Giant cell tumor of bone - Optimal strategy for use of denosumab and radiotherapy

I read with great interest the article “Comparison between radiotherapy and neoadjuvant denosumab followed by surgery in the treatment of giant cell tumor of bone: A retrospective observational study” published in the Cancer Research, Statistics and Treatment Journal by Saha et al.[1] I would like to make some comments and contributions. A giant cell tumor (GCT) is a benign but aggressive tumor of bone, with surgery being the preferred mode of treatment. Surgical intervention typically provides good local control and acceptable function. Most GCTs can be managed with extended intralesional curettage, without the need for pre-operative denosumab. This approach applies to Campanacci Grades I and II, as well as some Grade III GCTs. Adding denosumab in this subgroup may increase the rates of local failures.[2,3] Conversely, very large Campanacci Grade III GCTs or lesions in expendable bones like the lower end of the ulna may require resection. In these cases, patients can benefit from pre-operative denosumab, which helps in ossifying the tumor, reducing blood loss, improving intra-operative handling, and decreasing the chances of tumor spillage.[4] Intralesional extended curettage is the preferred surgical treatment for GCTs, providing an acceptable rate of local control while preserving joint function.[5] Denosumab is effective in downstaging the tumor, allowing for less invasive surgical interventions in large tumors with borderline chances of joint preservation. However, this approach can result in higher recurrence rates. Recent studies have suggested that neoadjuvant denosumab increases the risk of local recurrence in patients treated with curettage.[2,3,6] With the availability of definitive long-term denosumab, the indications for radiotherapy have been reduced. However, radiotherapy is still used for unresectable tumors and in cases where surgery results in unacceptable morbidity.[7] Long-term denosumab, either alone or in combination with embolization, effectively controls symptoms and disease activity and is now preferred over radiotherapy in most centers.[8] Typically, a patient requires 3-4 sessions of angioembolization along with 8-10 doses of denosumab to achieve disease control. Despite this, radiotherapy remains in use at many centers. The prescribed dose for radiotherapy in giant cell tumors of bone is 45-50 Gy, delivered in fractions of 1.8-2 Gy for adequate control. Modern treatment planning systems enable the safe delivery of higher doses without major toxicities. Although radiotherapy appears to be a more cost-effective strategy and can offer durable local control, especially after the initial 5-6 weeks of treatment, prospective studies comparing it with other nonsurgical modalities will help decide the best approach for unresectable GCTs or cases where surgical treatment leads to very high morbidity.[9] To emphasize, most appendicular GCTs are managed with curettage without the use of neo-adjuvant denosumab or radiotherapy. A small fraction of appendicular GCTs that require resection may benefit from a short course of neo-adjuvant denosumab (3-4 doses). Radiotherapy is reserved for unresectable GCTs (such as those in the spine and pelvis) or in cases where surgical resection would result in unacceptable morbidity (e.g., sacrum), particularly when long-term denosumab cannot be offered to the patient. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.