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1.
Surg Endosc ; 34(2): 899-906, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31139985

RESUMO

BACKGROUND: 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). METHODS: 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. RESULTS: 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 15.8 months (interquartile range 7.1-37.4) in all 121 patients, overall survival rate at 1 year 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]). CONCLUSIONS: L-PDT represented better short-term outcomes than P-PDT as a salvage treatment for local failure following CRT or RT for esophageal cancer.


Assuntos
Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/terapia , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Terapia de Salvação , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/efeitos adversos , Éter de Diematoporfirina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de Tratamento
2.
Photochem Photobiol Sci ; 18(5): 1275-1279, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30892313

RESUMO

Cervical cancer is the fourth-most common type of cancer and cause of death in women. Human papilloma virus (HPV) infection is responsible for over 90% of cervical cancers. The recommended treatment is multidisciplinary, consisting of a combination of surgery, chemotherapy, and radiation therapy. The standard treatment in advanced stages, such as FIGO IIIb, is radio-chemotherapy with overall 5-year survival of 32%. Photofrin II has been demonstrated to serve as a specific and selective radiosensitizing agent in both in vitro and in vivo tumor models, admitted for radiation therapy. We describe a patient with advanced cervical carcinoma (squamous cell) who contacted us for further therapy in 2003. Staging included a gynecological examination, colonoscopy, explorative laparotomy, biopsy and pelvic MRI. The explorative laparotomy showed enlarged pelvic and para-aortal lymph nodes. The histologic examination described tumor infiltrated, positive lymph nodes (Stage FIGO IIIb). Contrary to recommendations, the patient refused standard treatment with a combination of chemotherapy and radiotherapy, but accepted a combined treatment of Photofrin II as a radiosensitizer and a radiotherapy procedure. She underwent irradiation with a 50.4 + 14 Gy boost with fractionation of 1.8 Gy day-1 for 5 days per week; the boost was given with 2 Gy fractions. She was injected with a single intravenous dose in a slow infusion (30 min) of 1 mg kg-1 of Photofrin II 24 h prior to radiation therapy. A localized relapse in the cervix appeared after 30 months, and was resected by hysterectomy. The patient is still alive with no evidence of disease after 15 years.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma/tratamento farmacológico , Éter de Diematoporfirina/uso terapêutico , Radiossensibilizantes/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Carcinoma/patologia , Terapia Combinada , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias do Colo do Útero/patologia
3.
Br J Cancer ; 119(10): 1191-1199, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30353043

RESUMO

BACKGROUND: Currently delivered light dose (J/cm2) is the principal parameter guiding interstitial photodynamic therapy (I-PDT) of refractory locally advanced cancer. The aim of this study was to investigate the impact of light dose rate (irradiance, mW/cm2) and associated heating on tumour response and cure. METHODS: Finite-element modeling was used to compute intratumoural irradiance and dose to guide Photofrin® I-PDT in locally advanced SCCVII in C3H mice and large VX2 neck tumours in New Zealand White rabbits. Light-induced tissue heating in mice was studied with real-time magnetic resonance thermometry. RESULTS: In the mouse model, cure rates of 70-90% were obtained with I-PDT using 8.4-245 mW/cm2 and ≥45 J/cm2 in 100% of the SCCVII tumour. Increasing irradiance was associated with increase in tissue heating. I-PDT with Photofrin® resulted in significantly (p < 0.05) higher cure rate compared to light delivery alone at same irradiance and light dose. Local control and/or cures of VX2 were obtained using I-PDT with 16.5-398 mW/cm2 and ≥45 J/cm2 in 100% of the tumour. CONCLUSION: In Photofrin®-mediated I-PDT, a selected range of irradiance prompts effective photoreaction with tissue heating in the treatment of locally advanced mouse tumour. These irradiances were translated for effective local control of large VX2 tumours.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Éter de Diematoporfirina/uso terapêutico , Neoplasias Experimentais/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Feminino , Temperatura Alta , Camundongos , Camundongos Endogâmicos C3H , Coelhos , Termometria
4.
Scand J Gastroenterol ; 53(5): 527-532, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29161901

