araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 64-year-old male with head and neck squamous cell carcinoma; genetic feature: CDKN2A

Clinical trial: Randomized Phase II Study of DCE-MRI-based Dose Escalation for Poor-prognosis and Neck Cancer

Summary: This study aims to improve locoregional control of poor prognosis Head and Neck Cancer (HNC) patients by selectively escalating the radiotherapy dose to subvolumes of tumor likely to be resistant to standard Radiation Therapy (RT) using DCE-MRI (Dynamic Contrast Enhanced Magnetic Resonance Imaging). Standard doses of radiotherapy to the rest of the tissues and surrounding normal tissues will be maintained.


Eligibility: Inclusion Criteria:
  -  Patients must have pathologically‐confirmed, previously untreated, non‐metastatic locally/regionally advanced squamous cell carcinoma of the head and neck, stage III/IV, referred for definitive chemo‐RT, and meet one of the following six criteria:
  1. Primary tumor and/or metastatic lymph nodes are: unresectable, resection is considered by the treating surgeon or patient to result in unacceptable functional or oncological results, patient refuses surgery, or surgery is not possible due to comorbidities.
  2. HPV(‐) (Human Papillomavirus) or p16(-) locally/regionally advanced (T3‐4 or N2‐3) oropharyngeal cancer.
  3. HPV(+) or p16(+) locally/regionally advanced (T4 or N3) oropharyngeal cancer with >10 pack year smoking history.
  4. T3 or T4 laryngeal or hypopharyngeal cancer that is locally advanced, bulky (>30 cc*), unresectable, or patient declines surgery.
  5. Stage III/IV oral cavity or paranasal sinus cancers in patients who refuse surgery or are unfit for surgery.
  6. Locally/regionally advanced (stage T3‐4 and/or N3) nasopharyngeal cancer which is EBV (‐) (Epstein‐Barr Virus).
  -  KPS (Karnofsky Performance Status: A measure of general well being and activities of daily living; scores range from 0 to 100 where 100 represents perfect health) >70 (see Appendix A) within two weeks of enrollment.
  -  Pre‐treatment laboratory criteria within four weeks of enrollment:
  -  WBC (White Blood Cell) > 3500/ul, granulocyte > 1500/ul.
  -  Platelet count > 100,000/ul.
  -  Total Bilirubin < 1.5 X ULN.
  -  AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase) < 2.5 X ULN.
  -  Estimated Creatinine clearance >30cc/min.
  -  Patients must be able to receive protocol chemotherapy in the judgment of the treating Medical Oncologist.
  -  Patients are adults (Age >18).
  -  All patients must be informed of the investigational nature of this study and given written informed consent in accordance with institutional and federal guidelines.
  Exclusion Criteria:
  -  EBV (+) Nasopharyngeal Carcinoma.
  -  Prior head and neck radiation.
  -  Documented evidence of distant metastases.
  -  Patients with active infection.
  -  Pregnant women.
  -  Patients should have no contraindications to having a contrast enhanced MRI scan. These contraindications will be assessed at the time of enrollment using the guidelines set up and in clinical use by the Institutional Standard Practice.

Relevance to patient case: not relevant
Patient case: 64-year-old male with head and neck squamous cell carcinoma; genetic feature: CDKN2A

Clinical trial: Assessing Tumor Response and IMRT Treat Plan After IC Based on FDG-PET/CT for Locally Advanced HNSCC

Summary: To evaluate the safety and efficacy of cisplatin plus intensity-modulated radiotherapy (IMRT) based on FDG-PET/CT after induction chemotherapy (IC) for locally advanced head and neck squamous cell carcinoma.

Detailed description: Current guidelines define that pre-IC target volumes must be used for radiotherapy (RT) planning. This prospective, phase II trial assessed the results of patients with locally advanced squamous cell carcinoma of head and neck treatment with IC following by chemoradiotherapy (CRT), using post-IC PET/CT images for IMRT planning.

