Background:
* Although surgical resection is the treatment of choice in participants with localized or regionalized primary and recurrent abdominal adrenocortical carcinoma (ACC), loco-regional recurrence following complete resection of ACC occurs in 50-80% of the participants, most commonly in the first five years postoperatively.
* Retrospective single institutional series report improvement in local control with postoperative adjuvant radiotherapy (RT) in selected participants with ACC.
* Preoperative RT is used in several abdominal and retroperitoneal malignancies to improve local control. There is no prospective data available for the use of this treatment approach for participants with resectable ACC.
* We hypothesize that preoperative RT alone is safe and can result in a lower loco-regional recurrence in participants with resectable recurrent ACC with no peritoneal carcinomatosis. Thus, this phase I dose-escalation trial aims to evaluate the safety and feasibility of preoperative RT in participants with resectable recurrent ACC.
* Health-related quality of life (QOL) is a well-accepted tool to measure the outcome of cancer treatments. SF-36 V1 questionnaire has been frequently used to evaluate the QOL in participants with cancer. There is no study evaluating the difference in QOL in participants with resectable recurrent ACC undergoing preoperative RT and surgery.
Objectives:
-To determine the maximum tolerated dose and the safety and toxicity profile of preoperative external beam RT with or without standard of care mitotane, before surgical resection in participants with resectable ACC
Eligibility:
* Age \>= 18 years
* Pathological confirmation of ACC with clinical evidence of abdominal recurrence
* ECOG 0-2
* Surgically resectable disease at presentation with no or limited extra-abdominal disease and without ACC peritoneal carcinomatosis based on a diagnostic laparoscopy at screening.
* The last dose of chemotherapy treatment except for mitotane more than 4 weeks prior to starting treatment with this protocol, and participants must have recovered from chemotherapy.
* No prior abdominal RT
* No contraindication to abdominal RT
Design:
* This study will enroll up to 24 evaluable participants as follows:
* Participants will be enrolled in Cohort 1 or 2 based on mitotane use or serum level. Up to 6-18 evaluable participants per these cohorts (i.e., resectable ACC with and without mitotane use) will be enrolled to assess the safety of 3-level dose-escalating preoperative RT.
* Participants will be enrolled in Cohort 3 regardless of mitotane use or serum level, and will only start enrollment when we observe no DLTs in \> 1 participant in Cohort 1 at Dose Level 1. Up to 12 evaluable participants will be enrolled in this cohort.
* Preoperative assessment of QOL using a standardized questionnaire (SF-36 V1) will be obtained at baseline.
* Participants will be treated with preoperative RT, followed by a planned surgical resection, 4 weeks after the completion of RT.
* A standard "3 + 3" design will be used to determine the MTD of dose-escalated RT, with 3 dose levels (DL1- 30 Gy delivered in 10 fractions, DL2-36 Gy in 12 fractions, DL3-42 Gy in 14 fractions).
* Postoperative surveillance imaging studies and laboratory tests will be performed every 3 months in the first 3 years, then every 6 months thereafter in years 4-10. FDG-PET scan will be performed every 6 months postoperatively in the first 3 years, then every year in years 4-10. Additional assessments may be performed if clinically indicated.
