Cohort  (colorectal cohort) \r\n* Ability to undergo a fresh tumor biopsy for the purpose of screening for this clinical trial (including able and willing to give valid written consent) to ability or to provide an available archival tumor sample taken less than  months prior to study enrollment if a fresh tumor biopsy is not feasible with an acceptable clinical risk; tumor lesions used for fresh biopsies should be the same lesions to be irradiated when possible and should not be the same lesions used as RECIST target lesions, unless there are no other lesions accessible \r\n* Microsatellite stable (MSS) tumor as documented by either: \r\n** Immunohistochemistry (IHC) testing that does not suggest loss of MLH-, MSH-, PMS or MSH \r\n** Polymerase chain reaction (PCR) testing that does not suggest microsatellite instability (MSI)
No lytic lesions on skeletal survey and whole body PET/CT other than a single lesion associated with solitary bone plasmacytoma within  days prior to registration
Patients with ?  visceral metastases (excluding pulmonary lesions), with no lesions >. cm. Patients with substantial tumor burden of non-measurable disease may not be good candidates for an immunotherapy and should be discussed with the Medical Monitor.
Injected lesions (up to two) must be between  mm and  mm in diameter for IT injection; lesions must be accessible for baseline and on-treatment biopsies.
Indication A only: at least  measurable lesions as defined per modified RECIST . within  days prior to the first dose of AMG 
Participants with brainstem lesions
Ulcerated skin lesions
Participants must have progressive CNS lesions, as defined by one of the following:\r\n* Patients may have multiple progressive CNS lesions, some of which have been treated by stereotactic radiosurgery (SRS) or surgery; patients are eligible if they have one or more untreated (by surgery or SRS) progressive lesions that is measurable\r\n* Patients have measurable residual or progressive lesions after surgery\r\n* Patients who have had prior whole-brain radiotherapy (WBRT) and/or SRS are eligible but there needs to be unequivocal evidence of progression of at least one lesion treated by radiation (e.g. tissue diagnosis); biopsy can be considered for definitive diagnosis\r\n* Patients who have previously been treated with systemic therapy for CNS metastases are eligible
COHORT B: Progressive brain metastases after prior local CNS-directed therapy such as radiation or surgery as defined by:\r\n* Untreated measurable lesions in patients that have received surgery and/or SRS to one or more other lesions\r\n* Residual or progressive lesions after surgery if asymptomatic\r\n* Patients who have had prior whole-brain radiotherapy (WBRT) and/or SRS and then whose lesions have progressed are eligible; lesions treated with SRS may be eligible if there is unequivocal evidence of progression
Patients with untreated brainstem metastases are eligible if lesions are small and asymptomatic
Measurable Disease Progression: >% increase in the sum of diameters of measurable lesions from the time of maximal regression or appearance of one or more new lesions.
Pulmonary metastases found at relapse (does not have to be first relapse); no more than  lesions per hemi-thorax will be treated but other lesions in the lung may be present
New or progressive CNS lesions, as assessed by the patients treating physician\r\n* It is anticipated that some patients may have multiple progressive CNS lesions, one or several of which are treated with stereotactic radiosurgery (SRS) or surgery with residual untreated lesions remaining; such patients are eligible for enrollment on this study providing that at least one lesion is measurable (>=  mm) per RECIST .; the location of the measurable lesion should be documented in the patient chart and case report form\r\n* Patients who have had prior cranial surgery are eligible provided that there is evidence of measurable residual or progressive lesions, and at least  months have passed since surgery; if a patient has surgical resection followed by whole brain radiation therapy (WBRT), then there must be evidence of progressive CNS disease after the completion of WBRT\r\n* Patients who had had prior WBRT and/or SRS and then whose lesions have progressed thereafter are also eligible; in this case, lesions that have been treated with SRS may be considered as target lesions if there is unequivocal evidence, in the opinion of the treating physician, of progression\r\n* Patient who have not previously been treated with cranial radiation (e.g. WBRT or SRS) are eligible to enter the study, but such patients must be asymptomatic or minimally symptomatic from their CNS metastases and not requiring corticosteroids
Patients whose disease has progressed following at least  cycles of neoadjuvant chemotherapy as defined by at least one of the following:\r\n* Doubling of serum CA- level\r\n* At least a % increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions\r\n* Clinical deterioration (worsening ascites, carcinomatous ileus, malignant bowel obstruction, severe hypoalbuminemia, declining performance status)
Patients are stage IV (M) or recurrent with any combination of T and N with oligometastatic disease as defined by  or fewer total sites of metastatic disease \r\n* NOTE: number of metastatic sites based on most recent imaging studies in order to determine number of oligometastatic sites; for example, if patient initially had  sites of metastatic disease, was treated with chemotherapy resulting in complete response of  lesions and stable disease of  lesions, and no new lesions based on repeat imaging, the patient would be eligible for treatment on protocol
Patients are stage IV (M) with any combination of T and N with oligometastatic disease as defined by  or fewer total sites of metastatic disease involving  or fewer organ systems\r\n* Examples of patients eligible for trial\r\n** TNM non-small cell lung cancer (NSCLC) with  central nervous system (CNS) metastatic lesion,  liver lesions, and  adrenal lesion.\r\n** TNM colorectal cancer with  liver lesion,  bone lesions \r\n** TNM gastric cancer with  supraclavicular lymph node,  liver lesions, and  CNS lesions
Patients with other fibroblastic lesions or other fibromatoses are NOT eligible.
