Photofrin Research Articles

Recent Studies in Photodynamic Therapy for Cancer Treatment: From Basic Research to Clinical Trials.

Photodynamic therapy (PDT) is an emerging and less invasive treatment modality for various types of cancer. This review provides an overview of recent trends in PDT research, ranging from basic research to ongoing clinical trials, focusing on different cancer types. Lung cancer, head and neck cancer, non-melanoma skin cancer, prostate cancer, and breast cancer are discussed in this context. In lung cancer, porfimer sodium, chlorin e6, and verteporfin have shown promising results in preclinical studies and clinical trials. For head and neck cancer, PDT has demonstrated effectiveness as an adjuvant treatment after surgery. PDT with temoporfin, redaporfin, photochlor, and IR700 shows potential in early stage larynx cancer and recurrent head and neck carcinoma. Non-melanoma skin cancer has been effectively treated with PDT using methyl aminolevulinate and 5-aminolevulinic acid. In prostate cancer and breast cancer, PDT research is focused on developing targeted photosensitizers to improve tumor-specific uptake and treatment response. In conclusion, PDT continues to evolve as a promising cancer treatment strategy, with ongoing research spanning from fundamental investigations to clinical trials, exploring various photosensitizers and treatment combinations. This review sheds light on the recent advancements in PDT for cancer therapy and highlights its potential for personalized and targeted treatments.

Homology Modeling, Screening, and Identification of Potential FOXO6 Inhibitors Curtail Gastric Cancer Progression: an In Silico Drug Repurposing Approach.

Gastric cancer is the world's second leading cause of cancer-related fatalities, with the epidemiology changing over the previous several decades. FOXOs are the O subfamily of the forkhead box (FOX) transcription factor family, which consists of four members: FOXO1, FOXO3, FOXO4, and FOXO6. FOXO6 mRNA and protein levels are increased in gastric cancer tissues. FOXO6 forced overexpression enhances gastric cancer cell growth, while knockdown decreases proliferation. In our study, the GEPIA, Kaplan-Meier, KEGG, and STRING databases were used to determine FOXO6 mRNA expression, overall survival ratio, interactive pathways, and top 10 associated proteins in gastric cancer respectively. Due to the lack of a solved structure for FOXO6, homology modeling was performed to obtain a 3D structure model, and we used anti-cancer drugs and small molecules to target FOXO6 for identifying a potential selective FOXO6 inhibitor. The chemical composition of the proteins and ligands has a significant impact on docking procedure performance. With this in mind, a critical evaluation of the performance of three regularly used docking routines was carried out: MVD, AutoDock Vina in PyRx, and ArgusLab. The binding affinities, docking scores, and intermolecular interactions were used as assessment criteria. In the study, the porfimer sodium showed excellent binding affinity to the FOXO6 protein. The major three docking software packages were used to analyze the scoring/H-bonding energy and intermolecular interactions. Based on the results, we concluded that FOXO6 was upregulated in gastric cancer and the ligand porfimer sodium emerges as a promising potential FOXO6 inhibitor to curtail gastric cancer progression.

Abstract 2423: Image-guided interstitial photodynamic therapy with palliative radiotherapy for ablating extrabronchial malignant central airway obstruction

