[{"id":"tnbc-01","question":"Which TROP2 ADCs are approved for first-line metastatic triple-negative breast cancer?","category":"factual","difficulty":1,"audience":"clinician","expected":"Sacituzumab govitecan (Trodelvy), as monotherapy for PD-1-ineligible patients (ASCENT-03) and with pembrolizumab for PD-L1 CPS ≥10 disease (ASCENT-04), and datopotamab deruxtecan (Datroway) for PD-1/PD-L1-ineligible patients (TROPION-Breast02), both approved in 2026.","entities":["sacituzumab-govitecan","datopotamab-deruxtecan","ascent-03","ascent-04","tropion-breast02","tnbc-metastatic"],"rubric":[["sacituzumab govitecan","trodelvy"],["datopotamab deruxtecan","datroway","dato-dxd"],["2026"],["pembrolizumab","pd-l1","pd-1"]]},{"id":"tnbc-02","question":"What does 'triple-negative' mean in breast cancer?","category":"factual","difficulty":1,"audience":"patient","expected":"The tumour lacks the three receptors other breast cancers can be treated through: oestrogen receptor, progesterone receptor, and HER2 (IHC 0-1+ or 2+/ISH-negative).","entities":["tnbc","her2","estrogen-receptor"],"rubric":[["oestrogen","estrogen","er"],["progesterone","pr"],["her2"],["lack","negative","without","absence","does not have"]]},{"id":"tnbc-03","question":"What is the standard treatment for stage II-III triple-negative breast cancer today?","category":"factual","difficulty":2,"audience":"clinician","expected":"Neoadjuvant pembrolizumab with carboplatin/paclitaxel then anthracycline chemotherapy, surgery, and adjuvant pembrolizumab (KEYNOTE-522); adjuvant olaparib for germline BRCA carriers with residual disease (OlympiA); capecitabine for residual disease without BRCA.","entities":["tnbc","tnbc-early","keynote-522","pembrolizumab","olaparib","olympia"],"rubric":[["pembrolizumab","keytruda"],["keynote-522","keynote 522"],["carboplatin","chemotherapy"],["olaparib","parp","brca"],["surgery"]]},{"id":"tnbc-04","question":"Did KEYNOTE-522 improve overall survival?","category":"factual","difficulty":2,"audience":"clinician","expected":"Yes. Seven-year overall survival was 85.1% vs 77.2% (ASCO 2026 update); five-year EFS 81.2% vs 72.2%; pCR 64.8% vs 51.2%.","entities":["keynote-522"],"rubric":[["yes","improved","benefit"],["85.1","85%"],["77.2","77%"],["event-free","efs","pcr","pathologic complete"]]},{"id":"tnbc-05","question":"What is pathologic complete response and why does it matter in TNBC?","category":"factual","difficulty":1,"audience":"patient","expected":"pCR means no invasive cancer is left in the breast and lymph nodes when the surgeon removes the tissue after pre-surgery treatment. In TNBC patients with pCR have around 90% five-year event-free survival, and trials now test giving less treatment after pCR.","entities":["pcr","optimice-pcr","tnbc"],"rubric":[["no invasive","no cancer left","no residual","disappear"],["surgery","surgeon"],["prognos","survival","recurrence","outcome"],["de-escalat","less treatment","omit","skip","optimice"]]},{"id":"tnbc-06","question":"Which trial showed the first overall survival benefit for a first-line ADC in triple-negative breast cancer?","category":"factual","difficulty":2,"audience":"analyst","expected":"TROPION-Breast02: datopotamab deruxtecan vs chemotherapy in first-line PD-1/PD-L1-ineligible metastatic TNBC, OS 23.7 vs 18.7 months.","entities":["tropion-breast02","datopotamab-deruxtecan"],"rubric":[["tropion-breast02","tropion breast02","tropion-breast 02"],["datopotamab","dato-dxd","datroway"],["23.7"],["18.7"]]},{"id":"tnbc-07","question":"What is the first bispecific ADC to succeed in a phase 3 trial, and in which cancer?","category":"factual","difficulty":2,"audience":"analyst","expected":"Izalontamab brengitecan (iza-bren, BL-B01D1), an EGFR×HER3 bispecific ADC from SystImmune/BMS, met PFS and OS in previously treated TNBC (BL-B01D1-307, February 2026) and also in oesophageal squamous cell carcinoma.","entities":["izalontamab-brengitecan","bl-b01d1-307","bispecific-adc"],"rubric":[["izalontamab","iza-bren","bl-b01d1"],["egfr"],["her3"],["triple-negative","tnbc","breast"],["2026","february"]]},{"id":"tnbc-08","question":"Why does trastuzumab deruxtecan work in 'HER2-low' breast cancers that older HER2 drugs ignored?","category":"reasoning","difficulty":2,"audience":"clinician","expected":"Its cleavable linker releases a membrane-permeable topoisomerase-I payload (DXd) at high DAR, so a small amount of HER2 is enough to deliver drug and the payload diffuses to kill neighbouring cells (bystander effect); HER2-low is a delivery address, not a driver. DESTINY-Breast04 and -06 proved it.","entities":["trastuzumab-deruxtecan","her2-low","bystander-effect","destiny-breast04"],"rubric":[["bystander"],["payload","dxd","deruxtecan","topoisomerase"],["cleavable linker","linker","permeable"],["destiny-breast04","destiny-breast06","destiny breast"]]},{"id":"tnbc-09","question":"Should a patient get a second ADC with the same kind of payload straight after the first one fails?","category":"reasoning","difficulty":3,"audience":"clinician","expected":"Caution: retrospective series (SATEEN, BRE-354) show shorter PFS for a second TOP1-payload ADC given back-to-back; resistance is at the payload level (SLFN11 loss, TOP1 mutations, ABCG2 efflux). Some data suggest interposing chemotherapy or switching payload class; prospective trials (TRADE-DXd) are pending.","entities":["adc-after-adc-caution","adc-sequencing","idea-payload-switching"],"rubric":[["caution","less effective","shorter","may not work","reduced"],["payload"],["slfn11","top1","topoisomerase","efflux","resistance"],["chemotherapy between","interpos","switch payload","different payload","non-top1"]]},{"id":"tnbc-10","question":"What questions should someone newly diagnosed with triple-negative breast cancer ask before surgery?","category":"procedural","difficulty":2,"audience":"patient","expected":"Whether chemo-immunotherapy before surgery (KEYNOTE-522) is planned and why; germline BRCA testing; PD-L1 and HER2-low status; TIL score; clinical trial options; fertility preservation; breast-conserving versus mastectomy and sentinel node approach; what response (pCR/RCB) will mean for treatment afterwards.","entities":["tnbc","tnbc-early","keynote-522","germline-testing","tils","pcr","rcb"],"rubric":[["before surgery","neoadjuvant","keynote-522","immunotherapy"],["brca","germline","genetic"],["trial"],["fertility","sentinel","mastectomy","breast-conserving"],["pcr","residual","response"]]},{"id":"tnbc-11","question":"Does the TROP2 level measured on a biopsy tell you whether Trodelvy will work?","category":"reasoning","difficulty":3,"audience":"clinician","expected":"Not reliably. ASCENT showed benefit regardless of TROP2 IHC, so no companion diagnostic is required; expression is heterogeneous and archival tissue may not reflect current status. TROP2 PET tracers are being developed to map expression across the body and over time.","entities":["trop2","ascent","trop2-pet","idea-trop2-pet-selection"],"rubric":[["no","not","regardless"],["ascent"],["heterogene","archival","single biopsy"],["pet","tracer","imaging"]]},{"id":"breast-12","question":"What was the first PROTAC ever approved and for