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:

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

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

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:

Editorial: It takes a village: The expanding multi-disciplinary approach to brain metastasis.

Authors
Fecci, PE; Rao, G; Brastianos, PK; Dunn, GP; Anders, CK
MLA Citation
Fecci, Peter E., et al. “Editorial: It takes a village: The expanding multi-disciplinary approach to brain metastasis.Front Oncol, vol. 12, 2022, p. 1054490. Pubmed, doi:10.3389/fonc.2022.1054490.
URI
https://scholars.duke.edu/individual/pub1556925
PMID
36338769
Source
pubmed
Published In
Frontiers in Oncology
Volume
12
Published Date
Start Page
1054490
DOI
10.3389/fonc.2022.1054490

Commentary: Laser Interstitial Thermal Therapy for First-Line Treatment of Surgically Accessible Recurrent Glioblastoma: Outcomes Compared With a Surgical Cohort.

Authors
Schwalb, AM; Srinivasan, ES; Fecci, PE
MLA Citation
Schwalb, Allison M., et al. “Commentary: Laser Interstitial Thermal Therapy for First-Line Treatment of Surgically Accessible Recurrent Glioblastoma: Outcomes Compared With a Surgical Cohort.Neurosurgery, vol. 91, no. 6, Dec. 2022, pp. e160–63. Pubmed, doi:10.1227/neu.0000000000002184.
URI
https://scholars.duke.edu/individual/pub1556661
PMID
36377926
Source
pubmed
Published In
Neurosurgery
Volume
91
Published Date
Start Page
e160
End Page
e163
DOI
10.1227/neu.0000000000002184

Neuronal CaMKK2 promotes immunosuppression and checkpoint blockade resistance in glioblastoma.

Glioblastoma (GBM) is notorious for its immunosuppressive tumor microenvironment (TME) and is refractory to immune checkpoint blockade (ICB). Here, we identify calmodulin-dependent kinase kinase 2 (CaMKK2) as a driver of ICB resistance. CaMKK2 is highly expressed in pro-tumor cells and is associated with worsened survival in patients with GBM. Host CaMKK2, specifically, reduces survival and promotes ICB resistance. Multimodal profiling of the TME reveals that CaMKK2 is associated with several ICB resistance-associated immune phenotypes. CaMKK2 promotes exhaustion in CD8+ T cells and reduces the expansion of effector CD4+ T cells, additionally limiting their tumor penetrance. CaMKK2 also maintains myeloid cells in a disease-associated microglia-like phenotype. Lastly, neuronal CaMKK2 is required for maintaining the ICB resistance-associated myeloid phenotype, is deleterious to survival, and promotes ICB resistance. Our findings reveal CaMKK2 as a contributor to ICB resistance and identify neurons as a driver of immunotherapeutic resistance in GBM.
Authors
Tomaszewski, WH; Waibl-Polania, J; Chakraborty, M; Perera, J; Ratiu, J; Miggelbrink, A; McDonnell, DP; Khasraw, M; Ashley, DM; Fecci, PE; Racioppi, L; Sanchez-Perez, L; Gunn, MD; Sampson, JH
MLA Citation
Tomaszewski, William H., et al. “Neuronal CaMKK2 promotes immunosuppression and checkpoint blockade resistance in glioblastoma.Nat Commun, vol. 13, no. 1, Oct. 2022, p. 6483. Pubmed, doi:10.1038/s41467-022-34175-y.
URI
https://scholars.duke.edu/individual/pub1555261
PMID
36309495
Source
pubmed
Published In
Nature Communications
Volume
13
Published Date
Start Page
6483
DOI
10.1038/s41467-022-34175-y

Prognostic Model for Intracranial Progression after Stereotactic Radiosurgery: A Multicenter Validation Study.

