{
  "status_code": 200,
  "request": {
    "papers": [
      {
        "id": "5",
        "title": "The NEXT-1 (Next generation pErsonalized tX with mulTi-omics and preclinical model) trial: prospective molecular screening trial of metastatic solid cancer patients, a feasibility analysis.",
        "abstract": "We conducted a prospective genomic screening trial with high throughput sequencing and copy number variation (CNV) assay, and immunohistochemistry array in metastatic solid cancer patients. We used Ion AmpliSeq Cancer Hotspot Panel v2 and nCounter Copy Number Variation Assay (21 genes) to identify molecular targets for potential matched therapy. Metastatic solid tumor patients were prospectively consented for molecular profiling tests. The primary outcome for this trial was the feasibility of molecular tests and response rate (matched vs non-matched treatment). Between November 2013 and August 2014, a total of 428 metastatic solid tumor patients were enrolled on to this study. The mutational profiles were obtained for 407 (95.1%) patients. CNV 21-gene assays were successfully performed in 281 (65.7%) of 428 patients. Of the 407 patients with molecular profiling results, 342 (84.0%) patients had one or more aberrations detected. Of the 342 patients, 103 patients were matched to molecularly targeted agents in the context of clinical trials or clinical practice. The response rate was significantly higher in the genome-matched treated group for gastrointestinal/hepatobiliary/rare tumors (matched vs non-matched treatment, 42.6% vs 24.3%, P = .009) and lung cancer cohort (matched vs non-matched treatment, 61.2% vs 28.6% < P = .001) when compared with the non-matched group. In this trial, we demonstrate that genome-matched treatment based on molecular profiling result in better treatment outcome in terms of response rate.",
        "citation": "Kim ST, Lee J, Hong M, Park K, Park JO, Ahn T, Park SH, Park YS, Lim HY, Sun JM, Ahn JS, Ahn MJ, Kim HC, Sohn TS, Choi DI, Cho JH, Heo JS, Kwon W, Uhm SW, Lee H, Min BH, Hong SN, Kim DH, Jung SH, Park W, Kim KM, Kang WK, Park K. (2015). The NEXT-1 (Next generation pErsonalized tX with mulTi-omics and preclinical model) trial: prospective molecular screening trial of metastatic solid cancer patients, a feasibility analysis. Oncotarget. 6(32):33358-68. http://doi.org/10.18632/oncotarget.5188. PMID: 26396172."
      },
      {
        "id": "8",
        "title": "Precision Oncology: The UC San Diego Moores Cancer Center PREDICT Experience.",
        "abstract": "By profiling their patients' tumors, oncologists now have the option to use molecular results to match patients with drug(s) based on specific biomarkers. In this observational study, 347 patients with solid advanced cancers and next-generation sequencing (NGS) results were evaluated. Outcomes for patients who received a \"matched\" versus \"unmatched\" therapy following their NGS results were compared. Eighty-seven patients (25%) were treated with a \"matched\" therapy, 93 (26.8%) with an \"unmatched\" therapy. More patients in the matched group achieved stable disease (SD) \u2265 6 months/partial response (PR)/complete response (CR), 34.5% vs. 16.1%, (P \u2264 0.020 multivariable or propensity score methods). Matched patients had a longer median progression-free survival (PFS; 4.0 vs. 3.0 months, P = 0.039 in the Cox regression model). In analysis using PFS1 (PFS on the prior line of therapy) as a comparator to PFS after NGS, as expected, the unmatched group demonstrated a PFS2 significantly shorter than PFS1 (P = 0.009); however, this shortening was not observed in the matched patients (P = 0.595). Furthermore, 45.3% of the matched patients (24/53) had a PFS2/PFS1 ratio \u22651.3 compared with 19.3% of patients (11/57) in the unmatched group (P = 0.004 univariable and P \u2265 0.057 in multivariable/propensity score analysis). Patients with a \"matching-score\" (the number of matched drugs divided by the number of aberrations; unmatched patients had a score of zero) > 0.2 had a median overall survival (OS) of 15.7 months compared with 10.6 months when their matching-score was \u2264 0.2, (P = 0.040 in the Cox regression model). Matched versus unmatched patients had higher rates of SD \u2265 6 months/PR/CR and longer PFS, and improvement in OS correlated with a higher matching score in multivariable analysis. Mol Cancer Ther; 15(4); 743-52. \u00a92016 AACR.",
        "citation": "Schwaederle M, Parker BA, Schwab RB, Daniels GA, Piccioni DE, Kesari S, Helsten TL, Bazhenova LA, Romero J, Fanta PT, Lippman SM, Kurzrock R. (2016). Precision Oncology: The UC San Diego Moores Cancer Center PREDICT Experience. Molecular cancer therapeutics. 15(4):743-52. http://doi.org/10.1158/1535-7163.MCT-15-0795. PMID: 26873727."
