araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 34-year-old female with melanoma; genetic feature: NRAS (Q61L)

Clinical trial: miRNA Machinery in Melanoma, Melanoma Metastases and Benign Melanocytic Naevi

Summary: MicroRNAs (miRNAs) are very small endogenous RNA molecules about 22-25 nucleotides in length, capable of post-transcriptional gene regulation. miRNAs bind to their target messenger RNAs (mRNAs), leading to cleavage or suppression of target mRNA translation based on the degree of complementarity. miRNAs have recently been shown to play pivotal roles in diverse developmental and cellular processes and linked to a variety of skin diseases and cancers. In the present study, the investigators examines the expression profiles of miRNA machinery components such as miRNA maturation and transport factors, microprocessor complex and RISC subunits in cutaneous melanoma, cutaneous melanoma metastases and benign melanocytic nevi.

Detailed description: Patients with cutaneous melanoma, cutaneous melanoma metastases and benign melanocytic nevi were included in the study. Punch biopsies were harvested from the center of the tumors. The miRNA machinery components were detected by quantitative real-time reverse transcriptase polymerase chain reaction.

Eligibility: Inclusion Criteria:
  -  cutaneous melanoma
  -  cutaneous melanoma metastases
  -  benign melanocytic nevi
  Exclusion Criteria:
  -  other forms of malignancy

Relevance to patient case: not relevant
Patient case: 34-year-old female with melanoma; genetic feature: NRAS (Q61L)

Clinical trial: cKIT, BRAF/NRAS Mutations in Advanced Melanoma : Clinical Outcome in Response to Tyrosine-kinase Inhibitors - KitMel Project

Summary: Background: Metastatic melanoma has a devastating prognosis and is one of the top causes of cancer death in young patients. Until now, available therapies were few and unreliable, but recent understanding of melanomas' molecular pathways has improve their classification and new clinical strategies have been proposed.
  Initial studies showed that B-Raf/N-Ras mutations (respectively V600E and Q61) are the most frequent alteration being present in 70 to 80% of melanomas, characterizing non Chronic Sun-induced Damage skins (CSD). These include Superficial Spreading Melanomas (SSM) and Nodular Melanomas (NM). Other studies showed that c-Kit mutations are presently the predominant activating mutation (20 - 40 %) in Acro-Lentiginous Melanomas (ALM), Mucous Melanomas (MM) and in melanomas arising on CSD skin. c-Kit mutation pattern is more complex with four exons being affected leading to different mutations, which incidence and biological impact are less documented.
  BRAF/NRAS genetics alterations drive constantly cell growth, being thus attractive targets. Spectacular results have indeed been obtained with the BRAF inhibitor that targets the V600E BRAF-mutated form. Data from GIST disease revealed that the different c-Kit mutations modulate differently c-Kit function and the response to targeted therapies.
  Because c-Kit targeted therapy is a critical clinical issue, the investigators aimed to identify the most frequent mutations present in our population to propose appropriate screening test and adapt the therapy.
  Methods: 250 melanoma samples corresponding to an homogeneous white-Caucasian population (Brittany, France) will be screened. c-Kit exons 11, 13, 17 and 18 will be sequenced (direct sequencing and pyrosequencing when possible). c-Kit copy number will be quantified by q-PCR and level of c-Kit determined by immunohistochemistry (IHC, CD117). Samples will also be analyzed for B-Raf mutations in codon 464, 466, 469 and 600, and for N-Ras mutations in codon 12, 13 and 61 (Pyrosequencing).
  Expected Results:
  Taken together, the investigators anticipate that the present genetic analysis of the tumours from patients with advanced melanoma will first document the type and frequency of cKit mutations, will confirm or not that BRAF, NRAS and cKit mutations are mutually exclusive and document their repartition in the melanomas sub-types. Finally this study will clue researchers in to how well patients will respond to a therapy that targets the growth-promoting proteins BRAF/NRAS and cKIT.