Stereotactic radiosurgery (SRS) is a standard of care for many patients with brain metastases. To optimize post-SRS surveillance, this study aimed to validate a previously published nomogram predicting post-SRS intracranial progression (IP). We identified consecutive patients completing an initial course of SRS across two institutions between July 2017 and December 2020. Patients were classified as low- or high-risk for post-SRS IP per a previously published nomogram. Overall survival (OS) and freedom from IP (FFIP) were assessed via the Kaplan-Meier method. Assessment of parameters impacting FFIP was performed with univariable and multivariable Cox proportional hazard models. Among 890 patients, median follow-up was 9.8 months (95% CI 9.1-11.2 months). In total, 47% had NSCLC primary tumors, and 47% had oligometastatic disease (defined as ≤5 metastastic foci) at the time of SRS. Per the IP nomogram, 53% of patients were deemed high-risk. For low- and high-risk patients, median FFIP was 13.9 months (95% CI 11.1-17.1 months) and 7.6 months (95% CI 6.4-9.3 months), respectively, and FFIP was superior in low-risk patients (p < 0.0001). This large multisite BM cohort supports the use of an IP nomogram as a quick and simple means of stratifying patients into low- and high-risk groups for post-SRS IP.
Authors
Carpenter, DJ; Natarajan, B; Arshad, M; Natesan, D; Schultz, O; Moravan, MJ; Read, C; Lafata, KJ; Giles, W; Fecci, P; Mullikin, TC; Reitman, ZJ; Kirkpatrick, JP; Floyd, SR; Chmura, SJ; Hong, JC; Salama, JK
MLA Citation
Carpenter, David J., et al. “Prognostic Model for Intracranial Progression after Stereotactic Radiosurgery: A Multicenter Validation Study.Cancers (Basel), vol. 14, no. 21, Oct. 2022. Pubmed, doi:10.3390/cancers14215186.
URI
https://scholars.duke.edu/individual/pub1555466
PMID
36358606
Source
pubmed
Published In
Cancers
Volume
14
Published Date
DOI
10.3390/cancers14215186

Factors Associated With New-Onset Seizures Following Stereotactic Radiosurgery for Newly Diagnosed Brain Metastases.

PURPOSE: Stereotactic radiosurgery (SRS) is a highly effective therapy for newly diagnosed brain metastases. Prophylactic antiepileptic drugs are no longer routinely used in current SRS practice, owing to a perceived low overall frequency of new-onset seizures and potential side effects of medications. It is nonetheless desirable to prevent unwanted side effects following SRS. Risk factors for new-onset seizures after SRS have not been well established. As such, we aimed to characterize variables associated with increased seizure risk. METHODS AND MATERIALS: Patients treated with SRS for newly diagnosed brain metastases between 2013 and 2016 were retrospectively reviewed at a single institution. Data on baseline demographics, radiation parameters, and clinical courses were collected. RESULTS: The cohort consisted of 305 patients treated with SRS without prior seizure history. Median age and baseline Karnofsky Performance Scale score were 64 years (interquartile range, 55-70) and 80 (interquartile range, 80-90), respectively. Twenty-six (8.5%) patients developed new-onset seizures within 3 months of SRS. There was no association between new-onset seizures and median baseline Karnofsky Performance Scale score, prior resection, or prior whole brain radiation therapy. There were significant differences in the combined total irradiated volume (12.5 vs 3.7 cm3, P < .001), maximum single lesion volume (8.8 vs 2.8 cm3, P = .003), lesion diameter (3.2 vs 2.0 cm, P = .003), and number of lesions treated (3 vs 1, P = .018) between patients with and without new-onset seizures, respectively. On multivariate logistic regression, total irradiated volume (odds ratio, 1.09 for every 1-cm1 increase in total volume; confidence interval, 1.02-1.17; P = .016) and pre-SRS neurologic symptoms (odds ratio, 3.08; 95% confidence interval, 1.19-7.99; P = .020) were both significantly correlated with odds of seizures following SRS. CONCLUSIONS: Our data suggest that larger total treatment volume and the presence of focal neurologic deficits at presentation are associated with new-onset seizures within 3 months of SRS. High-risk patients undergoing SRS may benefit from counseling or prophylactic antiseizure therapy.
Authors
Lerner, EC; Srinivasan, ES; Broadwater, G; Haskell-Mendoza, AP; Edwards, RM; Huie, D; Vaios, EJ; Floyd, SR; Adamson, JD; Fecci, PE
MLA Citation
Lerner, Emily C., et al. “Factors Associated With New-Onset Seizures Following Stereotactic Radiosurgery for Newly Diagnosed Brain Metastases.Adv Radiat Oncol, vol. 7, no. 6, 2022, p. 101054. Pubmed, doi:10.1016/j.adro.2022.101054.
URI
https://scholars.duke.edu/individual/pub1511851
PMID
36420187
Source
pubmed
Published In
Advances in Radiation Oncology
Volume
7
Published Date
Start Page
101054
DOI
10.1016/j.adro.2022.101054

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