P E R S P E C T I V E P A P E R

Physical Agents for Cancer

Survivors: An Updated Literature
Review
Ann Wilson, PT, MEd, GCS1 ; Gentry Ensign, DPT2 ; Kathryn Flyte, DPT2 ; Michael Moore, DPT2 ; Katelyn Ratliff, DPT2
1
Clinical Associate Professor and Director of Clinical Education, University of Puget Sound School of Physical Therapy,
Tacoma, WA; and 2 University of Puget Sound School of Physical Therapy, Tacoma, WA

Background: A 2001 review by Lucinda Pfalzer, PT, PhD, titled, “Physical Agents/Modalities for Survivors of
Cancer,” was the first to examine the safety and efficacy of physical agent use for individuals with cancer. The
agents included in that review were those predominantly used in clinical practice at that time. As the physical
therapy profession has evolved, the use of some physical agents has changed. Purpose: The purpose of this
literature review was to update Pfalzer’s original work and to discuss the contemporary use of physical agents
as part of a comprehensive rehabilitation program for individuals with cancer. Methods: A comprehensive
review of literature published between 2001 and 2016 regarding the safety, efficacy, and use of physical
agents was conducted. Information was extracted, and the findings were compared with the original article.
Results: Much of the information in Pfalzer’s review remains unchanged; however, new agents such as low-
level laser and scrambler therapy have emerged. The safety, use, and efficacy of those agents are described.
Limitations: The literature search focused only on articles written in English. Therefore, information regarding
contemporary use of physical agents in other countries may have been missed. Conclusions: No new evidence
was found for many of the physical agents described by Pfalzer. This may be due to the reluctance of clinicians
to use physical agents on patients with cancer because of possible adverse effects or because physical agents
are not as widely used now as in the past. (Rehab Oncol 2018;36:132–140) Key words: cancer rehabilitation,
physical agents, physical therapy

Physical therapists sometimes use physical agents as
part of a comprehensive rehabilitation program to de-
crease pain, increase strength, and facilitate tissue heal-
ing while avoiding possible malignant tumor growth in
individuals with cancer.1 The benefits of physical agents
in cancer treatment have not been well defined but may
have the potential to improve quality of life and functional
abilities.
Preferences for the use of physical agents change as
new evidence emerges and new agents are established. A
comprehensive review article by Lucinda Pfalzer,2 titled
“Physical Agents/Modalities for Survivors of Cancer,” was
Rehabilitation Oncology
Copyright C 2018 Oncology Section, APTA.
The authors declare no conflicts of interest.
Correspondence: Ann Wilson, PT, MEd, GCS, University of Puget Sound
School of Physical Therapy, 1500 N Warner St #1070, Tacoma, WA
98416 (awilson@pugetsound.edu).
DOI: 10.1097/01.REO.0000000000000081
the first to examine the safety and efficacy of physical agent
use with patients with cancer. The agents included in that
review were those predominantly in clinical use at that
time. Pfalzer’s literature review spanned the years 1972-
2001, with the majority stemming from work published in
the 1990s. Since then, there have been a number of changes
and advances in the physical therapy profession with re-
gard to more clearly defining parameters for existing agents
and the emergence of new physical agents. For example,
low-level laser therapy (LLLT) was approved by the Food
and Drug Administration in 2002.3 Similarly, scrambler
therapy emerged as an alternative to traditional transcu-
taneous electrical nerve stimulation (TENS) in 2003.4 In
contrast, the use of whirlpool has largely been discontin-
ued because of a lack of positive effects.1 In light of these
and other changes, there is a need to review the current lit-
erature regarding the safety and efficacy of physical agents
for individuals with cancer. Therefore, the aim of this
article was to update Pfalzer’s original work, report any
new findings, and relate them to standard practice guide-
lines and insights provided in the original article.

132 Wilson et al Rehabilitation Oncology

Copyright © 2018 Oncology Section, APTA. Unauthorized reproduction of this article is prohibited.
 The authors of this article reviewed the physical
agents included in the original article and included,
excluded, and introduced new physical agents based on
their contemporary use in clinical practice. A literature
search was performed to identify studies published
between 2001 and 2016 evaluating the safety and efficacy
of physical agents using the following databases: PubMed,
SPORTDiscus, CINAHL, PEDro, and Rehabilitative On-
cology using a combination of the following key words:
physical agents, physical agent modalities, ultrasound,
electrical stimulation, transcutaneous nerve stimulation,
compression, laser, cancer, oncology, metastatic disease,
and metastasis. In addition, 2 well-respected physical
therapy textbooks were scanned for relevant references.1,5
After screening for relevance, a total of 27 studies were
identified as providing updated information related to the
safety and applicability of the use of physical agents for
individuals with cancer. Because this review is a search
of all available literature, the quality of individual studies
was not systematically evaluated.
