No evidence of bone metastases (M0) on bone scan within 120 days prior to registration (sodium fluoride [NaF] positron emission tomography [PET]/CT is an acceptable substitute)\r\n* Equivocal bone scan findings are allowed if plain films (or CT or magnetic resonance imaging [MRI]) are negative for metastasis
Patients with histologic diagnosis (by institutional pathologist) of newly diagnosed Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) arising from bone or soft tissue and with metastatic disease involving lung, bone, bone marrow, or other metastatic site
For the purpose of this study metastatic disease is defined as one or more of the following:\r\n* Lesions which are discontinuous from the primary tumor, are not regional lymph nodes, and do not share a bone or body cavity with the primary tumor; skip lesions in the same bone as the primary tumor do not constitute metastatic disease; skip lesions in an adjacent bone are considered bone metastases; if there is any doubt whether lesions are metastatic, a biopsy of those lesions should be performed\r\n* Contralateral pleural effusion and/or contralateral pleural nodules\r\n* Distant lymph node involvement\r\n* Patients with pulmonary nodules are considered to have metastatic disease if the patient has:\r\n** Solitary nodule >= 0.5 cm or multiple nodules of >= 0.3 cm unless lesion is biopsied and negative for tumor\r\n** Patients with solitary nodule < 0.5 cm or multiple nodules < 0.3 cm are not considered to have lung metastasis unless biopsy documents tumor\r\n* Bone marrow metastatic disease is based on morphologic evidence of Ewing sarcoma based on hematoxylin and eosin (H&E) stains; in the absence of morphologic evidence of marrow involvement on H&E, patients with bone marrow involvement detected ONLY by flow cytometry, reverse-transcriptase (RT)-polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), or immunohistochemistry will NOT be considered to have clinical bone marrow involvement for the purposes of this study\r\n** This study requires bilateral bone marrow biopsies at study entry; the suggested approach for patients with large pelvic tumors in which a posterior iliac crest bone marrow biopsy would track through the tumor is to instead undergo 2 marrow biopsies on the contralateral side (either 2 posterior biopsies or one posterior and one anterior biopsy)\r\n* Bone metastasis: This study utilizes whole body FDG-PET scans to screen patients for bone metastases; areas suspicious for bone metastasis based on FDG-PET scans require confirmatory anatomic imaging with either MRI or computed tomography (CT) (whole body FDG-PET/CT or FDG-PET/magnetic resonance [MR] scan acceptable); whole body technetium bone scans may be performed at the discretion of the investigator and are not required; for patients without other sites of metastatic disease whose sole metastatic site to qualify for study entry is a single area suspicious for bone metastasis identified by FDG-PET, confirmatory biopsy or anatomic imaging evidence of an associated soft tissue mass at that site is required for study entry
Metastases with indistinct borders making targeting not feasible\r\n* NOTE: A potential issue with bone metastases is that they often are not discrete; since many patients on this protocol will have bone metastases, this will be an important issue; theoretically, Houndsfield units might provide an appropriate measure; however, a sclerotic lesion against dense cortical bone will not have a sharp demarcation based on Houndsfield units (HU); therefore, we acknowledge that such determinations will pose a challenge and thus the physician’s judgment will be required
Bone scan as clinically indicated within 90 days prior to registration
Bone Scan Progression: Appearance of one or more new lesions on bone scan attributable to prostate cancer.
Exercise Coordination Centre (ECC) review and approval of subject's screening bone scan/ areas with bone metastases.
Prior therapy for metastatic TNBC (chemotherapy, hormone therapy or biological therapy), Patients may receive bisphosphonates and other therapies to treat bone metastases, however if used, bone lesions will not be considered as measurable disease.
A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)
Bone metastases
Subjects with chronic conditions associated with non-malignant abnormal bone growth (e.g., Paget’s disease of bone)
Bone metastases
Bone metastases as manifested by one or more lesions on a bone scan performed within 2 months of screening
Other bone and soft tissue sarcomas cohort only: Subjects with dedifferentiated chondrosarcomas, dedifferentiated giant cell tumor of bone, giant cell tumor of bone, undifferentiated pleomorphic sarcoma of bone, or high-grade unclassified sarcomas of bone must have received at least one prior line of therapy unless no standard first-line therapy exists in which case enrollment as initial therapy is allowed.
