John Kirkpatrick

Overview:

Malignant and benign tumors of the brain, spine and base of skull. Mathematical modelling of tumor metabolism, mass transfer and the response to ionizing radiation. Enhancing clinical outcome in stereotactic radiosurgery, fractionated stereotactic radiotherapy and stereotactic body radiotherapy.

Positions:

Professor of Radiation Oncology

Radiation Oncology
School of Medicine

Professor in Neurosurgery

Neurosurgery
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 1978

Rice University

M.D. 1999

University of Texas Health Science Center San Antonio

Grants:

Validation of Novel Therapeutic Approach for Leptomeningeal Metastases

Administered By
Neurosurgery
Role
Investigator
Start Date
End Date

BMX-001 AS A THERAPEUTIC AGENT FOR TREATMENT OF MULTIPLE BRAIN METASTASES

Administered By
Radiation Oncology
Role
Principal Investigator
Start Date
End Date

Publications:

Long-Term Outcomes for Patients With Atypical or Malignant Meningiomas Treated With or Without Radiation Therapy: A 25-Year Retrospective Analysis of a Single-Institution Experience.

Purpose: Atypical (World Health Organization [WHO] grade 2) and malignant (WHO grade 3) meningiomas have high rates of local recurrence, and questions remain about the role of adjuvant radiation therapy (RT) for patients with WHO grade 2 disease. These patients frequently require salvage therapy, and optimal management is uncertain given limited prospective data. We report on the long-term outcomes for patients with atypical and malignant meningiomas treated with surgery and/or RT at our institution. Methods and Materials: Data were collected through a retrospective chart review for all patients with WHO grade 2 or 3 meningiomas treated with surgery and/or RT at our institution between January 1992 and March 2017. Progression-free survival (PFS) and overall survival (OS) were described using the KaplanMeier estimator. The outcomes in the subgroups were compared with a log-rank test. A Cox proportional hazards model was used for the univariable and multivariable analyses of predictors of PFS. Results: A total of 66 patients were included in this analysis. The median follow-up was 12.4 years overall and 8.6 years among surviving patients. Fifty-two patients (78.8%) had WHO grade 2 meningiomas, and 14 patients (21.2%) had WHO grade 3 disease. Thirty-six patients (54.5%) were treated with surgery alone, 28 patients (42.4%) with surgery and adjuvant RT, and 2 patients (3%) with RT alone. Median PFS and OS were 3.2 years and 8.8 years, respectively. PFS was significantly improved with adjuvant RT compared with surgery alone (hazard ratio, 0.36; 95% confidence interval, 0.18-0.70). Patients with Ki-67 index >10% showed a trend toward worse PFS compared with patients with Ki-67 ≤10% (hazard ratio, 0.51; 95% confidence interval, 0.25-1.04). No significant differences in PFS or OS were observed with respect to Simpson or WHO grade. Conclusions: For patients with atypical or malignant meningiomas, adjuvant RT was associated with significantly improved PFS, and Ki-67 index >10% was associated with a trend toward worse PFS. Given the long-term survival, high recurrence rates, and efficacy of salvage therapy, patients with atypical and malignant meningiomas should be monitored systematically long after initial treatment.
Authors
Kent, CL; Mowery, YM; Babatunde, O; Wright, AO; Barak, I; McSherry, F; Herndon, JE; Friedman, AH; Zomorodi, A; Peters, K; Desjardins, A; Friedman, H; Sperduto, W; Kirkpatrick, JP
MLA Citation
Kent, Collin L., et al. “Long-Term Outcomes for Patients With Atypical or Malignant Meningiomas Treated With or Without Radiation Therapy: A 25-Year Retrospective Analysis of a Single-Institution Experience.Adv Radiat Oncol, vol. 7, no. 3, May 2022, p. 100878. Pubmed, doi:10.1016/j.adro.2021.100878.
URI
https://scholars.duke.edu/individual/pub1510656
PMID
35647401
Source
pubmed
Published In
Advances in Radiation Oncology
Volume
7
Published Date
Start Page
100878
DOI
10.1016/j.adro.2021.100878

Accurate Three-Dimensional Thermal Dosimetry and Assessment of Physiologic Response Are Essential for Optimizing Thermoradiotherapy.

Numerous randomized trials have revealed that hyperthermia (HT) + radiotherapy or chemotherapy improves local tumor control, progression free and overall survival vs. radiotherapy or chemotherapy alone. Despite these successes, however, some individuals fail combination therapy; not every patient will obtain maximal benefit from HT. There are many potential reasons for failure. In this paper, we focus on how HT influences tumor hypoxia, since hypoxia negatively influences radiotherapy and chemotherapy response as well as immune surveillance. Pre-clinically, it is well established that reoxygenation of tumors in response to HT is related to the time and temperature of exposure. In most pre-clinical studies, reoxygenation occurs only during or shortly after a HT treatment. If this were the case clinically, then it would be challenging to take advantage of HT induced reoxygenation. An important question, therefore, is whether HT induced reoxygenation occurs in the clinic that is of radiobiological significance. In this review, we will discuss the influence of thermal history on reoxygenation in both human and canine cancers treated with thermoradiotherapy. Results of several clinical series show that reoxygenation is observed and persists for 24-48 h after HT. Further, reoxygenation is associated with treatment outcome in thermoradiotherapy trials as assessed by: (1) a doubling of pathologic complete response (pCR) in human soft tissue sarcomas, (2) a 14 mmHg increase in pO2 of locally advanced breast cancers achieving a clinical response vs. a 9 mmHg decrease in pO2 of locally advanced breast cancers that did not respond and (3) a significant correlation between extent of reoxygenation (as assessed by pO2 probes and hypoxia marker drug immunohistochemistry) and duration of local tumor control in canine soft tissue sarcomas. The persistence of reoxygenation out to 24-48 h post HT is distinctly different from most reported rodent studies. In these clinical series, comparison of thermal data with physiologic response shows that within the same tumor, temperatures at the higher end of the temperature distribution likely kill cells, resulting in reduced oxygen consumption rate, while lower temperatures in the same tumor improve perfusion. However, reoxygenation does not occur in all subjects, leading to significant uncertainty about the thermal-physiologic relationship. This uncertainty stems from limited knowledge about the spatiotemporal characteristics of temperature and physiologic response. We conclude with recommendations for future research with emphasis on retrieving co-registered thermal and physiologic data before and after HT in order to begin to unravel complex thermophysiologic interactions that appear to occur with thermoradiotherapy.
Authors
Dewhirst, MW; Oleson, JR; Kirkpatrick, J; Secomb, TW
MLA Citation
Dewhirst, Mark W., et al. “Accurate Three-Dimensional Thermal Dosimetry and Assessment of Physiologic Response Are Essential for Optimizing Thermoradiotherapy.Cancers (Basel), vol. 14, no. 7, Mar. 2022. Pubmed, doi:10.3390/cancers14071701.
URI
https://scholars.duke.edu/individual/pub1515674
PMID
35406473
Source
pubmed
Published In
Cancers
Volume
14
Published Date
DOI
10.3390/cancers14071701

