araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: Early Rebiopsy to Identify Biomarkers of Tumor Cell Survival Following EGFR, ALK, ROS1 or BRAF TKI Therapy

Summary: A comparison of baseline tumor characteristics in oncogene-driven cancers to tumor characteristics after early response to Tyrosine Kinase Inhibitor (TKI) targeted treatment will allow identification of early adaptive mechanisms of cell survival. This will facilitate targeting and termination of these survival/ resistance pathways before they develop with rational combinations of therapeutic agents to improve outcomes.


Eligibility: Inclusion Criteria:
  -  Carry a diagnosis of stage IV lung adenocarcinoma with an activating mutation determined to respond to an estimated glomerular filtration rate (EGFR) TKI, alkaline phosphatase (ALK) or ROS Proto-Oncogene 1 (ROS1) fusion or BRAF V600E.
  -  Aged 18 - 85 years or older
  -  ECOG 0-2
  -  Have a histologically confirmed diagnosis of lung adenocarcinoma harboring an EGFR sensitizing mutation (including, but not limited to: G719X, del exon 19, or L858R).
  -  No prior therapy for metastatic disease.
  -  Planned treatment with a single agent EGFR TKI including but not limited to:
  1. erlotinib,
  2. gefitinib,
  3. rociletinib (CO-1686),
  4. afatinib, or
  5. osimertinib (AZD-9291).
  -  Patients must have at least one site of measurable disease ≥ least 2cm.
  -  Primary disease site or site of metastatic disease must be amenable to biopsy.
  -  Patients must have the ability to understand and willingness to sign an informed consent document.
  -  Patients must be willing to undergo an initial pre-treatment biopsy of tumor tissue (or have previously collected frozen tissue) and a follow-up biopsy 2 weeks (+/- 1 week) after treatment start
  Exclusion Criteria:
  -  Concurrent health problem which would preclude tissue biopsy (eg hemophilia or other bleeding predisposition).
  -  Patients whose only source of biopsiable disease is:
  1. intracranial,
  2. pleural effusion or any lesion that is deemed unsafe to biopsy by the treating physician or,
  3. interventional radiology.

Relevance to patient case: possibly relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: Impact of Three-dimensional Visualization on Operation Strategy and Complications for Hilar Cholangiocarcinoma

Summary: The aim of the multi-centre study is to evaluate correctly the impact of three-dimensional visualization on operation strategy and complications for hilar cholangiocarcinoma.

Detailed description: Because of the complexity of hilar cholangiocarcinoma,the limitations of 2D images of CT/MRI and the uncertainty of surgeons'experience, it is difficult for the surgeons to diagnosis and assess the operation strategy accurately based on traditional 2D imaging(CT/MRI).The aim of the multi-centre study is to evaluate correctly the impact of three-dimensional visualization on operation strategy and complications for hilar cholangiocarcinoma.

Eligibility: Inclusion Criteria:
  1. 18 years≤ Age ≤70 years
  2. Complying with the diagnosis criteria of hilar cholangiocarcinoma.
  3. Without intrahepatic or extrahepatic extensive cancer metastasis.
  4. Preoperative serum bilirubin ≤51.3 umol/L or preoperative serum bilirubin < 200 umol/L after the drainage by PTCD(percutaneous transhepaticcholangial drainage)/ENBD(endoscopic nasobiliary drainage).
  5. The patients are volunteered for the study.
  Exclusion Criteria:
  1. Patients with mental illness.
  2. Patients can't tolerate the operation owe to a variety of basic diseases (such as severe cardiopulmonary insufficiency, renal insufficiency, cachexia and blood system diseases, etc.)
  3. The patients refused to take part in the study.
  4. There are other co-existed malignant tumors.

Relevance to patient case: not relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: Bone Healing Study

Summary: The aim of the research is to identify structural tissue changes in the early fracture hematomas.

Detailed description: The fracture hematomas obtained during reconstructive bone surgery from patients with bone fractures will be examined. Histological methods and ultra-thin sections for electron microscopy will be used to identify structural tissue changes in the granulation tissue in different period of time after bone fracture. Immunohistochemical analysis will be performed to estimate the dynamic of proliferation, differentiation and cell migration during granulation and reticulofibrosis bone tissues development.

