Photodynamic Therapy Dosimetry

Gal Shafirstein, DSc Professor of OncologyDirector of Clinical ResearchPhotodynamic Center Department of Cell Stress BiologyRoswell Park Cancer Institute (RPCI)E-mail: Gal.Shafirstein@RoswellPark.org

PDT Dose

– Light dose rate and 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]

PDT Dosimetry

Treatment parameters – Fluence rate and fluence

In real-time– Light dosimetry system

Post treatment– Biomarker

Real Time Light Dosimetry System

3D Model of the Tumor

m

2 cm

J/cm²

Simulate Light Fluence Distribution

Oakley et al. Lasers Surg Med 47, 60-67 (2015).

Treatment Day

Absorbed PDT Dose

Biomarker for photoreaction

– Signal transducer and activator of transcription 3 (STAT3) crosslinking

– Proportional to the absorbed PDT dose

STAT3 Crosslink Different PSs

PDT with HPPH in SCCVII. (A) STAT3 crosslinking, (B) Survival

PDT with Photofrin in SCCVII

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.

Promising Prognostic Marker

Percent conversion of STAT3 monomer to cross-linked STAT3 in biopsies of dysplasia/CIS and SCC lesions obtained immediately following HPPH-PDTRigual, Shafirstein. Clin Cancer Res 2013;19(23): 6605-13.

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).

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): 6605-13.

Summary

Real time dosimetry – Measure light fluence rate and

fluence during treatment

STAT3 crosslinking is a promising dosimetry marker

Open Questions

Should we aim to measure local PS levels?

How about tissue oxygenation?

Do we need to standardize PDT dosimetry measurements?

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

Acknowledgments

NCI /NIH 5P30CA016056-36 and PO1CA055791

Roswell Park Cancer Institute, Alliance Foundation

Pinnacle Biologics Inc.

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

STAT3 Crosslink Different PSs