Surgical Downstaging in an Open-Label Phase II Trial of Denosumab in Patients with Giant Cell Tumor of Bone

Rutkowski, Piotr; Ferrari, Stefano; Grimer, R. J.; Stalley, Paul; Dijkstra, Sander; Pieńkowski, Andrzej; Vaz, Gualter; Wunder, Jay S.; Seeger, Leanne L.; Feng, Amy; Roberts, Zachary J.; Bach, Bruce Allen

doi:10.1245/s10434-015-4634-9

Cited by 148 publications

(147 citation statements)

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“…Rutkowski et al (16) reported an open-label Phase II study showing clinical benefits of denosumab treatment in 222 patients with GCTB. Four patients developed malignant GCTB transformation: two radiation-associated sarcomatous transformations at 4 and 6 years after radiotherapy, respectively, and two pelvic or sacral GCTB lesions that progressed under denosumab after 257 days of exposure.…”

Section: Discussionmentioning

confidence: 99%

Development of high-grade osteosarcoma in a patient with recurrent giant cell tumor of the ischium while receiving treatment with denosumab

Tsukamoto

Righi²,

Vanel³

et al. 2017

Japanese Journal of Clinical Oncology

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Malignant transformation of giant cell tumor of bone (GCTB) without radiotherapy exposure is exceptionally rare, occurring in less than 1% of GCTBs. The safety and efficacy of denosumab in patients with GCTB was recently reported. We herein report a case of a benign recurrent GCTB with an H3F3A mutation that underwent secondary malignant transformation during treatment with denosumab. A 29-year-old woman underwent curettage of a GCTB of the left ischium in 2005. Ten years after the first surgery, the GCTB recurred locally. We started treatment with denosumab. During the first 5 months of treatment, we observed a demarcated area of osteosclerosis in the recurrent lesion, and the patient's clinical condition improved. At 6 months, however, the patient developed pain, and a rapidly growing mass was detected by computed tomography. An incisional biopsy was performed. Histologic analysis showed a high-grade osteosarcoma. The patient developed lung metastases and died soon after beginning chemotherapy. The mechanism of sarcomatous transformation of GCTB during denosumab therapy is unclear. These findings suggest that the scientific community should be aware of the possible malignant transformation of GCTB during denosumab treatment.

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Section: Discussionmentioning

confidence: 99%

Development of high-grade osteosarcoma in a patient with recurrent giant cell tumor of the ischium while receiving treatment with denosumab

Tsukamoto

Righi²,

Vanel³

et al. 2017

Japanese Journal of Clinical Oncology

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“…In contrast to the previous studies [13, 14], all included patients underwent a surgical procedure already indicated at diagnosis, giving denosumab the role of an adjuvant treatment comparable to radiation therapy in soft tissue sarcomas.…”

Section: Introductionmentioning

confidence: 99%

Risks and benefits of combining denosumab and surgery in giant cell tumor of bone—a case series

et al. 2016

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BackgroundThe RANK ligand inhibitor denosumab is being investigated for treatment of giant cell tumor of bone, but the available data in the literature remains sparse and controversial. This study analyzes the results of combining denosumab with surgical treatment and highlights possible changes for the oncologic surgeon in daily practice.MethodsA total of 91 patients were treated surgically for giant cell tumor of bone between 2010 and 2014 in an institution, whereas 25 patients of the total additionally received denosumab and were part of this study. The average age of the patients was 35 years. Eleven patients received denosumab pre- and postoperatively, whereas with 14 patients, the denosumab treatment was applied either before (7 patients) or after (7 patients) the surgery. The average preoperative therapy duration was 3.9 months and the postoperative therapy 6 months by default.ResultsSixteen patients presented a large tumor extension necessitating a resection of the involved bone or joint. In 10 of these patients, the indication for a resection procedure was abandoned due to the preoperative denosumab treatment and a curettage was performed. In the remaining six cases, the surgical indication was not changed despite the denosumab treatment, and two of them needed a joint replacement after the tumor resection. Also with patients treated with curettage, denosumab seems to facilitate the procedure as a new peripheral bone rim around the tumor was built, though a histologic analysis reveals viable tumor cells persisting in the denosumab-induced bone formation.After an average follow-up of 23 months, one histologically proven local recurrence occurred, necessitating a second curettage. A second patient showed a lesion in the postoperative imaging highly suspicious for local relapse which remained stable under further denosumab treatment. No adverse effect of the denosumab medication was observed in this study.ConclusionsDenosumab can be a help to the oncologic surgeon by reconstituting a peripheral rim and switching the stage from aggressive to active or latent disease. But as tumor cells remain in the new-formed bone, the surgical technique of curettage has to be changed from gentle to more aggressive to avoid higher local recurrence rates.