what?","category":"factual","difficulty":2,"audience":"analyst","expected":"Vepdegestrant (Veppanu, Arvinas/Pfizer), an oral oestrogen receptor degrader, approved in 2026 for ESR1-mutated ER+/HER2- advanced breast cancer (VERITAC-2).","entities":["vepdegestrant","protac-degrader","veritac-2"],"rubric":[["vepdegestrant","veppanu"],["esr1"],["breast"],["2026"]]},{"id":"breast-13","question":"Which CDK4/6 inhibitors are approved after surgery for early hormone-positive breast cancer, and on what trials?","category":"factual","difficulty":2,"audience":"clinician","expected":"Abemaciclib (monarchE, high-risk node-positive) and ribociclib (NATALEE, stage II-III including node-negative).","entities":["abemaciclib","ribociclib","monarche","natalee","hr-positive-early-high-risk"],"rubric":[["abemaciclib","verzenio"],["ribociclib","kisqali"],["monarche","monarch e"],["natalee"]]},{"id":"breast-14","question":"What can a 21-gene test tell a woman with early hormone-positive breast cancer?","category":"factual","difficulty":1,"audience":"patient","expected":"Oncotype DX gives a recurrence score; TAILORx showed women with a score of 25 or below (over 50) get no benefit from chemotherapy and can safely skip it; RxPONDER extended this to 1-3 positive nodes in postmenopausal women.","entities":["oncotype-dx","breast-hr-positive","hr-positive-early-high-risk"],"rubric":[["oncotype"],["chemotherapy"],["skip","avoid","no benefit","spare","safely"],["tailorx","recurrence score"]]},{"id":"breast-15","question":"In what setting did T-DXd move into early-stage HER2-positive breast cancer in 2026?","category":"factual","difficulty":2,"audience":"clinician","expected":"Neoadjuvant (DESTINY-Breast11, T-DXd followed by THP, pCR 67.3% vs 56.3%) and post-neoadjuvant residual disease (DESTINY-Breast05, beating T-DM1), both approved Q2 2026.","entities":["trastuzumab-deruxtecan","destiny-breast11","breast-her2-positive","her2-positive-early-breast-cancer"],"rubric":[["neoadjuvant","before surgery"],["destiny-breast11","destiny breast 11","destiny-breast05"],["residual","post-neoadjuvant","after surgery"],["2026"]]},{"id":"lung-16","question":"Which biomarkers must be tested at diagnosis of advanced non-small-cell lung cancer?","category":"factual","difficulty":2,"audience":"clinician","expected":"EGFR, ALK, ROS1, BRAF V600E, MET exon 14/amplification, RET, NTRK, KRAS G12C, HER2 mutations, and PD-L1 TPS.","entities":["nsclc","egfr","alk","kras","pdl1"],"rubric":[["egfr"],["alk"],["kras"],["pd-l1","pdl1"],["ret","met","braf","ros1","ntrk","her2"]]},{"id":"lung-17","question":"What is the standard adjuvant treatment after resection of EGFR-mutant lung cancer and what did it do to survival?","category":"factual","difficulty":2,"audience":"clinician","expected":"Three years of osimertinib (ADAURA): DFS HR 0.20 in stage II-IIIA and OS HR 0.49, five-year OS 88% vs 78%.","entities":["osimertinib","adaura"],"rubric":[["osimertinib","tagrisso"],["adaura"],["three years","3 years"],["0.49","halv","88%"]]},{"id":"lung-18","question":"Which regimen beat osimertinib in first-line EGFR-mutant lung cancer?","category":"factual","difficulty":2,"audience":"analyst","expected":"Amivantamab plus lazertinib (MARIPOSA): PFS 23.7 vs 16.6 months and an OS benefit of more than a year.","entities":["amivantamab","mariposa"],"rubric":[["amivantamab","rybrevant"],["lazertinib"],["mariposa"],["survival","os","pfs"]]},{"id":"lung-19","question":"What is the first T-cell engager to improve survival in a common solid tumour?","category":"factual","difficulty":2,"audience":"analyst","expected":"Tarlatamab (Imdelltra), DLL3×CD3, in second-line small-cell lung cancer: OS 13.6 vs 8.3 months in DeLLphi-304.","entities":["tarlatamab","dellphi-304","sclc"],"rubric":[["tarlatamab","imdelltra"],["dll3"],["small-cell","small cell","sclc"],["13.6","8.3","dellphi"]]},{"id":"lung-20","question":"Why did the first KRAS inhibitors need an EGFR antibody added in colorectal cancer but not in lung cancer?","category":"reasoning","difficulty":3,"audience":"clinician","expected":"Colorectal epithelium has strong EGFR-driven adaptive feedback that reactivates MAPK within hours of KRAS G12C inhibition, so monotherapy response is ~10%; adding cetuximab or panitumumab (CodeBreaK 300, KRYSTAL-1) raises it to 30-45%.","entities":["kras-plus-egfr-crc","codebreak-300","sotorasib","adagrasib"],"rubric":[["feedback","reactivat","bypass","adaptive"],["egfr"],["cetuximab","panitumumab","antibody"],["codebreak","krystal"]]},{"id":"lung-21","question":"Which drug beat pembrolizumab head to head on progression-free survival in lung cancer?","category":"factual","difficulty":2,"audience":"analyst","expected":"Ivonescimab, a PD-1×VEGF bispecific (Akeso/Summit): PFS 11.1 vs 5.8 months in PD-L1-positive first-line NSCLC (HARMONi-2, China).","entities":["ivonescimab","vegf","pd1"],"rubric":[["ivonescimab"],["vegf"],["pd-1","pd1"],["harmoni"]]},{"id":"lung-22","question":"What is the longest progression-free survival ever reported for a targeted pill in metastatic lung cancer?","category":"factual","difficulty":2,"audience":"analyst","expected":"Lorlatinib in ALK-positive NSCLC (CROWN): five-year PFS about 60% versus 8% for crizotinib.","entities":["lorlatinib","alk"],"rubric":[["lorlatinib","lorbrena"],["alk"],["60%","five-year","5-year"],["crown"]]},{"id":"prostate-23","question":"What is theranostics and what is the best-known example?","category":"factual","difficulty":1,"audience":"patient","expected":"Using the same targeting molecule for a diagnostic scan and a treatment: PSMA PET shows where prostate cancer is, and 177Lu-PSMA-617 (Pluvicto) delivers radiation to the same target.","entities":["theranostics","psma-pet","pluvicto","psma"],"rubric":[["same","pair","diagnos"],["psma"],["pet","scan","imag"],["pluvicto","lutetium","177lu","radioligand"]]},{"id":"prostate-24","question":"What did the VISION trial show?","category":"factual","difficulty":2,"audience":"clinician","expected":"177Lu-PSMA-617 plus standard care improved overall survival (15.3 vs 11.3 months, HR 0.62) in PSMA-positive metastatic castration-resistant prostate cancer after ARPI and taxane.","entities":["vision","pluvicto"],"rubric":[["pluvicto","177lu","lutetium","psma-617"],["overall survival","os","15.3","11.3"],["castration-resistant","mcrpc"],["0.62"]]},{"id":"prostate-25","question":"Why might an alpha-emitting PSMA drug work after lutetium PSMA has stopped working?","category":"reasoning","difficulty":3,"audience":"clinician","expected":"Alpha particles (actinium-225) deposit far more energy over 50-100 µm, causing clustered double-strand breaks independent of oxygen and cell cycle, so beta-resistant, hypoxic, or small-volume disease can still be killed; retrospective series show PSA responses in about half after 177Lu failure. Supply of Ac-225 and salivary toxicity are the limits.","entities":["beta-then-alpha","targeted-alpha-therapy","ac225-psma","alpha-vs-beta"],"rubric":[["alpha"],["actinium","225ac","ac-225"],["double-strand","energy","let","clustered"],["supply","salivary","xerostomia","toxicity"]]},{"id":"prostate-26","question":"What is the first FDA-cleared AI pathology tool that predicts treatment benefit, and in