Let There Be Light: Diverse applications for low-level laser therapy in oncology practice

Katherine Neubauer, ND

Heliotherapy, the therapeutic use of sunlight, has long been a core treatment in naturopathic medicine. Current understanding of vitamin Ds importance in oncology supports its value. With the advent of laser technology, the benefit of specific wavelengths of light has been investigated and has yielded fascinating information.

This article discusses applications for light therapy in the form of low-level laser therapy in the oncology patient population. Some applications, such as those for mucositis and carpal tunnel syndrome, are well-established. Other applications, such as those for acute ischemic stroke and ototoxicity, are in the preliminary stages of research. Overall, low-level laser therapy is a safe therapy, with multiple benefits to this patient population, while offering physicians the opportunity to expand their physical medicine practices.

Oncology Studies

Among oncology patients, low-level laser therapy 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. Dosage intensity is critical to the effectiveness of this regimen, so treatment delays adversely affect prognosis. Oral mucositis is the dose-limiting toxicity for this regimen. At the hospital where I practice, percutaneous endoscopic gastrostomy tube placement is a routine step in the initiation of chemoradiation therapy because these patients are likely to develop grade 2-3 oral mucositis during treatment.

In multiple clinical trials involving adults and children, low-level laser therapy has been shown to prevent and treat oral mucositis associated with chemotherapy, radiation, or allogenic stem cell transplant.1-9 A Belgian trial examined patients who previously had developed chemotherapy-associated mucositis; they healed and then restarted the identical chemotherapy. Among these high-risk patients, low-level laser therapy prevented mucositis in 81%. Furthermore, low-level laser therapy 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

Posttreatment lymphedema develops in 15% to 20% of breast cancer patients owing to axillary node radiation or resection.10 Established treatments include therapeutic exercise, lymphatic drainage massage, and compression garments. Botanical lymphagogues also have been discussed in NDNR.

Low-level laser therapy has been studied as a treatment for postmastectomy lymphedema in clinics in China, Turkey, and Australia.11-13 A placebo-controlled clinical trial published in Cancer found that 2 low-level laser therapy treatments decreased the total limb volume and extracellular fluid volume in 33% of patients treated, with results continuing at 3-month follow-up.14

Comorbidities

Low-level laser therapy also has been assessed in other patient populations as a treatment for several comorbid conditions that frequently affect the 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 owing to paraneoplastic hypercoagulability and to the adverse effects of cardiotoxic chemotherapies and biotherapies. Comorbid cardiovascular disease also limits patient access to radiation and surgical oncology therapies. Low-level laser therapy is being studied to improve patient outcomes after an 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 2 double-blind randomized studies involving 120 and 600 patients, 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 comorbid condition in oncology patients. Current therapy involves medications with narrow therapeutic index and significant toxicity. Preliminary low-level laser therapy research in other patient populations with hypercoagulability poses intriguing possibilities for enhancing this aspect of oncology care. Chinese scholars are investigating the effects of low-level laser therapy on blood hypercoagulability in obstetrics patients, finding decreases in prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen with intranasal laser therapy.17

Neurology

Peripheral neuropathy and peripheral nerve injury are common issues in oncology practice. These include chemotherapy-induced peripheral neuropathy, diabetic peripheral neuropathy, and postsurgical peripheral nerve injury.

A Serbian randomized study assessed 45 patients with chronic diabetic peripheral neuropathy, comparing the efficacy of 780 nm low-level laser therapy with oral multivitamin therapy over the course of 12 weeks. Outcomes included statistically significant improvements in electroneurographic conductivity and spatial perception threshold in the low-level laser therapy group.18

The Israelis are studying low-level laser therapy as a treatment for chronic peripheral nerve injury. A small pilot study assessed the effects of 780 nm low-level laser therapy 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 to 3 hours per treatment. Nevertheless, this study, with extended treatment times, found improvements in motor function and electroneurographic activity at 3 and 6 months after low-level laser therapy.

Ototoxicity is also common in oncology practice, often manifesting as chronic tinnitus. Cisplatin, vincristine, and antibiotics such as gentamycin are common causes of tinnitus. Three preliminary clinical trials have assessed the efficacy of low-level laser therapy for chronic tinnitus owing to a variety of causes. A small Italian study assessed the use of a 650-nm laser applied daily for 3 months in 26 patients with chronic idiopathic tinnitus of at least 3 years duration. In all, 61% of treated patients improved at least 1 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, although the laser group had significant improvements in subjective and objective hyperacusis.21 A Turkish study assessed transmeatal laser application and found a 48% improvement in tinnitus loudness and a 58% improvement in duration of the tinnitus.22 Future research should assess the therapeutic efficacy and the potential for applying medication-induced, ototoxic tinnitus. Meanwhile, laser therapy may be a reasonable treatment option for this patient population given its excellent safety record and the limited availability of alternative treatments.

Pain Management and Orthopedics

Oncologic pain management involves a holistic perspective. While acute pain crises may involve metastatic disease, comorbid, nonmalignant conditions may contribute significantly to the overall pain burden. Improving pain associated with comorbid conditions can decrease pain medication use, decrease associated sedation and constipation, and enhance the quality of life for oncology patients. Therefore, treating conditions such as osteoarthritis or tendonopathy can be an essential part of improving the quality of life in patients with advanced cancer.