Cohort B1\r\n* Newly diagnosed low-volume metastatic disease with either:\r\n** Bone metastases as documented by radionuclide bone scan amenable to treatment with a maximum of 3 radiation isocenters* (note: a patient will be considered eligible if entering the study with a positive positron emission tomography (PET) scan without restriction to the number of isocenters and otherwise meets eligibility requirements) And/Or\r\n** Retroperitoneal nodes up to the level of the renal hilum with/without pelvic nodal metastasis < 1.5 cm in the short axis OR
Patients must have measurable disease by RECIST v1.1, or evaluable disease with bone metastases demonstrated by Tc99 bone scan; patients with bone metastases only are allowed (NOTE: nodes >= 1.5 cm (not >= 2 cm) in the short axis are considered measurable, per The Prostate Cancer Working Group 3 [PCWG3])
Combo C : Hypocalcemia, clinically significant bone disease or recent bone fracture (within 12 weeks prior study entry)
Bone only patients during expansion/efficacy portion.
No clinical or imaging evidence of distant metastases by PA and Lateral CXR, Radionuclide Bone scan, and LFTs including total bilirubin, ALT, AST, and alkaline phosphatase
Paget’s disease of bone
At least 1 osteolytic bone metastases must be present
Localized pain resulting from no more than two sites total of metastatic disease in the bone and/or benign bone tumors (Benign Bone Tumors are restricted to Europe and Canada only)
Subjects must have at least 1 bone metastasis of any size on imaging
No evidence of metastasis on bone scan within 120 days prior to registration
Subjects with metastatic bone disease, progression defined by 2 or more new lesions in a radionuclide bone scan.
Metastatic disease as defined by two or more bone metastases confirmed by bone scintigraphy or radiographic soft tissue metastasis
Confirmed bone metastases on imaging
Metastatic disease as evidenced by the presence of soft tissue and/or bone metastases on imaging studies (CT of abdomen/pelvis, bone scintigraphy)
The patient should not have direct evidence of regional or distant metastases after appropriate staging studies, including no distant metastases (M0) on bone scan within 90 days of study enrollment; equivocal bone scan findings are allowed if plain films are negative for metastasis; positron emission tomography (PET) or prostate specific membrane antigen (PSMA) scans can be performed instead of a bone scan
Bone-predominant metastatic castration resistant prostate cancer (CRPC): at least two skeletal metastases on bone scan with no lung, liver, and/or brain metastasis (lymph node metastasis is allowed)
No evidence of bone metastases (M0) on bone scan, only for PSA > 20 or Gleason >= 8, (sodium fluoride [NaF] positron emission tomography [PET]/CT is an acceptable substitute) performed no more than 120 days prior to registration; equivocal bone scan findings are allowed if plain films and/or MRI are negative for definite metastases
Bone scan completed within 90 days
No evidence of bone metastases (M0) on bone scan within 90 days prior to registration
Subjects with pathologic long-bone fractures
Paget’s disease of bone
No evidence of bone metastases (M0) on bone scan\r\n* Patients with intermediate risk factors only do not require a bone scan, but these studies may be obtained at the discretion of the treating physician\r\n* Patients with any high risk factors are required to undergo a bone scan; it is recommended that the duration between these scans and study registration be less than 60 days, but if the time period is > 60 days and the opinion of the clinician is that repeat studies would offer limited benefit, then these studies do not need to be repeated\r\n* Equivocal bone scan findings are allowed if additional imaging (e.g. plain film x-rays, or CT) does not confirm metastasis
Metastatic disease documented by CT/MRI or bone scan (not older than 28 days at enrollment) revealing at least one metastatic lymph-node, visceral metastasis and/or bone metastasis
Previously administered chemotherapy or 223Ra-therapy within the context of diffuse bone or bone-marrow involvement (i.e. \superscan\ defined as bone scintigraphy in which there is excessive skeletal radioisotope uptake [>20 bone lesions] in relation to soft tissues along with absent or faint activity in the genitourinary tract due to diffuse bone/ bone marrow metastases)
Patients who are suffering from symptoms of bone metastases
Patient whose targeted (most painful) tumors are on bone and bone-lesion interface is deeper than 1cm from the skin.
Presence of metastatic disease on bone or computed tomography (CT) scan \r\n* Evaluable disease progression by modified RECIST 1.1 (Response Evaluation Criteria in Solid Tumors)\r\n* Bone disease on bone scan
Oligometastatic prostate cancer patients who have not received primary therapy are eligible; (oligometastatic disease is defined as a patient with ? 3 metastatic bone lesions on the bone scan or tissue metastasis)
Subjects must have a negative bone scan
The subject must have clear evidence of metastases to bone on isotope bone scan at screening, with or without soft tissue metastases; in subjects with bone-only disease, at least two bone lesions must be evident on baseline imaging that are not within a previously irradiated field
Metastatic disease by bone scan
Soft tissue components of bone metastases >= 1.0 cm in longest axis\r\n* Soft tissue components of bone metastases < 1.0 cm that have been stable for > 6 months (must not have enlarged > 5 mm) are permitted
Multiple bone metastases within 12 weeks prior to study drug
Bone disease progression defined by ?2 new lesions on bone scan at Screening, or ?28 days of C1D1
Bone scan or positron emission tomography (PET) scan; required only if alkaline phosphatase (ALP) is ?2 x upper limit of normal (ULN) and/or there are symptoms of metastatic bone disease. A confirmatory imaging study is required if the results from the bone scan are questionable
Alkaline phosphatase =< 2.5 x IULN for patients without bone metastases and =< 5.0 x IULN for patients with bone metastases
Bone-limited and exclusively metastases.
