Neoplasms

Symptoms and General Pathology

All Conditions

Wounds and Injuries

Musculoskeletal Diseases

Neoplasm Metastasis

Fractures, Bone

Bone Neoplasms

Fractures, Spontaneous

standard length femoral stem arthroplasty applied for patients with proximal femoral metastasis either impending or pathological fracture

long femoral stem arthroplasty applied for patients with proximal femoral metastasis either impending or pathological fracture

using lateral approach to the hip we will compare the effect of femoral stem length on the oncological and functional outcomes in patients with proximal femoral metastasis.hip arthroplasty is a surgical procedure that involves changing the head of the femur (the ball) with or without replacing the articular surface of the acetabulum (the socket ).and replacing it with metal head based on a stem covered with cement to fix it to the bone of the femur.

femoral stem in hip arthroplasty

Proximal femoral metastatic disease is a common cause of morbidity and mortality in cancer patients.protecting the entire femur using long nail or long femoral stem was hypothesized to prevent future fracture.However we believe that long stem isn't always necessary and won't decrease the complication rate.noting it's increased complication rate in this high risk patient category .

Skeletal metastasis is the third most common site of cancer metastasis after the lungs and liver, almost all patients with metastatic prostate cancer will have bone metastasis. And about 90% of patients dying from breast cancer has skeletal metastasis.

The most common site to which cancer metastasize to long bones is the proximal femur, especially to the intertrochanteric region and femoral neck, contributing to increasing incidence of impending and pathologic fractures of this site.(8) Recent advances in cancer treatment increased the longevity of patients, with subsequent increase in morbidity of metastatic disease and increased number of patients living longer with this condition .

To date, long femoral stem is most frequently used in cases of pathological and impending proximal femoral fractures. Its use is believed to add more stability and prophylactically protect the entire femur from newly developed distal lesions. However, long stems has more operative time, more cardiopulmonary complications and are more technically demanding compared to standard femoral stems arthroplasty.(5) Recent retrospective study by Xing et al reported comparable outcomes between standard, medium and long stems and concluded that the routine use of long stems is unjustified.Another recent report by Joel et al investigated the use of long femoral stem in 22 limbs, they reported no hardware failure with no cases of intraoperative cardiopulmonary complications, however they recommended larger comparative trials with rigorous methods to investigate the functional outcomes and complications of long femoral stems in proximal femoral metastatic lesions.

In face of the potential advantages in this patient population, the goal of this study is to investigate the use of standard length femoral stems and its results compared to long femoral stems in proximal femoral metastasis .

two comparative groups, standard and long femoral stem arthroplasty

only participants were blinded from treatment group.

Length of the Femoral Stem in Arthroplasty Done for Patients With Proximal Femoral Metastatic Lesion

Cemented Long Versus Standard Femoral Stem Arthroplasty for Proximal Femoral Metastasis

The Musculoskeletal Tumor Society (MSTS) scoring system is a disease-specific instrument to determine the physical and mental health for patients with extremity sarcoma

is a simple measure of functional status. It has scores ranging from 0 to 5

postoperative infection (superficial or deep),dislocation

Ain Shams University

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Disease Progression

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

Bone Diseases

Central Nervous System Depressants

All Drugs and Chemicals

Anesthetics

Patients in the experimental group receive the protocolized anesthetic care bundle including EEG spectrum-guided multimodal anesthesia and HPI-guided hemodynamic therapy.

Patients in the control group receive standard anesthetic care including bispetral index-guided balanced anesthesia and regular hemodynamic care protocols.

The ERAS anesthetic care includes EEG spectrum-guided multimodal anesthesia and HPI-guided hemodynamic therapy.

ERAS anesthetic care

The standard anesthetic care includes bispectral index guided general anesthesia and arterial line monitored hemodynamic care.

Standard anesthetic care

Chun-Yu Wu

Spinal metastases account for 60% of all malignant bone metastases and represent a medically important treatment goal. For patients with malignant tumors diagnosed at this stage, performing En bloc spondylectomy with wide margin of resection facilitate the improvement in quality of life including ambulatory ability, daily activities independence and attenuation of bone pain. However, En bloc spondylectomy is a major operation with long operation time and frequent hemodynamic instability during the operation. Therefore, the anesthetic care plays an important role and an enhanced recovery after surgery (ERAS) is the goal.