      },
      {
        "id": "11",
        "title": "Comprehensive Genomic Profiling Identifies Frequent Drug-Sensitive EGFR Exon 19 Deletions in NSCLC not Identified by Prior Molecular Testing.",
        "abstract": "PURPOSE: Reliable detection of drug-sensitive activating EGFR mutations is critical in the care of advanced non-small cell lung cancer (NSCLC), but such testing is commonly performed using a wide variety of platforms, many of which lack rigorous analytic validation. EXPERIMENTAL DESIGN: A large pool of NSCLC cases was assayed with well-validated, hybrid capture-based comprehensive genomic profiling (CGP) at the request of the individual treating physicians in the course of clinical care for the purpose of making therapy decisions. From these, 400 cases harboring EGFR exon 19 deletions (\u0394ex19) were identified, and available clinical history was reviewed. RESULTS: Pathology reports were available for 250 consecutive cases with classical EGFR \u0394ex19 (amino acids 743-754) and were reviewed to assess previous non-hybrid capture-based EGFR testing. Twelve of 71 (17%) cases with EGFR testing results available were negative by previous testing, including 8 of 46 (17%) cases for which the same biopsy was analyzed. Independently, five of six (83%) cases harboring C-helical EGFR \u0394ex19 were previously negative. In a subset of these patients with available clinical outcome information, robust benefit from treatment with EGFR inhibitors was observed. CONCLUSIONS: CGP identifies drug-sensitive EGFR \u0394ex19 in NSCLC cases that have undergone prior EGFR testing and returned negative results. Given the proven benefit in progression-free survival conferred by EGFR tyrosine kinase inhibitors in patients with these alterations, CGP should be considered in the initial presentation of advanced NSCLC and when previous testing for EGFR mutations or other driver alterations is negative. Clin Cancer Res; 22(13); 3281-5. \u00a92016 AACR.",
        "citation": "Schrock AB, Frampton GM, Herndon D, Greenbowe JR, Wang K, Lipson D, Yelensky R, Chalmers ZR, Chmielecki J, Elvin JA, Wollner M, Dvir A, -Gutman LS, Bordoni R, Peled N, Braiteh F, Raez L, Erlich R, Ou SH, Mohamed M, Ross JS, Stephens PJ, Ali SM, Miller VA. (2016). Comprehensive Genomic Profiling Identifies Frequent Drug-Sensitive EGFR Exon 19 Deletions in NSCLC not Identified by Prior Molecular Testing. Clinical cancer research : an official journal of the American Association for Cancer Research. 22(13):3281-5. http://doi.org/10.1158/1078-0432.CCR-15-1668. PMID: 26933124."