A present or past history of cancer is either a con-
traindication or precaution for many physical agents;
therefore, therapists should screen for the possibility of
cancer before applying any physical agent. The screening
questions used during the systems review in a comprehen-
sive physical examination, particularly for individuals with
a history of cancer or current malignancy, should include
the presence of fever, chills, sweats, or night pain; pain at
rest; recent unexplained weight loss; or constant pain that
does not change with rest.6
There are specific conditions that prohibit the use of
a particular physical agent due to the potential for harmful
effects.1 If an agent is contraindicated for a particular con-
dition, it should not be used for any individual who has
that condition. There are also precautions for some phys-
ical agents that indicate that caution should be exercised
when applying them to an individual with a particular
condition. Malignancy is often cited as either a contraindi-
cation or precaution for a physical agent. In general, the
decision as to whether malignancy is listed as a precau-
tion or a contraindication depends on whether the agent
has localized or systemic effects. For example, the local
application of superficial heat directly over a known ma-
lignancy would be contraindicated because of potential
increase in circulation. In contrast, the application of su-
perficial heat at a site distant from the malignant tumor
would be a precaution because the extent of the increased
circulation caused by the agent may not reach the tumor
itself. Given that the physical agents discussed in this re-
view have local, instead of systemic, effects, their use is
contraindicated directly over the area of malignancy. Ma-
lignant tumor or malignancy is often listed as a precaution
rather than a contraindication when there is no research to
support that application of the physical agent increases
tumor growth, but there is theory to support that the
effects may stimulate metastasis. Metastasis is the process
by which cancer cells break away from the site of the origi-
Rehabilitation Oncology
Copyright © 2018 Oncology Section, APTA. Unauthorized reproduction of this article is prohibited.
nal tumor, spread to 1 or more other places in the body, and
form new tumors. Cancer cells can spread through blood
vessels, lymphatic cells, and/or along surfaces inside the
body cavity through a series of steps that include growing
into nearby surrounding tissue, traveling through the lym-
phatic system and bloodstream, invading the blood vessel
walls and moving into surrounding tissue, and growing
and multiplying until a new (metastatic) tumor forms.7
Carcinomas typically begin via the lymphatics and then
later spread via blood vessels. Bone and soft-tissue sarco-
mas usually metastasize via blood vessels. Tumors such as
mesotheliomas or ovarian carcinomas spread through the
body cavity.8 The energy produced by a physical agent or
its physiologic effects may affect malignant tissue and alter
cellular growth, with the possibly of metastasis. See Table 1
for contraindications and precautions for each classifica-
tion of agent, particularly with respect to metastases or
suspected malignancies.
The potential benefits of physical agents include mod-
ification of tissue inflammation and healing, pain man-
agement, alteration of collagen extensibility, or modifi-
cation of muscle tone.1,2 Potential risks for malignancy
include those physical agents that may reach malig-
nant tissue or alter circulation to that tissue. Therefore,
clinical decisions regarding the use of physical agents
must take disease stage, progression, and prognosis into
consideration.
CLINICAL DECISION-MAKING BY STAGE
AND PROGNOSIS
The following subdivisions are based on the (tumor,
node, metastases) TNM classification system used to deter-
mine interventions. Further descriptions of cancer staging
are beyond the scope of this review, and the reader is re-
ferred to Goodman and Fuller5 for further information.
Stage I: There are no restrictions related to the use
of physical agents at this stage, assuming the in-
dividual has had a recent medical checkup includ-
ing testing such as a bone scan that is negative for
cancer. The general contraindications/precautions
described for each agent apply (see Table 1).
Stages II and III: The restrictions and recommenda-
tions given for individuals in stage I should be fol-
lowed in this stage (see Table 1).
Stage IV: Physical therapists should exercise extreme
caution when deciding whether or not to use phys-
ical agents over painful areas or masses because
of the high risk of facilitating replication and tu-
mor growth. Thermal agents should not be used
in close proximity to any adjuvant treatment such
as radiation or chemotherapy.2 The general con-
traindications and precautions for each individual
agent apply (see Table 1).