For the ERAS anesthesia protocol for En bloc spondylectomy, we propose two major components to achieve this goal: (1) an encephalographic spectrum guided multimodal anesthesia combined with ultrasound-guided nerve block and (2) the advanced machine-learning algorithm index, namely the hypotension predictive index (HPI) guided hemodynamic protocol.

The anesthetic protocol comprises of two major proposed components to enhanced recovery after spine cancer total en bloc resection. First, a multimodal general anesthesia consisting of GABAnergic hypnotic agent (propofol or sevoflurane), ketamine and dexmedetomidine was conducted by using the encephalographic density spectrum array. In addition, ultrasound-guided erector spinae plane block is applied. These techniques potentially prevent anesthesia induced delirium and may profoundly improve postoperative analgesic quality. Second, advanced hemodynamic monitoring device, namely the hypotensio predictive index, will be used for prevention of intraoperative hypotension and facilitate precise transfusion protocol.

Patients in the treatment group received the study protocolized care bundle including multimodal anesthesia and HPI-assisted hemodynamic therapy.

ERAS Anesthetic Care for Metastatic Spine Cancer Resection

Anesthetic Protocols for Enhance Recovery After Metastatic Spine Tumor Resection Surgery: a Randomized Controlled Trial

Comparing the quality of recovery-15 score (0-150) at the first and third postoperative days

Delirium diagnosed based on the Confusion Assessment Method (CAM) criteria during three days after surgery

Postoperative pain intensity measure by using the visual analogue scale (0-10)

National Taiwan University Hospital

Experimental Radiation Dose

Conventional Radiation Dose

UCCC Clinical Trials Office

Christine Vollmer

Timothy Struve, MD

This is a randomized Phase III study evaluating the efficacy of hypofractionated and dose-escalated palliative radiation therapy in metastatic bone disease (MBD). Patients will be randomized 1:1 to the conventional (8 Gy in a single fraction) and experimental (16 Gy in 2 fractions) groups with baseline and subsequent assessment of both pain and quality of life metrics.

Metastatic Bone Disease (MBD) has been demonstrated to be a common clinical problem, and often presents with severe, if not debilitating pain. This often proceeds to affect a patient's emotional and even global functioning. Radiation therapy is an effective treatment commonly used in the palliation of these metastatic lesions, and improvements in QOL scores are associated with response to radiotherapy treatment. Although both 30 Gy/10 fractions and 8 Gy in a single fraction are considered standard of care in the palliative setting, single fraction treatment is associated with increased rates of local failure and retreatment. Considering that patients with MBD often have life-limiting disease, and frequently have great difficulty with undergoing extended radiotherapy treatments, there is a significant unmet need for palliative treatments that are effective, safe, timely, and provide a durable local tumor and pain control. The investigators hypothesize that utilizing a fractionation scheme with an escalated biologically equivalent dose will result in a higher proportion of patients responding to treatment, and will also lead to more durable responses.

Palliative UNConventional Hypofractionation Trial for Metastatic Bone Disease

1-2 PUNCH: Palliative UNConventional Hypofractionation Trial for Metastatic Bone Disease

A primary objective evaluate the efficacy of the addition of a second 8 Gy fraction administered 1 week following the standard 8 Gy treatment currently utilized for palliation of symptomatic bone metastases in solid cancers, as measured by pain response at 1 month. The primary endpoint for this objective is pain response which will be determined using the Brief Pain Inventory (BPI) at one month.

A primary objective evaluate the efficacy of the addition of a second 8 Gy fraction administered 1 week following the standard 8 Gy treatment currently utilized for palliation of symptomatic bone metastases in solid cancers, as measured by pain response at 1 month. The primary endpoint for this objective is pain response which will be classified using the International Consensus on Palliative Radiation for Future Trials on Bone Mets, which is a 4-point scale ranging from complete response to pain progression. Pain relief as measured by this scale and daily oral morphine equivalents (OME) will be graded at 1 month.

