araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: The Oncopanel Pilot (TOP) Study

Summary: The BCCA Oncopanel is a clinical assay being developed to determine genotype status of a prospectively defined set of genes.
  The purpose of this pilot study is to assess the feasibility and effect on clinical-decision-making of the Oncopanel test. Eligible patients are those with advanced lung, colorectal, melanoma and GIST cancers and patients with diagnosed malignancies being considered for clinical trials.

Detailed description: Somatic mutations in solid tumors represent an established means of characterizing malignancies for prognostic, diagnostic and therapeutic purposes. Mutations in EGFR, KRAS, BRAF, and KIT and PDGFRA genes direct therapy in patients with advanced lung, colorectal, melanoma, and GIST tumors, respectively. Known or novel mutations in other genes may also be of clinical significance but are not identified by current genotyping offered to BC Cancer Agency (BCCA) patients. Furthermore, numerous candidate genes have been implicated as potential prognostic and predictive biomarkers in patients with solid tumours. As such, the Oncopanel is a clinical assay being developed to determine genotype status of a prospectively defined set of genes. The following clinically relevant set of genes and exons are included in the Oncpanel: KRAS, EGFR, BRAF, NRAS and HRAS, PIK3CA Signal Transduction Pathway Genes, RAS-RAF-MEK-MAPK Pathway, HER2, IDH1 and IDH2, ALK, TP53, c-KIT, STAT1&3 and PDGFRA. Additional testing on the tumour material will also include analysis of specific gene variants associated with adverse events or response to therapy.
  Numerous studies have documented the presence of circulating tumour DNA (ctDNA) among patients with advanced and early stage malignancies (20-22). The ability to diagnose standard cancer mutations with a blood-based assay (a "liquid biopsy") has not yet been established but presents obvious advantages. The emergence of "resistance" mutations arising in the metastatic tumor or throughout the course of therapy is well documented (21, 22). A blood biopsy may represent more accurate determination of the tumor's genetic features than archival DNA specimen. Adequate tissue specimens can be difficult to obtain from some patients with diagnosed malignancies, particularly lung cancer. A blood biopsy may represent a less invasive and timelier means of diagnosing both standard and translational cancer mutations.

Eligibility: Patients with archival tumor tissue and a known history of invasive malignancies are eligible if they meet one or more of the following criteria:
  -  Advanced colorectal cancer and eligible for standard KRAS testing,
  -  Advanced non-small cell lung cancer and eligible for standard EGFR testing,
  -  Advanced melanoma and eligible for standard BRAF testing,
  -  Gastrointestinal stromal tumors (GISTs) eligible for standard c-KIT and PDGFRA testing,
  -  Being considered for potential eligibility in clinical trial.

Relevance to patient case: definitely relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: A Trial of Trametinib and Panitumumab in RAS/RAF Wild Type Advanced Colorectal Cancer

Summary: This is a phase 2 study (the second phase in testing a new drug or drug combination) to see how useful the combination of two drugs, panitumumab and trametinib, are in patients with advanced colorectal cancer with KRAS, NRAS, or BRAF wild type (genes that are not mutated).
  Panitumumab is a drug that is approved by Health Canada for the treatment of advanced colorectal cancer with KRAS wild type. Panitumumab works by binding to and blocking the protein, epidermal growth factor receptor (EGFR) from working.
  Trametinib is a drug that is approved by Health Canada for the treatment of melanoma with a mutation in the BRAF gene. Trametinib works by binding to and blocking mitogen-activated protein kinase kinase (MEK) 1 and MEK2 from working.
  Previous studies have shown that the combination of panitumumab and trametinib may be more useful in KRAS, NRAS, or BRAF wild type colorectal cancer.


