In this study the investigators will study the effects of neoadjuvant radiation therapy (RT), in the form of either proton therapy or stereotactic body radiation therapy (SBRT), on the Circulating tumor DNA (ctDNA), radiographic changes and radiomics, and the validity of these findings will be compared using the current gold standard- pathologic findings. The purpose of this work is to explore whether the biomarkers may be used diagnostically to better understand radiographic changes following RT. The investigators hypothesize that ctDNA levels in combination with imaging biomarkers identified through radiomics will be a sensitive and specific tool for predicting histopathologic response to RT.

Inclusion Criteria:

• Age ≥18 years
• Histologically proven chordoma of the skull base, spine, or sacrum (coccyx lesions are eligible).
• Radiographic evidence of spinal sacral chordoma is required and may be obtained from computed tomography imaging and/or magnetic resonance imaging. Other studies may be used with principal investigator approval.

Note: Patients enrolled in Dr. Chetan Bettegowda's J1576 study, (IRB00075499) may be considered eligible for this trial. The J1576 study enrolls patients who have been diagnosed with Chordoma. Prior to enrollment, all patients must be consented specifically for participation in this Chordoma study (IRB00291203).

• Treating physician must deem that neoadjuvant proton therapy or SBRT is appropriate treatment for the chordoma.
• Surgical resection with curative intent must be planned.
• The patient must have a Karnofsky Performance Score of 40 or greater.
• If a woman is of child-bearing potential, a negative urine or serum pregnancy test must be demonstrated prior to treatment. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation and for up to 12 weeks following the study. Should a woman become pregnant or suspect she is pregnant while participating in this study she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Prior radiation or radiosurgery to the involved level of the spine.
• Patients with metastatic disease will be excluded.
• Prior malignancies are excluded except for adequately treated basal cell or squamous cell skin cancer, cervical carcinoma in situ, or other cancer from which the patient has been disease free for at least 1 year.
• Patients with 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 will be excluded.
• Pregnant women are excluded. Women of child-bearing potential who are unwilling or unable to use and acceptable method of birth control to avoid pregnancy for the entire study period and up to 12 weeks after the study are excluded. Male subjects must also agree to use effective contraception for the same period as above.

Potential participants who are clinical patients of the PI or co-investigators may be identified during chart review in advance of a routine clinic visit or during a routine clinic visit with a provider.

Patients who are enrolled in IRB: IRB00075499 (PI: Dr. Chetan Bettagowda) may be eligible for this trial as well. Once identified as a potential study participant, the study team for this ctDNA study would have to confirm eligibility as for any potential participant.

In addition, potential participants may contact the study team directly.

Some of these potential participants may also be identified during the multidisciplinary clinic as part of the standard clinic case review process.