Christopher Willett

Positions:

Chair, Department of Radiation Oncology

Radiation Oncology
School of Medicine

Mark W. Dewhirst Distinguished Professor of Radiation Oncology

Radiation Oncology
School of Medicine

Professor of Radiation Oncology

Radiation Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 1977

Tufts University

M.D. 1981

Tufts University

Grants:

Cancer Care Quality Measures: Diagnosis and Treatment of Colorectal Cancer

Administered By
Institutes and Centers
Awarded By
Agency for Healthcare Research and Quality
Role
Investigator
Start Date
End Date

Angiogenic Profile of Rectal Cancer

Administered By
Radiation Oncology
Awarded By
National Cancer Institute
Role
Principal Investigator
Start Date
End Date

Publications:

Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Gastric cancer is the third leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability (MSI) status, and the expression of programmed death-ligand 1 (PD-L1), has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with localized gastric cancer. This selection from the NCCN Guidelines for Gastric Cancer focuses on the management of unresectable locally advanced, recurrent, or metastatic disease.
Authors
Ajani, JA; D'Amico, TA; Bentrem, DJ; Chao, J; Cooke, D; Corvera, C; Das, P; Enzinger, PC; Enzler, T; Fanta, P; Farjah, F; Gerdes, H; Gibson, MK; Hochwald, S; Hofstetter, WL; Ilson, DH; Keswani, RN; Kim, S; Kleinberg, LR; Klempner, SJ; Lacy, J; Ly, QP; Matkowskyj, KA; McNamara, M; Mulcahy, MF; Outlaw, D; Park, H; Perry, KA; Pimiento, J; Poultsides, GA; Reznik, S; Roses, RE; Strong, VE; Su, S; Wang, HL; Wiesner, G; Willett, CG; Yakoub, D; Yoon, H; McMillian, N; Pluchino, LA
MLA Citation
Ajani, Jaffer A., et al. “Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.J Natl Compr Canc Netw, vol. 20, no. 2, Feb. 2022, pp. 167–92. Pubmed, doi:10.6004/jnccn.2022.0008.
URI
https://scholars.duke.edu/individual/pub1509520
PMID
35130500
Source
pubmed
Published In
J Natl Compr Canc Netw
Volume
20
Published Date
Start Page
167
End Page
192
DOI
10.6004/jnccn.2022.0008

The Role of Hypofractionated Radiation Therapy in the Management of Unresectable Hepatocellular Carcinoma (HCC).

<h4>Purpose/objective(s)</h4>Management of HCC without surgical resection or transplantation is poorly defined with no standard. Stereotactic body radiation therapy (SBRT) or hypofractionated image-guided radiotherapy (HIGRT), is an evolving, non-invasive, therapeutic option for patients with HCC delivering ablative doses with modest toxicity.<h4>Materials/methods</h4>We retrospectively identified all patients with unresectable, non-metastatic HCC treated with SBRT/HIGRT who presented to our University and Veterans Affairs (VA) radiation oncology departments from 2013 to 2019. Primary study endpoints included freedom from local progression, progression free survival, overall survival, and treatment-related toxicity.<h4>Results</h4>149 patients were included in our analysis with median delivered radiation dose of 50 Gy in 5 fractions. This included a total of 172 treatment courses, as 21 patients received more than one course (19 patients received 2 courses; 2 patients received 3 courses). Twenty-two of the re-treatment courses were to previously unirradiated lesions, while one course was delivered to a previously treated lesion exhibiting local progression. Sixty-nine percent (69%) of patients were Child-Pugh A and 89% had a baseline ALBI grade of 1-2 prior to treatment. A majority of patients (59%) had a single lesion with a median size of 2.70 cm (Q1 2.00, Q3 3.95). Fifty-seven percent (57%) of patients received a biologically effective dose (BED<sub>α/β = 10</sub>) of at least 75 Gy and 48% of patients had undergone prior liver-directed therapy. All patients completed their intended treatment course with 1 patient (0.7%) experiencing Grade 3+ acute and 4 patients (2.6%) experiencing Grade 3+ late toxicities. Fifteen treatment courses (8.7%) resulted in non-classical radiation-induced liver disease (RILD), defined as an increase of 2 or more points in Child-Pugh score following radiation. With median follow up of 40 months, median overall survival was 25 months (95% CI 18-30 months). The 2-year freedom from local progression was 75% (95% CI 65-83%) overall, 64% (95% CI 48-77%) among patients who received BED ≤75 Gy and 86% (95% CI 72-93%) among those who received BED > 75 Gy. Median progression free survival was not reached. During the study period, 8.1% of patients developed regional nodal progression and 18.8% developed distant metastatic disease (42.9% osseous, 50.0% lung, 46.4% soft tissue/peritoneal/other involvement; multiple patients with more than one site of metastatic involvement).<h4>Conclusion</h4>SBRT/HIGRT results in high rates of local control with minimal treatment related toxicities. Randomized, prospective trials should seek to establish SBRT/HIGRT as a standard local therapeutic option for patients with unresectable, non-metastatic HCC.
Authors
MLA Citation
Stephens, S. J., et al. “The Role of Hypofractionated Radiation Therapy in the Management of Unresectable Hepatocellular Carcinoma (HCC).International Journal of Radiation Oncology, Biology, Physics, vol. 111, no. 3S, 2021, pp. e78–79. Epmc, doi:10.1016/j.ijrobp.2021.07.444.
URI
https://scholars.duke.edu/individual/pub1502973
PMID
34701968
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
111
Published Date
Start Page
e78
End Page
e79
DOI
10.1016/j.ijrobp.2021.07.444