RESUMO

OBJECTIVE: Photodynamic therapy (PDT) was used as therapy for early neoplasia associated with Barrett's oesophagus (BE). This is 5-year follow-up of patients enrolled into randomised controlled trial of 5-aminolaevulinic acid (ALA) vs. Photofrin PDT. METHODS: Biopsies were taken from original Barrett's segment during endoscopic follow up using Seattle protocol. Endoscopic mucosal resection (EMR) ± radiofrequency ablation (RFA) was preferred therapy in patients who failed PDT and/or had recurrent neoplasia. RESULTS: Fifty eight of 64 patients enrolled in the original trial were followed up including 31 patients treated with ALA PDT (17 patients with ≤6 cm, 14 patients with >6 cm segment of BE) and 27 treated with Photofrin PDT (14 patients with ≤6 cm, 13 patients with >6 cm BE). Initial success was achieved in 65% (20/31) ALA and 48% (13/27) Photofrin patients (p = .289). Thirty five percent patients (7/20) relapsed in ALA group and 54% (7/13) relapsed in Photofrin group (p = .472). At a median follow-up of 67 months, no significant difference was found in long-term complete reversal of intestinal metaplasia (CR-IM) and complete reversal of dysplasia (CR-D) between ALA and Photofrin groups (78% vs. 63%; p = .18; 90% vs. 76%; p = .26). Original length of BE did not alter long-term outcome. Four patients from each group progressed to invasive oesophageal adenocarcinoma. Initial success of ALA PDT was associated with significantly better likelihood of long-term remission (p = .03). CONCLUSIONS: Initial response to PDT plays key role in long term outcome. RFA ± EMR have, however, become preferred minimally invasive ablative therapy for BE-related neoplasia due to poor efficacy of PDT.


Assuntos
Adenocarcinoma/terapia , Ácido Aminolevulínico/uso terapêutico , Esôfago de Barrett/terapia , Éter de Diematoporfirina/uso terapêutico , Neoplasias Esofágicas/terapia , Fotoquimioterapia , Adulto , Idoso , Esôfago de Barrett/complicações , Ablação por Cateter , Progressão da Doença , Ressecção Endoscópica de Mucosa , Feminino , Humanos , Hiperplasia/patologia , Estimativa de Kaplan-Meier , Masculino , Metaplasia/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Indução de Remissão , Resultado do Tratamento
5.
Clin Exp Dermatol ; 43(1): 46-49, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28940572

RESUMO

Folliculitis decalvans (FD) is classified as a primary neutrophilic cicatricial alopecia, and is estimated to account for approximately 10% of all cases of primary cicatricial alopecia. The role of dysfunctional immune activity and the presence of bacteria, particularly Staphylococcus aureus, appear pivotal. We describe a 26-year-old man with a 4-year history of FD that was recalcitrant to numerous systemic and topical therapies, whose disease was virtually cleared during a follow-up of 25 months following a course of treatment with systemic photodynamic therapy (PDT) using ultraviolet light (100-140 J/cm2 ) with porfimer sodium 1 mg/kg as monotherapy. This is the first report of the use of systemic PDT as a treatment for FD. Systemic PDT has potent antibacterial effects with little or no resistance. In addition, systemic PDT provides local immunomodulation and improved scar healing. Significant adverse effects following systemic PDT with appropriate aftercare are rare. This case demonstrates that systemic PDT is a useful therapy option in the treatment of recalcitrant FD.


Assuntos
Alopecia/tratamento farmacológico , Antibacterianos/uso terapêutico , Éter de Diematoporfirina/uso terapêutico , Fotoquimioterapia , Infecções Estafilocócicas/tratamento farmacológico , Adulto , Alopecia/microbiologia , Alopecia/patologia , Foliculite/tratamento farmacológico , Humanos , Masculino , Couro Cabeludo/patologia , Pele/patologia , Staphylococcus aureus/isolamento & purificação
6.
Lasers Surg Med ; 50(5): 420-426, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29399863

RESUMO

BACKGROUND: Photodynamic therapy (PDT) is a minimally invasive treatment for malignant tumors. The aim of this study was to determine the efficacy of PDT in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Thirty-three patients with HNSCC were treated with porfimer sodium-mediated PDT followed by intraoperative light activation at 630 nm via fiber optic microlens delivered after 48 hours of injection. RESULTS: The complete response (CR) rate was 72.7%, while the efficacy (CR + partial response) rate was 97.0%. The rate of good local control (i.e., CR without recurrence after PDT) achieved after the initial PDT (82.6%) was significantly higher than that achieved after the second or third PDT (10%); this rate remained at 62.1% without functional disturbance and disfigurement even after excluding four previously untreated patients. The final local control rate following PDT plus additional therapies was 73.8%. CONCLUSIONS: PDT is an effective therapy to treat HNSCC, and leads to an improved quality of life in patients with residual or recurrent disease. Lasers Surg. Med. 50:420-426, 2018. © 2018 Wiley Periodicals, Inc.


