let there be light: diverse applications for low level ... · enhancing this aspect of oncology...

Let There Be Light: Diverse Applications for Low Level Laser Therapy in Oncology Practice

Katherine Neubauer, N.D.

As published in Naturopathic Doctor News and Review, October, 2010.

Heliotherapy, the therapeutic use of sunlight, has long been a core treatment in naturopathic tradition.

Current understanding of vitamin D’s importance in oncology supports the value we have placed on

heliotherapy. With the advent of laser technology, the benefit of specific wavelengths of light have been

investigated and yielded fascinating information.

This article discusses applications for light therapy in the form of low level laser therapy (LLLT) in the

oncology patient population. Some applications, such as mucositis and carpal tunnel syndrome, are well-

established. Other applications, such as for acute ischemic stroke and ototoxicity, are in the preliminary

stages of research. Overall, LLLT is a safe therapy with multiple benefits to this patient population, while

offering physicians opportunities for expanding their physical medicine practices.

Oncology studies

Among oncology patients, LLLT has specifically been assessed in clinical trials as a treatment for

iatrogenic mucositis and lymphedema.

Mucositis

Patients diagnosed with squamous cell carcinomas of the head and neck, typically receive radiation

therapy with concurrent low dose platinum chemotherapy. Dose intensity is critical to the efficacy of this

regimen, so treatment delays adversely affect prognosis. Oral mucositis is the dose limiting toxicity for

this regimen. At the hospital where the author practices, PEG tube placement is a routine step in the

initiation of chemoradiation therapy since these patients are likely to develop grade 2-3 oral mucositis

during treatment.

In multiple clinical trials involving both adults and children, low level laser therapy has been shown to

both prevent and treat oral mucositis associated with chemotherapy, radiation, or allogenic stem cell

transplant. 1 2 3 4 5 6 7 8 9

A Belgian trial examined patients who had previously developed chemotherapy-

associated mucositis, healed, and then restarted the identical chemotherapy. Among these high-risk

patients, LLLT prevented mucositis in 81%. Furthermore, LLLT resolved 83% of existing mucositis

lesions, compared to 11% in those treated with sham therapy.6 A phase II trial at the Seattle Cancer Care

Alliance confirmed these findings.8

Lymphedema

Post-treatment lymphedema develops in 15-20% of breast cancer patients due to axillary node radiation or

resection.10

Established treatments include therapeutic exercise, lymphatic drainage massage, and

compression garments. Botanical lymphagogues have also been discussed in this journal.

LLLT has been studied as a treatment for post-mastectomy lymphedema in clinics in China, Turkey, and

Australia.11 12 13

A placebo-controlled clinical trial published in Cancer found that two LLLT treatments

www.ml830clearance.com


decreased total limb volume and extracellular fluid volume in 33% of patients treated, with results

continuing at 3 month follow up.14

Co-morbidities:

LLLT has also been assessed in other patient populations as a treatment for several co-morbid conditions

that frequently impact quality of life for oncology patients. These include musculoskeletal pain,

neuropathy, fatigue, weakness, decreased exercise tolerance and wound healing.

Cardiology

Oncology patients can be at increased risk for cardiovascular disease due to paraneoplastic

hypercoagulability and due to side effects of cardiotoxic chemotherapies and biotherapies. Co-morbid

cardiovascular disease also limits patient access to radiation and surgical oncology therapies. LLLT is

being studied to improve patient outcomes after acute ischemic cerebrovascular accident and also as a

treatment for blood hypercoagulation. The University of California at San Diego is studying the use of

infrared transcranial laser therapy within the first 24 hours of acute ischemic stroke. In two double blind

randomized studies involving 120 and 600 patients respectively, this therapy improved outcomes on the

National Institutes of Health Stroke Score and the Glasgow Outcome Score. 15 16

Hypercoagulability is a common paraneoplastic syndrome and co-morbid condition in oncology patients.

