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1.
Giant cell tumour of bone (GCTB) is an intermediate locally aggressive primary bone tumour, occurring mostly at the meta-epiphysis of long bones. Overexpression of receptor activator of nuclear factor kappa-B ligand (RANKL) by mononuclear neoplastic stromal cells promotes recruitment of numerous reactive multinucleated osteoclast-like giant cells, causing lacunar bone resorption. Preferential treatment is curettage with local adjuvants such as phenol, alcohol or liquid nitrogen. The remaining cavity may be filled with bone graft or polymethylmethacrylate (PMMA) bone cement; benefits of the latter are a lower risk of recurrence, possibility of direct weight bearing and early radiographic detection of recurrences. Reported recurrence rates are comparable for the different local adjuvants (27–31%). Factors increasing the local recurrence risk include soft tissue extension and anatomically difficult localisations such as the sacrum. When joint salvage is impossible, en-bloc resection and endoprosthetic joint replacement may be performed. Local tumour control on the one hand and maintenance of a functional native joint and quality of life on the other hand are the main pillars of surgical treatment for this disease. Current knowledge and development in the fields of imaging, functional biology and systemic therapy are forcing us into a paradigm shift from a purely surgical approach towards a multidisciplinary approach. Systemic therapy with denosumab (RANKL inhibitor) or zoledronic acid (bisphosphonates) blocks, respectively inhibits, bone resorption by osteoclast-like giant cells. After use of zoledronic acid, stabilisation of local and metastatic disease has been reported, although the level of evidence is low. Denosumab is more extensively studied in two prospective trials, and appears effective for the optimisation of surgical treatment. Denosumab should be considered in the standard multidisciplinary treatment of advanced GCTB (e.g. cortical destruction, soft tissue extension, joint involvement or sacral localisation) to facilitate surgery at a later stage, and thereby aiming at immediate local control. Even though several questions concerning optimal treatment dose, duration and interval and drug safety remain unanswered, denosumab is among the most effective drug therapies in oncology. 相似文献
2.
《Annals of oncology》2015,26(10):2149-2154
BackgroundGiant cell tumor of bone (GCTB) is a rare primary bone tumor, characterized by osteoclast-like giant cells that express receptor activator of nuclear factor-kappa B (RANK), and stromal cells that express RANK ligand (RANKL), a key mediator of osteoclast activation. A RANKL-specific inhibitor, denosumab, was predicted to reduce osteolysis and control disease progression in patients with GCTB.Patients and methodsSeventeen patients with GCTB were enrolled. Patients were treated with denosumab at 120 mg every 4 weeks, with a loading dose of 120 mg on days 8 and 15. To evaluate efficacy, objective tumor response was evaluated prospectively by an independent imaging facility on the basis of prespecified criteria.ResultsThe proportion of patients with an objective tumor response was 88% based on best response using any tumor response criteria. The proportion of patients with an objective tumor response using individual response criteria was 35% based on the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria, 82% based on the modified European Organization for Research and Treatment of Cancer (EORTC) criteria, and 71% based on inverse Choi criteria. The median time of study treatment was 13.1 months.ConclusionThe findings demonstrate that denosumab has robust clinical efficacy in the treatment of GCTB. 相似文献
3.
