Cholestatic disorders or unresolved veno-occlusive disease of the liver.
Patients with a history of venous occlusive disease of the liver
Participants who have undergone a liver transplant or those who are in the waiting list for liver transplantation
Cirrhotic liver disease from any cause
Hepatic metastases on imaging meeting the following criteria:\r\n* Liver-only or liver-dominant metastases, defined as:\r\n** At least % liver parenchyma replacement by tumor, but less than % replacement of the hepatic parenchyma by tumor\r\n*** For the imaging sub-study: at least one liver lesion must measure greater than  cm in size\r\n*** For the imaging sub-study: treatment must only be performed using a single dose, and so arterial variant anatomy that would result in a split treatment will not be allowed\r\n** And, progression of the liver metastases demonstrated within the past twelve months defined as either:\r\n*** Appearance of any new liver lesion or\r\n*** % increase in size of at least one liver lesion\r\n** Presence of low-volume extrahepatic lesions (including primary tumor) is allowed if they are asymptomatic\r\n* SUVmax on Ga-DOTA-TOC PET of the liver metastases two times greater than the adjacent liver parenchyma
Greater than % tumor burden in the liver by imaging.
Has metastatic liver involvement that does not exceed / of the total liver volume in participants to be treated by liver IT injection. Hepatocellular carcinoma participants are excluded from eligibility of IT liver injection.
No prior local, liver-directed therapy; prior surgical resection of oligometastatic liver disease is allowed
History of cirrhotic liver disease
Known history of chronic liver disease
Participant has a history of liver disease
Prior radioembolization to the liver
Chronic liver disease
Have pre-existing alcoholic liver injury or significant liver disease.
High screening liver function tests
Presence of parenchymal liver metastases on imaging
Patients with recent (within  days preoperatively) history severe hepatic disease (defined as liver injury with encephalopathy plus impaired synthetic liver function (i.e. > .).
Patients who have been previously treated with non-SBRT liver directed therapies (with the exception of intrahepatic Y infusion) may be enrolled on study; at least  months must have elapsed between the most recent liver-directed therapy and study entry
Any condition that, in the opinion of the investigator, might be significantly exacerbated by the known side effects associated with the administration of pirfenidone e.g., presence of active GVHD of the liver as manifested by rising liver function tests (LFTs) prior to initiation of study treatment
Uncontrolled adrenal insufficiency or active chronic liver disease
Liver metastases with no other metastatic sites
Participants must have biopsy-proven diagnosis of a colorectal cancer with - liver metastases; there is no upper size limit and participants must have at least  mL of uninvolved liver; liver metastases may be diagnosed by imaging alone, no liver biopsy is required; extrahepatic disease is allowed if ) it has been stable for  months prior to study entry, ) the dominant disease burden is intrahepatic and ) the patient is referred for definitive radiation therapy to the disease in the liver
Participants must have liver metastases deemed unresectable due to anatomy, medical fitness, or presence of extrahepatic disease
Childs class C liver disease or worse
No history of severe prior or ongoing chronic liver disease
History of cirrhotic liver disease
Patients with greater than % liver tumor burden
Abnormal liver function tests (LFTs) in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the LFTs as being consistent with hepatic cGVHD and a liver biopsy will not be mandated in this situation
Patients must have liver-only metastases or predominant liver metastatic disease
Liver involvement by > % with metastatic disease determined by the investigator
Known liver disease
Subjects with diagnosed active liver disease or with elevation of liver enzymes/bilirubin.
