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.

受到印度口腔癌的严峻形势的激励，并受到我们在 UH2/UH3 中取得的成功的鼓舞 诊断和治疗前期和早期癌症的机制，一种新的综合“筛查、成像和治疗” 当前申请中提出了“光学系统”（SITOS），它结合了 3 个美国站点的专业知识 与 2 个印度临床团队合作。所有中心均作为 2 个个人参加了之前的 NCI 奖项。 UH2/UH3 项目侧重于检测或治疗 治疗仍然是光动力疗法。 (PDT)，一种基于光化学的 FDA 批准的模式，而检测基于荧光和白光 光成像与基于云的深度学习人工智能方法相结合进行图像分类。 实现图像引导 PDT，同时局部应用双特性荧光团/光敏剂前体 口腔，更适合中低收入国家，旨在比以前的局部用药实现更好的肿瘤渗透 交付，也将在 3 个具体目标 1 的基础上实现。 用于口腔内成像和口腔内成像的独立低成本设备的成功开发和临床验证 PDT 产生了一种新型、手持式、低成本、易于使用的 SITOS 集成平台。 用于初始成像的相同硬件，以及用于图像引导 PDT 和在线监测的单个热疗分子 治疗期间纳入了符合人体工程学的口腔内光传输，用于 PDT 并在光学方面进行了初步验证。 Aim 2A 使用光敏剂建立了局部光敏化的条件。 Photonamic GmbH 在离体猪粘膜模型中提供的粘性 ALA 贴片 基于 2A 的数据， Aim 2B 在鼠异种移植模型中建立了最佳 PDT 参数，Aim 2C 验证了其中的最佳参数。 致癌物诱导的仓鼠颊袋模型中的参数，该模型概括了从前的转变 目标 3 应用 SITOS 识别和治疗高危口腔潜在恶性病变。 病变（OPML）和早期口腔癌，使用临床前研究筛查的广泛指导。 与 UH 的患者工作一样，患者将在印度临床团队领导的营地和偏远村庄接受治疗。 经组织学证实的 HGD/OPML（并满足其他纳入标准）的患者将符合资格。 使用 ALA 局部贴剂进行治疗（在一小群人确定安全性和最佳接触时间后，基于 目标 2) 最后，使用光传输和同步图像对高危 OPML 和早期癌症患者进行 PDT。 将使用新的口腔内探头进行引导。 影响和相关性：该研究首次提供了一种全面的低成本方法，使 不仅可以检测恶变前/恶性口腔病变，而且还是中低收入国家的有效、受监测的治疗方法 SITOS 平台是移动式、手持式的，适用于护理点应用。 合作者（科学家、口腔癌外科医生、肿瘤学家和行业）帮助 FDA 批准 ALA 补丁和 SITOS。能力建设：一种新的临床模式和人工智能/工程开发平台。