A second primary objective is to characterize the safety profile and adverse events (AE) of dose-escalated palliative radiotherapy. The primary endpoint for this objective is Adverse events will be described and coded based upon the NCI CTCAE v5.0 through 30 days after end of a subject's treatment.

A secondary objective is to determine time to maximal pain relief, and to determine pain response at 2, 3, and 6 months. Pain response at 2, 3, and 6 months will be assessed using the Brief Pain Inventory (BPI), and classified using the International Consensus on Palliative Radiation for Future Trials on Bone Mets; as well as daily oral morphine equivalents (OME). Time to maximal pain relief will be determined from BPI questionnaires and International Consensus on Palliative Radiation for Future Trials on Bone Mets scale data.

Another secondary objective is to evaluate the impact of standard and dose-escalated arms of palliative radiotherapy on quality of life. Quality of life data will be obtained via European Organisation for Research and Treatment of Cancer Quality of Life Cancer Patients (EORTC QLQ-C30 (version 3)) at baseline and 1-, 3-, and 6-months post-treatment.

Another secondary objective is to evaluate the impact of standard and dose-escalated arms of palliative radiotherapy on quality of life. Quality of life data will be obtained via European Organisation for Research and Treatment of Cancer Quality of Life Bone Metastases (EORTC QLQBM22) at baseline and 1-, 3-, and 6-months post-treatment.

Another secondary objective is to determine differences in overall survival between subjects receiving standard and dose-escalated palliative radiotherapy. Overall survival (OS) data from the date of completion of radiation therapy will be obtained from departmental records and electronic medical records through 2 years post end of radiation treatment.

Another secondary objective is to determine differences in retreatment rates between subjects receiving standard and dose-escalated palliative radiotherapy. Retreatment rates data from the date of completion of radiation therapy will be obtained from departmental records and electronic medical records through 2 years post end of radiation treatment.

University of Cincinnati

Assistant Professor

Skin and Connective Tissue Diseases

Sarcoma

Osteosarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Antineoplastic Agents

Gemcitabine

Ascorabte is administered on Days 1, 2, 8, 9, 15 and 16 of a 28-day cycle. Gemcitabine will be administered on Days 1, 8 and 15, after the infusion of ascorbate. Concomitant treatment will continue for 6 cycles. Patients whose disease has not progressed while receiving gemcitabine and ascorbate and who are tolerating therapy may continue either single agent gemcitabine or concomitant treatment beyond 6 cycles at the discretion of the investigator. Treatment will be terminated with progression of disease. Disease will be assessed by CT of the chest, abdomen and pelvis or MRI of the lesion every 2 cycles for progression.

Following 15g test dose, 75g administered 75g dose on days 1 and 2. Further doses of ascorbate will be determined by serum ascorbate levels measured by the end of the week to reach a target serum concentration between 20 -30 mM. Ascorbate doses will continue to be escalated until either the target serum concentration or maximum dose of 125 g is administered.

Ascorbate

John Rieth, MD

This study will enroll patients who have a diagnosis of locally advanced, unresectable or metastatic soft tissue or bone sarcoma (except gastrointestinal stromal tumors and Kaposi's sarcoma) from any site.

The primary objectives of this pilot study are to assess the feasibility of pharmacokinetically-guided, patient-individualized dosing and to obtain preliminary evidence of anti-tumor activity of intravenous ascorbate in combination with gemcitabine to inform a subsequent Phase II trial. Soft tissue and bone sarcomas will be studied as different cohorts given the differences in biology and historical responses to single agent gemcitabine in these disease types. As such, 10 evaluable patients per disease cohort will be included.

Gemcitabine Plus Ascorbate for Sarcoma in Adults (Pilot)

A Pilot Study of Gemcitabine Plus High-Dose Ascorbate in Locally Advanced Unresectable or Metastatic Soft Tissue and Bone Sarcomas in Adults

The primary endpoint of interest is PFS12 defined as the proportion of patients without progressive disease per RECIST 1.1 at 12 weeks after treatment initiation. A sample size of 10 evaluable patients per disease cohort (soft tissue and bone) will allow for the estimation of PFS12 per the 90% exact confidence intervals as follows:

PFS12 Exact 90% confidence interval:

1/10 10% (1-39%); 2/10 20% (4-51%); 3/10 30% (9-61%); 4/10 40% (15-70%); 5/10 50% (22-78%); 6/10 60% (30-85%); 7/10 70% (39-91%); 8/10 80% (49-96%); 9/10 90% (61-99%);

Time from start of therapy (day 1, cycle 1) to death.