which cancer?","category":"factual","difficulty":2,"audience":"analyst","expected":"ArteraAI Prostate (de novo authorisation, August 2025) predicts prognosis and benefit from short-term androgen deprivation with radiotherapy in localised prostate cancer.","entities":["artera-ai-prostate","digital-pathology-ai"],"rubric":[["artera"],["prostate"],["androgen deprivation","adt","hormone"],["2025"]]},{"id":"bladder-27","question":"What regimen replaced platinum chemotherapy as first-line treatment for advanced bladder cancer, and how big was the effect?","category":"factual","difficulty":2,"audience":"clinician","expected":"Enfortumab vedotin plus pembrolizumab (EV-302): OS 31.5 vs 16.1 months, HR 0.47.","entities":["enfortumab-vedotin","ev-302","urothelial"],"rubric":[["enfortumab","padcev"],["pembrolizumab","keytruda"],["ev-302","ev 302"],["31.5","16.1","0.47","nearly doubled","doubled"]]},{"id":"bladder-28","question":"What was the first cancer drug approved on the basis of a blood test for leftover disease?","category":"factual","difficulty":2,"audience":"analyst","expected":"Atezolizumab for ctDNA-positive muscle-invasive bladder cancer after cystectomy (IMvigor011, using Signatera), approved Q2 2026; DFS HR 0.64, OS HR 0.59.","entities":["atezolizumab","imvigor011","signatera","mrd-testing"],"rubric":[["atezolizumab","tecentriq"],["ctdna","signatera","minimal residual","mrd"],["bladder","nmibc-vs-mibc"],["imvigor011","imvigor 011"]]},{"id":"gi-29","question":"Which cancer gene was called undruggable for forty years and what changed?","category":"factual","difficulty":2,"audience":"patient","expected":"KRAS. In 2013 a covalent pocket was found in the G12C mutant; sotorasib (2021) and adagrasib followed, and pan-RAS(ON) inhibitors such as daraxonrasib are now in phase 3 for pancreatic cancer.","entities":["kras","kras-inhibitors","sotorasib","daraxonrasib","kras-roadmap"],"rubric":[["kras","ras"],["sotorasib","lumakras","adagrasib","krazati"],["g12c","pocket","covalent"],["daraxonrasib","pan-ras","rmc-6236","pancrea"]]},{"id":"gi-30","question":"What is daraxonrasib and where does it stand?","category":"factual","difficulty":2,"audience":"analyst","expected":"Revolution Medicines' pan-RAS(ON) tri-complex inhibitor; phase 3 RASolute 302 in second-line pancreatic cancer (reported OS benefit, HR 0.40 per the pancreatic cancer deep dive), with first-line and NSCLC phase 3 trials ongoing.","entities":["daraxonrasib","revolution-medicines","pancreatic"],"rubric":[["daraxonrasib","rmc-6236"],["revolution medicines"],["pancrea"],["phase 3","rasolute"]]},{"id":"gi-31","question":"What did the dostarlimab rectal cancer study show?","category":"factual","difficulty":2,"audience":"clinician","expected":"In mismatch-repair-deficient locally advanced rectal cancer, dostarlimab alone produced a complete clinical response in 100% of patients, sustained in more than 40 patients by 2025, allowing surgery and radiation to be avoided.","entities":["dostarlimab","msi","colorectal"],"rubric":[["dostarlimab","jemperli"],["mismatch","dmmr","msi"],["complete response","100%","disappear"],["without surgery","avoid surgery","organ preserv","no surgery"]]},{"id":"gi-32","question":"Can a blood test decide who needs chemotherapy after colon cancer surgery?","category":"reasoning","difficulty":2,"audience":"clinician","expected":"Yes in stage II: the DYNAMIC trial used ctDNA to guide adjuvant chemotherapy, halving its use (15% vs 28%) with non-inferior recurrence-free survival (93.5% vs 92.4% at two years).","entities":["dynamic","mrd-testing","ctdna"],"rubric":[["dynamic"],["ctdna","circulating tumour dna","circulating tumor dna"],["halv","15%","28%","fewer"],["non-inferior","no worse","same","safely"]]},{"id":"gi-33","question":"What was the first approval in nearly thirty years specific to locally advanced pancreatic cancer?","category":"factual","difficulty":2,"audience":"analyst","expected":"Optune Pax (tumour treating fields) with gemcitabine/nab-paclitaxel, approved Q1 2026 on PANOVA-3.","entities":["optune","ttfields","pancreatic"],"rubric":[["optune","tumor treating fields","tumour treating fields","ttfields"],["pancrea"],["2026"],["panova"]]},{"id":"gi-34","question":"Which new target has an approved antibody, an approved CAR-T in China, and ADCs in phase 3 for gastric cancer?","category":"factual","difficulty":2,"audience":"analyst","expected":"Claudin 18.2: zolbetuximab (Vyloy), satricabtagene autoleucel (satri-cel, CARsgen, China), and ADCs such as CMG901/AZD0901.","entities":["cldn18-2","satricabtagene-autoleucel","cmg901","gastric"],"rubric":[["claudin","cldn18"],["zolbetuximab","vyloy"],["satri-cel","satricabtagene","car-t"],["cmg901","azd0901","adc"]]},{"id":"gi-35","question":"Why is pancreatic cancer so hard to treat with immunotherapy?","category":"reasoning","difficulty":3,"audience":"clinician","expected":"It is immunologically cold: dense desmoplastic stroma blocks drug and T-cell entry, low mutational burden gives few neoantigens, and an immunosuppressive myeloid microenvironment. Vaccines (autogene cevumeran) and RAS inhibitors that may increase antigen presentation are the main hopes.","entities":["pancreatic","cold-vs-hot","autogene-cevumeran","fap"],"rubric":[["cold","immunosuppress","immune desert","excluded"],["stroma","desmoplas","fibro"],["neoantigen","mutational burden","tmb"],["vaccine","cevumeran","kras","ras inhibitor"]]},{"id":"io-36","question":"What fraction of advanced melanoma patients on nivolumab plus ipilimumab are alive at ten years?","category":"factual","difficulty":2,"audience":"clinician","expected":"About 43% overall survival (CheckMate 067), with melanoma-specific survival around 52%.","entities":["checkmate-067","nivolumab","ipilimumab"],"rubric":[["43%","about half","nearly half","43"],["checkmate 067","checkmate-067"],["ten years","10 years","10-year"],["nivolumab","ipilimumab"]]},{"id":"io-37","question":"What was the first personalised cancer vaccine to win a phase 3 trial?","category":"factual","difficulty":2,"audience":"analyst","expected":"Intismeran autogene (V940/mRNA-4157, Moderna/Merck) with pembrolizumab in resected stage IIB-IV melanoma: INTerpath-001 met recurrence-free and distant-metastasis-free survival, announced 19 August 2026.","entities":["intismeran-autogene","interpath-001","neoantigen-mrna-vaccine"],"rubric":[["intismeran","v940","mrna-4157"],["moderna","merck"],["melanoma"],["interpath","2026"]]},{"id":"io-38","question":"How is a personalised mRNA cancer vaccine made?","category":"factual","difficulty":2,"audience":"patient","expected":"The tumour and normal DNA are sequenced, software predicts up to 34 neoantigens unique to the tumour, a patient-specific mRNA encoding them is manufactured in lipid nanoparticles over about six weeks, and it is given with a PD-1 blocker.","entities":["neoantigen-mrna-vaccine","neoantigen","intismeran-autogene"],"rubric":[["sequenc"],["neoantigen","mutation"],["mrna"],["pembrolizumab","pd-1","checkpoint"],["weeks","manufactur","custom","personal"]]},{"id":"io-39","question":"What is the first approved TIL therapy and how well does it work?","category":"factual","difficulty":2,"audience":"clinician","expected":"Lifileucel (Amtagvi, Iovance), approved 2024 for anti-PD-1-refractory melanoma: response rate about 31%, with roughly a third of responders still responding at five years.","entities":["lifileucel","til-therapy"],"rubric":[["lifileucel","amtagvi"],["melanoma"],["31%","third","a third"],["2024"]]},{"id":"io-40","question":"What are the main side effects of checkpoint inhibitors and how are they handled?","category":"procedural","difficulty":2,"audience":"patient","expected":"Immune-related adverse events such as colitis, thyroid problems, rash, hepatitis, and pneumonitis, most common with CTLA-4 plus PD-1 combinations; treated with steroids and sometimes other immunosuppressants, some endocrine effects are permanent.","entities":["irae","checkpoint-inhibitor"],"rubric":[["immune-related","autoimmune","irae"],["colitis","thyroid","rash","hepatitis","pneumonitis"],["steroid","corticosteroid"],["combination","ctla-4","ipilimumab"]]},{"id":"io-41","question":"Why did TIGIT-blocking antibodies fail despite promising early data?","category":"reasoning","difficulty":3,"audience":"analyst","expected":"Phase 3 trials (SKYSCRAPER-01, -02 and others) did not add benefit to PD-(L)1 blockade in NSCLC and SCLC; phase 2 signals did not reproduce, and the roles of Fc-effector function and patient selection remain debated.","entities":["tigit","tigit-plus-pd1-caution"],"rubric":[["skyscraper","phase 3"],["did not","failed","negative","no benefit"],["fc","patient selection","redundan","unclear","debated"],["nsclc","lung"]]},{"id":"io-42","question":"What does 'hot' versus 'cold' tumour mean?","category":"factual","difficulty":1,"audience":"patient","expected":"Hot tumours are full of immune cells and tend to respond to immunotherapy; cold tumours have kept the immune system out (immune-excluded or immune-desert), such as pancreatic, prostate, glioblastoma, and most HR+ breast cancers.","entities":["cold-vs-hot"],"rubric":[["immune cells","t cells","infiltrat"],["respond"],["excluded","desert","kept out","few immune"],["pancrea","prostate","glioblastoma"]]},{"id":"heme-43","question":"What is CAR-T and which cancers is it approved for?","category":"factual","difficulty":1,"audience":"patient","expected":"A patient's T cells are engineered with a synthetic receptor, multiplied, and returned. Approved CD19 products treat B-cell lymphomas and leukaemias; BCMA products treat multiple myeloma; the first solid-tumour approval (Claudin 18.2, gastric) is in China.","entities":["car-t","cd19","bcma"],"rubric":[["t cell","t-cell"],["engineer","receptor","modified"],["lymphoma","leukaemia","leukemia"],["myeloma"]]},{"id":"heme-44","question":"What were the first checkpoint inhibitor and the first ADC ever approved?","category":"factual","difficulty":2,"audience":"analyst","expected":"Ipilimumab (2011) was the first checkpoint inhibitor; gemtuzumab ozogamicin (Mylotarg, 2000) was the first ADC, withdrawn in 2010 and re-approved in 2017.","entities":["ipilimumab","gemtuzumab-ozogamicin","adc-generations"],"rubric":[["ipilimumab","yervoy"],["2011"],["gemtuzumab","mylotarg"],["2000"]]},{"id":"heme-45","question":"What is the first menin inhibitor and who is it for?","category":"factual","difficulty":2,"audience":"clinician","expected":"Revumenib (Revuforj, Syndax), approved 2024 for relapsed KMT2A-rearranged acute leukaemia and 2025 for NPM1-mutant AML.","entities":["revumenib","menin"],"rubric":[["revumenib","revuforj"],["menin"],["kmt2a","npm1"],["leukaemia","leukemia","aml"]]},{"id":"heme-46","question":"How did CAR-T change second-line treatment of large B-cell lymphoma?","category":"factual","difficulty":2,"audience":"clinician","expected":"ZUMA-7 showed axicabtagene ciloleucel beats standard chemotherapy plus transplant for early relapse; CAR-T is now second-line standard, curing around 40% of relapsed patients.","entities":["axicabtagene-ciloleucel","dlbcl"],"rubric":[["axicabtagene","axi-cel","yescarta"],["zuma-7","zuma 7"],["transplant"],["second line","second-line","early relapse"]]},{"id":"heme-47","question":"Why does venetoclax work in leukaemia?","category":"reasoning","difficulty":2,"audience":"patient","expected":"It blocks BCL-2, the protein that stops leukaemia cells from self-destructing, so the built-in death programme (apoptosis) can run; used in CLL (fixed duration with obinutuzumab) and AML (with azacitidine).","entities":["venetoclax","bcl2","apoptosis-bcl2"],"rubric":[["bcl-2","bcl2"],["apoptosis","self-destruct","die","death"],["cll","chronic lymphocytic"],["aml","azacitidine"]]},{"id":"img-48","question":"What is the difference between a CT scan and a PET scan?","category":"factual","difficulty":1,"audience":"patient","expected":"CT is a fast 3D X-ray showing size and shape; PET shows biology by tracking where a radioactive tracer accumulates (for example glucose uptake with FDG or a specific protein such as PSMA). PET/CT combines both.","entities":["ct","pet","pet-ct","fdg-pet"],"rubric":[["x-ray","anatom","shape","size"],["tracer","radioactive","biolog","metabol"],["glucose","fdg","psma"],["pet/ct","combine","both"]]},{"id":"img-49","question":"What does a FAPI PET scan see that an FDG scan often misses?","category":"factual","difficulty":2,"audience":"clinician","expected":"The activated fibroblasts (FAP) in tumour stroma, present in more than 90% of epithelial cancers, giving high contrast in pancreatic, gastric, HCC, and peritoneal disease where FDG is weak; it is not yet approved.","entities":["fapi-pet","fap"],"rubric":[["fibroblast","fap","stroma"],["pancrea","gastric","peritoneal","hcc","liver"],["contrast","background","sensitiv"],["not yet approved","registration","trial","investigational"]]},{"id":"img-50","question":"What is the Galleri test and where does it stand with the FDA?","category":"factual","difficulty":2,"audience":"analyst","expected":"GRAIL's methylation-based multi-cancer early detection blood test for more than 50 cancers; PMA submitted January 2026 on PATHFINDER 2 and NHS-Galleri data, FDA advisory committee 23 September 2026. NHS-Galleri missed its primary stage III-IV reduction endpoint (stage IV fell ~14%).","entities":["galleri","mced","nhs-galleri","pathfinder-2"],"rubric":[["grail"],["methylation","cfdna","blood"],["advisory committee","september 2026","pma","fda"],["nhs-galleri","pathfinder"]]},{"id":"img-51","question":"What is positive predictive value and why does it matter for a cancer screening blood test?","category":"reasoning","difficulty":2,"audience":"patient","expected":"The chance that a positive result is truly cancer. With a low-prevalence disease even a highly specific test yields many false positives; Galleri's PPV in PATHFINDER 2 was around 40-60%, so roughly half of positives lead to a diagnostic workup that finds no cancer.","entities":["ppv","mced","galleri"],"rubric":[["positive result","test says","positive is"],["false positive","prevalence","half","40","60"],["workup","anxiety","follow-up","further tests"],["galleri","mced","screening"]]},{"id":"img-52","question":"What is a liquid biopsy used for in cancer care today?","category":"factual","difficulty":1,"audience":"patient","expected":"A blood test reading