araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 70-year-old male with melanoma; genetic feature: NF1 truncation

Clinical trial: Efficacy of Chemotherapy Combined With Regional Hypothermia in Advanced Malignant Melanoma Patients With Progressive Soft Tissue Metastases

Summary: The incidence of malignant melanoma continues to rise throughout the world. Approximately 12 in 100,000 Germans are diagnosed with malignant melanoma per year. Malignant melanoma is often very aggressive since it may spread both through the lymphatic system and the bloodstream at an early stage of disease.
  While treatment of localized disease is mostly surgical, in patients with extensive disease, prognosis remains poor; the primary standard therapy of metastastic disease comprises dacarbazine (DTIC) eventually combined with other chemotherapeutic agents e.g., cisplatin or BCNU. The duration of response to systemic chemotherapy is generally short and so far, no standard second-line treatment has been established.
  To study the potential additional therapeutic effects of regional hyperthermia in advanced malignant melanoma patients with progressive chemotherapy refractory soft tissue metastases, in the present trial, we sought to compine local hyperthermia with concomitant systemic second-line chemotherapy.


Eligibility: Inclusion Criteria:
  -  age between 18 and 70
  -  histologically proven malignant melanoma with advanced inoperable soft tissue metastases
  -  progressive disease upon systemic first-line chemotherapy
  -  2 or more bidimensionally measurable soft tisue lesions
  -  WHO performance status (ECOG) of 2 or more
  -  life expectancy of 8 weeks and more
  -  prior informed consent
  Exclusion Criteria:
  -  participation in other therapy studies
  -  pregnancy or breast feeding
  -  concomitant clinically significant infection
  -  cardiac pacemaker or other medical implants, or implants within the hyperthermia treated region (including a safe distance of 5 cm)
  -  lack of physiological heat sensitivity within the hyperthermia treated region (including a safe distance of 5 cm)

Relevance to patient case: not relevant
Patient case: 70-year-old male with melanoma; genetic feature: NF1 truncation

Clinical trial: The Final Diagnosis and Treatment Result of Metastatic Cervical Carcinoma of Unknown Primary

Summary: Investigate the final diagnosis and treatment result of metastatic cervical carcinoma of unknown primary

Detailed description: Carcinoma of unknown primary (CUP) is defined as biopsy-proven metastasis of an epithelial malignancy in the absence of an identifiable primary site after complete history and physical examination, basic laboratory studies, chest X-ray and additional directed studies indicated by positive findings during the initial work-up. It is characterized by its slow local development and its high metastatic potential.1,2 Patients with CUP represent 4–10% of all new cancer patients.3,4 The presenting sites of metastasis identified pathologically, radiographically or by physical examination were found most frequently in the lymph nodes (37.1%), followed by the liver, bone, lung, pleura/pleural space, brain, peritoneum, adrenal and skin. Of the lymph nodes of metastasis, the supraclavicular cervical area is the leading site (31.3%), followed by the mediastinum, axilla, retroperitonium, and inguina.5 The incidence of metastatic cervical CUP (MCCUP) varies between 2% and 9% of all head and neck cancers.6-8 The level of cervical metastatic involvement may give some clue as to the likely primary site. A submandibular mass (level I) would most commonly be related to a primary in the oral cavity or skin. Level II nodes, including the jugulodigastric node, may point to a primary in the oral cavity, oropharynx, or supraglottic larynx. Tumours of the nasopharynx generally spread to level II or the posterior triangle, as well as retropharyngeal nodes. Middle and lower jugular nodes (levels III and IV) are more likely related to a laryngeal or hypopharyngeal cancer. Metastatic disease restricted to the supraclavicular region is often due to an infraclavicular primary site.9 The prognosis is different according to the involved lymph node level and possible primary site. Modern cancer management relies heavily on recognition of the primary tumor; thus the absence of a primary site poses major diagnostic and therapeutic problems. The patient benefits from identification of the initial tumor site because postoperative irradiation ports may be reduced and because surveillance for recurrence may be improved.10 In order to identify the likely primary site of MCCUP and compare the prognoses of known and unknown primary groups, we report the results according to the different levels of metastatic cervical lymph nodes.