Eligibility: Inclusion Criteria:
  -  Male or female patients aged 18 years or over;
  -  Histologically confirmed locally advanced (stage III and IV) head and neck squamous cell carcinoma (HNSCC);
  -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
  -  Signed written informed consent approved by the Lithuanian Bioethics Committee (LBEC);
  Exclusion Criteria:
  -  Positive serum pregnancy test in women of childbearing potential or breastfeeding;
  -  Presence of distant metastasis;
  -  Second primary tumor;
  -  History of other malignancy within the last 5 years;
  -  Recurrent head and neck cancer;
  -  Serious uncontrolled concomitant disease that would contraindicate the use of any drugs use in this study as chemotherapy or radiotherapy; ;
  -  Inadequate organ function, evidenced by the following laboratory results:
  1. Absolute neutrophil count <1,500 cells/mm3;
  2. Platelet count <100,000 cells/mm3;
  3. Hemoglobin <9 g/dL;
  4. Total bilirubin greater than the upper limit of normal (ULN);
  5. AST (SGOT) or ALT (SGPT) >1,5 x ULN;
  6. Alkaline phosphatase levels >2,5 x the ULN;
  7. Serum creatinine >2,0 mg/dl or 177 umol/l.

Relevance to patient case: not relevant
Patient case: 64-year-old male with head and neck squamous cell carcinoma; genetic feature: CDKN2A

Clinical trial: Lavage of the Uterine Cavity for the Diagnosis of Ovarian and Tubal Carcinoma and Their Premalignant Changes.

Summary: Epithelial Ovarian cancer (EOC) is the leading cause of death among gynaecologic malignancies in western civilized countries, with an estimated prevalence in Europe and the US of 752,600 in 2007 and 59,828 deaths annually.
  State-of-the-art diagnostic tests for EOC include transvaginal ultrasonography and serum cancer antigen (CA-125) measurements; the specificity of these diagnostic tools however is low, and both tests are not effective enough at detecting EOC early enough to improve clinical outcomes. Definitive diagnosis of EOC still relies on histological or cytological confirmation. These findings underline the importance for an effective test for early detection of EOC.
  In the current project we will obtain a lavage of the uterine cavity. It will be investigated whether cells from EOCs or genetic material from those cells can be detected in the lavage fluid.
  Aim of this study:
  There is a clear clinical need for a diagnosis test to detect EOC at an earlier stage.

Detailed description: Epithelial Ovarian cancer is the leading cause of death among gynaecologic malignancies in western civilized countries, with an estimated prevalence in Europe and the US of 752,600 in 2007 and 59,828 deaths annually. Treatment and survival of the patients depend primarily on the stage of the disease. Of all EOC patients only 25% are diagnosed at an early stage while the tumour is confined to the pelvis. In these cases the five-year survival rate is 80% to 90% and the disease can often be cured by the combination of surgery and chemotherapy. Unfortunately, almost 75% of women affected have advanced stage disease with metastatic spread throughout the abdominal cavity or to retroperitoneal lymph nodes at the time of diagnosis; five-year survival rates drop to 10%-30% for advanced disease, despite maximum surgical effort and combination chemotherapy.
  State-of-the-art diagnostic tests for EOC include transvaginal ultrasonography and serum cancer antigen (CA-125) measurements; the specificity of these diagnostic tools however is low, and both tests are not effective enough at detecting EOC early enough to improve clinical outcomes. Definitive diagnosis of EOC still relies on histological or cytological confirmation. These findings underline the importance for an effective test for early detection of EOC.
  In the current project we will obtain a lavage of the uterine cavity. It will be investigated whether cells from EOCs or genetic material from those cells can be detected in the lavage fluid.
  Aim of this study:
  There is a clear clinical need for a diagnosis test to detect EOC at an earlier stage.

Eligibility: Inclusion Criteria:
  -  suspected ovarian cancer
  -  verified ovarian cancer
  Exclusion Criteria:
  -  pregnant
  -  incapacitated persons

Relevance to patient case: not relevant
Patient case: 64-year-old male with head and neck squamous cell carcinoma; genetic feature: CDKN2A

Clinical trial: Progressive Resistance Training Program in Head and Neck Cancer Patients

Summary: The purpose of this study is to evaluate the feasibility of a 12-week progressive resistance training (PRT) during concurrent chemoradiotherapy in head and neck cancer patients compared to usual care.

