et al. state that the ideal care for patients facing surgery for spinal metastases comes from a team of experienced surgeons, medical oncologists, radiation oncologists, nurses, and support staff. They conclude that their findings “speak to the need for regionalization of subspecialty spinal oncology care as a means to optimize treatment for this cohort of patients.”
Aggressive Treatment Improves QOL in Many Cases of Spinal Metastases
A significant portion of metastatic disease comes with no clear identification of a primary tumor; this is unfortunately the case with many spinal metastases. In the October 4, 2017 issue of The Journal, Ma et al. evaluate the survival and patient-reported quality-of-life (QOL) outcomes for patients with spinal metastases from cancer of unknown primary origin.
Their prospective longitudinal study confirms that a more aggressive strategy that combines surgery and radiation therapy results in better QOL (as measured with the four-domain FACT-G instrument) than radiation alone. There was no significant difference in survival time between the two groups. In a subgroup analysis of patients receiving surgery, those who underwent circumferential decompression had significantly better functional and physical well-being and higher total QOL scores than those who underwent decompressive laminectomy.
These findings emphasize the critical role of shared decision making in such difficult situations. A dire diagnosis with poor statistical chances of long-term survival does not mean that patients should not be informed of treatment options and have the opportunity to opt for an aggressive surgical approach, especially if that decision is likely to result in improved QOL. Let us endeavor to compassionately provide patients with the facts, as we understand them, and let them select from among the medical and surgical options that are at their disposal. More often than not, in this sad scenario, it seems aggressive is better in terms of quality of life.
Faster Relief for Patients with Painful Bone Metastases
A technique that combines magnetic resonance (MR) imaging with high-intensity focused ultrasound hyperthermia provides faster pain relief than conventional radiation therapy (RT) for patients with a painful bone metastasis.
In the September 20, 2017 issue of JBJS, Lee et al. report on a matched-pair study of 63 patients with a painful bone metastasis who received either magnetic resonance-guided focused ultrasound (MRgFUS) or RT as first-line treatment. Both modalities were effective overall, yielding response rates of >70% at the three-month follow-up evaluation. However, MRgFUS was more efficient, providing a 71% response rate at 1 week after treatment, compared with 26% for RT at that same time point.
The total treatment time and cost of the two modalities were similar, and neither was associated with adverse events above grade 2. Among MRgFUS patients, there was a 14% rate of positioning-related pain and a 33% rate of sonication-related pain, which typically resolved within 1 day after treatment.
Lee et al. report that the median overall survival of patients in the study was 12.7 months in the MRgFUS group and 9.8 months in the RT group, a statistically nonsignificant difference. But the authors emphasize that the study was more about pain relief than extending life. “Reduc[ing] pain, restor[ing] function, and maintain[ing] quality of life is imperative” for those with bone metastasis, the authors conclude. They also caution that MRgFUS is not appropriate for bone metastases of the skull or most of the spine, or for any lesion that is not at least 1 cm away from “tissues at risk.”
JBJS Editor’s Choice—VTE Risk with Metastatic Skeletal Lesions: Fix Prophylactically or Not?
In the February 15, 2017 issue of The Journal, Aneja et al. utilize a large administrative database to examine the critical question of venous thromboembolism (VTE) risk as it relates to managing patients with metastatic femoral lesions. The authors found that prophylactic intramedullary (IM) nailing clearly resulted in a higher risk of both pulmonary embolism and deep-vein thrombosis, relative to IM nailing after a pathologic fracture. Conversely, the study found that patients managed with fixation after a pathological fracture had greater need for blood transfusions, higher rates of postoperative urinary tract infections, and a decreased likelihood of being discharged to home.
The VTE findings make complete clinical sense, because when we ream an intact bone, the highly pressurized medullary canal forces coagulation factors into the peripheral circulation. When we ream after a fracture, the pressures are much lower, and neither the coagulation factors nor components of the metastatic lesion are forced into the peripheral circulation as efficiently, although some may partially escape through the fracture site.
One might conclude that we should never consider prophylactic fixation in the case of metastatic disease in long bones, but that would not be a patient-centric position to hold. In my opinion, the decision about whether to prophylactically internally fix an impending pathologic fracture should be based on patient symptoms and consultations with the patient’s oncologist and radiation therapist.
If all of the findings from Aneja et al. are considered, and if the patient’s symptoms are functionally limiting after initiation of appropriate radiation and chemotherapy, prophylactic fixation should be performed, along with vigilantly managed VTE-prevention measures. This study is ideally suited to inform these discussions for optimum patient care.
Marc Swiontkowski, MD
JBJS Editor-in-Chief
JBJS Case Connector Debuts Whole-Slide Images
It is not often that readers of scholarly journals have a “Wow!” moment, a chance to be unexpectedly delighted by a new discovery.1 In the September 14, 2016 edition of JBJS Case Connector, Zhang et al. provide readers of the JBJS family of journals the first of what we hope will be many such moments: the ability to link to and navigate a digital, whole-slide image (WSI) of an entire microscope slide.
Figure 1
Illustrating the histology of tumors and the tissue-level details in basic science studies has long been a challenge. Until recently, readers were usually subjected to the few fields of view that the author chose to photograph. The more senior among you may remember with nostalgia attempting to make sense of fuzzy, black-and-white, circular, histology images viewed as if seen through an antique monocular microscope (Fig. 1). The advent of color printing (often at the author’s extra expense) and eventually digital photographs improved somewhat the quality of each image, but readers were still required to accept that the author had selected fields of view that were truly representative of the subject matter.
In their case report titled “Morphological Transformation of Giant-Cell Tumor of Bone After Treatment with Denosumab,” Zhang et al. include two links to whole-slide images. In the first, readers can link from a conventional digital photograph of a core needle biopsy to the whole-slide image of the giant cell tumor. The authors also include several conventional photographs of the tumor after resection, along with a link to the corresponding scanned microscope slide.
The use of a viewing algorithm similar to that used by Google Earth allows readers to navigate and zoom in on not just the few isolated fields of view selected by the authors, but the hundreds to thousands of additional fields contained in the original microscope slide of this complicated tumor. While it’s very helpful for illustrating tumor histology, we anticipate that WSI technology will be even more valuable when applied to basic science studies of fracture healing or cartilage, nerve, and tendon repair—as well as many other possible applications.
Thomas Bauer, MD
JBJS Case Connector Co-Editor
Reference
- Glassy EF, Rebooting the Pathology Journal. Learning in the Age of Digital Pathology. Archiv Pathol Lab Med 2014;138:728-729.
Recent Comments