Physical therapy interventions for stages I to III fo-
cus on the restoration of functional capacity, maintaining
Physical Agents for Cancer Survivors 133

Classification of Agent
Thermotherapy (superficial
heat and cold)
Ultrasound
Mechanical
agents—Traction
Mechanical
agents—Compression
Electromagnetic agents
(light and laser)
Electrotherapy agents
(transcutaneous electrical
nerve stimulation,
neuromuscular electrical
stimulation, functional
electrical stimulation, etc)
Abbreviations: DVT, deep vein thrombosis; RA, rheumatoid arthritis.
a Data from Cameron1 and Pfalzer.2
134 Wilson et al
Copyright © 2018 Oncology Section, APTA. Unauthorized reproduction of this article is prohibited.
TABLE 1
General Contraindications and Precautions for Physical Agentsa
Precautions Contraindications
Acute injury or inflammation Directly over malignant tumor (due to increasing
Pregnancy metabolic rate of malignant tissue)
Impaired circulation Recent or potential hemorrhage
Poor thermoregulation Thrombophlebitis
Edema Impaired sensation
Cardiac insufficiency Impaired mentation
Metal in the area Irradiation of the eyeballs
Over an open wound Over an infected area where infections may spread or
Over areas where topical counter irritants have cross-contaminate
recently been applied Cold sensitivity symptoms (ie, Raynaud’s
Demyelinated nerves phenomenon)
Over superficial peripheral nerves
Acute inflammation Directly over malignant tumor
Epiphyseal plates Active malignancy should be ruled out prior to physical
Fractures agent use if history of cancer within 5 y
Breast implants Pregnancy
Central nervous system tissue
Joint cement
Plastic components
Pacemaker
Thrombophlebitis
Eyes
Reproductive organs
Infection
Over the heart, stellate, or cervical ganglia
Structural diseases or conditions affecting the spine (eg, Where motion is contraindicated
tumor, infection, RA, osteoporosis, prolonged Acute injury or inflammation
steroid use) Joint hypermobility or instability
When pressure of the belts may be hazardous (ie, Peripheralization of symptoms with traction
pregnancy) Uncontrolled hypertension
Displaced annular fragment Recent trauma if diagnostic have not ruled out
Medial disc protrusion fracture, subluxation, or dislocation of the spine
When severe pain does not fully resolve with traction, Aortic aneurysm
indicating possible increased compression on nerve Temporomandibular joint pain
root and causing a complete nerve block
Claustrophobia
Inability to tolerate prone or supine positions
Disorientation
Acute neck and back pain
Directly over malignant tumor or when increased Heart failure or pulmonary edema
circulation may cause tumor to move or grow more Recent or acute DVT, thrombophlebitis, or pulmonary
rapidly embolism
Impaired sensation or mentation Completely obstruction in lymphatic or venous return
Uncontrolled hypertension (requiring surgery)
Stroke or significant cerebrovascular insufficiency Severe peripheral arterial disease or ulcers resulting
Superficial peripheral nerves from arterial insufficiency
Acute local skin infection
Significant hypoproteinemia (<2 g/dL)
Acute trauma or fracture
Arterial revascularization
Low back or abdomen during pregnancy Directly over malignant tumor
Epiphyseal plates Eyeballs
Impaired sensation or mentation Within 4-6 mo after radiotherapy
Photophobia or abnormally high sensitivity to light Over hemorrhaging regions
Pretreatment with 1 or more photosensitizers Over the thyroid or other endocrine glands
Epilepsy
Directly malignant tumor Demand pacemaker or unstable arrhythmias
Cardiac disease, including previous myocardial Over the carotid sinus
infarction or other specifically known congenital or Venous or arterial thrombosis or thrombophlebitis
acquired cardiac abnormalities Pelvis, abdomen, trunk, and low back during
Impaired mentation or sensation pregnancy
Skin irritation or open wounds
Rehabilitation Oncology
function during cancer therapy, and improving quality of
life once the cancer has been cured or is in remission. The
goals of interventions provided during these stages differ
from those of patients in stage IV.9,10 Rather than focus-
ing on restoring function, the focus during this stage is on
palliative care or balancing the management of symptoms
such as fatigue, pain, loss of autonomy, and generalized
weakness and increasing comfort and maintaining opti-
mal movement.9,11 Palliative care can be defined as the
complete care of patients whose diseases/conditions are
no longer responsive to curative treatment with the goal
of achieving the best possible quality of life for them and
their families.9 Since these individuals are in the final stages
of life and no known pharmacologic or nonpharmacologic
treatments will stop the progression of the disease, a physi-
cal therapist need not worry about the effect of the physical
agents they are using may have on the spread of the can-
cer; rather, agents should be selected on the basis of their
efficacy managing pain or other impairments to provide
a reasonable degree of independence or comfort, thereby
improving quality of life.9-11 This is not the case with the
early stages where the risk to benefit ratio should be care-
fully considered. Selecting the wrong modality could be
detrimental and could facilitate the progression of the dis-
ease. For individuals with end-stage cancers, pain-relieving
physical agents that may improve quality of life may be
used with their consent despite the potential adverse ef-
fects on disease progression.1,2
AGENT CLASSIFICATIONS
Physical agents can be used to help manage inflamma-
tion and promote healing, aid in nonpharmacologic pain
modulation, control muscle tone, increase collagen tissue
extensibility, and overcome motion restrictions. Physical
agents may be useful to help manage pain in individu-
als with cancer; however, one must be aware of the effect
of each agent’s interaction with cancerous cells.1,2,5 As
the understanding of cancer-related impairments has im-
proved, so too has the understanding of the type, use, and
delivery of physical agents. For the purpose of this article,
physical agents have been divided into 4 broad classifica-
tions based on the type of energy each delivers.
