1. Current Status of PDT in Gastroenterology 2015: Esophageal Carcinoma & Cholangiocarcinoma Herbert C. Wolfsen pdt@mayo.edu Mayo Clinic, Jacksonville, Florida Linda R. Jones Department of Physics College of Charleston Charleston, South Carolina

2. Early Esophageal Cancer Treatment: Is it Now an Endoscopic Disease? Ngamruengphong S, Wolfsen HC, Wallace MB. Clin Gastro Hep 2013

3. Porfimer sodium PDT for Esophageal Carcinoma and HGD High-Grade Dysplasia Laser Fiber Spacing Balloon

4. Photodynamic Therapy: The PHOBAR Trial RCT of 208 subjects with HGD Intervention: PDT+PPI or PPI alone (2:1) Follow-up: mean of 24.2 (PDT) and 18.6 (PPI) months Assessment: Bx’s every 6 months 1° Outcome: Ablation of all HGD 77% of PDT, 39% of PPI only 2° Outcome: 52% had complete eradication of IM Overholt BF et al, Gastrointest Endosc 2005;62:488-98. 28% 13%

5. Early Esophageal Cancer Survival 1618 pts HGD or T1aN0: 1998-2009 U.S. Population Stage, treatment, outcome from CMS-linked SEER database 306 (19%) Endoscopic Rx 1312 (81%) Surgical Rx

6. Barrett’s esophagus with Adenocarcinoma

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10. Balloon-based Bipolar Electrode 350 W at 465 kHz Short RF burst ~300 msec Standardized energy density Controls depth of ablation Enables uniform ablation Eliminates point-and-shoot

11. Ps-PDTRFA n= 208, 30 centers n= 127, 19 centers Drug therapy Omeprazole 20 mg bid Esomep 40 mg bid Nodular disease Additional 50 J/cmEndoscopic mucosal PDT light dose resection Ablation TxUp to 3 sessions,Up to 4 sessions circumferential only(circum and focal) (mean 2.3)(mean 3.5) CR-IM52%77% CR-HGD77%81% Progression to13% (28% Con)2% (19% Con) cancer Stricture36% 6% Follow-up24 months12 months

12. Primary endpoint: occurrence of complete remission of intestinal metaplasia At 24 months, likelihood of CRIM was higher after Ps-PDT (92%) compared to RFA (56%; RR: 4.47, p<0.001) & EMR-RFA (75%, RR: 2.69, p<0.001)

13. Conclusions Ps-PDT patients achieved remission from BE faster than EMR-RFA and RFA groups without a substantially higher recurrence rate Ps-PDT patients had fewer complications compared to EMR treated patients Bleeding significantly more common in EMR-RFA patients (12.2%) than both RFA patients (0.8%, P<0.001) and PDT patients (1.6%, P=0.001) Strictures less common in RFA patients (2.4%) compared to both EMR-RFA patients (13.3, P=0.001) and PDT patients (10.4%, P=0.043) Photosensitivity was reported in 10.4% of Ps-PDT patients.

15. Diffuse reflectanceFluorescence Determine Ps tissue content

16. Determine desired depth of treatment Mucosal thickness Esophageal wall 1.7 to 6.0 mm Mucosal thickness 1.0 to 2.0 mm

17. Use Monte Carlo simulation to predict the optimal light dose create enough singlet oxygen molecules to overcome the natural repair mechanisms and cause irreversible damage

18. Optical Model for BE: vasculature scatter thickness: mucosa wall

19. Cholangiocarcinoma 19 2 nd most common hepatic neoplasm; Most patients are not candidates for surgery For non-resectable cases, the 5-year survival rate is 0% and less than 5% in general. Overall median duration of survival is less than 6 months Extra hepatic and hilar tumors are the focus of PDT

20. Cholangiocarcinoma 20

21. 0500100015002000 0 50 100 PDT + E* E * p < 0.0001 Days % Survival time Ortner et al. Gastroenterology 2003 N = 39 *E = Endoprostheses Porfimer sodium 2 mg/kg i.v. 630nm, 180J/cm 2 Ps-PDT Associated with Increased Survival Compared with Endoscopic Drainage Alone Patients with unsuccessful drainage, tumors > 3 cm, n= 39 CONFIDENTIAL