The Abscopal Effect

It is sometimes asserted, as a matter of dogma, that a local treatment cannot have systemic effects. However, treatment directed at a tumor at one site can in fact profoundly affect tumors at other locations in the body. Fifty years ago, Dr. R. J. Mole called this surprising phenomenon the "abscopal effect." The word "abscopal" is derived from the Latin prefix "ab," meaning "away from," and the Greek word "skopos," meaning "target." CancerWeb defines the abscopal effect as "a reaction produced following irradiation but occurring outside the zone of actual radiation absorption."

Some years ago, such an abscopal regression was seen in Nagasaki, Japan. A 76-year-old man who was being treated for hepatocellular carcinoma (liver cancer) was irradiated to control the spread of his bone metastases. This was intended as palliative, not curative, therapy. Yet following palliative radiotherapy, the man's primary (non-irradiated) liver cancer regressed. His physicians also found an increase in blood levels of an inflammatory compound called tumor necrosis factor (TNF), which has known anticancer effects. The physicians suggested that the regression may have been caused by an immune response spearheaded by TNF.

Abscopal effects are usually associated with radiation, but are sometimes seen after other treatments as well, such as surgery or even heat treatment (hyperthermia). Anecdotally, I have heard of a laboratory experiment in which photodynamic therapy (PDT) directed at one tumor caused a non-illuminated tumor to shrink by 20 percent. In an experiment conducted in India, administering hyperthermia to the leg of a mouse for 40 minutes before transplanting a sarcoma reduced the growth of the tumor in the heated leg. More surprisingly, it inhibited the growth of a tumor transplanted to the unheated leg as well. In fact, two or three weeks after treatment, the growth retardation had ceased in the leg that had been heated, but was still noticeable in the leg that had not been heated! In some sense, the abscopal effect of hyperthermia turned out to be greater than its direct effect on local tissue.

The authors concluded, "Local hyperthermia induces both direct and abscopal antitumor effects which may probably be the result of a systemic effect of hyperthermia in the host animal."

In 1990, a Japanese scientist conducted a clinical study to investigate the mechanism of the abscopal effect in patients with breast cancer. There were 62 women in his study, most of them with advanced disease. They were irradiated before surgery and then underwent mastectomy or tumor resections. Physical examination (palpation) indicated an abscopal effect on metastatic lymph nodes in 15 out of 42 cases (35.7 percent). Laboratory studies revealed an even greater abscopal effect, with tissue samples from 22 of 42 cases (52.4 percent) demonstrating an abscopal effect. Thus, more than half of these women with advanced breast cancer exhibited some sort of abscopal effect following irradiation and surgery.

The incidence of the abscopal effect was significantly higher in patients under 55 years old and was most frequent in patients who had "infiltrating lymphocytes around the degenerated cancer cells in the irradiated primary tumor nests." In other words, if there was a vigorous immune reaction to the tumor (as indicated by the presence of white blood cells), the body was more likely to attack it and bring about an abscopal response.

What sort of white blood cells were present? These were identified as primarily CD8 and CD4 lymphocytes, which play a role in cellular defense against pathogens, malignant cells, and other foreign substances. According to the study's author, "these findings suggest that the abscopal effect was caused by activated cellular immunity in hosts." Although this study was not large or powerful enough to reach statistical significance, the survival rate of patients who exhibited the abscopal effect was higher than for those patients who had no such reaction.

The logical inference from this research is that the abscopal effect is a desirable and common systemic reaction to localized cancer treatment. Since it is dependent on a healthy immune system, one might infer that immune-damaging treatments should be kept to a minimum. Unfortunately, the trend in most parts of the world is in the opposite direction, and immunosuppressive chemotherapy is given at every opportunity.