Participants must not have more than  new or progressive lesions in the brain requiring SRS treatment (greater than  total brain lesions are allowed as long as no more than  lesions require SRS treatment)
Presence of metastatic disease that would be amenable to the required biopsies; ideally pre and post biopsies should be from the same lesion and otherwise from lesions in the same organ; if not possible, then biopsy of the lesions in different organs will be permitted
Unequivocal evidence of new and/or progressive brain metastases, and at least one of the following scenarios:\r\n* Treated with stereotactic radiosurgery (SRS) or surgery with residual un-treated lesions remaining; such participants are eligible for immediate enrollment on this study providing that at least one untreated lesion is measurable\r\n* Participants who have had prior whole- brain radiation therapy and/or SRS and then whose lesions have subsequently progressed are also eligible; in this case, lesions which have been treated with SRS may be considered as target lesions if there is unequivocal evidence, in the opinion of the treating physician, of progression following SRS \r\n* Participants who have not previously been treated with cranial radiation (e.g., WBRT or SRS) are eligible to enter the study, but such participants must be asymptomatic from their CNS metastases and not requiring corticosteroids for symptom control\r\n* Both participants who present with systemic stable/absent or progressive disease are eligible to this trial, as long as they fulfill one of the above criteria
?  lesions in the liver
Active oral or genital herpes lesions
Participant must be a candidate for palliative radiation treatment to at least one bone, lymph node, or soft tissue lesion; radiation of visceral lesions (such as lung or hepatic lesions) is not permitted
Participants with bone lesions requiring surgical fixation to provide mechanical stability are ineligible; participants with previously fixed lesions are allowed
MK- (cut/subcut lesions) and MK-+pembro (cut/subcut lesions) Arms:
Measurable disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable; any tumor mass > . cm is acceptable; lesions that are considered non-measurable include the following:\r\n* Bone lesions (lesions if present should be noted)\r\n* Ascites\r\n* Pleural/pericardial effusion\r\n* Lymphangitis cutis/pulmonis\r\n* Bone marrow (involvement by lymphoma should be noted)
The presence of  or more MR Visible lesions positive on biopsy.
Subjects with CNS lesions are excluded
Radiotherapy: at least  weeks since most recent radiotherapy; prior radiated lesions will not be evaluable unless there is documented progression post therapy; palliative radiotherapy to localized painful lesions is acceptable when the patient is on study: at least one week after completion of radiation therapy (RT) and recovery from associated toxicities before restarting ARQ ; irradiated lesions will not be evaluable for response
The PN must be inoperable, defined as a PN that cannot be surgically completely removed without risk for substantial morbidity due to: encasement of or close proximity to vital structures, invasiveness, or high vascularity of the PN; the PN either causes morbidity or it is growing and has the potential to cause morbidity such as (but not limited to): head and neck lesions that could compromise the airway or great vessels, paraspinal lesions that can cause myelopathy, brachial or lumbar plexus lesions that could cause nerve compression and loss of function, lesions that could result in major deformity (e.g., orbital lesions) or are significantly disfiguring, and lesions of the extremity that cause limb hypertrophy or loss of function or pain; PN growth will be defined as a >= % increase in PN volume within approximately  years prior to enrollment on this trial
Presence of brainstem lesions or lesions that are less than  mm from the hypophysis or cranial nerves
Patients with multifocal tumors must have resectable lesions
Structurally unstable bone lesions suggesting impending fracture
Must be candidates for radiation treatment to bone lesions
Two or more bone lesions
Have a target lesion/s deemed suitable by the treating physicians for stereotactic body radiation therapy (SBRT) with the intent of palliation or prevention of symptoms; this lesion must be: a) - non overlapping sites in the H&N region OR  b) metastatic lesions outside the head and neck (H&N) region in the lung or bone (a minimum of  and a maximum  lesions will be irradiated), provided there is no significant overlap between the lesions; patients should have RECIST . criteria measurable disease in addition to the lesion/s treated with SBRT; if the site/s of SBRT were previously radiated to > Gy, there should be >  month time interval between the last dose of radiation and the start of SBRT
Patients with active central nervous system (CNS) lesions are excluded (i.e., those with radiographically unstable, symptomatic lesions); however, patients treated with stereotactic therapy or surgery are eligible if they remain without evidence of disease progression in the brain for >=  weeks
Patients will be excluded from randomization if they meet any of the following criteria:\r\n* Any of the exclusion criteria; \r\n* Complete response to osimertinib or prior treatment to all visible lesions, such that no lesion is amenable to LCT. Note that patients can receive palliative radiation therapy prior to randomization to CNS lesions or those requiring urgent treatment (e.g. for pain or bleeding), but are only eligible for the study if they have one site amenable to further radiation therapy. In addition, these lesions will be counted towards the total number of metastases, and will also be counted as target lesions
Lesions of any surface span as long as =<  cm in maximal height measured from the skin surface for which local control is desired are eligible; a single patient may have multiple eligible lesions that are individually enrolled for the study.
Subjects must have a minimum of three () evaluable, discrete lesions.
Anal HSIL lesions are visible at randomization and no lesions are suspicious for invasive cancer
Patients requiring palliative radiotherapy to lesions that are defined as target lesions by RECIST criteria at the time of study entry.
Up to  metastatic lesions: \r\n* Must have at least  bone lesion AND each non-visceral lesion should be less than  cm\r\n* Visceral lesions will be limited to one lung lesion (<  cm); no liver lesions allowed
Structurally unstable bone lesions suggesting impending fracture
Presence of a candidate treatment lesion (subcutaneous or nodal lesions are preferable but visceral lesions will be considered) accessible and safe for radiotherapy and serial intralesional injections
Patients must have evaluable disease by clinical exam (i.e. palpable lymphadenopathy, measurable skin lesions, etc.), laboratory assessment (i.e. lymphoma involvement of bone marrow or peripheral blood by morphology, cytology or flow cytometry), and/or imaging (measurable lymph nodes or masses on computed tomography [CT] or magnetic resonance imaging [MRI] and/or evaluable fludeoxyglucose [FDG]-avid lesions on positron emission tomography [PET])\r\n* NOTE: lesions that have been irradiated cannot be included in the tumor assessment unless unequivocal tumor progression has been documented in these lesions after radiation therapy
For Arms A-F, subjects must have biopsiable disease. For Arms A, B, and C, subjects must have at least two lesions amenable to biopsy and response evaluation. For Arms D, E, and F, subjects must have at least three lesions amenable to biopsy, response evaluation, and radiation. Tumor lesions used for biopsy should not be lesions used as RECIST target lesions.
