Neoplasms

Digestive System Diseases

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Esophageal Neoplasms

Head and Neck Neoplasms

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

All Drugs and Chemicals

Fluorodeoxyglucose F18

Aerodigestive tract cancers are common malignancies. These cancers were ranked to be top-ten cancer-related deaths in Taiwan. Although many new target therapies and immunotherapies have emerged, many of the treatment eventually fail. For example, a 30-40% failure rate has been reported for target therapy, and, even higher for immune checkpoint inhibitors. A reliable model to more accurately predict treatment response and survival is warranted. The radiomic features extracted from F-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) can be used to figure tumor biology such as metabolome and heterogeneity. It can therefore be used to predict treatment response and individual survival. On the other hand, genomic data derived from next-generation sequencing (NGS) can interrogate the genetic alteration of cancer cells. It can be used to feature genetic identification of the tumor and can also be used to identify target genes. However, both modalities have their weakness; a combination of the two may devise a more powerful predictive model for more precise clinical decision. The investigators plan to recruit patients aged at least 20-year with the diagnosis of aerodigestive tract cancers for radiogenomic study. Our previous studies have found that radiomic features derived from 18F-FDG PET can predict treatment response and survival in patients with esophageal cancer treated with tri-modality method. The investigators also discovered that radiomics could predict survival in patients with EGFR-mutated lung adenocarcinoma treated with target therapy. In addition, our study results showed that the level of PD-L1 expression is associated with radiomics as well. The investigators plan to add genomic data into radiomics and interrogate cancers from different aspects. The investigators seek to devise a more precise model to predict the treatment response and survival in patients with aerodigestive tract cancers.

This is a prospective study and The investigators use the routine pathological specimens for next generation sequencing (NGS), microsatellite instability (MSI) and immunohistochemical stains.

Pathological examinations including PD-L1, EGFR status, ALK and ROS-1.

NGS (Next Generation Sequencing)： Total DNA were extracted from EDTA-peripheral venous blood and paraffin-embedded tumor specimens with the QIAamp® DNA Blood Mini Kit and QIAamp DNA FFPE Tissue Kit (QIAGEN GmbH, Hilden, Germany), respectively. For DNA whole exome sequence, briefly, tumor and blood DNA were sonicated by Covaris M220 sonicator (Life Technologies Europe, Gent, Belgium) and then ligated to adaptor for further amplification (Illumina® TruSeq Exome Library Prep, USA). All of library preparation were performed in the Cancer Translational Core Facility of Taipei Medical University. After library preparation, all samples were sequenced using the NextSeq500 system according to the manufacturer's instructions (Illumina, San Diego, USA). After sequencing performance, quality of reads file (fastq) was assessed by FastQC and then mapped using human Hg19 as the reference. Bam files were used as input for the Varscan algorithm to identify germline and somatic mutations. Variants annotated and filtered were manually checked using IGV (Integrative Genomics Viewer), then confirmed by Sanger sequence.

To calculate the TMB (total mutation burden) per megabase, the total number of mutations counted is divided by the size of the coding region of the targeted territory.

To calculate MATH (mutant-allele tumor heterogeneity), The investigators will first obtain the MAF (the fraction of DNA that shows the mutated allele at a gene locus) of each tumor specimen. The MAF distribution will be used to calculate the median (center of distribution) and the MD (median deviation) of MAFs in a tumor. The MD is determined by obtaining the absolute differences of all MAFs from the median MAF. Then the median of the absolute differences is multiplied by a factor of 1.4826 to obtain the MD. The MATH value is calculated as the percentage ratio of the MD to the median: MATH = (MD/median)×100.

MSI (Microsatellite instability) Microsatellite instability polymerase chain reaction (MSI-PCR) MSI-PCR testing was performed by the Cancer Translational Core Facility of Taipei Medical University using Promega MSI analysis kit (Promega). The MSI analysis consists of five nearly monomorphic mononucleotide markers (BAT-25, BAT-26, NR- 21, NR-24, and MONO-27) for MSI determination. MSI analysis was performed according to the manufacturer's directions (Promega). Products were analyzed by capillary electrophoresis and the investigators interpreted microsatellite instability at 2 or more of the 5 mononucleotide loci as MSI-high, microsatellite instability at a single mononucleotide locus as MSI-low, and no instability at any of the loci as microsatellite stable (MSS).