Eligibility: Inclusion Criteria:
  -  Patients with fractures of the upper and lower extremities
  -  Patients for whom the surgical bone reconstruction are indicated

Relevance to patient case: not relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: A Study of Second-line Treatment With Apatinib in Patients With Advanced Intrahepatic Cholangiocarcinoma

Summary: The purpose of this study is to explore the efficacy and safety of second-line treatment of apatinib in advanced intrahepatic cholangiocarcinoma patients and evaluate drug safety, progression free and overall survival. The primary endpoint of this study is objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS).


Eligibility: Inclusion Criteria:
  -  Patients with a histologic or cytologic diagnosis of intrahepatic cholangiocarcinoma with stage IV;
  -  Have progressed after systematic chemotherapy/target therapy, or cannot tolerated with first-line treatment;
  -  The previous treatment and the present trial registration must be at least 2 weeks apart, and they must have recovered from any toxicity of a previous treatment;
  -  Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1;
  -  Eastern Cooperative Oncology Group performance score (ECOG): 0-2;
  -  Life expectancy of at least 12 weeks;
  -  Subjects who understand and voluntarily signed a written informed consent form.
  Exclusion Criteria:
  -  Previous locoregional therapy within 4 weeks prior to enrollment.
  -  Diagnosed with hepatocellular carcinoma, mixed cell carcinoma and fibrolamellar hepatocellular carcinoma.
  -  History of other malignancy within 5 years except for non-melanoma skin cancer, cervix in situ carcinoma.
  -  Prepared for liver transplantation.
  -  Patients with contraindications (active bleeding, ulcers, intestinal perforation, intestinal obstruction, within 30 days after major surgery, uncontrolled high blood pressure medication, III-IV level cardiac insufficiency, severe liver and kidney dysfunction).
  -  A previous history of Interstitial pulmonary disease, drug-induced interstitial disease, radiation pneumonitis requiring hormonal therapy or active interstitial lung disease with any clinical evidence.
  -  Use of CYP3A4 inhibitor within 7 days or CYP3A4 inducer within 12 days prior to enrollment.
  -  Patients with central nervous system metastases or brain metastasis
  -  Previous definite diagnosis of neuropsychiatric disturbances, including epilepsy or dementia.
  -  Pregnant or lactating women.
  -  Patients with bone metastasis received palliative radiation within 4 weeks prior to enrollment.

Relevance to patient case: not relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: RALPPS in Patients With Hilar and Intrahepatic Cholangiocarcinoma

Summary: Unsatisfactory immediate outcomes of Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in surgery of cholangiocarcinoma suggested that patients with biliary cancer should not be treated by ALPPS. Short-term results of ALPPS variants with reduced surgical trauma on the first stage in patients with cholangiocarcinoma were not yet estimated. The objective of the study was estimation of the short-term results of split-in-situ resection with radio-frequency ablation (RFA) instead of liver partition on the first stage (RALPPS) in patients with hilar (h-CCA) and intrahepatic (i-CCA) cholangiocarcinoma compared with portal vein embolization (PVE).

Detailed description: ALPPS has been recently proposed as the most effective method to induce marked and rapid hypertrophy of FLR with 95-100% completion rate of the second stage. The most common indication for ALPPS is locally advanced multiple colorectal liver metastases. Unsatisfactory immediate outcomes of ALPPS in surgery of cholangiocarcinoma (CCA) including high mortality reached 48% in patients with h-CCA suggested that patients with biliary cancer should not be treated by ALPPS.
  Recently reported modifications of in situ splitting (partial ALPPS, RALPPS (radio-frequency-assisted liver partition with portal vein ligation for staged hepatectomy) and ALTPS (associating liver tourniquet and right portal vein ligation for staged hepatectomy) etc) have been aimed to minimize the operating injury on the first stage, hereby reducing postoperative morbidity.
  The other important idea was to preserve all initial benefits of ALPPS in terms of liver hypertrophy and completeness of the second stage. To date, there is no evidence of the benefits of any new ALPPS modification over others in reducing the morbidity of procedure, particularly in patients with CCA..