Thermal Agents
Thermal agents can be used to either increase or
decrease tissue temperature. Examples of thermal agents
include those with superficial effects such as hot packs,
paraffin, and cold packs and deep thermal agents such as
ultrasound (US). Thermotherapy is often used to manage
pain and inflammation. Because of their potential effect
on circulation, heat agents have the potential to increase
growth or metastasis of a tumor.1,2 Ultrasound has been
used to improve tissue extensibility, diminish pain, and
promote healing of bone and soft tissues.1,2
Malignancy has been a long-standing general con-
traindication for use of therapeutic US. Studies conducted
Rehabilitation Oncology
Copyright © 2018 Oncology Section, APTA. Unauthorized reproduction of this article is prohibited.
during the 1990s on mice demonstrated an increase
in tumor size after direct application of continuous
therapeutic US,12,13 low-power continuous therapeutic
US,13 and pulsed therapeutic US.13 One study found
tumor spread to lymph nodes in 5% of mice after direct
tumor exposure to therapeutic US.12 A more recent study
applied therapeutic US to mice after tumor excision and
found a risk of recurrence with both continuous and
pulsed US application.14 It should also be noted that
application of US in an area distant to location or previous
location of cancerous cells might not be safe. This is
due to the risk of metastasis, which could be the cause
of the pain for which they are seeking physical therapy
intervention. It is important for physical therapists to
screen for cancer risk and refer for further testing as
needed.
Mechanical Agents
Mechanical agents such as traction and compression
units apply forces to increase or decrease pressure on the
body or to elongate tissues. Mechanical traction is used to
mobilize vertebrae, decrease muscle spasms, reduce disc
protrusion, and stretch the soft tissue around the spine.1
These conditions may be comorbid with cancer. In addi-
tion, if there is a tumor near the spine, the integrity of the
spine must be considered prior to the application of trac-
tion. Because of this, the use of mechanical agents has typ-
ically been considered a precaution/contraindication for
individuals with cancer.2
Intermittent compression units exert external pres-
sure on a specific body region to manage acute edema
or lymphedema. Mechanical compression should not
be applied in the area of a malignant tumor or when
it is thought that an increase in circulation may cause
a tumor to move or grow more rapidly. In addition,
mechanical compression should not be used in the
presence of a known venous or lymphatic obstruction.
There are many forms of intermittent pneumatic compres-
sion (IPC) including advanced pneumatic compression
devices and standard pneumatic compression devices.