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“…Cerrahi geçiren 116 hastanın (sadece 13 aylık ortalama cerrahi sonrası takip) 17' sinde (% 15) lokal nüks mevcuttu ve bu hastaların büyük çoğunluğunda sadece intralezyoner cerrahi ile tedavi edildiler (57).…”

Section: Denosumab Tedavisi Sonrası Dev Hücreli Tümörde Tekrarlamaunclassified

Denosumab Therapy in Giant Cell Bone Tumor: Review of Literature

Balta¹,

Kurnaz²,

Aytekin³

et al. 2017

Acta Oncol Tur.

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ÖZETDenosumab kemik dev hücreli tümörünü yönetmek için etkili ve kullanışlı bir ilaçtır. İnoperable veya metastatik dev hücreli tümörlü hastalar için birinci basamak tedavide altın standart olarak düşünülmektedir. Dev hücreli kemik tümöründe denosumabınetkinliği prospektifrandomize çalışmalarda kanıtlanmıştır. Nörovasküler yapılara yakın büyük dev hücreli tümörde daha fazla morbiditeye yol açaçak rezeksiyona yönelmek yerine denosumab ile neoadjuvan tedavi dev hücreli tümörde intralezyonel cerrahiyi kolaylaştırabilir. Farklı sebeplerden dolayı tedaviyi bıraktıktan sonra yapılan biyopside psödosarkomatöz değişiklikler görülebileceği unutulmamalıdır. Dev hücreli tümörde denosumab tedavisi sonrası kalınlaşmış korteks ve subkondral kemik içerisinde tümör hücrelerinin gizlenmesi sonucu lokal tümör rekürrensi görülebilir. Denosumab çenede osteonekroz oluşumu ile ilişkilendirilmiştir. Bu makalede denosumab tedavisi alan hastaların sistematik değerlendirilmesi,risk faktörleri, tanı-tedavi yararlığı, tedavi seçeneklerini öngören kılavuzlar sunulmuştur. Anahtar Kelimeler: denosumab, dev hücreli tümörü, cerrahi ABSTRACT Denosumab is an effective and usefull drug for managing the giant cell bonetumor. It is considered the gold standard for treatment of the inoperable or metastatic giant cell tumors. Theefficacy of denosumab in giant cell bone tumors has been demonstrated in prospective randomized trials. Neoadjuvant therapy with denosumab may facilitate intralesional surgery in giant cell tumor instead of resection leading to more morbidity in a large giant cell tumor close to the neurovascular structure. It should not be forgotten that pseudosarcomatous changes in biopsies may ocur after denosumab treatment due to different reasons. Giant cell tumor may result in dense cortex after denosumab treatment and local tumor recurrence after concealment of tumor cells within the subchondral bone. Denosumab is associated with jaw osteonecrosis formation. In this article, guidelines for systematic evaluation, risk factors, diagnostic-therapeutic usefullness and treatment options for patients treated with denosumab are presented. Keywords: denosumab, giant cell bone tumor, surgery GirişDev hücreli kemik tümörü benign fakat lokal olarak agresif davranış gösteren ve genellikle genç erişkinleri etkileyen bir lezyondur (1). Dev hücreli kemik tümöründen etkilenen hastaların % 1-4 ünde çoğu benign olmak üzere akciğer metastazı görülür (2, 3). Dev hücreli kemik tümörleri tüm primer kemik tümörlerinin % 4-5'ini ve tüm benign tümörlerin % 20'sini oluşturur. Kadınlarda 1,5-2 kat daha fazla görülür ve genellikle genç kadınları (20-40 yaş arası) etkiler (1, 4). Dev hücreli kemik tümörünün distal femur, proksimal tibia, distal radius ve proksimal humerus en sık rastlanan tutulum yeridir (5). Aksiyel iskelette en fazla sakrumda görülür (1,4,5). Kemiğin korteksini genellikle inceltir, çoğunlukla ekspanse olur. Yumuşak doku genişlemesi ile veya yumuşak doku genişlemesi olmadan kortekste lizis yapabilir (6). Anterior vertebral kolon tutulumu sıklıkla ...

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Surgical Downstaging in an Open-Label Phase II Trial of Denosumab in Patients with Giant Cell Tumor of Bone

Cited by 148 publications

References 32 publications

Development of high-grade osteosarcoma in a patient with recurrent giant cell tumor of the ischium while receiving treatment with denosumab

Development of high-grade osteosarcoma in a patient with recurrent giant cell tumor of the ischium while receiving treatment with denosumab

Risks and benefits of combining denosumab and surgery in giant cell tumor of bone—a case series

Denosumab Therapy in Giant Cell Bone Tumor: Review of Literature

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