Eligibility: Inclusion Criteria:
  -  h-CCA, type II-IV, T1-3N0-1M0, volume of FLR<40%
  -  i-CCA, T1-3N0-1M0, volume of FLR<40%
  -  Physical status 1-4 according to American Society of Anesthesiologists Physical Status Classification System
  -  BMI up to 40 kg/m2
  -  If cirrhosis is present, class A according to Child-Turcotte-Pugh score
  Exclusion Criteria:
  -  h-CCA, stage 4A, B
  -  i-CCA, stage 4B
  -  i-CCA, T4N0-1M0
  -  i-CCA, h-CCA with volume of FLR >45%
  -  acute cholangitis and/or infected fluid collections, liver abscesses, other unresolved surgical complications of biliary draining procedures.
  -  jaundice with total bilirubin >50 µmol/L
  -  prior anamnestic allergic reaction or any other sign of intolerance to iodinated contrast media
  -  Age under 18 years
  -  Age above 80 years
  -  Persons who are incapable of giving consent
  -  Pregnant or breast-feeding women
  -  Physical status >4 according to American Society of Anesthesiologists Physical Status Classification System
  -  BMI > 40 kg/m2
  -  If cirrhosis is present, class B, C according to Child-Turcotte-Pugh score

Relevance to patient case: not relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: Enhancing Diagnosis in Chronic B-cell Lymphoproliferative Disorders Using Next-Generation Sequencing

Summary: To enhance the diagnosis of unclassifiable, non-CLL B-LPDs using next-generation sequencing technology.

Detailed description: In recent years, next generation sequencing has revealed the genomic landscape of lymphoid disorders and identified mutations that have improved our understanding of their pathogenesis. It has also revealed new targets for drug development. While some of these mutations, such as the BRAF V600E mutation in Hairy Cell Leukaemia (HCL)2, are now accepted as disease defining mutations, others such as MYD88 and NOTCH1/2 mutations are found in more than one subtype of B-LPD3. The overlapping nature of some of these molecular aberrations could have important implications for treatment of these disorders as we move towards targeted therapy. EZH2 inhibitors, which are currently in early phase trials, are one such example of targeted therapy for B-LPDs based on mutations identified by next generation sequencing (NGS)4. The genetic makeup of these tumours is also likely to influence future classification systems.
  At present, an integrated approach incorporating morphology and immunophenotyping remains integral to the classification of B-LPDs. The Haemato-oncology department at the Royal Marsden Hospital has an international reputation in the development of immunophenotyping as a tool for the diagnosis of lymphoproliferative disorders. For example, the CLL score developed by the Haemato-Oncology department continues to be used in several centres around the world for the diagnosis of CLL5. A similar score proposed for HCL by our Haemato-Oncology department is also widely used (6). On a service evaluation, we found 100% concordance between a HCL score of 4 and presence of the BRAF mutation in samples referred to us (unpublished data).
  Our plan therefore is to systematically study unclassifiable groups of B-LPD by creating a well-defined immunomorphology work flow for their identification. Samples thus identified will be screened using a next-generation sequencing (NGS) panel which is able to detect well established, B-LPD associated translocations and genetic mutations.

Eligibility: Inclusion Criteria:
  -  Chronic, mature clonal B-cell malignancy that is not assignable to a specific WHO category by current technology (see flowchart in section below).
  Exclusion Criteria:
  -  Non-clonal B-cell proliferation.
  -  High grade and/or immature clonal B-cell malignancy.
  -  Bone marrow samples with less than 20% infiltration will be excluded
  -  Samples from patients with a known classifiable chronic B-LPD based on lymph node biopsy for e.g. staging bone marrow samples on a patient with marginal zone lymphoma. If a definitive diagnosis is established on a subsequent lymph node biopsy, patient will remain on study and this will be correlated with NGS findings.
  -  Patient unable to provide consent for tumour and germ line samples.

Relevance to patient case: possibly relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: Bortezomib in Intrahepatic Cholangiocellular Carcinoma

Summary: This study evaluates the efficacy and safety of second-line treatment of bortezomib in advanced intrahepatic cholangiocarcinoma patients.Half of participants will receive bortezomib while the other half will receive best supporting care.