Pathological or clinical (i.e., by imaging) diagnosis of brain metastatic tumor lesions
Presence of unreachable (e.g. located in a region that cannot be reached by needle) or untreatable tumor lesions so that the benefit from the treatment of the treatable lesions does not justify patient's inclusion
Oligometastatic prostate cancer: stage T-, N- and/or Ma-b (up to  metastatic lesions-including bone lesions and non-regional lymph nodes)
Patients must have measurable or non-measurable disease\r\n* Measurable disease\r\n** For visceral or extra-nodal lesions to be considered measurable, they must be >=  mm in one dimension, using spiral computed tomography (CT)\r\n** For lymph nodes to be considered measureable (i.e., target or evaluable lesions), they must be >=  mm in at least one dimension, using spiral CT\r\n* Non-measurable disease\r\n** All other lesions, including small lesions (longest diameter <  mm with conventional techniques or <  mm with spiral CT scan) and truly non-measurable lesions.\r\n*** Lesions that are considered non-measurable include bone lesions (only)
Soft tissue disease progression is defined as at least a % increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study); in addition to the relative increase of %, the sum must also demonstrate an absolute increase of at least  mm; (Note: the appearance of one or more new non-osseous lesions is also considered progression); clinical lesions will only be considered measurable when they are superficial (e.g., skin nodules, palpable lymph nodes) and at least  mm in diameter as assessed using calipers (e.g., skin nodules)\r\n* Per Prostate Cancer Working Group  (PCWG): Visceral (lung, liver adrenal) or extranodal lesions need to be >=  mm in one dimension, using spiral CT; however, lymph nodes need to be >=  mm in at least one dimension to be considered new
No structurally unstable bone lesions suggesting impending fracture
Subjects must have plexiform neurofibroma(s) that are progressive OR are causing significant morbidity, such as (but not limited to) head and neck lesions that are compromising the airway or great vessels, brachial or lumbar plexus lesions that are causing nerve compression and loss of function, lesions causing major deformity (e.g., orbital lesions) or are significantly disfiguring, lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions; patients with paraspinal plexiform neurofibromas will be eligible for this trial; histologic confirmation of tumor is not necessary in the presence of consistent clinical and radiographic findings, but should be considered if malignant degeneration of a plexiform neurofibroma is clinically suspected
Patients must consent to undergo biopsies of externally visible CSCC lesions (Group  only)
Surgical or radiological treatment of lesions contraindicated
No more than  lesions in the liver
Patient must have at least one measurable untreated lesion as per modified RECIST criteria; measurable disease may include extrahepatic lesions; abdominal imaging should employ a liver protocol image capture technique; the following are not considered measurable lesions: bone lesions, ascites, and pleural effusions; prior radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), or transarterial chemoembolization (TACE) of non-target lesions is allowed
Subjects with PE lesions only in the sub-segmental or smaller arteries;
Target lesions that have previously received radiation must have shown radiographic progression following radiation or must have other non-radiated lesions present
=<  liver lesions
Willingness to provide consent for biopsy samples; tumor biopsies will be required for all subjects, tumor lesions used for biopsy should not be lesions used as RECIST target lesions, unless there are no other lesions suitable for biopsy; if a RECIST target lesion is used for biopsy the lesion must be >=  cm in longest diameter
Five or more metastatic brain lesions
 or fewer brain metastases; Note: if lesions are symptomatic or greater than or equal to  cm each, these lesions must have been treated and stable for  months for the patient to be eligible
Have biopsiable disease; subjects must have at least one lesion amenable to biopsy; tumor lesions used for biopsy should not be lesions used as RECIST target lesions; in cohort : paraganglioma-pheochromocytoma or cohort , where there is prominent bony disease, biopsies may not be possible due to the nature of the disease
Oligometastatic prostate cancer: stage T-, N- and/or Ma-b (up to  metastatic lesions-including bone lesions and non-regional lymph nodes)
Lesions located outside of the spinal segments of T to T
Patients receiving any other investigational agents for any reason or non-investigational agents administered for the purpose of controlling cancer growth (use of conventional external beam radiation therapy will be allowed during protocol therapy solely for palliation of localized painful lesions or bone lesions at risk of fracture provided the radiation field does not encompass any selected target lesions required for assessment)
Patients may have either metastatic lesions from another primary site or primary hepatocellular carcinoma; patients with one histologically confirmed metastatic lesion of the liver who are presenting for local therapy for lesions concerning for metastases that cannot or should not be biopsied will also be considered for enrollment on a case by case basis; patients can simultaneously receive treatment for multiple hepatic lesions meeting the prior two requirements, at the discretion of the treating radiation oncologist
Disease that is measurable; this is defined as lesions measuring at least  mm on radiologic imaging; for lymph node disease, the lesion must measure at least  mm or have been biopsied and shown to contain melanoma; skin or mucosal lesions that are not measurable on radiologic imaging but measure at least  mm on clinical exam are also acceptable
Patients must have pathologic diagnosis of adenocarcinoma or large cell carcinoma of the lung with confirmation by immunohistochemistry (e.g., transcription termination factor  [TTF-] positivity) (histologic tissue diagnosis is recommended, but cytology is acceptable); stage IIIA/IIIB or oligometastatic stage IV in which the patient is still considered an appropriate candidate for aggressive chemoradiotherapy for the primary tumor; oligometastatic disease is defined as =<  metastatic sites (=<  lesions per organ); for intracranial metastasis, the patient should have asymptomatic disease that is stable on steroids or  to  symptomatic metastatic lesions treated with stereotactic radiosurgery (SRS)
Tumor lesions in the CNS are permitted but lesions must have been stable for at least  months prior to Cycle  Day  (CD). Stable CNS lesions are defined as not requiring steroid prophylaxis or other medications to prevent seizures or other complications associated with CNS lesions and no evidence of worsening of CNS disease.
