Radiation Biology

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SU_38_2381 - Immuno-profile of a phase II clinical trial utilizing preoperative stereotactic radiosurgery followed by surgery in cancer patient with metastatic lesions in the brain

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Immuno-profile of a phase II clinical trial utilizing preoperative stereotactic radiosurgery followed by surgery in cancer patient with metastatic lesions in the brain
U. K. Iheagwara1,2, K. Holeva1, C. J. Bakkenist1, J. Shogan1, J. Engh3, N. Amankulor3, and D. A. Clump II1; 1UPMC Hillman Cancer Center, Department of Radiation Oncology, Pittsburgh, PA, 2University of Pittsburgh School of Medicine, Pittsburgh, PA, 3UPMC Hillman Cancer Center, Department of Neurosurgery, Pittsburgh, PA

Purpose/Objective(s): Metastatic disease to the brain is a common cause of death in cancer patients. Various treatment modalities have been deployed in efforts to improve local control and overall survival. Interestingly, stereotactic radiosurgery (SRS) has also been shown to promote Th1 lymphocyte mediated immune responses which could aid in improving local control. We therefore investigated the impact and influence of SRS in shaping the immuno-profile of peripheral blood mononuclear cell (PBMC) percentages post SRS/prior to surgical resection for the initial six patients enrolled in our phase II study investigating brain metastasis treated with pre-operative SRS followed by surgical resection.

Materials/Methods: A phase II institutional non-randomized clinical trial was initiated enrolling patients with metastatic disease to the brain of any tissue histology (except lymphoma, leukemia, multiple myeloma, or germ cell tumor) to receive SRS followed by surgical resection. Inclusion criteria include ≥18yo, KPS>/=50 with a life expectancy of 12 weeks. These patients must have no more than four lesions measuring 1.5-4.0cm in size. If tumors are smaller than 3cm, the patient must be symptomatic to enroll. Patients were then selected to receive 15Gy, 18Gy, or 24Gy, based on tumor size. All patients were then to undergo surgical resection within seven days of SRS. Each patient had post-SRS/pre-surgical resection blood draws. PBMC samples were subsequently separated, immunostained with various antibodies staining for T-regulatory cells (T-regs), T-effector cells (T-eff), Myeloid derived suppressor cells (MDSCs), and T-cells functionality.

Results: Eight patients were treated with pre-operative SRS. If tumors were <2cm, 2.1-3cm, 3.1-4cm, patients received 24Gy, 18Gy and 15Gy respectively. Two patients received 15Gy and the remaining four received 18Gy. Five of six patient had lesions involving the frontal or parietal lobes. The initial six enrolled patients (2 breast, two rectal, one colon, and one renal cell carcinoma) had their PBMCs analyzed via flow cytometry. Surgery was completed on average within 2.5days of SRS treatment. Three normal healthy donor controls were directly compared to patient PBMC samples. Below are their reported flow cytometry mean percentages: CD3+/CD4+: 38.1→19.9%, CD3+CD8+: 35.5→21.8%, circulating T-regs 0.2→0.6%, Cytotoxic T Lymphocytes (CTL) (CD3+CD8+Granzyme B+ IFN-g-): 52.8→54% of the CD3/CD8+ cell population, effector CD4 (CD3+CD4+INF-g+Granzymbe B-): 5.5→0.2% of the CD3/CD4+ cell population.

Conclusion: Stereotactic radiosurgery appears to have decreased the total percentage of CD4 and CD8+ T cells. However, T-regs were decreased as well. CD4 effector function seems to be dampened however CTL activity appears to be intact after SRS. Further studies on the immune response post SRS prior to surgery may lead to the correct prediction of patient who will have good local or lead to the development of new strategies aimed at optimizing the immune response.

Author Disclosure: U.K. Iheagwara: None. K. Holeva: None. J. Engh: None. N. Amankulor: None. D.A. Clump: None.

Uzoma Iheagwara, MD, PhD

Biography:
Uzoma K. Iheagwara MD, PhD. PGY-4. UPMC Hillman Cancer Center

HIgh School: Phillips Academy, Andover
College: University of Maryland, Baltimore County. Meyerhoff Scholar Program, MARCUSTAR Scholar
Medical School: University of Pittsburgh School of Medicine
Graduate School: University of Pittsburgh School of Medince. PhD: Cancer Immunology. Thesis Advisor: Olivera J. Finn PhD
UNCF MERCK Gradute Fellow
Residentcy: UPMC Hillman Cancer Center, Radiation Oncology
Email: iheagwarauk2@upmc.edu

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