Patients must have liver metastasis
Patients with a history of prior irradiation or other treatment to the liver or abdomen who after treatment on this protocol would have a cumulative dose to the liver or other normal tissues greater than the protocol defined constraints
Uncontrolled adrenal insufficiency or active chronic liver disease
Active hepatitis B or C infection with abnormal liver functions (i.e., liver function tests [LFTs] >  X upper normal limits)
Patients must have histologically or cytologically confirmed colorectal cancer with liver metastases deemed resectable by a general or liver surgeon (resectability may involve the use of ablative techniques to some but not all liver metastases); those patients with known disease outside of the liver are not eligible (except for patients with primary lesions in place that are planned for resection or nonspecific lung metastases < cm)
Patients with synchronous or metachronous diagnosis of resectable liver metastases by computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen: a) patients requiring percutaneous or intraoperative ablation of liver metastases <  cm in size are eligible; b) patients who underwent prior liver resection or ablation for colorectal liver metastases are eligible
Compromised liver function as defined by any of the following:\r\n*  Cohort : Advanced cirrhosis group\r\n** Borderline Child-Pugh class A\r\n** Child-Pugh class B\r\n*** The patients in this advanced cirrhosis group must have at least  ml of functional liver, as estimated on either diagnostic imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) or single photon emission computed tomography (SPECT)/CT with Tc-m sulfur colloid; there is no upper limit on the functional liver volume for these patients\r\n* Cohort : Low functional liver volume without underlying chronic liver disease\r\n** Previous irinotecan or oxaliplatin chemotherapy\r\n** Previous liver resection(s)\r\n*** These patients must have at least  ml of functional liver, as estimated by either diagnostic imaging computed tomography or magnetic resonance imaging (CT or MRI) or SPECT/CT with Tc-m sulfur colloid\r\n* Cohort : History of prior liver-directed radiation therapy with either fractionated external beam radiation therapy (EBRT), stereotactic body radiation therapy (SBRT) or yttrium- radioembolization (Y RE); the interval between prior EBRT and re-irradiation on protocol should be equal to or greater than  months; the interval between prior Y RE and re-irradiation on protocol should be equal to or greater than  months; \r\n** Cirrhosis group:\r\n*** Child-Pugh class A; \r\n*** Borderline Child-Pugh class A; \r\n*** The patients in this group must have at least  ml of functional liver, as estimated on either diagnostic imaging (CT or MRI) or SPECT/CT with Tc-m sulfur colloid; there is no upper limit on the functional liver volume for these patients\r\n*Low functional liver volume without underlying liver disease\r\n** Previous irinotecan or oxaliplatin chemotherapy\r\n** Previous liver resection(s)\r\n** These patients must have at least  ml of functional liver, as estimated by either diagnostic imaging (CT or MRI) or SPECT/CT with Tc-m sulfur colloid; there is no upper limit on the functional liver volume for these patients
Metastatic disease outside of the liver
In patients with liver metastases, there should be < % involvement of the liver
Liver tumors must not be estimated to invade approximately more than one-third of the liver.
Patients with parenchymal liver metastases.
At least one thoracic or liver lesion amenable to radiation, for group  we need one area that can safely receive SBRT or WFRT, not restricted to lung or liver sites
Liver function tests >  x upper limit of normal
Bilirubin < . x normal except in cases where abnormal liver function tests (LFTS) are due to involvement with T-NHL
Known or active hepatitis B or C with abnormal liver function tests
Liver function test (LFTs) =<  x upper limit of normal
Tumor involving > % of the liver
Patients with a history of or active liver failure
Liver enzymes <  fold the upper limit of normal
Scans used to determine eligibility (CT scan of the chest/abdomen/pelvis and MRI of the liver) must be performed within  days prior to randomization. An MRI of the liver is required at screening to validate that CT accurately reflects the extent of disease in the liver. For patients with MRI intolerance, a -phase liver CT is to be done in place of liver MRI.
Extensive liver tumor burden, defined as more than % of the liver
Histologically confirmed diagnosis of cancer with liver metastases, or histologically confirmed primary liver cancer (e.g. hepatocellular carcinoma, cholangiocarcinoma, or gallbladder carcinoma); subjects may have extrahepatic spread of malignancy, except they may not have brain metastases; subjects with a history of more than one invasive malignancy remain eligible for this study, but in these instances, a liver biopsy is required to document the histology of the liver tumor; an exception to this criterion is made for basal cell carcinoma
Prior liver resection of greater than  anatomic segments as defined by Couinaud; (subjects that have undergone prior liver wedge excisions or segmental resections are not excluded on this basis alone)
No history of severe prior or ongoing chronic liver disease
Loco-regional therapy to the liver within  days before randomization
History of chronic liver disease.
History of chronic liver disease.
Chronic inflammatory liver condition.
History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)
Liver tumors must not be estimated to invade approximately more than one-third of the liver.
Chronic liver dysfunction prior to development of liver metastases (Child-Pugh C or greater).