BackgroundGiant-cell tumours of bone (GCTB) are RANK/RANK-ligand (RANKL) positive, aggressive and progressive osteolytic tumours. Denosumab, a RANKL inhibitor, was FDA-approved for adults and skeletally mature adolescents with unresectable GCTB or when surgical resection is likely to result in severe morbidity. Data on long-term toxicity and activity of denosumab monthly ‘GCTB-schedule’ (120 mg per 12/year, 1440 mg total dose/year) are lacking.MethodsPatients with GCTB receiving denosumab, 120 mg on days 1, 8, 15, 29 and every 4 weeks thereafter, from 2006 to 2015 treated in two centres were included. Long-term toxicity was evaluated.ResultsNinety-seven patients were identified. 43 patients underwent resection of the tumour with a median time on denosumab treatment of 12 months (range 6–45 months). Fifty-four patients had unresectable GCTB's (male/female 23/31, median age 35 years [range: 13–76 years], 26% presented with lung metastases, 31% had primary tumor located to the spine, 63% were relapsed after previous surgery) with a median time on denosumab of 54 months (9–115 months). In the unresectable GCTB group, tumour control and clinical benefits were observed in all patients undergoing denosumab, whereas 40% of patients discontinuing denosumab had tumour progression after a median of 8 months (range 7–15 months).Adverse eventsOverall, six (6%) patients developed osteonecrosis of jaw (ONJ): 1/43 (2%) in the resectable group, 5/54 (9%) in the unresectable group, with a 5-year ONJ-free survival of 92% (95% CI 84–100). Only patients with prolonged treatment experienced mild peripheral neuropathy (6/54, 11%), skin rash (5/54, 9%), hypophosphataemia (2/54, 4%) and atypical femoral fracture (2/54, 4%).ConclusionsProlonged treatment with denosumab has sustained activity in GCTB, with a mild toxicity profile. The dose-dependent toxicity observed recommends a careful and strict monitoring of patients who need prolonged treatment. Decreased dose-intensity schedules should be further explored in unresectable GCTB. 相似文献
4.
Shinji Tsukamoto Andreas F. Mavrogenis Suraj Hindiskere Kanya Honoki Akira Kido Hiromasa Fujii Tomoya Masunaga Yasuhito Tanaka Pramod S. Chinder Davide Maria Donati Costantino Errani 《Current oncology (Toronto, Ont.)》2022,29(9):6383
En bloc resection is typically performed to treat giant cell tumors of bone (GCTB), particularly when curettage can be challenging owing to extensive bone cortex destruction with soft tissue extension. Few reports have addressed the clinical outcomes after reoperation for local recurrence in patients with GCTB who underwent en bloc resection. In this multicenter retrospective study, we investigated local recurrence, distant metastasis, malignant transformation, mortality, and limb function in patients treated for local recurrence following en bloc resection for GCTB. Among 205 patients who underwent en bloc resection for GCTB of the extremities between 1980 and 2021, we included 29 with local recurrence. En bloc resection was performed for large tumors with soft tissue extension, pathological fractures with joint invasion, complex fractures, and dispensable bones, such as the proximal fibula and distal ulna. Local re-recurrence, distant metastasis, malignant transformation, and mortality rates were 41.4% (12/29), 34.5% (10/29), 6.9% (2/29), and 6.9% (2/29), respectively. The median Musculoskeletal Tumor Society score was 26 (interquartile range, 23–28). The median follow-up period after surgery for local recurrence was 70.1 months (interquartile range, 40.5–123.8 months). Local recurrence following en bloc resection for GCTB could indicate an aggressive GCTB, necessitating careful follow-up. 相似文献
5.
Maurice Balke Laura Campanacci Carsten Gebert Piero Picci Max Gibbons Richard Taylor Pancras Hogendoorn Judith Kroep John Wass Nicholas Athanasou 《BMC cancer》2010,10(1):462
Background
Giant cell tumour of bone (GCTB) is an expansile osteolytic tumour which contains numerous osteoclast-like giant cells. GCTB frequently recurs and can produce metastatic lesions in the lungs. Bisphosphonates are anti-resorptive drugs which act mainly on osteoclasts. 相似文献6.
