CT contrast predicts pancreatic cancer treatment response to verteporfin-based photodynamic therapy

Michael Jermyn,Tayyaba Hasan,Stephen G Bown,Scott C Davis,Hamid Dehghani,Matthew T Huggett,Brian W Pogue,Stephen P Pereira

doi:10.1088/0031-9155/59/8/1911

Abstract

The goal of this study was to determine dominant factors affecting treatment response in pancreatic cancer photodynamic therapy (PDT), based on clinically available information in the VERTPAC-01 trial. This trial investigated the safety and efficacy of verteporfin PDT in 15 patients with locally advanced pancreatic adenocarcinoma. CT scans before and after contrast enhancement from the 15 patients in the VERTPAC-01 trial were used to determine venous-phase blood contrast enhancement and this was correlated with necrotic volume determined from post-treatment CT scans, along with estimation of optical absorption in the pancreas for use in light modeling of the PDT treatment. Energy threshold contours yielded estimates for necrotic volume based on this light modeling. Both contrast-derived venous blood content and necrotic volume from light modeling yielded strong correlations with observed necrotic volume (R2 = 0.85 and 0.91, respectively). These correlations were much stronger than those obtained by correlating energy delivered versus necrotic volume in the VERTPAC-01 study and in retrospective analysis from a prior clinical study. This demonstrates that contrast CT can provide key surrogate dosimetry information to assess treatment response. It also implies that light attenuation is likely the dominant factor in the VERTPAC treatment response, as opposed to other factors such as drug distribution. This study is the first to show that contrast CT provides needed surrogate dosimetry information to predict treatment response in a manner which uses standard-of-care clinical images, rather than invasive dosimetry methods.

Highlights

Pancreatic cancer is the fourth leading cause of cancer-related death in the United States (Hariharan et al 2008), with an estimated 37 390 deaths from the disease in 2012
This paper presents an analysis of 15 patients with locally advanced pancreatic cancer treated with photodynamic therapy, and estimates the extent of treatment response based on information derived from contrast CT scans
The light dose maps produced from light modeling can be used to estimate necrotic volume provided a suitable energy threshold value is determined

Summary

Introduction

Pancreatic cancer is the fourth leading cause of cancer-related death in the United States (Hariharan et al 2008), with an estimated 37 390 deaths from the disease in 2012. The overall 5-year survival rate is estimated at 5.8%, and treatment options are limited, with surgical removal as an option for only 15% of patients (Howlader et al 2012). Patients unable to undergo surgery are generally treated with chemotherapeutics which offer marginal improvements in survival, and an urgent need exists for alternative strategies to treat pancreatic cancer more effectively. Photodynamic therapy (PDT) is a minimally invasive and nontoxic method of treating cancer using the interaction of light and a photosensitizer, in the presence of oxygen, to kill tumor cells (Wilson and Patterson 1986). There is indirect cell death caused by induced hypoxia through tumor vasculature damage. Since the effect is photochemical, rather than thermal, there is no significant damage to connective tissues (Barr et al 1987)

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