Clinical Efficacy of HiPorfin Photodynamic Therapy for Advanced Obstructive Esophageal Cancer.

OBJECTIVE: To explore the clinical efficacy of HiPorfin photodynamic therapy for advanced esophageal cancer and evaluate its impact on survival. METHODS: Retrospective analysis of 32 patients with advanced obstructive esophageal cancer at our institution from September 2013 to December 2016. HiPorfin was infused as the photosensitizer at a dose of 5 mg/kg, and after 48 hours, 630-nm laser irradiation was subsequently performed through an optical fiber that passed through the biopsy channel of a flexible endoscope. RESULTS: The effectiveness rate was 78.1% (25/32), and the significant efficacy rate was 56.3% (18/32). The dysphagia score decreased from 3.43 ± 0.73 to 1.79 ± 0.53 (P < .05). There was no grade 3 or more toxicity. The median overall survival was estimated to be 16 months. Univariate analysis showed higher overall survival with a Karnofsky Performance Status score ≥80 compared with a Karnofsky Performance Status score <80 (hazard ratio: 2.626; 95% CI: 1.091-6.322; P = .024). Overall survival was higher in patients who had received radiation therapy than in patients who did not receive radiation therapy (hazard ratio: 3.574; 95% CI: 1.501-8.510; P = .002). CONCLUSION: Photodynamic therapy is an effective method for advanced esophageal cancer. The side effects are mild, and the short-term effect is good, especially in the relief of dysphagia. Photodynamic therapy can prolong the survival of patients with advanced esophageal cancer, and the Karnofsky Performance Status score and previous radiation therapy have a significant effect on the overall survival.

First autopsy analysis of the efficacy of intra-operative additional photodynamic therapy for patients with glioblastoma.

The study aim to demonstrate the therapeutic tissue depth of photodynamic therapy (PDT) using the photosensitizer talaporfin sodium and semiconductor laser for malignant glioma from an autopsy finding. Three patients diagnosed with glioblastoma by pre-operative imaging (1 newly diagnosed patient and 2 patients with recurrence) were treated with intra-operative additional PDT and adjuvant therapy such as post-operative radiotherapy or chemotherapy. All three patients died of brain stem dysfunction owing to cerebrospinal fluid dissemination or direct invasion of the tumor cells from 13, 18, or 20 months after PDT. Antemortem magnetic resonance images demonstrated no tumor recurrence in the site of PDT, and autopsy was performed for the pathological analysis. Macroscopic observation demonstrated no tumor recurrence in two patients, but one patient demonstrated tumor recurrence in the therapeutic depth of PDT. Microscopic analysis demonstrated histopathological changes reaching depths of 9, 11, and 18 mm (mean: 12.7 mm) from the surface of the cavity of tumor resection, suggesting the therapeutic tissue depth of PDT to be in this range. This region demonstrated glial scarring with infiltration of T lymphocytes and macrophages, with slight degeneration of small vessel walls. However, viable tumor tissues were observed beyond or around the therapeutic tissue depth of PDT in two patients. PDT for glioblastoma prevented early local recurrence, which suggests the possibility that activation of the immune mechanisms was involved. The therapeutic tissue depth was suggested to be 9-18 mm from the surface of the cavity of tumor resection; however, the viable tumor tissues were demonstrated beyond this therapeutic range.

ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY VERSUS PHOTODYNAMIC THERAPY IN THE TREATMENT OF CHOROIDAL NEOVASCULARIZATION SECONDARY TO CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To evaluate the efficacy of photodynamic therapy (PDT) compared with intravitreal vascular endothelial growth factor (VEGF) inhibitors alone or combined with PDT in the treatment of choroidal neovascularization (CNV) secondary to chronic central serous chorioretinopathy (CSCR). METHODS: Retrospective study of a consecutive series of 34 white patients (34 eyes) with angiographic evidence of choroidal neovascularization secondary to chronic central serous chorioretinopathy, divided into two groups followed for at least 12 months: 16 were treated with full fluence PDT (PDT group) and 18 with vascular endothelial growth factor inhibitors (intravitreal [IVT] group). RESULTS: In the PDT group, mean best-corrected visual acuity (BCVA) was 20/40 (0.30 ± 0.69 logMAR) at baseline and did not change after 12 months (20/40; 0.30 ± 0.49 logMAR [P = 0.49]). In the IVT group mean, best-corrected visual acuity was 20/40 (0.30 ± 0.69 logMAR) at baseline and also did not change at the 12-month follow-up (20/32; 0.20 ± 0.49 logMAR [P = 0.20]). There was no statistically significant difference between the two groups in terms of best-corrected visual acuity. A statistical significance difference was found in central macular thickness between the two groups with a better reduction of the thickening in the PDT group (P = 0.05); moreover, indocyanine green angiography analysis revealed that 50% of the polypoidal lesions were closed after PDT and 25% of the polypoidal lesions disappeared after anti-vascular endothelial growth factor therapy at 12-month follow-up. CONCLUSION: PDT and IVT inhibitors alone or combined show similar clinical effects in chronic central serous chorioretinopathy eyes with choroidal neovascularization.