Assuntos
Éter de Diematoporfirina/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Neoplasia Residual , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Taxa de Sobrevida , Resultado do Tratamento
7.
Lasers Surg Med ; 50(5): 483-490, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29399826

RESUMO

OBJECTIVE: In the setting of lung cancer, photodynamic therapy (PDT) is typically used to treat centrally located endobronchial tumors. The development of navigational bronchoscopy has opened the potential for using PDT to treat peripheral lung tumors. However, there is limited information about the feasibility of this approach for treating peripheral lung cancers, and about its effects on surrounding healthy lung tissue. We studied the use of PDT delivered by electromagnetic navigational bronchoscopy to treat peripheral lung cancer in dogs. MATERIALS AND METHODS: Three dogs with peripheral lung adenocarcinomas were given intravenous porfimer sodium (Photofrin® [Pinnacle Biologics, Inc., Chicago, IL]) to photosensitize the tumors, then navigational bronchoscopy was used to deliver photoradiation. One week after PDT, the tumors and involved lung lobe were surgically excised and evaluated histologically. RESULTS: PDT was successful in all three dogs and was associated with tolerable and manageable adverse effects. Tissue sections from within PDT-treated tumors showed regions of coagulative central necrosis admixed with small numbers of inflammatory cells, and arterial thrombosis. Viable adenocarcinoma was seen in the surrounding areas. CONCLUSION: These results suggest that PDT can be successfully deployed to treat peripheral lung cancers using navigational bronchoscopy. Furthermore, damage to surrounding noncancerous tissues can be minimized with accurate placement of the optical fiber. Studies of this modality to treat peripheral lung cancers in humans may be warranted. Lasers Surg. Med. 50:483-490, 2018. © 2018 Wiley Periodicals, Inc.


Assuntos
Adenocarcinoma/tratamento farmacológico , Broncoscopia/métodos , Éter de Diematoporfirina/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Animais , Modelos Animais de Doenças , Cães , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Pneumonectomia
8.
Gastrointest Endosc ; 83(6): 1130-1139.e3, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26608125

RESUMO

BACKGROUND AND AIMS: Photodynamic therapy (PDT) is a less-invasive salvage treatment option for local failure at the primary site after chemoradiotherapy (CRT) for esophageal squamous cell carcinoma. The objective of this study was to clarify the long-term outcomes and prognostic factors of salvage PDT. METHODS: One hundred thirteen consecutive patients treated in our institution with PDT for local failure limited to within T2 without any metastases after definitive CRT performed between 1998 and 2008 were retrospectively enrolled. The complete response rate, adverse events, and survival outcomes were assessed and prognostic factors were investigated using a multivariate analysis. RESULTS: The complete response rate was 58.4% (95% confidence interval [CI], 49.3%-67.5%). The progression-free survival (PFS) and the overall survival (OS) rates at 5 years after salvage PDT were 22.1% (95% CI, 14.3%-30.0%) and 35.9% (95% CI, 26.7%-45.1%). N0 before CRT was significantly associated with OS (hazard ratio [HR], 0.54; 95% CI, 0.33-0.91, P = .020), whereas the impact of T1 or T2 before CRT on PFS (HR, 0.63; 95% CI, 0.38-1.04, P = .068) and that of a longer period between CRT and PDT on OS (HR, 0.64; 95% CI, 0.39-1.05, P = .078) were marginal. The treatment-related death rate was 1.8%. CONCLUSIONS: Salvage PDT was found to have a superior outcome and a satisfactory safety profile. An earlier clinical stage before CRT and a longer interval between CRT and PDT may be associated with a longer survival period.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Éter de Diematoporfirina/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Terapia de Salvação , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Intervalo Livre de Doença , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasia Residual , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Falha de Tratamento , Resultado do Tratamento
9.
J Surg Res ; 200(1): 8-12, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26494011