Eligibility: Inclusion Criteria:
  -  18 years of age or older
  -  KRAS/NRAS/BRAF wild type colorectal cancer, not responsive to standard therapies, no approved or curative therapy, refuse standard therapy
  -  Prior 5-FU, oxaliplatin and irinotecan
  -  ECOG Performance Status of 0 or 1
  -  Able to swallow/retain oral drugs
  -  Able and agree to have provide tumor tissue/have biopsies
  -  Agree to use contraception
  -  Not pregnant
  -  Adequate organ system function
  Exclusion Criteria:
  -  Chemotherapy, radiotherapy, immunotherapy, or other anti-cancer therapies <28 days or 5 half lives
  -  Prior EGFR, MEK, or RAF inhibitor or regorafenib
  -  Current use of prohibited medications
  -  Unresolved side effects
  -  GI disease or other condition affecting GI absorption
  -  Mucosal or internal bleeding
  -  Any major surgery <four weeks
  -  HIV, HBV, or HCV positive
  -  Active infection
  -  Leptomeningeal disease
  -  Brain metastases
  -  Unacceptable QTcF interval
  -  Significant uncontrolled arrhythmias
  -  Acute coronary syndromes, myocardial infarction, coronary angioplasty, or stenting or bypass grafting < 6 mos.
  -  Class II, III, or IV heart failure
  -  Other clinically significant ECGs
  -  Intra - cardiac defibrillators
  -  Cardiac metastases
  -  Condition that may interfere with patient safety
  -  Hypersensitivity to study drugs
  -  Severe or uncontrolled systemic diseases
  -  Pregnant or lactating
  -  Retinal vein occlusion
  -  Interstitial lung disease or pneumonitis
  -  Active liver or biliary disease

Relevance to patient case: not relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: Circulating Cell-free Tumor DNA in the Plasma of Patients With Gastrointestinal Stromal Tumors (GIST)

Summary: This observational study is proposed to evaluate if the trend in the levels of cf-DNA evaluated on a sample of peripheral blood may be related to different clinical behaviors of the disease monitored by radiological investigations conducted.

Detailed description: Demetri and colleagues presented, at the AACR and ASCO Annual Meeting 2013, an exploratory analysis to assess GIST genotypes on patients in the GRID study. Mutations in the KIT gene were detected in 58 percent of the blood samples compared with 66 percent of the tumor tissue samples (31). However, when focusing their analysis on secondary KIT mutations, which are the mutations that drive resistance to targeted therapies like imatinib and sunitinib, the researchers found mutations in 47 percent of blood samples compared with only 12 percent of tissue samples. In addition, nearly half of blood samples in which secondary KIT mutations were found, harbored multiple secondary mutations. Therefore, cf-DNA may become an efficient marker of mutational GIST status and disease itself.
  On this basis, this trial aims to evaluate whether tumor DNA carrying mutations (for KIT, PDGFRα, BRAF, RAS, SDH) can be detected and quantified in the plasma of patients with GISTs, either with active disease or during follow-up, and whether detection can be correlated with the disease status.

Eligibility: -  Male or female patients aged >= 18 years
  -  Histologically confirmed diagnosis of GIST of any anatomical location either by biopsy or surgical specimen
  -  Available archival tumor tissue
  -  Signed informed consent form
  Exclusion Criteria:
  -  Impossibility to ensure adequate clinical and serum sample follow-up
  -  Serious psychiatric disease that precludes informed consent or limits compliance

Relevance to patient case: definitely relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: Patients With Refractory, Metastatic Cancer Harboring KIT Mutation or Amplification to Investigate the Clinical Efficacy and Safety of Imatinib Therapy

Summary: KIT is a receptor tyrosine kinase that binds to stem-cell factor (SCF), activating a series of downstream effector pathways. KIT is an established therapeutic target in cancer with activating mutations of KIT, such as gastrointestinal stromal tumors (GIST), and significant benefit is achieved with various small molecule inhibitors of KIT such as imatinib mesylate. Moreover, there is increasing evidence implicating KIT mutations as tractable therapeutic targets in melanoma. Additional information is required to characterize the functional role of low-frequency mutations in KIT and to determine whether amplification of wild type KIT is a real driver that can be targeted therapeutically. Except GIST and melanoma, other solid cancers were reported to have KIT mutation even in low frequency. A molecular profiling of the tumors of patients referred to the phase I clinic at the M.D. Anderson Cancer Center showed KIT mutation in 7 patients in total of 431 patients (2%).
  Hence, the investigators planned this study to apply the molecularly targeted agent, imatinib to various types of cancers harboring KIT mutation or amplification.