Treatment of unresectable extrahepatic cholangiocarcinoma using hematoporphyrin photodynamic therapy: A prospective study.

BACKGROUND: The available evidence of Photodynamic therapy (PDT) combined with stent placement treatment for unresectable extrahepatic cholangiocarcinoma (EHCC) is still insufficient. It also remains unclear whether PDT influences systemic inflammatory response. AIM: To explore the clinical efficacy and safety of the combination treatment and the systemic inflammatory response in patients with EHCC. METHODS: Patients with unresectable EHCC underwent either the combined treatment using Hematoporphyrin PDT and stent placement (PDT+stent group, n=12) or stent-only (stent group, n=27). The primary end-point was overall survival. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were measured. Quality of life was assessed using the Karnofsky performance scale (KPS) every 3 months. RESULTS: Average survival time (13.8 vs. 9.6 months), and 6-month (91.7% vs. 74.1%), and 1-year (58.3% vs. 3.7%) survival rates of PDT+stent group were significantly increased compared with the stent group. KPS scores in the PDT+stent group were significantly improved. TNF-α and IL-6 levels were significantly increased in the PDT+stent group. CONCLUSION: Hematoporphyrin-PDT combined with stent placement is an effective and safe treatment for EHCC. The treatment might promote systemic inflammatory response.

Retrospective analysis of therapeutic effect and prognostic factors on early glottic carcinoma.

OBJECTIVE: To investigate the therapeutic effect of surgery, radiotherapy and photodynamic therapy on early glottic carcinoma and prognostic factors. METHODS: Retrospective analysis of 202 cases with early glottic carcinoma (Tis-T2N0M0) underwent surgery (n=152), radiotherapy (n=20) and PDT (n=30) from 2000 to 2013 The KPS score, the disease-free survival (DFS), overall survival (OS), local control (LC), larynx preservation rate, laryngeal function were evaluated. The methods of χ (2)test or Fisher's exact probability method, Kaplan Meier method, log-rank test of Kaplan-Meier method, Cox proportional hazards model were used to analyze the data. RESULTS: There was no statistical significance in OS, DFS and LC among the three groups. The laryngeal function preservation rate of RT group, PDT group and Surgery group were 90%, 86.7% and 65.1% respectively, with the former two groups significantly superior to Surgery group. While there is no statistical significance between RT group and PDT group. Single factor analysis showed that KPS score before treatment, vocal fold mobility limitation and differentiation degree could have an effect on prognosis. Multivariate regression analyses indicated that anterior commissure invasion, T stage and KPS score before treatment were independent adverse prognostic factors for OS. T stage and differentiation degree were adverse prognostic factors for DFS. T stage was also an adverse factor of LC. Thirty-three cases experienced local recurrence or cervical lymph node metastasis. Three groups showed no statistical difference in local recurrence or lymph node metastasis, with twenty-two cases in Surgery group, four in RT group and seven in PDT group. CONCLUSIONS: The therapeutic effect was approximate in surgery group, radiotherapy group and photodynamic group, and all three treatment regimens achieved good clinical effect. Radiotherapy and photodynamic therapy may be the first or very important treatment on early stage glottic squamous cell cancer (Tis∼T2N0M0). However only 6 patients underwent PDT for T2 disease, making definitive treatment conclusions for this subgroup unclear.

Photodynamic Therapy Plus Chemotherapy Compared with Photodynamic Therapy Alone in Hilar Nonresectable Cholangiocarcinoma.

