araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 50-year-old male with glioblastoma; genetic feature: IDH1 (R132H)

Clinical trial: NovoTTF Treatment Signatures in Glioblastoma Patients at Autopsy

Summary: This study will assess whole brain samples from glioblastoma patients at autopsy to determine the underlying pathological signatures of tumor treatment fields at autopsy.

Detailed description: RATIONALE:
  Optune therapy with tumor treatment fields (TTFields) has recently been FDA approved for the treatment of newly diagnosed glioblastoma due to a recent clinical trial that showed improvement in progression free survival and overall survival compared to standard therapy. (1) TTFields also have a role in the recurrent glioblastoma treatment where it has demonstrated equal efficacy to second-line chemotherapy also has been shown to tumor progression and improve overall survival.(2) Though preclinical studies are ongoing, glioblastoma patients who have undergone TTField therapy have not yet been assessed at autopsy to determine both the pathological signature of TTField treatment, and the pattern of failure. This study will determine how the underlying pathological signatures of tumors treated with TTFields differ from those naïve to TTFields by comparing tumor tissue at autopsy.
  STUDY:
  All patients undergoing TTField therapy for newly diagnosed and recurrent glioblastoma will be considered for inclusion for this study. The investigators expect to enroll five patients per year for four years, totaling 10 patients treated upfront and 10 patients treated at tumor recurrence. An objective of this study is to determine differences in the pathological pattern of failure when patients are treated with TTFields at initial diagnosis (up-front) compared to those treated at tumor recurrence.

Eligibility: Inclusion Criteria:
  -  Newly diagnosed glioblastoma, WHO grade IV, patients undergoing TTField therapy.
  -  Recurrent glioblastoma WHO grade IV, patients undergoing TTField therapy.
  Exclusion Criteria:
  -  TTField compliance < 75%.
  -  Any contraindication to Optune TTField treatment.
  -  Initial brain tumor diagnosis < WHO grade IV.
  -  Duration of TTField therapy < 3 months.

Relevance to patient case: not relevant
Patient case: 50-year-old male with glioblastoma; genetic feature: IDH1 (R132H)

Clinical trial: Spectral Analysis Probe to Identify Glioblastoma Cells

Summary: This is a pilot, observational study to evaluate the intraoperative sensitivity of the Chaos Wand in detecting tumor tissue with glioblastoma disease.

Detailed description: This is a pilot study to investigate if the Chaos Wand Spectral Diagnosis Probe can be used to identify Glioblastoma (GBM) cancer cells in patients undergoing standard surgical resection. Eligible patients who have consented to the use of the Chaos Wand will be scheduled for surgery as standard cancer care for GBM. During the surgical procedure, the Chaos Wand Spectral Diagnosis Probe will be utilized. Fifteen intraoperative readings and signal recordings of GBM tissue will be taken. The wand will only be used in areas that have already been deemed in need of resection due to GBM disease. Each site identified for spectral analysis will be marked. The wand does not come into contact with the brain at any point during this procedure. Following surgical resection of the GBM tumor, tissue will be collected from the same 15 sites where the Chaos Wand was used. The pathology report will be compared with the results of spectral analysis.

Eligibility: Inclusion Criteria:
  1. Male or Female and over 18 years of age.
  2. Patients with histologically proven GBM who are newly diagnosed and eligible to undergo surgical treatment or patients who are suspected of having glioblastoma on pre-operative imaging which is subsequently confirmed by histopathology following tumor resection.
  3. Patients must be able to understand and willing to sign the informed consent document.
  Exclusion Criteria:
  1. Patients with absence of glioblastoma.
  2. Patients who are not undergoing tumor resection.
  3. Patients who have prior brain radiotherapy
  4. Patients who have prior systemic chemotherapy
  5. Patients who are not willing to sign the informed consent and agree to participate.
  6. Patients who are pregnant or nursing

Relevance to patient case: not relevant
Patient case: 50-year-old male with glioblastoma; genetic feature: IDH1 (R132H)

Clinical trial: Study of AG-120 and AG-881 in Subjects With Low Grade Glioma

Summary: Study to evaluate the suppression of 2-HG (2-hydroxyglutarate) in IDH-1 mutant gliomas in resected tumor tissue following pre-surgical treatment with AG-120 or AG-881.

