araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

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: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

Clinical trial: Pilot Study of 99mTc-MIP-1404 SPECT/CT Imaging in Men With Prostate Cancer Undergoing Prostatectomy and/or Pelvic Lymph Node Dissection

Summary: This is a single arm, open label study of up to 24 high risk prostate cancer patients scheduled for prostatectomy and/or pelvic lymph node dissection. Patients receive a single IV dose of 99mTc-MIP-1404 (study drug) followed by SPECT/CT scan 3-6 hours after injection. As standard of care, patients will undergo prostatectomy and/or pelvic lymph node dissection (PLND) within two weeks of study drug dosing. Patients may receive a second injection of study drug within 24 hours of surgery to measure activity counts in tissue samples post-surgery, but prior to pathology processing. 99mTc-MIP-1404 image data will be evaluated for visible uptake and compared with histopathology.


Eligibility: Inclusion Criteria:
  1. Male aged 21 years or older.
  2. Ability to provide signed informed consent and willingness to comply with protocol requirements.
  3. Past biopsy indicating the presence of adenocarcinoma of the prostate gland.
  4. Participant is deemed to be high-risk with potential for pelvic lymph node involvement. The criteria for high-risk are:
  -  Patient has PSA value >10 and clinical stage T2 or higher, and Gleason score 8, 9 or 10.
  -  Patient has PSA value >20 and clinical stage T2 or higher, and Gleason score
  5. Participant is or will be scheduled to undergo standard of care prostatectomy and/or pelvic lymph node dissection.
  6. Have had (within previous 2 months) or will undergo diagnostic CT or MRI imaging prior to surgery.
  7. Have had (within previous 2 months) or will undergo bone scan imaging prior to surgery.
  8. Participants must agree to use an acceptable form of birth control throughout the study period. Participants must use condoms for a period of seven days after each injection, if engaged in sexual activity.
  Exclusion Criteria:
  1. Participants for whom participating would significantly delay the scheduled standard of care therapy.
  2. Participants administered a radioisotope within 5 physical half lives prior to study enrollment.
  3. Participants with any medical condition or other circumstances that, in the opinion of the Investigator, would significantly decrease obtaining reliable data, achieving study objectives or completing the study.

Relevance to patient case: not relevant
Patient case: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

Clinical trial: Study of Circulating Tumor Cells Before and After Treatment in Patients With Metastatic Melanoma

Summary: Circulating tumor cells (CTC) are the subject of increasing interest in clinical oncology as a prognostic factor and predictor of therapeutic response. The detection of CTC by immunomagnetic method has proved its reliability and its usefulness for monitoring breast cancer, colon and prostate in the metastatic and immunomagnetic detection system (CellSearch, Veridex LLC) was approved by the FDA in these indications. However, to date there is no reliable method to detect CTCs in melanoma (CMC). Studies based on PCR amplification of mRNA by reverse specific melanoma is disappointing. Recently, a new detection system of CMC immunomagnetic was presented (CellSearch, Veridex LLC, United States). This system has the advantage of combining immunomagnetic selection step and a step of identifying by immunofluorescence. A preclinical study on serial dilutions of melanoma cells has shown encouraging results. The investigators propose a prospective study of the CellSearch system in patients with melanoma.
  Primary objective: To determine the effect of treatment on the number of circulating melanoma cells in patients with metastatic melanoma.
  Secondary objectives:
  -  determine the percentage of patients with metastatic melanoma with melanoma cells circulating
  -  seek a relationship between the number of circulating melanoma cells and prognosis in patients with metastatic melanoma
  -  seek a relationship between the change in the number of circulating melanoma cells before / after treatment and tumor response in patients with metastatic melanoma


Eligibility: Inclusion Criteria:
  -  Patients > or = 18 years
  -  Patients with advanced melanoma stage IIIC (unresectable) or stage IV
  -  Patient not treated or not responding to chemotherapy with chemotherapy session last> 1 month
  -  Patients who signed informed consent
  -  Patients presenting no socio-economic, psychological, familial or geographical allow proper understanding of the information leaflet of the protocol or the regular monitoring in the department of dermatology
  -  Patients with a life expectancy greater than 3 months
  -  Patients with melanoma measurable by RECIST version 1.1
  -  Patients with venous good for venipuncture
  Exclusion Criteria:
  -  Patients with contraindication for treatment with chemotherapy or V600E BRAF inhibitor or ipilimumab or have conditions concomitant heavy may interfere with the treatment of metastatic melanoma
  -  Pregnant women or nursing
  -  People vulnerable detainees, adults under guardianship or curatorship, minors.