Patients with either measurable disease as defined by RECIST criteria or bone only disease are eligible; Note: those patients with both non-measurable disease and bone metastases are eligible\r\n* Non-measurable bone only disease: Non-measurable bone only disease may include any of the following: blastic bone lesions, lytic bone lesions without a measurable soft-tissue component, or mixed lytic-blastic bone lesions without a measurable soft-tissue component\r\n* Lytic bone lesions, with an identifiable soft tissue component, evaluated by computed tomography (CT) or magnetic resonance imaging (MRI), can be considered as measurable lesions if the soft tissue component otherwise meets the definition of measurability previously described
Subjects with bone dominant disease with at least 2 skeletal metastases identified at baseline by bone scintigraphy and confirmed by CT/magnetic resonance imaging (MRI). Presence of metastases in soft tissue (skin, subcutaneous, muscle, fat, lymph nodes)and/or visceral metastases is allowed.
Metastatic disease documented by greater than or equal to (>=) 1 bone lesions on 99mTc bone scan. Participants with a single bone lesion must have confirmation of bone metastasis by computed tomography (CT) or magnetic resonance imaging (MRI)
Progression of bone disease (evaluable disease) or (new bone lesion(s)) by bone scan.
No evidence of bone metastases (M0) on bone scan (Na F positron emission tomography (PET)/CT is an acceptable substitute) within 120 days prior to step 1 registration\r\n* Equivocal bone scan findings are allowed if plain films and/or MRI are negative for metastasis
Bone-directed radiotherapy to pelvic region for ease of pain from painful bone metastases is allowed up to 14 days before
Progression of bone disease (evaluable disease) (new bone lesion(s)) by bone scan.
Evidence of metastatic disease in bone on bone scan, CT scan, and/or by MRI at any time following the initial diagnosis of prostate cancer
No evidence of bone metastases (M0) on bone scan within the past 60 days prior to registration        \r\n* Bone scan not required for patients enrolled with a single intermediate-risk factor only but this scan may be obtained at the discretion of the treating physician; patients with 2 or 3 risk factors will require a negative bone scan for eligibility\r\n* Equivocal bone scan findings are allowed if plain film x-rays are negative for metastasis
Patients with Paget's disease of the bone
No distant metastases (M0) on bone scan or NaF PET/CT within 14 weeks prior to registration; equivocal bone scan findings are allowed if the physician determines that distant metastases are unlikely based on clinical judgment
Presence of at least one metastatic bone lesion(s); patients with non-measurable bone-only disease are allowed
Presence of bone metastatic disease as assessed by at least two lesions on whole body metastable technetium-methylene diphosphonate (99mTc-MDP) bone scintigraphy;
Bone metastases
Stage IV breast cancer with metastases to the bone and/or bone marrow
Pathological or radiographically confirmation of metastases to the bone and/or bone marrow; (the definition of radiologic diagnosis of bone metastasis is based on typical and highly reliable imaging findings in studies such as bone scan [new or multiple TC99m positive lesions], PET/computed tomography [CT] [new or multiple FRG positive lesions], and magnetic resonance imaging [MRI] [typical T1w replacement, T2w positive and T1 plus contrast media positive] for bone metastasis with 2 or more lesions; if the bone metastasis is highly suspected or not well defined by imaging, bone biopsy is necessary for confirmation)
Bone-only disease and/or disease that cannot be biopsied.
Symptomatic bone metastases
Current, untreated pathologic long-bone fractures or imminent pathologic long-bone fracture (cortical erosion on radiography > 50%)
Two or more bone metastases on bone scan within 4 weeks prior to randomization with no lung, liver, other visceral and/or brain metastasis.
Multiple skeletal metastases (?2 hot spots) on bone scan
Chronic conditions associated with non-malignant abnormal bone growth (e.g., confirmed Paget's disease of bone)
Two or more skeletal metastases (? 2 hot spots) on bone scintigraphy within 8 weeks of randomization
Chronic conditions associated with non-malignant abnormal bone growth (e.g. confirmed Paget's disease of bone)
COHORT A: The subject must have a history or presence of =< 10 bony metastatic lesions \r\n* Note: bone metastases (mets) that are not clearly identified on bone imaging, but are biopsy proven are allowed
Patients currently receiving bone loss prevention treatment with bone-sparing agents must be on stable doses for at least 4 weeks prior to randomization
Patients with progressive, locally recurrent, or metastatic osteosarcoma (i.e. high-risk only) with no standard curative options available with at least one indicator lesion avid on 99mTc-MDP scan or a Sodium Fluoride (Na F) Bone PET scan will be eligible. In addition, subjects with extremely rare bone forming osteosarcoma-like tumors that behave like osteosarcoma phenotypically and are clinically treated like osteosarcoma (eg. Malignant Fibrous Histiocytoma of Bone or malignant transformation of giant cell tumor of bone) may be included if they satisfy all of the inclusion criteria.
