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Topical MAL-PDT for cervical intraepithelial neoplasia treatment: a non-surgical option to prevent a cervical cancer
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Abstracts / Photodiagnosis and Photodynamic Therapy 12 (2015) 325–375
Topical MAL-PDT for cervical intraepithelial neoplasia treatment: a non-surgical option to prevent a cervical cancer Natalia Mayumi Inada 1 , Welington Lombardi 2 , Natalia Cossetin 2 , Fernanda Carbinatto 1 , Jose Roberto Trujillo 3 , Cristina Kurachi 1 , Vanderlei Salvador Bagnato 1 1 São Carlos Institute of Physics, University of Sao Paulo, Brazil 2 Woman Health Ambulatory, UNIARA, Brazil 3 Trubios, Johns Hopkins University, Rockville, MD, United States of America
Cervical cancer is the third most commonly diagnosed cancer and the fourth leading cause of cancer death in women worldwide. The highest incidence rates are in Africa, as well as South-Central Asia and South America. According to the National Institute of Cancer (INCA) at the last year, it was estimated 15,590 new cases of cervical cancer in Brazil. About 90% of cervical cancers originate in the evolution of cervical intraepithelial neoplasia (CIN) which is classified on the basis of cyto-histological characteristics (low and high grade lesions). The equipment (CerCa 150 System, MMOptics Ltda., Trubios LLC, Brazil-USA) and the medication (20% MAL cream, PDTPharma, Brazil) are produced in Brazil with relative low cost. The Photodynamic Therapy is a promising procedure and it is even known as safe to normal tissue. The device includes two components specifically adapted to detect and treat abnormal cervical tissue, enabling proper lighting of the cervix. It is portable and does not require special infrastructure or installation. More than 60 patients between the ages of 14-57 years and with CIN 1 were treated and presented 100% of cure. Based on these results a larger randomized study with patients with CIN 2, placebo and follow-up only is ongoing. http://dx.doi.org/10.1016/j.pdpdt.2015.07.202 Endobronchial Photodynamic Therapy in the Octogenarian Patrick Ross, Patsy Skabla, Priyal Shah, Rabih Bechara, David Berkowitz, Ayesha Bryant, Gregory Loewen, Daniel Nader, Momen Wahidi The Ohio State University College of Medicine, Columbus, OH, USA Purpose: Photodynamic therapy (PDT) has been used successfully in patients with endobronchial non-small cell lung cancer (NSCLC) with curative and palliative intent. We assessed short and long-term outcomes of PDT in octogenarian patients. Methods: This is a records review using a multicenter registry that consists of patients who received endobronchial PDT for curative intent or for management of symptoms including hemoptysis, post-obstructive pneumonia, and dyspnea. We evaluated adverse events and clinical outcomes including survival. All patients received porfimer sodium at 2 mg/kg intravenously as the photosensitizer. Light was administered at 630 nm for a total dose of 200 J. Results: Between 1998 and 2014, 893 patients were treated with 1061 courses of PDT at 5 centers. Endobronchial PDT accounted for 530 of the cases. Thirty patients were over 80 years old (>80). Eleven of 30 patients >80 had early stage endobronchial tumors (I/II); 19 patients had advanced stage (III/IV). Two patients >80 received multiple courses of PDT; 60 patients <80 had a second course of PDT. In the >80 cohort, 5 patients had received chemotherapy prior to PDT; in the < 80 cohort, 58 patients had received chemotherapy. In