Detailed description: 12 patients with head and neck cancer will be recruited to this trial. Entering a 12-week PRT program which will start one week before radiotherapy. The tested training program is a 12-week, supervised, group based, progressive resistance training program involving the major muscle groups of the body. The program has previously been found to successfully restore the loss of lean body mass (LBM) in head and neck cancer patients post-treatment. A group based approach will be used to facilitate a social and motivating training environment for the patients. This approach has previously been used for exercise interventions for lung cancer patients at our facility, and was highly appreciated by the patients.
  In addition to baseline data (height, tumor stage, performance status, etc), the following parameters will be registered on a weekly basis: Weight, patient reported side effects, as well as a questionnaire on amount of physical activity and food intake.
  Physical function and strength will be tested at baseline, after the course of chemoradiotherapy and at the end of the 12-week PRT programme, and at 2, 5, 9 and 13 months follow-up. At similar time points dual energy x-ray absorptiometry (DXA) scans for body composition will be performed using a Lunar iDXA (GE Healthcare).
  Blood samples will be drawn at baseline, an additional three times during the first 6 weeks and then weekly in relation to training sessions, and at 2, 5, 9 and 13 months follow-up.
  Patient reported quality of life (EORTC Quality of Life Questionaire (QLQ)-C30 and QLQ-H&N35) will be registered at baseline, after 12-weeks PRT and during 5 and 13 months follow-up.
  Study duration is expected to be 7 months for the pilot-trial, with a follow-up of additional 13 months after the last patient has completed the intervention.

Eligibility: Inclusion Criteria:
  -  Patients with head and neck squamous cell carcinoma
  -  Candidates for concomitant chemoradiotherapy according to Danish Head and Neck Cancer Group (DAHANCA) guidelines.
  -  Performance status 0-1
  -  Expected to be able to complete the intervention, i.e. no major comorbidities or social issues that could compromise attendance.
  -  At least 18 years of age.

Relevance to patient case: not relevant
Patient case: 64-year-old male with head and neck squamous cell carcinoma; genetic feature: CDKN2A

Clinical trial: Study of HPV Specific Immunotherapy in Patients With HPV Associated Head and Neck Squamous Cell Carcinoma

Summary: This is a Phase I/IIa, open-label study to evaluate the safety, tolerability, and immunogenicity of INO-3112 DNA vaccine delivered by Electroporation to subjects with HPV associated head and neck squamous cell cancer.

Detailed description: This is a Phase I/IIa, open-label, study to evaluate the safety, tolerability, and immunogenicity of INO-3112 [6 mg of VGX-3100 (2 separate DNA plasmids respectively encoding E6 and E7 proteins of HPV 16 and HPV 18) and 1 mg of INO-9012 (DNA plasmid encoding human interleukin 12)] delivered by electroporation (EP) in up to 25 (twenty five) subjects with HPV positive head and neck cancer. The immunotherapy will be studied in following two groups of subjects:
  1. Subjects who will receive immunotherapy before and after definitive surgery (Cohort I)
  2. Subjects who will receive immunotherapy at least 2 months after chemoradiation therapy (Cohort II).

Eligibility: Inclusion Criteria:
  1. Signed and dated written Ethics Committee approved informed consent.
  2. Age ≥18 years.
  3. Histologically confirmed HPV-positive (as assessed by p16 IHC or oncogenic HPV ISH or PCR) mucosal squamous cell head and neck cancer:
  -  For pre-surgical subjects, p16 positivity must be confimed prior to first dose
  -  For subjects post-chemoradiation, HPV 16 and HPV 18 positivity must be confirmed prior to first dose.
  4. Adequate bone marrow, hepatic, and renal function. ANC (Absolute Neutrophil Count) ≥ 1.5x109 cell/ml, platelets ≥75,000 cells/mm3, hemoglobin ≥9.0 g/dL, concentrations of total serum bilirubin within 1.5 x upper limit of normal (ULN), AST, ALT within 2.5x institutional ULN, CPK within 2.5 x ULN.
  5. ECOG (Eastern Cooperative Oncology Group) performance status of 0-1.
  Exclusion Criteria:
  1. Anticipated concomitant immunosuppressive therapy (excluding non-systemic inhaled, topical skin and/or eye drop-containing corticosteroids).
  2. Any concurrent condition requiring the continued use of systemic steroids (>10 mg prednisone or equivalent per day) or the use of immunosuppressive agents. All other corticosteroids must be discontinued at least 4 weeks prior to Day 0 of treatment.
  3. Administration of any vaccine within 6 weeks of enrollment.

Relevance to patient case: definitely relevant
Patient case: 64-year-old male with head and neck squamous cell carcinoma; genetic feature: CDKN2A

Clinical trial: Window Trial 5-aza in HNSCC, T-tare

Summary: The purpose of this study is to assess the activity of 5-azacitidine in patients with Human Papilloma Virus (HPV)-positive and HPV- negative head and neck squamous cell carcinoma (HNSCC). The response activity will be determined by analyzing your tumor tissue prior to and after treatment with 5-azacitidine. Preliminary studies in mice bearing human head and neck cancers or head and neck cancer cells cultured in laboratories suggest that treatment with 5-azacitidine increases changes in cancer cells that lead to their death. This study is designed to determine if similar changes occur in cancer cells of patients with head and neck cancer.
  The study also aims to determine the amount of a specific type of protein, p53 before and after treatment. Research has shown that the p53 protein is associated with anti-tumor activity.
  Finally, this study is measuring the amount of a specific type of protein called interferon in your tumor tissue. Interferons are proteins made and released by the body in response to pathogens (disease causing agents) such as viruses, bacteria, or tumor cells. Interferons allow for communication between cells to trigger the protective defenses of the immune system that remove pathogens (disease causing agents) or tumors.