Current therapy involves medications with narrow therapeutic index and significant toxicity. Preliminary

LLLT research in other patient populations with hypercoagulability poses intriguing possibilities for

enhancing this aspect of oncology care. Chinese scholars are investigating the impact of LLLT on blood

hypercoagulability in obstetrics patients, finding decreases in PT, aPTT, TT, and fibrinogen with

intranasal laser therapy.17

Neurology

Peripheral neuropathy and peripheral nerve injury are common issues in oncology practice. This includes

chemotherapy-induced peripheral neuropathy, diabetic peripheral neuropathy, and post-surgical peripheral

nerve injury.

A Serbian randomized study assessed 45 patients with chronic diabetic peripheral neuropathy, comparing

the efficacy of 780 nm LLLT with oral multivitamin therapy over the course of 12 weeks. Outcomes

included statistically significant improvements in electroneurographic conductivity and spatial perception

threshold in the LLLT group.18

The Israelis are studying LLLT as a treatment for chronic peripheral nerve injury. A small pilot study

assessed the effects of 780 nm LLLT in a randomized double blind placebo-controlled trial involving 18

patients. 19

Patients were treated daily for 21 days and then followed for 6 months. Interestingly, treatment

durations were 2-3 hours per treatment. Nevertheless, this study with extended treatment times found

improvements in motor function and electroneurographic activity at 3 months and 6 months following

LLLT.

Ototoxicity is also common in oncology practice, often manifesting as chronic tinnitus. Cisplatin,

vincristine, and antibiotics such as gentamycin are common causes. Three preliminary clinical trials have

assessed the efficacy of LLLT for chronic tinnitus of diverse causes. A small Italian study assessed the

use a 650 nm laser applied daily for 3 months in 26 patients with chronic idiopathic tinnitus of at least 3

years duration. 61% of treated patients improved at least one level on a standardized tinnitus severity



scale, compared with 35% in the placebo group.20

Another Italian study of tinnitus in patients with

sensorineural hearing loss found no significant benefit as measured by the Tinnitus Handicap Index,

though the laser group was noted to have a significant improvement in subjective and objective

hyperacusis.21

A Turkish study assessed transmeatal laser application and found a 48% improvement in

tinnitus loudness and 58% improvement in duration.22

Further research is needed to assess therapeutic

efficacy and the potential for application to medication-induced ototoxic tinnitus. In the meantime, laser

therapy is a reasonable consideration for this patient population, given excellent safety and the limited

availability of alternative treatments.

Pain Management and Orthopedics

Oncologic pain management involves a holistic perspective. While the acute pain crises may involve

metastatic disease, co-morbid non-malignant conditions may contribute significantly to the overall pain

burden. Improvement in pain associated with the co-morbid conditions can decrease pain medication use,

decrease associated sedation and constipation, and enhance quality of life for oncology patients.

Therefore, treating conditions such as osteoarthritis or tendinopathy can be an essential part of improving

quality of life in patients with advanced cancer.

LLLT has demonstrated efficacy for multiple painful co-morbid conditions that affect this patient

population. These include tendinopathies such as osteoarthritis, 23 24

lateral epicondylitis, 25 26 27 28

and

Achilles tendinopathy, 29

acute and chronic neck pain, 30

tension and migraine headache, 31

myofascial

pain syndrome, 32 33

knee pain, 34

chronic low back pain, 35 36

lumbar disc herniation, 37

frozen shoulder, 38

plantar fasciitis, 39

and limb pain and swelling after ischemic stroke. 40

Carpal tunnel syndrome (CTS) can be a dose limiting side effect of aromatase inhibitors (AIs) used in

breast cancer therapy. There are no clinical trials specifically assessing the use of LLLT for AI-induced

carpal tunnel syndrome. However, LLLT is established as an effective treatment for CTS in 5 clinical

trials. 41 42 43 44 45

A prospective randomized placebo controlled trial compared the efficacy of standard conservative

management with splinting alone, LLLT or splinting plus LLLT in 45 patients with mild or moderate

idiopathic CTS. The LLLT intervention involved 10 treatments over 3 months. Compared to the other two

groups, the patients receiving LLLT plus splinting experienced a higher rate of full or partial recovery,

improved EMG-measured median nerve conduction and increased grip strength. 46

Based on the

evidence from this and other studies, the FDA has approved CTS as an indication for certain LLLT lasers.