Relevance to patient case: not relevant
Patient case: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

Clinical trial: Anesthesia and Cancer Recurrence im Malignant Melanoma

Summary: Studies in animals and retrospective studies in humans show that regional anesthesia reduces metastatic cancer dissemination.
  The investigators hypothesize that in patients suffering from malignant melanoma who have to undergo radical inguinal lymph node dissection immune function will be less compromised and long term survival will be superior when spinal anesthesia is compared to general anesthesia.

Detailed description: Results of basic science indicate that regional anesthesia prevents perioperative immunosuppression and reduces postoperative metastatic cancer dissemination. If this would occur in humans, optimised anesthetic management might improve long-term outcome after cancer surgery.

Eligibility: Inclusion Criteria:
  -  Patients scheduled for inguinal lymph node dissection because of malignant melanoma of the lower limb
  -  Signed informed consent
  Exclusion Criteria:
  -  Age < 18 years
  -  Female patients who are pregnant or nursing
  -  Multiple organ failure
  -  Contraindications

Relevance to patient case: not relevant
Patient case: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

Clinical trial: Autonomic Phenotype Before and After Akt Inhibition

Summary: Some Akt inhibitors have produced functional cardiovascular effects such as marked hypotension that may limit their clinical benefit. There are no current data on whether this autonomic failure presents in humans at clinically used doses. We will test the hypothesis that Akt inhibition causes an acute decrease in sympathetic tone and lowers blood pressure.


Eligibility: Inclusion Criteria:
  -  Diagnosed with melanoma with a BRAF mutation and relapse following therapy with a BRAF inhibitor
  -  Enrolled in a clinical trial through the Vanderbilt Ingram Cancer Center (VICC) including an arm with an oral Akt inhibitor
  -  Able and willing to provide informed consent
  Exclusion Criteria:
  -  Factors which in the investigator's opinion would prevent the participant from completing the protocol, including poor compliance during previous studies or an unpredictable schedule
  -  Unable to give informed consent

Relevance to patient case: not relevant
Patient case: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

Clinical trial: COPARIME: Pilot Study of a Target Detection of Malignant Melanoma

Summary: Melanoma is nowadays an important public health problem because its growing incidence. Mass screening for melanoma is not recommended worldwide because of its low cost-effectiveness. Nevertheless targeted screening for patients at high risk for melanoma is promoted. This study is designed to assess the effectiveness and the acceptability of a melanoma targeted screening of melanoma, to estimate the risk function to develop a melanoma among patients at high risk according to the SAMScore and to estimate the ratio cost/ efficacy of the melanoma targeted screening. A cohort of 7700 patients is carried out in 2 departments covered by a registry of cancers. The recruitment had began in April 2011. Patients assessed at high risk according to the SAMScore were proposed a skin examination by their GP every year.


Eligibility: Inclusion Criteria:
  -  patients more than 18 years old,
  -  consulting their GP,
  -  assessed at risk for melanoma according to the SAMScore
  -  signed the consent.

Relevance to patient case: not relevant
Patient case: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

Clinical trial: A Phase 1 Pilot Study of 99mTc-MIP-1404 SPECT/CT Imaging to Histology in Men With Prostate Cancer

Summary: This is a single arm, open label study of up to 24 prostate cancer patients scheduled for prostatectomy and/or pelvic lymph node dissection. Patients receive a single IV dose of 99mTc-MIP-1404 (study drug) followed by SPECT/CT scan 3-6 hours after injection. As standard of care, patients will undergo prostatectomy and/or pelvic lymph node dissection (PLND) within two weeks of study drug dosing. 99mTc-MIP-1404 image data will be evaluated for visible uptake and compared with histopathology.


Eligibility: Inclusion Criteria:
  -  Male aged 21 years or older.
  -  Ability to provide signed informed consent and willingness to comply with protocol requirements.
  -  Past biopsy indicating the presence of adenocarcinoma of the prostate gland.
  -  Participant is deemed to have tissue suspicious of prostate cancer involvement that is amenable to biopsy/resection.
  -  Have had, or will undergo diagnostic CT or MRI imaging prior to surgery.
  -  Participants must agree to use an acceptable form of birth control throughout the study period. Participants must use condoms for a period of seven days after study drug administration, if engaged in sexual activity.
  Exclusion Criteria:
  -  Participants for whom participating would significantly delay the scheduled standard of care therapy.
  -  Participants administered a radioisotope within 5 physical half lives prior to study enrollment.
  -  Participants with any medical condition or other circumstances that, in the opinion of the investigator, would significantly decrease obtaining reliable data, achieving study objectives or completing the study.