RESUMO

BACKGROUND: There is a need to develop novel therapies for non-small cell lung cancer (NSCLC). Photodynamic therapy has been used successfully for endobronchial palliation of NSCLC, and its role in early stages of disease is being explored. We hypothesized that a novel photosensitizer, PS1, would be more effective than the standard agent, porfimer sodium (Photofrin or PFII), in treating human lung cancer xenografts in mice. MATERIALS AND METHODS: Patient-derived NSCLC xenografts were established subcutaneously in severe combined immune deficiency mice. Two groups of five mice were injected with PS1 (3-[1'-m-iodobenzyloxy]ethyl-3-devinylpyropheophorbide-a), a chlorophyll-a derivative, or PFII (a purified version of hematoporphyrin derivative) and then treated with nonthermal laser light. Four mice were treated with laser light without photosensitizer and six mice received no treatment at all. All mice were then observed for tumor growth. The tumor growth end point, time-to-1000 mm(3), was evaluated using standard Kaplan-Meier methods and the log-rank test. Tumor hematoxylin and eosin and caspase 3 staining was done to evaluate necrosis and apoptosis. RESULTS: The median time-to-1000 mm(3) was 12, 12, 26, and 52 d for the control, light only, PFII, and PS1 groups. There was a significant association between the tumor growth end point and treatment (P < 0.05). Hematoxylin and eosin staining revealed <1%, 0%, 67%, and 80% necrosis, and caspase 3 positivity was 2%, <1%, 17%, and 39%, respectively, in the same four groups. CONCLUSIONS: The mice treated with PS1 exhibited a longer time for tumor regrowth and showed more tumor necrosis and apoptosis compared with the other treatment groups. Thus, the novel photosensitizer, PS1, was demonstrated to be more effective than porfimer sodium in this preclinical pilot study.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Clorofila/análogos & derivados , Éter de Diematoporfirina/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Clorofila/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Camundongos , Camundongos SCID , Transplante de Neoplasias , Projetos Piloto , Transplante Heterólogo , Resultado do Tratamento
10.
Gastrointest Endosc ; 82(5): 793-803.e3, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26071064

RESUMO

BACKGROUND: There are few data comparing endoscopic treatment outcomes for Barrett's esophagus (BE). OBJECTIVE: To compare treatment outcomes in BE patients treated with radiofrequency ablation (RFA), RFA after EMR, and porfimer sodium photodynamic therapy (Ps-PDT). DESIGN: Retrospective, observational study. SETTING: Single tertiary center between 2001 and 2013. PATIENTS: A total of 342 BE patients treated with RFA (n = 119), EMR+RFA (n = 98), and Ps-PDT (n = 125). MAIN OUTCOME MEASUREMENTS: Rates of complete remission of intestinal metaplasia (CRIM), BE recurrence, and adverse events. RESULTS: Baseline BE high-grade dysplasia (HGD) and adenocarcinoma were more common in the Ps-PDT group (89%) compared with the EMR-RFA (70%) and RFA (37%) groups. At a median follow-up of 14.2 months, 173 patients (50.6%) achieved CRIM. CRIM was significantly more common in Ps-PDT patients compared with RFA (P < .001) and EMR-RFA (P < .001) patients on multivariable analysis. In patients who achieved CRIM, the rates of subsequent BE recurrence were relatively similar among the 3 groups. Although the rates of bleeding were similar, strictures were less common in RFA patients (2.4%) compared with EMR-RFA (13.3%, P = .001) and Ps-PDT (10.4%, P =.043) patients. CONCLUSION: This study of endoscopic treatment for Barrett's dysplasia and neoplasia found that complete remission was achieved more often and more rapidly after Ps-PDT with similar disease recurrence rates compared with EMR or RFA. Adverse events were more common after EMR and Ps-PDT. Further studies are required to determine which ablation and resection techniques are ideally suited for each BE patient.


Assuntos
Esôfago de Barrett/terapia , Éter de Diematoporfirina/uso terapêutico , Esofagoscopia/métodos , Esôfago/patologia , Fotoquimioterapia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Ablação por Cateter/métodos , Feminino , Humanos , Masculino , Metaplasia/patologia , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
11.
Lasers Med Sci ; 30(9): 2353-61, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26450615

RESUMO

Esophageal squamous cell carcinoma (ESCC), the most prevalent cell type of esophageal cancer, remains a dismal disease with poor prognosis. Photodynamic therapy (PDT) is a minimally invasive treatment option for early esophageal cancer. To explore possible factors involved in resistance to PDT in esophageal cancer cells, we selected PDT-resistant subcell lines by repeated treatment of CE48T/VGH (CE48T) ESCC cells with Photofrin-PDT and then analyzed the global gene modulations in the PDT-resistant cells by whole-genome microarray. More than 700 genes reached a fold change greater than 1.5 in each of the PDT-resistant cells compared to parental cells. Among these genes, both tumor necrosis factor (TNF) and EFNA1 genes were significantly upregulated in resistant cell lines. However, they were significantly downregulated in Photofrin-PDT-treated cells compared to untreated cells. The observations made in the microarray analysis were further confirmed by quantitative PCR. We observed that recombinant tumor necrosis factor alpha (TNF-α) activated the gene expression of EFNA1 at both the messenger RNA (mRNA) level and the protein level in CE48T cells. Functional analysis showed that when incubated with oligomeric and monomeric ephrin-A1 simultaneously, ESCC cells became significantly resistant to Photofrin-PDT. Functional analysis further suggested that transmembrane and soluble ephrin-A1 may cooperate to enhance resistance to Photofrin-PDT in ESCC cells.


