Clinical orthopaedics and related research, Jan 28, 2016
Reconstruction of periacetabular defects after pelvic tumor resection ranks among the most challe... more Reconstruction of periacetabular defects after pelvic tumor resection ranks among the most challenging procedures in orthopaedic oncology, and reconstructive techniques are generally associated with dissatisfying mechanical and nonmechanical complication rates. In an attempt to reduce the risk of dislocation, aseptic loosening, and infection, we introduced the LUMiC(®) prosthesis (implantcast, Buxtehude, Germany) in 2008. The LUMiC(®) prosthesis is a modular device, built of a separate stem (hydroxyapatite-coated uncemented or cemented) and acetabular cup. The stem and cup are available in different sizes (the latter of which is also available with silver coating for infection prevention) and are equipped with sawteeth at the junction to allow for rotational adjustment of cup position after implantation of the stem. Whether this implant indeed is durable at short-term followup has not been evaluated. (1) What proportion of patients experience mechanical complications and what are th...
Background It is common practice nowadays to treat patients with metastatic epidural spinal cord ... more Background It is common practice nowadays to treat patients with metastatic epidural spinal cord compression (MESCC) surgically. Extend and type of surgery should be in proper relation to the expected survival time of the patient. It is still difficult to predict patient9s survival time and different scoring systems are used. Reliable prediction of survival is mandatory, in that way adjustable surgical treatment can be established. Aim Evaluating potential prognostic factors for survival after surgery for MESCC. Methods In this retrospective study we included 56 patients who underwent surgery for MESCC in two hospitals in the Netherlands between 2001 and 2007, Medical records were studied for the origin of the primary tumour, location of MESCC and the number of spots, presence of visceral or axial metastases, Karnofsky-score and ASA-score. Patients were grouped, according Tomita et al., for the localization of the primary tumour; fast (n=21), moderate (n=19) and slow (n=16) growing ...
The improved prognosis of cancer patients has led to an increased incidence of both bone metastas... more The improved prognosis of cancer patients has led to an increased incidence of both bone metastases and (impending) pathological fractures. A solitary bone lesion seen on radiography should never be assumed to be a metastasis. Preoperative biopsy is necessary in patients with a known malignancy and a solitary lytic bone lesion as well as in patients in whom the primary tumor is unknown, in order to prevent an incorrect operation (also known as 'whoops surgery'). If the patient has an (impending) pathological fracture, normal bone healing is not to be expected, not even after stable fixation. Surgical fixation of an impending pathologic fracture is recommended when radiography indicates that a length of more than 3 cm of the cortex of a long bone has been destroyed. If surgical treatment is necessary, it should support the whole long bone in order to enable full weight bearing. When the diagnosis of a bone lesion is uncertain, referral to an experienced treatment centre is re...
11026 Background: Retrospective study on locally advanced GCTB patients (pts) treated with neoadj... more 11026 Background: Retrospective study on locally advanced GCTB patients (pts) treated with neoadjuvant Denosumab (Db) outside clinical trials in 6 European reference centers. Methods: From 138 pts (median age 30yrs) with histologically confirmed advanced GCTB treated with Db(2011-2016), we included into analysis 87pts who underwent surgery after preoperative Db. All 87 patients had locally advanced tumors with extensive soft tissue involvement(54) or penetration to joint, not amenable to limb-sparing surgery/primary curettage or with high risk of recurrence. In 39/42(93%) cases diagnosis was confirmed by H3F3Agene mutation. Median follow-up time -22 months. Results: Primary tumor was located in lower limb(54%; n = 47) -mostly in tibia(25%) and femur(23%), upper limb(33%; n = 29), and pelvis/axial skeleton/ribs(13%; n = 11). 68(78%) patients had primary tumors, 19(22%) recurrent tumors after surgery (+/-radiotherapy). Median Db duration was 7months (range 1.5-35months), 17pts receive...