Emerging evidence suggests that any type of IPC will
reduce edema and that there are no significant differences
between the types of IPC used.15,16 There is some
evidence suggesting that although there are more effective
alternatives to treating postmastectomy lymphedema,
IPC is a safe and effective supplemental treatment.17-21
Imaging studies conducted during treatment with pneu-
matic compression devices on breast cancer–related
lymphedema show that IPC systematically stimulates
the lymphatic system.22 While IPC may have a positive
effect on breast cancer–related lymphedema, the time
since onset may play a critical role due to the progressive
loss of functioning lymphatic vessels within the affected
limbs.22 Although IPC may not be as effective as other
lymphedema treatments, it may be a feasible adjunct in the
management of cancer-related upper or lower extremity
lymphedema.23
Physical Agents for Cancer Survivors 135
Electromagnetic Agents
These agents use electromagnetic radiation to create
effects in tissues. Examples include infrared light, laser,
light-emitting diodes, ultraviolet light, and pulsed short-
wave diathermy. These agents may decrease pain and facil-
itate bone and soft-tissue healing; however, because of an
increase in circulation and cellular energy, tumor growth
in the area may increase.1 Diathermy creates an electro-
magnetic field adjacent to the targeted tissue that increases
circulation and has the potential to decrease pain and in-
crease tissue healing. This class of agents should be avoided
for 4 to 6 months after radiotherapy due to the increased
risk of malignancy and burns in the treated tissue.1 It is
suggested that LLLT stimulates mitogenic activity, syn-
thetic activity, and viability of fibroblasts in systems that
are operating under physiologic stress or in pathological
conditions.24 Evidence for the use of LLLT in treatment
of breast cancer–related lymphedema is often reported in
conjunction with other treatment options; therefore, it is
difficult to determine the effect of the laser alone. For ex-
ample, Ridner et al25 found that a 20-minute session of
LLLT for breast cancer–related lymphedema, followed by
compression bandaging, may be as effective as 40 minutes
of manual lymphatic drainage in arm volume reduction.
A double-blind, placebo-controlled, randomized trial of
LLLT in patients with postmastectomy lymphedema by
Carati et al24 found no immediate improvement in limb
volume; however, there was a significant decrease in limb
volume and tissue hardness 3 months following comple-
tion of 2 cycles of LLLT. In addition, no adverse effects
were reported following the application of LLLT. Despite
these promising findings, further research is needed to op-
timize treatment parameters including site, duration, and
laser application.
Electrotherapeutic Agents
The fourth class of agents includes electrical stim-
ulation, which uses transcutaneously applied electrical
currents to facilitate pain reduction, enhance medication
delivery, and augment muscle strengthening. Electrother-
apeutic agents including neuromuscular electrical stimula-
tion (NMES), functional electrical stimulation, and TENS
are typically used for acute, chronic, and postsurgical pain
reduction, muscular strengthening, and wound healing.
In addition to these physical agents, scrambler therapy
has recently been introduced as an alternative form of
TENS.4
While electrotherapeutic devices are occasionally
considered for use with patients with cancer, it is gen-
erally understood that the use of all electrical agents is
contraindicated directly over or adjacent to a malignant
tumor due to concerns about stimulation of malignant cell
proliferation and tumor growth.26 However, on the basis
of the fact that electrical stimulation has potential ben-
efits for treating cancer-related pain, recent studies have
examined the efficacy of electrotherapeutic agents for pain
modulation in individuals with cancer.4,26-31 Nevertheless,
136 Wilson et al
Copyright © 2018 Oncology Section, APTA. Unauthorized reproduction of this article is prohibited.
caution must be used to determine the benefit of electric
stimulation compared with the risk of tumor growth in
known cancer and unknown metastases.31
Chemotherapy-induced peripheral neuropathy
(CIPN) is one of the most frequently reported issues
associated with cancer treatment because of its potential
to cause long-term impairments affecting activities of
daily living and participation in individuals with cancer.32
A recent clinical practice guideline on the prevention and
management of CIPN from the American Society of Clin-
ical Oncology found a paucity of high-quality evidence
regarding the use of any pharmacologic agents for the
prevention of CIPN despite medication being the primary
method used for dealing with chemotherapy-associated
pain.32 However, a study by Marineo et al33 suggests that
TENS may be used to relieve refractory chronic pain. In
addition, a number of studies have looked at the efficacy
and acceptability of several types of electrical stimulation
for the relief of chronic pain associated with cancer.4,26-35
The use of TENS in cancer care is highly
controversial.33 While cancer-related pain can be success-
fully managed with opioid regimens in most cases, some
individuals experience treatment-related side effects with
minimal improvement in quality of life.32,33 There is in-
creasing recognition of the need for nonpharmacologic
approaches to pain management, and TENS may have a
significant role to play.
In a recent level III retrospective cohort review, Loh
and Gulati27 found that 69% of patients started on TENS
therapy showed some benefit in pain symptoms and quality
of life over a period of 2 months. While the location of pain
varied among patients, from metastasis to chemotherapy,
surgery, and radiation, patients with metastasis to bone
had good pain relief with the use of TENS. The authors
also concluded that while elevated blood flow at the TENS
stimulus site has been suggested to invoke increased tu-
mor growth, high-frequency TENS (above 80 Hz) has min-
imal effect on blood flow and is safe for individuals with
a diagnosis of cancer.27 All patients who benefitted from
application of TENS in this study were instructed in the
use of their device at home with the frequency set above
80 Hz for 4 to 6 times per day for 30 to 60 minutes with
variable pulse duration and amplitude that were adjusted
to their individual comfort level.27 Therefore, a common
TENS parameter for this cohort study could not be de-
termined because of the reported individual variability of
patient selected parameters. However, the authors found
that, during the trial period, patients responded best to
high-frequency TENS from 100 to 150 Hz, with premodu-
lated amplitude with a pulse duration of 1 to 6 seconds.