Detailed description: A phase-1, multi-center study in recurrent non-enhancing gliomas with IDH1 R132H mutation for patients who require surgery. The purpose of this study is to evaluate the suppression of 2-HG by comparing the concentration of 2-HG in resected tumors from IDH1 mutant glioma subjects following AG-120 or AG-881 treatment with the 2-HG concentration in untreated, control tumors. The safety, tolerability, PK/PD, and anti tumor activity data from the study in subjects with recurrent non-enhancing Grade 2/3 LGG with an IDH1 R132H mutation for whom surgical resection is indicated will identify the recommended dose of AG-120 and AG-881 for future studies in glioma.

Eligibility: Inclusion Criteria:
  1. Be ≥18 years of age.
  2. Have histologically or cytologically confirmed recurrent Grade 2 or 3 LGG (oligodendroglioma or astrocytoma according to World Health Organization 2016 classification).
  3. Have documented IDH1 R132H gene mutation by local testing and known 1p19q or ATRX mutation status by local testing.
  4. Have central confirmation of primarily non-enhancing disease by MRI with less than or equal to 5 mm slice thickness and up to 1 mm interslice gap on either 2D T2 weighted image, 3D T2 weighted image, or FLAIR, with at least 1 non-enhancing tumor measuring 1×1×1 cm.
  5. Be candidates for clinical resection but for whom surgery is not urgently indicated (eg, for whom surgery within the next 2-4 months is appropriate).
  6. Have KPS of ≥60%
  7. Have expected survival of ≥12 months.
  Exclusion Criteria:
  1. Have received prior systemic anti-cancer therapy within 1 month of the first dose of AG-120 or AG-881 or have received an investigational agent <14 days prior to their first dose of AG-120 or AG-881. In addition, the first dose of AG-120 or AG-881 should not occur before a period of ≥5 half-lives of the investigational agent has elapsed.
  2. Have had radiation within 6 months of the first dose of AG-120 or AG-881. (Note: Prior biopsy or surgery is allowed.)
  3. Have received any prior treatment with an IDH inhibitor.
  4. Have received any prior treatment with bevacizumab (Avastin).

Relevance to patient case: not relevant
Patient case: 50-year-old male with glioblastoma; genetic feature: IDH1 (R132H)

Clinical trial: Tumor-infiltrating T Lymphocyte（TIL）Adoptive Therapy for Patients With Glioblastoma Multiforme

Summary: Previously, the investigators constructed a transgenic modified tumor-infiltrating T lymphocytes (TILs) named pluripotent immune killer (PD1-PIK) cells, which can stablely express a high-level full-length PD-1 antibody. We submitted the protocol and approved by PRS in November, 2017. We have recruited ten patients and finished PD1-PIK cell therapy according to protocol from January in 2017. At the present, we need to change the protocol to determine the safety and efficacy of autologous TILs adoptive therapy in patients with glioblastoma, instead of PD1-PIK cell therapy because of the new problem in method of transgenic modification. Here. We will recruit the remaining 30 patients to have TIL cell adoptive therapy without transgenic modification to finish this clinical trial in order to evaluate safety and efficacy of cell therapy based on TIL in glioblastoma.


Eligibility: Inclusion Criteria:
  1. Patients with histologically confirmed brain glioblastoma multiforme.
  2. Patients with maximum safe resection of the tumor (≥95%) confirmed with contrast MR within 72 hours after surgery.
  3. Age from 18 to 70 years.
  4. Karnofsky performance score ≥ 60.
  5. Adequate organ function within 14 days of study registration including the following: Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count, (ANC) ≥ 1.0×10^9/L, platelets ≥100×10^9/L; hemoglobin ≥ 9 g/dL. Hepatic: bilirubin ≤1.3 mg/dL or 0-22 mmol/L, aspartate transaminase (AST) and alanine transaminase (ALT) < 3×upper limit of normal (ULN). Renal: Normal serum Creatinine for age (below) or creatinine clearance >60 ml/min/1.73 m2. Electrocardiogram: normal.
  6. Written informed consent must be obtained from all patients.
  Exclusion Criteria:
  1. Pregnant or breast-feeding patients. Pregnancy testing will be performed on all menstruating females within 14 days of study enrollment.
  Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
  2. Patients with history of immune system abnormalities such as hyperimmunity (e.g., autoimmune diseases) and hypoimmunity (e.g., myelodysplastic disorders, marrow failures, AIDS, ongoing pregnancy, transplant immuno-suppression), or medication of cortisol.
  3. Patients with any conditions that could potentially alter immune function (e.g., AIDS, multiple sclerosis, diabetes, renal failure).
  Patients currently received any other investigational agents.
  -