Eligibility: Inclusion Criteria:
  -  cases of metastatic cervical carcinoma of unknown primary
  Exclusion Criteria:

Relevance to patient case: not relevant
Patient case: 70-year-old male with melanoma; genetic feature: NF1 truncation

Clinical trial: Neurofibromatosis Type 1 (NF1) and Tibial Dysplasia

Summary: The study is a multicenter four-year outcome study of the natural history of tibial dysplasia in patients with NF1 and selected patients without NF1. We will obtain information on the natural history, burden, functional and health status, health-related quality of life, and surgical interventions/outcomes of tibial dysplasia. The project will also establish a Core Facility (NOCF) for tissue samples for future studies.

Detailed description: The three specific aims of this study are:
  -  Specific Aim 1 - To assess health status and health - related quality of life (HRQL) in 50 children and adolescents with NF1 and tibial dysplasia and in NF1 controls. We hypothesize that children and adolescents with NF1 and tibial dysplasia will experience an additional burden of morbidity due to tibial dysplasia and a downward trajectory of health status and HRQL over time.
  -  Specific Aim 2 - To assess the long term outcome of current treatment in 100 adult patients diagnosed with NF1 and tibial dysplasia in childhood. We hypothesize that better quality of life and function, in adults with NF1 and tibial dysplasia, are associated with amputation in childhood compared to multiple surgical procedures, the lack of fibular involvement, and fracture later in childhood. We also hypothesize that individuals with NF1 and tibial dysplasia have a higher risk of other bony dysplasias but are at no higher risk of fracture in other bones.
  -  Specific Aim 3 - To assess the natural history and short-term response to therapy in a cohort of at least 60 children with NF1 and tibial dysplasia and at least 60 children with tibial dysplasia presumably without NF1 prospectively diagnosed during the course of the four-year study period. We hypothesize that NF1 patients with earlier presentation, Crawford Class II A-C, male gender, and the lack of bracing prior to age two are more likely to fracture. We also postulate that individuals with and without NF1 have a similar outcome and response to treatment.
  The results of this project will provide a rational basis for future clinical and therapeutic trials.

Eligibility: Inclusion Criteria:
  -  Aim 1:
  -  Group 1, NF1 with Tibial Dysplasia, Ages: 3-18
  -  Group 2 (control), NF1 without Tibial Dysplasia, Ages 3-18
  -  Aim 2: NF1 with Tibial Dysplasia, 19+
  -  Aim 3: Tibial Dysplasia with or without NF1, Ages: birth to 18
  -  Tissue procurement, any participant undergoing surgery at the tibial site for routine standard of care
  Exclusion Criteria:
  -  Patients without a diagnosis of NF1 or Tibial Dysplasia

Relevance to patient case: not relevant
Patient case: 70-year-old male with melanoma; genetic feature: NF1 truncation

Clinical trial: A Study to Evaluate RAF265, an Oral Drug Administered to Subjects With Locally Advanced or Metastatic Melanoma

Summary: The purpose of this study is to determine the safety profile, pharmacokinetics, pharmacodynamics and maximum tolerated dose of RAF265 in patients with locally advanced and metastatic melanoma.
  Phase II portion of study (dose expansion) has been cancelled with Amendment 7 as of Dec 2011.

Detailed description: The Ras/Raf/MEK/ERK pathway plays a prominent role in controlling several key cellular functions including growth, proliferation and survival. B-Raf is a member of the Ras/Raf/MEK/ERK pathway and is frequently mutated in melanoma resulting in activation of the MAPK pathway. RAF265 is a novel, orally active, small molecule with potent inhibitory activity against B-Raf kinase and additional antiangiogenic activity through inhibition of vascular endothelial growth factor receptor type 2 (VEGFR-2) in non-clinical studies.
  The primary objectives of this study are to determine the maximum tolerated dose (MTD), dose limiting toxicities (DLTs), and the safety profile of RAF265 when administered orally to subjects with locally advanced or metastatic melanoma; to determine the plasma pharmacokinetics (PKs) of orally administered RAF265; and to evaluate potential pharmacodynamic effects of RAF265 using tumor biopsies, peripheral blood samples, and tumor imaging.

