araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Effects of Isotretinoin on CYP2D6 Activity

Summary: Specific Aim: To investigate if isotretinoin (13-cis-retinoic acid) administration decreases CYP2D6 activity in adolescent patients.

Detailed description: In this aim, we will conduct a drug-drug interaction study evaluating the effects of 13-cis-retinoic acid on non-induced CYP2D6 activity in adolescent patients. Secondary analysis will evaluate the relationship between retinoid concentrations and CYP2D6 activity in these special populations

Eligibility: Inclusion Criteria:
  -  Non-pregnant
  -  ≥ 12 years
  -  Patients with severe acne that are expected to receive isotretinoin for therapeutic reasons
  Exclusion Criteria:
  -  Weight < 80 lbs
  -  Allergy or adverse reaction to dextromethorphan, vitamin A or isotretinoin
  -  Pregnant or planning to become pregnant
  -  Unable to follow isotretinoin risk evaluation and mitigation strategies (REMS) program (also known as iPLEDGE program)
  -  Chronic or persistent cough accompanying asthma, smoking or COPD,
  -  Productive cough,
  -  Fever,
  -  Known kidney disease,
  -  Known liver disease,
  -  Diabetes
  -  Obesity, BMI ≥ 30 kg/m2
  -  Bipolar disease,
  -  Attention deficit disorder,
  -  Social phobia,
  -  Concurrent or use within 14 days of drugs known to interact with DM or CYP2D6 or drugs known to increase the risk of adverse effects from DM
  -  Concurrent use of any other product containing dextromethorphan
  -  Consuming foods, beverages or dietary supplements known to interact with DM or CYP2D6
  -  Unable to give written informed consent/assent,
  -  Inability to fast for 4 hours prior to study.
  -  Wards of the State

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Effects of Physical Exercise to Prevent Osteoporosis in Postmenopausal Women

Summary: According to the World Health Organization criteria, osteoporosis was defined as a bone mineral density that lies 2.5 standard deviations or more below the average value for young healthy women. Osteoporosis is a major cause of fractures and can lead to serious complications in postmenopausal women. For this reason, approaches to prevent the appearance and progression of osteoporosis are of primary importance. This randomized clinical trial analyzes the effects of two types of physical exercise oriented to prevent osteoporosis in postmenopausal women with pharmacological supplements of Calcium and Vitamin-D.


Eligibility: Inclusion Criteria:
  -  Postmenopausal woman
  -  Pharmacological treatment (VitaminD+Calcium)
  Exclusion Criteria:
  -  Disease or physical-mental condition which prevents to perform the proposed physical exercise

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: The p53 Colorectal Cancer Trial

Summary: Single center, open labeled, phase 2 clinical trial, where patients with metastatic colorectal cancer are selected for treatment with dose dense Cyclophosphamide every second week based on TP53 mutation status; i.e. only patients with TP53 mutated tumors may be included in the treatment arm.


Eligibility: Inclusion Criteria:
  -  Metastatic colorectal cancer patients for whom conventional therapy has failed; defined as 2 lines of chemotherapy including oxaliplatin or irinotecan- containing regimens as well as an EGFR inhibitor if applicable.
  -  Tumor lesion suitable for biopsy
  -  Age >18 years
  -  Clinically or radiologically measurable tumor deposits according to the RECIST criteria
  -  WHO performance status 0-1
  -  Radiology studies (CT thorax/abdomen/pelvis) and echo cor and ECG must be performed within 28 days prior to registration.
  -  Before patient registration in the trial, written informed consent must be given according to national and local regulations.
  -  Blood test requirements:
  Neutrophils > 1.0 e9/L Platelets > 75 e9/L Bilirubin < 20 µmol / L. Serum creatinine < 1.5 x ULN
  Exclusion Criteria:
  -  Co-morbidity including, but not limited to, impaired renal-, liver or bone marrow function, that based on the assessment of the treating physician, may preclude the use of cyclophosphamide at actual doses.
  -  Known hypersensitivity to the study drug, its metabolites or any excipients in the infusion solution.
  -  Psychological, familial, sociological or geographical condition(s) potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
  -  Pregnant or lactating patients cannot be included.
  -  Clinical evidence of serious coagulopathy. Prior arterial/venous thrombosis or embolism does not exclude patients from inclusion, unless patient is considered unfit by study oncologist.
  -  Patient not able to give an informed consent or comply with study regulations as deemed by study investigator.