tumour DNA fragments: to genotype a tumour when tissue is scarce, to track resistance mutations (EGFR T790M, ESR1), to detect minimal residual disease after surgery, and, experimentally, to screen for cancer.","entities":["liquid-biopsy","ctdna","mrd-testing"],"rubric":[["dna","ctdna"],["mutation","genotyp","resistance"],["residual","mrd","after surgery","recurrence"],["screen","early detection"]]},{"id":"img-53","question":"How could a TROP2 PET scan change how ADCs are used?","category":"reasoning","difficulty":3,"audience":"clinician","expected":"It would map antigen expression across all lesions and over time, potentially selecting patients, choosing between TROP2 ADCs, and detecting antigen loss at progression to guide a switch to a different target, as PSMA PET does for Pluvicto. First-in-human tracers exist; no outcome data yet.","entities":["trop2-pet","idea-trop2-pet-selection","trop2-pet-to-adc"],"rubric":[["select","choose","predict","eligib"],["heterogene","all lesions","whole-body","across"],["antigen loss","progression","switch","monitor"],["psma","early","first-in-human","no outcome","not yet"]]},{"id":"tech-54","question":"What are the three parts of an antibody-drug conjugate and what does each do?","category":"factual","difficulty":1,"audience":"patient","expected":"An antibody that finds the tumour cell, a linker that holds the payload in the blood and releases it inside the cell, and a payload, a very potent chemotherapy such as a topoisomerase-I inhibitor.","entities":["adc","payload","linker"],"rubric":[["antibody"],["linker"],["payload","chemotherapy","toxin","drug"],["target","find","bind","deliver"]]},{"id":"tech-55","question":"What is the bystander effect in ADCs?","category":"factual","difficulty":2,"audience":"clinician","expected":"A released, membrane-permeable payload diffuses out of the targeted cell and kills neighbouring cells that lack the antigen; requires a cleavable linker and permeable payload (DXd, MMAE, SN-38), explaining T-DXd's activity in HER2-low disease and T-DM1's lack of it.","entities":["bystander-effect","trastuzumab-deruxtecan","trastuzumab-emtansine"],"rubric":[["neighbour","neighbor","nearby","adjacent"],["antigen","lack","negative","don't express"],["permeable","cleavable"],["dxd","mmae","sn-38","t-dm1"]]},{"id":"tech-56","question":"What is drug-to-antibody ratio and why does it matter?","category":"factual","difficulty":2,"audience":"clinician","expected":"The number of payload molecules per antibody, typically 2-8. Higher DAR delivers more drug per binding event (T-DXd about 8) but increases hydrophobicity and clearance unless hydrophilic linkers are used.","entities":["dar","site-specific-conjugation"],"rubric":[["payload molecules","drugs per antibody","number of"],["2","8"],["more drug","potenc","deliver"],["hydrophob","aggregat","clearance","linker"]]},{"id":"tech-57","question":"What is synthetic lethality and what is the proven clinical example?","category":"factual","difficulty":2,"audience":"clinician","expected":"Two genes where losing either alone is survivable but losing both kills the cell; tumours with BRCA loss die when PARP is inhibited, the basis of olaparib and other PARP inhibitors.","entities":["synthetic-lethality","parp-inhibitor","brca"],"rubric":[["two genes","both","either alone"],["brca"],["parp"],["olaparib","parp inhibitor"]]},{"id":"tech-58","question":"How does a PROTAC differ from a conventional inhibitor?","category":"reasoning","difficulty":2,"audience":"clinician","expected":"Rather than blocking a protein's active site it recruits an E3 ubiquitin ligase to tag the protein for destruction by the proteasome, removing the whole protein including scaffolding functions, catalytically and at sub-stoichiometric doses.","entities":["protac-degrader","vepdegestrant"],"rubric":[["degrad","destroy","remov"],["e3","ubiquitin","ligase"],["proteasome"],["block","inhibit","active site"]]},{"id":"tech-59","question":"What is in vivo CAR-T and why is it exciting?","category":"factual","difficulty":2,"audience":"analyst","expected":"Targeted lipid nanoparticles or viral vectors deliver CAR-encoding mRNA or DNA to T cells inside the patient, avoiding manufacturing, lymphodepletion, and wait time and allowing redosing; first-in-human data in 2025-26 show B-cell depletion. AbbVie bought Capstan for up to $2.1B.","entities":["in-vivo-car-t","car-t"],"rubric":[["inside the body","in the patient","in vivo","injection"],["lipid nanoparticle","lnp","vector"],["manufactur","off-the-shelf","wait"],["capstan","abbvie","redos"]]},{"id":"tech-60","question":"What is a bispecific ADC and why might it beat a normal one?","category":"reasoning","difficulty":2,"audience":"clinician","expected":"Its antibody binds two different tumour antigens (for example EGFR and HER3), improving avidity, internalisation, and tumour selectivity and hitting cells that express either antigen, addressing heterogeneity; iza-bren is the first with positive phase 3 data.","entities":["bispecific-adc","izalontamab-brengitecan"],"rubric":[["two","dual","both"],["internalis","internaliz","avidity","selectiv"],["heterogene","either antigen"],["iza-bren","izalontamab","egfr","her3"]]},{"id":"tech-61","question":"What is FLASH radiotherapy?","category":"factual","difficulty":2,"audience":"analyst","expected":"Delivering a full radiation dose in under a second at ultra-high dose rates (>40 Gy/s), which spares normal tissue in animal models; first-in-human trials (FAST-01/02, Varian) show feasibility but the clinical benefit is unproven.","entities":["flash-rt"],"rubric":[["under a second","ultra-high","dose rate","milliseconds","40 gy"],["spar","normal tissue","toxicity"],["animal","preclinical","unproven","feasib"],["fast-01","varian","proton","electron"]]},{"id":"tech-62","question":"What is brachytherapy and where is it essential?","category":"factual","difficulty":1,"audience":"patient","expected":"Placing a radioactive source directly inside or next to the tumour; essential in cervical cancer, used in prostate (seeds or HDR), breast, skin, and eye melanoma.","entities":["brachytherapy","cervical","prostate"],"rubric":[["inside","next to","within","implant","seed"],["radioactive","radiation"],["cervical","cervix"],["prostate"]]},{"id":"tech-63","question":"What is the difference between lutetium-177 and actinium-225 as therapeutic isotopes?","category":"factual","difficulty":2,"audience":"clinician","expected":"177Lu emits beta particles (range 1-10 mm, crossfire helps bulky heterogeneous tumours, marrow toxicity, 6.7-day half-life); 225Ac emits alpha particles (range 50-100 µm, very high energy, oxygen-independent clustered DNA damage, good for micrometastases, daughter redistribution and supply constraints).","entities":["alpha-vs-beta","radioligand-therapy","targeted-alpha-therapy"],"rubric":[["beta"],["alpha"],["range","mm","µm","micromet"],["supply","daughter","marrow","toxicity"]]},{"id":"tech-64","question":"Why is actinium-225 supply a problem?","category":"reasoning","difficulty":2,"audience":"analyst","expected":"It is made in tiny quantities from a legacy thorium-229 stockpile or accelerators; commercial-scale expansion is a 3-5 year