Equally frustrating is the fact that there is little research underway into this well-established effect. Out of 12 million journal articles in the National Library of Medicine's database, a total of 22 concern the abscopal effect in cancer. Over the last two years only two articles have even mentioned it! The National Cancer Institute (NCI) website contains one fleeting mention of the phenomenon in a discussion of chronic lymphocytic leukemia: "Sometimes radiation of one nodal area or the spleen will result in abscopal effect (shrinkage of lymph node tumors in untreated sites)."

If and when oncology focuses on treatments that build up the body's defense system instead of tearing it down, the abscopal effect may finally come into its own.

Advanced Liver Cancer

I was recently asked for my opinion of the proper treatment of advanced liver cancer. The patient in question had developed hepatitis C, which was eventually followed by hepatocellular carcinoma (HCC). He had received a liver transplant but within six months the cancer had recurred in his new, presumably healthy liver.

What is a proven therapy in this situation? According to the NCI's statement on recurrent adult primary liver cancer, the treatment options include (in addition to liver transplantation):

1) transarterial oily chemoembolization (TOCE)
2) percutaneous ethanol injection therapy (PEIT)
3) systemic chemotherapy

The reference for all of these treatment options is a case series (or retrospective review) from a single institution in Hong Kong. Several hundred patients were treated and various survival figures are given for the different techniques. The problem is that statistics derived from retrospective reviews are inherently less reliable than those obtained from randomized controlled clinical trials. This is because it is not possible in a retrospective review to correct for selection bias (not a moral flaw, but simply an error in the way patients are allocated to different treatment methods). Because patients in this case series were not randomly assigned to different treatment groups, the possibility that patients with better or worse prognoses were assigned to particular treatment groups cannot be ruled out.

The NCI itself frankly rates this type of study as "the weakest form of study design," which is by its very nature subject to methodological problems. In actuality, the choice of treatment for patients with recurrent liver cancer rests on the opinions of experts, not on the results of randomized controlled trials. And expert or not, in the end their opinions are simply that, opinions, not facts.

An advocate of complimentary and alternative medicine (CAM) recently traveled over 7,000 miles to argue the case for non-conventional treatment before a board composed of the doctors treating this man. From his account of the meeting, they raked him over the coals for the "unproven" and "outlandish" nature of the treatments that he advocated. Yet a review of the NCI's statement on liver cancer reveals that the treatments they advocate are not as "proven" as they would have you think, for they are perched on the slippery slope of case series, not anchored in the bedrock of randomized controlled trials. Despite this shaky foundation, all funding and credibility is granted to the toxic methods of conventional oncology. This is yet another example of the "double standard" so prevalent in the West in the evaluation of cancer treatments. It is maddening and unfair.

--Ralph W. Moss, Ph.D.

References:

Ohba K et al. Abscopal regression of hepatocellular carcinoma after radiotherapy for bone metastasis. Gut 1998;43(4):575-7.

Vartak S et al. Antitumor effects of local hyperthermia on a mouse fibrosarcoma. Anticancer Res 1993;13(3):727-9.

Konoeda K. Therapeutic efficacy of pre-operative radiotherapy on breast carcinoma: in special reference to its abscopal effect on metastatic lymph-nodes. Nippon Gan Chiryo Gakkai Shi 1990;25(6):1204-14.

National Cancer Institute. Chronic lymphocytic leukemia PDQ: Treatment.
http://www.cancer.gov/cancerinfo/pdq/treatment/CLL/HealthProfessional

National Cancer Institute. Recurrent adult primary liver cancer.
http://www.cancer.gov/cancerinfo/pdq/treatment/adult-primary-liver/HealthProfessional#Section8

Poon RT et al. Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors. Ann Surg 1999;229(2): 216-22.

IMPORTANT DISCLAIMER

The news and other items in this newsletter are intended for informational purposes only. Nothing in this newsletter is intended to be a substitute for professional medical advice.

CancerDecisions® PO Box 1076, Lemont, PA 16851 Phone Toll Free: 800-980-1234 | Fax: 814-238-5865 Copyright © 1996-2004 All Rights Reserved