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THE MOSS REPORTS Newsletter (02/14/03)

 

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Ralph W. Moss, Ph.D. Weekly CancerDecisions.com

Newsletter #73 02/14/03

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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, PhD

 

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References

 

 

" Abscopal effect. " On-Line Medical Dictionary.

http://cancerweb.ncl.ac.uk/cgi-bin/omd?abscopal+effect

 

 

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/HealthProfess\

ional#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.

 

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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.

 

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