{"slug":"lung-evidence","tag":"lung-evidence","variants":["lung-evidence"],"description":"No description yet","count":51,"kinds":{"paper":44,"idea":7},"related":[],"records":[{"id":"paper-wynder-graham-tobacco-bronchiogenic-carcinoma-jama-1950","kind":"paper","name":"Tobacco smoking as a possible etiologic factor in bronchiogenic carcinoma; a study of 684 proved cases","route":"/key-papers/paper-wynder-graham-tobacco-bronchiogenic-carcinoma-jama-1950/","tldr":"One of the two 1950 studies that first tied cigarettes to lung cancer. Wynder and Graham compared the smoking histories of 684 people with proven lung cancer against people without it, and found heavy smoking almost everywhere in the cancer group."},{"id":"paper-doll-hill-mortality-of-doctors-smoking-bmj-1954","kind":"paper","name":"The mortality of doctors in relation to their smoking habits; a preliminary report","route":"/key-papers/paper-doll-hill-mortality-of-doctors-smoking-bmj-1954/","tldr":"Doll and Hill wrote to every doctor in Britain in 1951 asking how much they smoked, then waited to see who died. This first report, after two and a half years, is where the prospective evidence on smoking begins."},{"id":"paper-peto-smoking-cessation-lung-cancer-uk-bmj-2000","kind":"paper","name":"Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies","route":"/key-papers/paper-peto-smoking-cessation-lung-cancer-uk-bmj-2000/","tldr":"Quitting works, and it works even in middle age. Men who stopped at 30 had a 2 percent lifetime risk of dying of lung cancer, at 40 it was 3 percent, at 50 it was 6 percent, and those who carried on had 16 percent."},{"id":"paper-caret-beta-carotene-retinol-lung-cancer-nejm-1996","kind":"paper","name":"Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease","route":"/key-papers/paper-caret-beta-carotene-retinol-lung-cancer-nejm-1996/","tldr":"A vitamin trial in 18,314 smokers and asbestos workers was stopped early because the people taking the supplements were getting more lung cancer, not less."},{"id":"paper-hill-lung-adenocarcinoma-air-pollutants-nature-2023","kind":"paper","name":"Lung adenocarcinoma promotion by air pollutants","route":"/key-papers/paper-hill-lung-adenocarcinoma-air-pollutants-nature-2023/","tldr":"Healthy lungs already carry cancer-causing mutations. This study argues that fine particles in polluted air do not create the mutation but wake it up, which is why lung cancer happens in people who never smoked."},{"id":"paper-zhang-lung-cancer-never-smokers-nat-genet-2021","kind":"paper","name":"Genomic and evolutionary classification of lung cancer in never smokers","route":"/key-papers/paper-zhang-lung-cancer-never-smokers-nat-genet-2021/","tldr":"The Sherlock-Lung study sequenced 232 lung cancers from people who never smoked and found three distinct types, none of them carrying the tobacco damage signature. One type appears to begin decades before it is diagnosed."},{"id":"paper-plco-chest-radiograph-lung-cancer-mortality-jama-2011","kind":"paper","name":"Screening by chest radiograph and lung cancer mortality: the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized trial","route":"/key-papers/paper-plco-chest-radiograph-lung-cancer-mortality-jama-2011/","tldr":"154,901 people were randomised to yearly chest X-rays or usual care. After 13 years the number who died of lung cancer was the same in both groups. The test that had been used for decades did not work."},{"id":"paper-uspstf-lung-cancer-screening-jama-2021","kind":"paper","name":"Screening for Lung Cancer: US Preventive Services Task Force Recommendation Statement","route":"/key-papers/paper-uspstf-lung-cancer-screening-jama-2021/","tldr":"In 2021 the United States task force lowered the age at which lung screening starts from 55 to 50 and halved the smoking history needed from 30 to 20 pack-years, roughly doubling the number of people eligible."},{"id":"paper-aldrich-uspstf-screening-african-american-smokers-jama-oncol-2019","kind":"paper","name":"Evaluation of USPSTF Lung Cancer Screening Guidelines Among African American Adult Smokers","route":"/key-papers/paper-aldrich-uspstf-screening-african-american-smokers-jama-oncol-2019/","tldr":"The screening rules were written from a trial in which only 4 percent of participants were Black. In a southern United States cohort, 31 percent of white smokers qualified for screening but only 17 percent of Black smokers, even though Black smokers develop lung cancer at fewer cigarettes."