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Electrotherapy and Cancer - May 2007 -

ACPOPC Belfast

ACPOPC Spring Conference Electrotherapy & Cancer


May 2007
What is the problem?
Electrotherapy & Cancer Is it real, imagined, evidenced . . . ?
Dangers and Contraindications for Are there guidelines that can help?
Electrotherapy in Cancer Care
How can we interpret the grey areas?
Professor Tim Watson How can we be safe, and effective
University of Hertfordshire and provide benefit for the patient?
www.electrotherapy.org

What is the Problem? What is the Problem?. . .


The problem, as widely viewed, is that Some modalities are generally
the application of electrotherapy considered to be more of a problem
modalities to a patient who has than others
cancer could have a detrimental e.g. ultrasound, laser, pulsed shortwave
effect on the disease progress and Many practitioners are unsure
hence constitutes a contraindication whether it is OK to apply or not and
therefore tend to shy away
or at the very least, a danger

What is the Problem?. . . Is it real, imagined, evidenced ?


If it is a problem, then clearly we
Is there a known adverse effect of
should not be applying the modalities
some or all electrotherapy modalities
If it is not a problem, yet we treat it on some or all cancers?
as such, then the patient could miss
Is this proposed, considered or
out on a potentially beneficial
directly evidenced?
treatment / modality
Absence of evidence vs evidence of
There will always be some grey areas,
absence . . . .
but should be able to have some
sound guidelines

(C) Tim Watson 1


Electrotherapy and Cancer - May 2007 -
ACPOPC Belfast

Can electrotherapy Effects of electrotherapy


influence cancer? on cancer
Useful point at which to start If one considers electrotherapy in its
If electrotherapy modalities are not widest context (i.e. the delivery of
able to influence cancers (in general electrophysical agents to the body
terms) then how could they tissues) and you leave out the ionising
constitute a danger? radiations, is electrotherapy used as
Growing body of evidence to strongly a treatment?
support the fact that electrotherapy Avoiding the topics already covered,
can have an influence worth a brief exploration

Snapshot of Electrotherapy and Cancer


Quick search of the related references from Database
literature . . .
If you do a quick lit search on a
limited number of databases and seek
a specific combination of
ELECTROTHERAPY and CANCER you
come up with a significant number of
references
Over 600 without any trouble at all

Some of the literature is more


directly relevant than others, but to Examples of Published
be able to find 800+ refs and when Research that Identifies
sorted to find 500+ particularly
relevant ones, is not bad going
Definite Link between
Some relate to electrodiagnosis and
Electrotherapy Modalities and
some to therapy Cancer / Tumour / Malignancy
Some are experimental and others
review

(C) Tim Watson 2


Electrotherapy and Cancer - May 2007 -
ACPOPC Belfast

O' Clock, G. (1997).


The effects of in vitro electrical stimulation on Vodovnik, L. et al. (1992). Modified cell
eukaryotic cells: suppression of malignant cell proliferation due to electrical currents.
proliferation Med Biol Eng Comput 30(4): CE21-8.
J Orthomol Med 12(3): 173-81 It is known that non-dividing cells, e.g. mature neurons, have
high transmembrane potential (TMP) whereas fast-dividing cells,
This technique offers a relatively comfortable, low
e.g. cancerous cells, have low TMP.
cost and minimally toxic approach towards the
When a cell is exposed to an electrical field, one side of the cell
treatment of cancer, and it also provides an
becomes hyperpolarised while the opposite side is depolarised.
alternative treatment for malignancies that have
It can be shown that in non-dividing cells their high TMP is
developed a resistance to conventional therapeutic lowered; whereas in cells with a high division rate, their low TMP
approaches. is raised due to cell exposure to the external electrical field.
The in vitro results reported in this paper strongly These alterations in transmembrane potential could contribute to
indicate that some of the mechanisms associated with the normalisation of abnormal cell proliferation.
electrotherapy may also be occurring at the cellular
level.

Habal, M. B. (1980). Effect of applied dc Taylor, T. et al. (1994). Ablation of


currents on experimental tumor growth in rats. neoplasia by direct current.
J Biomed Mater Res 14(6): 789-801. Br J Cancer 70(2): 342-5.
. . . . In humans, the application of low voltage direct
An experimental tumour in rats is treated with
current to two patients with benign anal condyloma
small anodal direct current. acuminata, three patients with inoperable obstructing
There was major retardation in tumour growth oesophageal cancer and one patient with
when the treatment was started early. disseminated Kaposi sarcoma resulted in striking
necrosis of tumour tissue that was confirmed by
There was enhancement of tumour growth when macroscopic and microscopic studies.
the treatment was started early and then was These initial findings imply promising therapeutic
discontinued. potential for the use of direct current as a simple,
effective, safe, low-cost alternative for ablation of
neoplasia.