Detailed description: Primary Objectives:
  The primary objectives of this study are
  • to investigate response (proliferation, apoptosis), as well as reactivation of p53 pathways in patients treated with 5-azacitadine for HPV-positive and HPV-negative HNSCC.
  Secondary Objectives
  The secondary objectives of this study are:
  -  to investigate response (proliferation, apoptosis), as well as reactivation of IFN pathways in patients treated with 5-azacitadine for HPV-positive and HPV-negative HNSCC.
  -  to investigate the clinical activity of 5-azacitadine in patients with HPV-positive and HPV-negative HNSCC.
  -  to investigate the safety of 5-azacitadine in patients with HPV-positive and HPV-negative HNSCC

Eligibility: Inclusion Criteria:
  1. Histologically confirmed HNSCC with surgically resectable disease
  2. Age ≥18 years of age.
  3. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2
  4. ANC greater than or equal to 1500, Hb greater than or equal to 8, platelet count greater than or equal to 100,000
  Exclusion Criteria:
  1. AST or ALT greater than 2.5 x ULN
  2. Known brain metastases
  3. Women must not be pregnant or breastfeeding
  4. Known allergy to 5-azacitadine
  5. Patients receiving any other investigational agents within 4 weeks of starting the study

Relevance to patient case: definitely relevant
Patient case: 64-year-old male with head and neck squamous cell carcinoma; genetic feature: CDKN2A

Clinical trial: LEE011 for Patients With CDK4/6 Pathway Activated Tumors (SIGNATURE)

Summary: The purpose of this signal seeking study is to determine whether treatment with LEE011 demonstrates sufficient efficacy in CDK4/6 pathway activated solid tumors and/or hematologic malignancies to warrant further study.


Eligibility: Inclusion Criteria:
  -  Patient has a confirmed diagnosis of a select solid tumor (except breast cancer (however, triple negative will be included), liposarcoma, CRPC, melanoma and teratoma) or hematological malignancy (except mantle cell lymphoma).
  -  Patient must have been pre-identified as having a tumor with CDK4 amplification or mutation, CDK6 amplification or mutation, Cyclin D1 (CCND1) amplification, Cyclin D3 (CCND3) amplification, or p16 (CDKN2A) mutation
  -  Patient has received at least one prior treatment for recurrent, metastatic and /or locally advanced disease and for whom no standard therapy options are anticipated to result in a durable remission.
  -  Patient has progressive and measurable disease as per RECIST 1.1. or other appropriate hematological guidelines.
  -  Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  Exclusion Criteria:
  -  Patients has received prior treatment with LEE011.
  -  Patient has clinically significant resting bradycardia (heart rate < 50 at rest), tachycardia (heart rate > 90 at rest), PR interval > 220 msec, QRS interval > 109 msec, or QTcF > 450 msec.
  -  Patients has primary CNS tumor or CNS tumor involvement
  -  Patient has received chemotherapy or anticancer therapy ≤ 4 weeks prior to starting study drug

Relevance to patient case: possibly relevant
Patient case: 64-year-old male with head and neck squamous cell carcinoma; genetic feature: CDKN2A

Clinical trial: Multibending vs Conventional Endoscope for Direct Peroral Cholangioscopy

Summary: The aim of this study is to evaluate the usefulness of a newly developed multibending ultra-slim upper endoscope for the successful direct peroral cholangioscopy (POC) without assisting accessory in comparison with conventional ultra-slim endoscope. The investigators expect that multibending endoscope will show more higher successful performance than conventional endoscope.

Detailed description: Direct POC using an ultra-slim upper endoscope permits various diagnostic and/or therapeutic intraductal interventions under direct endoscopic visualization in selected patients who has dilated distal CBD and widened papillary orifice. Because the bile duct has anatomical position in acute angle with the duodenum, assisting accessories such as intraductal anchoring balloon, guidewire or overtube is usually required for the successful direct POC. Recently, direct peroral cholangioscopes have been developed for free-hand direct advancement of the endoscope into the bile duct from duodenum. Multibending ultra-slim endoscope may be expected to facilitate the advance into the bile duct by overcoming the acute angle between the bile duct and the duodenum. After randomization of enrolled patients into two groups, direct POC will be performed by using a conventional slim endoscope in control group and by using a multibending endoscope in study group.