Relevance to patient case: not relevant
Patient case: 50-year-old male with glioblastoma; genetic feature: IDH1 (R132H)

Clinical trial: Prognosis and Therapeutic Biomarkers for Glioblastoma Patients

Summary: The purpose of this study is to investigate if the potential biomarkers identified could be used for facilitating the diagnosis and prognosis of patients with glioblastoma (GBM).

Detailed description: The objective of this proposed study is to determine the expression levels of a panel of markers including CD133, CD44, ABCC3, TNFRSF1A, AKT1, IDH2, and MGMT in GBM tissues and the CSF, blood, and saliva from patients with GBM receiving different types of treatment (Optune only or Optune with TMZ) and the non-brain tumor patients (controls). Our aims are: 1) To compare the differences of CD44 between the control group and the combined cancer groups at baseline; and 2) To compare the levels of CD44 and other markers among the 3 different groups such as control vs. GBM patients and Optune vs. Optune + TMZ after 8 weeks of treatment. Exploratory analysis of all other markers will be performed.

Eligibility: Inclusion Criteria:
  -  22 years old
  -  Control Group (only patients evaluated for neurological disorders whose evaluation require a lumbar puncture)
  -  Non-Control Group - Diagnosed with GBM (Glioblastoma)
  Exclusion Criteria:
  -  Pregnancy
  -  Infectious Disease to include cold, flu, HIV, etc.
  -  Blood Disorder (example:low platelets, anemia, thrombosis)
  -  Vascular Malformations

Relevance to patient case: not relevant
Patient case: 50-year-old male with glioblastoma; genetic feature: IDH1 (R132H)

Clinical trial: Ketogenic Diet in Combination With Standard-of-care Radiation and Temozolomide for Patients With Glioblastoma

Summary: Enrolled subjects will be placed on a 16-week ketogenic diet (subject specific as prescribed by RD) while receiving standard of care cancer treatment (Radiation + Temozolomide). Study dietitians will create personalized meal plans for each patient with the goal of achieving and maintaining protocol defined metabolic ketosis. Subjects will be monitored for safety, nutrition, quality of life, and standard of care tumor assessments over the course of the study.

Detailed description: Enrolled subjects will be placed on a 16-week ketogenic diet (subject specific as prescribed by RD) while receiving standard of care cancer treatment (Radiation + Temozolomide). Study dietitians will place patients on a strict and controlled diet that manages daily macronutrient breakdown and increases the ratio of dietary fat relative to protein and carbohydrate consumption. Dietitians will provide guidance and teaching of the diet, as well as, monitoring and diet adjustment to ensure metabolic ketosis. Dietitians and study physicians (and their staff) will monitor subjects for safety, nutrition, quality of life, and standard of care tumor assessments over the course of the study.

Eligibility: Inclusion Criteria:
  -  3.1.1 Adults (age ≥ 18 years)
  -  3.1.2 Newly or recently diagnosed glioblastoma. Patients may enroll in the study from the time of diagnosis (prior to the initiation of standard-of-care chemoradiation) up until the initiation of post-radiation adjuvant chemotherapy (typically approximately 3-4 weeks after the completion of radiation therapy). Overall, this provides a window of approximately 3 months from the time of diagnosis for patients to enroll in this study. No recurrent glioblastoma is allowed on trial.
  -  3.1.3 Being seen for treatment of GBM at Cedars-Sinai Medical Center
  -  3.1.4 Patients on low and managed doses of steroids are permitted. Up to 8 mg dexamethasone or steroid equivalent.
  Exclusion Criteria:
  -  3.2.1 Karnofsky Performance Status of <70 as deemed by physician or equivalent
  -  3.2.2 Body Mass Index of <24 (rounded to nearest integer)
  -  3.2.3 Patients with disorders that affect lipid metabolism such as pyruvate carboxylase deficiency, porphyria, primary carnitine deficiency, carnitine palmitoyltransferase I or II deficiency, carnitine translocase deficiency, Beta-Oxidation Defects
  -  3.2.4 Pregnancy
  -  3.2.5 Patients who are vegan or vegetarian will be excluded, as the ketogenic diet includes foods that may interfere with these preferences
  -  3.2.6 Patients on high doses of steroids will be excluded
  -  3.2.7 Inability to adhere to the protocol

