Daily Adaptive Radiation Therapy an Individualized Approach for Carcinoma of the Cervix

Inclusion Criteria:

1. Patients must have histologically confirmed, newly diagnosed advanced cervicalcancer (squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma):FIGO 2018 clinical stages IB2-IVA, without involved paraaortic lymph nodes.

2. For patients with involved pelvic lymph nodes, the upper border of the CTV nodalvolume may not extend above the confluence of the common iliac arteries with theaorta (i.e., aortic bifurcation).

3. Patients must NOT have had a hysterectomy.

4. Pelvic nodal status is to be confirmed by one or more of the followingstudies/procedures: PET/CT scan, CT scan, MR Scan, fine needle biopsy, extraperitoneal biopsy or laparoscopic biopsy, per institutional standard of care.

5. Patients must be planning to undergo concurrent pelvic radiation and chemotherapy.

6. ECOG performance status ≤ 2 (Karnofsky ≥60%).

7. Patient must be willing and able to complete the PRO-CTCAE, EQ-5D, EPIC and EORTCquestionnaires as described in the study protocol.

8. Patient must have normal organ and marrow function as defined below:

• leukocytes ≥ 2,500/mcL

• absolute neutrophil count ≥ 1,500/mcL

• platelets ≥ 100,000/mcL

• hemoglobin ≥ 8 g/dL (can be transfused with red blood cells pre-study)

• total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)

• AST(SGOT)/ALT(SGPT) ≤ 3 × ULN

• alkaline phosphatase ≤ 2.5 × ULN

• creatinine < 1.5 mg/dL to receive weekly cisplatin*

• Patients whose serum creatinine is between 1.5 and 1.9 mg/dL are eligiblefor cisplatin if there is no hydronephrosis and the estimated creatinineclearance (CCr) is >30 ml/min. For the purpose of estimating the CCr, theformula of Cockcroft and Gault for females should be used:CCr=(0.85 ×(140-age)×IBW)/((Scr×72)) where age is the patient's age in years (from 20 to 80 years), Scr is the serum creatinine in mg/dL, and IBW is theideal body weight in kg (according to the calculation IBW = 45.5 kg + 2.3kg for each inch over 5 feet).

9. Age ≥ 18 years (or meets local age of consent).

10. Study participant is already intending to be prescribed a standard of care cisplatintreatment regimen.

11. Ability to understand and the willingness to sign a written informed consentdocument.

Exclusion Criteria:

1. Prior radiation therapy to the pelvis or abdominal cavity, para-aortic lymph glands (PALN) radiation, or previous therapy of any kind for this malignancy.

2. Patients with PALN nodal metastasis.

3. Patients who have undergone staging pelvic and/or paraaortic lymphadenectomy.

4. Prior allogeneic bone marrow transplantation or prior solid organ transplantation.

5. Prior systemic anticancer therapy due to a diagnosis of cancer (e.g., chemotherapy,targeted therapy, immunotherapy) within 3 years prior to entering the study.

6. Patients diagnosed on imaging or biopsy with a synchronous primary malignancy (withthe exception of DCIS of the breast, or early stage basal cell carcinoma of theskin).

7. Patients with a history of inflammatory bowel disease, including ulcerative colitisand Crohn's Disease.

8. Patients with a history of other symptomatic autoimmune disease: rheumatoidarthritis, systemic progressive sclerosis (scleroderma), systemic lupuserythematosus, autoimmune vasculitis (e.g., Wegener's Granulomatosis); CNS or motorneuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome andMyasthenia Gravis, multiple sclerosis.).

9. Patients with active tuberculosis (TB).

10. Patients who are pregnant.

11. Patients who are actively breastfeeding (or who do not agree to discontinuebreastfeeding before the initiation of protocol therapy).

12. Patients who are of child-bearing potential who do not agree to use birth control (for a minimum of 14 months after the last dose of cisplatin) in accordance withinstitution's standard of care.

13. Patients with a prior known history or current diagnosis of a vesicovaginal,enterovaginal, or colovaginal fistula.

14. Patients who undergo a pelvic or para-aortic lymph node dissection prior to plannedchemoradiation therapy.

15. Patients with known active infection of HIV.

16. Patients with hip prosthetics