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: The Efficiency of CAMS (Chinese Academy of Medical Sciences)-2016 Trial for Pediatric Acute Myeloid Leukemia

Summary: The purpose of this study is to evaluate that whether the AML (acute myeloid leukemia)-CAMS (Chinese Academy of Medical Sciences)-2016 regimen, includes risk-stratified therapy and the use of Dasatinib in CBF (Core binding factor)-AML, can improve the outcome in childhood AML.

Detailed description: Primary AML includes CBF(Core binding factor)-AML and non-CBF-AML. After the second course of therapy, CBF-AML are stratified into two risk groups: low-risk children are defined as those with CR after MAE or CAG, high-risk children are those with CR after consolidation course 1 or IAE. Non-CBF-AML patients in remission are stratified into three risk groups: low-risk children are defined as those with t(1；11)(q21；q23) , GATA1, NPM1/IDH1/IDH2 without FLT3/ITD,or an age younger than 2 years without high-risk factors; high-risk children are those with CR after consolidation course 1 or IAE or with abnormalities of monosomy 7, 5q- , t(16;21), t(9;22) (Philadelphia chromosome [Ph1]), FLT3/ITD,-17/TP53, RPN1-MECOM, RUNX1-EVI1, MLF1-NPM1, PRDM16-RPN1, DEK-NUP214, ETV6(TEL)-HLXB9(MNX1), NUP98-NSD1; intermediate-risk children are those who were not in either a low-risk or high-risk group.Low-risk children were treated only with chemotherapy, regardless the availability of a suitable HSCT donor. All high-risk children were allocated to Allo-hematopoietic stem cell transplantation (HSCT) in the first remission, including unrelated bone marrow transplantation (BMT). Auto-HSCT is recommended for intermediate-risk children. No prophylactic cranial irradiation is included in the protocol. Patients are treated on an inpatient basis during each treatment phase.

Eligibility: Inclusion Criteria:
  -  Newly diagnosis of de novo Acute Myeloid Leukemia
  Exclusion Criteria:
  -  Children with Down's syndrome and acute promyelocytic leukemia, hybrid acute leukemia

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Li-Fraumeni Syndrome Imaging Study

Summary: Li-Fraumeni Syndrome (LFS) is a cancer predisposition disorder in which most affected individuals develop cancer during their lifetime. The majority of LFS patients carry a mutation in a gene called TP53, whose normal function is to control cell growth and prevent cells with damaged DNA from becoming cancerous. There is currently no way to determine when, where or what type of tumour will develop. This project will use novel techniques utilizing magnetic resonance imaging (MRI) to determine how sensitive they are at detecting very small tumors and how specific they are in terms of distinguishing malignant tumors from benign tumors.


Eligibility: Inclusion Criteria:
  -  LFS kindreds who either carry a known TP53 mutation or are obligate mutation carriers
  Exclusion Criteria:
  -  General contraindications for an MRI scan (ferromagnetic prostheses, pacemaker, or other implants incompatible with the magnetic field of the MR scanner), claustrophobia.

Relevance to patient case: definitely relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Targeted-sequencing of PTC in Different Stages

Summary: The prevalence of papillary thyroid micro-carcinoma (PTMC) increased rapidly in recent years but the design of treatment is controversial because a majority of them are indolent. Therefore, to recognize which PTMC is of strong progressive potential which should be operated is very crucial. Fine needle aspiration (FNA) pre-surgery could obtain tumor cells which could be used in genetic analysis. To date, there is no specific way to evaluate the aggressive potential of a PTMC pre-surgery. So, the purpose of this proposal is to screen genetic mutations of the aggressive type of PTMC. The candidate did a whole exome sequencing on 3-3 pairs of PTCs and found some SNPs and Indels in TP53、TTN、PDF. To further investigate those mutations, a target region sequencing will be done in 40 pairs tumor samples. And ultimately to find out which genetic event could contribute to strong aggressive potential of PTC. The mutations details would be design to test the FNA and tissue sample to validate if the genetic testing based on FNA is reliable. The gene test results would be evaluated with sonographic features to predict the potential of small thyroid carcinoma before surgery. This project won't aim to study the function and mechanism of specific genes but just screen them out. So, the fund would cover the fee of the whole study and this study is very likely to achieve the goal.


