1. Proton Therapy for Thymic Malignancies: Multi-institutional Patterns-of-Care and Early Clinical Outcomes from the Proton Collaborative Group Registry & UF
Catherine Mercado, MD
Department of Radiation Oncology
University of Florida College of Medicine
October 23rd, 2017

2. Disclosures
None of the authors have conflicts of interest

3. Background
Thymoma and thymic carcinoma are rare malignancies arising in the anterior mediastinum from the thymus.
Median age of diagnosis: years old
Treatment:
Surgery +/- RT, chemo
If unresectable, chemoRT

4. Background
Long term survivorship common, causing concerns for radiotherapy related late side effects (i.e. cardiac disease or secondary malignancies)
OS (RT vs. no-RT)
5yr: 95% vs. 90%
10yr: 86% vs. 79 %
Rimner et al. J Thorac Oncol. 2016

5. Background NCCN Guidelines RT Techniques for TM:
“...Since these patients are younger and mostly long-term survivors, the mean dose to the total heart should be as low as reasonably achievable.”
Proton therapy (PT) reduces the radiation dose to organs at risk, potentially improving disease control and decreasing long-term toxicity

6. Colorwash isodose distribution for IMRT (left) and PT (right).
Background
Photon vs. Proton: Dosimetry demonstrates reduced RT dose to the OARs with PT
Colorwash isodose distribution for
IMRT (left) and PT (right). 
DVH representing the percentage of each organ irradiated at each RT dose level with IMRT or PT.
Figura et al., J Thorac Oncol May;8(5):e38-40.

7. Background
Parikh et al. demonstrated significant reductions in heart, lung, and esophagus dose in PT plan compared to analogous IMRT plan
Parikh et al., Clin Lung Cancer. 2016
Vogel et al. assessed risk of predicted secondary malignancies (SMNs) following adjuvant proton vs. photon therapy in thymoma patients
Results: 5 excess SMNs per 100 patients can potentially be avoided using protons vs. photons
Vogel et al., Int J Radiation Oncol Biol Phys, Vol. 99, 2017

8. Objective
This study reports on the patterns-of-care and early clinical outcomes of patients treated with PT for thymoma and thymic carcinoma.

9. Methods
From January 2008 to March patients received post-operative or definitive proton therapy for thymoma or thymic carcinoma All patients were treated on the institutional review board-approved University of Florida outcomes tracking protocol or PCG registry Clinical outcomes, pathology, treatment dose, acute toxicities, and follow-up information were analyzed.

10. Patient Characteristics
Thymoma
Thymic Carcinoma
Characteristic
Thymoma (n=21)
Median Age
52 years (range, 23-72)
Median RT dose
54 CGE (range, 45-70)
Post-operative RT
86 % (18)
Definitive RT
14 % (3)
Adjuvant chemotherapy
24 % (5)
Characteristic
Thymic Carcinoma (n=9)
Median Age
65 years (range, 38-88)
Median RT dose
60 CGE (range, 45-70)
Post-operative RT
67 % (6)
Definitive RT
33 % (3)
Adjuvant chemotherapy

11. Clinical Outcomes Median follow-up: 22 months (range, 3-60 months)
Local recurrence: 2 thymoma and 1 thymic carcinoma patient
Median time from completion of PT to local recurrence: 13 months (range, 2-26)
Patient deaths: 3
1 patient died who also had locally recurrent thymic carcinoma
1 patient died due to metastatic disease
1 patient died due to intercurrent disease
No patient experienced grade ≥3 toxicities after PT

12. 3 patients with recurrence after PT Disease Status at Last Follow-Up
Clinical Outcomes
3 patients with recurrence after PT
Patient
Diagnosis
Def vs. Post-op PT
Dose
Time to Recurrence
(months)
Type of Recurrence
Disease Status at Last Follow-Up 1
Thymic Ca
Definitive
70 CGE
13 months
Local and Distant
(In and out of field)
Dead 2
Thymoma
Post-op
50 CGE
2 months
Local Only
(subpleural nodules, out of field)
Alive 3
45 CGE
26 months
1 patient in cohort had oligometastatic disease prior to PT, at last follow-up patient died with distant metastasis

13. Discussion Single institution, 27 patients Median follow-up: 2 years
No patient experienced grade ≥3 toxicities
At 3 years: Regional control 96%, Distant control 74%, Overall Survival 94%
Vogel et al., Radiotherapy and Oncology 118 (2016) 504–509

14. Discussion Comparable Results: Institution Regional Control
Distant Control
Overall Survival
Toxicity
PCG + UF
(22 mo f/u)
90%
93%
Grade ≥3 toxicities
UPenn
(36 mo f/u)
96%
74 %
94 %
Vogel et al., Radiotherapy and Oncology 118 (2016) 504–509

15. Conclusions
Adjuvant and definitive PT is being used in the treatment of thymic malignancies.
Early results demonstrate an acceptable rate of recurrence with a tolerable toxicity profile.
Longer follow-up and a larger patient cohort are needed to confirm these findings.

16. Acknowledgements Questions Bradford Hoppe, MD Randal Henderson, MD
Amanda Price
PCG Collaborators:
Henry Tsai, MD (NJ Procure Proton Therapy Center)
Carlos Vargas, MD (Mayo Clinic Arizona)
George E. Laramore, MD, PhD (University of Washington)
Shahed Badiyan, MD (University of Maryland)
William Hartsell, MD (Northwestern Chicago Proton Center)
Gary Larson, MD (Oklahoma City Procure Proton Therapy Center)
Questions