Eligibility: Inclusion Criteria:
  1. Confirmed diagnosis of melanoma, locally advanced AJCC Stage IIIB to metastatic Stage IV
  2. Measurable disease - at least one lesion measured in at least one dimension as ≥ 20 mm with conventional techniques or ≥ 10 mm with spiral computed tomography (CT) scan
  3. ECOG performance status of 0 or 1
  4. No concurrent anticancer or investigational therapy for at least 4 weeks prior to enrollment
  5. No major surgery for at least 4 weeks prior to enrollment
  Exclusion Criteria:
  1. Significant cardiac disease or other significant medical/psychiatric disease
  2. History of primary central nervous system tumor or brain metastases onths
  3. History of melena, hematemesis, or hemoptysis within the last 3 months
  4. Previous therapy with certain molecularly targeted agents

Relevance to patient case: not relevant
Patient case: 70-year-old male with melanoma; genetic feature: NF1 truncation

Clinical trial: Bevacizumab, Dacarbazine and Interferon-Alfa to Treat Metastatic Melanoma

Summary: The purpose of this study is to determine whether combination therapy with bevacizumab (Avastin), dacarbazine and interferon-alfa-2a (Roferon-A) is effective in patients with locally advancing or metastatic melanoma.

Detailed description: Dacarbazine (DTIC) has been approved for treating metastatic melanoma in the 1970s, and after that numerous schedules and dacarbazine-based combinations have been studied in this disease. DTIC as a single agent gives a response rate of only 20%, but there have been efforts to improve this poor result by using DTIC in different combinations.Treatment of melanoma with combination chemotherapy and interferon-α (IFN-α) has given 50-60% response rates,but increase in the overall survival time has not been reached in controlled phase III studies. Thus, standard reference therapy in treatment of metastatic melanoma still is single dacarbazine or its combination with s.c. IFN-α. In addition, new studies with melanoma cells in vitro show that dacarbazine causes transcriptional up-regulation of vascular endothelial growth factor (VEGF), suggesting a potential clinical benefit of combination of DTIC and anti-VEGF therapy. IFN-α has been used in adjuvant therapy and in treatment of metastatic melanoma. IFN-α exerts its effects through antiproliferative, apoptosis-inducing and particularly antiangiogenic effects in addition to immunologic modulation.
  The purpose of this study is to determine whether combination therapy with bevacizumab (Avastin), dacarbazine and interferon-alfa-2a (Roferon-A) can increase progression-free survival and overall survival in patients with locally advancing or metastatic melanoma.

Eligibility: Inclusion Criteria:
  -  histologically confirmed malignant melanoma either locally progressing inoperable or metastatic
  -  measurable/evaluable disease in accordance with RECIST criteria
  -  WHO performance status 0-2
  -  normal organ function
  -  signed written informed consent
  Exclusion Criteria:
  -  unevaluable disease
  -  major surgery within 28 days prior to day 0
  -  uncompleted radiotherapy
  -  CNS metastases
  -  serious non-healing wound or ulcer
  -  bleeding diathesis or coagulopathy
  -  uncontrolled hypertension
  -  clinically significant cardiovascular disease
  -  depression or psychosis, which needs medication
  -  ongoing treatment with aspirin (>325 mg/day)
  -  pregnancy
  -  any other serious or uncontrolled illness
  -  previous chemotherapy for metastatic melanoma

Relevance to patient case: not relevant
Patient case: 70-year-old male with melanoma; genetic feature: NF1 truncation

Clinical trial: The Influence of the 34C>T Variant in the AMPD1 Gene Ischemic Tolerance