BACKGROUND/AIMS: Standard treatments are not available for hilar nonresectable cholangiocarcinoma (NCC). It is unknown whether combination therapy of photodynamic therapy (PDT) plus systemic chemotherapy is superior to PDT alone. METHODS: We retrospectively reviewed 68 patients with hilar NCC treated with either PDT plus chemotherapy (PTD-C) or PDT monotherapy (PDT-M). The primary endpoint was the mean overall survival rate. Secondary endpoints included the 1-year survival rate, risk of cholangitic complications, and outcomes, which were evaluated according to the chemotherapy protocol. RESULTS: More than 90% of the study population had advanced hilar NCC Bismuth type III or IV. In the PDT-M group (n=35), the mean survival time was 374 days compared with 520 days in the PDT-C group (n=33, p=0.021). The 1-year survival rate was significantly higher in the PDT-C group compared with the PDT-M group (88% vs 58%, p=0.001) with a significant reduction of mortality (hazard ratio, 0.20; 95% confidence interval, 0.07 to 0.58; p=0.003). Gemcitabine monotherapy resulted in a shorter survival time compared with the gemcitabine combination therapy (mean, 395 days vs 566 days; p=0.09). Cholangitic complications were observed at a similar frequency in the PDT-C and PDT-M groups. CONCLUSIONS: Combining repeated PDT with a gemcitabine-based combination therapy might offer a significant survival benefit in patients with hilar NCC.

Long-term outcome of photodynamic therapy with systemic chemotherapy compared to photodynamic therapy alone in patients with advanced hilar cholangiocarcinoma.

BACKGROUND/AIMS: Patients with cholangiocarcinoma usually present at an advanced stage, and more than 50% of cases are not resectable at the time of diagnosis. Recently, photodynamic therapy (PDT) has been proposed as a palliative and neoadjuvant modality. We evaluated whether combination of PDT and chemotherapy is more effective than PDT alone. METHODS: In total, 161 patients with cholangiocarcinoma diagnosed between February 1999 and September 2009 were evaluated. Sixteen patients were treated with PDT and chemotherapy (group A), and 58 were treated with PDT (group B). RESULTS: The median survival was 538 days (95% confidence interval [CI], 475.3 to 600.7) in group A and 334 days (95% CI, 252.5 to 415.5) in group B (p=0.05). Lymph node metastasis status, serum bilirubin of pretreatment, tumor node metastasis stage, treatment method (PDT with chemotherapy vs PDT alone), time to PDT and the number of PDT sessions were prognostic factors with statistical significance in the univariate analysis. A multivariate analysis showed that PDT with chemotherapy and more than two sessions of PDT were significant independent predictors of longer survival in advanced cholangiocarcinoma (hazard ratio [HR], 2.23; 95% CI, 1.18 to 4.20; p=0.013 vs HR, 1.79; 95% CI, 1.044 to 3.083; p=0.034). CONCLUSIONS: PDT with chemotherapy results in longer survival than PDT alone.

Efficacy and safety of photodynamic therapy for cervical intraepithelial neoplasia: a systemic review.

BACKGROUND: The current treatment of cervical intraepithelial neoplasia (CIN) is primarily based on surgical excision using laser, a loop electrosurgical procedure, or a cold knife technique. Unfortunately, these treatments often lead to obstetrical problems during the subsequent pregnancy, particularly in young women. Photodynamic therapy (PDT), which uses a topical or intravenous photosensitizer (PS) activated by a light source to ablate abnormal tissue, offers a minimally invasive alternative. The purpose of this study was to comprehensively assess the effectiveness and safety of PDT in the treatment of CIN. METHODS: Following Cochrane guidelines, a comprehensive systematic review of all clinical studies and reports examining the use of PDT for CIN was conducted. Study quality was assessed using the Oxford Levels of Evidence Scale. RESULTS: The 14 studies included two randomized control trials (RCTs), one case-control study, and 11 case series. Among the 506 patients studied, 472 were included to study the effectiveness of PDT on CIN and 10 were lost to follow-up. An assessment of clinical effectiveness included the response of the lesion to treatment (may include lesion recurrence) reported by all 14 studies. The complete response rate (CRR) of PDT on CIN ranged from 0% to 100%. HPV eradication rate (HER) was reported in seven studies, with rates ranging from 53.4% to 80.0%. CONCLUSIONS: PDT is a safe and tolerable treatment for CIN. Evidence regarding the efficacy of PDT for CIN is conflicting, which may, in part, be explained by the limited number of controlled comparative clinical trials.

