Current Status of PDT in Gastroenterology 2015:

Esophageal Carcinoma & Cholangiocarcinoma

Herbert C. Wolfsenpdt@mayo.eduMayo Clinic, Jacksonville, Florida

Linda R. JonesDepartment of PhysicsCollege of CharlestonCharleston, South Carolina

Early Esophageal Cancer Treatment: Is it Now an Endoscopic Disease?

Ngamruengphong S, Wolfsen HC, Wallace MB. Clin Gastro Hep 2013

Porfimer sodium PDT for Esophageal Carcinoma and HGD

High-GradeDysplasia

LaserFiber

Spacing Balloon

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

0

5

10

15

20

25

30

Cancer Incidence (%)

PPI

PDT + PPI

Overholt BF et al, Gastrointest Endosc 2005;62:488-98.

28%

13%

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

Barrett’s esophagus with Adenocarcinoma

©2011 MFMER | slide-7

©2011 MFMER | slide-8

©2011 MFMER | slide-9

Balloon-based Bipolar Electrode350 W at 465 kHz

Short RF burst ~300 msec

Standardized energy densityControls depth of ablationEnables uniform ablation

Eliminates point-and-shoot

Ps-PDT RFAn= 208, 30 centers n= 127, 19 centers

Drug therapy Omeprazole 20 mg bid Esomep 40 mg bid

Nodular disease Additional 50 J/cm Endoscopic mucosal PDT light dose resection

Ablation Tx Up to 3 sessions, Up to 4 sessionscircumferential only (circum and focal)(mean 2.3) (mean 3.5)

CR-IM 52% 77%CR-HGD 77% 81%

Progression to 13% (28% Con) 2% (19% Con)cancer

Stricture 36% 6%Follow-up 24 months 12 months

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)

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.

Diffuse reflectance Fluorescence

0

20

40

60

80

100

120

140

160

180

600 650 700 750

Barrett's

Normal esophagus

Determine Ps tissue content

Determine desired depth of treatmentMucosal thickness

Esophageal wall 1.7 to 6.0 mm

Mucosal thickness 1.0 to 2.0 mm

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

Optical Model for BE:

vasculaturescatterthickness:mucosawall

Cholangiocarcinoma

19

2nd 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

Cholangiocarcinoma

20

0 500 1000 1500 20000

50

100PDT + E*E *

p < 0.0001

Days

% S

urvi

val ti

me

Ortner et al. Gastroenterology 2003

N = 39

*E = EndoprosthesesPorfimer sodium 2 mg/kg i.v. 630nm, 180J/cm2

Ps-PDT Associated with Increased Survival Compared with Endoscopic Drainage AlonePatients with unsuccessful drainage, tumors > 3 cm, n= 39

CONFIDENTIAL