AI-guided radiation therapy for lung tumors

Inclusion Criteria:

* Patients with radiographic findings consistent with lung cancer or solitary or oligometastatic disease in the lung. Most patients will have primary non-small cell lung cancer. For primary lung cancers, we include lesions with ground glass opacities with a solid component of 50% or greater. Patients with solitary or oligo-metastatic disease in the lung may have any other histology or cancer type.
* Patients must have radiographically measurable or evaluable disease per RECIST v. 1.1.
* Patients must be age \>= 18 years.
* Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
* Patients of child-bearing potential (POCBP) must have a negative urine or serum pregnancy test prior to registration on study.

  * NOTE: A POCBP is any person with an egg-producing reproductive tract (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

    * Has not undergone a hysterectomy or bilateral oophorectomy
    * Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \> 12 months)
* Radiation therapy is known to be teratogenic. Patients of child-bearing potential (POCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from time of informed consent, for the duration of study participation, and for 7 days following completion of therapy. Should a patient become pregnant or suspect they are pregnant while they or their partner are participating in this study, they should inform their treating physician immediately. People who can impregnate their partners treated or enrolled on this protocol must also agree to use adequate contraception from time of informed consent, for the duration of study participation, and 90 days after completion of administration.
* Patients must have the ability to understand and the willingness to sign a written informed consent document. Informed consent must be signed prior to registration on study.

Exclusion Criteria:

* Patients who have had prior radiotherapy with radiation field overlap.
* For primary lung cancers, patients with ground glass opacities without a solid component will be excluded.
* Patients who have not recovered from adverse events confined to the thorax (i.e. pneumonitis, bronchial insufficiency, bronchial hemorrhage, esophagitis) due to prior anticancer therapy (i.e., have residual toxicities \>= grade 2) with the exception of alopecia. low blood counts (neutropenia, anemia, etc), or anatomically distinct toxicities (i.e. cystitis).
* Patients who are receiving any other concurrent investigational agents or genotoxic chemotherapy for cancer treatment.

  * Note: Patients receiving targeted therapies are permitted to enroll on the study. However, patients must pause treatment with targeted therapy 3 days prior to SBRT and restart medication at least 2 days after SBRT. Concurrent immunotherapy (if not investigational) is permitted. Coronavirus disease 2019 (COVID-19) vaccinations are allowed.
* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:

  * Ongoing or active infection requiring systemic treatment
  * Unstable angina pectoris
  * Stage 3 or greater idiopathic pulmonary fibrosis
  * Cardiac arrhythmia
  * Psychiatric illness/social situations that would limit compliance with study requirements
  * Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
* Female patients who are pregnant or nursing. Pregnant women are excluded from this study because radiation therapy has teratogenic or abortifacient effects.