Summary: Previous epidemiological studies have shown that in cardiovascular patients, the 34C>T variant in the gene encoding for the enzyme Adenosine Mono Phosphate Deaminase (AMPD1) is associated with prolonged survival.
  The 34 C>T variant encodes a severely truncated, metabolically inactive protein. We hypothesize that during ischemia, in these patients AMP in preferentially converted into adenosine instead of IMP. Adenosine receptor stimulation, in turn, will increase resistance to ischemia-reperfusion in the myocardial tissue.
  To test this hypothesis, 7 male healthy volunteers heterozygous for the 34C>T variant will be selected from 100 healthy volunteers, which we have previously genotyped. These subjects will be compared with 7 matched control subjects. Individual ischemic tolerance will be assessed in the thenar muscle using 99mTc-Annexin A5 scintigraphy.
  Briefly, the circulation of the nondominant forearm will be interrupted for 10 minutes by inflation of an upperarm cuff to 200mmHg en concomitantly, the subjects will perform isometric rhythmic handgripping until exhaustion. Immediately upon reperfusion, 400 MBq of 99mTc-Annexin A5 will be administered intravenously. Finally, 1 and 4 hours post-injection, scintigrapghi imaging of both hand will be performed. Targeting of annexin A5 will be expressed as percentage difference between the experimental and control hand.


Eligibility: Inclusion Criteria:
  -  male
  -  18-40 years
  -  healthy
  -  AMPD1 34C>T variant (heterozygous) or matched control
  Exclusion Criteria:
  -  cardiovascular / pulmonary disease
  -  diabetes / hypertension

Relevance to patient case: not relevant
Patient case: 70-year-old male with melanoma; genetic feature: NF1 truncation

Clinical trial: Observational Safety Study of Etanercept (Enbrel) for Treatment of Psoriasis

Summary: This is an observational safety study tracking psoriasis patients on etanercept (Enbrel) for 5 years.

Detailed description: This is a prospective, multi-center, observational surveillance registry to evaluate data on the long-term safety of etanercept (Enbrel) use in the treatment of psoriasis.

Eligibility: Inclusion Criteria:
  -  Patients with plaque psoriasis
  Exclusion Criteria:
  -  Prior exposure to any tumor necrosis factor (TNF)-inhibitor
  -  Patients for whom Enbrel is contraindicated
  -  Patients currently enrolled in or has not yet completed at least 30 days since ending other investigational drug study.

Relevance to patient case: not relevant
Patient case: 70-year-old male with melanoma; genetic feature: NF1 truncation

Clinical trial: Genetic Analysis of Familial Melanoma

Summary: In collaboration with members of The International Melanoma Consortium, we propose to study melanoma in families lacking mutations in the cyclin-dependent kinase inhibitor 2 (CDKN2 or p16) gene, or the cyclin-dependant kinase 4 (CDK4). CDKN2 and CDK4 are both genes that encode presumed tumor suppressor genes, mutant forms of which are known to cause increased susceptibility to melanoma. The purpose of the present study then is to confirm the existence of and to identify additional gene(s) involved in heritable melanoma (cutaneous and ocular) and their precursor lesions (atypical nevi) by linkage analysis and gene mapping strategies. It is clear that the risk to develop atypical nevi and/or melanoma is strongly influenced by genetic and environmental factors (e.g. sun exposure). Characterization of such genes could provide important insights into the inheritance, pathogenesis, and treatment of this increasingly important disease.

Detailed description: In collaboration with members of The International Melanoma Genetics Consortium, we propose to study melanoma in families lacking mutations in the cyclin-dependent kinase inhibitor 2 (CDKN2A), or the cyclin-dependant kinase 4 (CDK4) genes. CDKN2 and CDK4 are both genes that encode presumed tumor suppressor genes, mutant forms of which are known to cause increased susceptibility to melanoma. The purpose of the present study then is to confirm the existence of and to identify additional gene(s) involved in heritable melanoma (cutaneous and ocular) and their precursor lesions (atypical nevi) by linkage analysis and gene mapping strategies. It is clear that the risk to develop atypical nevi and/or melanoma is strongly influenced by genetic and environmental factors (e.g. sun exposure). Characterization of such genes could provide important insights into the inheritance, pathogenesis, and treatment of this increasingly important disease.

Eligibility: -  INCLUSION CRITERIA:
  Inclusion into this study was restricted to families containing at least three CMM cases with DNA available for genotyping, and CDKN2A and CDK4 involvement and had been excluded.
  All families must be mutation negative for both CDKN2A and CDK4.
  This study will also include families with at least one case of ocular and two cases of other cutaneous melanomas, or at least 2 ocular melanomas (except where they occur in parent and child).
  EXCLUSION CRITERIA:
  Any family showing evidence of haplotype sharing in the 9p21-p22 region, where CDKN2A is located, was also excluded.

