An introduction to the clinical practice of theranostics in oncology

"Those who cannot remember the past are condemned to repeat it." George Santayana 1905 "If men could learn from history, what lessons it might teach us! But passion and party blind our eyes, and the light which experience gives is a lantern on the stern, which shines only on the waves behind us!" Samuel Taylor Coleridge 1835 The medical speciality of theranostic nuclear oncology has taken three-quarters of a century to move the stern light cast retrospectively by single-centre clinical reports, to the forepeak in the bow of our theranostic craft, where prospective randomised controlled multicentre clinical trials now illuminate the way forward. This recent reorientation of nuclear medicine clinical research practice to align with that of standard medical and radiation oncology protocols, reflects the paradigm shift toward individualised molecular oncology and precision medicine. Theranostics is the epitome of personalised medicine. The specific tumour biomarker is quantitatively imaged on positron emission tomography (PET)/CT or single photon emission computed tomography (SPECT)/CT. If it is clearly demonstrated that a tumoricidal radiation absorbed dose can be delivered, the theranostic beta or alpha-emitting radionuclide pair, coupled to the same targeted molecule, is then administered, to control advanced metastatic cancer in that individual patient. This prior selection of patients who may benefit from theranostic treatment is in direct contrast to the evolving oncological indirect treatments using immune-check point inhibitors, where there is an urgent need to define biomarkers which can reliably predict response, and thus avoid the high cost and toxicity of these agents in patients who are unlikely to benefit. The immune and molecular treatment approaches of oncology are a recent phenomenon and the efficacy and safety of immune-check point blockade and chimeric antigen receptor T-cell therapies are currently under evaluation in multicentre randomised controlled trials. Such objective evaluation is compromised by the inadequacy of conventional response evaluation criteria in solid tumour (RECIST) CT/MR anatomical/functional imaging to define tumour response, in both immune-oncology and theranostic nuclear oncology. This introduction to the clinical practice of theranostics explores ways in which nuclear physicians can learn from the lessons of history, and join with their medical, surgical and radiation oncology colleagues to establish a symbiotic collaboration to realise the potential of personalised molecular medicine to control advanced cancer and actually enhance quality of life whilst prolonging survival.