Tumor response will be defined using the RECIST 1.1 guidelines as below

* Complete response is the disappearance of all target lesions; Any pathological lymph nodes ( whether target or Non-target) must have reduction in short axis to \<10mm.
* Partial response is a 30% decrease in the sum of the longest dimension (LD) of target lesions, relative to baseline measurement;
* Progressive disease is an increase of 20% or more in the sum of the LD of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of at least 5 mm.Or appearance of a new malignant lesion.
* Stable disease is a decrease in tumor size of less than 30% or increase of less than 20%.

Evaluate the safety and tolerability of this regimen by the incidence of AEs per CTCAE 4.03

University of Iowa

Mohammed Milhem, MBBS

Clinical Assistant Professor

Bone Marrow Diseases

Neoplastic Processes

chemotherapy, surgery, radiotherapy, interventional radiology.

Maud Toulmonde, MD

Bone tumors make up about 3-5% of childhood cancers and less than 1% of cancers in adults. Of these, osteosarcoma (OSS) is the most commonly diagnosed primary malignant bone tumor. OSS is a primary mesenchymal malignant tumor of bone characterized by the production of osteoid or immature bone by the malignant cells. Despite its rarity, OSS is the most common primary malignancy of bone in children and adolescents, and the fifth most common malignancy among adolescents and young adults aged 15 to 19 years.

Ewing sarcoma (ES) is the second most frequent bone tumors in children and may arise also in soft tissues. This disease encompasses tumors formerly known as Askin's tumor, Peripheral Neuroectodermal Tumor (PNET) and the Ewing Sarcoma Family of Tumors (ESFT).

Chondrosarcoma are rare sarcoma reputed chemorefractory in the non-operable setting and for which little is known in terms of palliative management with systemic treatments.

Despite adequate loco-regional treatment, up to 40% of patients with sarcoma, soft tissue or bone, will develop metastatic disease. When metastases are detected, the standard of care is based on palliative chemotherapy with a median survival in this setting of only 18 months.

A slight improvement has been obtained over years thank to registration of a couple of drugs such as Trabectedin and Pazopanib, the first antiangiogenic registered for soft tissue sarcoma patients. Pazopanib is routinely prescribed worldwide after failure of first line chemotherapy in soft tissue sarcoma. However, bone tumors have not benefited from these small advances yet and treatment still rely on chemotherapy combining doxorubicine cisplatinum and ifosfamide. There is no standard in relapse and palliative settings, and after failure of these agents the survival is very poor. Bone sarcomas are therefore tumors with very little available data and low level of evidence on palliative systemic treatments in clinical trials and in the real life setting.

The primary objective of the METABONE study is to conduct a retrospective descriptive analysis of clinic-biological profiles, patterns of care and modalities of treatment for a set of patients with malignant bone tumors in a real-life national setting.

Patterns of Care and Outcomes in Patients With Metastatic Bone Tumors (METABONE)

Patterns of Care and Outcomes of Patients With METAstatic BONE Tumors in a Real-life Setting

Interval between the diagnosis of metastatic disease or the first-line systemic therapy onset and the time of death.

time from the systemic treatment onset to the next treatment or death due to any cause, whichever comes first

French Sarcoma Group

Institut Bergonié

Micronutrients

Vitamins

Ascorbic Acid

Trace Elements

Antimetabolites

Antioxidants

Protective Agents

Vitamin C

Subjects will receive ascorbate, 75g, on Days 1, 2, 8, 9, 15 and 16 of a 28-day cycle. Gemcitabine will be administered on Days 1, 8 and 15, after the infusion of ascorbate. Concomitant treatment will continue for 6 cycles. Patients whose disease has not progressed while receiving gemcitabine and ascorbate and who are tolerating therapy may continue either single agent gemcitabine or concomitant treatment beyond 6 cycles at the discretion of the investigator.