Abstract Background: Patients with extrabronchial tumors that induce malignant central airway obstruction (MCAO) face dire prognoses with significant morbidity and 1-7 months overall survival. These tumors are inoperable. High-dose curative radiotherapy is associated with significant toxicity. Chemotherapy has limited localized benefits and immunotherapy cannot address the immediate need to halt tumor progression. Our preliminary data suggest that image-guided interstitial photodynamic therapy (I-PDT) with porfimer sodium is safe and potentially effective in patients with extrabronchial tumors that induce MCAO and there is a need to further improve the rate of response. Here we present results showing an improved tumor response rate by augmenting I-PDT with palliative radiotherapy (p-XRT). Methods: We investigated the addition of p-XRT prior to I-PDT to sensitize the target tumor to subsequent photoreaction in mouse models. Eight- to twelve-week-old C3H and C57B/6 mice with locally advanced (400-600 mm3) SCC-VII or LLC tumors, respectively, were treated with I-PDT alone or with p-XRT followed by I-PDT. The p-XRT regimen was 10 Gy x2 over two days. At 24-26 h after the second 10 Gy fraction, the I-PDT was administered with 5 mg/kg porfimer sodium activated with 630-nm laser light at 5.0 mW/cm2 and 45 J/cm2 at tumor margins. Photoacoustic imaging and light dosimetry measurements were used to investigate the impact of p-XRT on the tumor microenvironment as it pertains to the response to I-PDT. Tumor progression was monitored over 60 days. Image-based treatment planning was used to translate the preclinical findings into a treatment in clinical settings (8 Gy x1 followed by I-PDT) for patients with extrabronchial MCAO. Results: Preceding I-PDT with p-XRT increases tumor oxygenation for 1-2 days after the last radiation fraction and improves light penetration within mouse tumors. Administering p-XRT 24-48 h before I-PDT significantly (p<0.05, log-rank test) increases the rate of complete tumor response and control from 0% in p-XRT alone or 0-6% in I-PDT alone, to 31-64% for p-XRT followed by I-PDT. In patients, administration of I-PDT with porfimer sodium 48 h after 8Gy x1 p-XRT is feasible and can provide control of extrabronchial MCAO accompanied by symptomatic relief. Conclusions: Augmenting I-PDT with p-XRT improves the rate of tumor response. Murine studies show that p-XRT increases tumor blood oxygenation and light penetration which could contribute to better response to I-PDT. I-PDT with porfimer sodium preceded by p-XRT is feasible with possible benefits in patients with extrabronchial MCAO. Citation Format: Emily Oakley, Sarah Chamberlain, Nathaniel Ivanick, Alan Hutson, Theresa Busch, Gal Shafirstein. Image-guided interstitial photodynamic therapy with palliative radiotherapy for ablating extrabronchial malignant central airway obstruction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2423.

Safety and Feasibility of Photodynamic Therapy for Ablation of Peripheral Lung Tumors.

Newer navigational bronchoscopy technologies render peripheral lung lesions accessible for biopsy and potential treatment. We investigated whether photodynamic therapy (PDT) delivered via navigational bronchoscopy is feasible and safe for ablation of peripheral lung tumors. Two studies evaluated PDT in patients with solid peripheral lung tumors followed by clinical follow-up (nonresection study, N=5) or lobectomy (resection study, N=10). Porfimer sodium injection was administered 40 to 50 hours before navigational bronchoscopy. Lesion location was confirmed by radial probe endobronchial ultrasonography. An optical fiber diffuser was placed within or adjacent to the tumor under fluoroscopic guidance; laser light (630nm wavelength) was applied at 200J/cm of diffuser length for 500 seconds. Tumor response was assessed by modified Response Evaluation Criteria in Solid Tumors at 3 and 6 months postprocedure (nonresection study) and pathologically (resection study). There were no deaths, discontinuations for adverse events, or serious or grade ≥3 adverse events related to study treatments. Photosensitivity reactions occurred in 8 of 15 patients: 6 mild, 1 moderate, 1 severe (elevated porphyrins noted in blood after treatment). Among 5 patients with clinical follow-up, 1 had complete response, 3 had stable disease, and 1 had progressive disease at 6 months follow-up. Among 10 patients who underwent lobectomy, 1 had no evidence of tumor at resection (complete response), 3 had 40% to 50% tumor cell necrosis, 2 had 20% to 35%, and 4 had 5% to 10%. PDT for nonthermal ablation of peripheral lung tumors was feasible and safe in this small study. Further study is warranted to evaluate efficacy and corroborate the safety profile.

Long-term effect of photodynamic therapy on oral squamous cell carcinoma and epithelial dysplasia.

Oral squamous cell carcinoma (OSCC) treatment consists mainly of surgery, chemotherapy, and radiotherapy, alone or in combination. Epithelial dysplasia (ED) is also treated with surgery. However, these treatments can induce functional and/or aesthetic disturbances. Photodynamic therapy (PDT) can preserve organs. Although short-term studies have shown good progress, long-term evaluations have not yet been conducted. This study aimed to clarify the long-term effects of PDT on OSCC and ED. Patients who underwent PDT with the first (porfimer sodium) or second generation photosensitizers (talaporfin sodium) for early OSCC (T1 and T2) and ED were included in this study. The long-term prognosis was assessed. Twenty-three patients were included. Complete response (CR) was observed in 19 patients (82.6%) and partial response (PR) in 4 patients (17.4%) 4 weeks after PDT. Regarding long-term progress, local region recurrence occurred in 11 of 19 CR cases (57.9%), and the term of recurrence was 27.4 ± 30.4 months. Surgical resection was performed in all local recurrence and PR cases, and 3 patients died of the underlying disease. PDT provides a good outcome in the short term, but its long-term effects are limited.