effort (TerraPower's Philadelphia plant aims for a 20-fold increase), so phase 3 alpha trials and future launches are gated by production.","entities":["terrapower-isotopes","targeted-alpha-therapy","orano-med","itm"],"rubric":[["thorium","stockpile","accelerator","produc"],["terrapower"],["years","scale","capacity"],["trials","launch","gate","bottleneck","constraint"]]},{"id":"tech-65","question":"What is tumour treating fields and which cancers is it approved for?","category":"factual","difficulty":1,"audience":"patient","expected":"Wearable electrode arrays delivering alternating electric fields that disrupt cell division; approved for glioblastoma, mesothelioma, NSCLC after platinum, and (2026) locally advanced pancreatic cancer.","entities":["ttfields","optune"],"rubric":[["electric field","electrode","wearable"],["glioblastoma"],["pancrea"],["lung","nsclc","mesothelioma"]]},{"id":"tech-66","question":"What are foundation models in pathology and what have they enabled?","category":"factual","difficulty":2,"audience":"analyst","expected":"Very large self-supervised models trained on millions of slides (Virchow, UNI, CONCH, Prov-GigaPath) that adapt to many tasks; they predict molecular status from H&E and power FDA-cleared tools such as ArteraAI Prostate and ArteraAI Breast.","entities":["pathology-foundation-model","digital-pathology-ai","artera"],"rubric":[["self-supervised","millions of slides","large","pretrain"],["virchow","uni","conch","gigapath"],["molecular","msi","her2","predict"],["artera","fda"]]},{"id":"path-67","question":"Explain the PI3K/AKT/mTOR pathway in one paragraph and name approved drugs against it.","category":"factual","difficulty":2,"audience":"clinician","expected":"Growth receptors activate PI3K (PIK3CA), which produces PIP3 and recruits AKT; PTEN reverses it; AKT releases mTORC1 to drive growth. Drugs: alpelisib and inavolisib (PI3Kα), capivasertib (AKT), everolimus (mTOR), gedatolisib (PI3K/mTOR, 2026).","entities":["pi3k-akt-mtor","capivasertib","inavolisib","gedatolisib"],"rubric":[["pi3k","pik3ca"],["akt"],["mtor"],["pten"],["capivasertib","inavolisib","alpelisib","everolimus","gedatolisib"]]},{"id":"path-68","question":"Why does blocking BRAF alone cause problems that adding a MEK inhibitor fixes?","category":"reasoning","difficulty":3,"audience":"clinician","expected":"BRAF inhibitor monotherapy causes paradoxical MEK/ERK reactivation through CRAF dimers (and secondary skin cancers); blocking MEK downstream closes the escape and improves PFS and OS in melanoma.","entities":["braf-plus-mek","braf","ras-mapk"],"rubric":[["paradox","reactivat"],["mek"],["craf","dimer","downstream"],["skin cancer","squamous","toxicity","survival","pfs"]]},{"id":"path-69","question":"What does the cGAS-STING pathway have to do with radiation and ADCs?","category":"reasoning","difficulty":3,"audience":"clinician","expected":"DNA damage from radiation, PARP inhibitors, and TOP1 payloads spills DNA into the cytoplasm; cGAS senses it, STING triggers type I interferon and chemokines that recruit and prime T cells, underlying immunogenic cell death, the abscopal effect, and ADC+IO synergy.","entities":["cgas-sting","abscopal-effect","adc-plus-io"],"rubric":[["cgas","sting"],["cytoplasm","cytosol","micronucle"],["interferon"],["t cell","immune","abscopal","synergy"]]},{"id":"path-70","question":"What is oncogene addiction?","category":"factual","difficulty":1,"audience":"patient","expected":"When a cancer depends so completely on one mutated gene that blocking it collapses the tumour, as with EGFR, ALK, BCR-ABL, KIT, and BRAF V600E; dramatic responses then acquired resistance.","entities":["oncogene-addiction","kinase-inhibitors"],"rubric":[["depend","rel","addict"],["one gene","single","one mutated"],["egfr","alk","bcr-abl","kit","braf"],["resistance"]]},{"id":"who-71","question":"Which hospital is ranked first in the world for oncology in 2026 and by whom?","category":"factual","difficulty":1,"audience":"analyst","expected":"Memorial Sloan Kettering Cancer Center, by Newsweek/Statista's World's Best Specialized Hospitals 2026; MD Anderson is second.","entities":["mskcc","md-anderson","newsweek-hospitals"],"rubric":[["memorial sloan kettering","msk"],["newsweek","statista"],["md anderson"],["2026"]]},{"id":"who-72","question":"How many NCI-designated cancer centers are there and what types?","category":"factual","difficulty":1,"audience":"analyst","expected":"74 in 2026: 58 Comprehensive, 8 Clinical, 8 Basic Laboratory.","entities":["nci-cancer-centers","nci"],"rubric":[["74"],["58","comprehensive"],["clinical"],["basic"]]},{"id":"who-73","question":"Where was FAPI PET invented?","category":"factual","difficulty":2,"audience":"analyst","expected":"Heidelberg (University Hospital, DKFZ/NCT; Haberkorn, Giesel, Kratochwil), which also ran the first-in-human 225Ac-PSMA therapy.","entities":["heidelberg-nct","fapi-pet"],"rubric":[["heidelberg"],["dkfz","nct","university hospital"],["haberkorn","giesel","kratochwil","germany"],["psma","actinium","225ac"]]},{"id":"who-74","question":"Which company owns Trodelvy and how did it get it?","category":"factual","difficulty":1,"audience":"analyst","expected":"Gilead Sciences, through its $21 billion acquisition of Immunomedics in 2020.","entities":["gilead","sacituzumab-govitecan"],"rubric":[["gilead"],["immunomedics"],["21","acqui","bought"],["2020"]]},{"id":"who-75","question":"Which company develops sacituzumab tirumotecan and who holds ex-China rights?","category":"factual","difficulty":2,"audience":"analyst","expected":"Sichuan Kelun-Biotech developed sac-TMT (approved in China 2024); Merck holds ex-Greater-China rights and runs the TroFuse phase 3 programme; FDA priority voucher July 2026.","entities":["sacituzumab-tirumotecan","kelun-biotech","merck"],"rubric":[["kelun"],["merck","msd"],["china"],["trofuse","phase 3","voucher"]]},{"id":"who-76","question":"Where can I look up whether a specific tumour mutation has an approved drug?","category":"procedural","difficulty":1,"audience":"clinician","expected":"OncoKB (MSK, FDA-recognised levels of evidence) and CIViC (open, community-curated); cBioPortal to see mutation frequency; ClinicalTrials.gov for trials.","entities":["oncokb","civic","cbioportal","clinicaltrials-gov"],"rubric":[["oncokb"],["civic"],["cbioportal","clinicaltrials"],["evidence","level","actionab"]]},{"id":"who-77","question":"What is DepMap for?","category":"factual","difficulty":2,"audience":"analyst","expected":"The Broad Institute's Cancer Dependency Map: genome-wide CRISPR and drug screens across more than 1,000 cancer cell lines showing which genes each line cannot live without, the source of synthetic-lethal targets like PRMT5/MTAP.","entities":["depmap","crispr-screens","broad-institute"],"rubric":[["crispr","knockout","screen"],["cell lines","1,000","1000"],["depend","cannot live without","essential"],["broad"]]},{"id":"who-78","question":"Which cooperative group ran the trial that put nivolumab into first-line Hodgkin lymphoma?","category":"factual","difficulty":2,"audience":"analyst","expected":"SWOG (S1826, nivolumab-AVD vs BV-AVD), leading to FDA approval in March 2026 for ages 12 and