Neoplasms

Eye Diseases

All Conditions

Diseases and Abnormalities at or Before Birth

Rare Diseases

Retinoblastoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Retinal Neoplasms

Eye Neoplasms

Eye Diseases, Hereditary

Retinal Diseases

Neuroepithelioma

MR imaging protocol should include a thin-slice (3-4 mm) short TI inversion recovery (STIR) sequence or fat-saturated T2-weighted images in axial direction. Furthermore, a 3D-T1 weighted sequence with isotropic voxels will be obtained, with reconstruction in 3 directions. If suspicious lesions are detected, additional MR imaging has to be performed, including contrast-enhanced images.

Magnetic resonance imaging

Marcus C de Jong, MD, MSc

Marcus C de Jong, MC, MSc

Jonas A Castelijns, PhD

Rationale: Hereditary retinoblastoma survivors have an increased risk to develop second primary tumors (SPT) at a later age (with the highest risk in their teens), especially when they have been irradiated for retinoblastoma. The investigators hypothesize that regular screening with magnetic resonance imaging (MRI) could lead to early detection of SPTs leading to improved survival.

Objective: To evaluate the potential benefit of craniofacial MRI screening for early detection subclinical secondary cancers in patients previously irradiated for hereditary retinoblastoma.

Study design: Prospective multicenter non-invasive screening study. The total study duration will be four years of screening plus five years of follow-up.

Study population: Irradiated hereditary retinoblastoma patients 8-18 years old Main study parameters/endpoints: To evaluate the ability of craniofacial MRI for early detection of SPTs, the investigators will determine the sensitivity and specificity of MRI at detecting SPTs in irradiated hereditary retinoblastoma patients.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Included patients will undergo yearly craniofacial MRI for a period of 4 years. They will also be asked to fill out a psychological burden assessment form each visit. A potential risk of screening might be associated anticipatory anxiety, but screening also could be reassuring for patients and their parents; the investigators are not sure which will outweigh. False-positive results from MRI screening could lead to unnecessary further diagnostics leading to possible added anxiety and diagnostics (e.g., biopsies). However, this group of patients have a high risk of developing SPTs, with poor 5-year survival statistics. Early detection and therefore treatment of earlier stage (smaller) tumors, might therefore increase survival of this patient group.

SPT Screening in Irradiated Hereditary Retinoblastoma Survivors

Multicenter Implementation of MR Imaging Studies in Irradiated Hereditary Retinoblastoma Survivors for Assessment of the Value of Craniofacial MRI Screening for Early Detection of Second Craniofacial Primary Tumors and to Enhance Survival

The primary objective of the study is to evaluate the benefit of early detection of craniofacial second primary tumors with MRI in previously irradiated hereditary retinoblastoma survivors. The main outcome measure for assessing the benefit of screening will be the diagnostic accuracy of MRI for detecting craniofacial SPTs: sensitivity (true-positive and false-negative results) and specificity (true-negative and false-positive results).

A secondary objective is to assess the 5-year survival of second primary tumors (SPT) found by screening, SPTs missed by screening, and the non-SPT patients

Recording and monitoring location and characteristics (clinical, radiological, histological, treatment) of patients with SPTs: total number of patients included, median follow-up time + range, number of asymptomatic SPTs detected by screening, number of symptomatic SPTs missed by screening, number of SPTs developed after the end of screening, number of SPTs that were totally resected, location of tumor, type of tumor, size of tumor

Assessment of the feasibility of such this screening program: (a) percentage of patients (or family) willing to participate; (b) compliance of patients and their families to the screening program

Once a year during the visits, the patient will be asked to fill out the Hospital Anxiety and Depression Scale (HADS).

ODAS

Amsterdam UMC, location VUmc

Symptoms and General Pathology

Mouth and Tooth Diseases

Recurrence

Carcinoma

Carcinoma, Squamous Cell

Neoplasm Metastasis

Mouth Neoplasms

Neoplastic Cells, Circulating

Squamous Cell Carcinoma of Head and Neck

Head and Neck Neoplasms

Oral Squamous Cell Carcinoma

Oral Cancer

Anti-Infective Agents

Central Nervous System Depressants

All Drugs and Chemicals

Ethanol

Patients with oral cavity squamous cell carcinoma post-surgery no need for any adjuvant therapy

Patients with oral cavity squamous cell carcinoma post-surgery with major risk factor(s) or 2 minor risk factors Stratification by Risk factors, alcohol, betel nut chewing and cigarette use status

Yo-Ting Hsueh

Chia-Hsun Hsieh, M.D,M.S.