Can a less radical surgery using photodynamic therapy with acridine orange be equal to a wide-margin resection?

BACKGROUND: Wide-margin resections are an accepted method for treating soft tissue sarcoma. However, a wide-margin resection sometimes impairs function because of the lack of normal tissue. To preserve the normal tissue surrounding a tumor, we developed a less radical (ie, without a wide margin) surgical procedure using adjunctive photodynamic therapy and acridine orange for treating soft tissue sarcoma. However, whether this less radical surgical approach increases or decreases survival or whether it increases the risk of local recurrence remains uncertain. QUESTIONS/PURPOSES: We determined the survival, local recurrence, and limb function outcomes in patients treated with a less radical approach and adjunctive acridine orange therapy compared with those who underwent a conventional wide-margin resection. METHODS: We treated 170 patients with high-grade soft tissue sarcoma between 1999 and 2009. Fifty-one of these patients underwent acridine orange therapy. The remaining 119 patients underwent a conventional wide-margin resection for limb salvage surgery. We recorded the survival, local recurrence, and functional score (International Society of Limb Salvage [ISOLS]) score) for all the patients. RESULTS: The 10-year overall survival rates in the acridine orange therapy group and the conventional surgery group were 68% and 63%, respectively. The 10-year local recurrence rate was 29% for each group. The 5-year local recurrence rates for Stages II, III, and IV were 8%, 36%, and 40%, respectively, for the acridine orange group and 13%, 27%, and 33%, respectively, for the conventional surgery group. The average ISOLS score was 93% for the acridine orange group and 83% for the conventional therapy group. CONCLUSION: Acridine orange therapy has the potential to preserve limb function without increasing the rate of local recurrence. This therapy may be useful for eliminating tumor cells with minimal damage to the normal tissue in patients with soft tissue sarcoma. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of the levels of evidence.

Longterm outcome of photodynamic therapy compared with biliary stenting alone in patients with advanced hilar cholangiocarcinoma.

OBJECTIVES: This study aimed to determine longterm outcomes and factors associated with increased survival after photodynamic therapy (PDT) compared with endoscopic biliary drainage alone in patients presenting with advanced hilar cholangiocarcinoma (CC). METHODS: A retrospective analysis of the institutional database identifying all patients who presented with a diagnosis of hilar CC between December 1999 and January 2011 was conducted. RESULTS: Of the 232 patients identified, 72 (31%) were treated with PDT (Group A) and 71 (31%) were treated with endoscopic biliary drainage alone (Group B). Median survival was 9.8 months [95% confidence interval (CI) 7.42-12.25] in Group A and 7.3 months (95% CI 4.79-9.88) in Group B (P= 0.029). On multivariate analysis, biliary drainage without PDT (P= 0.025) and higher T-stage (P= 0.002) were significant predictors of shorter survival in all patients. In a subgroup analysis of patients in the PDT group, lower pre-PDT bilirubin level (P= 0.005), multiple PDT treatments (P= 0.044) and shortened time to treatment after diagnosis (P= 0.013) were significant predictors of improved survival. Median metal stent patency was longer in Group A than in Group B (215 days vs. 181 days; P= 0.018). CONCLUSIONS: Photodynamic therapy with stenting resulted in longer survival than stenting alone. Early PDT after diagnosis and multiple PDT treatments were shown to have survival benefits. Metal stent patency was longer in patients receiving PDT. Higher T-stage appears to be a predictor of early mortality in advanced bile duct cancer treated with PDT.

Imaging tumor variation in response to photodynamic therapy in pancreatic cancer xenograft models.

