Peter Fecci

Overview:

As the Director of both the Brain Tumor Immunotherapy Program and the Center for Brain and Spine Metastasis at Duke University, I focus our programmatic interests on the design, optimization, and monitoring of immune-based treatment platforms for patients with intracranial tumors, whether primary or metastatic. Within this broad scope, however, my own group looks more specifically at limitations to immunotherapeutic success, with a particular focus on understanding and reversing T cell dysfunction in patients with glioblastoma (GBM) and brain metastases. We employ a systematic approach to categorizing T cell dysfunction (Woroniecka et al, Clin Cancer Res 2018 Aug 15;24(16):3792-3802), and whereas our earlier work addressed concerns for regulatory T cell-induced tolerance, we now heavily study T cell ignorance and exhaustion, as well. Regarding the former, we recently published the novel phenomenon of S1P1-mediated bone marrow T cell sequestration in patients with intracranial tumors (Chongsathidkiet et al, Nat Medicine 2018 Sep;24(9):1459-1468). Regarding the latter, we have likewise recently identified and characterized exhaustion as a significant limitation to T-cell function within GBM (Woroniecka et al, Clin Cancer Res 2018 Sep 1;24(17):4175-4186). I very much look to collaboratively integrate our approaches with others investigating innovative treatment options. I continue my focus on combining strategies for reversing T cell deficits with current and novel immune-based platforms as a means of deriving and improving rational and precise anti-tumor therapies. It is my sincerest desire to forge a career focused on co-operative, multi-disciplinary, organized brain tumor therapy. Ultimately, my goal is to help coordinate the efforts of a streamlined and effective center for brain tumor research and clinical care. I hope to play some role in ushering in a period where the science and treatment arms of brain tumor therapy suffer no disjoint, but instead represent the convergent efforts of researchers, neuro-oncologists, medical oncologists, radiation oncologists, biomedical engineers, and neurosurgeons alike. I hope to see such synergy become standard of care.

Positions:

Associate Professor of Neurosurgery

Neurosurgery
School of Medicine

Associate Professor of Biomedical Engineering

Biomedical Engineering
Pratt School of Engineering

Associate Professor in Immunology

Immunology
School of Medicine

Associate Professor in Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2007

Duke University School of Medicine

Ph.D. 2007

Duke University

Internship, General Surgery

Massachusetts General Hospital

Residency, Neurosurgery

Massachusetts General Hospital

Postdoctoral Fellow

Dana-Farber Cancer Institute

Instructor, Neurosurgery

Massachusetts General Hospital

Grants:

Laser Ablation of Abnormal Neurolgoical Tissue using Robotic Neuroblate System (LAANTERN) Prospective Registry

Administered By
Neurosurgery
Awarded By
Monteris Medical, Inc.
Role
Principal Investigator
Start Date
End Date

NINDS Research Education Programs for Residents and Fellows in Neurosurgery

Administered By
Neurosurgery
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

LITT and Short Course Radiation for Patients with GBM Requiring Standard Treatment Alternatives (LASR)

Administered By
Duke Cancer Institute
Awarded By
Monteris Medical, Inc.
Role
Principal Investigator
Start Date
End Date

Directed Chemotherapy Delivery for Leptomeningeal Metastases

Administered By
Neurosurgery
Awarded By
Minnetronix, Inc
Role
Co Investigator
Start Date
End Date

Validation of Novel Therapeutic Approach for Leptomeningeal Metastases

Administered By
Neurosurgery
Awarded By
Minnetronix, Inc
Role
Co Investigator
Start Date
End Date

Publications:

Outcomes in Patients With 4 to 10 Brain Metastases Treated With Dose-Adapted Single-Isocenter Multitarget Stereotactic Radiosurgery: A Prospective Study.