Lizz van der Heijden P.D. Sander Dijkstra Michiel A.J. van de Sande Judith R. Kroep Remi A. Nout Carla S.P. van Rijswijk Judith V.M.G. Bovée Pancras C.W. Hogendoorn Hans Gelderblom 《The oncologist》2014,19(5):550-561
We provide an overview of imaging, histopathology, genetics, and multidisciplinary treatment of giant cell tumor of bone (GCTB), an intermediate, locally aggressive but rarely metastasizing tumor. Overexpression of receptor activator of nuclear factor κB ligand (RANKL) by mononuclear neoplastic stromal cells promotes recruitment of numerous reactive multinucleated giant cells. Conventional radiographs show a typical eccentric lytic lesion, mostly located in the meta‐epiphyseal area of long bones. GCTB may also arise in the axial skeleton and very occasionally in the small bones of hands and feet. Magnetic resonance imaging is necessary to evaluate the extent of GCTB within bone and surrounding soft tissues to plan a surgical approach. Curettage with local adjuvants is the preferred treatment. Recurrence rates after curettage with phenol and polymethylmethacrylate (PMMA; 8%–27%) or cryosurgery and PMMA (0%–20%) are comparable. Resection is indicated when joint salvage is not feasible (e.g., intra‐articular fracture with soft tissue component). Denosumab (RANKL inhibitor) blocks and bisphosphonates inhibit GCTB‐derived osteoclast resorption. With bisphosphonates, stabilization of local and metastatic disease has been reported, although level of evidence was low. Denosumab has been studied to a larger extent and seems to be effective in facilitating intralesional surgery after therapy. Denosumab was recently registered for unresectable disease. Moderate‐dose radiotherapy (40–55 Gy) is restricted to rare cases in which surgery would lead to unacceptable morbidity and RANKL inhibitors are contraindicated or unavailable. 相似文献
7.
骨巨细胞瘤是一种以溶骨性破坏为特征的侵袭性肿瘤,手术治疗后复发率高,少数会出现肉瘤样恶变及转移。近年来,针对特异性靶向核因子κB受体活化因子配体(receptor activator of nuclear factor kappa B ligand,RANKL)的地诺单抗治疗高级别、不可切除和转移性骨巨细胞瘤疗效显著,能够降低外科分期,增加手术切除几率,减少术后功能丧失,控制肿瘤进展;同时,用药后影像及病理学出现特征性改变,对临床诊断及手术治疗提出新的问题。最后,地诺单抗在用药时间、安全性方面尚有部分争议,有待进一步临床试验证实。 相似文献
8.
Catherine L. McCarthy Christopher L. M. H. Gibbons Kevin M. Bradley A. Bass Hassan Henk Giele Nicholas A. Athanasou 《Clinical sarcoma research》2017,7(1):19
Background
Treatment of giant cell tumour of bone (GCTB) of the distal radius/ulna poses a surgical challenge, as complex reconstructive surgery may be required. This study evaluates the clinical, radiological and pathological findings in five cases of GCTB of the distal forearm where a 3 month course of denosumab was given prior to surgery.Methods
Patients with biopsy proven distal forearm GCTB, treated for 3 months with denosumab, followed by salvage surgery (curettage and cementation) were included. Wrist pain and function were assessed using the modified Mayo Wrist Score (MMWS). Plain radiographs, MRI and PET/CT were performed pre-treatment and 2 months after initiation of denosumab therapy. Histological comparison was made between the original biopsy and surgical curettage specimens.Results
Five patients with an average age of 25 years were included in the study. Improvement in wrist pain and function was seen in all patients with the average MMWS increasing from 30 pre-treatment to 85 at 3 months. Plain radiographs demonstrated marginal sclerosis in all cases with reconstitution of cortical and subarticular bone by 2 months; internal matrix sclerosis and osseous consolidation was more variable. Increased tumour heterogeneity and low signal were observed on T2-weighted MR images. PET/CT revealed a decrease in average SUV from 14.8 pre-treatment to 4.7 at 2 months. Histology showed disappearance of osteoclasts and increased fibro-osseous tissue. Denosumab treatment has the potential to facilitate salvage surgery, thus avoiding bone resection and graft reconstruction. A good outcome was achieved apart from local recurrence in one case. Follow up ranged from 17 to 54 months.Conclusion
Distal forearm GCTB responds clinically, radiologically and histologically to a short course of pre-operative denosumab therapy, which has the potential to facilitate salvage surgery.9.