Eligibility: Inclusion Criteria:
  1. age ≥ 20
  2. advanced, refractory cancer patients who failed standard of care (SOC)
  3. KIT aberration: defined as mutation in exons 9, 11, 13, 17 or 18, or nanostring CNV by quantitative PCR (greater than 3 copies) or subject with specific sensitivity (Z-score<-1) to imatinib by Avatar scan whose disease has progressed following standard therapy or that has not responded to standard therapy or for which there is no standard therapy
  4. ECOG performance status of 0~2
  5. measurable or evaluable lesion per RECIST 1.1 criteria
  6. adequate marrow, hepatic, renal and cardiac functions
  -  Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN), or AST and ALT ≤ 5 x ULN if liver function abnormalities are due to underlying malignancy
  -  Total serum bilirubin ≤ 1.5 x ULN
  -  Absolute neutrophil count(ANC) ≥ 1,500/uL
  -  Platelets ≥ 100,0000/uL
  -  Hemoglobin ≥ 9.0 g/dL
  7. provision of a signed written informed consent
  Exclusion Criteria:
  1. severe co-morbid illness and/or active infections
  2. pregnant or lactating women
  3. history of major surgery or radiotherapy within 4 weeks
  4. active CNS metastases not controllable with radiotherapy or corticosteroids (however, CNS metastases (except for leptomeningeal seeding) are allowed if controlled by gamma knife surgery or surgery or radiotherapy or steroid)
  5. known history of hypersensitivity to study drugs

Relevance to patient case: possibly relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: A Clinical Trial Evaluating the Efficacy and Safety of Dasatinib in Refractory Metastatic GIST

Summary: The purpose of this study is to determine whether dasatinib is effective and safe in the treatment of refractory metastatic gastrointestinal stromal tumor


Eligibility: Inclusion Criteria:
  -  Histologically confirmed recurrent/metastatic gastrointestinal stromal tumor (GIST). Immunohistochemically, the detection KIT and/or DOG-1 are/is positive
  -  Patients must have measurable disease meeting the requirement of RECIST 1.1
  -  Received the gene mutation detection of c - kit/PDGFRA
  -  Subjects with mutation in exon 11, in exon 9 and wild type c-kit/PDGFRA have failed to imatinib and sunitinib
  -  Subjects with primary mutation in exon 17 or 18 have failed to imatinib
  -  Subjects with primary mutation in exon 11 and secondary mutation in exon 17 or 18 have failed to imatinib
  -  Subjects with mutation in exon 18 of PDGFRA,have received TKI or not
  -  Eastern Cooperative Oncology Group (ECOG) performance status = 0-2
  -  Expected OS ≥3 months
  -  Ability to understand and the willingness to sign a written informed consent document
  -  Subject will comply with the study procedures and therapy
  Exclusion Criteria:
  -  Local or metastatic GIST is resectable
  -  Unable to receive the gene mutation detection of c-kit (c-kitproto-oncogeneprotein)/PDGFRA
  -  AST and/or ALT > 2.5 times ULN, or Bilirubin >1.5 times upper limit of normal (ULN)
  -  Neutrophil count < 1.5 x 10^9/L, or Platelet count <75 x 10^9/L, or Hemoglobin<90g/L
  -  Cr >1.5×ULN
  -  Other malignancy within the past 5 years except for adequately treated carcinoma in situ of the cervix or cutaneous basal cell carcinoma
  -  Known brain metastasis, spinal cord compression, carcinomatous meningitis, or cerebral or soft meningeal disease through CT or MRI during screening stage
  -  Within the past 5 years, subjects have one of the following disease: myocardial infarction, serious/instable angina pectoris, symptomatic congestive heart failure or cerebrovascular accident from coronary/peripheral artery bypass grafting
  -  Known human immunodeficiency virus positivity
  -  Joining in other trail
  -  Women who are pregnant or lactating; No contraception for subject during childbearing period
  -  Subject with other serious acute and chronic physical or mental problems, or laboratory abnormality, will increase the risks associated with trail or drug. It will also interference the judgment of the results. In the judgment of the investigator, subject is inadequate to participant the study

