A comprehensive platform for low-cost screening and image-guided photodynamic therapy (PDT) of pre-malignant and malignant oral lesions in low resource settings

一个综合平台，用于在资源匮乏的环境中对癌前和恶性口腔病变进行低成本筛查和图像引导光动力治疗 (PDT)

• 批准号: 10648426
• 负责人: Jonathan P Celli
• 金额: $ 63.79万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-15 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10648426
• 关键词: 3-Dimensional; Address; Adhesives; Adoption; Aftercare; Agreement; Aminolevulinic Acid; Artificial Intelligence; Artificial Intelligence platform; Astronomy; Award; Capital; Carcinogens; Carcinoma in Situ; Cessation of life; Cheek structure; Classification; Clinical; Collaborations; Country; Data; Detection; Development; Devices; Diagnosis; Disease; Disease Progression; Eligibility Determination; Engineering; FDA approved; Family suidae; Fluorescence; Future; Germany; Goals; Hamsters; High grade dysplasia; Histologic; Histopathology; Image; Imaging Device; In Vitro; Incidence; Income; India; Individual; Industry; Infrastructure; Learning; Lesion; Letters; Light; Low income; Malignant - descriptor; Malignant Neoplasms; Mastication; Medical; Modality; Modeling; Monitor; Mucous Membrane; Mus; Oncologist; Optics; Oral; Oral Stage; Oral cavity; Oral mucous membrane structure; Outcome; PUVA Photochemotherapy; Participant; Pathology; Patients; Penetration; Performance; Photobleaching; Photochemistry; Photosensitization; Photosensitizing Agents; Property; Public Health; Radiation therapy; Resource-limited setting; Safety; Scientist; Screening for Oral Cancer; Screening for cancer; Sensitivity and Specificity; Site; Surgeon; Surgical Oncology; System; Technology; Testing; Therapeutic Agents; Time; Topical application; Training; Treatment Efficacy; Tumor Burden; Validation; Work; Xenograft Model; Xenograft procedure; augmented intelligence; cancer site; carcinogenicity; clinical center; clinical implementation; cloud based; cohort; convolutional neural network; cost; deep learning; design; dosimetry; ergonomics; experience; handheld equipment; healing; high risk; image guided; imaging approach; imaging system; inclusion criteria; innovation; intraoral probe; light weight; malignant mouth neoplasm; meetings; molecular imaging; oral lesion; oral premalignancy; patient screening; point of care; portability; pre-clinical; preclinical study; premalignant; response; rural area; rural setting; screening; subcutaneous; success; systemic toxicity; therapeutic evaluation; tumor; validation studies

Motivated by the bleak situation of oral cancer in India and encouraged by our successes in the UH2/UH3 mechanism for diagnosing and treating pre- and early cancers, a new integrated “Screen, Image and Treat Optical System” (SITOS) is proposed in the current application which combines the expertise of 3 US sites in collaboration with 2 clinical Indian teams. All sites were participants in the previous NCI awards as 2 individual UH2/UH3 projects focused on either detection or therapy. The treatment continues to be photodynamic therapy (PDT), a photochemistry-based, FDA approved modality while the detection is based on fluorescence and white light imaging combined with a cloud-based deep-learning AI approach for image classification. The SITOS enables image guided PDT, while a topical application of the dual property flourophore/photosensitizer precursor to the oral cavity, more suitable for LMICs and designed to achieve better tumor penetration than previous topical deliveries, is also developed. The goals will be accomplished in 3 Specific Aims. Aim 1 builds on previous successful development and clinical validation of separate low-cost devices for intraoral imaging, and intraoral PDT to produce a new, handheld, low-cost, easy-to-use, SITOS. The integrated platform enables the use of the same hardware for initial imaging, and a single thernostic molecule for image-guided PDT and online monitoring during therapy. Incorporated is an ergonomic intraoral light delivery for PDT and preliminarily validated in optical phantoms and in vitro 3D tumor models. Aim 2A establishes conditions for topical photosensitization using an adhesive ALA patch provided by Photonamic GmbH in ex vivo porcine mucosa model. Based on data from 2A, Aim 2B establishes optimal PDT parameters in a murine xenograft model. Aim 2C validates the best of these parameters in a carcinogen-induced hamster cheek pouch model which recapitulates transition from pre- malignant to malignant lesions. Aim 3 applies SITOS to identify and treat high-risk oral potentially malignant lesions (OPML), and early-stage oral cancer using broad guidance from the preclinical studies. Screening of patients will take place at camps and remote villages led by the clinical teams in India as in the UH effort. Patients with histologically confirmed HGD/OPML (and meeting other inclusion criteria) will be eligible. Patients will be treated using the ALA topical patch, (after a small cohort establishes safety and optimal contact time, based on Aim 2). Finally, PDT of high-risk OPML and early cancer in patients using light delivery and simultaneous image guidance with the new intraoral probe will be performed. Impact and relevance: The study provides, for the first time, a comprehensive low-cost approach that enables not only detection of pre-malignant/malignant oral lesions, but also an effective, monitored therapy in LMIC settings. The SITOS platform is mobile, handheld and appropriate for point of care applications. It brings together collaborators (scientists, oral cancer surgeons, oncologists and industry) to help with FDA clearance of ALA patch and SITOS. Capacity building: a new clinical modality and a platform for AI/engineering development.

