Data dictionary

{
  "id": "nsclc",
  "kind": "cancer",
  "name": "Non-small-cell lung cancer",
  "tldr": "Non-small-cell lung cancer is the biggest cancer killer, and the proving ground for precision medicine: a dozen targetable mutations, immunotherapy for the r...",
  "summary": "Non-small-cell lung cancer is ~85% of lung cancer and the leading cause of cancer death worldwide (~1.8 million deaths a year, all lung cancer). Adenocarcino...",
  "asOf": "2026-09-06",
  "wikipedia": "https://en.wikipedia.org/wiki/Non-small-cell_lung_cancer",
  "tags": [
    "lung",
    "spike"
  ],
  "related": [
    "kras-roadmap",
    "adc-generations",
    "immunotherapy-roadmap"
  ],
  "technologies": [
    "kinase-inhibitors",
    "checkpoint-inhibitor",
    "adc"
  ],
  "targets": [
    "egfr",
    "alk",
    "kras"
  ],
  "companies": [
    "astrazeneca",
    "johnson-johnson",
    "pfizer"
  ],
  "pathways": [
    "ras-mapk",
    "pi3k-akt-mtor",
    "pd1-checkpoint"
  ],
  "terms": [
    "tps",
    "egfr-exon19-l858r",
    "egfr-exon20-insertion"
  ],
  "group": "lung",
  "burden": "~85% of lung cancer; lung cancer kills ~1.8 million people a year, more than any other cancer.",
  "subtypes": [
    "Adenocarcinoma",
    "Squamous",
    "EGFR-mutant"
  ],
  "biomarkers": [
    "EGFR",
    "ALK",
    "ROS1"
  ],
  "standardOfCare": [
    {
      "setting": "Screening",
      "approach": "Annual low-dose CT for high-risk smokers (NLST, NELSON); AI nodule scoring emerging.",
      "refs": [
        "ct",
        "radiology-ai-screening"
      ],
      "guideline": {
        "version": "NCCN Guidelines: Non-Small Cell Lung Cancer",
        "url": "https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1450"
      }
    },
    {
      "setting": "Early stage",
      "approach": "Surgery or SBRT; perioperative chemo-immunotherapy; adjuvant osimertinib (EGFR) or alectinib (ALK).",
      "refs": [
        "sbrt",
        "adaura",
        "osimertinib"
      ],
      "guideline": {
        "version": "NCCN Guidelines: Non-Small Cell Lung Cancer",
        "url": "https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1450"
      }
    },
    {
      "setting": "Stage III unresectable",
      "approach": "Chemoradiation → durvalumab (PACIFIC) or osimertinib (LAURA, EGFR).",
      "refs": [
        "durvalumab",
        "imrt-igrt"
      ],
      "guideline": {
        "version": "NCCN Guidelines: Non-Small Cell Lung Cancer",
        "url": "https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1450"
      }
    }
  ],
  "stateOfArt": [
    "5-year PFS 60% with lorlatinib in ALK+ disease.",
    "Adjuvant osimertinib halves death risk.",
    "First regimen to beat osimertinib (MARIPOSA) and first to beat pembrolizumab (ivonescimab, China)."
  ],
  "history": [
    {
      "year": 2002,
      "title": "Gefitinib approved; dramatic responses in a minority",
      "refs": []
    },
    {
      "year": 2004,
      "title": "EGFR mutations explain gefitinib responses",
      "refs": []
    },
    {
      "year": 2004,
      "title": "EGFR mutations explain gefitinib responses",
      "note": "Lynch, Paez, and Pao identify activating EGFR mutations; the birth of lung cancer precision medicine.",
      "refs": [
        "egfr",
        "egfr-exon19-l858r"
      ]
    }
  ],
  "pipeline": [
    "ivonescimab",
    "izalontamab-brengitecan",
    "sacituzumab-tirumotecan"
  ],
  "openProblems": [
    "Resistance to every TKI.",
    "Squamous histology has few targets.",
    "Screening uptake below 20% in the US."
  ]
}

{
  "id": "ai-computation",
  "kind": "section",
  "name": "AI & Computation",
  "tldr": "Software that reads scans and slides, predicts outcomes, designs drugs, and matches patients to trials.",
  "summary": "FDA-cleared digital pathology risk tools (ArteraAI), radiology triage and screening models, pathology and radiology foundation models, multimodal patient-lev...",
  "asOf": "2026-09-04",
  "order": 15,
  "icon": "chip"
}