The image features of FDG PET the investigators extracted as followed:

The traditional image parameters include SUVmax, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary tumor. The traditional FDG PET parameters were calculated using commercialized software (PBAS, PMOD 4.0). Radiomics (texture analysis) will be calculated only for pre-treatment FDG PET. The matrices of radiomic analysis include histogram analysis, Gray-level co-occurrence matrix (GLCM)、texture feature coding co-occurrence matrix (TFCCM)、gray-level run-length matrix (GLRLM)、gray-level size zone matrix (GLSZM)、neighborhood gray-tone difference matrix (NGTDM)、Texture Feature Coding Matrix (TFCM)、Texture Feature Coding Co-Occurrence Matrix (TFCCM) and Neighbouring Gray Level Dependence Matrix (NGLD).

Radiogenomics in Aerodigestive Tract Cancers

Study the correlation of radiomics and genomics and pathological features

Study the association of radiogenomics with the treatment response and survival

Buddhist Tzu Chi General Hospital

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antimetabolites

During the first cycle of chemotherapy, patients will receive electroporation of the primary pancreatic tumor prior to administration of chemotherapy with gemcitabine and abraxane. The schedule of administration of gemcitabine and nab-paclitaxel will be administered as per standard of care. The chemotherapy schedule will include administration of nab-paclitaxel 125mg/m2 intravenous (IV) over approximately 30 to 45 minutes on Days 1, 8, and 15, followed by gemcitabine 1000mg/m2 IV infusion over approximately 30 minutes on days 1, 8, and 15 of each 28 day cycle.

Irreversible electroporation (IRE) will be performed under computed tomography (CT) guidance, during which 2 to 6 needles are advanced into the pancreatic tumor where a specified field strength will be applied.

Electroporation

The chemotherapy schedule will include administration of gemcitabine 1000mg/m2 IV infusion over approximately 30 minutes on days 1, 8, and 15 of each 28 day cycle.

gemcitabine

The chemotherapy schedule will include administration of nab-paclitaxel 125mg/m2 intravenous (IV) over approximately 30 to 45 minutes on Days 1, 8, and 15.

nab-paclitaxel

Anil K Pillai, MD

The purpose of this study is to see how well electrochemotherapy works at treating people with Stage III pancreatic adenocarcinoma. Electrochemotherapy is a treatment that combines electroporation and chemotherapy administration. Electroporation uses an electric current to produce holes in pancreatic tumor, which causes the tumor cells to die or take up a higher concentration of administered chemotherapy agent. This study will test the safety and look at the effect of electrochemotherapy in the treatment of stage III pancreatic adenocarcinoma. This study will also help to find the safest and most effective amount of electroporation voltage to apply to this type of tumor.

This is a phase I dose escalation trial using a 3 + 3 dose escalation scheme to evaluate the maximum tolerated field strength dose of administered irreversible electroporation in combination with chemotherapy. During the first cycle of chemotherapy, patients will receive electroporation of the primary pancreatic tumor prior to administration of chemotherapy with gemcitabine and nab-paclitaxel. The schedule of administration of gemcitabine and nab-paclitaxel will be administered as per standard of care. The investigators will use non-invasive dynamic magnetic resonance imaging and magnetic resonance spectroscopy to detect and describe changes within the tumor. Safety will be determined by assessing the number of class three or higher toxicity events in cohorts of 6 patients at progressively higher electroporation voltages. The maximum tolerated dose (MTD) will be defined as one voltage level less than the voltage at which two or more patients out of six total patients have a class three or higher toxicity event.