over.","entities":["swog","nivolumab","hodgkin-lymphoma"],"rubric":[["swog"],["s1826"],["nivolumab","opdivo"],["hodgkin"]]},{"id":"proc-79","question":"My relative has metastatic pancreatic cancer. How do we find a clinical trial?","category":"procedural","difficulty":1,"audience":"patient","expected":"Ask the oncologist about trials at the treating centre and referral to an NCI-designated or major academic centre; search ClinicalTrials.gov (status recruiting, condition pancreatic cancer, filter by location); OnCo's cancer page has a live recruiting-trials list; ask about RAS inhibitor trials such as daraxonrasib.","entities":["pancreatic","clinicaltrials-gov","daraxonrasib","cancer-commons"],"rubric":[["clinicaltrials.gov","clinicaltrials"],["oncologist","doctor","referral","centre","center"],["recruiting","location","near"],["daraxonrasib","kras","ras"]]},{"id":"proc-80","question":"What should I ask before starting an ADC such as Enhertu?","category":"procedural","difficulty":2,"audience":"patient","expected":"How lung inflammation (ILD) will be monitored and what symptoms to report immediately; HER2 status and how it was scored; expected nausea, hair loss, and blood counts; dosing schedule (every three weeks); how response will be assessed and when; what comes next if it stops working.","entities":["trastuzumab-deruxtecan","ild","her2-low"],"rubric":[["ild","lung","pneumonitis","interstitial","breath","cough"],["her2"],["nausea","hair","blood count","neutropen","side effect"],["schedule","three weeks","every 3 weeks","how often"],["next","if it stops","after","progress"]]},{"id":"proc-81","question":"Who should have germline genetic testing when diagnosed with cancer?","category":"procedural","difficulty":2,"audience":"clinician","expected":"All patients with TNBC, ovarian, pancreatic, or metastatic prostate cancer, increasingly all breast cancer, and anyone with suggestive family history; results change surgery, drug choice (PARP inhibitors), and family screening.","entities":["germline-testing","brca","tnbc","ovarian","pancreatic","prostate"],"rubric":[["triple-negative","tnbc","breast"],["ovarian"],["pancrea"],["prostate"],["parp","family","surgery"]]},{"id":"proc-82","question":"How do I get a second opinion for a rare cancer?","category":"procedural","difficulty":1,"audience":"patient","expected":"Ask your oncologist for referral to a high-volume centre (NCI-designated in the US, ESMO-accredited or national reference centres elsewhere); nonprofits such as Cancer Commons offer free navigation; bring pathology slides, genomic reports, and imaging; telemedicine second opinions exist.","entities":["cancer-commons","nci-cancer-centers","mskcc"],"rubric":[["refer","ask"],["nci","high-volume","reference","academic","comprehensive"],["cancer commons","navigat","nonprofit","advocacy"],["slides","reports","imaging","records"]]},{"id":"proc-83","question":"What is exercise oncology and is there real evidence?","category":"factual","difficulty":1,"audience":"patient","expected":"Structured exercise during and after treatment; the CHALLENGE trial (2025) randomised colon cancer survivors and showed improved disease-free and overall survival, the first level-1 evidence, plus less fatigue and neuropathy.","entities":["exercise-oncology","colorectal"],"rubric":[["challenge"],["colon","colorectal"],["survival"],["randomis","randomiz","trial","level-1","evidence"]]},{"id":"proc-84","question":"Does scalp cooling prevent hair loss from chemotherapy?","category":"factual","difficulty":1,"audience":"patient","expected":"Partly: roughly half of patients on taxane-based regimens keep at least 50% of their hair with DigniCap or Paxman; it is less effective with anthracyclines and reimbursement varies.","entities":["scalp-cooling"],"rubric":[["half","50%","partly","some"],["taxane","paclitaxel","docetaxel"],["anthracycline","less effective","doxorubicin"],["dignicap","paxman","cold cap","cooling cap"]]},{"id":"proc-85","question":"What does a 'Phase 3' trial mean compared with Phase 1?","category":"factual","difficulty":1,"audience":"patient","expected":"Phase 1 tests safety and dose in a small group; Phase 2 looks for activity; Phase 3 randomises hundreds to thousands of patients against the current standard to prove benefit, the usual basis for full approval.","entities":["first-line","accelerated-approval","standard-of-care"],"rubric":[["safety","dose"],["random","compar","standard"],["hundreds","thousands","large"],["approval"]]},{"id":"proc-86","question":"What is accelerated approval and what are its risks for patients?","category":"reasoning","difficulty":2,"audience":"patient","expected":"FDA approval based on early evidence such as tumour shrinkage or pCR, conditional on a confirmatory trial; if confirmation fails the drug is withdrawn (atezolizumab in TNBC, belantamab in 2022, sacituzumab in bladder cancer), so benefit is not yet proven when prescribed.","entities":["accelerated-approval","impassion130","belantamab-mafodotin"],"rubric":[["surrogate","early","shrink","response","pcr"],["confirmatory"],["withdraw"],["atezolizumab","belantamab","sacituzumab","not yet proven","unproven"]]},{"id":"pipe-87","question":"List the generations of ADC technology and what defined each.","category":"factual","difficulty":3,"audience":"analyst","expected":"First (gemtuzumab, 2000: unstable linker, heterogeneous); second (brentuximab 2011, T-DM1 2013: humanised antibodies, potent tubulin payloads, stable linkers, no bystander for T-DM1); third (T-DXd, sacituzumab, 2019-22: high-DAR TOP1 payloads with bystander effect); fourth emerging (bispecific, dual-payload, degrader, immune-stimulating, masked, radio-ADCs).","entities":["adc-generations","adc"],"rubric":[["gemtuzumab","mylotarg","first"],["brentuximab","t-dm1","second"],["dxd","sacituzumab","topoisomerase","bystander","third"],["bispecific","dual-payload","dual payload","degrader","fourth","next"]]},{"id":"pipe-88","question":"What are the three approved or near-approved TROP2 ADCs and how do their payloads differ?","category":"factual","difficulty":3,"audience":"analyst","expected":"Sacituzumab govitecan (SN-38, DAR ~7.6, hydrolysable linker), datopotamab deruxtecan (DXd, DAR ~4, GGFG cleavable linker), and sacituzumab tirumotecan (belotecan-derived T030, DAR ~7.4, stable linker; approved in China, US decision pending).","entities":["sacituzumab-govitecan","datopotamab-deruxtecan","sacituzumab-tirumotecan","trop2-adc-roadmap"],"rubric":[["sacituzumab govitecan","trodelvy"],["datopotamab","dato-dxd","datroway"],["tirumotecan","sac-tmt","skb264","mk-2870"],["sn-38","dxd","belotecan","payload"]]},{"id":"pipe-89","question":"Which oncology drugs were approved in the US in July 2026?","category":"factual","difficulty":3,"audience":"analyst","expected":"Isatuximab subcutaneous (Sarclisa Escena), pembrolizumab SC plus enfortumab vedotin, selpercatinib label update, gedatolisib (Revtorpyk), zidesamtinib (Jideytro), and a Pluvicto label expansion.","entities":["gedatolisib","zidesamtinib","pluvicto","selpercatinib","fda-approvals"],"rubric":[["gedatolisib","revtorpyk"],["zidesamtinib","jideytro"],["pluvicto","lutetium"],["isatuximab","sarclisa","selpercatinib","enfortumab"]]},{"id":"pipe-90","question":"What