Eligibility: Inclusion Criteria:
  -  patients who will receive thyroid resection
  Exclusion Criteria:
  -  patients who has been radiologically treated

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: CD19-CART Treatment for ALL

Summary: This study aims to evaluate the safety and efficacy of a novel CD19-CART in the treatment of refractory or recurrent ALL.

Detailed description: Chimeric antigen receptor T cell (CART) is a kind of engineered immunotherapy by transferring an artificial antigen binding receptor and also intercellular co-stimulating molecules into T cells. This kind of engineered T cells gains the ability to recognize antigen specific tumor cells and initiate the killing process in a HLA-independent way. CD19 is the specific cellular marker of B lineage acute leukemia (B-ALL), thus CD19-CART will be efficient in treating B lineage ALL. The investigators have constructed two kinds of CD19-CART. One is equipped with a murine CD19 scFv (single-chain variable fragmentt), while the other with a humanized scFv. This study aims to evaluate the safety and efficacy of both murine and humanized CD19-CART in treating refractory or recurrent ALL.

Eligibility: Inclusion Criteria:
  1. previously identified as CD19+ ALL.
  2. ALL patients not eligible for allogeneic SCT or relapse after allogeneic SCT.
  3. Expected survival >12W.
  4. Creatinine < 2.5 mg/dl.
  5. Alanine transaminase (ALT)/Aspartate Aminotransferase (AST) < 3x normal
  6. Bilirubin <2.0 mg/dl
  7. Voluntary informed consent is given.
  Exclusion Criteria:
  1. Pregnant or lactating women.
  2. Uncontrolled active infection.
  3. Active hepatitis B or hepatitis C infection.
  4. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
  5. Previously treatment with any gene therapy products.
  6. Any uncontrolled active medical disorder that would preclude participation as outlined.
  7. HIV infection.

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Color Doppler U/S vs MSCT Venography in May-Thurner Syndrome

Summary: May-Thurner syndrome is the result of compression of the left common iliac vein between the right common iliac artery and overlying vertebrae.
  In This Study , We will detect the role of color doppler US in the diagnosis of May-Thurner Syndrome in comparison to Direct CT Venography

Detailed description: May-Thurner syndrome (MTS) is a venous compression syndrome in which the left common iliac vein is compressed between the lower lumbar spine and the right common iliac artery. While asymptomatic compression is very common, the process can lead to morbidity in selected individuals, most commonly deep venous thrombosis (DVT) and the sequelae thereof. Radiologists must recognize the diagnosis because of the unique management, which differs from DVT without iliac vein compression.
  The most common clinical presentation is unilateral leg swelling due to acute DVT. It can also present as chronic venous insufficiency or chronic thrombosis with symptoms of venous hypertension and venous stasis namely claudication, pain, swelling, varicose veins and / or ulceration.
  Conventional invasive catheter venography remains the gold standard for diagnosis,but the decision to undertake invasive venography should be made only after reviewing all available clinical data and alternative, less invasive imaging options have been exhausted.
  When visualization of the common iliac veins is possible, MTS may be diagnosed with transabdominal color Doppler U/S.
  MDCT with IV contrast is a fast, widely available examination for the diagnosis of MTS and accompanying complications .
  Magnetic resonance imaging (MRI) with MR venography is an attractive modality for the diagnosis, However, MRI is expensive, time consuming, has more limited availability than computed tomography (CT) and ultrasound, and may be impossible in select patients.