Assuntos
Carcinoma de Células Escamosas/patologia , Éter de Diematoporfirina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Efrina-A1/farmacologia , Neoplasias Esofágicas/patologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Éter de Diematoporfirina/uso terapêutico , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/efeitos da radiação , Resistencia a Medicamentos Antineoplásicos/efeitos da radiação , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago , Humanos , Fármacos Fotossensibilizantes/uso terapêutico , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/efeitos da radiação
12.
Int J Mol Sci ; 16(2): 3434-40, 2015 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-25690028

RESUMO

Photodynamic therapy (PDT) is an effective local treatment modality as a cancer-specific laser ablation in malignancy of some organs including digestive tracts or bile duct. In Japan, PDT has been applied at the early period after the first clinical induction in 1980's. Although the useful efficacy was clarified, PDT has not been fully applied because of the phototoxicity of the porfimer sodium. The next generated talaporfin-sodium was used for PDT, in which phototoxicity was reduced and, however, the clinical efficacy for digestive tract malignancy has not yet been clarified. By proceeding the experimental and clinical trials, it is necessary to clarify the evidence of efficacy as a local powerful treatment with the conventional surgery, brachiotherapy and chemotherapy in the future step.


Assuntos
Carcinoma/tratamento farmacológico , Neoplasias Gastrointestinais/tratamento farmacológico , Fotoquimioterapia/tendências , Fármacos Fotossensibilizantes/uso terapêutico , Éter de Diematoporfirina/uso terapêutico , Endoscopia Gastrointestinal , Humanos , Japão , Lasers , Porfirinas/uso terapêutico
13.
Int J Mol Sci ; 16(11): 26619-28, 2015 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-26561801

RESUMO

Hilar cholangiocarcinoma (CC) is non-resectable in the majority of patients often due to intrahepatic extension along bile duct branches/segments, and even after complete resection (R0) recurrence can be as high as 70%. Photodynamic therapy (PDT) is an established palliative local tumor ablative treatment for non-resectable hilar CC. We report the long-term outcome of curative resection (R0) performed after neoadjuvant PDT for downsizing of tumor margins in seven patients (median age 59 years) with initially non-resectable hilar CC. Photofrin(®) was injected intravenously 24-48 h before laser light irradiation of the tumor stenoses and the adjacent bile duct segments. Major resective surgery was done with curative intention six weeks after PDT. All seven patients had been curatively (R0) resected and there were no undue early or late complications for the neoadjuvant PDT and surgery. Six of seven patients died from tumor recurrence at a median of 3.2 years after resection, the five-year survival rate was 43%. These results are comparable with published data for patients resected R0 without pre-treatment, indicating that neoadjuvant PDT is feasible and could improve overall survival of patients considered non-curatively resectable because of initial tumor extension in bile duct branches/segments--however, this concept needs to be validated in a larger trial.


Assuntos
Neoplasias dos Ductos Biliares/tratamento farmacológico , Éter de Diematoporfirina/uso terapêutico , Tumor de Klatskin/tratamento farmacológico , Terapia Neoadjuvante/métodos , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Adulto , Idoso , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/efeitos dos fármacos , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/cirurgia , Feminino , Humanos , Injeções Intravenosas , Tumor de Klatskin/mortalidade , Tumor de Klatskin/patologia , Tumor de Klatskin/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Paliativos/métodos , Projetos Piloto , Recidiva , Análise de Sobrevida
14.
Gastrointest Endosc ; 80(5): 794-804, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24836747