Eligibility: Inclusion Criteria:
  -  melanoma
  -  white caucasian population

Relevance to patient case: possibly relevant
Patient case: 34-year-old female with melanoma; genetic feature: NRAS (Q61L)

Clinical trial: Dabrafenib Plus Trametinib vs Vemurafenib Alone in Unresectable or Metastatic BRAF V600E/K Cutaneous Melanoma

Summary: This is a two-arm, open-label, randomised, Phase III study comparing dabrafenib (GSK2118436) and trametinib (GSK1120212) combination therapy to vemurafenib. Subjects with histologically confirmed cutaneous melanoma that is either stage IIIc (unresectable) or stage IV, and BRAF V600E/K mutation positive will be screened for eligibility. Subjects who have had prior systemic anti-cancer treatment in the advanced or metastatic setting will not be eligible although prior systemic treatment in the adjuvant setting will be allowed. Approximately 694 subjects will be randomised 1:1 (combination therapy:vemurafenib). The primary endpoint is overall survival (OS) for subjects receiving the combination therapy compared with those receiving vemurafenib.


Eligibility: Inclusion Criteria:
  -  >= 18 years of age
  -  Stage IIIc or Stage IV BRAF V600E/K cutaneous melanoma
  -  Measurable disease according to RECIST 1.1
  -  Women of childbearing potential with negative serum pregnancy test prior to randomisation
  -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  -  Adequate baseline organ function
  Exclusion Criteria:
  -  Any prior use of a BRAF or MEK inhibitor
  -  Prior systemic anti-cancer treatment in the advanced or metastatic setting; prior systemic treatment in the adjuvant setting is allowed
  -  History of another malignancy (except subjects who have been disease free for 3 years or with a history of completely resected non-melanoma skin cancer)
  -  Known HIV, HBV, HCV infection (except chronic or cleared HBV and HCV infection which will be allowed)
  -  Brain metastases (except if all known lesions were previously treated with surgery or stereotactic radiosurgery and lesions, if still present, are confirmed stable for >= 12 weeks prior to randomisation or if no longer present are confirmed no evidence of disease for >= 12 weeks, and are asymptomatic with no corticosteroid requirements for >= 4 weeks prior to randomisation, and no enzyme inducing anticonvulsants for >= 4 weeks prior to randomisation
  -  History or evidence of cardiovascular risk (LVEF < LLN; QTcB >= 480 msec; blood pressure or systolic >=140 mmHg or diastolic >= 90 mmHg which cannot be controlled by anti-hypertensive therapy)
  -  History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)

Relevance to patient case: not relevant
Patient case: 34-year-old female with melanoma; genetic feature: NRAS (Q61L)

Clinical trial: Phase II Safety Study of Vemurafenib Followed by Ipilimumab in Subjects With V600 BRAF Mutated Advanced Melanoma

Summary: The purpose of this study is to assess the safety profile of vemurafenib, 960 mg, administered for 6 weeks, followed by ipilimumab monotherapy in patients with BRAF V600 mutated advanced/metastatic melanoma.


Eligibility: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
  Key Inclusion Criteria:
  -  Men and women 18 years of age and older
  -  Histologic diagnosis of malignant melanoma tested positive for the BRAF V600 mutation
  -  Previously untreated unresectable Stage III or Stage IV melanoma
  -  Complete set of brain/neck, chest, abdomen/pelvis axial radiographs taken within 28 days of first dose of study drug
  -  Measurable melanoma by physical or radiographic examination
  -  Brain metastases stable after radiation for at least 1 month and off corticosteroid therapy for ≥30 days prior to enrollment
  -  Eastern Cooperative Oncology Group performance status of 0 or 1
  -  Adequate hematologic parameters and renal and hepatic function
  Key Exclusion Criteria:
  -  Primary ocular melanoma
  -  Active brain metastases with symptoms or requiring corticosteroid treatment
  -  Any other malignancy from which the patient has been disease-free for less than 2 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix
  -  History of or current active autoimmune diseases, including but not limited to inflammatory bowel diseases, rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis, systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies
  -  History of or current immunodeficiency disease, splenectomy, or splenic irradiation
  -  Prior anticancer therapy or investigational products <4 weeks prior to enrollment
  -  Prior therapy with a BRAF or MEK inhibitor and prior investigational anticancer immunotherapies;
  -  Prior therapies with immunosuppressive agents within the past 2 years
  -  Concomitant therapy with any anticancer or potent immunosuppressive agent, surgery, radiotherapy, other investigational anticancer therapies, or chronic use of systemic corticosteroids

Relevance to patient case: not relevant
Patient case: 34-year-old female with melanoma; genetic feature: NRAS (Q61L)

Clinical trial: Vitamin D Supplementation in Cutaneous Malignant Melanoma Outcome

Summary: To assess whether vitamin D supplementation after surgery of a first cutaneous malignant melanoma protects against relapse of the disease.