All metastatic lesions must be separated by a minimum of  cm as measured from the peripheral edges of the lesions which are in closest proximity to one another; if multiple lesions are present and are not all >=  cm away from each other, the patient will be deemed ineligible
Recurrent lesions with dimension and contour that are determined by the treating neurosurgeon to be appropriate for MLA
Patients with intradural or intramedullary lesions, or lesions with <  mm distance from tumor to spinal cord
Patients with a history of complete surgical resection of CNS lesions are eligible if there is no evidence of CNS lesions (MRI or CT required) at study entry evaluation and if other entry criteria are met
Patients with CNS parenchymal or meningeal-based lesions that are present at study entry evaluation are NOT eligible
Patients presenting with lesions that may harbor an occult infectious source
Patients with ulcerated depressed lesions (as defined by Paris Classification type III)
Lesions not amenable to GTR
Patients will be excluded if they have <  lesions, or >  lesions at enrollment or >  lesions at the time of treatment (note: patients who qualify for enrollment based on having - lesions, but who are discovered to have up to  lesions on the volumetric MRI used for treatment planning will be allowed to continue on study)
Dermatology evaluation with excision of any suspicious lesions prior to initiation of therapy
. Stage II-IV disease; T -, N any, M. Measurable disease is required with the following criteria: Measurable lesions can be accurately measured, with at least one diameter >\\= . cm by spiral CT scan or MRI. Lesions can be bidimensionally measurable or unidimensionally measurable. Every effort should be made to measure lesions in two dimensions. Measurable disease is present if the patient has one or more measurable lesions. Non-measurable lesions/disease are all other lesions, including small lesions (those with measurements < . cm; or < . cm with spiral CT).
Patients may have brain lesions which measure =< cm each; lesions that are >  cm that have been treated with stereotactic radiosurgery (SRS) and in the opinion of the PI or his designee no longer represents active disease will also be allowed (Turnstile II - Chemotherapy/Cell Infusion- Inclusion Criteria)
Bone lesions: lytic lesions, severe osteopenia or pathologic fractures
presence of  brain lesions or less
One to  painful lesions.
More than  painful lesions or more than  requiring immediate localized treatment
Presence of ulcerating or fungal skin lesions or infection of the breasts
Concurrent vaginal, vulvar, anal lesions or symptomatic infections
Eligible for neutron radiation treatment to - sites of metastatic disease (lesions do not have to be symptomatic)
Measurable disease, according to RECIST v.. Note that lesions intended to be biopsied should not be target lesions
Structurally unstable bone lesions suggesting impending fracture
Phase II: inoperable PN causing morbidity, such as (but not limited to) head and neck lesions that could compromise the airway or great vessels, brachial or lumbar plexus lesions that could cause nerve compression and loss of function, lesions that could result in major deformity (e.g., orbital lesions) or significant cosmetic problems, lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions in patients with NF; histologic confirmation of PN tumor is not necessary in the presence of consistent clinical and radiographic findings, but should be considered if malignant degeneration of a PN is clinically suspected; a PN is defined as a neurofibroma that has grown along the length of a nerve and may involve multiple fascicles and branches; a spinal PN involves two or more levels with connection between the levels or extending laterally along the nerve; in addition to PN, all study subjects must have either positive genetic testing for NF confirmed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory or have at least one other diagnostic criterion for NF listed below (National Institutes of Health [NIH] Consensus conference):\r\n* Six or more caf-au-lait macules (>= . cm in prepubertal subjects or >= . cm in post pubertal subjects)\r\n* Freckling in axilla or groin\r\n* Optic glioma\r\n* Two or more Lisch nodules\r\n* A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)\r\n* A first-degree relative with NF
Ulcerated skin lesions
No prior radiation to lesions being treated
Pulmonary metastasis permissible; appropriate candidates with lung lesions may be considered for ablative hypofractionation using stereotactic body radiation therapy (SBRT)
Patients having no distinct measurable lesions outside of the field of radiation
Patients with active central nervous system (CNS) malignancy; asymptomatic small lesions are not considered active; treated lesions may be considered inactive if they are stable for at least  months
Patients must have baseline skeletal survey to document lytic lesions, osteopenia or compression fracture within  days prior to registration
Participants must have measurable melanoma; measurable disease is defined as at least one lesion that can be measured accurately in at least one dimension (longest diameter to be recorded) as >=  mm with conventional techniques or as >=  mm with spiral computed tomography (CT) scan; cutaneous or subcutaneous lesions may be considered measurable if they can be measured reliably as >=  mm by direct physical exam measurement; in addition, participants must also have separate disease, which may or may not be measurable as defined by Response Evaluation Criteria in Solid Tumors (RECIST), but must be readily accessible for core needle biopsy, excisional biopsy, and/or surgical resection; this disease may include one large tumor tissue deposit from which biopsies can be harvested multiple times or may include multiple deposits which can be biopsied, or excised individually, on different dates; please see below for suggested minimum size requirements of tumor tissue to be used for biopsy for research:\r\n*  lesion >=  cm^ or\r\n*  lesions >=  cm^ each\r\n*  lesions >=  cm^each OR\r\n* >=  skin lesions, such that the surface area is approximately  cm^ each (or in aggregate for several lesions) and the total volume of tumor is approximately - mm^ or greater for each biopsy time point; these subjects will need >=  such epidermal/dermal tumor lesions; excisional tumor tissue biopsies will be performed on one or more lesions at each time point; it is acceptable to biopsy more than one lesion, that may be less than  cm^ in surface area, as long as the total tissue removed has a surface area of approximately  cm^ or greater\r\n* A combination of these may be acceptable, as long as there appears to be enough tumor tissue to remove approximately  mm^ or more of tissue at each time point
One to ten brain metastatic lesions
Subjects must have measurable disease and be a candidate for intralesional therapy administration into cutaneous, subcutaneous, or nodal lesions.
Has evaluable disease as defined as lesions that can be accurately measured at least in one dimension by radiographic examination or physical examination and other lesions such as bone lesions, leptomeningeal disease, ascites, hepatosplenomegaly from disease.