PURPOSE: To examine the effectiveness and safety of single-isocenter multitarget stereotactic radiosurgery using a volume-adapted dosing strategy in patients with 4 to 10 brain metastases. METHODS AND MATERIALS: Adult patients with 4 to 10 brain metastases were eligible for this prospective trial. The primary endpoint was overall survival. Secondary endpoints were local recurrence, distant brain failure, neurologic death, and rate of adverse events. Exploratory objectives were neurocognition, quality of life, dosimetric data, salvage rate, and radionecrosis. Dose was prescribed in a single fraction per RTOG 90-05 or as 5 Gy × 5 fractions for lesions ≥3 cm diameter, lesions involving critical structures, or single-fraction brain V12Gy >20 mL. RESULTS: Forty patients were treated with median age of 61 years, Karnofsky performance status 90, and 6 brain metastases. Twenty-two patients survived longer than expected from the time of protocol SRS, with 1 living patient who has not reached that milestone. Median overall survival was 8.1 months with a 1-year overall survival of 35.7%. The 1-year local recurrence rate was 5% (10 of 204 of evaluable lesions) in 12.5% (4 of 32) of the patients. Distant brain failure was observed in 19 of 32 patients with a 1-year rate of 35.8%. Grade 1-2 headache was the most common complaint, with no grade 3-5 treatment-related adverse events. Radionecrosis was observed in only 5 lesions, with a 1-year rate of 1.5%. Rate of neurologic death was 20%. Neurocognition and quality of life did not significantly change 3 months after SRS compared with pretreatment. CONCLUSIONS: These results suggest that volume-adapted dosing single-isocenter multitarget stereotactic radiosurgery is an effective and safe treatment for patients with 4 to 10 brain metastases.
Authors
Kim, GJ; Buckley, ED; Herndon, JE; Allen, KJ; Dale, TS; Adamson, JD; Lay, L; Giles, WM; Rodrigues, AE; Wang, Z; Kelsey, CR; Torok, JA; Chino, JP; Fecci, PE; Sampson, JH; Anders, CK; Floyd, SR; Yin, F-F; Kirkpatrick, JP
MLA Citation
Kim, Grace J., et al. “Outcomes in Patients With 4 to 10 Brain Metastases Treated With Dose-Adapted Single-Isocenter Multitarget Stereotactic Radiosurgery: A Prospective Study.Adv Radiat Oncol, vol. 6, no. 6, Nov. 2021, p. 100760. Pubmed, doi:10.1016/j.adro.2021.100760.
URI
https://scholars.duke.edu/individual/pub1504691
PMID
34934856
Source
pubmed
Published In
Advances in Radiation Oncology
Volume
6
Published Date
Start Page
100760
DOI
10.1016/j.adro.2021.100760

Time to Steroid Independence After Laser Interstitial Thermal Therapy vs Medical Management for Treatment of Biopsy-Proven Radiation Necrosis Secondary to Stereotactic Radiosurgery for Brain Metastasis.

BACKGROUND: Radiation necrosis (RN) after stereotactic radiosurgery (SRS) for brain metastases (BM) can result in significant morbidity, compounded by the effects of extended steroid therapy. Laser interstitial thermal therapy (LITT) is a minimally invasive procedure that can offer definitive treatment for RN while potentially obviating the need for prolonged steroid use. OBJECTIVE: To compare LITT vs medical management (MM) in the treatment of RN. METHODS: A multicenter, retrospective study was performed of SRS-treated patients with BM who developed biopsy-proven RN and were treated with LITT or MM. Clinical outcome data were compared by treatment modality. RESULTS: Seventy-two patients met criteria with a median follow-up of 10.0 months (4.2-25.1), and 57 patients (79%) underwent LITT. Four MM (27%) and 3 LITT patients (5%) demonstrated radiographic progression (P = .031) at a median of 5.3 and 4.0 months (P = .40). There was no significant difference in overall survival (LITT median of 15.2 vs 11.6 months, P = .60) or freedom from local progression (13.6 vs 7.06 months, P = .40). Patients stopped steroid therapy earlier in the LITT cohort at a median of 37 days compared with 245 days (P < .001). When controlled for follow-up duration, patients treated with LITT were 3 times more likely to be weaned off steroids before the study end point (P = .003). CONCLUSION: These data suggest that LITT for treatment of biopsy-proven RN after SRS for BM significantly decreases time to steroid independence. Prospective trials should be designed to further validate the utility of LITT for RN and its impact on steroid-induced morbidity.
Authors
Sankey, EW; Grabowski, MM; Srinivasan, ES; Griffin, AS; Howell, EP; Otvos, B; Tsvankin, V; Barnett, GH; Mohammadi, AM; Fecci, PE
MLA Citation
URI
https://scholars.duke.edu/individual/pub1522734
PMID
35311745
Source
pubmed
Published In
Neurosurgery
Volume
90
Published Date
Start Page
684
End Page
690
DOI
10.1227/neu.0000000000001922

Laser ablation: Heating up the anti-tumor response in the intracranial compartment.