Novel light delivery method for performing transbronchial photodynamic therapy ablation to treat peripheral lung cancer: A pilot study

BackgroundPhotodynamic therapy involves using a photosensitizer with l illumination and is recommended for treating early, centrally located lung cancers, but it is not a standard treatment for peripheral lung tumor.. We previously proposed a novel light delivery method, in which lipiodol is perfused into the bronchial tree to increase the scope of illumination via the fiber effect. Herein, we attempted this novel technique under electromagnetic bronchoscope guidance in a hybrid operation room where lipiodol facilitated light diffusion, and evaluated the effectiveness and feasibility of this technique for peripheral lung cancers. MethodsThis phase 0 pilot study included three patients with peripheral lung cancers (primary tumors ≤20-mm diameter). The photodynamic therapy was administered using Porfimer sodium as the photosensitizer, and an electromagnetic navigation bronchoscope in a hybrid operating room to guide the catheter to the tumor. This facilitated lipiodol infusion to encase the tumor and permit the transbronchial photodynamic therapy ablation. ResultsAdministering 630 nm 200 J/cm (400mW/500sec) energy through a 3-cm cylindrical diffusing laser fiber was safe; no significant acute complications were observed. Although the treatment outcome was unsatisfactory due to the low light dose, tumor pathology in one case revealed tumor necrosis, with no significant damage to the surrounding lung tissue. ConclusionsNovel light delivery transbronchial photodynamic therapy ablation for peripheral lung tumors is feasible and safe. Additional clinical trials may help determine the best illumination plan and light dose through multiple deliveries from multiple angles.

Development of Novel Tetrapyrrole Structure Photosensitizers for Cancer Photodynamic Therapy.

The effectiveness of photodynamic therapy (PDT) is based on the triad effects of photosensitizer (PS), molecular oxygen and visible light on malignant tumors. Such complex induces a multifactorial manner including reactive-oxygen-species-mediated damage and the killing of cells, vasculature damage of the tumor, and activation of the organism immunity. The effectiveness of PDT depends on the properties of photosensitizing drugs, their selectivity, enhanced photoproduction of reactive particles, absorption in the near infrared spectrum, and drug delivery strategies. Photosensitizers of the tetrapyrrole structure (porphyrins) are widely used in PDT because of their unique diagnostic and therapeutic functions. Nevertheless, the clinical use of the first-generation PS (sodium porfimer and hematoporphyrins) revealed difficulties, such as long-term skin photosensitivity, insufficient penetration into deep-seated tumors and incorrect localization to it. The second generation is based on different approaches of the synthesis and conjugation of porphyrin PS with biomolecules, which made it possible to approach the targeted PDT of tumors. Despite the fact that the development of the second-generation PS started about 30 years ago, these technologies are still in demand and are in intensive development, especially in the direction of improving the process of optimization split linkers responsive to input. Bioconjugation and encapsulation by targeting molecules are among the main strategies for developing of the PS synthesis. A targeted drug delivery system with the effect of increased permeability and retention by tumor cells is one of the ultimate goals of the synthesis of second-generation PS. This review presents porphyrin PS of various generations, discusses factors affecting cellular biodistribution and uptake, and indicates their role as diagnostic and therapeutic (theranostic) agents. New complexes based on porphyrin PS for photoimmunotherapy are presented, where specific antibodies are used that are chemically bound to PS, absorbing light from the near infrared part of the spectrum. Additionally, a two-photon photodynamic approach using third-generation photosensitizers for the treatment of tumors is discussed, which indicates the prospects for the further development of a promising method antitumor PDT.