Mir, L. et al. (1998). Effective treatment of


cutaneous and subcutaneous malignant Mir et al 1998 (contd)
tumours by electrochemotherapy. A total of 291 cutaneous or subcutaneous
Br J Cancer 77(12): 2336-42. tumours of basal cell carcinoma (32), malignant
melanoma (142), adenocarcinoma (30) and head
Electrochemotherapy (ECT) enhances the effectiveness of
chemotherapeutic agents by administering the drug in and neck squamous cell carcinoma (87) were
combination with short intense electric pulses. treated in 50 patients.
ECT is effective because electric pulses permeabilize tumour
cell membranes and allow non-permeant drugs, such as
Short and intense electric pulses were applied to
bleomycin, to enter the cells. tumours percutaneously after intravenous or
The aim of this study was to demonstrate the anti-tumour intratumour administration of bleomycin.
effectiveness of ECT with bleomycin on cutaneous and
subcutaneous tumours. The tumours were measured and the response
This article summarizes results obtained in independent clinical to the treatment evaluated 30 days after the
trials performed by five cancer centres.
treatment.

(C) Tim Watson 3


Electrotherapy and Cancer - May 2007 -
ACPOPC Belfast

Ye, F.et al. (2002). Effects of electro-


Mir et al (1998) Contd acupuncture on immune function after
chemotherapy in 28 cases.
Objective responses were obtained in 233 (85.3%) of J Tradit Chin Med 22(1): 21-3.
the 273 evaluable tumours that were treated with
ECT. Clinical complete responses were achieved in PURPOSE: To observe the effects of electroacupuncture therapy
154 (56.4%) tumours, and partial responses were on T cells and activity of NK cell in the patient of Chemotherapy.
observed in 79 (28.9%) tumours. METHOD: Electro-acupuncture therapy was simultaneously applied
The application of electric pulses to the patients during chemotherapy,
was safe and well tolerated. RESULTS: Before chemotherapy, CD3 was low within the normal
Minimal adverse side-effects were observed. range, CD4 was much lower than the normal range, and CD8,
CD4/CD8 and activity of NK cell were within the normal range. After
ECT was shown to be an effective local treatment. one month of chemotherapy combined with electro-acupuncture, no
ECT was effective regardless of the histological decline of all the indices was found (P > 0.05).
type of the tumour. CONCLUSION: Electro-acupuncture can really increase the
immune function of patients of chemotherapy.

Various heat related therapies New areas . . .


Aleksandrov, N. et al. (1973). "Use of thermal effects
in the compound treatment of malignant tumors." New work includes for example the
Vopr Onkol 19(4): 78-88. use of ultrasound as a tumour ablation
Babbs, C. F. and D. P. DeWitt (1981). "Physical method
principles of local heat therapy for cancer." Med
Instrum 15(6): 367-73.
High Intensity Focussed Ultrasound
Dickson, J. A. et al. (1977). "Tumor eradication in the
(HIFU)
rabbit by radiofrequency heating." Cancer Res 37(7 WELL above the levels that we would
Pt 1): 2162-9. employ in the clinical environment
Israel, L. et al. (1982). "Localized hyperthermia by
radiofrequency waves in the treatment of cancer."
BUT very effective for some tumour
Prog Clin Biol Res 107: 721-9. types

Wu, F.et al. (2004). Extracorporeal high intensity Wu et al (2004) Contd


focused ultrasound ablation in the treatment of 1038 Pathological examination showed that the target region
patients with solid carcinomas in China: an overview. presented clear evidence of cellular destruction.
Ultrason. Sonochem. 11;149-154. Small blood vessels less than 2 mm in diameter were
severely damaged.
The ideal treatment of localized cancer should directly cause an Follow-up diagnostic imaging revealed that there was no,
irreversible and complete death of tumor cells without damage to or reduced, blood supply, and no uptake of radioisotope in
surrounding normal tissue. High intensity focused ultrasound the treated tumor after HIFU, both indicating a positive
(HIFU) is such a potential treatment, which induces a complete therapeutic response and an absence of viable tumor.
coagulative necrosis of a tumor at depth through the intact skin.
The idea that using an extracorporeal source of therapeutic Imaging at 6-12 months showed obvious regression of the
ultrasound was introduced more than 50 years ago. Up to now, lesion.
most of the studies on HIFU have been dealing with animal Four-year follow-up data were significantly observed in
experiments because this extracorporeal technique is very patients with hepatocellular carcinoma, osteosarcoma, and
complicated in clinical applications. breast cancer.
The purpose of this study is to introduce Chinese clinical An extremely low major complication rate was noted.
experience of using extracorporeal HIFU for the treatment of
patients with various kinds of solid tumor. From December 1997 It is concluded that HIFU ablation is a safe, effective,
to October 2001, a total of 1038 patients with solid tumors and feasible modality for the ablation of carcinomas.
underwent HIFU ablation in China.