Severe liver disease
Severe liver disease
Uncontrolled adrenal insufficiency or active chronic liver disease
Liver function tests performed within  weeks prior to starting study therapy must have albumin >= . g/dL
Liver function tests >  x upper limit of normal
History or current evidence of malabsorption or liver disease that would impair the absorption of itraconazole
ARM A: Disease burden in liver not affecting more than % of liver
ARM A: Predominant intrahepatic burden (> %) of disease (i.e. patients with widespread extrahepatic disease to organs other than the liver will not be included)
ARM B: Disease burden in liver not affecting more than % of liver
Total bilirubin =< . x ULN; unless presence of Gilbert's syndrome, liver involvement by CLL or MM, or stable chronic liver disease per investigator's assessment
Liver disease, except Gilbert's syndrome, liver involvement by CLL or MM, or stable chronic liver disease per investigator's assessment
Decompensated liver disease in which pegylated interferon is contraindicated
History or other evidence of decompensated liver disease
History or other evidence of decompensated liver disease
Liver disease.
Ongoing liver injury
Abnormal liver function test results
Liver function tests (LFTs) greater than twice the upper limit of normal
Cancer that has spread to the liver or brain
Subjects with known history, or clinical or laboratory evidence of liver disease
Patients must have liver metastases.
History of current evidence of malabsorption or liver disease
Suspected pulmonary and/or liver metastases (greater >=  mm in largest axis)
Any of the following liver findings: ALT >.xULN, ALT > xULN with liver metastases/tumor infiltration, Bilirubin >.xULN (isolated bilirubin >.xULN is acceptable if bilirubin is fractionated and direct bilirubin <%), Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator assessment). NOTE: Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices, persistent jaundice or cirrhosis
Has clearly resectable colon cancer liver metastases (CCLM), for example oligometastatic disease involving only one lobe of the liver. Subjects with suspected resectable CCLM should undergo evaluation by a liver surgeon prior to enrollment to document the incurable nature of their disease.
For patients with abnormal liver function tests (LFTs) as the sole manifestation of cGVHD, documented GVHD on liver biopsy will be required prior to enrollment; abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with hepatic cGVHD, and a liver biopsy will not be mandated in this situation
For participants with abnormal liver function tests (LFTs) as the sole manifestation of cGVHD, documented GVHD on liver biopsy will be required prior to enrollment; abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with hepatic cGVHD, and a liver biopsy will not be mandated in this situation
History of chronic liver disease.
History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)
Liver metastases
Prior liver directed therapies will be permitted (i.e. chemoembolization, radioembolization) as long as target lesions in the liver have demonstrated growth since the liver directed treatment
Prior peptide receptor radionuclide therapy (PRRT) will be permitted as long as target lesions in the liver have demonstrated growth since the liver directed treatment
Abnormal liver function tests (bilirubin more than .xULRR, and ALT, AST, or ALP more than .xULRR or .xULRR if related to liver metastases).
Known hepatitis B virus carriers who have liver function tests within the accepted limits are eligible
LIVER (ONLY APPLIES TO PATIENTS WITH METASTATIC LIVER LESIONS NOT PREVIOUSLY TREATED WITH RT):
History of serious liver disease
Chronic or active hepatitis B or hepatitis C; if questions about liver health, discuss with principal investigator (PI) and strongly consider liver biopsy
Acute liver disease or previously diagnosed liver tumor (benign or malignant)
Subjects with unresolved veno-occlusive disease of the liver.
Preserved liver function
Presence of advanced liver disease.
Ongoing liver injury
History of chronic liver disease.
Patients must have liver-only or liver-predominant disease to be eligible for this study; liver predominant disease is defined dominant metastatic burden in the liver, with extra-hepatic disease that is judged by the investigator as unlikely to be life threatening within  months
Patients with previous chemoembolization to liver metastases
Ongoing liver injury
Patients with liver metastases that replace greater than % of the liver parenchyma
Significant liver disease or metastatic disease to the liver
Patients with abnormal liver function will be eligible and will be grouped according to the criteria described; patients with active hemolysis should be excluded; no distinction will be made between liver dysfunction due to metastases and liver dysfunction due to other causes
History of cirrhotic liver disease
Patients with >  liver metastases at time of enrollment
Patients must have one focus of metastatic disease in the liver that is amenable to SBRT in the opinion of radiation oncology
Prior liver directed radiation
Liver function tests (LFTs) >  x nl
Patients should have hepatic function (alkaline phosphatase, AST and ALT) < ULN and renal functions with serum creatinine - <. x UNL. If a patient has liver metastasis and/or a history of liver disease - they will receive a lower dose of the drug per treatment protocol.
