Histology

The organising framework for every small-cell lung cancer trial designed since. It is also why the slow progress in the disease is now attributed to treating four diseases as one rather than to the biology being intractable.

The case for re-biopsy at progression, for treating resistance as a diagnosis rather than an endpoint, and for the idea of a drug holiday. It is also the origin of resistance-directed sequencing: what you give next should depend on what the tumour became.

The trial that turned EGFR testing into a standard of care rather than a research assay, and the clearest demonstration in oncology that a clinically selected population can hide two opposite treatment effects inside one positive result.

The moment lung cancer stopped being one disease for treatment purposes. Before this trial the pathology report said cancer or not cancer; after it, the subtype chose the drug, and the tissue had to be preserved well enough to answer the question.

The first time a targeted biological agent extended survival in lung cancer, and the first time median survival in the advanced setting crossed twelve months. It also set the pattern that a drug's exclusion criteria can matter as much as its mechanism.

Half of the evidence base on which every tobacco control policy in the world rests. Lung cancer was a rare disease at the start of the twentieth century and the commonest cause of cancer death by its end; this paper and Doll and Hill's are where the cause was named.