Relevance to patient case: not relevant
Patient case: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

Clinical trial: Observational Study on Treatment of Metastatic Colorectal Cancer and the Role of K-Ras

Summary: The purpose of this study is to describe the treatments received and outcomes of patients with metastatic colorectal cancer, what percentage of these patients have K-Ras mutation of the tumor, and to describe the costs of treatments. Information will also be collected regarding risk factors, variables among treatment centers and patients, and explorative analyses will be done to try to identify factors that impact prognosis and factors that predict tolerability and response to treatment.


Eligibility: Inclusion Criteria:
  -  Histologic diagnosis colorectal carcinoma
  -  Metastatic disease
  -  Signed informed consent
  Exclusion Criteria:
  -  Prior treatment of metastatic colorectal cancer
  -  Refusal or incapability of providing informed consent

Relevance to patient case: not relevant
Patient case: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

Clinical trial: A Phase 2 Study With MIP-1404 in Men With High-Risk PC Scheduled for RP and EPLND Compared to Histopathology

Summary: This was a multicenter, multi-reader, open-label, Phase 2 study assessing the safety and performance characteristics of MIP 1404 imaging in the detection of prostate gland and pelvic lymph node cancer. Comparative performance characteristics between MIP 1404 imaging and MRI were also assessed, as judged by histopathology results.

Detailed description: This is a single arm, open label study of approximately 100 high-risk prostate cancer patients scheduled for prostatectomy and extended pelvic lymph node dissection. Patients receive a single IV dose of 99mTc-MIP-1404 (study drug) followed by SPECT/CT scan 3-6 hours after injection. As standard of care, patients will undergo prostatectomy and extended pelvic lymph node dissection (EPLND) within three weeks of study drug dosing. 99mTc-MIP-1404 image data will be evaluated for visible uptake and compared with histopathology.

Eligibility: Inclusion Criteria:
  -  Male aged 21 years or older.
  -  Ability to provide signed informed consent and willingness to comply with protocol requirements.
  -  Biopsy confirmed presence of adenocarcinoma of the prostate gland.
  -  At high-risk for metastatic disease by a stage of cT3, cT4, or a total nomogram score of greater than or equal to 130.
  -  Scheduled to undergo radical prostatectomy with extended pelvic lymph node dissection.
  -  Agree to use an acceptable form of birth control for a period of 7 days after the 99mTc MIP-1404 injection.
  Exclusion Criteria:
  -  Participating would significantly delay the scheduled standard of care therapy.
  -  Administered a radioisotope within 5 physical half lives prior to study drug injection.
  -  Have any medical condition or other circumstances that, in the opinion of the investigator, would significantly decrease obtaining reliable data, achieving study objectives or completing the study.
  -  Have a contraindication for MR imaging.

Relevance to patient case: not relevant
Patient case: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

Clinical trial: Sentinel Lymph Node Total Tumoral Load as a Predictor of Non Sentinel Node Involvement in Early Breast Cancer

Summary: This is a retrospective, multicentric cohort study of patient cases with cT1-3, N0 early breast cancer, who previously had intraoperative sentinel lymph node (SLN) evaluation by one-step nucleic acid amplification (OSNA) assay with a complete axillary dissection.
  The aim of the present study is to assess the intraoperative positive SLN total tumor load (TTL) obtained from the OSNA assay and to determine whether this TTL predicts non-SLN metastasis in patients with clinically node-negative early-stage breast cancer.


Eligibility: Inclusion Criteria:
  -  Pathologically confirmed invasive breast carcinoma
  -  Stage T1-3,N0 evaluated by physical exam or imaging according to AJCC v.7 and best clinical local practices
  -  Intraoperative evaluation of sentinel lymph node (SLN) by OSNA
  -  Complete dissection of axillary lymph nodes after the evaluation of the SLNs by OSNA
  -  Pathology report of the tumor and dissected lymph nodes that includes the following information:
  -  primary tumor size (mm), tumor grade (Scarff-Bloom Richardson), estrogen receptor status
  -  progesterone receptor status
  -  HER2 status (ASCO/CAP guidelines)
  -  Ki67 index
  -  presence/absence of lymphovascular invasion
  -  total number of sentinel and non-sentinel lymph nodes dissected during surgery
  -  total number of positive and negative sentinel and non-sentinel lymph nodes, *size of the metastasis in both sentinel and non-sentinel lymph nodes
  -  total tumoral load in each sentinel lymph node, expressed as number of CK19 mRNA copies per microliter.
  Exclusion Criteria:
  -  Patients who underwent neoadjuvant chemotherapy
  -  CK19-negative breast tumor
  -  ALND with <10 lymph nodes
  -  In situ carcinoma only
  -  Metastatic breast cancer at time of diagnosis

Relevance to patient case: not relevant
Patient case: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

Clinical trial: A Study of the BRAF Inhibitor Dabrafenib in Combination With the MEK Inhibitor Trametinib in the Adjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma After Surgical Resection.