Evaluation of Safety and Efficacy of Electrochemotherapy in the Treatment of Pancreatic Adenocarcinoma

A dose limiting toxicity (DLT) is any Grade 3 or 4 adverse event (AE) using the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE 4.0) that is possibly related to the electrochemotherapy treatment. CTCAE 4.0 Grade 3 is a severe AE and Grade 4 is a life-threatening or disabling AE. DLTs are collected to determine the Maximum Tolerated Dose (MTD), which is defined as as one field strength level less than the field strength at which two or more patients out of six total patients experience a DLT.

Time to progression is the time after treatment until tumor enlargement or metastatic disease is identified.

One year survival is the number of patients who are alive one year after treatment.

We will assess tumor size changes and tumor staging through magnetic resonance imaging (MRI).

Gene expression characteristics are identified by biopsy specimen evaluation. Imaging characteristics are evaluated by MRI and MRS.

Gene expression characteristics are identified by biopsy specimen evaluation. Clinical outcomes are evaluated by time to progression and 1 year survival. Time to progression is the time after treatment until tumor enlargement or metastatic disease is identified. One year survival is the number of patients who are alive one year after treatment.

The University of Texas Health Science Center, Houston

Assistant Professor

Carcinoma, Non-Small-Cell Lung

Carcinoma, Bronchogenic

Bronchial Neoplasms

Yu-Hung Chen, M.D.

Lung cancer is currently the leading cause of cancer-related mortality worldwide, and the dominant histopathology is non-small cell lung cancer (NSCLC). Although many new targeted and immunomodulation therapies have emerged, not all patients are responsive to novel therapeutics. A more reliable and accurate risk stratification model to predict the treatment response and survival outcomes are still lacking. The 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) derived radiomics can be used to interrogate tumor biologies such as glycolytic activity and heterogeneity. It can, therefore, be used to predict treatment response and survival outcomes. Cancer genomics derived from gene sequencing can evaluate cancer's genetic alterations. It can be used to feature the genotype of the tumor. However, both tools have drawbacks; combining these two modalities may enable a more robust predictive model for more precise clinical decisions. During the investigator's former study project, the investigators published four Science Citation Index journal papers using the investigators' research results, which found that 18F-FDG PET radiomics can independently predict regional lymph node metastasis in NSCLC and cancer survival by stage. The preliminary findings of the investigator's former research project also disclosed an association between 18F-FDG PET-derived molecular radiomics with genomic heterogeneity and mutation of specific glucose metabolic genes. This time, the investigators plan to include deep radiomics in addition to traditional handcrafted radiomics. The investigators aim to investigate the radiogenomic patterns in different driver gene mutation statuses and clinical scenarios. Finally, the investigators seek to use radiogenomics as a prognostic stratification tool in patients with NSCLC.

This is a prospective study and The investigators use routine pathological specimens for whole exome sequencing (WES) and immunohistochemical stains.

Pathological examinations include PD-L1, EGFR status, ALK, and ROS-1.

WES： Total DNA were extracted from paraffin-embedded tumor specimens with the QIAamp DNA FFPE Tissue Kit (QIAGEN GmbH, Hilden, Germany). The coding size was 45 Mb. For DNA whole exome sequence, briefly, tumors were sonicated by Covaris M220 sonicator (Life Technologies Europe, Gent, Belgium) and then ligated to adaptor for further amplification (Illumina® TruSeq Exome Library Prep, USA). After library preparation, all samples were sequenced using the NextSeq500 system according to the manufacturer's instructions (Illumina, San Diego, USA). The investigators run sequencing with 12 samples simultaneously (a total of 100 Gb). The sequence length was 150 bp with a paired-end (2\*150bp). The average depth of sequencing is 100X. After sequencing performance, quality of reads file (fastq) was assessed by FastQC and then mapped using human Hg19 as the reference. Bam files were used as input for the Varscan algorithm to identify germline and somatic mutations. Variants annotated and filtered are manually checked using IGV (Integrative Genomics Viewer), then confirmed by Sanger sequence. The investigators analyze the clinical related gene alterations including actionable gene mutations (EGFR, BRAF, KRAS, and MET.) Also, clinically important genes including the mutation status of TP53 and SDH genes are analyzed. The investigators also analyzed the mutation status of glucose metabolic cluster genes.

