Wounds and Injuries

All Conditions

Neoplasms

Symptoms and General Pathology

Fractures, Bone

Neoplasm Metastasis

Fractures, Spontaneous

Neoplastic Processes

This is the group of patients with metastatic pathologic fractures treated with endoprosthesis. For example, proximal femur prosthesis for femoral neck fractures.

This is the group of patients with metastatic pathologic fractures treated with intramedullary nail, and additional bone cement if needed. For example, proximal femur nail for trochanteric fractures, or long femoral nail for femoral shaft fractures.

This is the group of patients with metastatic pathologic fractures treated with open reduction internal fixation; with plates and screws. For example, reconstruction plates for pelvic fractures or 3.5 locking compression plates for humeral or femur shaft fractures.

This is a type of surgery in which the affected part of the bone and joint is removed, and replaced by a prosthesis.

endoprosthetic reconstruction

This is a type of surgery in which the affected bone is stabilized by a nail. The affected part could be removed or retained. If removed, the defect is filled with bone cement.

Intramedullary nailing

This is a type of surgery in which the affected part of the bone is visualized completely, after the reduction is achieved, the fixation is provided with appropriate plates and screws. Again the affected part could be removed or retained. If removed, the defect is filled with bone cement.

Open reduction internal fixation with plate and screws

Merve Dursun Savran, MD

Mustafa Onur Karaca, Assc. Proff

This is a single center prospective study to compare the short term results of prosthesis, nail and plate-screw surgeries for metastatic pathologic fractures.

The most common bone tumor in elderly is metastatic bone tumors. With the prolonged life expectancy in cancer patients, the management of the metastases became an essential topic.

Pathological fractures should be examined and managed with a different perspective. They usually cannot be healed by conservative methods and require surgical intervention. The primary goals of surgical intervention are to relieve pain and mobilize the patient as soon as possible.

The aim of the study is to compare the short-term functional endoprosthetic recontruction, intramedullary nailing and open reduction internal fixation.

The primary tumor of the patient, applied chemotherapy and radiotherapy, Mirel risk score, Charlson comorbidity index, and PathFx 3.0 survival will be evaluated preoperatively.

The type of the operation will be decided at the multidisciplinary tumor council of ankara University.

Metastatic Pathologic Fractures, Short Term Results

Metastatic Pathologic Fractures: Short Term Results of Endoprosthetic Reconstruction, Intramedullary Nail and Open Reduction Internal Fixation

Final MSTS, TESS, UEFS, LEFS, DASH, WOMAC, VAS will be shared when the study is completed.

MSTS score is for evaluating the patients with bone tumors. It consists of six domains; scored on a 0 to 5 scale and transformed into an overall score ranging from 0 to 100% with a higher score indicating better function.

TESS is widely used for the functional assessment of patients following surgery for musculoskeletal tumours. In the TESS system, specific movements for independent living and functionality are questioned and scored.While the worst score is 0, the best score for the lower extremity is 150, and the best score for the upper extremity is 145.

VAS is a widely used scale for pain. 0 means no pain where 10 means unbearable pain.

UEFS is a functional scale for upper extremity. It is not specific for tumor patients.

DASH is a widely used functional scale for upper extremity. It is not specific for tumor patients.

LEFS is a functional scale for lower extremity. It is not specific for tumor patients.

WOMAC is a widely used functional scale for lower extremity. It is not specific for tumor patients.

Hospitalization length required after the surgery.

Time that the patient lives after the surgery

Ankara University

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Musculoskeletal Diseases

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Disease Progression

Bone Neoplasms

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Disease Attributes

All patients referred to the Hematology clinic for diagnosis and treatment of active multiple myeloma will be asked to participate in the study and undergo 3 consecutive low-dose CT scans over a period of 12 months. For non-consenting patients only minimal demographic data will be documented.

Eligible consenting patients will sign informed consent.

CTFEA is a computerized analysis of CT-scans which simulates stress testing of finite element models of various bones (in this study - femurs and vertebrae).

No intervention is planned - the study is observational. CT scans are performed for follow-up as an accepted standard of care. Secondary use of CT scans for CTFEA is in addition to the standard of care.

In a case when CTFEA analysis detects a high risk of pathologic fracture, the treating hematologist will be informed and will refer the patient for evaluation at the National Unit of Orthopedic Oncology.

