Availability of pulmonary function tests (PFTs  spirometry, diffusing capacity of the lungs for carbon monoxide [DLCO], +/- arterial blood gases) within  days prior to registration; patients with tracheotomy, etc, who are physically unable to perform PFTs are potentially still eligible if a study credentialed thoracic surgeon documents that the patients health characteristics would otherwise have been acceptable for eligibility as a high risk but nonetheless operable patient (in particular be eligible for sublobar resection)
Normal pulmonary function tests (including diffusion capacity of the lung for carbon monoxide [DLCO]) if there is clinical indication for determination (e.g. dyspnea at rest, known requirement for supplemental oxygen); for patients who do not have respiratory symptoms or requirement for supplemental oxygen, pulmonary function tests (PFTs) are NOT required
Participants with significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, carbon monoxide diffusing capability test (DLco), oxygen (O) saturation at rest on room air should be considered to exclude restrictive pulmonary disease, pneumonitis or pulmonary infiltrates
Normal pulmonary functions tests (including carbon monoxide diffusing capability test [DLCO]) if there is a clinical indication for determination (dyspnea at rest, known requirement for supplemental oxygen); for subjects who do not have respiratory symptoms (no dyspnea at rest, oxygen [O] saturation [sat] >= % on room air), full pulmonary function tests (PFTs) are NOT required
Patients with pulmonary, cardiac, hepatic or renal impairment that would limit their ability to receive cytoreductive therapy and compromise their survival; this should include patients with any of the following:\r\n* Severe pulmonary dysfunction associated with a carbon monoxide diffusing capacity (DLCO) (corrected for hemoglobin) < %, or requires supplemental oxygen\r\n* Uncontrolled malignant arrhythmias, or clinical evidence of congestive heart failure (New York class III-IV) or ejection fraction < %\r\n* Renal disease with estimated glomerular filtration rate (GFR) by creatinine clearance or iothalamate clearance <  ml/min/. m^ body surface area\r\n* Serum glutamate pyruvate transaminase (SGPT)/aspartate aminotransferase (AST) >  times normal or direct bilirubin greater than . mg/dL on two repeated tests
Carbon monoxide diffusing capability (DLCO) > % predicted (in children, oxygen [O] saturation > % on room air)
Subjects must have adequate lung function to permit surgical resection determined by pre-enrollment pulmonary function tests to include diffusion capacity of the lung for carbon monoxide (DLCO) as follows:\r\n* DLCO >= % predicted OR DLCO < % but >= % with an oxygen consumption (VO) max >=  L/min/kg (assessed by cardiopulmonary exercise testing) or  minute walk test >=  meters\r\n* Subjects with a DLCO < % are excluded from this study\r\n* Subjects must have a baseline oxygen (O) saturation by pulse oximetry that is >= % both at rest and while walking, off supplemental oxygen
Pulmonary: For patients > . years of age: Diffusing capacity of the lung for carbon monoxide (DLCO) (corrected/adjusted for hemoglobin) > % and forced expiratory volume in one second (FEV) > % predicted (without administration of bronchodilator) and forced vital capacity (FVC) > % predicted. For patients < . years of age unable to perform pulmonary function tests (PFT) due to age or developmental ability: () no evidence of dyspnea at rest and () no need for supplemental oxygen and () O saturation > % on room air at sea level (with lower levels allowed at higher elevations per established center standard of care (e.g., Utah, , feet above sea level, does not give supplemental oxygen unless below %)).