(C) Tim Watson 4


Electrotherapy and Cancer - May 2007 -
ACPOPC Belfast

Other Recent HIFU Papers Effects of electrotherapy


Kratzik, C. et al. (2006). Transcutaneous high-
intensity focused ultrasonography can cure
testicular cancer in solitary testis. Urology 67(6): It would seem from the published
1269-73.
Lynch, J. H. and S. Loeb (2007). The Role of High- literature that various forms of
intensity Focused Ultrasound in Prostate Cancer.
Curr Oncol Rep 9(3): 222-5. electrotherapy, including electrical
Ren, X. L. et al. (2007). Extracorporeal ablation of
uterine fibroids with high-intensity focused stimulation thermal therapies and
ultrasound: imaging and histopathologic evaluation.
J Ultrasound Med 26(2): 201-12. ultrasound can have a direct and real
Wu, F. et al. (2007). Wide local ablation of
localized breast cancer using high intensity effect on cancer
focused ultrasound. J Surg Oncol.

Effects of electrotherapy Good or Bad . . . ?


Assuming that several hundred Most of the examples cited from the
references are not all wrong, then if literature have shown a positive
electrotherapy has the capacity to (beneficial) effect in relation to
influence abnormal growth at a cancer therapy
physiological / biochemical / cellular There are examples which
level, then an electrotherapy modality demonstrate less positive effects in
applied for therapeutic reasons that the rate of tumour growth
COULD also have such an effect increases following exposure

Positive and Negative Effects of Electrotherapy


the Same Modality Contraindications
Worthington, A. E. et al. (1997). Mechanism As previously identified, generally
of ultrasound enhanced porphyrin held belief that electrotherapy
cytotoxicity. Part I: A search for free radical modalities are contraindicated in
effects. Ultrasound Med Biol 23(7): 1095-105.
relation to cancer, tumours, active TB
Sicard-Rosenbaum, L. et al. (1995). Effects of Difficult to find any definitive lists
continuous therapeutic ultrasound on growth to which everybody agrees
and metastisis of subcutaneous murine Some in books, articles and
tumours. Physical Therapy 75(1): 3-13. manufacturers guidelines

(C) Tim Watson 5


Electrotherapy and Cancer - May 2007 -
ACPOPC Belfast

CSP Guidelines
CSP Standards
published in 1991
Do not identify
contraindications
for the individual
modalities Identifies that you need to check the
contraindications, but not what they are
Also states that you need to minimise the
exposure to undesirable effects

Current Guidance
More recent series of meetings and
discussion with group of experts who
tried to identify a set of good
practice guidelines and standards for
all commonly applied modalities
Started in 1997, completed in 1999
Updated in 2002 and again in 2006
Now actually published (launched Feb
2007)

Guidelines . . . the process . . . Generic Guidance


Considerable controversy with
regards what IS and what IS NOT
an EVIDENCED contraindication and
/ or precaution and / or danger for
specific modalities
Had to combine published evidence
where it existed and use expert
opinion and clinical norms where not

(C) Tim Watson 6


Electrotherapy and Cancer - May 2007 -
ACPOPC Belfast

Reference Support General Precautions and


Health / Safety

Contraindications Grid
It was identified that there was a
considerable overlap between
numerous modalities in terms of CIs
and Precautions
The GRID solution was a way to
resolve the common issues and also to
provide a quick reference for clinical
practice

Malignancy on the How can we interpret the


contraindication lists grey areas?
Still some debate, especially with regards Still some difficulty in terms of the
some of the electrical stimulation list
modalities ??what counts as malignant tissue
The GRID is a summary for the general ??is it malignant post surgery
therapist ??how long after Rx does it no longer
Play it safe conservative for the most count
part ??what about palliative / terminal /
hospice care

(C) Tim Watson 7


Electrotherapy and Cancer - May 2007 -
ACPOPC Belfast

Suggestions Suggestions II
If the cancer / tumour is being
Some modalities present a higher risk
actively treated, best to avoid
E.g. ultrasound, laser and pulsed electrotherapy
shortwave
If it is being monitored, but not
But still only in the local area treated as such, have to make a
Although this may be quite extensive clinical judgement
for large field modalities such as If in doubt best avoid the LOCAL
shortwave / pulsed shortwave area

Suggestions III Palliative / Hospice Care


There is LEAST evidence for an adverse
effect with regards the electrical Suggest that quality of life is the
stimulation modalities main issue
DC type stimulation is still best avoided as If (??) electrotherapy has an adverse
it has the greatest capacity to influence effect on progress of cancer /
tumour growth and development tumour, which is the worse option -
TENS, IFT and NMES are not DC in nature leave the patient in pain / discomfort
and therefore present a minimal (if any) or run the potential risk of increased
risk division rate

Palliative / Hospice Care Summary

Informed consent applies as it would Cancer / malignancy / tumour widely


to any intervention considered to be a contraindication
for all forms of electrotherapy
Outline the options and relative
Some evidence base, but not as
benefits categorical as once thought
Follow normal clinical practice in such Potential treatment in the not too
circumstances distant future???

(C) Tim Watson 8


Electrotherapy and Cancer - May 2007 -
ACPOPC Belfast

Summary II Summary III


Electrotherapy has the same OK to use in palliative etc care
potential benefit as it would for OK to use if tumour is not being
other patients actively treated
Best avoided in the local region of the Need consent in the normal way
rapidly dividing tissue If in doubt think DIVIDING
Can apply elsewhere (especially TISSUE EXPOSURE
localised treatments) If still in doubt, then dont!

(C) Tim Watson 9