Saturday, August 18, 2018

The Abscopal Effect

In the waning years of my career as a Nuclear Radiologist, I have become somewhat more jaded than I was as a younger doc. When you see cancer and other diseases fifty times a day, sometimes getting better, sometimes getting worse, that's bound to happen. Of course, I far prefer reporting improvement, but relapses are also part of this job. The oncologists wander into the reading room every few minutes, or so it seems, anyway, to look at their patients' scans (the gantry is generally still warm). If the news is bad, I will tell them in all honesty that I admire the strength it will take to deliver the bad news. On those occasions I'm quite content to sit in the dark and stare at my 8 monitors.

One day last week, one of the Med Onc's came in to the reading room with a rather odd look on his face. "You didn't read this scan, but I want you to look at it," he said, which immediately set my mind at ease. (The four most dreaded words in this business are: "You read a scan...") 

He had me look first at a PET/CT from earlier in the year on this elderly patient:

You don't need me to interpret this for you, which is a bad sign. We see several lesions in the liver, presumably metastatic spread of cancer. There is a small focus in the upper thoracic spine, and a much larger coalescence of several lesions involving the lower thoracic spine. There are other lesions, and there is (benign) calcification around the mitral valve of the heart., here is the most recent study:

Just about all the bad stuff is gone. Most everything we see is physiologic. (The hotspot in left upper abdomen is in the stomach, and the CT didn't show anything there, but we'll still watch it.)

This isn't a particularly unusual scenario following therapy, and I complimented my friend on another successful administration of his potions and poisons. At this point, he shifted uncomfortably from foot to foot. He finally looked up and said, "But we only treated the lower spine lesion with radiotherapy. We didn't treat the other areas!" We called in the treating Rad Onc, who was equally surprised. "Wow. This would have to be an abscopal effect. I've never seen one before. There might be 20 or so reports out there..."

What in the world is the "Abscopal Effect"?

From the Wikipedia:

The abscopal effect is a phenomenon in the treatment of metastatic cancer where localized treatment of a tumor causes not only a shrinking of the treated tumor, but also a shrinking of tumors outside the scope of the localized treatment. R.H. Mole proposed the term “abscopal” (‘ab’ - away from, ‘scopus’ - target) in 1953 to refer to effects of ionizing radiation “at a distance from the irradiated volume but within the same organism.”

Initially associated with single-tumor, localized radiation therapy, the term “abscopal effect” has also come to encompass other types of localized treatments such as electroporation and intra-tumoral injection of therapeutics. However, the term should only be used when truly local treatments result in systemic effects. For instance, chemotherapeutics commonly circulate through the blood stream and therefore exclude the possibility of any abscopal response.

The mediators of the abscopal effect of radiotherapy were unknown for decades. In 2004, it was postulated for the first time that the immune system might be responsible for these “off-target” anti-tumor effects. Various studies in animal models of melanoma, mammary, and colorectal tumors have substantiated this hypothesis. Furthermore, immune-mediated abscopal effects were also described in patients with metastatic cancer. Whereas these reports were extremely rare throughout the 20th century, the clinical use of immune checkpoint blocking antibodies such as ipilimumab or pembrolizumab has greatly increased the number of abscopally responding patients in selected groups of patients such as those with metastatic melanoma.
Visually (also from the Wiki):

"Proposed mechanism of the abscopal effect, mediated by the immune system. Here, local radiation causes tumor cell death, which is followed by adaptive immune system recognition, not unlike a vaccine.'

So, this rare phenomenon probably has a scientific explanation. I'm used to seeing various cancers and other diseases cured, or at least kept at bay, including things we were taught not that long ago were "incurable". I see what was once impossible happen pretty much every day. And that's amazing enough when you think about it. 

Arthur C. Clarke once said, "Any sufficiently advanced technology is indistinguishable from magic." While there is science behind the Abscopal effect, it is still unusual enough that I have no problem calling it a miracle. As a rare perk in my end of health-care, I had the great opportunity to show the scans to the patient herself. She and her husband and daughter took it all in with quiet faith and dignity, enough to make you cry. How many times in a career does the opportunity come along to tell someone their prayers have been answered? 

A miracle? Maybe. After all, we did have all the bases covered. The MedOnc is Muslim, I'm Jewish, and the patient is Christian. I wonder if that sort of coming-together would work in other venues...


Unknown said...

Tears of joy after reading this. What a wonderfully positive blog post in today's negative world. So many friends dealing with metastatic cancer right now but they have hope....not only in this life but also the next one. Thank you for reading those countless scans and for writing this!

stacey said...

Before I read your blog today, the few times I heard about the abscopal effect I would have guessed the same reason it works...
"Proposed mechanism of the abscopal effect, mediated by the immune system. Here, local radiation causes tumor cell death, which is followed by adaptive immune system recognition, not unlike a vaccine.'

To my way of thinking, in non scientific terms, once some cancer cells are killed by radiation (or perhaps other mechanical method?) somehow the immune system gets a hold of important bits of cancer DNA, RNA , or other as yet unknown tumor identifiers, without being thrown off track by surface proteins (because the cells are already dead) and "learns" to attack them, just like immune system "learns" via vaccine. It recognizes that even though the cancer cell is "self", it is not entirely self, so must be destroyed. This makes sense, at least anecdotally.

That would have been my theory as well. Which makes me recall that most (not all, but many) chemo seems bass ackwards. Yes, it's toxic and kills cancer cells, but it also kills immune cells and they never get the chance to learn and work in this manner. After a while... the cancer adapts to the chemo, and is no longer impacted by it... Cancer cells are learning and growing resistant, but the immune system has been held back and hamstrung. I see this, particularly in the case of metastatic disease where they are trying anything and everything, and things just negatively accelerate.

darrinj said...

Never seen it yet (that I'm aware of). There's apparently some evidence that immunotherapy enhanced this effect....

jb-pi said...

Doc I am an MD
Whenever I see discussion on abscopal effect my ears perk up .
It is one of my personal interests.
I have some interesting information on abscopal effects .
You may find it interesting ..maybe to help deepen ones understanding of the underlying mechanisms.
I suspect if one were to set up a tiral to see if could reliably engineer system-wide abscopal events , The canine osteosarcoma model would be the optimal model--given its similarities to human osteosarcoma..
I Also I think the pet canine diagnosed with osteosarcoma would be a better model than a lab dog model.
I think you have my email.
best regards,
J Berg MD