Detailed description: To assess whether vitamin D supplementation, in the follow up period after diagnosis and surgery of a first cutaneous malignant melanoma, has a protective effect on relapse of cutaneous malignant melanoma and whether this protective effect correlates with vitamin D levels in serum and vitamin D receptor (VDR) immunoreactivity in the primary tumor.

Eligibility: Inclusion Criteria:
  1. Older than 18 years and younger than 80 years of age.
  2. Histologically proven malignant melanoma, stage one B (IB) to three (III) Not participating in other clinical trial.
  3. The only treatment for melanoma is surgical treatment.
  4. Complete resection of melanoma.
  5. Single primary invasive cutaneous melanoma
  6. Signed ethical committee approved informed consent
  7. Serum phosphate, serum calcium at the entry of the study within normal limits of laboratory reference
  Exclusion criteria
  1. Pregnant/lactating women or planning on becoming pregnant during the study
  2. Known hypersensitivity to vitamin D or its components.
  3. Pre-existing renal stone disease, chronic renal disease with glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 or renal dialysis.
  4. Liver failure or chronic liver disease with liver enzymes > 2 fold upper limit of normal (ULN).
  5. History of parathyroid disease or granulomatous disease (TBC and sarcoidosis)
  6. History of malabsorption syndrome or any medical condition that might interfere with vitamin D absorption.
  7. History of small intestine resection.
  8. History of other malignancy within the last 5 years except for carcinoma in situ of the cervix or basal cell carcinoma or squamous cell carcinoma of the skin or in situ malignant melanoma.
  9. Chronic alcohol abuse.
  10. Medical or logistic problems likely to preclude completion of the study.
  11. Taking medication that predisposes to hypercalcemia (digoxin, lithium, thiazide diuretics) or taking medication that would affect metabolism of vitamin D (anticonvulsants, corticosteroids, H2-receptor antagonists)
  12. Intake of vitamin D supplements within 6 months prior to entry of the study.

Relevance to patient case: not relevant
Patient case: 34-year-old female with melanoma; genetic feature: NRAS (Q61L)

Clinical trial: Clinical and Histopathologic Characteristics of BAP1 Mutations

Summary: The goal of this protocol is to determine the prevalence of somatic and germline mutations in BAP1 (BRCA associated protein-1) among patients with mesothelioma , choroidal nevus, primary uveal melanoma (UM), or metastatic UM seen at our institution.


Eligibility: Inclusion Criteria:
  All consents:
  -  > or = to 18 years of age
  -  Ability to provide informed consent
  Consent 1:
  Mesothelioma
  -  Histologically proven diagnosis of Mesothelioma OR Choroidal nevus
  -  Diagnosis of choroidal nevus by direct examination and/or ultrasound/optical coherence tomography and possibly fluorescein angiography OR Primary uveal melanoma
  -  Diagnosis of uveal melanoma by direct examination and/or ultrasound/optical coherence tomography and possibly fluorescein angiography
  Consent 2:
  Mesothelioma
  -  Histologically proven diagnosis of Mesothelioma AND
  -  BAP1 mutation or loss of expression identified in tumor sample
  OR one of the following:
  -  Age<50 at diagnosis
  -  No history of asbestos exposure
  -  Personal history of choroidal nevus, uveal melanoma, melanoma, renal cell carcinoma, or cholangiocarcinoma
  -  Family history of choroidal nevus, uveal melanoma, mesothelioma, renal cell carcinoma, or cholangiocarcinoma
  -  History of malignancy in more than two first-degree relatives OR Choroidal nevus
  -  Diagnosis of choroidal nevus by direct examination and/or ultrasound/optical coherence tomography and possibly fluorescein angiography AND one of the following:
  -  More than one clinical risk factor, which may include: orange pigment, thickness > 1 < 2.5mm
  -  Personal history of uveal melanoma, skin melanoma, mesothelioma renal cell carcinoma, or cholangiocarcinoma
  -  Family history of choroidal nevus, uveal melanoma, mesothelioma renal cell carcinoma, or cholangiocarcinoma OR Primary uveal melanoma
  -  Diagnosis of uveal melanoma by direct examination and/or ultrasound/optical coherence tomography and possibly fluorescein angiography
  AND one of the following:
  -  Personal history of uveal melanoma, skin melanoma, mesothelioma, renal cell carcinoma, or cholangiocarcinoma
  -  Family history of choroidal nevus, uveal melanoma, mesothelioma, renal cell carcinoma, or cholangiocarcinoma
  -  History of malignancy in more than two first-degree relatives OR Metastatic uveal melanoma
  -  Histologically proven diagnosis of metastatic uveal melanoma AND
  -  BAP1 mutation or loss of expression identified in tumor sample
  OR one of the following:
  -  Personal history of uveal melanoma, skin melanoma, mesothelioma renal cell carcinoma, or cholangiocarcinoma
  -  Family history of choroidal nevus, uveal melanoma, mesothelioma renal cell carcinoma, or cholangiocarcinoma
  -  History of malignancy in more than two first-degree relatives
  Consent 3:
  -  Relative of patient with germline BAP1 mutation identified through identified testing
  Exclusion Criteria:

Relevance to patient case: not relevant
Patient case: 34-year-old female with melanoma; genetic feature: NRAS (Q61L)

Clinical trial: A Phase 2 Study of Panitumumab in Patients With Cetuximab-refractory Metastatic Colorectal Cancer

Summary: The purpose of this study is to assess if panitumumab is active enough to warrant comparative studies in patients with metastatic colorectal cancer that has progressed after treatment with cetuximab.

Detailed description: The study was amended with modification of inclusion criteria (from wild-type tumor KRAS gene to wild-type RAS gene, including KRAS and NRAS exons 2, 3 and 4)
  RAS mutational status of tumors of patients enrolled before amendment 1 approval will be centrally revised. Patients whose tumors will result RAS mutated at the biomarkers central revision, will be replaced. Therefore, the overall sample size at both the stages may be higher than the one initially planned.

Eligibility: Inclusion Criteria:
  -  Pathologic diagnosis of metastatic colorectal adenocarcinoma
  -  a wild-type RAS tumor (mutational status has to be determined by an experienced laboratory using validated test methods for detection of KRAS exons 2, 3, and 4, and NRAS exons 2, 3, and 4
  -  Failure from previous treatment with fluoropyrimidine, oxaliplatin and irinotecan. Patients may or may not have been treated with bevacizumab.
  -  Documented disease progression following a treatment with cetuximab in patients who showed either an objective response after 8 weeks or stable disease after 16 weeks of cetuximab treatment.
  -  Age at least 18 years
  -  ECOG Performance Status 0-2
  -  Neutrophils at least 1,500 mm3, platelets at least 100,000 mm3, and hemoglobin at least 9 g/dL
  -  Bilirubin level less than 1.5 times ULN
  -  AST (SGOT) and ALT (SGPT) not greater than 2.5 times ULN (or 5 times ULN in presence of liver metastasis)
  -  Serum creatinine less than 1.5 times ULN
  -  Effective contraception, if the risk of conception exists
  -  Life expectancy at least 3 months
  -  Written informed consent
  Exclusion Criteria:
  -  Symptomatic brain metastasis
  -  Interstitial pneumonitis or pulmonary fibrosis
  -  Any other malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or non melanoma skin cancer)
  -  Chemotherapy, radiotherapy or immunotherapy within the past 4 weeks
  -  Any unstable systemic disease (including active infections, any significant hepatic, renal or metabolic disease), metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of study drugs or render the patient at high risk from treatment complications
  -  Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment

Relevance to patient case: not relevant
Patient case: 34-year-old female with melanoma; genetic feature: NRAS (Q61L)

Clinical trial: Irradiated Donor Lymphocyte Infusion Plus High-dose IL-2

Summary: Partially HLA-matched irradiated donor lymphcyte infusion alone resulted in 27% overall response rate (ORR) in advanced renal cell carcinoma without significant toxicities. In addition, high-dose interleukin-2 (IL-2)showed an ORR of 6-21% in metastatic melanoma or renal cell carcinoma with a durable response in patients who achieved complete remission. Therefore, irradiated donor lymphocyte infusion plus high-dose IL-2 might show a synergistic anti-tumor activity agaist relapsed or metastatic melanoma or renal cell carcinoma.