Pulmonary function tests: diffusing capacity of the lungs for carbon monoxide (DLco) (corrected for hemoglobin) and forced expiratory volume in  second (FEV) >= % of predicted for the MAC arm, >= % of predicted for the RIC and RIC-MMF arm, and >= % predicted for the IOC arm; or in pediatric patients, if unable to perform pulmonary function tests, there should be no evidence of dyspnea at rest, no requirement for supplemental oxygen, and oxygen saturation > % on room air; calculations will be based on the Unites States of America National Institutes of Health (USA-ITS-NIH) reference
Patients without respiratory symptoms (e.g. dyspnea at rest, known requirement for supplemental oxygen therapy) and who have an oxygen saturation > % on room air, will be eligible; for patients not meeting this criteria, pulmonary function tests will be performed to confirm that the diffusion capacity of the lung for carbon monoxide (DLCO)/alveolar volume (VA)/Adj is % of the normal predicted value corrected for hemoglobin and alveolar volume in order to meet eligibility\r\n* (For children who are unable to cooperate for pulmonary function test [PFT]s, the criterion is: No evidence of dyspnea at rest, no exercise intolerance and no requirement for supplemental oxygen therapy)
Diffusing capacity of the lung for carbon monoxide (DLCO) corrected < %; patients who are unable to perform pulmonary function tests (for example, due to young age and/or developmental status) will be excluded if the oxygen (O) saturation is < % on room air
DLCO corrected < %; patients who are unable to perform pulmonary function tests (for example, due to young age and/or developmental status) will be excluded if the O saturation is < % on room air; patients with a DLCO -% must also have a partial pressure of oxygen (pO) of >  mmHg
Patients with impaired pulmonary function as evidenced by diffusion capacity of the lung for carbon monoxide (DLCO) < % of predicted (or, if unable to perform pulmonary function tests, then oxygen [O] saturation < % on room air)
Pulmonary function\r\n* Baseline oxygen saturation > % on room air at rest \r\n* Patients with respiratory symptoms must have a diffusing capacity of the lungs for carbon monoxide (DLCO)/adjusted > %; for children who are unable to cooperate for pulmonary function tests (PFTs) they must not have dyspnea at rest or known requirement for supplemental oxygen
For patients <  years of age unable to perform pulmonary function tests (PFTs) due to age or developmental ability: () no evidence of dyspnea at rest and () no need for supplemental oxygen and () oxygen (O) saturation > % on room air
Oxygen saturation >= % on room air and adjusted diffusing capacity of the lungs for carbon monoxide (DLCO) of at least %
Must have a minimum level of pulmonary reserve defined as =< grade  dyspnea, pulse oxygen > % on room air, and carbon monoxide diffusing capability test (DLCO) >= % (corrected for anemia)
Diffusion capacity of the lung for carbon monoxide (DLCO) >= % predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, the O saturation > % on room air
Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol\r\n* Significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, diffusing capacity of the lung for carbon monoxide (DLco), oxygen (O) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates
Diffusing capacity of the lung for carbon monoxide (DLCO) equal or greater than % predicted corrected for hemoglobin; for children =<  years of age who are unable to perform pulmonary function tests (PFT), oxygen saturation >= % on room air by pulse oximetry
Adequate pulmonary function defined as absence of oxygen (O) requirements and one of the following:\r\n* Diffusion lung capacity for carbon monoxide (DLCO) corrected >= % mm Hg\r\n* DLCO corrected between % - % mm Hg and partial pressure of oxygen (pO) >=  mm Hg\r\n* DLCO corrected between % - % mm Hg and pO >=  mm Hg\r\n* Pediatric patients unable to perform pulmonary function tests must have O saturation > % on room air; may not be on supplemental oxygen
Pulmonary: diffusing capacity of the lung for carbon monoxide (DLCO) > % predicted, and absence of oxygen (O) requirements; for children that are not able to cooperate with pulmonary function tests (PFTs), a pulse oximetry with exercise should be attempted; if nether test can be obtained it should be clearly stated in the physicians note
Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol\r\n* Significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, carbon monoxide diffusing capacity (DLco), oxygen (O) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates
Within  days of study registration ( days for pulmonary and cardiac): oxygen saturation >= % on room air with no symptomatic pulmonary disease. If symptomatic or prior known impairment single breath carbon monoxide diffusing capacity (DLCOc) or >= %.
TREATMENT: Patients with current or a history of interstitial lung disease, known severely impaired lung function (spirometry and carbon monoxide diffusing capability test (DLCO) % or less of normal and oxygen [O] saturation % or less at rest on room air) or non-infectious pneumonitis will not be assigned treatment with everolimus or trametinib DMSO; symptoms should have resolved and course of antibiotics been completed for patients with a history of infectious pneumonitis to be eligible
Known severely impaired lung function (spirometry and diffusing capacity of the lung for carbon monoxide [DLCO] % or less of normal and oxygen [O] saturation % or less at rest on room air)
With impaired pulmonary function as evidenced by partial pressure of oxygen (pO) <  mm Hg and carbon monoxide diffusing capability test (DLCO) < % of predicted or pO <  mm Hg and DLCO < % of predicted; (or, for pediatric patients unable to perform pulmonary function tests, then oxygen (O) saturation < % on room air), or receiving supplementary continuous oxygen
Severely impaired lung function as defined as spirometry and DLCO (corrected for Hgb)\n             that is <% of the normal predicted value and/or O saturation <% at rest on room\n             air.