},{"id":"paper-forrest-socioeconomic-inequalities-lung-cancer-treatment-plos-med-2013","kind":"paper","name":"Socioeconomic inequalities in lung cancer treatment: systematic review and meta-analysis","route":"/key-papers/paper-forrest-socioeconomic-inequalities-lung-cancer-treatment-plos-med-2013/","tldr":"Poorer patients with lung cancer are less likely to be given any treatment at all, and the gap is not explained by them being diagnosed later or by which country's health system they are in."},{"id":"paper-nsclc-collaborative-group-chemotherapy-meta-analysis-bmj-1995","kind":"paper","name":"Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials","route":"/key-papers/paper-nsclc-collaborative-group-chemotherapy-meta-analysis-bmj-1995/","tldr":"Before 1995 many doctors thought chemotherapy did nothing for lung cancer. Pooling 9,387 patients from 52 trials showed it did something: a 27 percent reduction in the risk of death when added to supportive care, worth about 10 percent more people alive at one year."},{"id":"paper-schiller-ecog-1594-four-chemotherapy-regimens-nejm-2002","kind":"paper","name":"Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer","route":"/key-papers/paper-schiller-ecog-1594-four-chemotherapy-regimens-nejm-2002/","tldr":"1,207 patients were randomised between four platinum doublets. All four gave the same result: about one in five responded and median survival was just under eight months. Chemotherapy had reached a ceiling."},{"id":"paper-scagliotti-cisplatin-pemetrexed-histology-jco-2008","kind":"paper","name":"Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer","route":"/key-papers/paper-scagliotti-cisplatin-pemetrexed-histology-jco-2008/","tldr":"1,725 patients, two chemotherapy combinations, identical survival overall. But split by what the tumour looked like down a microscope, one drug was better for adenocarcinoma and the other for squamous cancer. Histology started choosing the drug."},{"id":"paper-sandler-ecog-4599-bevacizumab-nsclc-nejm-2006","kind":"paper","name":"Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer","route":"/key-papers/paper-sandler-ecog-4599-bevacizumab-nsclc-nejm-2006/","tldr":"Adding an antibody against the tumour's blood supply to chemotherapy pushed median survival past a year for the first time in advanced lung cancer, at the cost of more treatment-related deaths."},{"id":"paper-lace-adjuvant-cisplatin-pooled-analysis-jco-2008","kind":"paper","name":"Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group","route":"/key-papers/paper-lace-adjuvant-cisplatin-pooled-analysis-jco-2008/","tldr":"Pooling 4,584 patients from the five big trials of chemotherapy after lung cancer surgery gave a clear answer: it helps, by about 5 percent at five years, and the benefit is in stage II and III rather than stage IA."},{"id":"paper-lynch-egfr-activating-mutations-gefitinib-nejm-2004","kind":"paper","name":"Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib","route":"/key-papers/paper-lynch-egfr-activating-mutations-gefitinib-nejm-2004/","tldr":"A drug that worked spectacularly in about one patient in ten and did nothing in the rest. Sequencing the tumours of nine responders found the answer: eight of them had a mutation in the gene the drug targets."},{"id":"paper-paez-egfr-mutations-gefitinib-science-2004","kind":"paper","name":"EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy","route":"/key-papers/paper-paez-egfr-mutations-gefitinib-science-2004/","tldr":"The second of the two 2004 papers that found EGFR mutations. It also explained why Japanese patients responded to gefitinib far more often than American ones: the mutation was simply much more common in Japan."},{"id":"paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009","kind":"paper","name":"Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma","route":"/key-papers/paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009/","tldr":"IPASS randomised 1,217 East Asian never-smokers and light former smokers between a tablet and chemotherapy. The tablet won, but only in the patients whose tumour carried an EGFR mutation; in the rest chemotherapy was better."},{"id":"paper-planchard-flaura2-osimertinib-chemotherapy-nejm-2023","kind":"paper","name":"Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC","route":"/key-papers/paper-planchard-flaura2-osimertinib-chemotherapy-nejm-2023/","tldr":"FLAURA2 added chemotherapy to the standard EGFR tablet in 557 patients and cut the risk of the cancer growing by 38 percent, at the cost of chemotherapy's side effects for everybody."},{"id":"paper-cho-mariposa-amivantamab-lazertinib-nejm-2024","kind":"paper","name":"Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC","route":"/key-papers/paper-cho-mariposa-amivantamab-lazertinib-nejm-2024/","tldr":"MARIPOSA beat osimertinib, the standard first treatment, by about seven months before the cancer grew again. It is the first trial to do so, and the first to show that hitting EGFR two ways at once is better than one."