current status of pdt in gastroenterology 2015: esophageal carcinoma & cholangiocarcinoma...
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Current Status of PDT in Gastroenterology 2015:
Esophageal Carcinoma & Cholangiocarcinoma
Herbert C. [email protected] 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