Patients with known liver metastases
History of chronic liver disease.
History of chronic liver disease
Patients with known liver disease
Underlying chronic liver disease with evidence of severe liver impairment.
History or current hepatitis or other liver disease
History or current evidence of malabsorption or liver disease that would impair the absorption of Itraconazole as measured by liver function tests within the past one year prior to enrollment
Normal liver function based on Liver Function Tests (Total Bilirubin and AST <. X Upper Limit of Normal).
Metastatic disease outside of liver
Greater than % tumor burden in the liver by imaging
Liver function tests with values >  x ULN
Liver metastases
History of veno-occlusive disease of the liver
Patients with history of severe liver disease, defined as and confirmed by albumin less than .
History of liver disease
Potential subjects will be excluded for a number of medical conditions that might represent a risk for riluzole (including history of allergic reaction to riluzole and evidence of liver disease) and potentially confound the relationship among CNS glutamate, inflammation and behavior/cognition, including: autoimmune or inflammatory disorders, chronic infectious diseases (e.g. human immunodeficiency virus [HIV], hepatitis B or C), pregnancy, neurologic disorders (including a history of serious head trauma or seizures), liver disease (as manifested as an elevation in liver transaminases), uncontrolled cardiovascular, metabolic, pulmonary or renal disease (as determined by medical history and laboratory testing)
Chronic liver disease
Liver tumor burden less than or equal to %
Patients undergoing open elective liver resection for primary liver pathology (benign or malignant) or secondary metastatic liver disease, including patients undergoing concomitant surgical procedures (such as colorectal resection or debulking procedures), with no contraindication to the insertion of an epidural catheter (localized infection, septicemia, or pre-operative coagulopathy)
Significant liver disease that would inhibit prescription of opioids
Patients must have liver tumors requiring a major liver resection, defined as removing at least three anatomical segments in patients without liver disease and two segments in patients with cirrhosis/fibrosis of the liver
No liver failure
Chronic liver disease or in participants without known liver disease, alanine aminotransferase (ALT) >=  x normal
Total bilirubin < . mg/dl; unless hepatic dysfunction is a manifestation of presumed cGVHD; for patients with abnormal liver function tests (LFTs) as the sole manifestation of active cGVHD, documented cGVHD on liver biopsy will be required prior to enrollment; abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with active hepatic cGVHD, and a liver biopsy will not be mandated in this situation
For participants with abnormal liver function tests (LFTs) as the sole manifestation of cGVHD, documented GVHD on liver biopsy will be required prior to enrollment; abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with hepatic cGVHD, and a liver biopsy will not be mandated in this situation
No significant synthetic dysfunction of the liver; if there is a question of such, a liver biopsy should be performed for further assessment
History of hepatitis or liver disease
Diffuse intrahepatic metastases that involves >  % of the liver
For patients with abnormal liver function tests (LFTs) above the thresholds, documented cGVHD on liver biopsy will be required prior to enrollment
Able to undergo:\r\n* Percutaneous or transjugular biopsy of cirrhotic liver at least  days prior to liver resection (surgical cohort), OR\r\n* A biopsy of the cirrhotic liver (non-surgical cohort)
Willingness to authorize collection of tissue from surgically-resected liver or clinical liver biopsy for analyses
Patients with end stage liver disease or anticipated liver transplant within the next two years will be excluded; a history of liver transplant is not an exclusion per se, if patient does not meet stated hepatic criteria
Individuals with history of liver disease in last  months
Liver metastases on most recent prior M.D. Anderson CT examination.
Patients with liver failure are NOT eligible.
History of liver disease within the last  months
Patients with confined liver disease or stable limited extrahepatic disease
Liver function tests (LFTS) =< . x upper limit of normal (ULN)
Patients must have liver-dominant or liver-only metastatic disease from any primary histology; patients with primary hepatocellular or biliary cancer are also eligible
Patients not undergoing radioembolization to the liver
History of having undergone any local ablative therapy to liver prior to enrollment on the trial
Prior systemic treatment or radiation therapy is allowed for patients with resectable liver metastases\r\n* The last dose of chemotherapy or radiation must have been administered at least  weeks prior to liver surgery\r\n* The last dose of bevacizumab must have been administered at least  weeks prior to liver resection
History of liver disease as defined with liver function tests (LFTs) above those in the inclusion
Criteria , More than one third of the liver is estimated to be involved with metastases