      },
      {
        "id": "54",
        "title": "Detection of Tumor NTRK Gene Fusions to Identify Patients Who May Benefit from Tyrosine Kinase (TRK) Inhibitor Therapy.",
        "abstract": "Chromosomal rearrangements involving the NTRK1, NTRK2, and NTRK3 genes (NTRK genes), which encode the high-affinity nerve growth factor receptor (TRKA), brain-derived neurotrophic factor/neurotrophin-3 (BDNF/NT-3) growth factor receptor (TRKB), and neurotrophin-3 (NT-3) growth factor receptor (TRKC) tyrosine kinases (TRK proteins), act as oncogenic drivers in a broad range of pediatric and adult tumor types. NTRK gene fusions have been shown to be actionable genomic events that are predictive of response to TRK kinase inhibitors, making their routine detection an evolving clinical priority. In certain exceedingly rare tumor types, NTRK gene fusions may be seen in the overwhelming majority of cases, whereas in a range of common cancers, reported incidences are in the range of 0.1% to 2%. Herein, we review the structure of the three NTRK genes and the nature and incidence of NTRK gene fusions in different solid tumor types, and we summarize the clinical data showing the importance of identifying tumors harboring such genomic events. We also outline the laboratory techniques that can be used to diagnose NTRK gene fusions in clinical samples. Finally, we propose a diagnostic algorithm for solid tumors to facilitate the identification of patients with TRK fusion cancer. This algorithm accounts for the widely varying frequencies by tumor histology and the underlying prevalence of TRK expression in the absence of NTRK gene fusions and is based on a combination of fluorescence in situ hybridization, next-generation sequencing, and immunohistochemistry assays.",
        "citation": "Hsiao SJ, Zehir A, Sireci AN, Aisner DL. (2019). Detection of Tumor NTRK Gene Fusions to Identify Patients Who May Benefit from Tyrosine Kinase (TRK) Inhibitor Therapy. The Journal of molecular diagnostics : JMD. 21(4):553-571. http://doi.org/10.1016/j.jmoldx.2019.03.008. PMID: 31075511."
      },
      {
        "id": "102",
        "title": "Assessment of Clinical Benefit of Integrative Genomic Profiling in Advanced Solid Tumors.",
        "abstract": "IMPORTANCE: Use of next-generation sequencing (NGS) to identify clinically actionable genomic targets has been incorporated into routine clinical practice in the management of advanced solid tumors; however, the clinical utility of this testing remains uncertain. OBJECTIVE: To determine which patients derived the greatest degree of clinical benefit from NGS profiling. DESIGN, SETTING, AND PARTICIPANTS: Patients in this cohort study underwent fresh tumor biopsy and blood sample collection for genomic profiling of paired tumor and normal DNA (whole-exome or targeted-exome capture with analysis of 1700 genes) and tumor transcriptome (RNA) sequencing. Somatic and germline genomic alterations were annotated and classified according to degree of clinical actionability. Results were returned to treating oncologists. Data were collected from May 1, 2011, to February 28, 2018, and analyzed from May 1, 2011, to April 30, 2020. MAIN OUTCOMES AND MEASURES: Patients' subsequent therapy and treatment response were extracted from the medical record to determine clinical benefit rate from NGS-directed therapy at 6 months and exceptional responses lasting 12 months or longer. RESULTS: During the study period, NGS was attempted on tumors from 1138 patients and was successful in 1015 (89.2%) (MET1000 cohort) (538 men [53.0%]; mean [SD] age, 57.7 [13.3] years). Potentially clinically actionable genomic alterations were discovered in 817 patients (80.5%). Of these, 132 patients (16.2%) received sequencing-directed therapy, and 49 had clinical benefit (37.1%). Exceptional responses were observed in 26 patients (19.7% of treated patients). Pathogenic germline variants (PGVs) were identified in 160 patients (15.8% of cohort), including 49 PGVs (4.8% of cohort) with therapeutic relevance. For 55 patients with carcinoma of unknown primary origin, NGS identified the primary site in 28 (50.9%), and sequencing-directed therapy in 13 patients resulted in clinical benefit in 7 instances (53.8%), including 5 exceptional responses. CONCLUSIONS AND RELEVANCE: The high rate of therapeutically relevant PGVs identified across diverse cancer types supports a recommendation for directed germline testing in all patients with advanced cancer. The high frequency of therapeutically relevant somatic and germline findings in patients with carcinoma of unknown primary origin and other rare cancers supports the use of comprehensive NGS profiling as a component of standard of care for these disease entities.",
        "citation": "Cobain EF, Wu YM, Vats P, Chugh R, Worden F, Smith DC, Schuetze SM, Zalupski MM, Sahai V, Alva A, Schott AF, Caram MEV, Hayes DF, Stoffel EM, Jacobs MF, Kumar-Sinha C, Cao X, Wang R, Lucas D, Ning Y, Rabban E, Bell J, Camelo-Piragua S, Udager AM, Cieslik M, Lonigro RJ, Kunju LP, Robinson DR, Talpaz M, Chinnaiyan AM. (2021). Assessment of Clinical Benefit of Integrative Genomic Profiling in Advanced Solid Tumors. JAMA oncology. 7(4):525-533. http://doi.org/10.1001/jamaoncol.2020.7987. PMID: 33630025."