CT-based finite element analysis

Amir Sternheim, MD

Haggai Schermann, MD

Patients with Multiple Myeloma are monitored for disease progression and for response to treatment by the treating hematologist or oncologist. Laboratory tests are usually utilized for these purposes. The role of imaging is confined to follow-up the progression of visible bone lesions. We suggest that microscopic bone lesions impair bone structure well before they grow enough to be visible on a CT scan. This impairment of bone strength can probably be captured by application of CT-based finite element analysis to the CT scans that were performed for monitoring of progression of the disease.

Background

Multiple myeloma (MM) is the most common primary bone malignancy, caused by proliferation of plasma cells secreting immunoglobulins. Active MM (aMM) is characterized in many patients by multiple lytic bone lesions, presenting with pain in the involved bones (e.g. pelvis, spine, etc.). In a recent publication, key-opinion leaders of multiple-myeloma state "MM-induced bone disease is a hallmark of MM; up to 80% of patients present with osteolytic bone lesions at diagnosis and have an increased risk of skeletal-related events (SREs) associated with increased morbidity and mortality" (Terpos et al, 2018). Approximately 60% of myeloma patients will develop a fracture during the disease course" (Terpos et al, 2018). Current CT scans provide qualitative measures of bone involvement detected only after irreversible damage has occurred and which cannot predict disease evolution so to optimize treatment and enhance life quality and longevity.

Medical treatment modalities, including multi-agent chemotherapy and bone marrow transplantation, may stop progression of MM, and prevent further bone lesions. Myeloma response to therapy is usually monitored by measurement of the monocloncal protein which is secreted by the malignant plasma cells into the blood and urine. This protein includes an intact immunoglobulin - M-SPIKE - which is measured by serum protein electrophoresis (SPEP) and, Circulating free light chains - kappa and lambda. Usually one of the chains is "involved" in the disease; The level of M-SPIKE and the ratio of the "involved" to "uninvolved" chains is used to monitor disease progression. The role of imaging technologies in monitoring progression of the disease is less defined. Low-dose total body CT scans are recommended as second-line imaging (total body MRI is first-line) during the initial diagnostic workup of MM by the most current guidelines of National Institute for Healthcare Excellence (NICE, 2016). The guidelines encourage further research of the role of various imaging modalities in treatment of MM:

"Newer imaging techniques are replacing skeletal surveys for assessing myeloma related bone disease in people with newly diagnosed myeloma. However, the most effective tech-nique is not known. Outcomes of interest are lesion detection, sensitivity and specificity for myeloma related bone disease, patient acceptability, incremental upstaging, radiation exposure, risk of second primary cancer, the impact of additional information on predicting progression-free survival, overall survival and skeletal related events." (NICE, 2016) As previously stated, current imaging modalities visualize bone lesions but do not quantify their progression, any response to therapy or their impact on bone strength. A novel scientific tool that describes bone's response by mathematical equations and is based on CT scans of MM patients, allows to construct a 3-D model of patient's femurs and vertebrae including the inhomogeneous material properties, virtually loads the bones by physiological loads associated with patient's weight and determine the deformations and strains by a computer simulation. This technology, termed CTFEA, allows a quantitative evaluation of bone's strength and risk of fracture, was double-blinded validated ex-vivo, and clinically validated in a retrospective clinical trial on a cohort of 50 patients with metastatic tumors to their femurs (Sternheim et al, 2018).

Combining the engineering and scientific expertise with the clinical knowledge and database of MM patients accumulated during the past ten years, may identify by monitoring femurs' and vertebrae' strength the evolution of MM, and trigger the need of prophylactic surgeries. Such CTFEA has the potential to revolutionize MM treatment by providing the MDs quantitative scientific measures to monitor and change treatment options so to optimize medication prescription and enhance life-quality and longevity of MM patients on one hand, and determine with high level of accuracy the risk of impending fracture due to metastatic tumors to the femurs and vertebrae.

Preliminary results on a cohort of seven MM patients (Cohen et al, 2017), has recently been presented in Dec 2017 at the ASH conference in the USA. These results showed the potential of assisting MDs to determine disease evolution and treatment. Since the vertebrae are prone to MM involvement, we plan to validate the CTFEA methods for such vertebrae with MM involvement by comparing experiments performed on cadaveric human vertebrae with the computational simulation. In addition, we propose to in-vivo validate the accuracy and predictability of patient specific CTFEA of vertebrae and femurs by a clinical trial on a cohort of MM patients treated at Sourasky medical center.

Rationale CTFEA may add efficacy to CT scans used for follow-up of disease progression. This analysis can detect differences of as little as 10% in bone strength. It has the ability to detect changes even in normal looking bone on CT and not just in lytic lesions. In addition, CTFEA characterises the effect of each myeloma lesion on bone structure and calculates the risk of a pathologic fracture.