Following 15g test dose, 75g administered on Days 1, 2, 8, 9, 15 and 16 of a 28-day cycle

Administered on Days 1, 8 and 15, after the infusion of ascorbate

Varun Monga, MD

This study will enroll male and female patients 18 years old or older who have a diagnosis of locally advanced, unresectable or metastatic soft tissue or bone sarcoma (except GIST and Kaposi's) from any site. A minimum of 1 prior chemotherapy regimen, including adjuvant and neo-adjuvant therapy for the treatment of sarcoma, must have been given. Patients eligible for an anthracycline should have received a prior anthracycline containing regimen. Patients who decline or are not eligible for anthracycline treatment may be considered for this protocol as a first line treatment. Patients with a diagnosis of liposarcoma should also have received eribulin.

During screening, subjects will receive a test dose (15g) of ascorbate. If the test dose results in any toxicity \>/= CTCAE grade 3 or a significant medical event in the opinion of the principal investigator, the patient will be considered a screen failure.

Subjects who pass screening will then receive ascorbate, 75g, on Days 1, 2, 8, 9, 15 and 16 of a 28-day cycle. Gemcitabine will be administered on Days 1, 8 and 15, after the infusion of ascorbate. Concomitant treatment will continue for at least 6 cycles. Patients whose disease has not progressed while receiving gemcitabine and ascorbate and who are tolerating therapy may continue either single agent gemcitabine or concomitant treatment beyond 6 cycles at the discretion of the investigator. Treatment will be terminated with progression of disease. Disease will be assessed by CT of the chest, abdomen and pelvis or MRI of the lesion every 2 cycles for progression.

Gemcitabine Plus Ascorbate for Sarcoma in Adults

A Phase II Trial of Gemcitabine Plus High-Dose Ascorbate in Locally Advanced Unresectable or Metastatic Soft Tissue and Bone Sarcomas in Adults

From first day of treatment to documented disease progression as described by RECIST 1.1 criteria. Results are provided in nominal categories (CR, PR, SD, PD) as per RECIST.

Time from start of therapy (day 1, cycle 1) to documented disease progression or death due to any cause. Progression will be defined using the RECIST 1.1 guidelines. Results are provided in nominal categories (CR, PR, SD, PD) as per RECIST.

Categorize and quantify adverse events from start of therapy (day 1, cycle 1) to end of study per (CTCAE) version 4.03.

University of Iowa Adolescent and Young Adult (AYA) Cancer Program

St. Baldrick's Foundation

Assistant Clinical Professor

Information about all adverse events, whether volunteered by the subject, discovered by investigator questioning, or detected through physical examination, laboratory test or other means, were collected and recorded and followed as appropriate. Adverse events were followed for 30 days post last dose of drug.

Subjects will receive ascorbate, 75g, on Days 1, 2, 8, 9, 15 and 16 of a 28-day cycle. Gemcitabine will be administered on Days 1, 8 and 15, after the infusion of ascorbate. Concomitant treatment will continue for 6 cycles. Patients whose disease has not progressed while receiving gemcitabine and ascorbate and who are tolerating therapy may continue either single agent gemcitabine or concomitant treatment beyond 6 cycles at the discretion of the investigator.

Ascorbate: Following 15g test dose, 75g administered on Days 1, 2, 8, 9, 15 and 16 of a 28-day cycle

Gemcitabine: Administered on Days 1, 8 and 15, after the infusion of ascorbate

Gemcitabine + High-Dose Ascorbate

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Study terminated early. Ten patients were enrolled in the first stage, and per protocol the study was terminated following interim analysis when 1 or fewer participants had a tumor response.

Tumor Response

2 months

3 months

6 months

9 months

Progression Free Survival

Alive

Dead

Overall Survival

Blood and lymphatic system disorders

Gastrointestinal disorders

Infections and infestations

Investigations

Metabolism and nutrition disorders

Musculoskeletal and connective tissue disorders

Psychiatric disorders

Renal and urinary disorders

Respiratory, thoracic and mediastinal disorders

Skin and subcutaneous tissue disorders

Vascular disorders

General disorders and administration site conditions

Incidence of Adverse Events (AE) Per CTCAE 4.03

Overall Study

Patients who underwent bone scintigraphy scanning between 2010 and 2018 at RTWH Aachen university hospital, and had a bone scan report that indicates the presence or absence of metastatic bone disease.