Eligibility: Inclusion Criteria:
  -  advanced chronic venous insufficiency submitted to clinical treatment for at least 1 year with no response.
  -  Subject must be > 18 and < 80 years of age.
  -  informed consent document before the planned procedure.
  -  On duplex ultrasound: patent common femoral vein, and patent deep femoral vein, and/or femoral vein of the study leg.
  Exclusion Criteria:
  -  Previous venous stent implantation involving the study leg or inferior vena cava
  -  Previous venovenous bypass surgery involving the study leg
  -  Known reaction or sensitivity to iodinated contrast that cannot be managed with premedication.
  -  Subjects who are pregnant (women of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment).
  -  Acute deep venous thrombosis involving either leg.
  -  Known history of chronic total occlusion of the common femoral vein of the study leg.
  -  Venous compression caused by tumor encasement.
  -  Venous outflow obstruction caused by tumor thrombus.
  -  Elevated baseline blood creatinine (value greater than the upper limit of the normal range).

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: p53 Activation in Platinum-Resistant High Grade Serous Ovarian Cancer, a Study of PLD With APR-246

Summary: The purpose of this study is to make a preliminary assessment of the efficacy of a combined APR-246 and PLD chemotherapy regimen in patients with platinum-resistant recurrent high grade serous ovarian cancer (HGSOC) with mutated TP53. In addition, the study aims to assess the safety profile of the combined APR-246 and PLD chemotherapy regimen, to evaluate potential biomarkers, and to assess the biological activity in tumor and surrogate tissues. The trial will enroll at least 25 evaluable patients.


Eligibility: Inclusion Criteria:
  -  Confirmed High Grade Serous Ovarian Cancer, and positive nuclear immunohistochemical (IHC) staining for p53
  -  Disease Progression between 4 weeks - 6 months after the last platinum-based treatment was administered
  -  At least a single measurable lesion
  -  Adequate organ function prior to registration
  -  Toxicities from previous cancer therapies (excluding alopecia) must have recovered to grade 1 (defined by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 4.0). Chronic stable grade 2 peripheral neuropathy secondary to neurotoxicity from prior therapies may be considered on a case by case basis
  -  ECOG performance status of 0 to 2
  Exclusion Criteria:
  -  Prior exposure to cumulative doses of doxorubicin >400 mg/m2 or epirubicin >720 mg/m2
  -  Hypersensitivity to PLD or to any of the excipients
  -  Unable to undergo imaging by either CT scan or MRI
  -  Evidence of any other medical conditions (such as psychiatric illness, infectious diseases, neurological conditions, physical examination or laboratory findings) that may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment related complications
  -  Concurrent malignancy requiring therapy (excluding non-invasive carcinoma or carcinoma in situ)
  -  Is taking concurrent (or within 4 weeks prior to registration) chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy that is considered to be investigational (i.e., used for non-approved indications(s) and in the context of a research investigation). Supportive care measures are allowed. Palliative limited radiation therapy for pain reduction is allowed

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Study of the Use of Venetoclax in Patients With Chronic Lymphocytic Leukemia (CLL) Under Real‑Life Setting

Summary: An observational study to assess the effectiveness, health economic‐relevant costs and patient reported outcomes in patients with Chronic lymphocytic leukemia (CLL) receiving venetoclax as prescribed at the discretion of the physician and in accordance with local clinical practice and label.


Eligibility: Inclusion Criteria:
  -  Patient with chronic lymphocytic leukemia (CLL) administering venetoclax and who meets the following conditions as specified in the label for venetoclax:
  -  Venetoclax monotherapy for the treatment of CLL in the presence of deletion chromosome 17 (del[17p]) or tumor protein p53 (TP53) mutation in adult patients, who are unsuitable for or have failed to a B‐cell receptor pathway inhibitor.
  -  Venetoclax monotherapy for the treatment of CLL in the absence of del(17p) or TP53 mutation in adult patients, who have failed both chemoimmunotherapy and a B‐cell receptor pathway inhibitor.
  Exclusion Criteria:
  -  None

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Rapamycin Treatment for Activated Phosphoinositide 3-Kinase δ Syndrome

Summary: The purpose of this proposed research is to evaluate the efficacy and safety of the rapamycin therapy in patients with activated phosphoinositide 3-kinase δ syndrome (APDS).