Chia-Hsun Hsieh, M.D, M.S

Chun-Ta Liao, M.D

Hung-Ming Wang, M.D

Chien-Yu Lin, M.D

Tzu-Chen Yen, M.D

Li-Yu Lee, M.D

Chun-Ta Liao, MD

Anti-cancer treatments have been thought to be closely related to their unique genetic alterations. In the past few years, the investigator have used cDNA microarray to delineate the transcriptome profiles of differentially-expressed genes between OSCC tumors and normal epithelium. By supervised hierarachical clustering analysis, the investigator further analyzed and validated the differentially-expressed genes for OSCC tumors. In the investigators' previous research, the investigators have used this strategy to analyze the potential tissue proteins associated with OSCC tumors, indicating the feasibility of this strategy. However, gene detection is a great limitation and challenge in CTCs researches owing to the small number of isolated cells by traditional methods. Fortunately, by means of the investigators' developing high-purity CTCs isolation techniques, some preliminary data implied that isolated CTCs by this method could achieve the criteria of Whole-genome analysis (WGA), which brings the investigators' passion for further investigation.

First Year

1. Negative Selection Method 2. Positive Selection method (Dynabeads) 3. ODEP devices 4. Flow Cytometry and Sorting System 5. Cell lines for Positive control Second Year \&Third year

1. Clinical Trial, Patient Enrollment and Design of Schedule

   The Inclusion criteria and aims are as followings:
   1. Patients with oral cavity squamous cell carcinoma (n=180), with age at diagnosis ≥ 20 years, will be enrolled before surgery at Ear-Nose-Throat department inpatient or outpatient service by Dr. Liao, Dr. Hsieh, Dr. Wang and co-PIs.
   2. All patients will be subgrouped by pathologic features and risk factors Group A (n=90): OSCC, post-surgery, no need for any adjuvant therapy Group B (n=90): OSCC, post-surgery, with major risk factor(s) or 2 minor risk factors Stratification by Risk factors, alcohol, betel nut chewing and cigarette use status
   3. Testing: Circulating tumor cells (CTCs) (x4) and NGS for WGA and transcriptomes (x4)
   4. Endpoints: Loco-regional recurrence, one-year distant metastasis rate, death, second primary tumor occurrence.
   5. Exclusion criteria are: (1) Patient's refusal; (2) Poor compliance, cannot cooperate for blood sampling for CTCs isolation as time schedule or clinical treatment or follow-up (3) Difficult blood sampling; (4) No more needs for CTCs evaluation, decided by clinicians.
2. Whole-Genome Analysis for Cancer Tissue Samples/Circulating Tumor Cells When needed, OncoScan™ FFPE Express Extraction will be performed

   Requirements need to be observed when submitting FFPE slices:

   Slices should be sent in 1.5mL conical vials Tumor samples in sections should have a surface area of 100 square mm (Minimum) to 1000 square mm (Maximum).

   Normal samples in sections should have a surface area of 200 square mm (Minimum) to 1000 square mm (Maximum).

   Section thickness should be 10 micron. The range of sections acceptable per sample is 2-6. Slices for OncoScan analysis and immunohistochemistry study are separated; and will be doubly charged by the Dep. of Clinical Pathology.

   The QIAamp DNA FFPE Tissue Kit is optimized for purification of DNA from FFPE tissue sections.

   OncoScan™ Express Samples will be performed in Chang Gung Memorial Hospital 1J GMRCL CoreLab or Chang Gung University Labs for whole-genome analysis.
3. Negative Selection Method
4. Positive Selection method (Dynabeads)
5. ODEP devices
6. Flow Cytometry and Sorting System

Feasibility of CTCs Isolation for Transcriptomes and Genome Wide Associated Analysis in Post-OP High Risk OSCC Patients.

The Feasibility of Circulating Tumor Cells Isolation for Transcriptomes and Genome-wide Associated Analysis in Post-surgically High-risk Oral Cavity Cancer Patients and Its Clinical Significance.

Measure response or progression events via all available imaging studies, including Chest-Xray, CT scans, or MRI, Positron Emission Tomography(PET)study. The relationship between CTCs number and time from CTCs checkpoint to disease progression will be analyzed.

All causes of death would be documented and the relationship between CTCs number and time from CTCs checkpoint to death will be analyzed.

Ministry of Science and Technology, Taiwan

Chang Gung Memorial Hospital

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
SPT Screening in Irradiated Hereditary Retinoblastoma Survivors	NCT02329002	Retinoblastoma	Magnetic resona...	8 Years - 18 Years	Amsterdam UMC, location VUmc
Feasibility of CTCs Isolation for Transcriptomes and Genome Wide Associated Analysis in Post-OP High Risk OSCC Patients.	NCT03917524	Oral Cavity Squ...		20 Years -	Chang Gung Memorial Hospital

Spots Global Cancer Trial Database for second primary tumor