TMB (tumor mutation burden) per megabase: The total number of mutations counted is divided by the size of the coding region of the targeted territory.

MATH (mutant-allele tumor heterogeneity): The investigators first obtain the MAF (the fraction of DNA that shows the mutated allele at a gene locus) of each tumor specimen. The MAF distribution will be used to calculate the median (center of distribution) and the MD (median deviation) of MAFs in a tumor. The MD is determined by obtaining the absolute differences of all MAFs from the median MAF. Then the median of the absolute differences is multiplied by a factor of 1.4826 to obtain the MD. The MATH is calculated as the percentage ratio of the MD to the median: MATH = (MD/median)×100 \[45\].

Shannon diversity index (Shannon entropy) \[50\]: The MAF distribution (histogram) of each patient's tumor specimen was obtained with different bin sizes (total bin size = S). The Shannon diversity index is then calculated according to the distribution of probabilities of each MAF bin.

The image features of FDG PET the investigators extracted as follows, \<Handcrafted radiomics\> The traditional image parameters include SUVmax, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary tumor. The traditional FDG PET parameters are calculated using commercialized software (PBAS, PMOD 4.0). Radiomics (texture analysis) will be calculated only for pre-treatment FDG PET. The matrices of radiomic analysis include histogram analysis, Gray-level co-occurrence matrix (GLCM), gray-level run-length matrix (GLRLM), gray-level size zone matrix (GLSZM), neighborhood gray-tone difference matrix (NGTDM), and shape features.

\<Deep radiomics\> The investigators put the segmented volume into convolutional neural network (CNN) for analysis. The investigators will use supervised CNN to analyze the relationship between imaging with other outcomes.

The Use of Molecular Radiogenomics in Non-small Cell Lung Cancer

Ho Yun Lee, Dr

The purpose of this study is to evaluate relationships between multiparametric imaging biomarkers and genetic analysis in NSCLC patients.

To evaluate relationships between multiparametric imaging biomarkers(CT, PET/CT, MRI) and genetic analysis in NSCLC patients

Radiomic Assessment in NSCLC: Correlation Between Multiparametric Imaging Biomarkers and Genetic Biomarkers

Prognostic stratification will be evaluated using following parameters:

1. Quantitative and qualitative parameters from CT, PET, MRI
2. Genomic data of lung cancer samples

We will evaluate if certain relationship exists between changes in multiparametric imaging markers from CT, PET, MRI and genomic informations of NSCLC.

following parameters exracted from whole lung will be evaluated: Quantitative parameters related to pulmonary function from CT, PET, MRI 2. Prediction of longitudinal changes of pulmonary function after the lung resection

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Radiogenomics in Aerodigestive Tract Cancers	NCT04314349	Cancer, Lung Cancer of Esoph... Cancer of Head ...		20 Years -	Buddhist Tzu Chi General Hospital
Radiogenomics in Aerodigestive Tract Cancers	NCT04314349	Cancer, Lung Cancer of Esoph... Cancer of Head ...		20 Years -	Buddhist Tzu Chi General Hospital
Evaluation of Safety and Efficacy of Electrochemotherapy in the Treatment of Pancreatic Adenocarcinoma	NCT02514421	Pancreatic Aden...	Electroporation gemcitabine nab-paclitaxel	18 Years -	The University of Texas Health Science Center, Houston
The Use of Molecular Radiogenomics in Non-small Cell Lung Cancer	NCT05541744	Lung Cancer		20 Years -	Buddhist Tzu Chi General Hospital
Radiomic Assessment in NSCLC: Correlation Between Multiparametric Imaging Biomarkers and Genetic Biomarkers	NCT01585545	Lung Cancer		20 Years -	Samsung Medical Center
The Use of Molecular Radiogenomics in Non-small Cell Lung Cancer	NCT05541744	Lung Cancer		20 Years -	Buddhist Tzu Chi General Hospital

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