PURPOSE: A treatment monitoring study investigated the differential effects of orthotopic pancreatic cancer models in response to interstitial photodynamic therapy (PDT), and the validity of using magnetic resonance imaging as a surrogate measure of response was assessed. METHODS AND MATERIALS: Different orthotopic pancreatic cancer xenograft models (AsPC-1 and Panc-1) were used to represent the range of pathophysiology observed in human beings. Identical dose escalation studies (10, 20, and 40J/cm) using interstitial verteporfin PDT were performed, and magnetic resonance imaging with T2-weighted and T1-weighted contrast were used to monitor the total tumor volume and the vascular perfusion volume, respectively. RESULTS: There was a significant amount of necrosis in the slower-growing Panc-1 tumor using high light dose, although complete necrosis was not observed. Lower doses were required for the same level of tumor kill in the faster-growing AsPC-1 cell line. CONCLUSIONS: The tumor growth rate and vascular pattern of the tumor affect the optimal PDT treatment regimen, with faster-growing tumors being relatively easier to treat. This highlights the fact that therapy in human beings shows a heterogeneous range of outcomes, and suggests a need for careful individualized treatment outcomes assessment in clinical work.

Photodynamic therapy with curative intent for Barrett's esophagus with high grade dysplasia and superficial esophageal cancer.

BACKGROUND: Photodynamic therapy (PDT) has been used to palliate advanced, obstructing, or bleeding esophageal cancers (ECs) and Barrett's high-grade dysplasia (HGD). Few investigators, though, have described using PDT to cure either disease. METHODS: We performed a retrospective review from 1997-2005 of 50 patients with HGD or EC. All patients refused surgical resection or were physiologically unfit. They were instead treated using PDT with curative intent. Clinical follow-up, long-term survival, complications, and recurrence were evaluated. RESULTS: Thirteen patients (26%) had Barrett's HGD, 6 (12%) had small, intramural carcinomas, 16 (32%) had T1 N0 tumors, 14 (28%) had T2 N0 tumors, and 1 (2%) had a small, polypoid T3 lesion. The mean length of follow-up was 28.1 months. Sixteen patients (32%) are alive without recurrence, 15 (30%) are living with residual or recurrent disease and have received additional PDT, and the remainder (38%) died of recurrent EC or other causes and had known recurrence. Sixteen (32%) patients received adjuvant chemotherapy, radiation, or both. Esophageal stricture occurred in 21 (42%) patients. There was no procedure-related mortality. CONCLUSIONS: PDT may represent a reasonable alternate to esophagectomy for high-risk patients with HGD or superficial esophageal cancer. Due to superior survival and local control, we still favor esophagectomy for patients without physiologic impairment. However, PDT appears to potentially cure approximately one-third of superficial esophageal cancers and provide local control of high-grade dysplasia in a similar subset of patients.

Photodynamic therapy (PDT) in Barrett's esophagus with dysplasia or early cancer.

OBJECTIVE: Esophagectomy is the standard treatment for high-grade dysplasia (HGD) and intramucosal adenocarcinoma (IMC) arising within Barrett's esophagus. Results of photodynamic therapy (PDT) were retrospectively studied to evaluate the effectiveness of PDT in ablating HGD and/or IMC complicating Barrett's esophagus. METHODS: Thirty-one patients unfit for or refusing esophagectomy (male: 20, mean age: 73.4+/-9.3 years) underwent Porfimer sodium PDT ablation of their HGD (15 patients), HGD plus IMC (10 patients) or submucosal/limited T2 adenocarcinoma (6 patients). The mean Barrett's length was 5.8+/-2.2 cm. Pre-PDT endoscopic mucosal resection or Nd:YAG laser ablation of mucosal nodularity within Barrett's segment was offered in six patients. RESULTS: The main PDT complications were esophagitis (16.1%), photoreactions (12.9%) and stricture requiring dilatation (6.25%). The median post-PDT follow-up was 14 months. The long-term results were (a) for HGD/IMC: initial complete response (endoscopic and histologic absence of HGD-IMC) to PDT was observed in 80.95% of patients, partial response (no endoscopic abnormality, residual IMC-HGD on biopsy) in 9.52%, no response in 9.52% (the recurrence rate after an initial complete response was 17.64%) and (b) for T1b/limited T2 tumors: two patients died from cancer after 24 and 46 months, no evidence of tumor was found in two patients after 12 and 19 months and tumor recurrence was seen in two after 15 and 17 months. The mean survival was 22.1+/-12.3 months. CONCLUSIONS: PDT is effective in ablating HGD/IMC complicating Barrett's esophagus in the majority of cases, while it also seems to be quite effective in treating T1b/limited T2 carcinomas.