Disinfection of radicular dentin using Riboflavin, Rose Bengal, Curcumin, and Porfimer sodium on extrusion bond strength of fiber post to radicular dentin

AimTo assess the influence of different photosensitizers activated by PDT as a disinfectant in comparison to conventional sodium hypochlorite (NaOCl) on the EBS (extrusion bond strength) of FRCP with radicular dentin. MethodsA total of fifty single-rooted human maxillary central incisors with fully developed apices were selected. Endodontic treatment of samples was performed using 10 K file to obtain patency than sequentially with a 25 K file followed by rotary pro tapers till F2 with constant irrigation. The canal was dried and obturated with corresponding gutta-percha and sealer. A Peso reamer was employed to prepare post space. Based on canal disinfection regimes, samples were divided into five groups. Group 1 Riboflavin (RF)+17%EDTA, group 2 Rose bengal (RB) +17%EDTA, group 3 Curcumin CP +17%EDTA, group 4 Porfimer sodium, Photofrin (PS) +17%EDTA and group 5 2.25% NaOCl +17% EDTA (control). Following disinfection, the canal space of all specimens was dried followed by FRCP cementation. Specimens were placed on a Universal testing machine (UTM) for EBS. The type of bond failure was evaluated using a stereomicroscope. ANOVA and Tukey multiple comparison tests were used to compare means. ResultsThe highest EBS was shown by group 1 canal disinfected with riboflavin (RF) and 17% EDTA at all three levels. The lowest EBS was displayed in group 5 canal cleaned with 2.25% NaOCl and 17% EDTA. Intragroup assessment disclosed a decrease in EBS from cervical one-third to apical one-third in all experimental groups. Intergroup comparison revealed group 4 using PS and 17% EDTA and group 5 canal disinfected with 2.25% NaOCl and 17% EDTA at all three levels of root structure coronal, middle, and apical exhibited comparable EBS (p>0.05). ConclusionRoot canal dentin treated with different PS (RF, RB, CP) has the potential to be used as canal disinfection as it demonstrates better EBS than the conventional disinfecting regime (2.25% NaOCl +17% EDTA). PS and 17% EDTA as a canal disinfectant need further investigation.

Repeated talaporfin sodium photodynamic therapy for esophageal cancer: safety and efficacy

BackgroundTalaporfin sodium photodynamic therapy (tPDT) is an effective salvage treatment for local failure after chemoradiotherapy for esophageal cancer. Repeated tPDT could also be indicated for local recurrence or residue after the first salvage tPDT. However, the safety and efficacy of repeated tPDT have not been elucidated.MethodsWe reviewed 52 patients with esophageal cancer who were treated with the first tPDT at Kyoto University Hospital between October 2015 and April 2020.ResultsAmong 52 patients, repeated tPDT after the first tPDT was indicated for 13 patients (25%), of which six had residual tumor, four had local recurrence after complete response (CR) after the first tPDT at the primary site, and six had metachronous lesion. The total session of repeated tPDT was 25; 16 were for primary sites and nine were for metachronous sites. Among them, six patients (46.2%) achieved local (L)-CR and nine lesions (56.3%) achieved lesion L-CR. By session, 10 sessions (40%) achieved L-CR. There were no severe adverse events except for one patient; this patient showed grade 3 esophageal stenosis and perforation after the third tPDT on the same lesion that was previously treated with porfimer sodium photodynamic therapy four times.ConclusionRepeated tPDT could be an effective and safe treatment for local failure even after salvage tPDT for esophageal cancer.

Porfimer Sodium Versus PS785 for Photodynamic Therapy (PDT) of Lung Cancer Xenografts in Mice

BackgroundLung cancer is the greatest cause of cancer mortality in the United States, necessitating ongoing improvements in current treatment techniques. Photodynamic therapy (PDT) involves the interaction between a photosensitizer, light, and oxygen. The resulting release of reactive oxygen species causes tumor necrosis. It has been used as an endoscopic technique for the palliation of lung cancer. Porfimer sodium (Photofrin) is the only Food and Drug Administration–approved photosensitizer for PDT but has limited depth of penetration and produces prolonged skin phototoxicity. Multiple newer photosensitizers are in development, including PS785. The effectiveness of PS785 was compared with porfimer sodium in the treatment of human lung cancer xenografts in mice. MethodsHuman non–small cell lung cancer (NSCLC) xenografts were established in severe combined immunodeficient mice and grouped into small (3-5 mm) and large tumors (6-10 mm). PS785 or porfimer sodium was administered intravenously, and PDT was executed at 24, 48, or 72 h after injection. The primary endpoint was the delay of tumor regrowth after PDT. ResultsPorfimer sodium and PS785 produced statistically similar delays of tumor regrowth after PDT when small tumors were treated at 24 and 48 h. At 72 h, PS785 performed better in small tumors. However, for large tumors, PS785 produced no delay in tumor regrowth at any time point. ConclusionsPS785 and porfimer sodium were able to effectively treat NSCLC to a depth of ≤5 mm. However, porfimer sodium was more effective in treating NSCLC tumors to a depth of 6-10 mm. Further efforts are required to produce photosensitizers that will facilitate PDT of larger tumors.

