Phase II Trial of Debulking Surgery and Photodynamic Therapy for Disseminated Intraperitoneal Tumors

Hendren, Samantha; Hahn, Stephen M.; Spitz, Francis R.; Bauer, Todd W.; Rubin, Stephen C.; Zhu, Timothy C.; Glatstein, Eli; Fraker, Douglas L.

doi:10.1007/s10434-001-0065-x

Cited by 99 publications

(53 citation statements)

References 12 publications

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“…The EF5 trials were approved by Cancer Therapy Evaluation Program, National Cancer Institute. Exclusion and inclusion criteria for these trials have been published previously (5,16). Patients provided separate written informed consent for each trial.…”

Section: Methodsmentioning

confidence: 99%

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Hypoxia and Photofrin Uptake in the Intraperitoneal Carcinomatosis and Sarcomatosis of Photodynamic Therapy Patients

Busch

Hahn

Wileyto³

et al. 2004

Clinical Cancer Research

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Purpose: Response to photodynamic therapy depends on adequate tumor oxygenation as well as sufficient accumulation of photosensitizer in the tumor. The goal of this study was to investigate the presence of hypoxia and retention of the photosensitizer Photofrin in the tumors of patients with intra-abdominal carcinomatosis or sarcomatosis.Experimental Design: Tumor nodules from 10 patients were studied. In nine of these patients, hypoxia was identified in histological sections of biopsied tumor after administration of the hypoxia marker 2-(2-nitroimidazol-1[H]-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide (EF5). In separate tumor nodules from 10 patients, Photofrin uptake was measured by fluorescence after tissue solubilization.Results: Hypoxia existed in the tumors of five patients, with three of these patients demonstrating at least one severely hypoxic nodule. Physiological levels of oxygen were present in the tumors of four patients. An association between tumor size and hypoxia was not evident because some tumor nodules as small as ϳ2 mm in diameter were severely hypoxic. However, even these tumor nodules contained vascular networks. Three patients with severely hypoxic tumor nodules exhibited moderate levels of Photofrin uptake of 3.9 ؎ 0.4 to 3.9 ؎ 0.5 ng/mg (mean ؎ SE). The four patients with tumors of physiological oxygenation did not consistently exhibit high tumor concentrations of Photofrin: mean ؎ SE drug uptake among these patients ranged from 0.6 ؎ 0.8 to 5.8 ؎ 0.5 ng/mg.Conclusions: Carcinomatosis or sarcomatosis of the i.p. cavity may exhibit severe tumor hypoxia. Photofrin accumulation in tumors varied by a factor of ϳ10؋ among all patients, and, on average, those with severe hypoxia in at least one nodule did not demonstrate poor Photofrin uptake in separate tumor samples. These data emphasize the need for reconsideration of the generally accepted paradigm of small tumor size, good oxygenation, and good drug delivery because this may vary on an individual tumor basis.

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Section: Methodsmentioning

confidence: 99%

“…Feasibility of this approach was demonstrated in a Phase I study of intraoperative Photofrin PDT after debulking surgery of i.p. disease (6), and a Phase II trial has recently been completed (5). The efficacy of this modality is determined by the simultaneous presence of the required components for PDT: photosensitizer; oxygen; and light.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia and Photofrin Uptake in the Intraperitoneal Carcinomatosis and Sarcomatosis of Photodynamic Therapy Patients

Busch

Hahn

Wileyto³

et al. 2004

Clinical Cancer Research

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“…This inherent capability to integrate imaging and PDT treatment, which makes PS imaging particularly conducive to online monitoring of therapy response, was not used in the studies referenced above. It is also worth noting that the application of PDT to the treatment of OvCa has shown promise in clinical trials (Sindelar et al, 1991;Hendren et al, 2001;Hahn et al, 2006), although further studies are warranted to establish optimal conditions for light and PS delivery in the clinic.…”

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confidence: 99%

In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring

et al. 2009

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BACKGROUND: In patients with advanced ovarian cancer (OvCa), microscopic residual tumour nodules that remain after surgical debulking frequently escape detection by current treatment assessment methods and lead to disease recurrence. The aim of this study was to evaluate the use of high-resolution fibre-optic fluorescence imaging of the clinically approved photodynamic therapy (PDT) agent benzoporphyin-derivative monoacid ring A (BPD-MA) for detection of microscopic OvCa and for monitoring treatment response. METHODS: Our fluorescence microendoscope consists of a flexible imaging fibre coupled to a custom epi-fluorescence system optimised for imaging BPD-MA, which, after a single administration, serves as both an imaging agent and a light-activated therapeutic agent. After characterisation in an in vitro OvCa 3D model, we used the flexible imaging fibre to minimally invasively image the peritoneal cavity of a disseminated OvCa murine model using BPD-MA administered intraperitoneally (i.p.). To evaluate longitudinal changes in response to treatment, we compared sets of images obtained before and after PDT with those from untreated mice imaged at the same time points. RESULTS: By comparison with histopathology, we report an 86% sensitivity for tumour detection in vivo using the microendoscope. Using a custom routine to batch process-image data in the monitoring study, treated mice exhibited an average decrease of 58.8% in tumour volumes compared with an increase of 59.3% in untreated controls (Po0.05). CONCLUSIONS: Our findings indicate the potential of this approach as a reporter of treatment outcome that could aid in the rational design of strategies to mitigate recurrent OvCa.

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“…Flat photodiode detectors have been used to measure the incident irradiance at the tissue surface in intraoperative PDT. 32 These measurements, however, may not accurately reflect the fluence rate in the tissue itself because they neglect contribution of backscattered light. Detectors based on optical fibers overcome this problem by collecting light isotropically.…”

Section: Iib2 Pdt Dosimetrymentioning

confidence: 99%

The role of photodynamic therapy (PDT) physics

2008

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Photodynamic therapy ͑PDT͒ is an emerging treatment modality that employs the photochemical interaction of three components: light, photosensitizer, and oxygen. Tremendous progress has been made in the last 2 decades in new technical development of all components as well as understanding of the biophysical mechanism of PDT. The authors will review the current state of art in PDT research, with an emphasis in PDT physics. They foresee a merge of current separate areas of research in light production and delivery, PDT dosimetry, multimodality imaging, new photosensitizer development, and PDT biology into interdisciplinary combination of two to three areas. Ultimately, they strongly believe that all these categories of research will be linked to develop an integrated model for real-time dosimetry and treatment planning based on biological response.

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Phase II Trial of Debulking Surgery and Photodynamic Therapy for Disseminated Intraperitoneal Tumors

Cited by 99 publications

References 12 publications

Hypoxia and Photofrin Uptake in the Intraperitoneal Carcinomatosis and Sarcomatosis of Photodynamic Therapy Patients

Hypoxia and Photofrin Uptake in the Intraperitoneal Carcinomatosis and Sarcomatosis of Photodynamic Therapy Patients

In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring

The role of photodynamic therapy (PDT) physics

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