Detailed description: There's no standard second-line treatment for advanced intrahepatic cholangiocarcinoma patients.
  Previous study indicated high mutation/deletion rate of PTEN gene in intrahepatic cholangiocarcinoma and poor prognosis of those patients with PTEN mutation/deletion. The investigators also found that the activity of proteasomes elevated in cholangiocarcinoma cells with PTEN mutation/deletion.
  So the investigators suppose proteasomes inhibitor could improve prognosis of intrahepatic cholangiocarcinoma patients with PTEN mutation/deletion

Eligibility: Inclusion Criteria:
  1. Patients with a histologic or cytologic diagnosis of intrahepatic cholangiocarcinoma with stage IV;
  2. Have progressed after at least 2 cycles of systematic chemotherapy therapy（gemcitabine+cisplatin/gemcitabine+oxaliplatin）;
  3. The previous treatment and the present trial registration must be at least 2 weeks apart, and they must have recovered from any toxicity of a previous treatment;
  4. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1;
  5. Eastern Cooperative Oncology Group performance score (ECOG): 0-2; Life expectancy of at least 12 weeks;
  6. Normal liver,kidney and bone marrow function；
  7. Subjects who understand and voluntarily signed a written informed consent form.
  Exclusion Criteria:
  1. History of other malignancy within 3 years. Patients with central nervous system metastases or brain metastasis
  2. There is any contraindication to use Bortezomib
  3. Patients with contraindications (active bleeding, ulcers, intestinal perforation, intestinal obstruction, within 30 days after major surgery, uncontrolled high blood pressure medication, III-IV level cardiac insufficiency, severe liver and kidney dysfunction).
  4. A previous history of Interstitial pulmonary disease, drug-induced interstitial disease, radiation pneumonitis requiring hormonal therapy or active interstitial lung disease with any clinical evidence.
  5. Pregnant or lactating women.
  6. History of radiation within 4 weeks prior to enrollment.

Relevance to patient case: not relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: BRAF V600E and Redifferentiation Therapy in Radioiodine-refractory Papillary Thyroid Cancer

Summary: Papillary thyroid cancer (PTC) is the most common neoplasia in the thyroid gland. The combination of surgery, followed by radioiodine therapy (RIT) and thyroid-stimulating hormone (TSH) suppressive therapy is usually a curative option for differentiated thyroid cancer (DTC). Although DTC has a good prognosis generally, it is problematic when dedifferentiation is suspected and radioiodine refractoriness presumed. One possible therapy option for redifferentiation is the pretreatment with retinoids. From 2008 to 2014 there were 13 patients with PTC who were treated with retinoids after thyroidectomy before a further course of radioiodine. A recent study has shown that the efficacy of Selumetinib, another option for redifferentiation depends on the mutational status of the treated patient. In this retrospective study the investigators looked for a similar association between BRAF V600E and redifferentiation therapy with retinoids. As retinoids have fewer side effects compared to TKI, it is worth performing studies to assess the importance of genetic marker for the response and to estimate the chances of this specific patient collective. BRAF V600E seems to be associated with better long-term response after redifferentiation therapy with 13-cis RA in RAI-R PTC. Therefore, evaluation of BRAF mutational status prior to redifferentiation therapy could be beneficial for predicting response.


Eligibility: Eligible criteria for radioiodine-refractory patients included:
  -  PTC
  -  no response to former RIT
  -  decrease or loss of initial sufficient RI-Uptake
  -  redifferentiation therapy with 13-cis-RA
  -  available FFPE tissue.
  Eligible criteria for radioiodine-sensitive patients included:
  -  PTC
  -  cured after a maximum of two RIT
  -  no redifferentiation therapy necessary
  -  available FFPE tissue.
  Exclusion criteria
  -  DTC other than PTC
  -  patients lost to follow-up
  -  other redifferentiation therapy than retinoids
  -  anaplastic or medullary thyroid cancer
  -  benign thyroid disease, no available FFPE tissue
  -  more than two RITs in the control group
  -  insufficient clinical information.