Diffusing capacity of the lung for carbon monoxide (DLCO) >= % of the expected value corrected for alveolar volume and hemoglobin (hgb) for reduced intensity transplant and DLCO >= % for myeloablative regimen; for children who are unable to cooperate for pulmonary function tests (PFTs), the criterion is, no evidence of dyspnea at rest, no exercise intolerance, and no requirement for supplemental oxygen therapy
Severely impaired lung function as defined as spirometry and diffusing capacity of the lungs for carbon monoxide (DLCO) that is < % of the normal predicted value and/or oxygen () saturation that is % or less at rest on room air
Normal pulmonary function tests (including diffusing capacity of the lungs for carbon monoxide [DLCO]) if there is clinical indication for determination (e.g. dyspnea at rest, known requirement for supplemental oxygen); Note: for patients who do not have respiratory symptoms or requirement for supplemental oxygen, pulmonary function tests (PFTs) are NOT required
Diffusing capacity for carbon monoxide (DLCO) >= % predicted corrected for hemoglobin; for children =<  years of age who unable to perform the pulmonary function test, an oxygen (O) saturation of >= % on room air
Patients must not have any known uncontrolled underlying pulmonary disease or severely impaired lung function (spirometry and diffusing capacity of the lung for carbon monoxide [DLCO] % or less of normal and oxygen [O] saturation % or less at rest on room air)
Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection; uncontrolled hypertension) that could cause unacceptable safety risks or compromise compliance with the protocol\r\n* Significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, diffusion capacity of the lung for carbon monoxide (DLco), oxygen (O) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates
Patients who can perform pulmonary function tests will be excluded if they have a diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) of < % predicted; patients who are unable to perform pulmonary function tests (for example, due to young age and/or developmental status) will be excluded if the oxygen (O) saturation is < % on room air
Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol\r\n* Significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, diffusing capacity of the lung for carbon monoxide (DLCO), oxygen (O) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates
Pulmonary function test (PFT) demonstrating a diffusion capacity of least % predicted; for children =<  years of age who are unable to perform PFT, oxygen saturation >= % on room air by pulse oximetry
Oxygen saturation >= % on room air and diffusing capacity of the lung for carbon monoxide corrected (DLCOcor) >= %
Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol\r\n* Significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, diffusing capacity of the lung for carbon monoxide (DLco), oxygen () saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates
Pulmonary function - diffusion capacity of at least % predicted; children unable to perform pulmonary function tests (e.g. less than  years old) pulse oximetry of >= % on room air
Patients must also have a resting multi gated acquisition scan (MUGA) (preferred) or echocardiogram (ECHO) and pulmonary function tests (PFTs) with diffusing capacity of the lung for carbon monoxide (DLCO) performed before transplant and found to be acceptable according to the treating institutions guidelines; recommended minimum standards include an ejection fraction (EF) greater than % and corrected DLCO greater than % for this less toxic regimen; if lower than this, single patient exemption may be sought
Pulmonary function test demonstrating a diffusion capacity of least % predicted (myeloablative regimen , reduced intensity regimen ) or at least % predicted (nonmyeloablative regimen ); for children <  years of age who are unable to perform pulmonary function test (PFT), oxygen saturation > % on room air by pulse oximetry
Severe pulmonary dysfunction with a hemoglobin corrected DLCO < % or FVC < % of predicted or O saturation < % at rest without supplemental oxygen
FEV, FVC > % of predicted; Note: If unable to perform pulmonary tests, then O saturation > % on room air.
Significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, diffusing capacity of the lung for carbon monoxide (DLco), oxygen (O) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates
Clinically significant pulmonary symptoms and signs, any active pulmonary or respiratory infection at enrollment, pulmonary infiltrates on screening CT scan of the chest that are associated with symptoms (including dyspnea), resting or exercise arterial oxygen saturation (SpO) less than (<)  percent (%), requirement for supplementary oxygen at rest or exercise (either continuously or intermittently), moderate (%-% predicted) or severe (<% predicted) decreased diffusing capacity for carbon monoxide (DLCO) or mild (>% </= lower limit of normal [LLN]% predicted) decrease with clinically significant symptoms
Pulmonary function test (PFT) demonstrating a diffusion capacity of least % predicted; for children =<  years of age who are unable to perform PFT, oxygen saturation >= % on room air by pulse oximetry
Diffusing capacity of the lungs for carbon monoxide (DLCO) >= % predicted corrected for hemoglobin; for pediatric patients, if unable to perform pulmonary function, >= % oxygen saturation with pulse oximetry
Impaired lung function: O saturation % or less at rest on room air by pulse oximetry; if O saturation is =< % at rest, further pulmonary function tests (PFTs) should be ordered to confirm normal pulmonary function and eligibility
Carbon monoxide diffusing capability test (DLCO) > % predicted and in children- room air oxygen saturation > %
Subjects with adequate physical function as measured by:a)Cardiac: Left ventricular ejection fraction at rest must be >%, or shortening fraction > %. b)Hepatic: Bilirubin < . mg/dL; and ALT, AST, and Alkaline Phosphatase <  x ULN. c)Renal: Serum creatinine within normal range for age, or creatinine clearance or GFR >  mL/min/.m. d)Pulmonary: FEV , FVC, DLCO (diffusion capacity) > % predicted (corrected for hemoglobin); or  saturation > % on room air.
Known severely impaired lung function (spirometry and DLCO % or less of normal and O saturation % or less at rest on room air)