BackgroundDenosumab is an effective treatment for giant cell tumor of the bone (GCTB) but can cause clinically significant adverse effects. Current approved dosing is every 4 weeks after 3 weekly loading doses. We assessed whether alternative, longer dosing intervals are associated with differences in efficacy or bone toxicity.MethodsSingle institution retrospective chart review was conducted on patients with GCTB over 18 years old who received at least 1 year of standard denosumab dosing. Patients identified using a free-text search engine with keywords “giant cell tumor” and “denosumab” from January 1998 to August 2020.ResultsApproximately 37 patients with GCTB (19F, 18M) were identified with median age of 37 years (range 22-73). Dosing interval was increased in 38% (n = 14), with the most common final dosing interval 12 weeks (n = 8). Six patients (16%) had bone complications: osteonecrosis of the jaw (n =5), atypical fracture (n = 1), and nonhealing dental wounds (n = 2). All patients with bone complications were on the monthly dosing schedule, but there was no statistically significant difference compared to longer dosing intervals (P = .22). No statistically significant difference in median PFS was noted (P = .97). However, 5-year PFS was superior in patients treated with less frequent versus standard dosing of denosumab (P = .036).ConclusionsIncreasing the interval of denosumab dosing for GCTB provided similar tumor control compared to standard dosing and lower absolute number of bone toxicity events. Larger studies are needed to better define the optimal interval of denosumab administration and the effect on efficacy, toxicity, and associated healthcare expense. 相似文献
10.
Clézardin P 《Bulletin du cancer》2011,98(7):837-846
Bone homeostasis is maintained by the remodelling of bone which depends on a balance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Malignant bone lesions are very common in patients with cancer; whether they result from a tumor in bone (giant cell tumour of bone, osteosarcoma, multiple myeloma...) or they are bony metastases from advanced cancers of which the most osteotropic are breast and prostate cancer. Malignant cells within the bone disrupt the normal bone remodelling process, leading to increased bone destruction and occurence of pathological fractures. Receptor activator of NF-kB (RANK) and its ligand (RANKL) play a pivotal role in the regulation of bone remodelling; by binding to RANK, RANKL stimulates osteoclastogenesis and bone resorption, whereas its cognate decoy receptor osteoprotegerin (OPG) blocks this process by interacting with RANKL. Tumour cells produce different factors that manipulate the RANK/RANKL/OPG pathway in order to stimulate bone destruction. Furthermore, pending on the tumour type, RANKL plays a role in the migration, invasion and proliferation of malignant cells within the bone, while OPG increases survival of tumour cells. Inhibition of RANK/RANKL system may therefore offer new therapeutic perspectives for the treatment of primitive and secondary bone cancers. 相似文献
11.
Abha Gupta Lisa Durocher-Allen Snezana Popovic Richard Tozer Xiaomei Yao Michelle Ghert 《Current oncology (Toronto, Ont.)》2021,28(2):1302
Background: The role of denosumab in patients with resectable giant cell tumour of bone remains unclear. We asked the following research question: for patients (aged ≥ 12 years) with resectable giant cell tumour of bone, what are the benefits and harms of denosumab compared with no denosumab in terms of (1) facilitation of surgery (operative time, blood loss), (2) disease recurrence, (3) pain control, (4) disease stability, and (5) adverse effects (e.g., malignant transformation, osteonecrosis of jaw, atypical femur fracture)? One previous systematic review addressed only one outcome—disease recurrence. Therefore, we undertook this new systematic review to address the above five outcomes. Methods: MEDLINE, EMBASE, PubMed, and Cochrane Database of Systematic Reviews databases were searched on June 30, 2020. Results: This systematic review included one previous systematic review and five comparative studies. Due to poor quality, non-randomized studies fraught with selection bias, it is difficult to determine if a significant difference exists in the outcomes for surgical giant cell tumour of bone with perioperative denosumab. There were no reported cases of adverse effects from denosumab. Conclusion: To date, there is insufficient evidence to understand the value of denosumab in the perioperative setting in patients with giant cell tumour of bone. 相似文献
12.
脊柱骨巨细胞瘤(giant cell tumor of bone,GCTB)较为少见,诊断依靠临床、影像和病理三结合原则。脊柱GCTB的治疗难度较大,目前还没有基于循证医学的治疗流程和共识,因而具有很强的挑战性。手术仍然是脊柱GCTB治疗的首选方法,术前选择性动脉栓塞、完整切除肿瘤及术后辅助使用地诺单抗(denosumab)是目前推荐的综合治疗方法。整块切除是脊柱GCTB的理想治疗方式,但手术方法的选择需要遵循个体化原则,根据不同的部位制定不同的手术方案。地诺赛麦对于手术无法完全切除、复发及转移性GCTB的治疗具有一定的优势,术前使用能够有效降低GCTB外科分期,并为整块切除手术创造条件,具有广泛的应用前景。 相似文献
13.