the >80 group the adverse event rate was 0. In the <80 group, there were 16 adverse events (3.2%) including phototoxicity, dyspnea, and hemoptysis. Mean survival in the early stage >80 cohort was 844 days (range 25 – 3983). Mean survival in the advanced stage >80 was 192 days (range 6 – 805). Conclusions: Endobronchial PDT with porfimer sodium is associated with minimal toxicity in the octogenarian. Phototoxicity was minimal overall and did not occur in the >80 group. Survival is excellent in the octogenarian for early and advanced stage patients treated with PDT. PDT should be considered as a single modality treatment where appropriate and as an adjunct when symptom management is necessary in the elderly patient. http://dx.doi.org/10.1016/j.pdpdt.2015.07.203 Perfusion CT examined as a surrogate dosimetry tool to estimate verteporfin uptake in rabbit orthotopic pancreas cancer Brian W Pogue, Jonathan Elliott, Kimberley S. Samkoe, Jason R. Gunn, Errol Stewart, Timothy Gardner, Ting-Yim Lee, P. Jack Hoopes, Steve Pereira, Tayyaba Hasan Engineering & Surgery, Dartmouth College, Hanover NH USA; Dept of Medical Biophysics, Western University, Canada,; Inst. for Liver & Digestive Disease, University College London, UK; Massachusetts General Hospital, Harvard Medical School, Boston MA USA It was hypothesized that perfusion computed tomography (CT) blood flow (BF), blood volume (BV) and vascular permeability surface-area (PS) product parameters would be predictive of photosensitizer uptake in pancreatic cancer, facilitating image-guided interpretation of human treatments. The hypothesis was tested in an orthotopic rabbit model of pancreatic cancer, by establishing the model, imaging with endoscopic ultrasound and contrast CT, and spatially comparing the perfusion maps to the ex vivo uptake values of injected photosensitizer, Vertepofin. Nine New Zealand White rabbits underwent direct pancreas implantation of VX2 tumors and CT perfusion or endoscopic ultrasound was performed 10 days post-implantation. Verteporfin was injected during CT imaging and tissue was removed 1 h post-injection for frozen tissue fluorescence scanning. Region-of-interest comparisons of CT data with ex vivo fluorescence and histopathological staining were performed. DCE-CT showed enhanced BF, BV, and PS in the tumor rim, and decreased BF, BV and PS in the tumor core. Significant correlations were found between ex vivo verteporfin concentration and each of BF, BV, and PS. The efficacy of verteporfin delivery in tumors is estimated by perfusion CT, providing a non-invasive method of mapping photosensitizer dose. http://dx.doi.org/10.1016/j.pdpdt.2015.07.204
Abstracts / Photodiagnosis and Photodynamic Therapy 12 (2015) 325–375
Topical MAL-PDT for cervical intraepithelial neoplasia treatment: a non-surgical option to prevent a cervical cancer Natalia Mayumi Inada 1 , Welington Lombardi 2 , Natalia Cossetin 2 , Fernanda Carbinatto 1 , Jose Roberto Trujillo 3 , Cristina Kurachi 1 , Vanderlei Salvador Bagnato 1 1 São Carlos Institute of Physics, University of Sao Paulo, Brazil 2 Woman Health Ambulatory, UNIARA, Brazil 3 Trubios, Johns Hopkins University, Rockville, MD, United States of America
Cervical cancer is the third most commonly diagnosed cancer and the fourth leading cause of cancer death in women worldwide. The highest incidence rates are in Africa, as well as South-Central Asia and South America. According to the National Institute of Cancer (INCA) at the last year, it was estimated 15,590 new cases of cervical cancer in Brazil. About 90% of cervical cancers originate in the evolution of cervical intraepithelial neoplasia (CIN) which is classified on the basis of cyto-histological characteristics (low and high grade lesions). The equipment (CerCa 150 System, MMOptics Ltda., Trubios LLC, Brazil-USA) and the medication (20% MAL cream, PDTPharma, Brazil) are produced in Brazil with relative low cost. The Photodynamic Therapy is a promising procedure and it is even known as safe to normal tissue. The device includes two components specifically adapted to detect and treat abnormal cervical tissue, enabling proper lighting of the cervix. It is portable and does not require special infrastructure or installation. More than 60 patients between the ages of 14-57 years and with CIN 1 were treated and presented 100% of cure. Based on these results a larger randomized study with patients with CIN 2, placebo and follow-up only is ongoing. http://dx.doi.org/10.1016/j.pdpdt.2015.07.202 Endobronchial Photodynamic Therapy in the Octogenarian Patrick