{
  "id": "checkpoint-inhibitor",
  "kind": "technology",
  "name": "Immune checkpoint inhibitors",
  "tldr": "Antibodies that release the brakes on immune cells so they can attack the cancer. They cure a minority of patients across many cancers, something chemotherap...",
  "summary": "Anti-CTLA-4 (ipilimumab), anti-PD-1 (pembrolizumab, nivolumab, cemiplimab, dostarlimab, toripalimab, tislelizumab), anti-PD-L1 (atezolizumab, durvalumab, ave...",
  "status": "standard-of-care",
  "asOf": "2026-09-04",
  "wikipedia": "https://en.wikipedia.org/wiki/Checkpoint_inhibitor",
  "sections": [
    "immunotherapy"
  ],
  "targets": [
    "pd1",
    "pdl1",
    "ctla4"
  ],
  "drugs": [
    "pembrolizumab",
    "nivolumab",
    "ipilimumab"
  ],
  "terms": [
    "cps",
    "tmb",
    "msi"
  ],
  "principle": "Blocking inhibitory receptor-ligand interactions restores T-cell priming (CTLA-4) and effector function (PD-1).",
  "strengths": [
    "Durable, sometimes curative responses",
    "Broad applicability"
  ],
  "limitations": [
    "Most patients do not respond",
    "Autoimmune toxicity",
    "Biomarkers are imperfect"
  ],
  "since": 2011
}

{
  "id": "pd1",
  "kind": "target",
  "name": "PD-1",
  "tldr": "PD-1 is a brake on T cells. Blocking it releases the immune system against the tumour and has cured some previously incurable cancers.",
  "summary": "PD-1 blockade (pembrolizumab, nivolumab, cemiplimab, dostarlimab and a growing list of biosimilar-adjacent agents) is standard across melanoma, NSCLC, RCC, u...",
  "asOf": "2026-09-04",
  "wikipedia": "https://en.wikipedia.org/wiki/Programmed_cell_death_protein_1",
  "tags": [
    "checkpoint"
  ],
  "cancers": [
    "melanoma",
    "nsclc",
    "rcc"
  ],
  "pathways": [
    "pd1-checkpoint"
  ],
  "symbol": "PDCD1",
  "biology": "Inhibitory receptor on activated T cells; ligands PD-L1/PD-L2. Tumour PD-L1 expression, TMB, and MSI predict response imperfectly.",
  "whereFound": [
    "Exhausted T cells in the tumour microenvironment"
  ],
  "targetClass": "checkpoint",
  "prevalence": [
    {
      "cancerId": "melanoma",
      "pct": "30-40",
      "measure": "Objective response to PD-1 monotherapy (proxy)",
      "source": "https://en.wikipedia.org/wiki/Programmed_cell_death_protein_1",
      "note": "Not an expression prevalence"
    },
    {
      "cancerId": "nsclc",
      "pct": "20-45",
      "measure": "Response by PD-L1 stratum (proxy)",
      "source": "https://en.wikipedia.org/wiki/Programmed_cell_death_protein_1"
    }
  ]
}