Furthermore, a 2009 update of a Cochrane system-
atic review of TENS by Robb et al31 found a lack of large
multicenter randomized controlled trials (RCTs), which
hindered definitive conclusions about the use of TENS. Of
the 43 identified studies, only 2 met the eligibility crite-
ria for review. The authors summarized that while experts
suggest TENS may play a role in treatment of cancer-related
pain, the clinical benefit remains unclear and there are no
Rehabilitation Oncology
current guidelines regarding the use of TENS in oncology
and palliative care settings. In addition, a 2012 systematic
review update by Hurlow et al28 on TENS for cancer pain
in adults ultimately came to the same conclusion. The sys-
tematic review identified 3 viable RCTs but were unable to
draw any definitive conclusions about the clinical utility of
TENS and its use with cancer pain due to the low number
of high-quality studies.28,31,35 These authors concluded
that there is insufficient evidence to determine whether
TENS should be used for adults with cancer-related pain
and that further research using well-designed clinical trials
is needed to improve knowledge in this area.35 This lack
of well-designed clinical trials was the main objective that
Loh and Gulati27 attempted to address in the previously
mentioned 2015 cohort study. While the study was a ret-
rospective cohort study of level III evidence, it is the most
recent and relevant research that has addressed the issue
of the use of TENS in the oncology population since the
publication of the Robb et al and Hurlow et al systematic re-
views and has offered initial insight into appropriate TENS
parameters for patients suffering from cancer-related pain.
However, because of the lack of additional RCTs, more
research will need to be conducted investigating specific
TENS parameters and their influence on cancer-related
pain and tumor growth.
In lieu of the paucity of recent evidence surrounding
the use of electrical stimulation agents and their use in can-
cer care, a 2014 literature review by Cheville and Basford36
confirmed that reasonable candidates for TENS are those
individuals whose localized pain is inadequately controlled
by conventional treatments, those who experience unten-
able adverse effects to medication, or those who prefer
to try nonpharmacologic approaches. In addition, Laakso
and Young26 reviewed literature regarding the use of elec-
trophysical agents for symptom control in cancer care in
Australia. Their review revealed that no strong evidence
exists for the efficacy of TENS and that without a clear un-
derstanding of its effects on malignant cells, it is reasonable
and prudent to limit the use of TENS only to the palliative
stage of care. Laakso and Young26 reached the same con-
clusion regarding the use of NMES in patients with cancer
despite several high-quality RCTs reporting good results
in quadriceps muscle strength and endurance, functional
gait, and dysphagia. Taken together, these findings suggest
that electrotherapy may play a role in palliative care as a
secondary option to pharmacologic treatment of cancer.
Scrambler therapy is a recent and novel approach to
TENS aimed at producing nonpainful stimuli in afferent
cutaneous nerves in the central nervous system. Scrambler
therapy is composed of 5 electrical stimulation channels
that produce 16 different electrical currents that stimu-
late normal nerve action potentials.4 According to Majithia
et al,29 scrambler therapy stimulates C pain fibers and re-
places the endogenous pain information with a synthetic
one of “nonpain” or “normal self” that travels through
the same pathways to the brain and “retrains” the brain.
Early results with using scrambler therapy for pain asso-
ciated with CIPN are promising. In a single-arm trial of
Rehabilitation Oncology
Copyright © 2018 Oncology Section, APTA. Unauthorized reproduction of this article is prohibited.
scrambler therapy in CIPN, Coyne et al30 found a sig-
nificant improvement in several areas including decreased
pain, improved mood, improved walking ability, improved
sleep, and improved sensory and motor outcomes. In ad-
dition, the study revealed a reduction in symptoms from
baseline up to 3 months after cessation of therapy with no
adverse effects.