},{"id":"paper-lu-laura-osimertinib-stage-iii-nejm-2024","kind":"paper","name":"Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC","route":"/key-papers/paper-lu-laura-osimertinib-stage-iii-nejm-2024/","tldr":"For stage III lung cancer with an EGFR mutation, the standard consolidation immunotherapy works poorly. LAURA gave the EGFR tablet instead and pushed median time to progression from 5.6 months to 39.1."},{"id":"paper-soda-eml4-alk-fusion-nature-2007","kind":"paper","name":"Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer","route":"/key-papers/paper-soda-eml4-alk-fusion-nature-2007/","tldr":"A small inversion on chromosome 2 fuses two genes and makes a kinase that drives lung cancer. Soda and Mano found it in 5 of 75 tumours, and a drug for it was approved four years later."},{"id":"paper-kwak-crizotinib-alk-nsclc-nejm-2010","kind":"paper","name":"Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer","route":"/key-papers/paper-kwak-crizotinib-alk-nsclc-nejm-2010/","tldr":"1,500 tumours were screened to find 82 patients with an ALK fusion. Of those, 57 percent responded to crizotinib, a drug originally developed against a different target."},{"id":"paper-peters-alex-alectinib-crizotinib-nejm-2017","kind":"paper","name":"Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer","route":"/key-papers/paper-peters-alex-alectinib-crizotinib-nejm-2017/","tldr":"A newer ALK drug that gets into the brain beat the original one, and did it with fewer side effects. ALEX is why nobody starts an ALK-positive patient on crizotinib any more."},{"id":"paper-shaw-crown-lorlatinib-crizotinib-nejm-2020","kind":"paper","name":"First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer","route":"/key-papers/paper-shaw-crown-lorlatinib-crizotinib-nejm-2020/","tldr":"CROWN's third-generation ALK drug kept 78 percent of patients free of progression at a year against 39 percent on crizotinib, and controlled disease inside the brain far better."},{"id":"paper-wu-alina-adjuvant-alectinib-nejm-2024","kind":"paper","name":"Alectinib in resected ALK-positive non-small-cell lung cancer","route":"/key-papers/paper-wu-alina-adjuvant-alectinib-nejm-2024/","tldr":"After surgery for ALK-positive lung cancer, two years of alectinib kept 93.8 percent of patients disease-free at two years against 63.0 percent on chemotherapy."},{"id":"paper-wolf-geometry-mono-1-capmatinib-nejm-2020","kind":"paper","name":"Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer","route":"/key-papers/paper-wolf-geometry-mono-1-capmatinib-nejm-2020/","tldr":"MET exon 14 skipping is found in 3 to 4 percent of lung cancers. Untreated patients given capmatinib responded 68 percent of the time; those already treated, 41 percent. Order of treatment mattered more than usual."},{"id":"paper-de-langen-codebreak-200-sotorasib-docetaxel-lancet-2023","kind":"paper","name":"Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRAS G12C mutation: a randomised, open-label, phase 3 trial","route":"/key-papers/paper-de-langen-codebreak-200-sotorasib-docetaxel-lancet-2023/","tldr":"The first randomised test of a KRAS inhibitor. Sotorasib beat docetaxel on time to progression by about a month, with fewer serious side effects. A real but modest win against the commonest driver in lung cancer."},{"id":"paper-kobayashi-egfr-t790m-gefitinib-resistance-nejm-2005","kind":"paper","name":"EGFR mutation and resistance of non-small-cell lung cancer to gefitinib","route":"/key-papers/paper-kobayashi-egfr-t790m-gefitinib-resistance-nejm-2005/","tldr":"One patient, two years in complete remission on gefitinib, then relapse. Sequencing the new biopsy found a second mutation in the same gene, at position 790, that stopped the drug binding."},{"id":"paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011","kind":"paper","name":"Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors","route":"/key-papers/paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011/","tldr":"37 patients were re-biopsied when their EGFR drug stopped working. Some had the expected resistance mutation; five had turned into small-cell lung cancer. In three, the resistance disappeared when the drug was stopped."},{"id":"paper-jamal-hanjani-tracerx-evolution-nsclc-nejm-2017","kind":"paper","name":"Tracking the evolution of non-small-cell lung cancer","route":"/key-papers/paper-jamal-hanjani-tracerx-evolution-nsclc-nejm-2017/","tldr":"TRACERx sequenced several regions of 100 lung tumours instead of one. The driver mutations were usually everywhere in the tumour, but three quarters had later mutations present in only part of it, and the messier the tumour, the worse the outcome."