Low-level laser therapy has demonstrated efficacy for multiple painful comorbid conditions that affect this patient population. These include tendonopathies such as osteoarthritis,23 , 24 lateral epicondylitis,25-28 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 can be a dose-limiting adverse effect of aromatase inhibitors used in breast cancer therapy. There are no clinical trials specifically assessing the use of low-level laser therapy for aromatase inhibitor-induced carpal tunnel syndrome. However, low-level laser therapy has been shown to be an effective treatment for carpal tunnel syndrome in 5 clinical trials.41-45

One prospective, randomized, placebo-controlled trial compared the efficacy of standard conservative management with splinting alone, low-level laser therapy, or splinting plus low-level laser therapy in 45 patients with mild or moderate idiopathic carpal tunnel syndrome. The low-level laser therapy involved 10 treatments over 3 months. Compared with the other 2 groups, the patients receiving low-level laser therapy plus splinting experienced a higher rate of full or partial recovery, improved electromyogram-measured median nerve conduction, and increased grip strength.46 Based on the evidence from this and other studies, the FDA has approved carpal tunnel syndrome as an indication for certain low-level laser therapies.

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 can be quite painful for the patient. Palliative treatment options include acupuncture and gentle physical medicine, such as use of a compression garment, manual lymph draining, skin care or therapeutic exercise. In the dental literature, low-level laser therapy is being actively studied as a potential treatment for temporomandibular joint dysfunction in otherwise healthy patients. In double-blind, placebo-controlled trials, low-level laser therapy have decreased subjective pain measured on a visual analog scale.47-52 Some studies found increases in joint mobility and chewing ability.53 It is reasonable to consider this therapy in the oncology patient population when temporomandibular joint dysfunction 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.

Low-level laser therapy offers an additional treatment option. In vitro studies show that low-level laser therapy supports energy metabolism by 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, low-level laser therapy increases nitric oxide release while decreasing reactive oxygen species.62

Low-level laser therapy increases activity of all enzymes of the electron transport chain.63 Furthermore, it increases mitochondrial membrane potential, adenosine triphosphate, and cAMP in hypoxic, anoxic, wounded cells.64

To date, clinical studies on low-level laser therapy and fatigue have assessed only healthy and/or athletic patient populations. Lasers of 650-860 nm have been shown to increase muscle endurance.65-67 Some studies also have found 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 nonsignificant trend in favor of increased exercise tolerance.66-70 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

Low-level laser therapy can address several dermatologic concerns of oncology patients, including wound healing, dermal ulcers, burns, and 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 tumors or comorbid diabetes, and postoperative conditions. In a clinical trial assessing chronic refractory wounds, low-level laser therapy 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 a 79.2% acceleration of healing compared with a placebo group.72 The dental literature extensively discusses the wound healing benefits of low-level laser therapy, particularly in terms of improving postoperative pain and swelling.73, 74 Further research is needed to assess the efficacy of low-level laser therapy for postoperative pain and swelling associated with general surgery and oncologic surgeries. Meanwhile, low-level laser therapy may be a reasonable treatment option.

Hospital-based burn units are adopting low-level laser therapy 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 I had access to a low-level laser to care for those patients.

Low-level laser therapy is being studied as a treatment for alopecia, primarily for alopecia areata and androgenetic alopecia.76, 77 The FDA has approved 1 low-level laser 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 low-level laser therapy for gastrointestinal and respiratory conditions. These include noncalculous cholecystitis,79 chronic gastritis,80 and acute and chronic asthma.81-84

Potentiation of Anti-Cancer Therapies

Low-level laser therapy may have benefit in potentiating other anti-cancer therapies, although 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 a 670-nm red laser after pretreatment with green tea.85 Low-level laser therapy also potentiates radiation therapy via local increases in adenosine triphosphate, which depletes tumor stores of reduced glutathione in mouse models.86 Similarly, increased adenosine triphosphate potentiated the effects of doxorubicin on an ovarian cancer cell line in vitro.87

Implementing Laser Therapy

There are multiple advantages to implementing low-level laser therapy in oncology practice. Foremost, patients appreciate having nothing to swallow. Because low-level laser therapy may lower the need for pain medication, laser therapy provides several benefits. Obviously, low-level laser therapy will not cause the constipation that opioids do. More importantly, low-level laser therapy does not have the sedating action of most pain medications, allowing for increased alert quality time with the family, which is especially precious to patients with advanced cancers. Low-level laser therapy has no known 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 low-level laser therapy 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 low-level laser therapy treatments in the United States last 2 to 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, although the ideal treatment schedule has not been conclusively established.

When purchasing a laser therapy system, consider the FDA approval category and wavelength. Food and Drug Administration 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- to 850-nm range is effective for most applications.

Low-level laser therapy 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

We would like to thank Katherine Anderson, ND; Larry Altshuler, MD; Mark Axness, MD; George River, MD; and Zack Varughese, MBA for their collaboration in bringing low-level laser therapy to oncology patients.

The Oncology Association of Naturopathic Physicians (OncANP) was founded in 2004 to enhance the quality of life of people living with cancer through both increasing the collaboration between NDs working with patients with cancer and integrating naturopathic practice into medical oncology care. With its co-organization, the American Board of Naturopathic Oncology (ABNO), the OncANP has set standards, instituted testing, and now credentials Fellows in Naturopathic Oncology.

The OncANP welcomes all NDs interested in improving their knowledge and ability to work with oncology patients. For more information, see www.OncANP.org.


 

Katherine Neubauer, ND is celebrating the completion of her two year residency in integrative oncology at Cancer Treatment Centers of America in Tulsa. 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 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.

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