∙ Patients should have clinical, radiographical, cytological, or histological confirmation of NSCLC or lung or nodal metastases from another primary cancer 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.

∙ OR Histologically or cytologically confirmed pancreatic ductal adenocarcinoma of the pancreatic head, body or tail.

• 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. See Section 11 for the evaluation of measurable disease.

∙ Eligible NSCLC patients must have no evidence of nodal involvement (N0), and disease has to be determined unresectable by a thoracic oncologist or the patient is medically inoperable.

• Locally advanced, unresectable pancreatic cancer as determined by a pancreaticobiliary surgeon as part of a multidisciplinary discussion at the investigative site, including multi-phasic CT demonstrating tumor abutment of the SMA or celiac axis, SMV or 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 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.

• Pancreatic or central NSCLC size ≤ 5cm.

• Age 18 years or older.

• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).

• Ability to understand and follow the breathing instructions involved in the respiratory gating procedure.

• Participants must have normal organ and marrow function as defined below:

‣ absolute neutrophil count ≥1,500/mcL

⁃ platelets ≥100,000/mcL

⁃ total bilirubin within normal institutional limits

⁃ AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

⁃ creatinine within normal institutional limits OR

• Creatinine clearance ≥60 mL/min/1.73 m2 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.