Summary: This is a two-arm, randomized, double-blind Phase III study of dabrafenib in combination with trametinib versus two placebos in the adjuvant treatment of melanoma after surgical resection. Patients with completely resected, histologically confirmed, BRAF V600E/K mutation-positive, high-risk [Stage IIIa (lymph node metastasis >1 mm), IIIb or IIIc] cutaneous melanoma will be screened for eligibility. Subjects will be randomized to receive either dabrafenib (150 milligram (mg) twice daily [BID]) and trametinib (2 mg once daily [QD]) combination therapy or two placebos for 12 months.


Eligibility: Inclusion Criteria:
  -  Completely resected histologically confirmed high-risk [Stage IIIa (LN metastasis more than 1 mm), IIIb or IIIc cutaneous melanoma determined to be V600E/K mutation positive by a central laboratory. Patients presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible.
  -  Surgically rendered free of disease no more than 12 weeks before randomization.
  -  Recovered from definitive surgery (e.g. no uncontrolled wound infections or indwelling drains).
  -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
  -  Adequate hematologic, hepatic, renal and cardiac function.
  Exclusion Criteria:
  -  Known mucosal or ocular melanoma or the presence of unresectable in-transit metastases.
  -  Evidence of distant metastatic disease.
  -  Prior systemic anti-cancer treatment and radiotherapy for melanoma; prior surgery for melanoma is allowed.
  -  History of another malignancy or concurrent malignancy including prior malignant melanoma. Exceptions to this include: Patients who have been disease-free for 5 years or patients with a history completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible, for example cervical cancer in situ, atypical melanocytic hyperplasia or melanoma in situ, multiple primary melanomas, or other malignancies for which the patient has been disease free for > 5 years.
  -  History or current evidence of cardiovascular risk.
  -  History or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR)

Relevance to patient case: not relevant
Patient case: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

Clinical trial: Impact of BRAFV600E Intratumor Heterogeneity in Thyroid Cancer Treated With Tyrosine Kinase Inhibitors

Summary: -  Background: BRAFV600E is the most frequent oncogene in differentiated thyroid cancer (DTC) occurring in about 50% of cases. Clinical trials with tyrosine kinase inhibitors (TKI) with specific activity against BRAF in metastatic radioiodine-resistant DTC (MRR-DTC) are ongoing. Very recently it has been demonstrated that DTC often consists of a mixture of tumor cells with wild-type and mutant BRAF. The subclonal occurrence of BRAFV600E in MRR-DTC could disable the therapy with BRAF targeted TKI and be responsible of the frequent defeats of this treatment. A therapeutic strategy based upon BRAF inhibitors in tumors bearing subclonal BRAFV600E could be initially successful hitting the tumor cells expressing the oncogene, and after the initial tumor growth arrest and/or shrinkage, the oncogene negative cells insensitive or less sensitive to the treatment, could restart the growth of the tumor causing the progression of the disease and the escape from the clinical response.
  -  Aims: To determine the impact of subclonal BRAFV600E on the efficacy of BRAF inhibitors in the treatment of MRR-DTC.
  -  Study design: Primary tumor tissues will be analyzed for the presence of BRAFV600E by pyrosequencing or other quantitative assay. If available, synchronous metastases and post-therapy metachronous metastases will be analyzed as well. The clinical response will be determined according to RECIST, and the association with the percentage of BRAFV600E alleles will be evaluated. Attention will be paid to the possible difference of BRAFwild-type/BRAFV600E ratio between primary tumors and synchronous metastases, primary tumors and post-therapy metachronous metastases, and between responsive and resistant synchronous tumor lesions.


Eligibility: Inclusion Criteria:
  -  subjects any sex any age with metastatic or unresectable thyroid carcinoma treated with tyrosine kinase inhibitors
  -  evidence of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST)
  -  availability of study end points including best response, duration of response, and time to disease progression (based on RECIST), clinical progression, or death
  -  availability of tumor tissue samples, frozen or formaldehyde fixed-paraffin embedded from block, genomic DNA already extracted from tumor tissue
  Exclusion Criteria:
  -  concurrent Hashimoto's thyroiditis

Relevance to patient case: not relevant