Temporomandibular joint dysfunction can develop as a complication of bulky tumor masses associated

with lymphoma or head and neck cancer. This improves with tumor debulking via chemotherapy,

radiation, surgery, or immune therapies. However, the interim period can be quite painful for the patient.

Palliative treatment options include acupuncture and gentle physical medicine. In the dental literature,

LLLT is being actively studied as a further potential treatment modality for TMJ in otherwise healthy

patients. In double blind placebo controlled trials, LLLT has decreased subjective pain measured on a

visual analog scale. 47 48 49 50 51 52

Some studies found increases in joint mobility and chewing

performance.53

It is reasonable to consider this therapy in the oncology patient population when TMJ

arises.

Fatigue and Exercise Tolerance



Fatigue, muscle weakness, and decreased exercise tolerance are common quality of life concerns for

patients with advanced cancer. Therapeutic exercise and l-carnitine can improve fatigue in oncology

patients. 54 55

However, poor patient performance status and/or limited oral intake can limit the application

of these therapies.

LLLT offers an additional treatment option. In vitro studies show that LLLT supports energy metabolism

via increasing adenosine triphosphate synthesis. 56

This has been confirmed in multiple cell types

including human red blood cells,57

lymphocytes, 58

neurons, 59 60

and adipose cells.61

In human

monocytes, LLLT increases nitric oxide release while decreasing reactive oxygen species. 62

LLLT increases activity of all enzymes of the electron transport chain. 63

Furthermore, it increases

mitochondrial membrane potential, ATP, and cAMP in hypoxic, anoxic, wounded cells. 64

So far, clinical studies on LLLT and fatigue have only assessed healthy and/or athletic patient

populations. Lasers of 650 – 860 nm have been shown to increase muscle endurance. 65 66 67

Some studies

also find decreased post-exercise levels of serum lactate and c-reactive protein. 65 66

The results were

statistically significant in 1 study, while 2 other studies showed a non-significant trend in favor of

increased exercise tolerance. 66 67 68 69 70

The potential to increase exercise tolerance via laser therapy is an

intriguing application that merits further research, both to clarify efficacy and to assess applications in

chronically ill populations.

Dermatology and Wound Care

LLLT can address several dermatologic concerns of oncology patients, including the healing of wounds,

dermal ulcers, and burns and the reduction of postoperative pain and swelling.

Oncology patients are often affected by dermal ulcers and wounds. This includes decubitus ulcers caused

by immobility, wounds associated with infiltrating tumor or co-morbid diabetes, and post-operative

conditions. In a clinical trial assessing chronic refractory wounds, LLLT increased heat shock protein

expression in wounds and accelerated wound closure. 71

A trial assessing chronic diabetic leg wounds

found 56% more granulation tissue deposition and 79.2% acceleration of healing compared to placebo.72

The dental literature discusses the wound healing benefits of LLLT extensively, particularly in terms of

improving post operative pain and swelling. 73 74

Further research is needed to assess the efficacy of LLLT

for post operative pain and swelling associated with general surgery and oncologic surgeries. In the

meantime, LLLT is a reasonable thing to try.

Hospital-based burn units are adopting LLLT for healing and pain control. 75

While I have not treated

severe burns in the oncology population, I have cared for inpatients with Stevens Johnson syndrome who

were later sent to a burn unit for further care. I wish that I had had access to LLLT in that setting to

enhance care for those patients.