A 2015 pilot study of scrambler therapy by Pachman
et al4 found that pain, tingling, and numbness decreased
in patients with CIPN symptoms of greater than 1 month
after chemotherapy. Similarly, Majithia et al29 found that
the benefit of scrambler therapy has been substantial in
some cases, with some patients achieving complete pain
resolution and substantially reduced dependence on phar-
macologic therapy. A small pilot randomized trial by
Marineo et al33 found that scrambler therapy, as compared
with guideline-based drug management, appeared to bet-
ter relieve chronic neuropathic pain in their patients. De-
spite these promising results, additional research is needed
to better understand the mechanism of scrambler ther-
apy and to investigate its efficacy for a number of chronic
pain states. The use of scrambler therapy to alleviate CIPN
symptoms has shown obvious potential but needs to be
assessed with larger high-quality RCTs by independent
groups before any definitive conclusion can be made.
NMES is widely used to augment strength, assist with
muscle reeducation, and manage acute spasms.37 Reduced
exercise capacity in patients with cancer is associated
with increased morbidity and mortality.38,39 Causative
factors include the cancer, via the cachexia syndrome,
and cancer treatments, with patients receiving palliative
chemotherapy experiencing an overall deterioration in
muscle strength, lean body mass, and physical activity
level.40-44 These effects arise in part from chemotherapy-
related fatigue contributing to a negative cycle of reduced
physical activity and muscle deconditioning. To date, there
is still little published data on the use of NMES in patients
with cancer in general, especially those with poor perfor-
mance status.37
A recent pilot study by Windholz et al37 assessed
the feasibility and acceptability of lower-limb NMES on
walking endurance capacity, lower extremity strength, and
global functional performance in patients who could not
attend hospital-based exercise training. The authors con-
cluded that NMES is both feasible and well-tolerated in
this group of patients with advanced cancer.
Similarly, Maddocks et al45 examined the use NMES of
the quadriceps in patients with non-small cell lung cancer
(NSCLC) receiving palliative chemotherapy. They found
no serious adverse events related to NMES during this
study; however, they concluded that there was no signifi-
cant difference between the NMES and control groups in
changes in peak quadriceps muscle strength, lean thigh
mass, or aspects of physical activity. Ultimately, the study
revealed that NMES is not sufficiently acceptable alongside
first-line palliative chemotherapy in patients with NSCLC
and that NMES may be impractical, given the challenges
patients in this group face with regard to morbidity related
Physical Agents for Cancer Survivors 137
to their disease and chemotherapy. In this regard, NMES
is unlikely to offer any distinct advantage over traditional
forms of exercise.45
Two recent animal studies evaluated the use of ion-
tophoresis in delivering chemotherapeutic agents into lo-
cal tissues with active ductal carcinoma in situ lesions
and buccal tissue during active head and neck cancer.46,47
It was proposed that topical iontophoresis would not
only target the tumor and offer a noninvasive alternative
to intravenous administration but also reduce the dose
administered, thereby concomitantly decreasing cost and
the risk of systemic exposure. Komuro et al46 com-
pared iontophoretic delivery of miproxifen phosphate
(TAT-59) in breast ductal carcinoma in situ lesions with
systemic oral administration of TAT-59 and found that
the amount of penetrating TAT-59 in rat skin was sig-
nificantly greater with iontophoresis than under passive
conditions. They also found that high concentrations
of TAT-59 and DP-TAT-59 could be delivered via ion-
tophoresis to mammary tissue through the milk ducts
and that this technique resulted in low systemic plasma
concentrations.
In another study, Gratieri and Kalia47 compared pas-
sive diffusion versus buccal iontophoresis for the deliv-
ery of chemotherapeutic agents for the treatment of head
and neck cancers. They found significantly improved mu-
cosal deposition of 5-fluorouracil and leucovorin, with
no detectable systemic permeation observed in vivo. Ion-
tophoresis shows promising results for local administra-
tion of chemotherapeutic drugs, with decreased systemic
effects for specific cancers; however, the implications of
these findings to rehabilitation professionals are unclear.
In summary, the general precautions and contraindi-
cations for the aforementioned classifications of physical
agents summarized in Table 1 are still applicable. Up-
dated considerations for each of the classifications of phys-
ical agents for which there is new information are sum-
marized in Table 2. Further recommendations regarding
precautions and contraindications for physical agents for
which there have been no recent studies can be found in
Cameron’s1 or Pfalzer’s2 original article.