      },
      "\u2026116 more"
    ],
    "criteria": [
      {
        "name": "Disease",
        "type": "exclude",
        "value": "Other diseases"
      },
      {
        "name": "Disease",
        "type": "exclude",
        "value": "Early stage cancer"
      },
      {
        "name": "Population",
        "type": "exclude",
        "value": "Laboratory studies"
      },
      {
        "name": "Population",
        "type": "exclude",
        "value": "Animal studies"
      },
      {
        "name": "Population",
        "type": "exclude",
        "value": "Drug discovery studies"
      },
      "\u202645 more"
    ],
    "questions": [
      "What is the incidence and prevalence of advanced cancers in Europe and other key jurisdictions?\n-   Focus on France, Italy, Spain, Belgium, Switzerland, UK; also include data for rest of Europe and Brazil, Chile, Columbia, Mexico, Canada.",
      "What are EMA-approved and ESMO guideline-recommended biomarker-guided treatments in advanced cancer types?\n-   Focus on the use of genomic testing in non-small-cell lung cancer, colorectal cancer, malignant melanoma, ovarian cancer and breast cancer, to reflect the different number and type of biomarkers associated with each type of malignant disease",
      "What are the types of precision medicine approaches in advanced cancers in Europe (that is, finding treatments that are effective for specific genomic biomarkers in a solid tumor)?\n-   Targeted therapies for specific cancer types\n-   Tissue-agnostic (pan-cancer) therapies\n-   Multi-tumor type targeted therapies\n-   Biomarker-based immunotherapy approaches\n-   Emerging molecularly targeted therapies and ongoing clinical trials",
      "What are the unmet needs with current practice of genomic testing in advanced cancers in Europe?\n-   What are the existing technologies for genomic testing?\n-   What are the technology requirements for identification of specific types of genomic aberrations?\n-   What are the key unmet needs in genomic testing workup approaches in current clinical practice?\n-   What are the challenges faced by people trying to implement genomic testing for rate mutations?",
      "What is the clinical utility of comprehensive genome profiling (CGP)?\n-   How far does CGP offer broader coverage of medically necessary biomarkers than more traditional methods of identifying mutations, such as polymerase chain reaction (PCR), chromosomal microarray (CMA) \u00c2\u00a0or small gene panel assays?\n-   Is the accuracy of CGP higher than traditional approaches in detecting biomarkers?\n-   Does the use of CGP improve patient outcomes, for example, do patients respond better to, or live longer with, therapies that target the patient's specific mutation?\n-   Does the use of CGP mean that fewer biopsy samples are needed?\n-   Does the use of CGP increase the number of patients who are eligible to be enrolled in clinical trials of new targeted therapies?",
      "Economic impact\n-   What is the budget impact of adopting CGP compared with traditional genetic testing?\n-   What is the cost-effectiveness of CGP?"
    ],
    "model": "gpt-5-nano",
    "repetitions": 2,
    "threshold": 1.0,
    "mock": true
  },
  "response": {
    "job_id": "d3ce189f-b1b7-45eb-91e3-946dfb6fdc72",
    "status": "pending",
    "progress": 0.0,
    "stage": ""
  }
}