Detailed description: Activated phosphoinositide 3-kinase δ syndrome (APDS) is a recently described autosomal dominant primary immunodeficiency (PID), caused by the mutations in PIK3CD gene. The manifestations of APDS mainly include recurrent respiratory tract infections, persistent Epstein-Barr virus (EBV)/ cytomegalovirus (CMV)infections, lymphadenopathy, splenomegaly, CD4+T cells lymphopenia, and hyper-IgM syndrome. PIK3CD encodes p110δ, the catalytic subunit of phosphatidylinositol 3-kinase (PI3K) which mainly expresses in leukocytes, being critical for their proliferation, activation and survival. Gain-of-function (GOF) PIK3CD mutations lead to PI3Kδ hyperactivity, with the downstream mediators Akt and mammilian target of rapamycin (mTOR) hyperphosphorylated. Patient-derived lymphocytes had increased levels of phosphatidylinositol 3,4,5-trisphosphate and phosphorylated AKT protein. Hyperactivation of mTOR increases phosphorylation of kinases and increased glycolysis that results in enhanced proliferation and senescence of terminally differentiated CD8+ Tcell populations.
  The optimal treatment for these APDS patients is not yet determined; however, there are many kinds of therapeutic approaches (anti-infection prophylaxis, immunoglobulin replacement, conventional immunosuppressants, PI3K/mTOR inhibitors and hematopoietic stem cell transplantation). The APDS patients frequently receive treatment with immunoglobulin replacement and antibiotics. Hematopoietic stem cell transplantation (HSCT) has been currently curative in APDS patients; however, longer-term follow-up to determine the degree of donor chimerism and efficacy is required. There are several subjects without a prompt suitable matched donor or for whom the critical disease conditions force to postpone HSCT.The mammalian/mechanistic target of inhibitor rapamycin was reported to improve circulating T-cell profiles. Individual patients in previous studies experienced a decrease in nonneoplastic lymphoproliferation while taking rapamycin.
  The investigators in this study hope to evaluate the efficacy and safety of rapamycin in the treatment for carefully selected patients with APDS.

Eligibility: Inclusion Criteria:
  1. Patients with activated phosphoinositide 3-kinase δ syndrome
  2. No more than 18 years old
  Exclusion Criteria:
  1. Patients with serious fungous infection
  2. Patients with serious complications
  3. Lack of parental consent

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: An Observational Study to Evaluate AZD9291 Treatment in Patients With T790M Positive Non-small Cell Lung Cancer

Summary: AZD9291 Early Access Program (EAP) was available in Taiwan during October 2015 to September 2016, a time period before the approval of AZD9291, to supply the unlicensed AZD9291 for the NSCLC patients who received at least one prior EGFR TKI therapy. At the end of September 2016, more than 450 patients have been under AZD9291 treatment through the EAP. This observational study aims to evaluate the clinical benefit of AZD9291 treatment for these patients who were in the EAP

Detailed description: AZD9291 Early Access Program (EAP) was available in Taiwan during October 2015 to September 2016, a time period before the approval of AZD9291, to supply the unlicensed AZD9291 for the NSCLC patients who received at least one prior EGFR TKI therapy. At the end of September 2016, more than 450 patients have been under AZD9291 treatment through the EAP. This observational study aims to evaluate the clinical benefit of AZD9291 treatment for these patients who were in the EAP

Eligibility: Inclusion Criteria:
  -  At least 20 years of age
  -  Patients who were in the AZD9291 Early Access Program
  -  Received at least one dose of AZD9291 treatment as mono-therapy, supported by available source documents
  -  Patient who discontinued the single use of AZD9291, had disease progression, or died under AZD9291 treatment, whichever comes last, during the period from October 01, 2015 to December 31, 2018
  -  Patients agree to provide the written informed consent or the informed consent is waived by IRB.
  Exclusion Criteria:
  • Patients who did not receive at least one dose of EGFR TKI for the treatment of EGFR mutation (+) NSCLC

Relevance to patient case: not relevant