Although the physical agents described earlier may
have the aforementioned effects, APTA’s Choosing Wisely
Campaign warns that the use of physical agents alone is

TABLE 2
Updated Precautions or Considerations for Use of Physical Agents

Classification of
Agent Concerns/Considerations for Use in Individuals With Cancer

Thermotherapy Ultrasound
r Venous or arterial thrombosis or thrombophlebitis2
r Breast implants2
r Over central nervous system tissue2
r Contraindicated directly over malignant tumor12,13
Mechanical Intermittent pneumatic compression
r Systematically stimulates the lymphatic system
r Positive effect on breast cancer–related lymphedema
r Safe and effective supplemental treatment17-20
r Caution in areas of obstructed venous or lymphatic return1
Traction
r Must consider structural integrity of spine; no previous spinal surgery or previous radiation therapy to the spine2
Electromagnetic Low-level laser therapy
r Effective and safe in postmastectomy lymphedema24,25
r Need for optimal treatment regimen parameters including site, duration, repeatability, and laser application1,24,25
r Contraindicated within 6 mo after radiation therapy2
Electrotherapy Scrambler therapy4,29,30,32
r May reduce neuropathic pain (CIPN) better than pharmacologic management33
r Significant improvement in pain level, mood, walking ability, sleep, and sensory and motor outcomes37
Iontophoresis
r Promising results in terms of local chemotherapeutic drug administration and decreased systemic effects with specific
cancers, and improved local concentration of the drug of choice46,47
TENS
r Elevated blood flow at the stimulus site may invoke increased tumor growth; high-frequency TENS should have
minimal effect on blood flow and is safe for patients with cancer34
r Insufficient evidence to determine whether TENS should be used in adults with cancer-related pain35,38
r Further research is needed35,38
NMES
r No serious adverse events reported, but no significant differences seen between the NMES and control groups37,45

Abbreviations: CIPN, chemotherapy-induced peripheral neuropathy; NMES, neuromuscular electrical stimulation; TENS, transcutaneous electrical nerve
stimulation.

138 Wilson et al Rehabilitation Oncology

Copyright © 2018 Oncology Section, APTA. Unauthorized reproduction of this article is prohibited.
not considered physical therapy or best practice.48 In-
stead, physical agents should be used as an adjunct to a
comprehensive rehabilitation program that includes other
treatment modalities. Although many of these agents have
been studied extensively and general guidelines have been
established for their safe use, there is still a potential risk of
harm. To prevent harm, therapists must consider the risks
and benefits and educate their patients about each agent
and what to expect.1,2
CONCLUSION
After a thorough search of the literature, no new evi-
dence was found for many of the physical agents described
in Pfalzer’s original work. This may be due to the unequiv-
ocal findings regarding their effects on malignant tissues or
the reluctance of clinicians to use physical agents for indi-
viduals with cancer because of the possible adverse effects.
It is also possible that no new information has emerged
because physical agents are not as widely used now as in
the past. Most of the new evidence was for agents that have
emerged or gained popularity since 2001. There is evidence
to support that both LLLT and IPC reduce breast cancer–
related lymphedema without adverse effects.15-25 Emerging
evidence suggests that scrambler therapy may be safe and
beneficial for individuals post-CIPN.4,29,30 In nonhuman
subjects, iontophoresis may improve chemotherapy deliv-
ery to local tissues with decreased systemic effects.46,47
There is no definitive conclusion as to whether TENS is ad-
vantageous in controlling cancer-related pain.26-28,31,34-36
Because of the lack of high-quality evidence, the general-
izability of these findings is limited to the specific popu-
lations and still has the potential to cause harm if applied
incorrectly. The major limitation of this review is that it
was limited to articles written in English. Therefore, infor-
mation regarding the contemporary use of physical agents
in other countries may have been missed. Future research
should focus on the safety and efficacy of new and emerg-
ing physical agents on individuals with cancer.
Despite the theoretical and practical benefits of physi-
cal agents, the risk of harmful effects of using these physical
agents on cancer patients may outweigh the benefits. As
Michelle Cameron, PT, MD, OCS, stated in Goodman
and Fuller,5 Pathology: Implications for the Physical
Therapist:
. . . I wonder, is the benefit worth the risk? I don’t
know. None of us really knows. We don’t know how
great the benefit will be. We don’t know the level of
risk. We each get to decide, together with our patients,
what makes the most sense in a specific circumstance.
For me, the risk is rarely worth it. I recognize that
physical agents can help but there’s no going back if
cancer recurs, and there’s no knowing why it did.(p390)
A careful analysis of the risk to benefit ratio should be
used to decide when to use physical agents with this pa-
tient population. In certain circumstances such as in pallia-
tive care, physical agents may provide patients with better
Rehabilitation Oncology
Copyright © 2018 Oncology Section, APTA. Unauthorized reproduction of this article is prohibited.
quality of life, better pain control, and improved functional
capabilities despite the possibility of cancer growth.
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Rehabilitation Oncology