S0969 Photodynamic Therapy for Cholangiocarcinoma Improves Survival Compared to Standard of Care Chemotherapy - A Ten-Year Single U.S. Center Experience

INTRODUCTION: Perihilar cholangiocarcinoma (CCa) is a frequently fatal cancer in which a minority of patients are eligible for surgical resection; survival is 3–6 months without additional therapies. The standard of care in the U.S. is chemotherapy (gemcitabine/cistplatin) that in a pivotal study improved survival from 8 to 11.7 months.1 Alleviating biliary obstruction improves survival in CCa, and European experience with photodynamic therapy (PDT) have yielded encouraging results leading us to initiate a PDT program. This study reports the outcomes of a 10-year experience in patients with unresectable hilar CCa treated with PDT. METHODS: Consecutive patients with biliary obstruction secondary to CCa undergoing PDT from 9/2009 through 4/2020 at a single center were included. Data were collected prospectively with retrospective review of endoscopic databases and electronic health records for missing data points. Porfimer sodium (Photophrin, Pinnacle Biologics, Chicago, IL) 2 mg/kg was administered intravenously as the photosensitizer 48 hours prior to PDT in all patients. Means were compared with two-tailed Students T Test. RESULTS: 41 patients were included in the analysis, 56% (n = 23) female, median age = 63.5 (range 44-88), 40/41had perihilar CCa 1 had extrahepatic cancer. All patients had either locally advanced unresectable tumors (stage T3/T4) and/or metastatic adenopathy at the time of diagnosis. One patient was diagnosed with intrahepatic metastasis within 2 weeks after his first PDT session. PDT was delivered endoscopically at ERCP in 95% (39/41) patients two treated percutaneously. A total of 112 PDT procedures were performed, mean = 2.8 procedures per patient (range 1–10), median = 2. The mean overall survival (OS) was 588 days in the entire cohort with a median = 553 days. Mean OS was significantly longer in those who had > 1 PDT session = 714 days vs. 418 days for those who had 1 session (P = 0.03). PDT was applied to 2 or more biliary segments in 83% of patients (34/41). Patients in whom multiple biliary segments were treated had a longer OS (627 vs. 416 days) although this did not reach statistical significance (P = 0.34). CONCLUSION: Patients with cholangiocarcinoma benefit from treatment with biliary photodynamic therapy with a mean survival that exceeds that of historical controls by approximately 1 year. Multiple PDT sessions appears to offer further the clinical benefit with a significant increase in overall survival.

Photodynamic therapy for extramammary Paget's disease: A systematic review of the literature.

Extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma that arises in areas rich in apocrine sweat glands. Photodynamic therapy (PDT) is a non-invasive technique demonstrating clinical efficacy in various case reports and case series for the treatment of EMPD. A review of the current literature of patients with EMPD treated with PDT. 177 patients with 211 lesions were included in this review with an overall complete response rate of 59.7 %. Lesion size was correlated with the efficacy of 5-aminolevulinic acid (ALA) PDT. Topical methyl-ALA had lower complete response rates compared to ALA. Systemic PDT with intravenous sodium porfimer had high response rates but can be associated with more adverse reactions. The efficacy of PDT was enhanced with the combination of other treatments such as surgery, imiquimod, or laser ablation. PDT was also shown to be effective for previously treated lesions, recurrent lesions, and select invasive lesions. PDT can be a therapeutic option for EMPD patients. Given the lack of PDT guidelines, general recommendations for treatment are offered.

Photodynamic Therapy for Esophageal Cancer.

Photodynamic therapy, a curative local treatment for esophageal squamous cell carcinoma, involves a photosensitizing drug (photosensitizer) with affinity for tumors and a photodynamic reaction triggered by laser light. Previously, photodynamic therapy was used to treat superficial esophageal squamous cell carcinoma judged to be difficult to undergo endoscopic resection. Recently, photodynamic therapy has mainly been performed for local failure after chemoradiotherapy. Although surgery is the most promising treatment for local failure after chemoradiotherapy, its morbidity and mortality rates are high. Endoscopic resection is feasible for local failure after chemoradiotherapy but requires advanced skills, and its indication is limited to within the submucosal layer by depth. Photodynamic therapy is less invasive than surgery and has a wider indication than endoscopic resection. Porfimer sodium (a first-generation photosensitizer) causes a high frequency of side effects related to photosensitivity and requires the long-term sunshade period. Talaporfin (a second-generation photosensitizer) requires a much shorter sun-shade period than porfimer sodium. Photodynamic therapy will profoundly change treatment strategies for local failure after chemoradiotherapy.