3288 Though less common than benign enchondromas, chondrosarcomas (CSs), their malignant counterp... more 3288 Though less common than benign enchondromas, chondrosarcomas (CSs), their malignant counterparts, still account for approximately 20% to 30% of all bone sarcomas, and their peak de novo incidence occurs between the ages of 40 and 60 years. With an increase in radiological examinations, the relative incidence of CSs has significantly increased over the last decades to approximately 9 per million citizens; this can be mostly explained by an increase in incidental findings of atypical cartilaginous tumors (ACTs)/grade 1 CSs. Ninety percent of all CSs are of the conventional type and are graded 1 to 3. Because of their benign biological behavior, the World Health Organization in 2013 reclassified grade 1 conventional central CSs as locally aggressive ACTs. We will limit our discussion to the appendicular skeleton because CSs in the axial skeleton exhibit a different, more aggressive behavior that requires a different diagnostic and therapeutic approach. Currently, only grade 2 and 3 conventional extremity CSs are considered full-blown malignant tumors. The 3-, 5-, and 10-year survival estimates are 82%, 74%, and 62%, respectively, for grade 2 CSs and 38%, 31%, and 26%, respectively, for grade 3 CSs. In the old grading system, treatment was based on radiologic and pathologic efforts to distinguish between benign enchondromas and malignant conventional CSs of all grades. However, the new classification of intermediate-grade ACTs challenges this old therapeutic paradigm. We should tailor our therapeutic goals for ACTs and CSs (grade 2 or higher) to their biologic behavior. This requires accurate radiological differentiation between ACTs and high-grade CSs. Current Practice In line with this reconsideration of the intermediate malignant potential of ACTs in the appendicular skeleton, treatment for ACTs in the long bone has evolved over the past 3 decades from radical resection into intralesional resection (curettage with local adjuvant therapy) or even wait and follow-up policies.
To support shared decision-making, we developed the first prediction model for patients with prim... more To support shared decision-making, we developed the first prediction model for patients with primary soft-tissue sarcomas of the extremities (ESTS) which takes into account treatment modalities, including applied radiotherapy (RT) and achieved surgical margins. The PERsonalised SARcoma Care (PERSARC) model, predicts overall survival (OS) and the probability of local recurrence (LR) at 3, 5 and 10 years. Development and validation, by internal validation, of the PERSARC prediction model. The cohort used to develop the model consists of 766 ESTS patients who underwent surgery, between 2000 and 2014, at five specialised international sarcoma centres. To assess the effect of prognostic factors on OS and on the cumulative incidence of LR (CILR), a multivariate Cox proportional hazard regression and the Fine and Gray model were estimated. Predictive performance was investigated by using internal cross validation (CV) and calibration. The discriminative ability of the model was determined with the C-index. Multivariate Cox regression revealed that age and tumour size had a significant effect on OS. More importantly, patients who received RT showed better outcomes, in terms of OS and CILR, than those treated with surgery alone. Internal validation of the model showed good calibration and discrimination, with a C-index of 0.677 and 0.696 for OS and CILR, respectively. The PERSARC model is the first to incorporate known clinical risk factors with the use of different treatments and surgical outcome measures. The developed model is internally validated to provide a reliable prediction of post-operative OS and CILR for patients with primary high-grade ESTS. LEVEL OF SIGNIFICANCE: level III.
Two male and one female patient, aged 64, 70 and 51 respectively, were surgically treated for pat... more Two male and one female patient, aged 64, 70 and 51 respectively, were surgically treated for pathological fracture of the proximal femur without preoperative biopsy. In contrast to their benign radiological diagnosis, all three patients were finally diagnosed as having a malignant primary bone tumour. The proximal femur is the primary location of pathological fractures in the appendicular skeleton. Metastases to bone are the most common cause of a destructive lesion of the skeleton in an adult. Although rare, a primary bone tumour must be included in differential diagnosis of a pathological fracture. A systematic diagnostic strategy is critical to avoid complications that make curative treatment impossible. A solitary bone lesion seen on radiography should never be assumed to be a bone metastasis. Without further diagnostic research, surgical treatment for a pathological fracture should never be commenced before a definitive diagnosis is made.