Brain lesions > lesions which were previously treated with SRT
Patients must have no lytic lesions on skeletal surveys and no hypercalcemia (i.e., >=  mg/dL)
Patients must not have baseline bone lesions or plasmacytomas
Lung tumor lesions with increased likelihood of bleeding;
Tumor biopsies are required. If a subject has inaccessible lesions, such as in ovarian cancer, HCC, or gastric cancer, or highly vascular lesions, such as RCC, enrollment may be considered with medical monitor approval, and archived tissue may be acceptable.
Bone lesions
(B) Bone lesions (lytic or osteopenic) one or more bone lesions on skeletal radiography, Computed tomography (CT), or PET-CT
Patients must have completed any prior chemotherapy, radiotherapy or major surgery at least  weeks before receiving study treatment; ongoing toxicities related to treatment must be =< grade  and patients with grade  alopecia or peripheral neuropathy can also be included; palliative radiation to < % of bone marrow is permissible if completed within one week of commencing study treatment as long as the toxicities secondary to palliative radiotherapy are limited to grade ; the lesions that have received radiation treatment immediately before will be excluded as target lesions; previously irradiated lesions can be considered as targeted lesions, as long as there is prove of radiological progression
Concurrent anticancer treatment (for example, cytoreductive therapy, radiotherapy [with the exception of palliative bone-directed radiotherapy, or radiotherapy administered on non-target superficial lesions], immune therapy, or cytokine therapy except for erythropoietin). Radiotherapy administered to superficial lesions is not allowed if such lesions are considered target lesions in the efficacy evaluation or may influence the efficacy evaluation of the investigational agent
A fresh tumor biopsy for the purpose of screening or an available archival tumor sample. Tumor lesions used for fresh biopsies should not be the same lesions used as RECIST target lesions, unless there are no other lesions suitable for biopsy.
Soft-tissue progression defined as an increase ? % in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions.
Soft-tissue progression defined as an increase ? % in the sum of the diameter (SOD; short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD, or the appearance of one or more new lesions, since the onset of the most recent prior therapy
Measurable disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable; any tumor mass >  cm is acceptable; lesions that are considered non-measurable include the following:\r\n* Bone lesions (lesions if present should be noted)\r\n* Ascites\r\n* Pleural/pericardial effusion\r\n* Lymphangitis cutis/pulmonis\r\n* Bone marrow (involvement by SLL or CLL should be noted)
Bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable disease as defined above.
Patients must have baseline skeletal survey (whole body x-ray) to document lytic lesions, osteopenia or compression fracture
Presence of at least  measurable lesions
Patients may receive bisphosphonates; however, if used, bone lesions may not be used for progression or response
Patients must have brain imaging by MRI, CT or PET within  days prior to lymphodepletion; patients may have asymptomatic brain lesions that are =<  cm each, lesions that are >  cm that have been irradiated and in the opinion of the investigator no longer represents active disease will also be allowed
Prostate with multiple cystic lesions.
Lesions that have been radiated previously cannot be considered target lesions
Bone only disease if there are lytic lesions is also allowed and treatment response will be evaluated based on the MD Anderson criteria
Note: Biopsied lesions should not be used as target lesions.
Note: Biopsied lesions should not be used as target lesions.
Patients with active central nervous system (CNS) malignancy; asymptomatic small lesions are not considered active; treated lesions may be considered inactive if they are stable for at least  months
Patients with active central nervous system (CNS) malignancy\r\n* Asymptomatic small lesions are not considered active\r\n* Treated lesions may be considered inactive if they are stable for at least  months
Subjects must have plexiform neurofibroma(s) that are progressive OR are causing significant morbidity, such as (but not limited to) head and neck lesions that are compromising the airway or great vessels, brachial or lumbar plexus lesions that are causing nerve compression and loss of function, lesions causing major deformity (e.g., orbital lesions) or are significantly disfiguring, lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions; subjects with paraspinal plexiform neurofibromas will be eligible for this trial; histologic confirmation of tumor is not necessary in the presence of consistent clinical and radiographic findings, but should be considered if malignant degeneration of a plexiform neurofibroma is clinically suspected
Patients with more than  discrete extra-cranial lesions
No more than  lesions
At least one bi-dimensionally measurable nodal lesion > . cm in its longest diameter by computed tomography (CT) scan or magnetic resonance imaging (MRI), as defined by the Lugano Classification\r\n* Site of disease deemed amenable to low-dose, local radiotherapy ( x Gy) should not be counted as target lesions\r\n* Previously irradiated lesions should not be counted as target lesions\r\n* Lesions that are intended to be used to collect tissue samples for biopsy should not be counted as target lesions\r\n* Bone lesions should not be counted as target lesions
Patients have progressive metastatic disease with predominantly bone metastasis with  or more lesions and at least  bone lesion has pathological confirmation, have not been treated or have been treated with any prior therapies (including bisphosphonate treatment and/or radiation therapy); patients can have soft tissue involvement (lymph node and skin) and/or metastatic lesions at major organ sites (i.e. lung, liver, etc)
For visceral or extra-nodal lesions to be considered measurable, they must be >=  mm in one dimension, using spiral CT
All other lesions, including small lesions (longest diameter <  mm with conventional techniques or <  mm with spiral CT scan) and truly non-measurable lesions; lesions that are considered non-measurable include bone lesions (only)
Patients with node only disease (i.e. no presence of visceral, extra nodal lesions or bone lesions) must have node(s) that measure >=  mm in short axis
No structurally unstable bone lesions suggesting impending fracture