Study hypothesis:

We hypothesize that CTFEA analysis of LDTBCT will detect changes over time in patients with a dynamic disease, even when these changes in CT are undetectable to the human eye.

Study objectives:

Primary objective:

To observe CTFEA-determined bone strength changes over time in patients with Active MM.

Secondary objectives

1. To measure CTFEA changes over a period of 12 months in lumbar vertebrae and femurs of patients with AMM.
2. To determine correlation between CTFEA and clinical indicators of response to treatment (e.g. light chains, clinical staging of bone lesions).
3. To compare CTFEA changes over time between patients responding to AMM treatment and those who do not respond to treatment.

Methods Study design This is a prospective study with one patient group. All patients will undergo three Low-Dose Total Body CT (LDTBCT) scans as part of diagnostic workup for MM, which represents our current common practice: at 0, 6 and 12 months into treatment (or 3 CT scans at least 6 months apart).

All three scans will be sent for CTFEA, which is not part of the common practice. The CTFEA results will be compared to clinical assessments as per patient files and light chain values on blood work. Changes in lesion size will be compared to changes that the lesion inflicts in bone structure and changes in the risk of fracture.

Bone strength in both femurs and lower lumbar vertebra will be analyzed even where there are no lytic lesions for changes in bone strength.

Results will be correlated with Myeloma clinical variables including baseline demographic and disease charateristics, therapy details and response to treatment over time.

Patients will continue followup, for recording of skeletal related events (fratures or new lytic lesions)

Measured parameters

1. Primary and secondary disease diagnoses and their ICD-9 codes.
2. Patient ambulatory status at time of MM diagnosis: independent walker; cane ambulator; walker ambulator; wheel chair bound.
3. Time since patient was independent walker, ECOG performance status (Oken et al, 1982)(Appendix A).
4. Treatment for osteoporosis and duration.
5. Date of diagnosis of active MM (and preceding plasma cell dyscrasia if relevant)
6. Myeloma treatment details (dose \& dates) and response to therapy according to IMWG criteria (IMWG, 2010)(Appendix B)
7. CT scans (used for CTFEA) dates.
8. Last patient follow-up date.

10) Medical center at which the patient received their oncology treatment before the hematology referral.

11) Laboratory results, specifically: Myeloma paraprotein measures including SPEP, quantitative immunoglobulins and free light chain values; kidney function; CBC; LDH; B2MG; FISH cytogenetics; BM PC% at diagnosis 12) active myeloma clinical presentation: CRAB criteria (hypercalcemia / renal / anemia / bone lesions); and or SLIM-CRAB criteria (FLC ratio\>100; focal lesions on MRI or PETCT; BM PC\>60%); 13) clinical status at time of CT scan (newly diagnosed MM (NDMM); relapsed refractory MM \[RRMM\]) 14) VAS (Visual Analogue Scale) for pain and Harris Hip Score

CTFEA Myeloma Study

Prospective Application of CTFEA for Monitoring Disease Progression in Active Multiple Myeloma

Identification of changes in bone strength on CT-based FE analysis on three consecutive CT scans that are not apparent to the human eye

Quantification of changes in bone strength in normal looking bone and areas of lytic lesions

Pathological fracture during 12 months of follow up - a diagnosis of fracture that occurred in a bone with a myeloma lesion, without significant trauma. Diagnosis by a primary care physician or a hospital diagnosis will count towards the outcome.

Becoming bed-ridden due to inability to ambulate - the patient will be contacted and asked regarding the ability to bear weight with or without a walking support. Patients who were able to walk independently at the time of study beginning and became dependent on chair or bed for transportation will count towards the outcome

Tel Aviv University

Tel-Aviv Sourasky Medical Center

Lymphoma

Femoral Fractures

Sarcoma

Osteosarcoma

Neoplasms, Connective and Soft Tissue

Leg Injuries

Lymphosarcoma

Soft Tissue Sarcoma

Fibrinolytic Agents

Anticoagulants

All Drugs and Chemicals

Heparin, Low-Molecular-Weight

Tinzaparin

Dalteparin

Heparin

Calcium heparin

Participants receive dalteparin SC QD starting 12-24 hours after surgery on post-operative day 1 until hospital discharge, about 7-10 days.

Patrick Lin

This trial studies how well dalteparin works in preventing deep vein thrombosis (DVT) (blood clots) in participants with cancer. Dalteparin is a blood thinner that can treat blood clots and may prevent them from forming.

