On June 20, 2020, ASCO approved the first joint Musculoskeletal Tumor Society (MSTS)/American Society for Radiation Oncology (ASTRO)/ASCO guideline on the care of patients with metastatic carcinoma and myeloma of the femur.1 Guideline recommendations were based on a systematic review of clinical trials and observational studies published between January 1946 and July 2019 and clinical experience. Studies conducted on at least 10 patients were included in the review.
Reducing the Dosing Frequency of Bone-Modifying Agents
“Based on the experience of the workgroup, we believe that bone-modifying agents were still widely being dosed on a monthly schedule, where there’s [now] substantial evidence that you don’t need to dose them monthly; you can dose them quarterly,” said Felasfa Wodajo, MD, Chair of Evidence-Based Medicine at MSTS and Guideline Co-Chair. “So, these latest recommendations may lead clinicians to reduce the frequency of bone-modifying agent dosing, and we believe that, over time, this would likely reduce the toxicity of bone-modifying agents.”
Felasfa Wodajo, MD
He also stressed the importance of professional societies and experts from different fields collaborating in drafting joint recommendations. “We feel strongly that there is much to be gained from medical and surgical societies cooperating on future guidelines, so we can benefit from each other’s perspective and develop better tools for our patients,” he said. “I hope that this [collaboration] continues.”
Recommendations Address Three Main Therapeutic Avenues
Guideline recommendations address three main therapeutic avenues—the use of bone-modifying agents, radiation therapy, and surgery—and are intended to guide medical oncologists, radiation oncologists, and primary care physicians in making timely referrals. Several recommendations from each area are highlighted below, along with the level of supporting evidence.*
Use of Bone-Modifying Agents:
- The frequency of zoledronic acid may be decreased to 12 weeks (compared with the standard 4-week interval) because of noninferior skeletal-related event outcomes and similar adverse event rates in patients with metastatic carcinoma or multiple myeloma. Long-term use of bone-modifying agents may be considered with the aim to reduce skeletal-related events in patients with multiple myeloma (Strong).
- Bone-modifying agents should be considered in patients with metastatic carcinoma or multiple myeloma with bone lesions, regardless of tumor histology, if they are considered at risk of fracture (Consensus).
Radiation Therapy:
- Radiation therapy should be considered in patients with metastatic carcinoma or multiple myeloma lesions who are deemed at increased risk of femur fractures based on imaging results and lesion-related pain (Moderate).
- Radiation therapy may be considered in patients undergoing prophylactic femur stabilization to improve functional status, reduce pain, and reduce the likelihood of additional intervention (Consensus).
- Multifraction radiation therapy, instead of single-fraction treatment, should be considered to reduce the risk of fracture in patients with metastatic carcinoma in the femur (Moderate).
Surgery:
- Surgeons should utilize a validated method of estimating patient survival when choosing the optimal surgical reconstruction method (Consensus).
- When a femoral neck fracture is treated using hemiarthroplasty, a long stem should be used only in patients with additional lesions in the femur, since it may be associated with a higher rate of complications (Consensus).
- Arthroplasty may be considered in patients with pathologic fractures from metastatic carcinoma in the femur (Limited).
- The expert panel found no advantage to routine use of cephalomedullary nails for diaphyseal metastatic lesions (Consensus).
Assessing the Risk of Fracture Before Treatment Selection
“The critical issue from the perspective of medical oncologists is which patients are at risk of fracture, in what ways a medical oncologist can modify those risks with the therapies available to them, and how much are those risks modified by the treatments they have,” Dr. Wodajo said. “We do think that radiation reduces the risk of fracture in the femur…, although there are, in fact, almost no data showing a benefit of radiation following the surgery, as the risk was relatively low, we went ahead with the consensus recommendation [of] radiation with the surgery.”
Although the benefits of radiation are not clear-cut, Dr. Wodajo noted there is stronger evidence supporting the use of bone-modifying agents. “There does seem to be implied evidence that bone-modifying agents can reduce the risk of fracture by extrapolating from available evidence,” he said. “Second, risk reduction appears to hold, even at lower dosing intervals.” He believes that adoption of these recommendations in clinical practice, particularly the reduced dosing of bone-modifying agents, will benefit patients over the long term by reducing the toxicity and frequency of adverse events associated with these agents.
Finally, Dr. Wodajo stressed the importance of including anatomic data when conducting studies on bone-modifying agents. “If the studies include data on where in the skeleton fractures occur, and not aggregate them as skeletal-related events, that could significantly help patients and physicians in the future,” he said.
DISCLOSURE: This clinical practice guideline was funded by the Musculoskeletal Tumor Society and the American Academy of Orthopaedic Surgeons and received no funding from outside commercial sources to support the development of this document.
REFERENCE
1. MSTS, ASTRO, ASCO: The treatment of metastatic carcinoma and myeloma of the femur: Clinical practice guideline. Available at http://msts.org/view/download.php/education/mbd-cpg-amended. Accessed October 13, 2020.
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, October 7, 2020. All rights reserved.
*This is not a comprehensive list of guideline recommendations. For additional details, please refer to the full text of the guideline.