Relevance to patient case: not relevant
Patient case: 50-year-old male with glioblastoma; genetic feature: IDH1 (R132H)

Clinical trial: Screening of IDH1 and IDH2 Gene Mutations in Adult Acute Myeloid Leukemia for Possible Targeted Therapy

Summary: 1. To assess the incidence of IDH1 and IDH2 mutations in adult AML patients, and to explore their associations with the patients' clinical, cytogenetic, and molecular characteristics as well as with treatment response and outcome.
  2. To delineate the similarities and distinctions among mutations at IDH1-R132, IDH2-R140 and IDH2-R172 in AML, both clinically and molecularly (including cytogenetics, immunophenotyping, mutation co-occurrence patterns).
  3. The results can be references for future selection of targeted therapy (targeting IDH mutant proteins).

Detailed description: Isocitrate dehydrogenases (IDH) are enzymes that catalyze oxidative decarboxylation of isocitrate into alpha-ketoglutarate (α-KG). IDH1 and IDH2 mutations in AML give the enzymes neomorphic enzymatic activity to transform α-KG to D-2HG, an oncometabolite which acts as a competitive inhibitor of dioxygenases, and causes dysregulation of TET2 and histone demethylases, consequently leading to epigenetic reprogramming of a cell, blocking differentiation and contributing to a transformed phenotype, and leukemogenesis. Investigators plan to recruit 300 adult AML patients (newly diagnosed or relapsed). 10mL of peripheral blood or marrow blood will be obtained from routine practice blood/marrow sampling specimens (no extra venipuncture or bone marrow aspiration would be required) and sent for routine tests such as cytogenetics, immunophenotyping, and gene mutation analyses. IDH1 R132, IDH2 R140, and IDH2 R172 mutations will be screened by PCR followed by Sanger sequencing, as previously described.
  Investigators will first assess the incidence of IDH1 and IDH2 mutations in adult AML patients, and then explore their associations with the patients' clinical course, cytogenetic, and molecular characteristics as well as with treatment response and outcome. Investigators also seek to delineate the similarities and distinctions among IDH mutation variants at IDH1-R132, IDH2-R140 and IDH2-R172, both clinically and molecularly (including cytogenetics, immunophenotyping, mutation co-occurrence patterns).

Eligibility: Inclusion criteria:
  1. Patients ≥20 Years with Diagnosed Acute Myeloid Leukemia
  2. Willing to provide voluntary written informed consent before study related procedures
  Exclusion criteria:
  1. Not acute myeloid leukemia patients
  2. Patients <20 Years with Diagnosed Acute Myeloid Leukemia

Relevance to patient case: not relevant
Patient case: 50-year-old male with glioblastoma; genetic feature: IDH1 (R132H)

Clinical trial: Temozolomide Plus Anti-angiogenesis Drugs and Radiotherapy as a Treatment for Glioblastoma

Summary: Temozolomide (TMZ) is an oral chemotherapy drug. It is an alkylating agent used as a first-line treatment for glioblastoma. This methylation damages the DNA and triggers the death of tumor cells. According to the results of several clinical studies, TMZ synchronous plus radiotherapy and subsequent as adjuvant therapy can significantly improve the survival rate of newly diagnosed glioblastoma patients.

Detailed description: Glioma is the highest incidence of the central nervous system tumor. Surgical treatment is one of the most important therapeutic methods in patients with glioblastoma. But since malignant glioma is a highly invasive tumor, the rate of surgery failure is . So the postoperative therapy shall be accompanied by radiotherapy. Since 1998, the clinical application of Temozolomide(TMZ) has brought hope for malignant glioma patients with its definite curative effect. According to the results of several clinical studies, TMZ synchronous plus radiotherapy and subsequent as adjuvant therapy can significantly improve the survival rate of newly diagnosed GBM patients and break the survival limit of malignant glioma patients. Besides, antiangiogenic therapy is also a choice for the treatment of glioblastoma patients. Vascular endothelial growth factor receptors (VEGFRs) inhibitors block the new formation around the tumor and cut down the supply of oxygen, nutrients and metabolic waste, so that the tumor is hard to proliferate and metastases.