Piotr Rutkowski Louie Gaston Aneta Borkowska Silvia Stacchiotti Hans Gelderblom Giacomo Giulio Baldi Emanuela Palmerini Paolo Casali Alessandro Gronchi Michael Parry Domenico Andrea Campanacci Guido Scoccianti Michal Wagrodzki Stefano Ferrari Sander Dijkstra Andrzej Pieńkowski Robert Grimer 《European journal of surgical oncology》2018,44(9):1384-1390
Background
Giant cell tumor of bone (GCTB) is an osteolytic, locally aggressive, rarely metastazing bone tumor. This is a retrospective study evaluating a large series of GCTB patients treated with denosumab in routine practice in 6 European reference centers.Methods
Patients with locally advanced, unresectable or metastatic GCTB, treated with denosumab outside clinical trials were eligible. Primary end-point was progression-free survival (PFS) for all patients; secondary end-points were: type of surgery, relapse rate and event-free survival for patients after preoperative denosumab + surgery.Results
We identified 138 patients treated in the period 2011–2016. In 40/43 cases the diagnosis was confirmed by H3F3A gene mutation. Median follow-up time was 23 months (range 6–48). Primary tumor was located in lower limb (38%) - mostly in femur and tibia, in upper limb (34%), and in pelvis/axial skeleton/ribs (28%). 110 (80%) patients had primary tumors, 28 (22%) recurrent tumors after previous surgical procedures (+/? radiotherapy). 89/138 patients had locally advanced GCTB and underwent neoadjuvant denosumab. The median denosumab treatment duration was 8 months (median number of cycles 11), 98% had clinical benefit from therapy. 39 (44%) had wide en-bloc resection - WE (+implantation of the prosthesis in 17 cases), the other 50 (56%) cases had intralesional curettage - C. Progression after surgical treatment was observed in 19 patients, 16 of them after C (32%); 13 patients underwent denosumab re-challenge, and all responded. Two-year progression-free survival (PFS; from denosumab start) rate was 81%; 2-year EventFS (from surgery) was significantly better in WE group (93%) vs 55% in C group (p = 0.006). Treatment was well tolerated with only 2 cases of grade 3 toxicity and one osteonecrosis of the jaw.Conclusion
Our retrospective study confirms that denosumab is extremely efficient in unresectable/metastatic disease as well as in a neoadjuvant setting. Our data confirm excellent efficacy and short-term tolerability of this drug. Our data suggest that neoadjuvant therapy with denosumab is the option for treatment of initially locally advanced tumors to facilitate complete surgical resection or avoid mutilating surgery. The risk of recurrences after curettage of GCTB following denosumab raises questions about the optimal management of such cases. 相似文献14.
Mengke Fan Guochuan Zhang Mingfang Xie Xinbo Liu Qi Zhang Ling Wang 《Current oncology (Toronto, Ont.)》2022,29(10):7655
The main features of a giant cell tumor of bone (GCTB) are frequent recurrence and aggressive osteolysis, which leads to a poor prognosis in patients. Although the treatment methods for a GCTB, such as scraping and resection, effectively inhibit the disease, the tendency toward malignant transformation remains. Therefore, it is important to identify new treatment methods for a GCTB. In this study, we first found high Siglec-15 expression in GCTB tissues, which was significantly associated with Campanacci staging and tumor recurrence. In Spearman’s analysis, Siglec-15 expression was significantly correlated with Ki-67 levels in tumor tissues. In vitro, the mRNA and protein levels of Siglec-15 were high in GCTB stromal cells (Hs737. T), and Siglec-15 knockdown inhibited the biological characteristics of GCTB stromal cells. The RNA sequencing results enabled a prediction of the downstream genes by using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and MCODE analyses, and the findings showed that CXCL8 was significantly regulated by Siglec-15 and might be a promising downstream target gene of Siglec-15. Therefore, Siglec-15 may be a potential immunotherapy target for a GCTB. 相似文献
15.