The Journal of Clinical Endocrinology & Metabolism
Context Fibrous dysplasia/McCune Albright syndrome (FD/MAS) is a rare bone disorder commonly trea... more Context Fibrous dysplasia/McCune Albright syndrome (FD/MAS) is a rare bone disorder commonly treated with bisphosphonates but clinical and biochemical responses may be incomplete. Objective To evaluate the efficacy and tolerability of the RANKL inhibitor denosumab in the treatment of patients with FD/MAS refractory to bisphosphonate therapy. Design Case series Setting Academic Center of Expertise for Rare Bone Diseases Patients Data was collected from twelve consecutive patients with FD/MAS with persistent pain and increased biochemical markers of bone turnover (BTMs) after long-term treatment with bisphosphonates (median 8.8 years) and were treated with subcutaneous Denosumab 60 mg at 3 or 6 monthly intervals with a follow up for at least 12 months. Main outcome(s)Sustained reduction of BTMs and bone pain. Results Denosumab 60 mg once every 3 months, but not once every 6 months, induced a sustained, significant reduction of BTMs. After a median treatment period of 15.5months (range...
Giant cell tumour of bone (GCTB) is an intermediate locally aggressive primary bone tumour, occur... more 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.
This study investigates the effect of surgical margins and radiotherapy, in the presence of indiv... more This study investigates the effect of surgical margins and radiotherapy, in the presence of individual baseline characteristics, on survival in a large population of high-grade soft tissue sarcoma of the extremities using a multistate model. A retrospective multicentre cohort study. 4 tertiary referral centres for orthopaedic oncology. 687 patients with primary, non-disseminated, high-grade sarcoma only, receiving surgical treatment with curative intent between 2000 and 2010 were included. The risk to progress from 'alive without disease' (ANED) after surgery to 'local recurrence' (LR) or 'distant metastasis (DM)/death'. The effect of surgical margins and (neo)adjuvant radiotherapy on LR and overall survival was evaluated taking patients' and tumour characteristics into account. The multistate model underlined that wide surgical margins and the use of neoadjuvant radiotherapy decreased the risk of LR but have little effect on survival. The main prognostic...
Clinical orthopaedics and related research, Jan 28, 2016
Reconstruction of periacetabular defects after pelvic tumor resection ranks among the most challe... more Reconstruction of periacetabular defects after pelvic tumor resection ranks among the most challenging procedures in orthopaedic oncology, and reconstructive techniques are generally associated with dissatisfying mechanical and nonmechanical complication rates. In an attempt to reduce the risk of dislocation, aseptic loosening, and infection, we introduced the LUMiC(®) prosthesis (implantcast, Buxtehude, Germany) in 2008. The LUMiC(®) prosthesis is a modular device, built of a separate stem (hydroxyapatite-coated uncemented or cemented) and acetabular cup. The stem and cup are available in different sizes (the latter of which is also available with silver coating for infection prevention) and are equipped with sawteeth at the junction to allow for rotational adjustment of cup position after implantation of the stem. Whether this implant indeed is durable at short-term followup has not been evaluated. (1) What proportion of patients experience mechanical complications and what are th...
Background It is common practice nowadays to treat patients with metastatic epidural spinal cord ... more Background It is common practice nowadays to treat patients with metastatic epidural spinal cord compression (MESCC) surgically. Extend and type of surgery should be in proper relation to the expected survival time of the patient. It is still difficult to predict patient9s survival time and different scoring systems are used. Reliable prediction of survival is mandatory, in that way adjustable surgical treatment can be established. Aim Evaluating potential prognostic factors for survival after surgery for MESCC. Methods In this retrospective study we included 56 patients who underwent surgery for MESCC in two hospitals in the Netherlands between 2001 and 2007, Medical records were studied for the origin of the primary tumour, location of MESCC and the number of spots, presence of visceral or axial metastases, Karnofsky-score and ASA-score. Patients were grouped, according Tomita et al., for the localization of the primary tumour; fast (n=21), moderate (n=19) and slow (n=16) growing ...