{
  "id": "pembrolizumab",
  "kind": "drug",
  "name": "Pembrolizumab",
  "tldr": "The most widely used cancer immunotherapy, approved in more than 40 settings, including before and after surgery for triple-negative breast cancer.",
  "summary": "Approvals span melanoma, NSCLC, head and neck, Hodgkin, urothelial, MSI-H/dMMR tumours (first tumour-agnostic approval, 2017), gastric, oesophageal, cervical...",
  "status": "approved",
  "asOf": "2026-09-04",
  "wikipedia": "https://en.wikipedia.org/wiki/Pembrolizumab",
  "cancers": [
    "tnbc",
    "nsclc",
    "melanoma"
  ],
  "technologies": [
    "checkpoint-inhibitor"
  ],
  "targets": [
    "pd1"
  ],
  "companies": [
    "merck"
  ],
  "trials": [
    "keynote-522",
    "keynote-355",
    "ascent-04"
  ],
  "brand": "Keytruda / Keytruda Qlex (SC)",
  "modality": "Monoclonal antibody (anti-PD-1)",
  "mechanism": "Humanised IgG4 blocking PD-1; restores T-cell effector function.",
  "approvals": [
    {
      "region": "US",
      "year": 2014,
      "indication": "Melanoma (first of >40 indications)"
    },
    {
      "region": "US",
      "year": 2017,
      "indication": "MSI-H/dMMR solid tumours (tumour-agnostic)"
    },
    {
      "region": "US",
      "year": 2020,
      "indication": "Metastatic TNBC, PD-L1 CPS ≥10, with chemotherapy"
    }
  ],
  "mechanismSteps": [
    "Antibody binds PD-1 on T cells",
    "PD-1/PD-L1 engagement between T cell and tumour is blocked",
    "Exhausted tumour-reactive T cells regain effector function"
  ],
  "dosing": {
    "route": "IV infusion over 30 min (subcutaneous Keytruda Qlex available)",
    "schedule": "200 mg every 3 weeks or 400 mg every 6 weeks; paediatric 2 mg/kg (max 200 mg) every 3 weeks; up to 24 months in most metastatic settings",
    "modifications": "Hold for grade 2 immune-mediated events; permanently discontinue for grade 4 or recurrent grade 3",
    "monitoring": "Thyroid function, LFTs, creatinine, glucose at baseline and periodically; patient education on immune-related symptoms",
    "source": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287"
  },
  "toxicity": [
    {
      "event": "Hypothyroidism (immune-mediated)",
      "anyGradePct": 8,
      "source": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287",
      "note": "Pooled monotherapy data, >2,800 patients"
    },
    {
      "event": "Pneumonitis (immune-mediated)",
      "anyGradePct": 3.4,
      "source": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287",
      "note": "Pooled monotherapy data, >2,800 patients"
    },
    {
      "event": "Colitis (immune-mediated)",
      "anyGradePct": 1.7,
      "source": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287",
      "note": "Pooled monotherapy data, >2,800 patients"
    }
  ],
  "access": [
    {
      "country": "US",
      "listPrice": "$11,564 per 200 mg dose (WAC, Merck price disclosure 2024)",
      "reimbursement": "Medicare Part B (physician-administered); commercial plans per formulary",
      "assistance": "https://www.merckaccessprogram-keytruda.com",
      "source": "https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files",
      "asOf": "2026-09-06"
    },
    {
      "country": "UK",
      "reimbursement": "NICE: recommended across many indications (melanoma, NSCLC, TNBC KEYNOTE-522/355, RCC, HNSCC, cervical, oesophageal and others)",
      "source": "https://www.nice.org.uk/guidance/published?ngt=Technology%20appraisal%20guidance",
      "asOf": "2026-09-06"
    },
    {
      "country": "EU",
      "reimbursement": "EMA approved; reimbursed in all member states for core indications",
      "asOf": "2026-09-06"
    }
  ],
  "regulatoryEvents": [
    {
      "date": "2014-09-04",
      "type": "approval",
      "region": "US",
      "note": "Accelerated approval, advanced melanoma after ipilimumab; first PD-1 inhibitor in the US",
      "source": "https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"
    },
    {
      "date": "2015-10-02",
      "type": "approval",
      "region": "US",
      "note": "PD-L1+ NSCLC after platinum",
      "source": "https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"
    },
    {
      "date": "2017-05-23",
      "type": "approval",
      "region": "US",
      "note": "MSI-H/dMMR solid tumours: first tumour-agnostic approval",
      "source": "https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"
    }
  ]
}

{
  "id": "bms",
  "kind": "company",
  "name": "Bristol Myers Squibb",
  "tldr": "Pioneer of checkpoint inhibitors (Opdivo, Yervoy), now betting on the first successful bispecific ADC and alpha radiopharmaceuticals.",
  "summary": "Nivolumab, ipilimumab, Opdualag; izalontamab brengitecan (SystImmune, $8.4B); RayzeBio ($4.1B, RYZ101); Mirati (adagrasib); Breyanzi and Abecma CAR-T; BioNTe...",
  "asOf": "2026-09-04",
  "sections": [
    "immunotherapy",
    "adcs",
    "radiopharma"
  ],
  "drugs": [
    "nivolumab",
    "ipilimumab",
    "relatlimab-nivolumab"
  ],
  "hq": "Princeton, NJ",
  "country": "US",
  "companyType": "pharma",
  "website": "https://www.bms.com",
  "ticker": "BMY"
}