Combination of ALA-induced fluorescence-guided resection and intraoperative open photodynamic therapy for recurrent glioblastoma: case series on a promising dual strategy for local tumor control.

High-grade glioma (HGG) prognosis remains dismal, with inevitable, mostly local recurrence. Regimens for improving local tumor control are therefore needed. Photodynamic therapy (PDT) using porfimer sodium has been investigated but was abandoned due to side effects and lack of survival benefits. Intracellular porphyrins induced by 5-aminolevulinic acid (5-ALA) are approved for fluorescence-guided resections (FGRs), but are also photosensitizers. Activated by light, they generate reactive oxygen species with resultant cytotoxicity. The authors present a combined approach of 5-ALA FGR and PDT. After 5-ALA FGR in recurrent HGG, laser diffusors were strategically positioned inside the resection cavity. PDT was applied for 60 minutes (635 nm, 200 mW/cm diffusor, for 1 hour) under continuous irrigation for maintaining optical clarity and ventilation with 100% oxygen. MRI was performed at 24 hours, 14 days, and every 3 months after surgery, including diffusion tensor imaging and apparent diffusion coefficient maps. Twenty patients were treated. One surgical site infection after treatment was noted at 6 months as the only adverse event. MRI revealed cytotoxic edema along resection margins in 16 (80%) of 20 cases, mostly annular around the cavity, corresponding to prior laser diffusor locations (mean volume 3.3 cm3). Edema appeared selective for infiltrated tissue or nonresected enhancing tumor. At the 14-day follow-up, enhancement developed in former regions of edema, in some cases vanishing after 4-5 months. Median progression-free survival (PFS) was 6 months (95% CI 4.8-7.2 months). Combined 5-ALA FGR and PDT provides an innovative and safe method of local tumor control resulting in promising PFS. Further prospective studies are warranted to evaluate long-term therapeutic effects.

Porfimer sodium-mediated photodynamic therapy in patients with head and neck squamous cell carcinoma.

Photodynamic therapy is a less invasive therapeutic procedure for carcinomas. The goal of this study was to evaluate the utility of Photofrin (porfimer sodium)-mediated photodynamic therapy in patients with head and neck squamous cell carcinoma. Forty-two head and neck squamous cell carcinoma patients who underwent Photofrin-mediated photodynamic therapy were treated by intraoperative light activation at 630 nm via a fiber optic microlens, 48 h after injection. We evaluated the impact of age, sex, tumor stage, primary site, light dose, and cancer history on overall survival using a Cox proportional hazards model. Information on the survival status of patients was obtained after a mean follow-up period of 51 months (range, 6-180 months). The 5-year overall survival for all patients was 57.8 % (95 % confidence interval of the survival rate: 39.8 %-72.1 %). The complete response rate was 69.0 %, and the efficacy (complete response + partial response) was 97.6 %. Earlier tumor stage was associated with increased survival (p = 0.012). Diseases of the respiratory tract also showed significant association with survival as compared to those of the alimentary tract (p = 0.01). Photofrin-mediated photodynamic therapy is useful for treating head and neck squamous cell carcinomas, and provides an improved quality of life in patients with recurrent or residual disease.

Verteporfin- and sodium porfimer-mediated photodynamic therapy enhances pancreatic cancer cell death without activating stromal cells in the microenvironment.