Relevance to patient case: definitely relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: Sarcopenia in Patients With Gastrointestinal Stromal Tumours

Summary: The treatment of advanced gastrointestinal stromal tumours (GIST) has shifted since the arrival of targeted therapies. Imatinib is an active multikinase inhibitor that mainly targets C-kit tyrosine-kinase receptors and the platelet-derived growth factor receptor. Imatinib use has been validated for adjuvant and palliative therapy settings. Imatinib is generally well-tolerated and known to improve performance status but up to 16% grades 3-4 toxicities, leading to at least 40% withdrawals, have been reported.
  Recently, in oncology, sarcopenia was shown to be a predictor of severe toxicity patients included in phase 1 trials, suggesting that it should be considered an inclusion criterion for such studies. Sarcopenic patients had low performance status, shorter survival, more chemotherapy toxicities and post-operative infections, and longer post-operative hospitalization times. In addition, exposure to tyrosine-kinase inhibitors (e.g. sorafenib or sunitinib) has been associated with dose-limiting toxicity (DLT) in patients with renal cell or hepatocellular carcinomas.
  Computed tomography (CT) scans acquired during routine care have been validated as an accurate and robust imaging technique to evaluate sarcopenia in cancer patients.

Detailed description: Aims of the study were:
  -  to assess the influence of imatinib on sarcopenia patients with advanced or high-risk resected gastrointestinal stromal tumours (GIST)
  -  to compare imatinib-induced toxicities between patients with advanced or high-risk resected gastrointestinal stromal tumours (GIST) with pre-treatment sarcopenia and patients with advanced or high-risk resected gastrointestinal stromal tumours (GIST) without pre-treatment sarcopenia

Eligibility: Inclusion Criteria:
  -  Patients with advanced or high-risk resected gastrointestinal stromal tumours (GIST)
  -  Patients treated with imatinib prescribed at a fixed dose of 400 mg/day from 1 January 2005 to 31 December 2013
  -  Aged > 18 years
  Exclusion Criteria:
  -  Patients who did not have CT imaging within the 30 days preceding treatment onset

Relevance to patient case: not relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: Opt-In Versus Opt-Out for Colorectal Cancer Screening Outreach

Summary: This is a randomized controlled pilot study aimed at testing different outreach strategies (opt-in versus opt-out) to increase colorectal cancer screening through completion of mailed home fecal immunohistochemical testing (FIT).

Detailed description: This is a randomized controlled pilot study aimed at testing different outreach strategies to increase colorectal cancer screening using mailed fecal immunohistochemical testing (FIT). The investigators will randomize a cohort of subjects between the ages of 50-74 into 2 arms:
  1. Opt-In - subject must actively choose to receive a home FIT kit.
  2. Opt-Out - a FIT kit is sent as a default unless the subject actives chooses not to receive the kit or reports prior screening.

Eligibility: Inclusion Criteria:
  -  Between 50 to 74 years old
  -  Has received care at the Division of Internal Medicine
  -  Due for screening
  -  Asymptomatic for colorectal cancer (CRC)
  Exclusion Criteria:
  -  Has had prior colonoscopy within 10 years, sigmoidoscopy within 5 years, and fecal occult blood test (FOBT)/FIT within twelve months of the chart review (We will exclude patients who self-report undergoing any of the above procedures)
  -  Has a history of CRC
  -  Has a history of other GI cancer
  -  Has history of confirmed Inflammatory Bowel Disease (IBD) (e.g. Crohn's disease, ulcerative colitis; Irritable bowel syndrome does not exclude patients)
  -  Has history of colitis other than Crohn's disease or ulcerative colitis
  -  Has had a colectomy
  -  Has a relative that has been diagnosed with CRC
  -  Has been diagnosed with Lynch Syndrome (i.e. HNPCC)
  -  Has been diagnosed with Familial Adenomatous Polyposis (FAP)
  -  Has iron deficiency anemia
  -  Has history of lower GI bleeding
  -  Has metastatic (Stage IV) blood or solid tumor cancer
  -  Has end stage renal disease
  -  Has cirrhosis
  -  Has heart failure
  -  Has dementia
  -  Has any other condition that, in the opinion of the investigator, excludes the patient from participating in this study

Relevance to patient case: not relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: Serum Dickkopf-4 as a Biomarker for the Diagnosis and Treatment of Gastrointestinal Stromal Tumor

Summary: Our study aims to evaluate the role of Dickkopf-4 as biomarkers in the treatment of gastrointestinal stromal tumor.