{
  "id": "nci",
  "kind": "institution",
  "name": "National Cancer Institute (NIH)",
  "tldr": "The NCI is the US government's cancer research agency, spending ~$7B a year and running the Cancer Centers Program, TCGA, and Rosenberg's cell therapy lab.",
  "summary": "Funds the 74 NCI-designated centres, ran TCGA and the RAS Initiative, runs SEER and ClinicalTrials-linked cooperative groups (NRG, SWOG, Alliance, ECOG-ACRIN...",
  "asOf": "2026-09-04",
  "technologies": [
    "til-therapy",
    "tcr-t"
  ],
  "city": "Bethesda, MD",
  "country": "US",
  "lat": 39.003,
  "lng": -77.104,
  "institutionType": "government",
  "website": "https://www.cancer.gov",
  "programs": [
    "Cancer Centers Program (74 centres)",
    "TCGA / GDC",
    "Cooperative groups"
  ]
}

{
  "id": "ras-mapk",
  "kind": "pathway",
  "name": "RAS / RAF / MEK / ERK (MAPK)",
  "tldr": "The RAS-MAPK pathway is the cell's 'divide' relay. A signal at the surface flips RAS on, which passes to RAF, MEK, and ERK, which tell the nucleus to make th...",
  "summary": "Growth-factor receptors recruit GRB2/SOS to load GTP onto RAS (KRAS, NRAS, HRAS). RAS-GTP recruits RAF (BRAF, CRAF) dimers, which phosphorylate MEK1/2, which...",
  "asOf": "2026-09-04",
  "wikipedia": "https://en.wikipedia.org/wiki/MAPK/ERK_pathway",
  "cancers": [
    "pancreatic",
    "colorectal",
    "nsclc"
  ],
  "targets": [
    "kras",
    "braf",
    "egfr"
  ],
  "drugs": [
    "sotorasib",
    "adagrasib",
    "daraxonrasib"
  ],
  "analogy": "A relay race: receptor hands the baton to RAS, RAS to RAF, RAF to MEK, MEK to ERK, ERK runs into the nucleus and shouts 'divide'. A KRAS mutation is a runner...",
  "nodes": [
    {
      "id": "rtk",
      "label": "RTK (EGFR, ALK, RET, MET)",
      "x": 50,
      "y": 5,
      "targetId": "egfr"
    },
    {
      "id": "sos",
      "label": "GRB2 / SOS1",
      "x": 50,
      "y": 20
    },
    {
      "id": "ras",
      "label": "RAS (KRAS)",
      "x": 50,
      "y": 36,
      "targetId": "kras"
    }
  ],
  "edges": [
    {
      "from": "rtk",
      "to": "sos",
      "type": "activates"
    },
    {
      "from": "sos",
      "to": "ras",
      "type": "activates"
    },
    {
      "from": "nf1",
      "to": "ras",
      "type": "inhibits"
    }
  ],
  "interventions": [
    "KRAS G12C inhibitors (sotorasib, adagrasib) ± anti-EGFR in colorectal cancer",
    "Pan-RAS(ON) inhibitor daraxonrasib (phase 3, pancreatic)",
    "BRAF + MEK inhibitors (dabrafenib/trametinib, encorafenib/binimetinib)"
  ]
}

{
  "id": "mrd",
  "kind": "term",
  "name": "Minimal / molecular residual disease (MRD)",
  "tldr": "Cancer still present after treatment but too small to see on scans, detected by blood or marrow tests.",
  "summary": "In leukaemia/myeloma: flow cytometry or NGS of marrow (clonoSEQ). In solid tumours: ctDNA after surgery. MRD positivity predicts relapse; MRD-guided escalati...",
  "asOf": "2026-09-04",
  "wikipedia": "https://en.wikipedia.org/wiki/Minimal_residual_disease",
  "technologies": [
    "mrd-testing"
  ],
  "trials": [
    "imvigor011",
    "dynamic"
  ],
  "category": "Biomarkers"
}