Toxicity and Dosimetric Parameters of Ablative Radiation Therapy in the Management of Patients with Child-Pugh B/C Liver Function and Unresectable Hepatocellular Carcinoma (HCC).

<h4>Purpose/objective(s)</h4>To date there is no clear standard non-surgical therapeutic option for HCC patients. Ablative radiation therapy (SBRT/HIGRT) is an emerging non-invasive treatment for patients with HCC. However, there is concern about the risk for radiation-induced liver toxicity following radiation in patients with decompensated liver function (Child-Pugh B/C).<h4>Materials/methods</h4>We retrospectively identified all patients with unresectable, non-metastatic HCC treated with SBRT/HIGRT and underlying Child-Pugh B or C liver function prior to radiation therapy at our University and Veterans Affairs (VA) radiation oncology departments from 2014 to 2019. Primary endpoints included treatment-related toxicity, as well as, evaluation of dosimetric parameters for OAR.<h4>Results</h4>38 patients (39 treatment courses) were included. Most patients (97%) had Child-Pugh B7-B9 (62% CP B7, 21% CP B8, 15% CP B9) or ALBI grade 2-3 (69% ALBI grade 2, 31% ALBI grade 3) liver disease prior to radiation therapy. A single patient had Child-Pugh C10 liver function. The most commonly utilized regimens include 50 Gy in either 5 or 10 fractions. The median delivered dose was 50 Gy (range 30-50) in an average of 7.5 fractions (range 5-10). Most patients had a single lesion (63%) with a median lesion size of 3.2 cm (range 1.10-7.40 cm). The mean liver dose was 9.40 Gy (range 3.38-23.94) with a liver D800cc of 4.14 Gy (range 0.35-17.31). All patients completed their intended treatment course with a median follow up of 43 months. Four (10.3%) treatment courses resulted in non-classical radiation-induced liver disease (RILD) (defined as an increase of 2 or more points in Child-Pugh score), compared to 8.3% for patients with Child-Pugh A liver function treated during a similar time period. Otherwise, one patient (2.6%) experienced acute grade 3+ (non-RILD) hepatobiliary toxicity (transient transaminitis). Two-year freedom from local progression was 73% (95% CI 37-90%), median overall survival 12 months (95% CI 5-25 months), and median progression free-survival was not reached.<h4>Conclusion</h4>Ablative radiation therapy as definitive management for patients with unresectable, non-metastatic HCC appears to be reasonably well tolerated in patients with decompensated liver function at baseline (Child-Pugh B7-B9), with low rates of RILD and encouraging local control. With careful selection, these patients appear to be reasonable candidates for consideration of SBRT/HIGRT. Our analysis did not include enough patients with Child-Pugh C10+ disease to draw meaningful conclusions.
Authors
Sperduto, W; Oyekunle, T; Niedzwiecki, D; Czito, B; Willett, CG; Salama, JK; Palta, M; Stephens, SJ
MLA Citation
Sperduto, W., et al. “Toxicity and Dosimetric Parameters of Ablative Radiation Therapy in the Management of Patients with Child-Pugh B/C Liver Function and Unresectable Hepatocellular Carcinoma (HCC).International Journal of Radiation Oncology, Biology, Physics, vol. 111, no. 3S, 2021, p. e78. Epmc, doi:10.1016/j.ijrobp.2021.07.443.
URI
https://scholars.duke.edu/individual/pub1502974
PMID
34701967
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
111
Published Date
Start Page
e78
DOI
10.1016/j.ijrobp.2021.07.443