Penelope D. Ottewell Ning Wang Hannah K. Brown C. Anne Fowles Peter I. Croucher Colby L. Eaton Ingunn Holen 《International journal of cancer. Journal international du cancer》2015,137(4):968-977
Dormant disseminated tumour cells can be detected in the bone marrow of breast cancer patients several years after resection of the primary tumour. The majority of these patients will remain asymptomatic, however, ~15% will go on to develop overt bone metastases and this condition is currently incurable. The reason why these dormant cells are stimulated to proliferate and form bone tumours in some patients and not others remains to be elucidated. We have recently shown that in an in vivo model, increasing bone turnover by ovariectomy stimulated proliferation of disseminated tumour cells, resulting in formation of bone metastasis. We now show for the first time that osteoclast mediated mechanisms induce growth of tumours from dormant MDA‐MB‐231 cells disseminated in the bone. We also show that disruption of RANK–RANKL interactions following administration of OPG‐Fc inhibits growth of these dormant tumour cells in vivo. Our data support early intervention with anti‐resorptive therapy in a low‐oestrogen environment to prevent development of bone metastases. 相似文献
16.
Significance of Histone H3.3 (G34W)-Mutant Protein in Pathological Diagnosis of Giant Cell Tumor of Bone
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Upik A MiskadFutriani SyamsulHaslindah DahlanNi Ketut SungowatiDjumadi AchmadMuhammad P Johan 《Asian Pacific journal of cancer prevention》2023,24(5):1737-1741
Objective: This study aimed to examine the expression of Histone H3.3 glycine 34 to tryptophan (G34W) mutant protein in Giant Cell Tumor of Bone (GCTB). Methods: This analytic observation research used a cross-sectional study design on 71 bone tumors. The cases involved 54 tissue samples diagnosed as GCBT. It was divided into GCTB primer (n=37), recurrent GCTB (n=5), GCTB with metastasis (n=9), and malignant GCTB (n=3). There were 17 samples mimics of GCTB also tested, including chondroblastoma (n=1), giant cell reparative granuloma (n=2), giant cell of tendon sheath (n=7), chondromyxoid fibroma (n=2), aneurysmal bone cyst (n=2), and giant cell-rich osteosarcoma (n=3). The Immunohistochemistry was used to evaluate the expression of G34W-mutated protein in these bone tumors. Result: The representation H3.3 (G34W) was expressed in the nuclei of mononuclear stromal cells but not stained on osteoclast-like giant cells. This study was analyzed by the Chi-square test, Fisher’s test, specificity test, and sensitivity test. We obtained p = 0.001 for Histone H3.3 (G34W) mutant expression in GCTB vs Non-GCTB. Statistically, there was no significant difference in the expression level of Histone H3.3 (G34W) in the GCTB and its variants p-value = 0.183. We also obtained that the specificity of Histone H3.3 expression on GCTB was 100% and the sensitivity of Histone H3.3 on GCTB was 77.8%. Conclusion: Histon H3.3 mutant as a mutated driver gene in an Indonesian GCTB can assist to diagnose GCTB and compare it from other bone tumors. 相似文献
17.
We investigated the clinical features of soft-tissue recurrence in giant cell tumor of bone (GCTB). Among 106 cases with GCTB
in our hospital, there were 2 cases occurring soft-tissue recurrence which histories were reported. These two soft-tissue
recurrences occurred with the interval of 6.9 years and 2.5 years respectively from primary diagnosis. The clinical presentation
was nonspecific masses in soft tissue. Radiographic ossification was not found at periphery or within the masses. Through
pathological examination peripheral ossification was found in 1 case and malignant transformation occurred in the other case.
Through retrieving and reviewing literatures in PubMed, 19 cases of soft-tissue recurrence with detailed materials were collected
and analyzed. Soft-tissue recurrence of GCTB is a rare episode which reflects its locally aggressive nature, the reasons of
which are tumor cells implantation and tumor residual. Ossification at periphery or in the masses can be considered as a pathognomonic
character of this episode in radiographic and pathohistological examination. The prevention lies in determining tumor extension
preoperatively, proper non-tumor manipulations, removing the tumor and irrigating operative wound as completely as possible. 相似文献
18.