{
  "id": "imvigor011",
  "kind": "trial",
  "name": "IMvigor011",
  "tldr": "The first trial to use a blood test for leftover cancer to decide who gets immunotherapy, and it worked.",
  "summary": "DFS HR 0.64; OS HR 0.59 in ctDNA-positive patients; ctDNA-negative patients had excellent outcomes without treatment. FDA approval Q2 2026, the first ctDNA-g...",
  "status": "positive",
  "asOf": "2026-09-04",
  "links": [
    {
      "label": "ClinicalTrials.gov NCT04660344",
      "url": "https://clinicaltrials.gov/study/NCT04660344"
    }
  ],
  "cancers": [
    "urothelial"
  ],
  "technologies": [
    "mrd-testing"
  ],
  "drugs": [
    "atezolizumab",
    "signatera"
  ],
  "terms": [
    "mrd",
    "ctdna"
  ],
  "nct": "NCT04660344",
  "phase": "3",
  "setting": "Muscle-invasive bladder cancer after cystectomy, ctDNA-positive (Signatera): atezolizumab vs placebo",
  "sponsor": "Roche",
  "result": "DFS HR 0.64; OS HR 0.59 in ctDNA+.",
  "yearReported": 2025,
  "enrolled": 761,
  "outcomes": [
    {
      "endpoint": "Disease-free survival (ctDNA-positive, randomised)",
      "primary": true,
      "unit": "months",
      "arms": [
        {
          "name": "Atezolizumab",
          "n": 167,
          "value": 9.9
        },
        {
          "name": "Placebo",
          "n": 83,
          "value": 4.8
        }
      ],
      "hr": 0.64,
      "ci": [
        0.47,
        0.88
      ],
      "p": "0.005",
      "source": "https://www.roche.com/media/releases/med-cor-2025-10-20b"
    },
    {
      "endpoint": "Overall survival (ctDNA-positive)",
      "unit": "months",
      "arms": [
        {
          "name": "Atezolizumab",
          "value": 32.8
        },
        {
          "name": "Placebo",
          "value": 21.1
        }
      ],
      "hr": 0.59,
      "ci": [
        0.41,
        0.86
      ],
      "p": "0.005",
      "source": "https://www.roche.com/media/releases/med-cor-2025-10-20b"
    },
    {
      "endpoint": "Disease-free survival at 12 months, persistently ctDNA-negative (untreated surveillance)",
      "unit": "%",
      "arms": [
        {
          "name": "ctDNA-negative, surveillance only",
          "n": 357,
          "value": 95.4,
          "note": "12-month OS 100% in this group"
        }
      ],
      "source": "https://www.roche.com/media/releases/med-cor-2025-10-20b"
    }
  ],
  "replication": "Contrasts with IMvigor010 (unselected adjuvant atezolizumab, negative), whose exploratory ctDNA analysis generated the hypothesis; IMvigor011 is the prospect..."
}

{
  "id": "btki-plus-venetoclax-fixed-duration",
  "kind": "pairing",
  "name": "BTK inhibitor + venetoclax, fixed duration",
  "tldr": "Block the survival signal and remove the death shield at the same time, for about a year, then stop and stay in remission for years.",
  "summary": "CAPTIVATE and GLOW (ibrutinib), AMPLIFY (acalabrutinib; FDA approved February 2026), SEQUOIA arm D (zanubrutinib), and CELESTIAL (sonrotoclax + zanubrutinib)...",
  "asOf": "2026-09-07",
  "cancers": [
    "cll"
  ],
  "targets": [
    "btk",
    "bcl2"
  ],
  "drugs": [
    "acalabrutinib",
    "ibrutinib",
    "zanubrutinib"
  ],
  "trials": [
    "amplify",
    "glow",
    "captivate"
  ],
  "a": "acalabrutinib",
  "b": "venetoclax",
  "rationale": "BTK inhibition mobilises CLL cells out of protective lymph-node niches and increases BCL-2 dependence; venetoclax then kills them. The two resistance mechani...",
  "evidence": "Multiple positive phase 3 trials; US approval 2026.",
  "pairingType": "combination"
}