},{"id":"paper-abbosh-phylogenetic-ctdna-lung-cancer-nature-2017","kind":"paper","name":"Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution","route":"/key-papers/paper-abbosh-phylogenetic-ctdna-lung-cancer-nature-2017/","tldr":"By building a family tree of each tumour's mutations first, the TRACERx team could find the cancer's DNA in blood after surgery and tell which patients would relapse, before any scan showed anything."},{"id":"paper-herbst-impower110-atezolizumab-pd-l1-nejm-2020","kind":"paper","name":"Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC","route":"/key-papers/paper-herbst-impower110-atezolizumab-pd-l1-nejm-2020/","tldr":"In the patients whose tumours showed the most PD-L1, immunotherapy alone gave a median survival of 20.2 months against 13.1 on chemotherapy, with far fewer severe side effects."},{"id":"paper-felip-impower010-adjuvant-atezolizumab-lancet-2021","kind":"paper","name":"Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010)","route":"/key-papers/paper-felip-impower010-adjuvant-atezolizumab-lancet-2021/","tldr":"The first trial to show that immunotherapy after lung cancer surgery delays recurrence. The benefit was concentrated in patients whose tumours expressed PD-L1."},{"id":"paper-heymach-aegean-perioperative-durvalumab-nejm-2023","kind":"paper","name":"Perioperative durvalumab for resectable non-small-cell lung cancer","route":"/key-papers/paper-heymach-aegean-perioperative-durvalumab-nejm-2023/","tldr":"Giving immunotherapy both before and after lung cancer surgery cut the risk of recurrence by about a third, and left 17.2 percent of tumours with no viable cancer at all in the specimen."},{"id":"paper-provencio-nadim-ii-perioperative-nivolumab-stage-iii-nejm-2023","kind":"paper","name":"Perioperative nivolumab and chemotherapy in stage III non-small-cell lung cancer","route":"/key-papers/paper-provencio-nadim-ii-perioperative-nivolumab-stage-iii-nejm-2023/","tldr":"A Spanish trial of 86 patients with stage III lung cancer. Adding immunotherapy before surgery left 37 percent with no viable tumour in the specimen against 7 percent, and 85 percent were alive at two years against 64."},{"id":"paper-spigel-pacific-five-year-survival-jco-2022","kind":"paper","name":"Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer","route":"/key-papers/paper-spigel-pacific-five-year-survival-jco-2022/","tldr":"Five years after the PACIFIC trial, 42.9 percent of patients given a year of immunotherapy after chemoradiotherapy were still alive, against 33.4 percent of those given placebo. A third of them had never relapsed."},{"id":"paper-turrisi-twice-daily-thoracic-radiotherapy-limited-sclc-nejm-1999","kind":"paper","name":"Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide","route":"/key-papers/paper-turrisi-twice-daily-thoracic-radiotherapy-limited-sclc-nejm-1999/","tldr":"Giving the same total radiation dose twice a day over three weeks instead of once a day over five raised five-year survival from 16 to 26 percent, at the cost of a much sorer gullet."},{"id":"paper-auperin-prophylactic-cranial-irradiation-sclc-nejm-1999","kind":"paper","name":"Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission","route":"/key-papers/paper-auperin-prophylactic-cranial-irradiation-sclc-nejm-1999/","tldr":"Pooling 987 patients from seven trials showed that irradiating the brain of people whose small-cell lung cancer had gone into remission, before any brain secondaries appeared, made them live longer."},{"id":"paper-paz-ares-caspian-durvalumab-es-sclc-lancet-2019","kind":"paper","name":"Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN)","route":"/key-papers/paper-paz-ares-caspian-durvalumab-es-sclc-lancet-2019/","tldr":"Adding immunotherapy to chemotherapy for advanced small-cell lung cancer raised median survival from 10.3 to 13.0 months. Small, but it was the second positive first-line trial in the disease in thirty years."},{"id":"paper-cheng-adriatic-durvalumab-limited-stage-sclc-nejm-2024","kind":"paper","name":"Durvalumab after chemoradiotherapy in limited-stage small-cell lung cancer","route":"/key-papers/paper-cheng-adriatic-durvalumab-limited-stage-sclc-nejm-2024/","tldr":"ADRIATIC gave immunotherapy after chemoradiotherapy for limited-stage small-cell lung cancer and lifted median survival from 33.4 to 55.9 months, the largest gain the disease has seen."