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Photodynamic therapy (PDT) centers on the photochemical interaction of 3 principal components: light, photosensitizer, and oxygen. Over the past 25 years, much has been learned about the basic biophysical mechanisms of PDT, and in the future, a clearer understanding of the physics of PDT will make it possible to translate this science into improved clinical treatments. This article explores the role of explicit dosimetry in PDT and the need for individualized determination of dosimetric parameters based on the heterogeneity of optical properties and photosensitizer drug concentration. In addition, the use of a navigation system to help deliver uniform light for pleural PDT is briefly discussed.

Accelerating cancer research is expected to require new types of clinical trials. This report describes the Intensive Trial of OMics in Cancer (ITOMIC) and a participant with triple-negative breast cancer metastatic to bone, who had markedly elevated circulating tumor cells (CTCs) that were monitored 48 times over 9 months. A total of 32 researchers from 14 institutions were engaged in the patient's evaluation; 20 researchers had no prior involvement in patient care and 18 were recruited specifically for this patient. Whole-exome sequencing of 3 bone marrow samples demonstrated a novel ROS1 variant that was estimated to be present in most or all tumor cells. After an initial response to cisplatin, a hypothesis of crizotinib sensitivity was disproven. Leukapheresis followed by partial CTC enrichment allowed for the development of a differential high-throughput drug screen and demonstrated sensitivity to investigational BH3-mimetic inhibitors of BCL-2 that could not be tested in the patient because requests to the pharmaceutical sponsors were denied. The number and size of CTC clusters correlated with clinical status and eventually death. Focusing the expertise of a distributed network of investigators on an intensively monitored patient with cancer can generate high-resolution views of the natural history of cancer and suggest new opportunities for therapy. Optimization requires access to investigational drugs.