Ross, Patsy Skabla, Priyal Shah, Rabih Bechara, David Berkowitz, Ayesha Bryant, Gregory Loewen, Daniel Nader, Momen Wahidi The Ohio State University College of Medicine, Columbus, OH, USA Purpose: Photodynamic therapy (PDT) has been used successfully in patients with endobronchial non-small cell lung cancer (NSCLC) with curative and palliative intent. We assessed short and long-term outcomes of PDT in octogenarian patients. Methods: This is a records review using a multicenter registry that consists of patients who received endobronchial PDT for curative intent or for management of symptoms including hemoptysis, post-obstructive pneumonia, and dyspnea. We evaluated adverse events and clinical outcomes including survival. All patients received porfimer sodium at 2 mg/kg intravenously as the photosensitizer. Light was administered at 630 nm for a total dose of 200 J. Results: Between 1998 and 2014, 893 patients were treated with 1061 courses of PDT at 5 centers. Endobronchial PDT accounted for 530 of the cases. Thirty patients were over 80 years old (>80). Eleven of 30 patients >80 had early stage endobronchial tumors (I/II); 19 patients had advanced stage (III/IV). Two patients >80 received multiple courses of PDT; 60 patients <80 had a second course of PDT. In the >80 cohort, 5 patients had received chemotherapy prior to PDT; in the < 80 cohort, 58 patients had received chemotherapy. In
the >80 group the adverse event rate was 0. In the <80 group, there were 16 adverse events (3.2%) including phototoxicity, dyspnea, and hemoptysis. Mean survival in the early stage >80 cohort was 844 days (range 25 – 3983). Mean survival in the advanced stage >80 was 192 days (range 6 – 805). Conclusions: Endobronchial PDT with porfimer sodium is associated with minimal toxicity in the octogenarian. Phototoxicity was minimal overall and did not occur in the >80 group. Survival is excellent in the octogenarian for early and advanced stage patients treated with PDT. PDT should be considered as a single modality treatment where appropriate and as an adjunct when symptom management is necessary in the elderly patient. http://dx.doi.org/10.1016/j.pdpdt.2015.07.203 Perfusion CT examined as a surrogate dosimetry tool to estimate verteporfin uptake in rabbit orthotopic pancreas cancer Brian W Pogue, Jonathan Elliott, Kimberley S. Samkoe, Jason R. Gunn, Errol Stewart, Timothy Gardner, Ting-Yim Lee, P. Jack Hoopes, Steve Pereira, Tayyaba Hasan Engineering & Surgery, Dartmouth College, Hanover NH USA; Dept of Medical Biophysics, Western University, Canada,; Inst. for Liver & Digestive Disease, University College London, UK; Massachusetts General Hospital, Harvard Medical School, Boston MA USA It was hypothesized that perfusion computed tomography (CT) blood flow (BF), blood volume (BV) and vascular permeability surface-area (PS) product parameters would be predictive of photosensitizer uptake in pancreatic cancer, facilitating image-guided interpretation of human treatments. The hypothesis was tested in an orthotopic rabbit model of pancreatic cancer, by establishing the model, imaging with endoscopic ultrasound and contrast CT, and spatially comparing the perfusion maps to the ex vivo uptake values of injected photosensitizer, Vertepofin. Nine New Zealand White rabbits underwent direct pancreas implantation of VX2 tumors and CT perfusion or endoscopic ultrasound was performed 10 days post-implantation. Verteporfin was injected during CT imaging and tissue was removed 1 h post-injection for frozen tissue fluorescence scanning. Region-of-interest comparisons of CT data with ex vivo fluorescence and histopathological staining were performed. DCE-CT showed enhanced BF, BV, and PS in the tumor rim, and decreased BF, BV and PS in the tumor core. Significant correlations were found between ex vivo verteporfin concentration and each of BF, BV, and PS. The efficacy of verteporfin delivery in tumors is estimated by perfusion CT, providing a non-invasive method of mapping photosensitizer dose. http://dx.doi.org/10.1016/j.pdpdt.2015.07.204