.The goal of our study was to determine the susceptibility of different pancreatic cell lines to clinically applicable photodynamic therapy (PDT). The efficacy of PDT of two different commercially available photosensitizers, verteporfin and sodium porfimer, was compared using a panel of four different pancreatic cancer cell lines, PANC-1, BxPC-3, CAPAN-2, and MIA PaCa-2, and an immortalized non-neoplastic pancreatic ductal epithelium cell line, HPNE. The minimum effective concentrations and dose-dependent curves of verteporfin and sodium porfimer on PANC-1 were determined. Since pancreatic cancer is known to have significant stromal components, the effect of PDT on stromal cells was also assessed. To mimic tumor–stroma interaction, a co-culture of primary human fibroblasts or human pancreatic stellate cell (HPSCs) line with PANC-1 was used to test verteporfin-PDT-mediated cell death of PANC-1. Two cytokines (TNF- and IL-) were used for stimulation of primary fibroblasts (derived from human esophageal biopsies) or HPSCs. The increased expression of smooth muscle actin (-SMA) confirmed the activation of fibroblasts or HPSC upon treatment with TNF- and IL-. Cell death assays showed that both sodium porfimer- and verteporfin-mediated PDT-induced cell death in a dose-dependent manner. However, verteporfin-PDT treatment had a greater efficiency with lower concentration than sodium porfimer-PDT in the PANC-1 incubated with stimulated fibroblasts or HPSC. Moreover, activation of stromal cells did not affect the treatment of the pancreatic cancer cell lines, suggesting that the effects of PDT are independent of the inflammatory microenvironment found in this two-dimensional culture model of cancers.

Advantages of salvage photodynamic therapy using talaporfin sodium for local failure after chemoradiotherapy or radiotherapy for esophageal cancer.

Photodynamic therapy (PDT) is a salvage treatment for local failure following chemoradiotherapy (CRT) for esophageal cancer. This study aimed to evaluate the efficacy and safety of salvage PDT using the second-generation photosensitizer, talaporfin sodium (L-PDT), and compare L-PDT to PDT using porfimer sodium (P-PDT). We retrospectively analyzed clinical outcomes of patients treated with L-PDT and P-PDT. Patients with histologically proven local failure limited to the shallow muscularis propria layer (T2) after CRT or radiotherapy (RT) for esophageal cancer were enrolled. A total of 121 patients were enrolled in this study. L-PDT and P-PDT groups consisted of 44 and 77 patients, respectively. The overall local complete response (L-CR) rate was 62.1% (95% confidence interval [CI], 52.6-70.9), and the L-PDT group showed a better L-CR rate than did the P-PDT group (69.0% [95% CI 52.9-82.4] vs. 58.1% [95% CI 46.1-69.5]). The common complications of skin phototoxicity, esophageal stricture, and esophageal fistula were all less frequent in the L-PDT group than in the P-PDT group. The only treatment-related death in this study was in the P-PDT group. With a median follow-up period of 15.8months (interquartile range 7.1-37.4) in all 121 patients, overall survival rate at 1year was significantly higher among patients who achieved L-CR (91.2% [95% CI 80.2-96.3]) than among those who could not achieve L-CR with PDT (50.8% [95% CI 33.6-65.6]). L-PDT represented better short-term outcomes than P-PDT as a salvage treatment for local failure following CRT or RT for esophageal cancer.

PHOTOSTENT-02: porfimer sodium photodynamic therapy plus stenting versus stenting alone in patients with locally advanced or metastatic biliary tract cancer

BackgroundEndobiliary stenting is standard practice for palliation of obstructive jaundice due to biliary tract cancer (BTC). Photodynamic therapy (PDT) may also improve biliary drainage and previous small studies suggested survival benefit.AimsTo assess the difference in outcome between patients with BTC undergoing palliative stenting plus PDT versus stenting alone.Methods92 patients with confirmed locally advanced or metastatic BTC, ECOG performance status 0–3 and adequate biliary drainage were randomised (46 per group) to receive porfimer sodium PDT plus stenting or stenting alone. The primary end point was overall survival (OS). Toxicity and progression-free survival (PFS) were secondary end points. Treatment arms were well balanced for baseline factors and prior therapy.ResultsNo significant differences in grade 3–4 toxicities and no grade 3–4 adverse events due to PDT were observed. Thirteen (28%) PDT patients and 24 (52%) stent alone patients received subsequent palliative chemotherapy. After a median follow-up of 8.4 months, OS and PFS were worse in patients receiving PDT compared with stent alone group (OS median 6.2 vs 9.8 months (HR 1.56, 95% CI 1.00 to 2.43, p=0.048) and PFS median 3.4 vs 4.3 months (HR 1.43, 95% CI: 0.93 to 2.18, p=0.10), respectively).ConclusionIn patients with locally advanced or metastatic BTC, PDT was associated with worse outcome than stenting alone, explained only in part by the differences in chemotherapy treatments. We conclude that optimal stenting remains the treatment of choice for malignant biliary obstruction and the use of PDT for this indication cannot be recommended outside of clinical trials.Trial registration numberISRCTN 87712758; EudraCT 2005-001173-96; UKCRN ID: 1461.