{
  "id": "frontier-2035",
  "kind": "roadmap",
  "name": "Radical oncology: what could change the war by 2035",
  "tldr": "Radical oncology is a horizon map of the wilder ideas in cancer, sorted by how close they are to mattering, with the reason each one might never arrive.",
  "summary": "Most of what is celebrated as a breakthrough is an incremental gain on an existing modality. This roadmap collects the ideas that would change the shape of t...",
  "asOf": "2026-09-08",
  "sections": [
    "drug-discovery",
    "radiation",
    "cell-therapy"
  ],
  "steps": [
    {
      "era": "Now (randomised data exists)",
      "title": "Ideas already being tested against a control arm",
      "description": "Microbiome modulation, spatially fractionated radiotherapy, sonodynamic therapy in glioblastoma, GDF-15 blockade for cachexia, and repurposed cheap drugs all...",
      "refs": [
        "microbiome-modulation-io",
        "lattice-radiotherapy",
        "sonodynamic-therapy"
      ],
      "status": "current"
    },
    {
      "era": "By 2027 (early clinical, readouts imminent)",
      "title": "Living drugs, logic gates, and designed proteins reach decision points",
      "description": "Engineered bacteria, logic-gated cell therapies, molecular glue platforms, and de novo designed binders all have first-in-human programmes running. The quest...",
      "refs": [
        "engineered-bacteria-therapy",
        "logic-gated-therapeutics",
        "molecular-glue-platforms"
      ],
      "status": "emerging"
    },
    {
      "era": "By 2030 (physics and chemistry maturing)",
      "title": "Radiation and radiopharmaceuticals get a second act",
      "description": "Auger emitters, contained alpha nanogenerators, proton arc delivery, and very-high-energy electrons are all limited today by engineering rather than biology:...",
      "refs": [
        "auger-electron-therapy",
        "alpha-nanogenerators",
        "proton-arc-therapy"
      ],
      "status": "emerging"
    }
  ]
}

{
  "id": "idea-fund-surgical-trials-network",
  "kind": "idea",
  "name": "A permanently funded international network for randomised cancer surgery trials",
  "tldr": "Surgery cures more cancer than any drug, yet most operations have never been compared in a proper trial. A standing network of hospitals, with core funding, ...",
  "summary": "A surgical oncology trials network with core funding for trial units, research nurses and data managers at fifty to one hundred hospitals, standing ethics an...",
  "asOf": "2026-09-08",
  "links": [
    {
      "label": "GlobalSurg Collaborative",
      "url": "https://globalsurg.org/"
    },
    {
      "label": "IDEAL Collaboration",
      "url": "https://www.ideal-collaboration.net/"
    }
  ],
  "related": [
    "idea-fund-non-drug-trial-quota",
    "idea-fund-surgical-video-registry",
    "idea-fund-organ-preservation-programme"
  ],
  "technologies": [
    "robotic-surgery",
    "sentinel-node"
  ],
  "institutions": [
    "jcog",
    "alliance-oncology",
    "royal-marsden"
  ],
  "people": [
    "kitagawa-yuko",
    "sano-takeshi",
    "chaturvedi-pankaj"
  ],
  "bottlenecks": [
    "b-surgery-radiation-innovation",
    "b-trial-enrolment"
  ],
  "hypothesis": "A funded network completes at least ten adequately powered randomised surgical trials per five years with more than 80% accrual to target, compared with the ...",
  "rationale": "Where surgical trial infrastructure has been funded, landmark results followed: the LACC trial on minimally invasive radical hysterectomy, the JCOG gastric l...",
  "test": "Fund the network for one five-year cycle with a portfolio of five trials and audit accrual, completion and guideline impact against surgical trials run witho...",
  "maturity": "early-clinical",
  "actor": "policy",
  "cost": "large",
  "horizonYears": 5
}

{
  "id": "clinicaltrials-gov",
  "kind": "collection",
  "name": "ClinicalTrials.gov",
  "tldr": "ClinicalTrials.gov is the master list of clinical trials. Every trial on this site links to its record.",
  "summary": "Mandatory registration for US trials; API v2 provides structured access to eligibility, arms, outcomes, and results. The backbone for any trial-matching tool.",
  "asOf": "2026-09-04",
  "technologies": [
    "ai-trial-matching"
  ],
  "url": "https://clinicaltrials.gov",
  "holds": "Registry and results database of >500,000 clinical studies worldwide.",
  "license": "Public domain (US Government)",
  "maintainer": "NIH / NLM"
}