happened to tazemetostat in 2026?","category":"factual","difficulty":2,"audience":"analyst","expected":"Ipsen withdrew Tazverik from all markets and indications on 9 March 2026 after SYMPHONY-1 showed excess secondary haematologic malignancies (5.7% vs none), and stopped its trials.","entities":["ezh2"],"rubric":[["withdr"],["march 2026","2026"],["secondary","blood cancer","haematologic","hematologic","malignanc"],["ipsen","symphony"]]},{"id":"pipe-91","question":"What is the readout calendar event on 23 September 2026?","category":"factual","difficulty":1,"audience":"analyst","expected":"The FDA advisory committee (Molecular and Clinical Genetics Panel) reviewing GRAIL's Galleri multi-cancer early detection PMA.","entities":["galleri","mced"],"rubric":[["advisory committee","adcom","panel"],["galleri","grail"],["fda"],["multi-cancer","mced","early detection"]]},{"id":"pipe-92","question":"Name three next-generation ADC concepts beyond bispecific antibodies.","category":"factual","difficulty":2,"audience":"analyst","expected":"Dual-payload ADCs, degrader-antibody conjugates, immune-stimulating antibody conjugates, masked or conditionally active ADCs, peptide-drug conjugates, radio-ADCs.","entities":["dual-payload-adc","degrader-antibody-conjugate","immune-stimulating-adc","masked-adc"],"rubric":[["dual-payload","dual payload","two payload"],["degrader"],["immune-stimulating","isac","tlr","sting"],["masked","probody","conditional","peptide","radio"]]},{"id":"pipe-93","question":"Which company's PD-1×VEGF bispecific did BMS license, and for how much?","category":"factual","difficulty":2,"audience":"analyst","expected":"BioNTech's pumitamig (BNT327), in a 2025 deal valued at about $11 billion.","entities":["biontech","bms"],"rubric":[["biontech"],["bnt327","pumitamig"],["11","billion"],["2025"]]},{"id":"pipe-94","question":"What is the rationale for combining an ADC with a checkpoint inhibitor, and where is it proven?","category":"reasoning","difficulty":2,"audience":"clinician","expected":"ADC payloads cause immunogenic cell death and STING activation, releasing antigens and depleting suppressive myeloid cells; PD-1 blockade converts that priming into durable control. Proven in urothelial cancer (EV-302) and TNBC (ASCENT-04).","entities":["adc-plus-io","ev-302","ascent-04"],"rubric":[["immunogenic","sting","antigen","prim"],["ev-302","enfortumab","bladder","urothelial"],["ascent-04","tnbc","sacituzumab"],["pembrolizumab","checkpoint","pd-1"]]},{"id":"pipe-95","question":"Why do OnCo's institution rankings differ from research-output rankings?","category":"reasoning","difficulty":2,"audience":"analyst","expected":"OnCo's score sums Newsweek 2026 rank points, NCI designation points, and links in the corpus, so it measures clinical reputation plus documentation coverage, while Nature Index and SCImago count publications; both formulas are disclosed and neither measures clinical benefit.","entities":["newsweek-hospitals","nature-index","scimago-oncology"],"rubric":[["newsweek"],["nci"],["link","corpus","coverage","documented"],["nature index","scimago","publication","output"]]},{"id":"reason-96","question":"A patient with HER2-low, hormone-positive metastatic breast cancer has progressed on a CDK4/6 inhibitor and one chemotherapy. What are the ADC options and how would you order them?","category":"reasoning","difficulty":3,"audience":"clinician","expected":"T-DXd (DESTINY-Breast04/06) is generally first among ADCs for HER2-low disease; sacituzumab govitecan (TROPiCS-02) or Dato-DXd (TROPION-Breast01) later. Both classes carry TOP1 payloads, so cross-resistance is a concern and interposing chemotherapy is debated; consider ESR1/PIK3CA-directed options if endocrine-sensitive.","entities":["trastuzumab-deruxtecan","sacituzumab-govitecan","datopotamab-deruxtecan","adc-sequencing","breast-hr-positive","hr-positive-metastatic-post-cdk46"],"rubric":[["t-dxd","enhertu","trastuzumab deruxtecan"],["sacituzumab","trodelvy","datopotamab","dato-dxd"],["her2-low","destiny-breast04","destiny-breast06"],["cross-resist","payload","sequenc"]]},{"id":"reason-97","question":"Why are mesenchymal or claudin-low triple-negative tumours hard to treat with any class of drug?","category":"reasoning","difficulty":3,"audience":"clinician","expected":"EMT programmes (ZEB1/2, SNAIL) confer stemness, apoptosis resistance, immune exclusion, and high ABC efflux transporters that pump out chemotherapy and ADC payloads (MMAE, DXd, SN-38), so efflux-independent approaches (radiation, radioligands, immune killing) are proposed.","entities":["emt","efflux-pump","idea-efflux-agnostic","tnbc"],"rubric":[["emt","epithelial","mesenchymal","zeb","snail"],["efflux","pump","abcb1","abcg2"],["immune exclu","stem","apoptosis"],["radiation","radioligand","immune","efflux-independent","agnostic"]]},{"id":"reason-98","question":"Is a positive ctDNA result after surgery a reason to start treatment right away?","category":"reasoning","difficulty":3,"audience":"clinician","expected":"It depends on proof that intervening helps: in bladder cancer IMvigor011 showed atezolizumab improves survival in ctDNA-positive patients (now approved); in colon cancer DYNAMIC supports de-escalation for negatives; in breast cancer trials are ongoing and lead time without a proven intervention mainly causes anxiety.","entities":["ctdna-mrd-to-adjuvant","imvigor011","dynamic","idea-ctdna-escalation-tnbc"],"rubric":[["depends","not always","evidence","proven"],["imvigor011","bladder","atezolizumab"],["dynamic","colon","de-escalat"],["breast","trial","anxiety","lead time","unproven"]]},{"id":"reason-99","question":"Why might personalised vaccines work better after surgery than in metastatic disease?","category":"reasoning","difficulty":2,"audience":"clinician","expected":"Tumour burden is low so immune responses are not overwhelmed, there is time for the six-week manufacturing, immunosuppression from bulky disease is absent, and recurrence-free survival is a clean endpoint; INTerpath-001 tested exactly this adjuvant setting.","entities":["neoantigen-mrna-vaccine","interpath-001","vaccine-plus-pd1"],"rubric":[["low tumour burden","low tumor burden","minimal disease","microscopic","residual"],["time","weeks","manufactur"],["immunosuppress","overwhelm","exhaust"],["adjuvant","after surgery","interpath","recurrence"]]},{"id":"reason-100","question":"What single change would most improve outcomes across all cancers, and what evidence supports it?","category":"reasoning","difficulty":3,"audience":"analyst","expected":"Prevention and early detection: HPV vaccination has driven cervical cancer toward elimination in vaccinated cohorts, tobacco control and screening (mammography, colonoscopy, low-dose CT) have proven mortality benefits, and early-stage disease is where surgery cures; MCED blood tests aim to extend this but are unproven.","entities":["hpv-vaccine","prevention","early-detection","mced","early-detection-roadmap"],"rubric":[["prevent","hpv","vaccin","tobacco","smoking"],["screen","early detection","early-stage","early stage"],["mortality","survival","cure"],["mced","blood test","galleri","unproven"]]}]