Answering the Big Clinical Questions in Brain Metastasis Management.

Management of brain metastases is challenging, both because of the historically guarded prognosis and evolving, more efficacious treatment paradigms for metastatic cancer. This perspective addresses several of the important difficult questions that practitioners treating patients with brain tumors face in the clinic. Successfully answering these questions requires knowledge of the clinical evidence, thoughtful discussion of the patient's goals of care and collaboration in a multi-disciplinary setting.
Authors
MLA Citation
Kirkpatrick, John P. “Answering the Big Clinical Questions in Brain Metastasis Management.Front Oncol, vol. 11, 2021, p. 834122. Pubmed, doi:10.3389/fonc.2021.834122.
URI
https://scholars.duke.edu/individual/pub1509766
PMID
35118002
Source
pubmed
Published In
Frontiers in Oncology
Volume
11
Published Date
Start Page
834122
DOI
10.3389/fonc.2021.834122

Pineal Parenchymal Tumors of Intermediate Differentiation Treated With Ventricular Radiation and Temozolomide.

Authors
MLA Citation
Low, Justin T., et al. “Pineal Parenchymal Tumors of Intermediate Differentiation Treated With Ventricular Radiation and Temozolomide.Adv Radiat Oncol, vol. 7, no. 1, Jan. 2022, p. 100814. Pubmed, doi:10.1016/j.adro.2021.100814.
URI
https://scholars.duke.edu/individual/pub1500511
PMID
34746517
Source
pubmed
Published In
Advances in Radiation Oncology
Volume
7
Published Date
Start Page
100814
DOI
10.1016/j.adro.2021.100814

Combination laser interstitial thermal therapy plus stereotactic radiotherapy increases time to progression for biopsy-proven recurrent brain metastases.

Background: Improved survival for patients with brain metastases has been accompanied by a rise in tumor recurrence after stereotactic radiotherapy (SRT). Laser interstitial thermal therapy (LITT) has emerged as an effective treatment for SRT failures as an alternative to open resection or repeat SRT. We aimed to evaluate the efficacy of LITT followed by SRT (LITT+SRT) in recurrent brain metastases. Methods: A multicenter, retrospective study was performed of patients who underwent treatment for biopsy-proven brain metastasis recurrence after SRT at an academic medical center. Patients were stratified by "planned LITT+SRT" versus "LITT alone" versus "repeat SRT alone." Index lesion progression was determined by modified Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. Results: Fifty-five patients met inclusion criteria, with a median follow-up of 7.3 months (range: 1.0-30.5), age of 60 years (range: 37-86), Karnofsky Performance Status (KPS) of 80 (range: 60-100), and pre-LITT/biopsy contrast-enhancing volume of 5.7 cc (range: 0.7-19.4). Thirty-eight percent of patients underwent LITT+SRT, 45% LITT alone, and 16% SRT alone. Median time to index lesion progression (29.8, 7.5, and 3.7 months [P = .022]) was significantly improved with LITT+SRT. When controlling for age in a multivariate analysis, patients treated with LITT+SRT remained significantly less likely to have index lesion progression (P = .004). Conclusions: These data suggest that LITT+SRT is superior to LITT or repeat SRT alone for treatment of biopsy-proven brain metastasis recurrence after SRT failure. Prospective trials are warranted to validate the efficacy of using combination LITT+SRT for treatment of recurrent brain metastases.
Authors
Grabowski, MM; Srinivasan, ES; Vaios, EJ; Sankey, EW; Otvos, B; Krivosheya, D; Scott, A; Olufawo, M; Ma, J; Fomchenko, EI; Herndon, JE; Kim, AH; Chiang, VL; Chen, CC; Leuthardt, EC; Barnett, GH; Kirkpatrick, JP; Mohammadi, AM; Fecci, PE
MLA Citation
Grabowski, Matthew M., et al. “Combination laser interstitial thermal therapy plus stereotactic radiotherapy increases time to progression for biopsy-proven recurrent brain metastases.Neurooncol Adv, vol. 4, no. 1, Jan. 2022, p. vdac086. Pubmed, doi:10.1093/noajnl/vdac086.
URI
https://scholars.duke.edu/individual/pub1526682
PMID
35795470
Source
pubmed
Published In
Neuro Oncology Advances
Volume
4
Published Date
Start Page
vdac086
DOI
10.1093/noajnl/vdac086