The improved prognosis of cancer patients has led to an increased incidence of both bone metastas... more The improved prognosis of cancer patients has led to an increased incidence of both bone metastases and (impending) pathological fractures. A solitary bone lesion seen on radiography should never be assumed to be a metastasis. Preoperative biopsy is necessary in patients with a known malignancy and a solitary lytic bone lesion as well as in patients in whom the primary tumor is unknown, in order to prevent an incorrect operation (also known as 'whoops surgery'). If the patient has an (impending) pathological fracture, normal bone healing is not to be expected, not even after stable fixation. Surgical fixation of an impending pathologic fracture is recommended when radiography indicates that a length of more than 3 cm of the cortex of a long bone has been destroyed. If surgical treatment is necessary, it should support the whole long bone in order to enable full weight bearing. When the diagnosis of a bone lesion is uncertain, referral to an experienced treatment centre is re...
11026 Background: Retrospective study on locally advanced GCTB patients (pts) treated with neoadj... more 11026 Background: Retrospective study on locally advanced GCTB patients (pts) treated with neoadjuvant Denosumab (Db) outside clinical trials in 6 European reference centers. Methods: From 138 pts (median age 30yrs) with histologically confirmed advanced GCTB treated with Db(2011-2016), we included into analysis 87pts who underwent surgery after preoperative Db. All 87 patients had locally advanced tumors with extensive soft tissue involvement(54) or penetration to joint, not amenable to limb-sparing surgery/primary curettage or with high risk of recurrence. In 39/42(93%) cases diagnosis was confirmed by H3F3Agene mutation. Median follow-up time -22 months. Results: Primary tumor was located in lower limb(54%; n = 47) -mostly in tibia(25%) and femur(23%), upper limb(33%; n = 29), and pelvis/axial skeleton/ribs(13%; n = 11). 68(78%) patients had primary tumors, 19(22%) recurrent tumors after surgery (+/-radiotherapy). Median Db duration was 7months (range 1.5-35months), 17pts receive...
3288 Though less common than benign enchondromas, chondrosarcomas (CSs), their malignant counterp... more 3288 Though less common than benign enchondromas, chondrosarcomas (CSs), their malignant counterparts, still account for approximately 20% to 30% of all bone sarcomas, and their peak de novo incidence occurs between the ages of 40 and 60 years. With an increase in radiological examinations, the relative incidence of CSs has significantly increased over the last decades to approximately 9 per million citizens; this can be mostly explained by an increase in incidental findings of atypical cartilaginous tumors (ACTs)/grade 1 CSs. Ninety percent of all CSs are of the conventional type and are graded 1 to 3. Because of their benign biological behavior, the World Health Organization in 2013 reclassified grade 1 conventional central CSs as locally aggressive ACTs. We will limit our discussion to the appendicular skeleton because CSs in the axial skeleton exhibit a different, more aggressive behavior that requires a different diagnostic and therapeutic approach. Currently, only grade 2 and 3 conventional extremity CSs are considered full-blown malignant tumors. The 3-, 5-, and 10-year survival estimates are 82%, 74%, and 62%, respectively, for grade 2 CSs and 38%, 31%, and 26%, respectively, for grade 3 CSs. In the old grading system, treatment was based on radiologic and pathologic efforts to distinguish between benign enchondromas and malignant conventional CSs of all grades. However, the new classification of intermediate-grade ACTs challenges this old therapeutic paradigm. We should tailor our therapeutic goals for ACTs and CSs (grade 2 or higher) to their biologic behavior. This requires accurate radiological differentiation between ACTs and high-grade CSs. Current Practice In line with this reconsideration of the intermediate malignant potential of ACTs in the appendicular skeleton, treatment for ACTs in the long bone has evolved over the past 3 decades from radical resection into intralesional resection (curettage with local adjuvant therapy) or even wait and follow-up policies.