PRIMARY OBJECTIVES:

I. To determine the safety of dalteparin as prophylaxis against deep venous thrombosis (DVT) in orthopedic oncology patients.

II. To determine whether there are significantly increased bleeding complications at the surgical site after major oncologic operations in the lower extremity.

OUTLINE:

Participants receive dalteparin subcutaneously (SC) once daily (QD) starting 12-24 hours after surgery on post-operative day 1 until hospital discharge, about 7-10 days.

Dalteparin in Preventing DVT in Participants With Cancer

DVT Prophylaxis in Orthopaedic Oncology Patients - A Safety Study

Our primary outcome was the incidence of post-surgical complications, to include wound dehiscence, infection, and seroma.

A secondary outcome was the occurrence of venous thrombolembolism in the post-operative period, to include both deep venous thrombosis in the lower extremity as well as pulmonary embolism.

The volume of packed red blood cell transfusion in the post-operative period

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Received dalteparin 5000 units daily postop, patients with metastatic disease.

Interventional (Dalteparin, Metastatic)

Received dalteparin 5000 units daily postop, patients with primary sarcomas.

Interventional (Dalteparin, Sarcoma)

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Femur/Thigh

Tibia/Calf

Popliteal

Tumor Location

Carcinoma

Tumor Type

Wide Excision Only

Segmental Reconstruction

Curettage, Internal Fixation

Surgery

Patrick Lin, MD/Professor, Orthopaedic Oncology

Seroma

Wound Infection

Wound Dehiscence

Number of Participants With Post-operative Wound Complications

Deep venous thrombosis

Pulmonary embolism

Number of Participants With Occurrence of Venous Thromboembolism

Post-Operative Blood Transfusion

Overall Study

Hip Fractures

Bone Diseases

Patients are being targeted because they have already agreed to the undergo the IlluminOss Pelvic Implant for standard clinical care. Patient-reported outcome surveys will be administered pre-operatively, as well as at 2 days, 2 weeks, 6 weeks, 3 months, 6 months, 1 year, and 2 years after surgery.

Impending or actual non-displaced or minimally displaced pathologic fractures of the pelvis

IlluminOss pelvic implant for oncologic indication

Pelvic fragility fracture in a geriatric patients (age 65 or older)

IlluminOss pelvic implant for geriatric trauma indication

Joseph O Werenski, BS

Santiago A Lozano-Calderon, MD, PhD

Emily A Berner, BS

The aim of this project is to assess the effectiveness of the IlluminOss pelvic implants in patients with pelvic metastatic disease presenting with pain, risk of pathologic fracture, non-displaced or minimally displaced pathologic fracture of the pelvis, and geriatric patients with pelvic fragility fractures. Results from this study will be used to confirm preliminary clinically and possibly statistically significant reductions in pain and improvements in function among these patients.

The matrix morphology of the tumors in metastatic bone disease (MBD) may be of blastic, lytic, or mixed characteristics. Cancers of purely lytic or mixed blastic-lytic composition are the most concerning, as they result in local destruction of the cortical and trabecular bone, causing significant pain and increasing the risk of a pathologic fracture. Function and mobility are severely affected in this patient population due to mechanical and oncogenic pain.

Prophylactic fixation of impending pathological fractures from MBD has demonstrated significant clinical benefit in terms of reducing mechanical pain and in decreasing the progression to complete pathologic fracture as well as minimizing the symptoms when these occur. In the later clinical scenario, the degree of fracture displacement, pain and functional limitation in most cases is minimal as the fracture is an already treated condition. In terms of surgical impact to the patient, prophylactic fixation is a faster procedure with lower blood loss rates. Other benefits include, shorter length of hospitalization and higher likelihood of discharge to home, in addition to reduction of pain, improvement in activities of daily living, and better quality of life.

Importantly, efforts have been made to predict fracture risk and the need for prophylactic fixation based upon the clinical and radiographic features of MBD. This is well stablished in long bones of the extremities but it is not as clear or conclusive in the pelvis.

