RESUMEN
PURPOSE: Glioblastoma remains incurable despite optimal multimodal management. The interim analysis of open label, single arm INDYGO pilot trial showed actuarial 12-months progression-free survival (PFS) of 60% (median 17.1 months), actuarial 12-months overall survival (OS) of 80% (median 23.1 months). We report updated, exploratory analyses of OS, PFS, and health-related quality of life (HRQOL) for patients receiving intraoperative photodynamic therapy (PDT) with 5-aminolevulinic acid hydrochloride (5-ALA HCl). METHODS: Ten patients were included (May 2017 - April 2021) for standardized therapeutic approach including 5-ALA HCl fluorescence-guided surgery (FGS), followed by intraoperative PDT with a single 200 J/cm2 dose of light. Postoperatively, patients received adjuvant therapy (Stupp protocol) then followed every 3 months (clinical and cerebral MRI) and until disease progression and/or death. Procedure safety and toxicity occurring during the first four weeks after PDT were assessed. Data concerning relapse, HRQOL and survival were prospectively collected and analyzed. RESULTS: At the cut-off date (i.e., November 1st 2023), median follow-up was 23 months (9,7-71,4). No unacceptable or unexpected toxicities and no treatment-related deaths occurred during the study. Kaplan-Meier estimated 23.4 months median OS, actuarial 12-month PFS rate 60%, actuarial 12-month, 24-month, and 5-year OS rates 80%, 50% and 40%, respectively. Four patients were still alive (1 patient free of recurrence). CONCLUSION: At 5 years-follow-up, intraoperative PDT with surgical maximal excision as initial therapy and standard adjuvant treatment suggests an increase of time to recurrence and overall survival in a high proportion of patients. Quality of life was maintained without any severe side effects. TRIAL REGISTRATION NCT NUMBER: NCT03048240. EudraCT number: 2016-002706-39.
Asunto(s)
Ácido Aminolevulínico , Neoplasias Encefálicas , Glioblastoma , Fotoquimioterapia , Fármacos Fotosensibilizantes , Humanos , Glioblastoma/tratamiento farmacológico , Glioblastoma/terapia , Glioblastoma/cirugía , Glioblastoma/mortalidad , Masculino , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/mortalidad , Femenino , Persona de Mediana Edad , Fotoquimioterapia/métodos , Estudios de Seguimiento , Anciano , Ácido Aminolevulínico/uso terapéutico , Ácido Aminolevulínico/administración & dosificación , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/administración & dosificación , Adulto , Calidad de Vida , Proyectos Piloto , Tasa de SupervivenciaRESUMEN
Advanced ovarian cancer is the most serious among gynecological malignancies and is associated with 35% five-year overall survival. Surgery is the first therapeutic indication, and the absence of remaining macroscopic lesions is the most important prognostic factor. However, tumor dissemination over the whole abdominal cavity largely contributes to the difficulty of complete surgical resection. Consequently, any therapeutic approach that may complete surgical resection should improve patient survival. Considering that some sites are not suitable for surgery because of their close location to vital organs, intraoperative photodynamic therapy (ioPDT) appears to be a complementary therapeutic approach to surgery to obtain the lowest residual disease.Relevant in vivo cancer models that closely resemble human ovarian cancer are essential for preclinical research of alternative antitumor therapeutic strategies. Thus, we propose a comprehensive protocol to set up an orthotopic ovarian xenograft in mice leading to peritoneal carcinomatosis that could be harnessed for antitumor therapeutic application and evaluation.
Asunto(s)
Neoplasias Ováricas , Neoplasias Peritoneales , Fotoquimioterapia , Animales , Carcinoma Epitelial de Ovario , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Neoplasias Ováricas/patologíaRESUMEN
BACKGROUND AND OBJECTIVES: Intraoperative photodynamic therapy (IO-PDT) is typically administered by a handheld light source. This can result in uncontrolled distribution of light irradiance that impacts tissue and tumor response to photodynamic therapy. The objective of this work was to characterize a novel optical surface applicator (OSA) designed to administer controlled light irradiance in IO-PDT. STUDY DESIGN/MATERIALS AND METHODS: An OSA was constructed from a flexible silicone mesh applicator with multiple cylindrically diffusing optical fibers (CDF) placed into channels of the silicone. Light irradiance distribution, at 665 nm, was evaluated on the OSA surface and after passage through solid tissue-mimicking optical phantoms by measurements from a multi-channel dosimetry system. As a proof of concept, the light administration of the OSA was tested in a pilot study by conducting a feasibility and performance test with 665-nm laser light to activate 2-(1'-hexyloxyethyl) pyropheophorbide-a (HPPH) in the thoracic cavity of adult swine. RESULTS: At the OSA surface, the irradiance distribution was non-uniform, ranging from 128 to 346 mW/cm2 . However, in the tissue-mimicking phantoms, beam uniformity improved markedly, with irradiance ranges of 39-153, 33-87, and 12-28 mW/cm2 measured at phantom thicknesses of 3, 5, and 10 mm, respectively. The OSA safely delivered the prescribed light dose to the thoracic cavities of four swine. CONCLUSIONS: The OSA can provide predictable light irradiances for administering a well-defined and potentially effective therapeutic light in IO-PDT. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
Asunto(s)
Láseres de Semiconductores/uso terapéutico , Fotoquimioterapia/instrumentación , Cavidad Torácica/efectos de la radiación , Animales , Humanos , Fantasmas de Imagen , Siliconas , PorcinosRESUMEN
Photodynamic therapy (PDT) is an established treatment modality for non-small cell lung cancer. Phototoxicity, the primary adverse event, is expected to be minimized with the introduction of new photosensitizers that have shown promising results in phase I and II clinical studies. Early-stage and superficial endobronchial lesions less than 1 cm in thickness can be effectively treated with external light sources. Thicker lesions and peripheral lesions may be amenable to interstitial PDT, where the light is delivered intratumorally. The addition of PDT to standard-of-care surgery and chemotherapy can improve survival and outcomes in patients with pleural disease. Intraoperative PDT has shown promise in the treatment of non-small cell lung cancer with pleural spread. Recent preclinical and clinical data suggest that PDT can increase antitumor immunity. Crosslinking of signal transducer and activator of transcription-3 molecules is a reliable biomarker to quantify the photoreaction induced by PDT. Randomized studies are required to test the prognosis value of this biomarker, obtain approval for the new photosensitizers, and test the potential efficacy of interstitial and intraoperative PDT in the treatment of patients with non-small cell lung cancer.