},{"id":"paper-ahn-dellphi-301-tarlatamab-sclc-nejm-2023","kind":"paper","name":"Tarlatamab for patients with previously treated small-cell lung cancer","route":"/key-papers/paper-ahn-dellphi-301-tarlatamab-sclc-nejm-2023/","tldr":"The first drug in decades built specifically for small-cell lung cancer. Tarlatamab grabs a protein called DLL3 on the tumour with one arm and a T cell with the other; 40 percent of heavily pretreated patients responded."},{"id":"paper-george-sclc-genomic-profiles-nature-2015","kind":"paper","name":"Comprehensive genomic profiles of small cell lung cancer","route":"/key-papers/paper-george-sclc-genomic-profiles-nature-2015/","tldr":"Sequencing 110 small-cell lung cancers found that losing both copies of TP53 and RB1 is obligatory. That is a loss of two brakes, not a gain of a target, which is why the disease has been so hard to drug."},{"id":"paper-rudin-sclc-molecular-subtypes-nat-rev-cancer-2019","kind":"paper","name":"Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data","route":"/key-papers/paper-rudin-sclc-molecular-subtypes-nat-rev-cancer-2019/","tldr":"Small-cell lung cancer, treated as one disease for fifty years, is at least four. The subtypes are named after the transcription factor each one leans on: ASCL1, NeuroD1, YAP1 and POU2F3."},{"id":"idea-lung-screening-eligibility-by-risk-not-pack-years","kind":"idea","name":"Decide who is screened for lung cancer by individual risk, not by pack-years","route":"/ideas/idea-lung-screening-eligibility-by-risk-not-pack-years/","tldr":"The rules that decide who gets a lung scan count cigarettes. A risk model that also uses age, sex, family history, deprivation and lung disease would find more cancers in the same number of scans, and would stop excluding people who smoke less but are more likely to get the disease."},{"id":"idea-lung-never-smoker-disease-its-own-programme","kind":"idea","name":"Treat lung cancer in never-smokers as its own disease, with its own detection programme","route":"/ideas/idea-lung-never-smoker-disease-its-own-programme/","tldr":"About one lung cancer in five happens to someone who never smoked, and they are outside every screening programme in the world. The genomes show it is a different disease that grows more slowly, which is exactly the kind of cancer a screening test could catch."},{"id":"idea-lung-resistance-directed-sequencing-at-every-progression","kind":"idea","name":"Make resistance a diagnosis: sequence at every progression and choose the next line from what the tumour became","route":"/ideas/idea-lung-resistance-directed-sequencing-at-every-progression/","tldr":"When a targeted drug stops working, the tumour has usually changed in a way you can read. Most patients still move to the next treatment on a protocol rather than on a test of what actually happened."},{"id":"idea-lung-brain-metastasis-prevention-as-a-primary-endpoint","kind":"idea","name":"Measure brain metastasis prevention as a primary endpoint, not as a secondary one","route":"/ideas/idea-lung-brain-metastasis-prevention-as-a-primary-endpoint/","tldr":"Lung cancer spreads to the brain more than any other common cancer, and the newest drugs seem to stop it happening. Almost no trial is designed to prove that, so the claim stays a footnote."},{"id":"idea-lung-deprivation-gradient-treated-as-a-defect-in-delivery","kind":"idea","name":"Treat the deprivation gradient in lung cancer as a defect in delivery that can be fixed and measured","route":"/ideas/idea-lung-deprivation-gradient-treated-as-a-defect-in-delivery/","tldr":"Poorer patients with lung cancer are less likely to be offered surgery or chemotherapy, at the same stage, in systems that are free at the point of use. That is a fixable problem in how care is delivered, not a fact about the disease."},{"id":"idea-lung-small-cell-platform-with-shared-controls-and-subtypes","kind":"idea","name":"Run small-cell lung cancer as one platform with shared controls and subtype stratification","route":"/ideas/idea-lung-small-cell-platform-with-shared-controls-and-subtypes/","tldr":"Small-cell lung cancer has had two real advances in twenty-five years. It is probably four diseases being tested as one, in separate small trials that each need their own control group."},{"id":"idea-lung-uk-screening-testing-and-access-gaps","kind":"idea","name":"Close the United Kingdom lung cancer gaps the UK page names: screening rollout, diagnostic pathway, molecular testing and drug access","route":"/ideas/idea-lung-uk-screening-testing-and-access-gaps/","tldr":"A placeholder for the United Kingdom-specific gaps: where the Targeted Lung Health Check programme has reached and who it misses, how long the pathway takes from scan to treatment, how fast a tumour is genotyped, and which of the drugs on this roadmap are funded."}]}