{
  "id": "sara-tolaney",
  "kind": "person",
  "name": "Sara M. Tolaney",
  "tldr": "Leads Dana-Farber's breast oncology division and many of the trials that moved ADCs and de-escalated therapy into breast cancer care.",
  "summary": "Led the APT trial establishing adjuvant paclitaxel-trastuzumab for small HER2-positive tumours, and is a principal investigator across the DESTINY, TROPION a...",
  "asOf": "2026-09-08",
  "cancers": [
    "breast-her2-positive",
    "breast-hr-positive",
    "tnbc"
  ],
  "technologies": [
    "adc"
  ],
  "targets": [
    "her2",
    "trop2"
  ],
  "drugs": [
    "trastuzumab-deruxtecan",
    "datopotamab-deruxtecan",
    "sacituzumab-govitecan"
  ],
  "institutions": [
    "dana-farber"
  ],
  "trials": [
    "apt-trial",
    "tropion-breast01",
    "destiny-breast09"
  ],
  "role": "Chief, Division of Breast Oncology; Associate Director, Susan F. Smith Center for Women's Cancers",
  "institutionId": "dana-farber",
  "specialisms": [
    "Breast cancer",
    "HER2-positive breast cancer",
    "Antibody-drug conjugates"
  ],
  "profiles": [
    {
      "label": "Dana-Farber profile",
      "url": "https://www.dana-farber.org/find-a-doctor/sara-m-tolaney"
    },
    {
      "label": "PubMed",
      "url": "https://pubmed.ncbi.nlm.nih.gov/?term=Tolaney%20SM%5BAuthor%5D"
    }
  ],
  "papers": [
    {
      "title": "Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer",
      "journal": "New England Journal of Medicine",
      "year": 2015,
      "url": "https://doi.org/10.1056/NEJMoa1406281",
      "doi": "10.1056/NEJMoa1406281"
    },
    {
      "title": "Datopotamab deruxtecan versus chemotherapy in previously treated inoperable/metastatic hormone receptor-positive HER2-negative breast cancer (TROPION-Breast01)",
      "journal": "Journal of Clinical Oncology",
      "year": 2025,
      "url": "https://doi.org/10.1200/JCO.24.00920",
      "doi": "10.1200/JCO.24.00920"
    }
  ]
}

{
  "id": "b-toxicity-qol",
  "kind": "bottleneck",
  "name": "Toxicity and quality of life are undervalued",
  "tldr": "Trials measure how long people live, not how they live. Side-effects are under-reported and under-treated.",
  "summary": "Oncology trials are designed around survival and progression, and the harms and lived experience of treatment are secondary at best. Clinicians systematicall...",
  "asOf": "2026-09-08",
  "links": [
    {
      "label": "Di Maio et al., Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting (JCO 2015)",
      "url": "https://doi.org/10.1200/JCO.2014.57.9334"
    },
    {
      "label": "Davis et al., Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by EMA 2009-13 (BMJ 2017)",
      "url": "https://doi.org/10.1136/bmj.j4530"
    },
    {
      "label": "EORTC Quality of Life Group",
      "url": "https://qol.eortc.org/"
    }
  ],
  "related": [
    "fda-approvals",
    "esmo-guidelines"
  ],
  "sections": [
    "supportive-care"
  ],
  "technologies": [
    "scalp-cooling",
    "cardio-oncology",
    "adc"
  ],
  "institutions": [
    "esmo",
    "asco",
    "nci"
  ],
  "terms": [
    "irae",
    "crs",
    "icans"
  ],
  "stage": "people-culture",
  "severity": "major",
  "metrics": [
    {
      "label": "Cancer drug indications approved by the EMA 2009-2013 with no evidence of quality-of-life or survival benefit at approval",
      "value": "57%",
      "source": "Davis et al., BMJ 2017",
      "url": "https://doi.org/10.1136/bmj.j4530"
    },
    {
      "label": "Agreement between physician and patient reporting of symptomatic toxicities (anorexia, nausea, vomiting, constipation, diarrhoea, hair loss) in three randomi...",
      "value": "Physicians under-reported all six symptoms",
      "source": "Di Maio et al., JCO 2015",
      "url": "https://doi.org/10.1200/JCO.2014.57.9334"
    },
    {
      "label": "Median overall survival with routine patient-reported symptom monitoring vs usual care during chemotherapy (randomised)",
      "value": "31.2 vs 26.0 months",
      "source": "Basch et al., JAMA 2017",
      "url": "https://doi.org/10.1001/jama.2017.7156"
    }
  ],
  "causes": [
    "Regulatory approval and pricing are based on efficacy endpoints, so sponsors invest little in quality-of-life measurement.",
    "Clinician-graded adverse event scales miss what patients feel and ignore chronic low-grade toxicity.",
    "Quality-of-life analyses are heterogeneous, unpublished or reported long after the primary paper."
  ],
  "currentEfforts": [
    "PRO-CTCAE (NCI) provides a validated patient-reported version of the toxicity scale now used in many trials.",
    "The FDA guidance on core patient-reported outcomes in cancer clinical trials (2021 draft) specifies which PRO domains should be measured.",
    "SISAQOL-IMI is developing consensus standards for analysing and reporting quality-of-life data in cancer trials."
  ],
  "successLooksLike": "Every registrational oncology trial collects and publishes patient-reported outcomes with the primary results, quality of life is graded in every value frame..."
}