Detailed description: To identify whether Dickkopf-4 (DKK4) could be a potential biomarker for diagnosis and prognosis in patients with gastrointestinal stromal tumor (GIST). Serum was collected from 50 patients with GIST. Serological levels of DKK4 were examined by enzyme-linked immunosorbent assay (ELISA). The sensitivity and specificity was compared with modified NIH risk criteria. A 3-year follow-up was monitored to evaluate the correlation between DKK4 serum levels and relapse-free or overall survival. The expression of DKK4 in GIST tumor tissues was also evaluated using immunohistochemistry staining.

Eligibility: Inclusion Criteria:
  -  Primary gastrointestinal stromal tumor confirmed pathologically by surgery or biopsy
  -  Age from 18 - 70 years
  -  No serious organic and mental illness;
  Exclusion Criteria:
  -  Pregnancy
  -  No pathologic result
  -  Suffering other malignancies at the same time.

Relevance to patient case: not relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: Development of the Tool " iPSC " for the Functional Study of Mutations Responsible for Mental Retardation

Summary: According to the World Health Organization (WHO), mental retardation (MR) is defined by an intelligence quotient (IQ) < 70 and touches between 1 to 3 % of the general population. Profound mental retardation (QI <25), severe (IQ: 25-40) and moderate (QI : 40-50) have a prevalence of 0,3-0,5% while the prevalence of mild MR, defined by an IQ between 50 and 70 is evaluated to about 1,5 %.
  The origin of MR can be infectious, toxic, traumatic, genetic or environmental. genetic causes of MR gather the number and structure anomalies of the chromosomes, the genomic microreorganization, monogenic diseases and more rarely other non Mendelian-inherited anomalies like print or epigenetic anomalies, mutations of the mitochondrial genome etc... Genetic causes represents 50% of moderate to severe, whereas environmental factors (malnutrition, cultural deprivation,...) plays an important role in mild MR.
  The main goal of this study is to get an innovative tool (neuronal distinction of iPSC) that wil allow to study the functionnal impact of mutations uppon genes probably involved in MR like MYT1L. The main criteria associated to characterisation of the tool by the trial is the study of the pluripotency of iPSC obtained and to highlight the mutation of the gene MYT1L in the iPSC.
  Neurons from the iPSC of the patient and his father du patient wille also be morphologically characterised, but also thanks to the expression of specifically neurals genes.
  Characteristics of iPSC and neurons from d'iPSC with MYT1L mutation will be compared among the patient and his father, in relation with the same cells coming from the two witnesses.


Eligibility: Inclusion Criteria :
  -  Patient with an intellectual deficiency and/or associated signs that received a chromosomic analysis by CGH-array revealing a variant of unknown signification involvingone or more genes candidates for mental retardation.
  -  Certificate of genetic genetic counselling and signed consent.
  -  Under 18 persons may be necessary because intellectual deficiency is often diagnosed before the adult age.
  -  Number of cases is very limited in this preliminary study and only one patient showing a rare mutation of MYT1L gene and his father ( asymptomatic carrier of the same mutation) will be study.
  -  Affiliation to a social security system
  Exclusion Criteria :
  -  Persons mentionned L1121-5 to L1121-8 of CSP (all protected persons)
  -  Persons suffering from acute infections for the practice of cutaneous biopsy under local anesthesia.
  -  Persons showing an hemostasis disorder acquired or induced
  -  Persons sous traitement antiagrégant anticoagulant
  -  Persons with a mutation in th gene MYT1L

Relevance to patient case: not relevant