RESUMO

BACKGROUND: Cholangiocarcinoma (CCA) is a malignancy with a poor 5-year survival rate (5%-10%). ERCP-directed radiofrequency ablation (RFA) or photodynamic therapy (PDT) can be performed as palliative therapy for unresectable CCA. ERCP with PDT is associated with improved survival compared with stent placement alone. However, ERCP-directed RFA has not been directly compared with PDT in patients with CCA. OBJECTIVE: To compare overall survival in patients with unresectable CCA who underwent palliative ERCP-directed RFA versus PDT. DESIGN: Retrospective cohort study. SETTING: Tertiary-care academic medical center. PATIENTS: Forty-eight patients with unresectable CCA who underwent ERCP-directed ablative therapy for palliation of unresectable CCA. INTERVENTIONS: ERCP-directed RFA or PDT. MAIN OUTCOME MEASUREMENTS: Overall survival by Kaplan-Meier analysis after initial treatment with either RFA or PDT. RESULTS: Patients who underwent RFA (n = 16) demonstrated an overall survival similar to that of those who underwent PDT (n = 32), with a median survival of 9.6 versus 7.5 months, respectively (P = .799). Patient age (P = .45), sex (P = .52), and lead time (P = .59) from presentation to initial RFA or PDT had no significant association with survival. The presence of distant metastasis was inversely associated with survival (hazard ratio 3.55; 95% confidence interval, 1.29-9.77; P = .014). Patients who underwent RFA (compared with PDT) had a lower mean number of plastic stents placed per month (0.45 vs 1.10, P = .001) but also had more episodes of stent occlusion (0.06 vs 0.02, P = .008) and cholangitis (0.13 vs 0.05, P = .008) per month. LIMITATIONS: Retrospective, single-center design. CONCLUSIONS: Survival after ERCP-directed RFA and PDT was not statistically different in patients with unresectable CCA. A randomized, controlled trial is warranted to validate these preliminary results.


Assuntos
Neoplasias dos Ductos Biliares/terapia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/terapia , Éter de Diematoporfirina/uso terapêutico , Lasers Semicondutores/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Ablação por Cateter/métodos , Colangiocarcinoma/mortalidade , Colangiopancreatografia Retrógrada Endoscópica , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Fotoquimioterapia/métodos , Estudos Retrospectivos , Cirurgia Assistida por Computador/métodos , Taxa de Sobrevida
15.
J Surg Res ; 192(2): 235-41, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25043529

RESUMO

BACKGROUND: Photodynamic therapy (PDT) is a binary therapy using a drug and high-energy light source. PDT is approved for several premalignant and malignant conditions. Recent in-vitro and animal data suggest that enhanced tumor-specific cytotoxicity can be achieved with far less collateral damage to normal surrounding tissues if PDT is administered continuously at a lower dose rate for extended periods of time. Based on these promising preclinical data, we conducted a Phase I clinical trial of continuous low-irradiance photodynamic therapy (CLIPT) using 630 nm laser energy and intravenously administered porforin sodium as the photosensitizer. We determined the maximum tolerated dose (MTD) of CLIPT on skin and tumor response in subjects with cutaneous and subcutaneous metastatic nodules who had failed radiation and surgery. METHODS: Patients with cutaneous and/or subcutaneous metastatic nodules that had failed radiation and surgery were offered enrollment into the trial. The initial study design planned for sequential cohorts of six subjects to be treated at increasing laser intensity, starting at 100 J/cm(2) administered continuously over 24 h (10(-2) dose rate compared with standard PDT). Dose-limiting toxicity was defined as partial or full-thickness necrosis of the surrounding tumor-free, previously irradiated skin. The MTD was defined as the highest laser energy at which ≤33% of subjects experienced the dose-limiting toxicity. Subjects received intravenous porfirmer sodium 0.8 mg/kg 48 h before commencing CLIPT. Response rates and quality of life measures were assessed. RESULTS: Nine subjects were enrolled with chest wall progression of breast cancer following mastectomy. All had failed prior surgery and electron-beam radiation therapy. The initial two subjects were treated at 100 J/cm(2) and developed partial thickness skin necrosis. Dose reduction was therefore instituted, and the next cohort was treated at 50 J/cm(2). None of the subsequent seven subjects suffered partial or full thickness necrosis, thus establishing the MTD at 50 J/cm(2) over 24 h (0.5 mW irradiance). Six of the nine subjects (67%) had either a complete or partial clinical response. Of note, two subjects had significant regression of tumor nodules distant from the treatment field. Of the eight subjects whose terminal deoxynucleotidyl transferase dUTP nick end labeling assay results were available, 8 (100%) demonstrated histologic response to treatment as evidenced by either tumor apoptosis or regression. Quality of life measures were improved following treatment-particularly bleeding and pain from the tumor nodules. CONCLUSIONS: The MTD of CLIPT was established at 50 J/cm(2) administered continuously over 24 h. These preliminary data suggest CLIPT may be an effective, low-morbidity therapeutic modality in the treatment of cutaneous and subcutaneous metastases of breast cancer following mastectomy. Further evaluation in a larger cohort is warranted to better assess efficacy and optimize the intervention.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Éter de Diematoporfirina/uso terapêutico , Fotoquimioterapia/métodos , Lesões por Radiação/prevenção & controle , Neoplasias Cutâneas/tratamento farmacológico , Parede Torácica/patologia , Adulto , Idoso , Neoplasias da Mama/secundário , Neoplasias da Mama/cirurgia , Progressão da Doença , Relação Dose-Resposta à Radiação , Feminino , Humanos , Lasers , Mastectomia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Fotoquimioterapia/efeitos adversos , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias Cutâneas/secundário , Neoplasias Cutâneas/cirurgia , Gordura Subcutânea/patologia , Gordura Subcutânea/efeitos da radiação , Parede Torácica/efeitos da radiação
16.
Photochem Photobiol Sci ; 13(9): 1281-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25005268