{
  "id": "paper-destiny-breast03-nejm-2022",
  "kind": "paper",
  "name": "DESTINY-Breast03: trastuzumab deruxtecan beats T-DM1 as second-line treatment of HER2-positive metastatic breast cancer",
  "tldr": "A newer antibody-drug conjugate, trastuzumab deruxtecan, kept HER2-positive metastatic breast cancer under control roughly four times longer than the previou...",
  "summary": "Open-label phase 3 trial of 524 patients with HER2-positive unresectable or metastatic breast cancer previously treated with trastuzumab and a taxane, random...",
  "asOf": "2026-09-08",
  "links": [
    {
      "label": "NEJM 2022",
      "url": "https://doi.org/10.1056/NEJMoa2115022"
    },
    {
      "label": "ClinicalTrials.gov NCT03529110",
      "url": "https://clinicaltrials.gov/study/NCT03529110"
    }
  ],
  "related": [
    "idea-payload-switching"
  ],
  "cancers": [
    "breast-her2-positive"
  ],
  "technologies": [
    "adc",
    "topoisomerase-inhibitors"
  ],
  "targets": [
    "her2"
  ],
  "drugs": [
    "trastuzumab-deruxtecan",
    "trastuzumab-emtansine"
  ],
  "companies": [
    "daiichi-sankyo",
    "astrazeneca"
  ],
  "terms": [
    "pfs",
    "os",
    "payload"
  ],
  "trials": [
    "destiny-breast03"
  ],
  "people": [
    "javier-cortes",
    "kim-sung-bae",
    "im-seock-ah"
  ],
  "bottlenecks": [
    "b-resistance",
    "b-toxicity-qol"
  ],
  "journal": "New England Journal of Medicine",
  "year": 2022,
  "doi": "10.1056/NEJMoa2115022",
  "authors": "Cortes J, Kim SB, Chung WP, et al.",
  "paperType": "rct",
  "findings": [
    "12-month progression-free survival 75.8% with T-DXd vs 34.1% with T-DM1; HR 0.28 (95% CI 0.22-0.37).",
    "Confirmed objective response 79.7% vs 34.2%.",
    "Updated analysis (Lancet 2023): median PFS 28.8 vs 6.8 months; overall survival HR 0.64."
  ],
  "whatItMeans": "For HER2-positive metastatic breast cancer that has progressed after trastuzumab and a taxane, trastuzumab deruxtecan is now the standard second-line treatme...",
  "caveats": [
    "Open-label design, though the primary endpoint was assessed by blinded central review.",
    "Interstitial lung disease requires proactive CT surveillance and dose interruption; fatal cases occurred in other T-DXd trials.",
    "Many patients had not received pertuzumab-based first-line therapy, so the population differs slightly from today's second line."
  ],
  "changedPractice": true,
  "participants": 524
}

{
  "id": "annals-of-oncology",
  "kind": "journal",
  "name": "Annals of Oncology",
  "aka": [
    "Ann Oncol"
  ],
  "tldr": "Annals of Oncology is ESMO's flagship journal, publishing European phase 3 trials, the ESMO Clinical Practice Guidelines and the abstract books for the ESMO ...",
  "summary": "Annals of Oncology appears monthly and publishes the ESMO Clinical Practice Guidelines (free to read), ESMO-MCBS benefit scores, trial results often presente...",
  "asOf": "2026-09-09",
  "links": [
    {
      "label": "ESMO Guidelines",
      "url": "https://www.esmo.org/guidelines"
    }
  ],
  "related": [
    "src-annals-oncology",
    "src-esmo-congress",
    "esmo-guidelines"
  ],
  "institutions": [
    "esmo"
  ],
  "publisher": "Elsevier",
  "url": "https://www.annalsofoncology.org",
  "issn": "0923-7534",
  "scope": "clinical oncology",
  "access": "hybrid",
  "founded": 1990,
  "impactFactor": {
    "value": 56.7,
    "year": 2023,
    "source": "Clarivate Journal Citation Reports 2024 (2023 JIF)"
  },
  "matchNames": [
    "Annals of Oncology",
    "Ann Oncol"
  ],
  "society": "European Society for Medical Oncology"
}