LLLT is being studied as a treatment for alopecia, primarily for alopecia areata and androgenetic alopecia.

76 77 The FDA has approved one LLLT device specifically for androgenetic alopecia.

78 Potential

applications for chemotherapy-induced alopecia are intriguing and merit further study.

Gastroenterology and Pulmonology

In researching this article, I was surprised to find clinical trials regarding the use of LLLT for

gastrointestinal and respiratory conditions. These include noncalculous cholecystitis,79

chronic gastritis,80

and both acute and chronic asthma. 81 82 83 84



Potentiation of Anti-cancer Therapies

LLLT may have benefit in potentiating other anti-cancer therapies though evidence has not reached the

level of clinical trials. A June 2010 German paper reports ‘extraordinary’ levels of growth inhibition

when HeLa cervical cancer cells were exposed to 670 nm red laser after pretreatment with green tea. 85

There is also potential for the potentiation of radiation therapy via local increases in ATP, which depletes

tumor stores of reduced glutathione in mouse models. 86

Similarly, increased ATP potentiated the effects

of adriamycin on an ovarian cancer cell line in vitro. 87

Implementing Laser Therapy

There are multiple advantages to implementing LLLT in oncology practice. Foremost, patients appreciate

having nothing to swallow. Because LLLT may also lower the need for pain medication, laser therapy

may provide a number of benefits. Obviously LLLT will not cause the constipation that opioids do.

Perhaps more importantly, LLLT does not have the sedating action of most pain medications, allowing for

increased alert quality time with family, which is especially precious to patients with advanced cancers.

LLLT has no interactions with other oncology treatments, so it can be used when other treatments are

precluded by interaction concerns. Considering these benefits to oncology patients, we are currently

exploring the addition of LLLT here at CTCA.

Properly-administered laser treatment is painless and does not damage the skin. Best results occur with

multiple treatments. Insurance reimbursement in the range of $45 per treatment area may be available via

category III CPT codes. 88

Most LLLT treatments in the United States last 2-5 minutes per treatment area, with some authors raising

the theory that shorter treatments biostimulate while longer treatments suppress.89

The Arndt-Schulz rule

and some clinical evidence suggest a biphasic dose-response curve favoring frequent, brief treatments,

though the ideal treatment schedule has not been conclusively established.

When purchasing a laser therapy system, consider the FDA approval category and wavelength. FDA

approval categories describe the laser’s documented mechanism of action. NHN approval indicates that a

laser has been proven to biostimulate cells via increases in ATP production. Examples are the Erchonia

and Microlight lasers. ILY approval indicates that the laser works via heating tissue, similar to that of a

heating lamp. Regarding wavelength, individual research studies list the wavelength used. Overall, the

630 – 850 nm range is effective for the majority of applications.

Conclusion

LLLT offers a variety of benefits to the oncology patient and the naturopathic physician. Advantages

include robust scientific evidence, brief treatment time, diverse clinical indications, and patient comfort.

Acknowledgments

Thank you to Katherine Anderson, N.D., Larry Altshuler, M.D., Mark Axness, M.D., George River,

M.D., and Zack Varughese, M.B.A. for their collaboration in bringing low level laser therapy to oncology

patients.



Katherine Neubauer, N.D., FABNO completed residency and fellowship in integrative

oncology through Bastyr University and Southwestern Regional Medical Center. She is a fellow of the

American Board of Naturopathic Oncology. Dr. Neubauer trained at Southwest College of Naturopathic

Medicine and at the University of California, Berkeley. She has taught graduate-level courses in

pathology, clinical nutrition, and the history of medicine. Her research has been presented to the

American Public Health Association, the Association of Operating Room Nurses, the Journal of

Correctional Healthcare, and the Centers for Disease Control. She is currently co-developing a low level

laser therapy program at Southwestern Regional Medical Center.

Contact: [email protected].

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