受到印度口腔癌的黯淡的动机，并受到我们在UH2/UH3的成功的鼓舞 诊断和治疗前和早期癌症的机制，这是一种新的集成的“屏幕，图像和治疗 在当前应用中提出了光学系统”（SITOS），该应用程序结合了3个美国站点的专业知识 与2个临床印度团队合作。所有站点都是前NCI奖的参与者，因为 UH2/UH3项目的重点是检测或治疗。该治疗继续是光动力疗法 （PDT），一种基于光化学的FDA批准的模态，而检测是基于荧光和白色的 光成像结合了基于云的深度学习AI方法进行图像分类。 Sitos 启用图像引导的PDT，而双重属性地板/光敏剂前体的局部应用 到口腔，更适合LMIC，并且旨在获得比以前的局部性更好的肿瘤穿透力 交付也是开发的。目标将以3个特定目标实现。 AIM 1建立在以前的 成功开发和临床验证口腔内成像和口腔内的单独的低成本设备 PDT生产新的手持式，低成本，易于使用的SITOS。集成平台可以使用 初始成像的相同硬件，以及用于图像引导的PDT和在线监视的单个thernostic分子 在治疗期间。合并是PDT的人体工程学内光输送，并在光学上进行了初步验证 幻影和体外3D肿瘤模型。 AIM 2A建立了使用一个局部光敏化的条件 光子症GmbH在离体猪粘膜模型中提供的粘合剂ALA斑块。基于来自2a的数据 AIM 2B在鼠标模型模型中建立了最佳的PDT参数。 AIM 2C验证其中最好的 致癌物诱导的仓鼠脸颊袋模型中的参数，该模型概括了从预先的过渡 恶性病变。 AIM 3应用SITOS来识别和治疗高风险的口​​服潜在恶性肿瘤 使用临床前研究的广泛指导，病变（OPML）和早期口腔癌。筛选 在UH工作中，患者将在印度临床团队领导的营地和偏远村庄举行。患者 通过组织学确认的HGD/OPML（并符合其他纳入标准）将符合条件。患者会 使用ALA局部贴片处理（小队列建立安全性和最佳接触时间之后 目标2）。最后，使用光输送和简单图像的患者中高风险OPML和早期癌症的PDT 将对新的口腔内探针进行指导。 影响与相关性：研究首次提供了一种全面的低成本方法 不仅检测恶性/恶性口腔病变，而且还检测有效的LMIC治疗 设置。 SITOS平台是移动的，手持式的，适用于护理点。它聚集在一起 合作者（科学家，口腔癌医生，肿瘤学家和行业），以帮助FDA清除ALA 补丁和SITOS。能力建设：一种新的临床方式和AI/工程开发的平台。