High Dose Re-Irradiation Utilizing Advanced Deformable Image Registration (DIR) and Individualized Organ At Risk (OAR) Dose Calculations With Organ Specific Toxicity Analysis

Inclusion Criteria:

1. Provision of signed informed consent
2. Patients ≥18 years of age receiving definitive or postoperative high dose radiation to volume that includes overlap with previously irradiated OAR(s).
3. Prior radiation dosimetry must be available.
4. Participants must have stage I-IV biopsy proven solid malignancy (histologic proof or unequivocal cytologic proof solid tumor malignancy from either the primary or any metastatic site). Documentation of pathology reports are required. Local review of pathology or cytology is at the discretion of the multidisciplinary team.
5. Histologic confirmation of target lesion recurrence is recommended.
6. Documentation of consensus for recommendation of reirradiation by multidisciplinary team and location of target lesion or postoperative site to be treated.
7. Documentation of whether or not concurrent cancer therapy drugs are recommended and rationale.
8. Documentation of rationale for not obtaining tissue confirmation of the target lesion, if applicable.
9. Baseline target lesion imaging with CT, positron emission tomography (PET) /CT, or MRI is required within six weeks of trial enrollment. CT or MRI simulation scans may be used for baseline imaging.
10. Patients who have had disease resected in a previously irradiated field and are at high pathological and clinical risk for recurrence as defined by the treating Radiation Oncologist and multidisciplinary team, are eligible for study.
11. Measurable disease is not required for patients being treated postoperatively.
12. Baseline labs are per standard practice. Values will be dependent on the OARs being treated. (Per standard practice, radiation therapy volumes to OARs are modified to accommodate compromised renal, liver, pulmonary or other OAR function). Recommended labs and values include:

    * Aspartate transaminase (AST) and alanine transaminase (ALT) \< 2.5 x upper limit of normal (ULN) or \< 5 x ULN with metastatic liver disease.
    * Total bilirubin \< 1.5 x ULN
    * Absolute neutrophil count (ANC) \> 500 cells/mm\^3
    * Platelets \> 50,000 cells/mm\^3
    * Creatinine \< 1.5 x ULN or Creatinine clearance \> 45 mL/min if creatinine is \> 1.5 x ULN (calculated Creatinine Clearance (CrCl) based on Cockcroft-Gault equation)
13. Eastern Cooperative Oncology Group (ECOG) Performance Score 0-2.
14. Patients must have resolution of acute toxic effect(s) of most recent cancer therapy to Grade 1 or 2.
15. Life expectancy of at least 6 months.
16. Female patients of childbearing potential must have negative urine or serum pregnancy test within 7 days prior to start of re-irradiation.
17. Ability to complete the self-reported questionnaires (translations will be made available if the patient's primary language is not English).
18. Concurrent participation on pharmaceutical, investigator-initiated, National Clinical Trials Network (NCTN), or other multisite clinical trials that include re-irradiation is allowed.

Exclusion Criteria:

1. Patients receiving low dose radiation for symptom management only.
2. Patients with evidence of severe or uncontrolled systemic conditions.
3. Life expectancy of less than 6 months.
4. ECOG Performance status ≥ 3.
5. Women of childbearing potential who are known to be pregnant or are unwilling to use an acceptable method of contraception from the time of informed consent until completion of the course of radiotherapy