Traditionally, Intramedullary devices are used for the purposes of prophylactic fixation and for treatment of pathologic fractures. Advantages include protection of the whole bone and ability to early bear weight given the biomechanical characteristics as a load sharing device. More commonly, these implants are made of titanium or other metal alloys. In recent years, the development of radiolucent implants has been important in orthopaedic oncology as these facilitate evaluation of bone involvement and radiation therapy planning. One of these radiolucent devices is IlluminOss PBSS. This UV light activated polymer has proved to be effective and safe in the treatment of impending pathologic fractures of the humerus. This intramedullary implant is inserted through small incisions and proved to be as effective as traditional intramedullary nails in relieving pain and returning patients faster to their pre-impending fracture level of activity. This product has been cleared by the FDA for use in the humerus, radius and ulna, clavicle, pelvis, fibula, metacarpals, metatarsals, and phalanges. The IlluminOss Photodynamic Bone Stabilization System can also be used in conjunction with FDA-cleared fracture fixation systems to provide supplemental fixation in these anatomic sites. The IlluminOss System may be used in the femur and tibia to provide supplemental fixation to an anatomically appropriate FDA-cleared fracture fixation system.

Pelvic fractures in the elderly are a growing concern as the population ages. While oftentimes treated non-operatively, some require surgical fixation. In addition to the stress which surgery especially puts on geriatric patients, a return to pre-injury mobility is also an important impact and a concern of such procedures.

Contrary to the extremities, there are minimal options for small incision pelvic implants to treat patients suffering from pain or fracture. The complex anatomy of the pelvis does not allow the use of rigid and precontoured implants. Fixation with screws is also challenging given the complex anatomy and high prevalence of vital neurovascular structures in the pelvis.

The non-rigid nature of this polymer in the IlluminOss PBSS makes it suitable to adapt to the complex anatomy of the pelvis. In addition, there is no need to use screws for additional fixation, which is ideal in the pelvis. This implant may allow surgeons to forego the use of screws for fixation because the implant has a 3D anti-rotational profile which generates intrinsic stability when in contact with the inner bone. However, if the surgeon considers that stability is not sufficient, screws may still be used in this study at the surgeon's discretion.

This device has been approved to be used in the pelvis after the experience in a previous study examining its effectiveness in the humerus, radius, and ulna. The purpose of this study is to collect information to effectively measure the improvement in pain control through functional scores after the surgery. We wish to see short term results (2 years) and to have a better understanding of the complication profile.

IlluminOss Photodynamic Bone Stabilization System for the Treatment of Impending and Actual Pelvis Fractures

A Prospective Study of the IlluminOss Photodynamic Bone Stabilization System for the Treatment of Impending and Actual Pathological Fractures in the Pelvis From Metastatic Bone Disease or Geriatric Pelvic Fractures

Patients treated with the IlluminOss pelvic implant will be given functional and pain surveys pre-operatively (within 2 weeks before surgery) and post-operatively (at 2 days, 2 weeks, 6 weeks, 3 months, 6 months, 1 year, and 2 years). 100 patients will be included in the study. The surveys include the VAS Pain, the EQ-VAS, the Combined Pain and Ambulatory Function, the PROMIS Pain Inteference, and the PROMIS Physical Function. Additionally, the MSTS survey will be collected for oncologic patients. If needed, the surveys will be mailed to the patient with a pre-stamped and pre-addressed envelope. When mailing patients MSTS surveys, we will include a set of instructions to guide participants through the questions.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Metastatic Pathologic Fractures, Short Term Results	NCT05825456	Pathologic Frac... Bone Metastases Metastatic Canc...	endoprosthetic ... Intramedullary ... Open reduction ...	-	Ankara University
CTFEA Myeloma Study	NCT04364724	Myeloma Multipl... Metastatic Bone...	CT-based finite...	18 Years - 95 Years	Tel-Aviv Sourasky Medical Center
Dalteparin in Preventing DVT in Participants With Cancer	NCT00525057	Bone Sarcoma Femur Fracture Lymphoma Metastatic Neop... Pathologic Frac... Plasma Cell Mye... Soft Tissue Sar...	Dalteparin	30 Years -	M.D. Anderson Cancer Center
Dalteparin in Preventing DVT in Participants With Cancer	NCT00525057	Bone Sarcoma Femur Fracture Lymphoma Metastatic Neop... Pathologic Frac... Plasma Cell Mye... Soft Tissue Sar...	Dalteparin	30 Years -	M.D. Anderson Cancer Center
CTFEA Myeloma Study	NCT04364724	Myeloma Multipl... Metastatic Bone...	CT-based finite...	18 Years - 95 Years	Tel-Aviv Sourasky Medical Center
IlluminOss Photodynamic Bone Stabilization System for the Treatment of Impending and Actual Pelvis Fractures	NCT04842266	Cancer Metastat... Trauma Pathologic Frac...	IlluminOss pelv... IlluminOss pelv...	21 Years -	Massachusetts General Hospital

Spots Global Cancer Trial Database for pathologic fracture