Eligibility: Inclusion Criteria:
  -  Histologically confirmed malignant melanoma or renal cell carcinoma
  -  At stage IV or relapse
  -  At least one prior chemotherapy including targeted agents
  -  At least one haploidential or partially matched-HLA donor
  -  ECOG performance status 0-1
  -  Age 18-75 years
  -  Measurable lesion
  -  Adequate bone marrow, liver, and renal functions
  Exclusion Criteria:
  -  Chemotherapy within 4 weeks
  -  Stem cell transplantation
  -  Active CNS metastasis
  -  Hypersensitivity to IL-2

Relevance to patient case: not relevant
Patient case: 34-year-old female with melanoma; genetic feature: NRAS (Q61L)

Clinical trial: Everolimus in Selected Patients With Metastatic Melanoma: Efficacy and Safety Study

Summary: This is a single-armed, open-labeled and single-centered study of everolimus in selective patients with metastatic melanoma for evaluation of the efficacy and safety. The study objective is to evaluate efficacy profile of everolimus.
  The patients who comply with the inclusion and exclusion criteria will be enrolled. The estimated recruiting duration is 18 months. Everolimus will be given in the dose of 10 mg orally each day at lease 6 months unless disease progression or intolerance. The follow-up is till death(at least 1 year).


Eligibility: Inclusion Criteria:
  Clinical diagnosis of metastases melanoma. Must have evidence of mutations(Kinase domain) of mTOR . Must be ECOG performance status 0,1, or 2 . Must be estimated life expectancy of 3 months or greater. Must be age 18 years or older, male or female. Must have at least one measurable site of disease as defined by at least 1 cm in greatest dimension.
  Adequate organ function. Must be willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
  Exclusion Criteria:
  Prior systemic therapy for metastatic disease within 4 weeks. Second malignancy within the last 5 years. Severe and/or uncontrolled medical disease. Received RAD001 or other mTOR inhibitors previously . Hypersensitivity to everolimus Current treatment on another clinical trial. Pregnancy or breastfeeding.

Relevance to patient case: not relevant
Patient case: 34-year-old female with melanoma; genetic feature: NRAS (Q61L)

Clinical trial: Nevus Doctor Clinical Decision Support

Summary: The "Nevus doctor" is a dermatoscopy based computer decision support tool to assist general practitioners (GPs) in the classification of pigmented skin lesions (PSLs). The aim of the program "Nevus doctor" is to help GPs increase their diagnostic accuracy, in particular regarding the selection of suspicious PSLs that need biopsy or referral to specialist health care for further assessment. The aim of this study is to investigate the diagnostic performance of the decision support tool in a primary care setting in Norway. We hypothesize that the diagnostic accuracy of the computer program "Nevus doctor" is better than the performance of the GPs.

Detailed description: In the trial GPs examine patients who attend a primary health care center. A given PSL is first assessed clinically by the GP and afterwards photographed. A clinical photograph as well as a dermatoscopic photograph is taken, the latter using a dermatoscope attached to the lens of the camera. The dermatoscopic image is then processed by the computer program. The performance of "Nevus doctor" is compared with the GPs' assessment. A dermatologist reviews all cases based on the clinical and dermatoscopic photographs and this assessment serves as the reference standard.

Eligibility: Inclusion Criteria:
  -  Pigmented skin lesion
  Exclusion Criteria:

Relevance to patient case: not relevant
Patient case: 34-year-old female with melanoma; genetic feature: NRAS (Q61L)

Clinical trial: Non-invasive Melanoma Assessment Using a Topical Fluorescence Reagent and Optical Imaging

Summary: The use of MDS to access the presence of melanoma in the skin.

Detailed description: A topical agent is applied to suspicious skin lesions and imaged. The images are analyzed to provide a score that correlates with the probability for the presence of melanoma in the lesion.

Eligibility: Inclusion Criteria:
  -  Individuals with skin lesion with one or more of the ABCDE features and recommended for a skin biopsy.
  -  The lesion is accessible to the imaging device, with at least 1 cm of skin around the lesion that is accessible to the MDS.
  -  Male and female ≥ 21 years old.
  -  Subject is capable of giving written informed consent.
  -  Primary excision.
  Exclusion Criteria:
  -  The lesion is less than 1 cm from the eyes.
  -  The lesion is on the palms of hands or soles of the feet.
  -  Mucosal lesion.
  -  Pregnant females.
  -  Low study procedure compliance.
  -  Patients who are mentally or physically unable to comply with all aspects of the study.
  -  Undergoing chemotherapy.
  -  Minor or legally incompetent and not able to sign the consent form.
  -  Patient previously tested by MDS and was diagnosed with melanoma during the study.

Relevance to patient case: not relevant