Cancer is an unreliable disease. Just as you think you are familiar with it and can begin treating and hopefully curing it, it is no longer as you thought it was.
It has coloured its hair, carries other garments, or has changed its lifestyle making it unrecognisable and impossible to manage efficiently.
A much-feared feature of cancer is its ability to metastasize, i.e., establish new colonies close to or far from its starting point in the body. Some primary tumours like brain cancers kill the patient because of their size. Most other cancers kill by spreading and harming in other places of the body. Once cancer starts to spread, it is the beginning of the end. When the surgeon proclaims: “I cut it all out, so now you’re cured,” he speaks against better judgment. The patient has received a respite until cancer finds an opportunity to grow again, spread and metastasize. In a few lucky instances, the patient’s natural mechanisms will kill the remaining cancer cells, with or without radio and chemotherapy. Unfortunately, this is the exception.
Cancer stem cells
The explanation seems to be that most cancers, presumably all, harbour a few particularly tough cells, often termed cancer stem cells, which hibernate and resist chemotherapy. When needed, they begin to divide and move to reach the vascular bed. Cells of most cancers or their DNA have been identified in the bloodstream, which is the highway of cancer spread. Most likely, circulating cancer cells are still present in the body, no matter how much cancer tissue has been removed by surgery or radiation therapy.
Cancer stem cells are a prime target for today’s biochemical and radiochemical diagnostic and therapeutic approaches. However, to detect them and their metastases is not a trivial task, as this requires a profound knowledge of the mechanisms of their development. An example is the story of bone metastases and how best to detect them.
Bone metastases
It should go without saying, although it doesn’t, that bone metastases originate from circulating cancer stem cells settling in the bone marrow. Here they live, divide and grow due to an enormous supply of blood and food. When they grow large enough the surrounding bone substance reacts by an iterative destruct-and-build process creating focal changes visible by CT, MRI, bone scintigraphy and PET/CT.
Of these, scintigraphy and PET/CT are less recognised modalities but based on multipotent principles. CT and MRI scanners use x-rays and magnetism/ radio waves, respectively, for making snapshots of structural changes. Scintigraphy and PET/CT are nuclear medicine modalities applying molecules labelled with a radioactive tracer making them visible by a gamma camera or PET/CT during their targeting of specific processes in the body following intravenous administration.
PET scans are not ultra-sharp like CT and MR images since radiation is transmitted in all directions. Yet PET is 1000 times or more sensitive with regard to detecting subtle changes. Moreover, it registers dynamic changes over time and the degree, extent and severity of the disease. These options are not available with other techniques, but pertinent for treatment triage and monitoring therapeutic efficacy. Nowadays, PET is always performed in combination with CT or MR using hybrid PET/CT or PET/MR scanners, which are the diagnostic modalities of the 21st Century. It is said that PET is not readily available, cumbersome and expensive. However, as the potential of PET becomes known to physicians, hospital owners, and health politicians, this may change dramatically. Part of the nuclear medicine community uses PET to detect bone metastases applying a sensitive tracer, i.e., sodium-fluoride where the fluoride part is the common radioactive isotope 18F, because this molecule is rapidly built into crystals which make up the bone substance. However, like CT, MRI and bone scintigraphy, this tracer depicts only what is happening in the bone matrix and not in the marrow, and such changes may persist long after the cancer cells were killed by for instance chemotherapy.
What can we learn from this?
All this leads to one conclusion: When looking for bone metastasis, one should start in the bone marrow and not the bone matrix, since the marrow is where it all begins, and still may be treatable if targeted early enough. For this purpose, the most common PET tracer of all, 18F-fluorodeoxyglucose (FDG) seems ideal as it depicts focally increased glucose consumption, a hallmark of cancer (Figure).
Things are often not as we think, and university hospital medicine can make mistakes if guided by misperceptions and outdated thinking. Instead, we should examine relevant new techniques and judge when they should replace traditional thinking and methodology. Today, this change of attitude is more necessary than ever, because the possibilities of the health care system are legio. Therefore, we urgently need more cost-effective ways to bring simplification in improvement.
Professor Poul Flemming
Høilund-Carlsen MD DMSci R
Tel: +45 3016 1445
Associate Professor Consultant
Søren Hess MD
Tel: +45 2154 2247
Soeren.Hess@rsyd.dk
Department of Nuclear Medicine – Odense University Hospital
University of Southern Denmark