《Clinical oncology (Royal College of Radiologists (Great Britain))》2021,33(12):e578-e585
AimsSacral chordomas are locally aggressive, radio-resistant tumours. Proton therapy has the potential to deliver high radiation doses, which may improve the therapeutic ratio when compared with conventional radiotherapy. We assessed tumour control and radiation-induced toxicity in a cohort of sacral chordoma patients treated with definitive or postoperative pencil beam scanning proton therapy.Methods and materialsSixty patients with histologically proven sacral chordoma treated between November 1997 and October 2018 at the Paul Scherrer Institute with postoperative (n = 50) or definitive proton therapy (n = 10) were retrospectively analysed. Only 10 (17%) patients received combined photon radiotherapy and proton therapy. Survival rates were calculated using the Kaplan–Meier actuarial method. The Log-rank test was used to compare different functions for local control, freedom from distant recurrence and overall survival. Acute and late toxicity were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.ResultsThe median follow-up was 48 months (range 4–186). Local recurrence occurred in 20 (33%) patients. The 4-year local control, freedom from distant recurrence and overall survival rates were 77%, 89% and 85%, respectively. On univariate analysis, subtotal resection/biopsy (P = 0.02), tumour extension restricted to bone (P = 0.01) and gross tumour volume >130 ml (P = 0.04) were significant predictors for local recurrence. On multivariate analysis, tumour extension restricted to bone (P = 0.004) and gross total resection (P = 0.02) remained independent favourable prognostic factors for local recurrence. Twenty-four (40%), 28 (47%) and eight (11%) patients experienced acute grade 1, 2 and 3 toxicities, respectively. The 4-year late toxicity-free survival was 91%. Two patients developed secondary malignancies to the bladder 3–7 years after proton therapy.ConclusionsOur data indicate that pencil beam scanning proton therapy for sacral chordomas is both safe and effective. Gross total resection, tumour volume <130 ml and tumour restricted to the bone are favourable prognostic factors for local tumour control. 相似文献
19.
癌症转移是致死的主要原因,骨是排第三的好发转移部位。OPG/RANKL—RANK骨调节轴是影响破骨细胞发育及功能的唯一途径。地诺单抗(denosumab)是全人源化结合RANKL的中和抗体,由FDA于2010年11月批准用于实体瘤骨转移的治疗。本文就地诺单抗用于骨转移癌治疗的机制及临床实验研究作一综述,为临床医生更合理的选择骨改构药物用于骨转移癌的治疗做指导。 相似文献
20.
Patrick Hundsdoerfer Marion Albrecht Ursula Rühl Rüdiger Fengler Andreas E. Kulozik Günter Henze 《European journal of cancer (Oxford, England : 1990)》2009,45(14):2447-2451
BackgroundCurrent standard therapy for high-grade osteosarcoma is neoadjuvant chemotherapy and complete resection of the primary tumour. Irradiation can improve local control if complete tumour resection is not possible or refused, but data on long-term outcome are not available.Patients and methodsWe report on long-term results for overall survival, occurrence of local recurrence and metastasis, joint function and side-effects in 13 patients with high-grade osteosarcoma having been treated with a combination of local irradiation and polychemotherapy (median follow-up of 13.5 years).ResultsTen of the 13 patients were alive 4–23 years after diagnosis. Three patients suffered local recurrence, in 2 of them tumour control and long-term survival could be achieved by secondary salvage surgery and polychemotherapy. In 5 patients pathological fractures of the irradiated bones occurred, none of them was associated with local recurrence. In 7 of the 10 long-term survivors good or fair joint function was achieved.ConclusionsWe conclude that combination of chemotherapy and intensive local irradiation can achieve long-term local control and even cure in high-grade osteosarcoma. Thus radiation therapy may represent an alternative to definite surgery in selected patients, in particular in those with good response to chemotherapy, when surgery is not feasible or refused. 相似文献