Radiation Injury

MLA Citation
Czito, B. G., and C. G. Willett. “Radiation Injury.” Sleisenger and Fordtran’s Gastrointestinal and Liver Disease- 2 Volume Set: Pathophysiology, Diagnosis, Management, Expert Consult Premium Edition - Enhanced Online Features and Print, 2010, pp. 639–51. Scopus, doi:10.1016/B978-1-4160-6189-2.00039-1.
URI
https://scholars.duke.edu/individual/pub1512248
Source
scopus
Published Date
Start Page
639
End Page
651
DOI
10.1016/B978-1-4160-6189-2.00039-1

Transfer learning for fluence map prediction in adrenal stereotactic body radiation therapy.

Objective:To design a deep transfer learning framework for modeling fluence map predictions for stereotactic body radiation therapy (SBRT) of adrenal cancer and similar sites that usually have a small number of cases.Approach:We developed a transfer learning framework for adrenal SBRT planning that leverages knowledge in a pancreas SBRT planning model. Treatment plans from the two sites had different dose prescriptions and beam settings but both prioritized gastrointestinal sparing. A base framework was first trained with 100 pancreas cases. This framework consists of two convolutional neural networks (CNN), which predict individual beam doses (BD-CNN) and fluence maps (FM-CNN) sequentially for 9-beam intensity-modulated radiation therapy (IMRT) plans. Forty-five adrenal plans were split into training/validation/test sets with the ratio of 20/10/15. The base BD-CNN was re-trained with transfer learning using 5/10/15/20 adrenal training cases to produce multiple candidate adrenal BD-CNN models. The base FM-CNN was directly used for adrenal cases. The deep learning (DL) plans were evaluated by several clinically relevant dosimetric endpoints, producing a percentage score relative to the clinical plans.Main results:Transfer learning significantly reduced the number of training cases and training time needed to train such a DL framework. The adrenal transfer learning model trained with 5/10/15/20 cases achieved validation plan scores of 85.4/91.2/90.7/89.4, suggesting that model performance saturated with 10 training cases. Meanwhile, a model using all 20 adrenal training cases without transfer learning only scored 80.5. For the final test set, the 5/10/15/20-case models achieved scores of 73.5/75.3/78.9/83.3.Significance:It is feasible to use deep transfer learning to train an IMRT fluence prediction framework. This technique could adapt to different dose prescriptions and beam configurations. This framework potentially enables DL modeling for clinical sites that have a limited dataset, either due to few cases or due to rapid technology evolution.
Authors
Wang, W; Sheng, Y; Palta, M; Czito, B; Willett, C; Yin, F-F; Wu, Q; Ge, Y; Wu, QJ
MLA Citation
Wang, Wentao, et al. “Transfer learning for fluence map prediction in adrenal stereotactic body radiation therapy.Phys Med Biol, vol. 66, no. 24, 2021. Pubmed, doi:10.1088/1361-6560/ac3c14.
URI
https://scholars.duke.edu/individual/pub1495079
PMID
34808605
Source
pubmed
Published In
Phys Med Biol
Volume
66
Published Date
DOI
10.1088/1361-6560/ac3c14