Eligibility: Inclusion Criteria:
  -  Pancreatobiliary diseases that are indicated for direct POC
  -  The patient who aged from 20 to 80 years. Legally acceptable representative must be capable of giving written informed consent prior to participation in this study
  -  The woman of child-bearing age must be negative from the pregnancy test in order to participate in this study
  -  Dilated common bile duct (> 8 mm)
  -  Having previous sphincterotomy and/or papillary balloon dilation
  -  The patients should not have any unacceptable conditions (e.g., physiological, familyish, social, geographical) for medical follow-up and adaptation of the study.
  Exclusion Criteria:
  -  Contraindicated for ERCP
  -  Patients with stricture on papillary orifice
  -  Patients with periampullary malignancy
  -  Bleeding tendency: International normalized ratio (INR) of prothrombin time < 1.5 or platelet count < 60,000/mm3
  -  Patients with other serious disease or medical condition
  -  Patients with past medical history of significant neurologic or Psychiatric disorders such as dementia or seizure
  -  Unstable heart disease despite of treatment, recent myocardial infarction within 6 month (Even though MI was diagnosed within 6 months, if it becomes stable presently, the patient can be possible to participate).

Relevance to patient case: not relevant
Patient case: 64-year-old male with head and neck squamous cell carcinoma; genetic feature: CDKN2A

Clinical trial: Phase I-II Study With Tumor Molecular Pharmacodynamic (MPD) Evaluation and Pharmacokinetics of PD-0332991 in Patients Suffering Metastatic Melanoma

Summary: An open label multicentre, phase I-II study with tumour molecular pharmacodynamics (MPD) evaluation and pharmacokinetics of PD-0332991 added to vemurafenib in patients suffering metastatic melanoma with BR.
  The main objective is to establish the Maximum Tolerated Dose (MTD) of PD-0332991 when added to standard vemurafenib therapy (960 mg BID). The estimated MTD is defined as the dose of PD-0332991 combined with vemurafenib that will be associated with a prespecified proportion of patients experiencing a Dose-Limiting Toxicity (DLT), ie, 1/3.


Eligibility: Inclusion Criteria:
  -  Age > 18 years
  -  Stage IV or un-resectable stage III melanoma
  -  Presence of BRAF V600E/K mutation and CDNKN2A loss and expression of Rb using immunohistochemistry in a recent metastatic sample (< 6 months)
  -  A previous exposure to BRAF inhibitor or combination of BRAF and MEK inhibitors therapy is allowed unless it has been stopped more than 3 months before study enrolment(This will defined the two strata of the trial)
  -  No previous therapy by MEK inhibitor unless associated with BRAF inhibitors
  -  No previous therapy with the AKT/PI3K pathway inhibitor
  -  Patients should have a tumour available for repeated biopsies for pharmacodynamics evaluation
  -  Life expectancy of > 3 months
  -  ECOG performance status <2
  -  Signed informed consent
  -  Patient with health insurance coverage
  -  No patient under guardianship or curators
  Exclusion Criteria:
  -  Inadequate hepatic function defined as serum bilirubin>25 μmol/l, transaminases > 3.0 times the upper limit of normal (ULN) or 5ULN in cases of liver metastases;
  -  Inadequate bone marrow function defined as absolute neutrophil count<1500/mcl, platelets<150000/mcl and haemoglobin<8g/dL
  -  Inadequate renal function with serum creatinine>2.0mg/dl) and /or creatinine clearance< 60 ml/min
  -  Untreated brain metastases : Patients with brain metastases will be eligible if they have completed treatment 1 months prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 5 days, and are neurologically asymptomatic
  -  Myocardial infarct or unstable angina within the past 6 months
  -  Concomitant take of drugs known to be strong inhibitor or inducers of CYP314
  -  HIV positive.
  -  Chemotherapy, immunotherapy within 4 weeks
  -  Drugs interfering with PD-0332991 and vemurafenib metabolism
  -  Malabsorption syndrome or other condition that would interfere with enteral absorption
  -  Congenital long QT syndrome or screening QTc > 470 msec
  -  Need for chronic corticosteroid therapy of ≥10 mg of prednisone per day

Relevance to patient case: not relevant