New or progressive CNS lesions, as assessed by the patients treating physician, with at least one of the following clinical scenarios:\r\n* It is anticipated that some participants may have multiple progressive CNS lesions, one or several of which are treated with stereotactic radiosurgery (SRS) or surgery with residual un-treated lesions remaining; such participants are eligible for immediate enrollment on this study providing that at least one untreated lesion is measurable; the location of the measurable lesion should be documented in the patient chart and case report form\r\n* Participants who have had prior cranial surgery are eligible, provided that there is evidence of measurable residual or progressive lesions; if a patient has surgical resection followed by whole brain radiation therapy (WBRT) and/or SRS, then there must be evidence of progressive CNS disease after the completion of WBRT and/or SRS\r\n* Participants who have had prior WBRT and/or SRS and then whose lesions have progressed thereafter are also eligible; in this case, lesions which have been treated with SRS may be considered as target lesions if there is unequivocal evidence, in the opinion of the treating physician, of progression following SRS\r\n* Participants who have not previously been treated with cranial radiation (e.g. WBRT or SRS) are eligible to enter the study, but such participants must be asymptomatic from their CNS metastases and not requiring corticosteroids
Patients must have measurable lesions
Patient with symptomatic or growing CNS metastatic lesions
Metastatic disease outside the intraperitoneal cavity and retroperitoneum, intrahepatic lesions, or pleural effusions; significant ascites precluding catheter placement; exception: intrahepatic lesions removed or planning to be removed during the debulking procedure
STEP  ENROLLMENT: three or less metastatic lesions (not sites); each lesion (including a satellite nodule) will individually be counted as one, and intrathoracic lymph node involvement (defined here as hilar, mediastinal, or supraclavicular nodes, N-N) will collectively be counted as one; in addition, patients can receive treatment to CNS lesions or other symptomatic lesions requiring urgent local therapy prior to randomization, but these lesions will be counted towards the total number after chemotherapy, and patients will only be eligible if there are remaining sites amenable to local therapy after up-front systemic therapy
STEP  ENROLLMENT AND RANDOMIZATION: treatment to central nervous system lesions, such as the brain or spine (prior to first line systemic therapy), or symptomatic lesions requiring urgent palliative radiation, is permitted prior to randomization, in which case the patient would be randomized to treatment of other metastatic sites or the primary sites (based on the disease remaining after first-line treatment); these treated lesions should be counted towards the total number of metastases at the time of enrollment
Patients must have disease that is refractory (unresponsive) to radioactive iodine (RAI) treatment as defined by one of the following: \r\n* One or more measurable lesions that do not demonstrate RAI uptake \r\n* One or more measurable lesions progressive by RECIST . within -months of prior RAI therapy and/or the appearance of one or more new lesion within  months of prior RAI therapy\r\n* Cumulative RAI dose of >  mCi\r\n* Measureable disease that is fludeoxyglucose (F) positron emission tomography (PET) scan positive
Have measurable skin disease with  to  eligible baseline target lesions with a total area >=  cm^ but =<  cm^; eligible lesions must be below the neck and may not involve the genitalia, intertriginous areas, internally, or to frankly ulcerated or infected skin
Patients with lesions in the upper cervical spine (C-C) or cervicothoracic junction (C-T)
Confirmed presence of somatostatin receptors on all target lesions (for target/non-target/measurable lesions definition see Appendix , Section  and , RECIST Criteria, Version .) documented by CT/MRI scans, based on positive OctreoScan imaging within  weeks prior to randomization in the study (to be centrally confirmed). The OctreoScan should be one that was performed while the patient was on a fixed dose of Octreotide LAR. If a patient has had an OctreoScan performed while Octreotide LAR treatment-nave, the patient must have a repeat OctreoScan performed after  months of Octreotide LAR treatments before entering the clinical study to prove that the index lesions or new lesions still meet the criteria for inclusion. It is acceptable to have patients temporarily switched to Octreotide s.c. (up to six weeks) in order to obtain an OctreoScan, provided they return to the same fixed dose of Octreotide LAR prior to the scan.
Non-measurable disease: all other lesions, including small lesions (less than . x . cm) and truly non-measurable lesions; lesions that are considered non-measurable include the following:\r\n* Bone lesions (lesions if present should be noted)\r\n* Ascites\r\n* Pleural/pericardial effusion\r\n* Lymphangitis cutis/pulmonis\r\n* Bone marrow (involvement by Hodgkins lymphoma should be noted)
Lesions must be amenable to accurate and repeat measurement.
It is anticipated that some patients may have multiple progressive CNS lesions, one or several of which are treated with SRS or surgery with residual untreated lesions remaining; such patients are eligible for enrollment on this study providing that at least one residual (i.e. non-SRS-treated or non-resected) lesion is measurable (>=  mm); the location of the measurable lesion should be documented in the patient chart and case report form
Patients who have had prior WBRT and/or SRS and then whose prior treated lesions have progressed thereafter are also eligible; in this case, lesions which have been treated with SRS may be considered as target lesions if there is unequivocal evidence, in the opinion of the treating physician, of progression
Subjects with benign lesions such as fibroadenoma, atypical ductal hyperplasia, sclerosing adenosis, Papilloma, fibrocystic disease of breast
All patients must be considered an eligible candidate for systemic therapy as determined by the investigator; to be eligible, LYP patients must be in need of systemic therapy i.e., have scarring or active lesions (>=  per month), or any number of active lesions on face, hands, or feet
Disease to be treated on protocol is less than  mm from the spinal cord and therefore will not meet dose constraints; Note: patients with eligible and ineligible lesions will be accrued to this protocol; only target eligible lesions will be treated per protocol; other eligible and ineligible lesions will be treated at the discretion of the treating physician
Lesions which comprise > % of the width of weight bearing bones, such as the femur
Areas to be treated on protocol do not include metastases to liver, brain or lung; Note: patients with eligible and ineligible lesions will be accrued to this protocol; only target eligible lesions will be treated per protocol; other eligible and ineligible lesions will be treated at the discretion of the treating physician
Maximum of number of lesions per patient will be  total for all disease sites
Patients cannot have more than  liver lesions
All active liver lesions must be discrete on CT or MRI imaging
BONE LESIONS:
SPINE AND PARASPINAL LESIONS:
Untreated T-N primary lesions may also be treated with SBRT
Patients with T, N lesions
Patients with neurofibromatosis type  (NF) and an inoperable plexiform neurofibroma that has the potential to cause significant morbidity, such as (but not limited to) head and neck lesions that could compromise the airway or great vessels, brachial or lumbar plexus lesions that could cause nerve compression and loss of function, lesions that could result in major deformity (e.g., orbital lesions) or significant cosmetic problems, lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions; histologic confirmation of tumor is not required in the presence of consistent clinical and radiographic findings; however, if any clinical observation or scan suggests possible malignant transformation, the tumor should be biopsied prior to therapy; patients without biopsy-proof of a plexiform neurofibroma must have at least one other diagnostic criteria for NF as defined by the National Institutes of Health (NIH) Consensus Conference:\t\r\n* Six or more caf-au-lait spots (> . cm in prepubertal subjects or > . cm in postpubertal subjects)\r\n* Freckling in the axilla or groin\r\n* Optic glioma\r\n* Two or more Lisch nodules\r\n* A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)\r\n* A first degree relative with NF
Subject has at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version .. Evaluable target lesions may not have been treated with local therapy; previously treated lesions may only be evaluated as target lesions if they are the only lesions available and have shown objective definite progression after prior treatment. Local therapy must have been completed at least four weeks prior to baseline tumor evaluation
Radiation therapy (except for localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture): ? weeks
Radiation therapy (localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture) ? weeks
Patients with active central nervous system (CNS) malignancy; asymptomatic small lesions are not considered active; treated lesions may be considered inactive if they are stable for at least  months
Brain lesions must be ) supratentorial, ) ten lesions or less, and ) not considered a candidate for surgical resection
For Phase I: Locally advanced or metastatic B-Raf proto-oncogene, serine/threonine kinase (BRAF) VE/K positive melanoma that is either treatment-nave or treatment-experienced; for the latter, progression, or stable as best response, or intolerance to the last treatment is required; previous treatments can be local or systemic therapies; there are no limits to the number of prior therapies; for all patients, disease does not have to be measurable but must be evaluable, which is defined as one or more lesions which are known to be present, but which cannot be measured; e.g.: bony lesions, pleural effusion, ascites
Multiple lesions that dont meet the criteria as satellite lesions
Participants must have cutaneous lesion(s) amenable to four total biopsies (either four lesions >  mm or one large lesion measuring  mm that can undergo serial biopsy) and at least five additional lesions measurable for assessment with no improvement over the four weeks prior to enrollment
KS patients with skin-only disease must have cutaneous lesions amenable to four  mm punch biopsies during the course of the study (either four separate lesions measuring >=  mm each OR two separate lesions measuring >=  mm each)
Patients with metastatic disease i.e. leptomeninges, multi-focal lesions in the CNS
Preferentially radiologically by tumor growth or new lesions, or by
Participants must have cutaneous lesion(s) amenable to four () -mm tumor biopsies during the study (either  separate lesions measuring >=  mm each OR  separate lesions measuring >=  mm each) and at least five additional lesions measurable for assessment with no improvement over the past month
Patients with single or multiple cerebellar or cerebral cortex lesions are eligible
Diagnosis must be confirmed clinically at baseline with - lesions having been biopsied no sooner than  weeks prior to treatment
Primary lesions may be acceptable for enrollment
Radiation for symptomatic lesions within  days of study enrollment
Either complete disappearance of all lesions, or persistence of metastatic disease (stable disease) without unequivocal progression or the occurrence of new lesions
Documentation of lesion response during the course of therapy received prior to randomization (i.e., improvement or no worsening of tumor burden; the absence of new lesions)
One or more of the following risk criteria for failure with conventional SBRT treatment alone:\r\n* Peripheral tumor >=  cm in any dimension\r\n* Central tumor (i.e. gross tumor within  cm of a major bronchus/vessel, or heart/pericardium), including hilar lymph node(s)\r\n* Multiple tumors (i.e. satellitosis-defined T-, or bilateral synchronous primary lung cancer; note that the maximum number of total lesions allowable on this study for treatment with SBRT is  (three), and all lesions must be amenable to SBRT and treated with SBRT on this study; note that it is not necessary for all lesions felt to be malignant to be biopsied
Radiotherapy within  days before the first dose of either study drug except localized radiation therapy for lytic bone lesions and plasmacytomas
No more than  treatable lesions as evaluated by an experienced interventional oncologic radiologist for eligibility and lesion accessibility as the ablation of more than  lesions becomes technically infeasible; these lesions must be treated in a two- to three-week time period from initial interventional radiology evaluation; lung and liver lesions can range from  cm to  cm for a single lesion and no greater than  cm for multiple lesions; there are no size criteria for the osseous lesions
The lesions will be amenable to a safe, ultrasound/computed tomographic/fluoroscopic guided percutaneous approach; the targeted metastases must be sufficiently separable from the central nervous system, major peripheral motor nerves, bowel, and bladder; all lesions must be amenable to treatment
Patients with symptomatic relapse, including those with new bone lesions, soft tissue plasmacytomas, an increase in the size of existing bone lesions or soft tissue plasmacytomas, decrease in hemoglobin, rise in serum creatinine or hypercalcemia
Participants with multiple basal cell carcinomas, including participants with Gorlin syndrome, with at least  clinically evident basal cell carcinomas at the time of randomization, of which  measure  mm or more in diameter and are considered target lesions. All other lesions are considered to be non-target lesions
Structurally unstable bone lesions suggesting impending fracture
. If lesions are too small to be visualized or palpable for accurate injection.
Presence of more than  melanoma lesions
Subjects with NF- and only PN lesions that cannot be evaluated by volumetric analysis (only applicable to Part B).