Indicator lesion that has uptake of 99mTc-MDP on bone scan or a Sodium Fluoride ( Na F) Bone PET scan and can be subjected to quantitative assessment by this scans and possibly other means.
99mTc-MDP bone scan with no significant uptake (i.e. \nothing\ for a bone-seeking isotope to target/ i.e. indicator lesion that would be expected to have the bone-seeking targeted uptake of 223-radium dichloride).
Patients with bone metastases only
Known brain metastasis or evidence of metastatic disease by computed tomography (CT) scan, physical exam, or bone scan within 4 weeks of registration\r\n* Patients with equivocal uptake on a bone scan that in the clinician's opinion do not definitively constitute metastatic disease are eligible
Patients with \anaplastic\ features are eligible for this trial as defined by at least one of the following: a) any of the following metastatic presentations: exclusive visceral metastases, radiographically predominant lytic bone metastases identified by plain X-ray or CT scan, bulky (> 5 cm in longest dimension) lymphadenopathy or high-grade (Gleason > 8) tumor mass in the prostate/pelvis; b) low PSA (=< 10 ng/ml) at initial presentation (prior to androgen ablation or at symptomatic progression in the castrate-setting) plus high volume (>= 20) bone metastases; c) elevated serum lactate dehydrogenase (LDH) (>= 2 x ULN) or elevated serum carcinoembryonic antigen (CEA) (>= 2 x ULN) in the absence of other etiologies; d) short interval (=< 180 days) to castrate-resistant progression following initiation of hormonal therapy
1 to 3 bone metastatic sites (metastatic lesions in the same bone that are within 3 cm of each other are considered as one site)
Negative bone scan within 6 months prior to enrollment to rule out possibility of metastases;
Histologically proven adenocarcinoma of the prostate with evidence for skeletal metastases on bone scan and/or CT scan.
The subject must be willing to undergo sequential biopsy of bone or bone metastases
Patients with bone metastases only
Patients with either skeletal pain or alkaline phosphatase that is > ULN must have a bone scan showing they do not have metastatic disease; suspicious findings on bone scan must be confirmed as benign by x-ray, magnetic resonance imaging (MRI), or biopsy
Bone metastases and one of the following:
Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
Metastatic prostate cancer to the bone as documented by positive bone scan imaging
Bone metastases and one of the following:
Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
Presence of 1 or more bone metastasis
Bone metastases and one of the following:
Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
Bone metastases and one of the following:
Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
Bisphosphonates or Zometa for bone metastases
Patients who have a solitary bone metastasis that has been irradiated are not eligible.
2 or more bone metastases demonstrated on bone scintigraphy
Patients who are suffering from symptoms of bone metastases or multiple myeloma bone lesions:
Children with any cancer diagnosis except for bone tumors or have bone metastasis
Receiving bone modifying agents for bone pain associated with metastatic disease or other chronic conditions
Have lesion or metastasis of bone
Solid organ malignancy with documented bone metastasis by imaging
Malignancy with bone instability
History of bone fractures
Measurable disease per RECIST 1.1 or bone-only disease with lytic component. Patients with bone-only metastatic cancer must have a lytic or mixed lytic-blastic lesion that can be accurately assessed by computerized tomography (CT) or magnetic resonance imaging (MRI). Patients with bone-only disease without a lytic component (ie, blastic-only metastasis) are not eligible.
Bone scan without evidence of skeletal metastases
Skeletal x-ray film or MRI confirmation of absent skeletal metastases if bone scan findings are equivocal
Biopsy proven or clinically obvious documented bone metastases from breast cancer (with the majority of the disease burden in the bone)
Patient has known bone metastases
No evidence of metastatic disease on conventional imaging, including a negative bone scan for skeletal metastasis and negative contrast-enhanced CT
Bone scan findings characteristic for metastatic prostate carcinoma
Untreated/unstabilized pathologic long bone fractures
?2 new metastases on transaxial imaging or radionuclide bone scan
Patients must have measurable disease by RECIST v.1.1 or bone disease as their only site of disease (with bone lesions confirmed by CT, MRI or bone X-ray).
No evidence of bone metastases (M0) on bone scan within 120 days prior to registration (PET/CT is an acceptable substitute). Equivocal bone scan findings are allowed if bone CT or MRI of hot spots are negative for metastasis