To support shared decision-making, we developed the first prediction model for patients with prim... more To support shared decision-making, we developed the first prediction model for patients with primary soft-tissue sarcomas of the extremities (ESTS) which takes into account treatment modalities, including applied radiotherapy (RT) and achieved surgical margins. The PERsonalised SARcoma Care (PERSARC) model, predicts overall survival (OS) and the probability of local recurrence (LR) at 3, 5 and 10 years. Development and validation, by internal validation, of the PERSARC prediction model. The cohort used to develop the model consists of 766 ESTS patients who underwent surgery, between 2000 and 2014, at five specialised international sarcoma centres. To assess the effect of prognostic factors on OS and on the cumulative incidence of LR (CILR), a multivariate Cox proportional hazard regression and the Fine and Gray model were estimated. Predictive performance was investigated by using internal cross validation (CV) and calibration. The discriminative ability of the model was determined with the C-index. Multivariate Cox regression revealed that age and tumour size had a significant effect on OS. More importantly, patients who received RT showed better outcomes, in terms of OS and CILR, than those treated with surgery alone. Internal validation of the model showed good calibration and discrimination, with a C-index of 0.677 and 0.696 for OS and CILR, respectively. The PERSARC model is the first to incorporate known clinical risk factors with the use of different treatments and surgical outcome measures. The developed model is internally validated to provide a reliable prediction of post-operative OS and CILR for patients with primary high-grade ESTS. LEVEL OF SIGNIFICANCE: level III.
Two male and one female patient, aged 64, 70 and 51 respectively, were surgically treated for pat... more Two male and one female patient, aged 64, 70 and 51 respectively, were surgically treated for pathological fracture of the proximal femur without preoperative biopsy. In contrast to their benign radiological diagnosis, all three patients were finally diagnosed as having a malignant primary bone tumour. The proximal femur is the primary location of pathological fractures in the appendicular skeleton. Metastases to bone are the most common cause of a destructive lesion of the skeleton in an adult. Although rare, a primary bone tumour must be included in differential diagnosis of a pathological fracture. A systematic diagnostic strategy is critical to avoid complications that make curative treatment impossible. A solitary bone lesion seen on radiography should never be assumed to be a bone metastasis. Without further diagnostic research, surgical treatment for a pathological fracture should never be commenced before a definitive diagnosis is made.
The Journal of Clinical Endocrinology & Metabolism
Context Fibrous dysplasia/McCune Albright syndrome (FD/MAS) is a rare bone disorder commonly trea... more Context Fibrous dysplasia/McCune Albright syndrome (FD/MAS) is a rare bone disorder commonly treated with bisphosphonates but clinical and biochemical responses may be incomplete. Objective To evaluate the efficacy and tolerability of the RANKL inhibitor denosumab in the treatment of patients with FD/MAS refractory to bisphosphonate therapy. Design Case series Setting Academic Center of Expertise for Rare Bone Diseases Patients Data was collected from twelve consecutive patients with FD/MAS with persistent pain and increased biochemical markers of bone turnover (BTMs) after long-term treatment with bisphosphonates (median 8.8 years) and were treated with subcutaneous Denosumab 60 mg at 3 or 6 monthly intervals with a follow up for at least 12 months. Main outcome(s)Sustained reduction of BTMs and bone pain. Results Denosumab 60 mg once every 3 months, but not once every 6 months, induced a sustained, significant reduction of BTMs. After a median treatment period of 15.5months (range...
Giant cell tumour of bone (GCTB) is an intermediate locally aggressive primary bone tumour, occur... more 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.
This study investigates the effect of surgical margins and radiotherapy, in the presence of indiv... more This study investigates the effect of surgical margins and radiotherapy, in the presence of individual baseline characteristics, on survival in a large population of high-grade soft tissue sarcoma of the extremities using a multistate model. A retrospective multicentre cohort study. 4 tertiary referral centres for orthopaedic oncology. 687 patients with primary, non-disseminated, high-grade sarcoma only, receiving surgical treatment with curative intent between 2000 and 2010 were included. The risk to progress from 'alive without disease' (ANED) after surgery to 'local recurrence' (LR) or 'distant metastasis (DM)/death'. The effect of surgical margins and (neo)adjuvant radiotherapy on LR and overall survival was evaluated taking patients' and tumour characteristics into account. The multistate model underlined that wide surgical margins and the use of neoadjuvant radiotherapy decreased the risk of LR but have little effect on survival. The main prognostic...
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Papers by Sander Dijkstra