RESUMO

Photodynamic therapy (PDT) by selective photosensitization of cancer cells and subsequent laser application results in local tumor necrosis. However, the effects of PDT on immune function, which may depend on the type of immune response, are controversial. We investigated the immunological changes induced by PDT and the effect of PDT on level and function of regulatory T cells (Treg) in patients with invasive esophageal squamous cell carcinoma (ESCC). We analyzed patient's blood samples before and after PDT. Blood CD4+CD25+CD127-FoxP3+ Treg levels were quantified by FACS, and Treg function was evaluated by coculture proliferation assays with T effector (Teff) cells. We found that PDT abrogated the suppressive capacity of peripheral Treg (Days 7 and 14, p = 0.016) but had no effect on Treg levels. The effect of PDT on Treg function at Day 7 was accompanied by slight but statistically significant increases in peripheral neutrophil granulocytes (p = 0.035) and monocytes (p = 0.013) and a statistically significant increase (approximately 18-fold) in serum IL-6 levels (p = 0.008). In conclusion, PDT abolished Treg function, possibly due to increased IL-6 levels in treated ESCC patients. This may be crucial for an improved therapeutic outcome.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Linfócitos T Reguladores/imunologia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Técnicas de Cocultura , Éter de Diematoporfirina/uso terapêutico , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/efeitos da radiação , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Fatores de Transcrição Forkhead/metabolismo , Granulócitos/citologia , Granulócitos/imunologia , Humanos , Interleucina-6/sangue , Lasers , Monócitos/citologia , Monócitos/imunologia , Fotoquimioterapia , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/metabolismo , Fator de Crescimento Transformador beta/sangue
17.
Gan To Kagaku Ryoho ; 41(12): 2042-3, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25731416

RESUMO

In case of central type lung cancer, it happens that tumors tend to grow at many foci of bronchial tree, sometimes simultaneously and sometimes not. And these patients with such abnormalities often suffer from pulmonary emphysema or chronic bronchitis because of heavy smoking habits. So it is important to choose the treatment which preserve the pulmonary function in these cases. Today among several kinds of treatments, photodynamic therapy (PDT) is the definite method to maintain lung function. We report here a case of multiple central type lung cancer treated successfully by PDT.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Éter de Diematoporfirina/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Primárias Múltiplas/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Carcinoma de Células Escamosas/diagnóstico por imagem , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/patologia , Fotoquimioterapia , Radiografia
18.
J Biomed Opt ; 29(1): 018001, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38223299