Eligibility: Search Criteria:
  1. Subjects received anti-angiogenesis drugs simultaneous accompanied with radio-and chemotherapy in Fuzhou Zongyuan since October, 2017;
  2. Age: 18-70 years;
  3. The first surgical pathology was diagnosed as glioblastoma, WHO grade III or IV;
  4. Patients who have previously received no more than one surgical treatment;
  5. ECOG performance status: 0-2;
  6. Survival expectation≥3 months.

Relevance to patient case: not relevant
Patient case: 50-year-old male with glioblastoma; genetic feature: IDH1 (R132H)

Clinical trial: Gut Microbiota and Glioblastoma Multiforme Prognosis

Summary: Glioma is the most common primary cancer of the central nervous system, and around 50% of patients present with the most aggressive form of the disease, glioblastoma. Conventional therapies, including surgery, radiotherapy, and pharmacotherapy (typically chemotherapy with temozolomide), have not resulted in major improvements in the survival outcomes with only a median survival of around 15 months.The main reason may be related to the highly immunosuppressive tumor microenvironment. In recent years, the microbiome has emerged as a key regulator of not only systemic immune regulation but brain circuitry, neuro-physiology and microglia development. We hypothesized that there is a link between the gut microbiota and the GBM development and evolution through the immune regulation cells (microglia and tumor related macrophagocyte) in the blood circulation to impact the prognosis( PFS and MST) of GBM patients.

Detailed description: We divide the paticipants into three groups. (total number = 200 subjects)
  1. Radio/Chemotherapy group - 80 subjects
  2. Radio/ without chemotherapy group - 70 subjects
  3. Healthy volunteer group - 50 subjects
  After the collection of stools before operation and 3 months after the operaton, we will analyze the composition and distribution of gut microbiota, and compare the results of three experiment groups.Then we will followe up the patients and analyze the correlation between gut microbiota and prognosis of GBM.

Eligibility: Inclusion Criteria:
  The participants diagnosed with glioblastoma multiforme by immunohistochemistry and molecular (IDH1, 1p19q, TERT) diagnosis of WHO 2016 classification of Gliomas.
  The healthy volunteers.
  Exclusion Criteria:
  1. No cancer or IBD (inflammatory bowel disease);
  2. No history of abdominal surgery;
  3. No medication related to gastrointestinal motility within 3 months;
  4. No oral antibiotic treatments previous 1 month before neurosurgery operation.

Relevance to patient case: not relevant
Patient case: 50-year-old male with glioblastoma; genetic feature: IDH1 (R132H)

Clinical trial: Metastatic Colorectal Cancer Treated With Regorafenib and FOLFIRI

Summary: The survey is a retrospective study to evaluate the prognotic value of EGFR expression, KRAS mutations and tumor sideness in patients with metastatic colorectal cancer treated with regorafenib and FOLFIRI as a third- or fourth-line setting.

Detailed description: Primary objective:
  Progression-free survival
  Secondary objecive:
  Overall survival, best objective response, disease control rate and adverse events
  Number of Subjects: 41 patients with metastatic colorectal cancer treated with regorafenib and FOLFIRI as a third- or fourth-line setting.
  Plan of the Study:
  1. This is a retrospective study.
  2. Study Schedule Study date: the time getting approval letter issued by both regulatory authority and institutional review board (IRB). Duration of the study: 5 years.
  3. Duration of Treatment: Treatment was administered until disease progressed.

Eligibility: Inclusion Criteria:
  -  Age between 20-85 years old
  -  Histologically proven metastatic colorectal cancer (mCRC).
  -  Patients with progressing mCRC who were previously treated with FOLFOX, FOLFIRI, anti-VGFR monoclonal antibody (MoAb), and anti-EGFR MoAb if KRAS-wild-type tumors were identified.
  -  Patient was able to understand the requirements of the study and written informed consent was obtained from each subject.
  Exclusion Criteria:
  -  Patients who do not meet the including criteria or unwilling to participate

Relevance to patient case: not relevant