Patients with NF and inoperable PN defined as PN that cannot be surgically completely removed without risk for substantial morbidity due to encasement of, or close proximity to vital structures, invasiveness, or high vascularity of the PN; the PN has to cause (stratum ) or have the potential to cause (stratum ) significant morbidity, such as (but not limited to) head and neck lesions that could compromise the airway or great vessels, paraspinal lesions that can cause myelopathy, brachial or lumbar plexus lesions that could cause nerve compression and loss of function, lesions that could result in major deformity (e.g., orbital lesions) or are significantly disfiguring, lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions; patients will be enrolled into stratum  or  based on PN related morbidity; histologic confirmation of tumor is not necessary in the presence of consistent clinical and radiographic findings, but should be considered if malignant degeneration of a PN is clinically suspected; a PN is defined as a neurofibroma that has grown along the length of a nerve and may involve multiple fascicles and branches; a spinal PN involves two or more levels with connection between the levels or extending laterally along the nerve; in addition to PN, all study subjects must have either positive genetic testing for NF or have at least one other diagnostic criterion for NF listed below (National Institutes of Health [NIH] Consensus conference):\r\n* Six or more caf-au-lait macules (>= . cm in prepubertal subjects or >= . cm in post pubertal subjects)\r\n* Freckling in axilla or groin\r\n* Optic glioma\r\n* Two or more Lisch nodules\r\n* A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)\r\n* A first-degree relative with NF
Except for patients with GBM/ AnaA in the Expansion Phase, patients with active CNS malignancy are excluded. Asymptomatic small lesions are not considered active. Treated lesions may be considered inactive if they are stable for at least  months.
Patients must have measurable disease in two dimensions and >=  cm is acceptable (or . cm if . slices are used, as in spiral computed tomography [CT] scans); lesions that are considered intrinsically non-measurable include the following:\r\n* Bone lesions\r\n* Leptomeningeal disease\r\n* Ascites\r\n* Pleural/pericardial effusion\r\n* Inflammatory breast disease\r\n* Lymphangitis cutis/pulmonis\r\n* Abdominal masses that are not confirmed and followed by imaging techniques\r\n* Cystic lesions\r\n* Lesions that are situated in a previously irradiated area
Measurable lesions are not required for admittance to the study - but are desirable.
Brain lesions with a propensity to bleed
Patients will have from  to  painful lesions and only the most painful lesion will be treated.
More than  painful lesions, or more than  requiring immediate localized treatment
Patients must, in the opinion of the treating physician, be candidates for intralesional administration into cutaneous, subcutaneous, or nodal lesions; patients must have at least  injectable lesions
Patients with lesions to the nasal mucosa
Traumatic lesions/hematomas
There can be multiple small metastatic lesions shown in other vertebral bodies; the metastatic lesion of each spine should be less than % of the vertebral body as opposed to the diffuse vertebral involvement; these small lesions are often seen in the MRI even when bone scan or PET was negative; most of these lesions are not clinically required to be treated and are therefore not included in the target volume of this protocol; only the painful spine (pain score >= ) is to be treated
TNM and TNM glottic lesions
Willingness to have photographs taken to document lesions
All visible papillary lesions must be macroscopically resected within  days of treatment initiation
Prostate with multiple cystic lesions.
Unmeasurable target tumor site by RECIST . or PRC (example [ex]: lesions <  cm on computed tomography [CT] or magnetic resonance [MR] scan, leptomeningeal disease, ascites, pleural/pericardial effusion, lymphangitis, non-fludeoxyglucose [FDG]-avid skin lesions)
Minimum of at least three discrete metastatic lesions in the bone and/or soft tissue amenable to whole body PET imaging per the judgment of study radiologist
Confirmed presence of somatostatin receptors (type ) on technically evaluable tumour lesions documented by a positive Somatostatin Receptor Scan acquired within  months prior to screening (Visit ) and showing minimally two lesions in at least one of the key organs; these images shall be available to be sent to the imaging core lab electronically to ascertain quality and admissibility
Fewer than five lesions in total and more than  lesions/organ detected by the previous somatostatin receptor scan in key organs: liver, lymph nodes, bone or lungs
Disease that is measurable; this is defined as lesions measuring at least  mm on radiologic imaging
Participants must present with a gadolinium-enhancing brain lesion (or lesions) that are thought by the neuroradiologist and the neurosurgeon to be consistent with high-grade glioma; these may be newly diagnosed lesions or recurrent tumors
Patients must have MRI findings reporting intraprostatic lesions suspicious for malignancy
Patient has:\r\n* Liver lesions that are untreated liver lesions or \r\n* Changing treatment regimen/type and/or receiving a new form of treatment and/or has been on a treatment break (holiday) for liver lesions
Adult subjects with oral lesions undergoing surgical resection (i.e., only patients who are scheduled to undergo a surgery of the head & neck area to remove or biopsy oral lesions will be eligible to participate in the study); patients with previous treatment are eligible
Visible lesions by either CT, bone imaging, or MRI consistent with disease
Patients with breast lesions that are non-palpable that require surgical removal
Lesions and/or clip targetable with image guidance
Evolving brain lesions post SRS requiring neurosurgical resection (whether for symptomatic control or to establish pathology)
Subjects must have solid tumors with malignant lesions in the thorax, abdominal cavity, head and neck region, or extremities (any histology) likely to benefit from palliative radiotherapy; subjects requiring palliative RT for lesions in the spine or lesions adjacent to the spinal cord are excluded from this study
Subjects enrolled into Part  must have metastatic lesions where repeated IT injections are not feasible and in whom SC injection is the only viable route of CMP- administration, based on Investigator judgment. Subjects with injectable lesions are NOT eligible to participate in Part . Subjects enrolled into Part  must have metastatic lesions that are amenable to repeated IT injections.
Radioiodine (RAI)-resistant disease as defined by one or more of the following criteria:\r\n* One or more measurable lesions that do not demonstrate RAI uptake\r\n* One or more measurable lesions progressive by RECIST . =<  months of prior RAI therapy\r\n* One or more measurable lesions present after cumulative RAI dose of >=  mCi\r\n* One or more measurable lesions that are fludeoxyglucose F- (FDG)-avid (>  standardized uptake value [SUV]), if positron emission tomography (PET)/CT scan performed; these lesions may also be RAI-avid
Patients with confirmed or suspected liver lesions
Any person with a lesion of the oral mucosa; persons with changes in existing lesions or those who develop new lesions can be re-evaluated, but it is not required
Purely cystic lesions
Subjects with active oral lesions or other mouth/throat soreness within d of study randomization.