Phase 1 study of EUS-guided photodynamic therapy for locally advanced pancreatic cancer

Locally advanced pancreatic cancer (LAPC) has a poor prognosis. There are limited data describing the use of photodynamic therapy (PDT) for pancreatic cancer in humans. We hypothesized that EUS-guided PDT for LAPC is safe, technically feasible, and produces a dose- and time-dependent increasing degree of image-defined tumor necrosis. In a single-center, prospective, dose-escalation phase 1 study, patients with treatment-naïve LAPC received intravenous porfimer sodium (Concordia Laboratories Inc, St Michael, Barbados) followed 2 days later by EUS-PDT. EUS-PDT was performed by puncture with a 19-gauge needle and insertion of a 1.0-cm light diffuser (Pioneer Optics, Bloomfield, Conn) and illumination with a 630-nm light (Diomed Inc, Andover, Mass). A CT scan 18 days after PDT was done to assess for change in pancreatic necrosis. Nab-paclitaxel (125 mg/ m2 intravenously) and gemcitabine (1000 mg /m2 intravenously) were initiated 7 days after CT and given weekly for 3 of 4 weeks (1 cycle) until disease progression or unacceptable toxicity. Twelve patients (mean age, 67 ± 6 years; 8 male) with tumors (mean diameter, 45.2 ± 12.9mm) in the head and/or neck (8) or body and/or tail (4) underwent EUS-PDT. Compared with baseline imaging, increased volume and percentage of tumor necrosis were observed in 6 of 12 patients (50%) after EUS-PDT. The mean overall increases in volume and percentage necrosis were 10 ± 26 cm3 (P= .20) and 18% ± 22% (P= .016), respectively. After a median follow-up of 10.5 months (range, 1.0-37.4 months), median progression-free (PFS) and overall survival (OS) were 2.6 months (95% confidence interval, 0.7, not estimable) and 11.5 months (95% confidence interval, 1.1, 16.9), respectively. Surgical resection was attempted in 2 patients, and pathology showed a complete response (n= 1) and residual 2-mm tumor (n= 1). There were 8 serious adverse events and none related to EUS or EUS-PDT. EUS-PDT for LAPC appears to be safe and produces measurable imaged-defined tumor necrosis. Phase 2 studies are warranted. (Clinical trial registration number: NCT01770132.).

PS02.038: SAFETY AND EFFICACY OF REPETITIVE PHOTODYNAMIC THERAPY FOR RESIDUAL ESOPHAGEAL CANCER LESIONS AFTER INITIAL PHOTODYNAMIC THERAPY

Abstract Background Photodynamic therapy (PDT) is an effective salvage treatment for local failure after chemoradiotherapy in patients with esophageal cancers. However, the treatment strategy for local failure after initial PDT has not been established, and the safety and efficacy of repetitive PDT for such lesions are also unknown. Methods We retrospectively investigated 33 esophageal cancer patients who received initial salvage PDT at Kyoto University Hospital between May 2012 and November 2017. Additionally, we examined the treatment outcomes of those patients who received repetitive PDT. Results Twenty-one patients (64%) achieved local complete response (CR) by initial PDT, and local recurrence did not occur in those patients. Eleven patients (33%) had residual lesions after initial PDT. Among these, 7 patients were treated with repetitive PDT, 2 patients selected best supportive care, 1 patient was treated with surgery, and 1 patient was treated with chemotherapy. Five of the 7 patients who received repetitive PDT were treated with talaporfin sodium, and 2 patients were treated with porfimer sodium. The median age of the patients who received repetitive PDT was 70 years old, and all patients were men. Regarding histology, 6 patients were squamous cell carcinoma and 1 patient was adenocarcinoma. The median period from initial PDT to repetitive PDT was 3 months (range 1–4). Lesion depth before initial PDT was T1 in 3 patients and T2 in 4 patients. Lesion depth before repetitive PDT was T1 in 5 patients, and T2 in 2 patients. Local CR rate in 7 patients treated with repetitive PDT was 42.9% (3/7). Additionally, local CR rate in T1 cases was 60% and 0% in T2 cases. Adverse events of grade 3 or higher were not observed in any patient. Conclusion Repetitive salvage PDT was considered to be an effective and safe treatment option in residual T1 lesions after initial PDT for local failure of esophageal cancer treated with chemoradiotherapy. Disclosure All authors have declared no conflicts of interest.