Patients who underwent bone scintigraphy scanning between 2010 and 2018 at Namur university hospital, and had a bone scan report that indicates the presence or absence of metastatic bone disease.

Patients who underwent bone scintigraphy scanning between 2010 and 2018 at Aalborg university hospital, and had a bone scan report that indicates the presence or absence of metastatic bone disease.

The aim is to investigate whether deep learning algorithms can detect bone metastasis with high accuracy and specificity.

Deep learning based detection of metastatic bone disease on bone scintigraphy scans.

Bone scintigraphy scans are two dimensional medical images that are used heavily in nuclear medicine. The scans detect changes in bone metabolism with high sensitivity, yet it lacks the specificity to underlying causes. Therefore, further imaging would be required to confirm the underlying cause. The aim of this study is to investigate whether deep learning can improve clinical decision based on bone scintigraphy scans.

Automated Detection of Metastatic Bone Disease on Bone Scintigraphy Scans

In Silico Clinical Trial Comparing the Reading Accuracy of Doctors and a Deep Learning Algorithm for Detection of Metastatic Bone Disease on Bone Scintigraphy Scans.

Reporting the performance measures (Area under the curve, accuracy, specificity..etc)

Correctness of the diagnosis of Dr versus AI (dichotomous variable: correct versus not correct) on a subset of the validation data, using a McNemar statistical test

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Length of the Femoral Stem in Arthroplasty Done for Patients With Proximal Femoral Metastatic Lesion	NCT04660591	Metastatic Bone... Pathological Fr... Arthroplasty	femoral stem in...	18 Years -	Ain Shams University
CTFEA Myeloma Study	NCT04364724	Myeloma Multipl... Metastatic Bone...	CT-based finite...	18 Years - 95 Years	Tel-Aviv Sourasky Medical Center
ERAS Anesthetic Care for Metastatic Spine Cancer Resection	NCT05427825	Metastatic Bone...	ERAS anesthetic... Standard anesth...	20 Years -	National Taiwan University Hospital
Palliative UNConventional Hypofractionation Trial for Metastatic Bone Disease	NCT05115331	Metastatic Bone...	Experimental Ra... Conventional Ra...	18 Years -	University of Cincinnati
CTFEA Myeloma Study	NCT04364724	Myeloma Multipl... Metastatic Bone...	CT-based finite...	18 Years - 95 Years	Tel-Aviv Sourasky Medical Center
Gemcitabine Plus Ascorbate for Sarcoma in Adults (Pilot)	NCT04634227	Sarcoma Soft Tissue Sar... Unresectable So... Metastatic Bone... Bone Sarcoma	Ascorbate	18 Years -	University of Iowa
Patterns of Care and Outcomes in Patients With Metastatic Bone Tumors (METABONE)	NCT03963531	Metastatic Bone...	chemotherapy, s...	-	Institut Bergonié
Gemcitabine Plus Ascorbate for Sarcoma in Adults	NCT03468075	Sarcoma Soft Tissue Sar... Unresectable So... Metastatic Bone... Bone Sarcoma	Ascorbate Gemcitabine	18 Years -	University of Iowa
Gemcitabine Plus Ascorbate for Sarcoma in Adults	NCT03468075	Sarcoma Soft Tissue Sar... Unresectable So... Metastatic Bone... Bone Sarcoma	Ascorbate Gemcitabine	18 Years -	University of Iowa
ERAS Anesthetic Care for Metastatic Spine Cancer Resection	NCT05427825	Metastatic Bone...	ERAS anesthetic... Standard anesth...	20 Years -	National Taiwan University Hospital
Automated Detection of Metastatic Bone Disease on Bone Scintigraphy Scans	NCT05110430	Metastatic Bone...	Deep learning b...	-	Maastricht University

Spots Global Cancer Trial Database for metastatic bone tumor