Immunotherapies, such as immune checkpoint inhibition (ICI), have had limited success in treating intracranial malignancies. These failures are due partly to the restrictive blood-brain-barrier (BBB), the profound tumor-dependent induction of local and systemic immunosuppression, and immune evasion exhibited by these tumors. Therefore, novel approaches must be explored that aim to overcome these stringent barriers. LITT is an emerging treatment for brain tumors that utilizes thermal ablation to kill tumor cells. LITT provides an additional therapeutic benefit by synergizing with ICI and systemic chemotherapies to strengthen the anti-tumor immune response. This synergistic relationship involves transient disruption of the BBB and local augmentation of immune function, culminating in increased CNS drug penetrance and improved anti-tumor immunity. In this review, we will provide an overview of the challenges facing immunotherapy for brain tumors, and discuss how LITT may synergize with the endogenous anti-tumor response to improve the efficacy of ICI.
Authors
Lerner, EC; Edwards, RM; Wilkinson, DS; Fecci, PE
MLA Citation
Lerner, Emily C., et al. “Laser ablation: Heating up the anti-tumor response in the intracranial compartment.Adv Drug Deliv Rev, vol. 185, June 2022, p. 114311. Pubmed, doi:10.1016/j.addr.2022.114311.
URI
https://scholars.duke.edu/individual/pub1522735
PMID
35489652
Source
pubmed
Published In
Adv Drug Deliv Rev
Volume
185
Published Date
Start Page
114311
DOI
10.1016/j.addr.2022.114311

Navigating the ventricles: Novel insights into the pathogenesis of hydrocephalus.

Congenital hydrocephalus occurs in one in 500-1000 babies born in the United States and acquired hydrocephalus may occur as the consequence of stroke, intraventricular and subarachnoid hemorrhage, traumatic brain injuries, brain tumors, craniectomy or may be idiopathic, as in the case of normal pressure hydrocephalus. Irrespective of its prevalence and significant impact on quality of life, neurosurgeons still rely on invasive cerebrospinal fluid shunt systems for the treatment of hydrocephalus that are exceptionally prone to failure and/or infection. Further understanding of this process at a molecular level, therefore, may have profound implications for improving treatment and quality of life for millions of individuals worldwide. The purpose of this article is to review the current research landscape on hydrocephalus with a focus on recent advances in our understanding of cerebrospinal fluid pathways from an evolutionary, genetics and molecular perspective.
Authors
Bramall, AN; Anton, ES; Kahle, KT; Fecci, PE
MLA Citation
Bramall, Alexa N., et al. “Navigating the ventricles: Novel insights into the pathogenesis of hydrocephalus.Ebiomedicine, vol. 78, Apr. 2022, p. 103931. Pubmed, doi:10.1016/j.ebiom.2022.103931.
URI
https://scholars.duke.edu/individual/pub1513775
PMID
35306341
Source
pubmed
Published In
Ebiomedicine
Volume
78
Published Date
Start Page
103931
DOI
10.1016/j.ebiom.2022.103931

Is There a Role for Immunotherapy in Central Nervous System Cancers?

Glioblastoma has emerged as an immunotherapy-refractory tumor based on negative phase III studies of anti-programmed cell death-1 therapy among newly diagnosed as well as recurrent patients. In addition, although much work on vaccine and cellular approaches is ongoing, therapeutic benefit with these approaches has been underwhelming. Much scientific insight into the multitiered layers of immunosuppression exploited by glioblastoma tumors is emerging that sheds light on the explanation for the disappointing results to date and highlights possible therapeutic avenues that may offer a better likelihood of therapeutic benefit for immune-based therapies.
Authors
Flores, C; Dunn, G; Fecci, P; Lim, M; Mitchell, D; Reardon, DA
MLA Citation
Flores, Catherine, et al. “Is There a Role for Immunotherapy in Central Nervous System Cancers?Hematol Oncol Clin North Am, vol. 36, no. 1, Feb. 2022, pp. 237–52. Pubmed, doi:10.1016/j.hoc.2021.09.002.
URI
https://scholars.duke.edu/individual/pub1503334
PMID
34801163
Source
pubmed
Published In
Hematol Oncol Clin North Am
Volume
36
Published Date
Start Page
237
End Page
252
DOI
10.1016/j.hoc.2021.09.002

Research Areas:

Blood-Brain Barrier
Brain metastasis
Cancer
Glioma
Glioma, Subependymal
Immunotherapy
Immunotherapy, Active
T cells
T cells--Effect of drugs on
T cells--Receptors
Translational Medical Research