Relevance to patient case: possibly relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: Expanded Access for the Treatment of Advanced Cholangiocarcinoma With ABC294640 (Yeliva ®)

Summary: This is an expanded access program (EAP) for eligible participants who do not qualify for participation in, or who are otherwise unable to access, the ongoing clinical trial ABC-108. This program is designed to provide access to ABC294640 (Yeliva ®) for treatment of cholangiocarcinoma (CCA) prior to approval by the local regulatory agency. Availability will depend on territory eligibility. Participating sites will be added as they apply for and are approved for the EAP. An oncologist must decide whether the potential benefit outweighs the risk of receiving an investigational therapy based on the individual patient's medical history and program eligibility criteria.


Eligibility: Inclusion Criteria:
  1. Diagnosis of cholangiocarcinoma
  2. Ineligible to participate in the ABC294640 clinical trial for the treatment of cholangiocarcinoma or geographically inaccessible to the trial.
  3. Judged by the treating oncologist to be medically suitable for treatment with ABC294640
  4. Willing and able to provide written, signed informed consent
  5. Approval by RedHill of the treating oncologist's clinical trial experience for the purpose of making ABC294640 available
  6. Regulatory approval by the appropriate jurisdiction
  Exclusion Criteria:
  1. Any medical condition that may cause treatment with ABC294640 to be potentially harmful as judged by RedHill

Relevance to patient case: not relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: Therapeutic Drug Monitoring of BRAF-mutated Advanced Melanoma

Summary: BRAF V600-mutant metastatic melanoma are commonly treated using a combination of anti-BRAF and anti-MEK tyrosine kinase inhibitors (TKIs). The OPTIMEL trial aims to study the interest of therapeutic drug monitoring (TDM) of TKIs and circulating tumor DNA (ctDNA) detected in plasma of patients with metastatic melanoma for disease monitoring. 35 patients with metastatic melanoma and treated with dabrafenib and trametinib will be enrolled in this trial. Blood samples will be collected for the determination of TKIs concentration and ctDNA detection.


Eligibility: Inclusion Criteria:
  -  Men and women 18 years of age and older
  -  Histologic proven advanced skin melanoma (Stage IV or stage IIIc inoperable) with BRAF V600 mutation
  -  Patient who will treated with combined kinase inhibitors (dabrafenib + trametinib).
  -  Patient able to stand a blood collection of 20 mL
  -  Ability to provide an informed written consent form
  -  Patient must be affiliated to a social security system
  -  Patient's legal capacity to consent to study participation and to understand and comply with the requirements of the study.
  Exclusion Criteria:
  -  Patient with mucosal melanoma
  -  Patient with non-metastatic skin melanoma (All stages except stage IV and stage III C inoperable)
  -  Patient with another synchronous cancer, or within 3 years
  -  Patient with a contraindication to blood collection of 20 mL
  -  Patient deprived of liberty or under supervision
  -  Patient unable to receive kinase inhibitor therapy
  -  Patient treated with another combined kinase inhibitors than dabrafenib and trametinib
  -  Pregnant or breastfeeding women
  -  Patient (man or woman) of childbearing age who does not agree to use of contraceptive methods validated during the study

Relevance to patient case: possibly relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: Precise Treatment System of Biliary Malignancies Based on Special Disease Database

Summary: Malignant tumors of biliary system lack standard treatment and precise prognosis assessment methods. This study including 12 hospitals, collecting clinical and follow-up data of patients with biliary malignant tumors including cholangiocarcinoma and gallbladder carcinoma in recent 10 years, aim to build a special disease database, then use Bayesian networks and importance theory to establish a mathematical model to assess treatment strategies and prognosis accurately. At the same time, data on biliary malignant tumors newly treated by multicenters from 2018 to 2020 will be included to validate, adjust and refine the models to guide clinical individualized precise treatment.


Eligibility: Inclusion Criteria：
  -  Clinical diagnosis of biliary malignancy including gallbladder carcinoma or cholangiocarcinoma verified by pathological results
  -  Must be able to undergo surgery
  -  Undergoing radical surgery for biliary malignancy (R0 or R1 resection)
  -  Not complicated with other malignancy
  -  No other treatments before and during surgery, such as radiotherapy and chemotherapy.
  Exclusion Criteria:
  -  Non-primary gallbladder or cholangiocarcinoma
  -  With distant metastasis (M1 phase)
  -  Incomplete follow-up data
  -  Died within 30 days after surgery.

Relevance to patient case: not relevant