1. Photodynamic Therapy Dosimetry
Gal Shafirstein, DSc
Professor of Oncology
Director of Clinical Research
Photodynamic Center
Department of Cell Stress Biology
Roswell Park Cancer Institute (RPCI)

2. PDT Dose Light dose rate and dose Photosensitizer dose
Fluence rate – Irradiance: mW/cm2
Fluence – Radiant Exposure: J/cm2
Photosensitizer dose
Systemic: mg/kg, or mg/m2
PDT dose= [Fluence]x[PS dose]

3. PDT Dosimetry Treatment parameters In real-time Post treatment
Fluence rate and fluence
In real-time
Light dosimetry system
Post treatment
Biomarker

4. Real Time Light Dosimetry System

5. 3D Model of the Tumor m
Tumor (red), Carotid Artery and Jugular Vein (purple), Exterior Jugular Vein (Blue), Hyoid (Light Green), Jaw (Dark Green), Vertebra (yellow), Cartilage (pink), Air (Light Blue)

6. Simulate Light Fluence Distribution
2 cm
J/cm²
Oakley et al. Lasers Surg Med 47, (2015).

7. Treatment Day

8. Absorbed PDT Dose Biomarker for photoreaction
Signal transducer and activator of transcription 3 (STAT3) crosslinking
Proportional to the absorbed PDT dose

9. STAT3 Crosslink Different PSs
PDT with HPPH in SCCVII. (A) STAT3 crosslinking, (B) Survival
PDT with Photofrin in SCCVII

10. SCC vs. Dysplasia
Lesion pathology (A) and STAT3 crosslinking (B) in corresponding halves of biopsies obtained immediately after HPPH-PDT at 140 J/cm2. Patient A = SCC, Patient B = severe dysplasia.

11. Promising Prognostic Marker
Data are derived from immunoblots and summarized as quartile (box-and-whisker) plots as described in Methods. Asterisks indicate significant differences between groups.
Percent conversion of STAT3 monomer to cross-linked STAT3 in biopsies of dysplasia/CIS and SCC lesions obtained immediately following HPPH-PDT
Rigual, Shafirstein. Clin Cancer Res 2013;19(23):

12. Fluorescence
Fluorescence values were significantly (P=0.0431) higher in SCC (median 9.73, mean 10.91) than in dysplasia and CiS (median 6.38, mean 6.80).

13. Clinical Outcomes
HPPH-PDT is more effective for SCC than CiS/Dysplasia
82% CR versus 46 %, at 140 J/cm2
The response was more durable, at 5-40 months follow up
Rigual, Shafirstein, et al. Photodynamic therapy with 3-(1'-hexyloxyethyl) pyropheophorbide a for cancer of the oral cavity. Clin Cancer Res 2013;19(23):

14. Summary Real time dosimetry
Measure light fluence rate and fluence during treatment
STAT3 crosslinking is a promising dosimetry marker

15. Open Questions Should we aim to measure local PS levels?
How about tissue oxygenation?
Do we need to standardize PDT dosimetry measurements?

16. Team Members and Collaborators
David Bellnier PhD, Heinz Baumann PhD, Barbara Henderson PhD, and Sandra Gollnick PhD, Director, PDT Center
Hassan Arshad, MD MPH, Dept. of Head and Neck Surgery
Thomas Laudico, DO, Dept. of Radiology
Shafirstein Laboratory: Emily Oakley BE, Tyger Howell MS
PDT Center: Brian Wrazen BSc, Michele Cooper, RN, CRC, Kenneth Keymel BSc
Thomas Foster, PhD, Timothy Baran PhD, Univ. of Rochester
Merrill Biel MD, PhD, Univ. of MN
Harry Quon MD, Johns Hopkins Univ.
Zenalux Biomedical, Durham, NC

17. Acknowledgments NCI /NIH 5P30CA016056-36 and PO1CA055791
Roswell Park Cancer Institute, Alliance Foundation
Pinnacle Biologics Inc.

18. Pending, IRB Approved Study
A Multicenter Randomized Phase II: HPPH PDT versus Standard Surgery in patients with T1/T2 N0 SCC of the oral cavity
Primary endpoints:
Disease free survival
Quality of life

20. STAT3 Crosslink Different PSs
SCCVII cells (105) were incubated for two hours with either Photofrin or Foscan. (A) Fluorescence images showing PS retention in the cells. (B) The level of STAT3 crosslinking following illumination of cells treated with Foscan or Photofrin mediated PDT.
Foscan: 652 nm, 5.5 mW/cm2, 3 J/cm2; Photofrin, 4.4 mW/cm2, 2.34 J/cm2