Relevance to patient case: not relevant
Patient case: 70-year-old male with melanoma; genetic feature: NF1 truncation

Clinical trial: Cytogenetic Study of Ocular Melanoma

Summary: Patients who are diagnosed with choroidal melanoma and undergo I-125 plaque or enucleation surgery consent to participate in the study. A tumor sample taken during surgery is studied in the lab for genetic features. These features and features of subjects' clinical course are recorded. Analysis of the data may identify genetic features that are indicative of prognostic factors including risk of metastasis.

Detailed description: The Jules Stein Eye Institute Ocular Melanoma Research Group is conducting cytogenetic studies of choroidal melanoma to improve the screening of biopsy samples of choroidal melanoma through cytogenetic analysis. Our goal is to identify molecular probes that specifically target regions of chromosomes that undergo changes characteristic of metastatic choroidal melanoma.

Eligibility: Inclusion Criteria:
  1. Patient with diagnosis of ocular melanoma
  2. Patient with local treatment plan for ocular melanoma- plaque brachytherapy or enucleation
  3. Patient 18 years of age or older
  4. Archival enucleation specimens with diagnosis of ocular melanoma
  Exclusion Criteria:
  1. Patient who refuses local melanoma treatment
  2. Patient who refuses to participate in this study

Relevance to patient case: not relevant
Patient case: 70-year-old male with melanoma; genetic feature: NF1 truncation

Clinical trial: Melanoma Biomarker Study

Summary: The purpose of this study is to measure the level of a specific protein, CXCL1, in the blood of patients with untreated, metastatic (Stage IV) melanoma. These levels will be compared to blood levels in normal controls. If the levels are elevated in metastatic melanoma, further studies to determine if this correlates with presence and extent of disease will be pursued.

Detailed description: Malignant Melanoma has rapidly increased in incidence over the past thirty years, at a rate of roughly 3% per year. In 2005, approximately 59,000 new cases of melanoma were diagnosed with 8000 deaths. While the majority of early melanomas can be surgically cured, advanced melanoma has an extremely poor prognosis. Current chemotherapy and immunotherapy options for advanced melanoma still offer response rates of only 10-20%. Thus, the elucidation of biomarkers in melanoma, both diagnostic and prognostic, is an important area for investigation.
  CXCL1 is a chemokine whose expression is upregulated in melanoma. We postulate that CXCL1 plays an important role in the progression of melanoma to invasive disease. Our hypothesis states that serum CXCL1 levels correlate with the presence of melanoma.
  Aims:
  1. To measure serum levels of CXCL1 in untreated, metastatic melanoma patients and to compare to serum CXCL1 levels in normal controls.
  2. To measure and compare centrally and peripherally collected serum CXCL1 levels in untreated, metastatic melanoma.
  Blood will be collected from metastatic melanoma patients on one occasion, both peripherally and centrally. Control will have blood collected peripherally on one occasion. The blood will be processed and then tested in a blinded, batched fashion.

Eligibility: Inclusion Criteria:
  1. Histologic diagnosis of melanoma; primary may be cutaneous, mucosal or ocular.
  2. Evidence of metastatic disease based on standard AJCC staging.
  3. Willing to give written informed consent.
  4. Willing and able to comply with protocol procedures.
  5. At least 18 years of age.
  6. No prior chemotherapy, immunotherapy, or radiotherapy.
  7. Are able to safely donate 50 mL of blood.
  8. Have a central venous catheter in place (this will not be placed for participation in this trial)
  Exclusion Criteria:
  1. Known diagnosis of a chronic inflammatory disease, ie: Rheumatoid Arthritis, Systemic Sclerosis, Inflammatory bowel disease
  2. Known diagnosis of NYHA class 3 or 4 Congestive Heart Failure
  3. Are unable to safely donate 50 mL blood
  4. Known HIV, Hepatitis B, or Hepatitis C infection.
  5. Any malignancy within 5 years, other than melanoma (for patients); Have any malignancy within the past 5 years including melanoma (for normal controls). Basal cell and squamous cell skin cancers are permitted in all participants.

Relevance to patient case: not relevant