RESUMO

Significance: Photodynamic therapy (PDT) is an established cancer treatment utilizing light-activated photosensitizers (PS). Effective treatment hinges on the PDT dose-dependent on PS concentration and light fluence-delivered over time. We introduce an innovative eight-channel PDT dose dosimetry system capable of concurrently measuring light fluence and PS concentration during treatment. Aim: We aim to develop and evaluate an eight-channel PDT dose dosimetry system for simultaneous measurement of light fluence and PS concentration. By addressing uncertainties due to tissue variations, the system enhances accurate PDT dosimetry for improved treatment outcomes. Approach: The study positions eight isotropic detectors strategically within the pleural cavity before PDT. These detectors are linked to bifurcated fibers, distributing signals to both a photodiode and a spectrometer. Calibration techniques are applied to counter tissue-related variations and improve measurement accuracy. The fluorescence signal is normalized using the measured light fluence, compensating for variations in tissue properties. Measurements were taken in 78 sites in the pleural cavities of 20 patients. Results: Observations reveal minimal Photofrin concentration variation during PDT at each site, juxtaposed with significant intra- and inter-patient heterogeneities. Across 78 treated sites in 20 patients, the average Photofrin concentration for all 78 sites is 4.98 µM, with a median concentration of 4.47 µM. The average PDT dose for all 78 sites is 493.17 µMJ/cm2, with a median dose of 442.79 µMJ/cm2. A significant variation in PDT doses is observed, with a maximum difference of 3.1 times among all sites within one patient and a maximum difference of 9.8 times across all patients. Conclusions: The introduced eight-channel PDT dose dosimetry system serves as a valuable real-time monitoring tool for light fluence and PS concentration during PDT. Its ability to mitigate uncertainties arising from tissue properties enhances dosimetry accuracy, thus optimizing treatment outcomes and bolstering the effectiveness of PDT in cancer therapy.


Assuntos
Éter de Diematoporfirina , Fotoquimioterapia , Humanos , Éter de Diematoporfirina/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Radiometria/métodos
19.
Photodiagnosis Photodyn Ther ; 48: 104242, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38857775

RESUMO

BACKGROUND: This systematic review assessed the effectiveness of photodynamic therapy (PDT) in patients with recurrent oral squamous cell carcinoma (OSCC). METHODS: Clinical studies on recurrent OSCC treated with PDT alone were included. Combined treatment strategies were excluded. The search was performed on Medline/Pubmed, Cochrane Library, Embase, Web of Science and ClinicalTrials.gov, manual search, and grey literature. RESULTS: The eleven included studies were observational. The risk of bias and methodological quality were evaluated using the Newcastle-Ottawa Quality Assessment Scale. The studies reported the use of hematoporphyrin derivative, PhotofrinⓇ, FoscanⓇ and 5-aminolevulinic acid. Data on treatment response and survival was collected. Secondarily, postoperative courses and patient's quality of life/acceptance were reported whenever available. PhotofrinⓇ and FoscanⓇ were the most used photosensitisers, with more complete responses. Lesions responding less favourably were on posterior regions or deep-seated in the tissue. CONCLUSIONS: Although treatment response differs between treatment protocols, PDT stands as a viable treatment option to be considered, as it can achieve therapeutic results and disease-free, long-lasting periods. Partial treatment responses may be of interest when achieving eligibility for other treatment strategies. Despite this study's limitations, which considered four photosensitisers, PhotofrinⓇ was the most used but more recent photosensitisers like FoscanⓇ have greater chemical stability, tissue penetration, and may be more efficacious on recurrent OSCC.


Assuntos
Ácido Aminolevulínico , Carcinoma de Células Escamosas , Neoplasias Bucais , Recidiva Local de Neoplasia , Fotoquimioterapia , Fármacos Fotossensibilizantes , Fotoquimioterapia/métodos , Humanos , Neoplasias Bucais/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Ácido Aminolevulínico/uso terapêutico , Éter de Diematoporfirina/uso terapêutico , Derivado da Hematoporfirina/uso terapêutico , Derivado da Hematoporfirina/farmacologia , Mesoporfirinas/uso terapêutico
20.
Strahlenther Onkol ; 189(11): 972-6, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24158603

RESUMO

INTRODUCTION: Astrocytomas are neoplasms that originate from glial cells. Anaplastic astrocytoma is classified as WHO III, with 27 % of the individuals with grade III astrocytoma living for at least 5 years even after treatment (radiation and chemotherapy). Photofrin II has been demonstrated to serve as a specific and selective radiosensitizing agent in both in vitro and in vivo tumor models. MATERIAL AND METHODS: This case report presents a woman suffering from an inoperable astrocytoma WHO III since 2004. The patient was treated with radiation therapy and Photofrin II as a radiosensitiser. The patient underwent irradiation with 40 + 20 Gy boost. The patient was given a single intravenous dose of 1 mg/kg Photofrin II 24 h prior to the initiation of radiation therapy. RESULTS: The patient is still alive without any significant side effect with a follow up of 106 months. MRI shows no evidence of disease. CONCLUSION: The follow-up results are encouraging regarding the application of Photofrin II as an effective radiosensitizing agent in the treatment of inoperable WHO III astrocytoma.


Assuntos
Astrocitoma/patologia , Astrocitoma/radioterapia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Éter de Diematoporfirina/uso terapêutico , Radiossensibilizantes/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Resultado do Tratamento
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