Stereotactic Magnetic Resonance-Guided Adaptive Radiation Therapy with or without AGuIX for the Treatment of Central Lung Tumors and Locally Advanced Pancreatic Ductal Adenocarcinoma

Inclusion Criteria

• Patients should have clinical, radiographical, cytological, or histological confirmation of non-small cell lung carcinoma (NSCLC) or lung or nodal metastases from another primary cancer that has a central location defined as within or touching the zone of the proximal bronchial tree, defined as a volume 2 cm in all directions around the trachea and proximal bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus right and left lower lobe bronchi). Tumors that are immediately adjacent (< 1 cm) to mediastinal or pericardial pleura or other radiation-sensitive organs such as the esophagus and brachial plexus also are considered central tumors and are eligible for this protocol. * Eligible NSCLC patients must have no evidence of nodal involvement (N0) or metastatic disease, and disease has to be determined unresectable by a thoracic oncologist or the patient is medically inoperable
• OR histologically or cytologically confirmed pancreatic ductal adenocarcinoma of the pancreatic head, body or tail. * Locally advanced, unresectable pancreatic cancer as determined by a pancreaticobiliary surgeon as part of a multidisciplinary discussion at the investigative site, including multi-phasic computed tomography (CT) demonstrating tumor abutment of the superior mesenteric artery (SMA) or celiac axis, superior mesenteric vein (SMV) or portal vein (PV) involvement which is not resectable without vascular reconstruction * Completion of at least 3 months of standard induction chemotherapy for LAPC, which should consist of either fluorouracil, irinotecan, leucovorin and oxaliplatin (FOLFIRINOX), gemcitabine and nab-paclitaxel, or another standard combination of induction chemotherapy agent, with a washout period no longer than 10 weeks prior to first dose of study drug * No evidence of distant metastasis
• Participants must have measurable disease, defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan, MRI, or calipers by clinical exam
• Pancreatic or central lung tumor size =< 5 cm in axial dimension
• Age 18 years or older
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Ability to understand and follow the breathing instructions involved in the respiratory gating procedure
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Platelets >= 75,000/mcL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/Alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (ULN)
• Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal
• The effects of AGuIX on the developing human fetus are unknown. For this reason, as well as the known teratogenic effects of radiation, women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Participants who have had prior radiation therapy to the chest or abdomen that would overlap with the current treatment field
• Participants who are receiving any other investigational agents
• Participants with known metastatic disease (lung cohort patients with metastatic disease undergoing stereotactic body radiation therapy [SBRT] are eligible)
• History of allergic reactions attributed to gadolinium-based IV contrast
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because AGuIX is contrast agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AGuIX, breastfeeding should be discontinued if the mother is treated with AGuIX.
• Severe claustrophobia or anxiety
• Known human immunodeficiency virus (HIV)-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AGuIX. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
• Active duodenal or gastric ulcer disease or evidence of tumor invasion of the bowel or stomach based on endoscopy.
• Presence of a duodenal stent
• Unable to undergo magnetic resonance imaging (MRI) due to any of the following: * Presence of MRI-incompatible metal material or devices in the human body * MRI-incompatible Pacemaker or defibrillator * Insulin pump * Aneurysm clip * Artificial heart valve * Cochlear implant * Shrapnel or gunshot injury * Cataract surgery with implant unsafe for MRI