Oncology

J Biomed Opt. 2012 Oct 25;17(10):101516-1. doi: 10.1117/1.JBO.17.10.101516.

Low-level laser therapy on MCF-7 cells: a micro-Fourier transform infrared spectroscopy study.

Magrini TD, Dos Santos NV, Milazzotto MP, Cerchiaro G, da Silva Martinho H.

Abstract

ABSTRACT. Low-level laser therapy (LLLT) is an emerging therapeutic approach for several clinical conditions. The clinical effects induced by LLLT presumably scale from photobiostimulation/photobioinhibition at the cellular level to the molecular level. The detailed mechanism underlying this effect remains unknown. This study quantifies some relevant aspects of LLLT related to molecular and cellular variations. Malignant breast cells (MCF-7) were exposed to spatially filtered light from a He-Ne laser (633 nm) with fluences of 5, 28.8, and 1000 mJ/cm2. The cell viability was evaluated by optical microscopy using the Trypan Blue viability test. The micro-Fourier transform infrared technique was employed to obtain the vibrational spectra of each experimental group (control and irradiated) and identify the relevant biochemical alterations that occurred due to the process. It was observed that the red light influenced the RNA, phosphate, and serine/threonine/tyrosine bands. We found that light can influence cell metabolism depending on the laser fluence. For 5 mJ/cm2, MCF-7 cells suffer bioinhibition with decreased metabolic rates. In contrast, for the 1 J/cm2 laser fluence, cells present biostimulation accompanied by a metabolic rate elevation. Surprisingly, at the intermediate fluence, 28.8 mJ/cm2, the metabolic rate is increased despite the absence of proliferative results. The data were interpreted within the retrograde signaling pathway mechanism activated with light irradiation.

Photomed Laser Surg. 2012 Aug 1. [Epub ahead of print]

A Preliminary Study of the Safety of Red Light Phototherapy of Tissues Harboring Cancer.

Myakishev-Rempel M, Stadler I, Brondon P, Axe DR, Friedman M, Nardia FB, Lanzafame R.

Source

1 Department of Dermatology, University of Rochester , Rochester, New York.

Abstract

Abstract Objective: Red light phototherapy is known to stimulate cell proliferation in wound healing. This study investigated whether low-level light therapy (LLLT) would promote tumor growth when pre-existing malignancy is present.

Background data: LLLT has been increasingly used for numerous conditions, but its use in cancer patients, including the treatment of lymphedema or various unrelated comorbidities, has been withheld by practitioners because of the fear that LLLT might result in initiation or promotion of metastatic lesions or new primary tumors. There has been little scientific study of oncologic outcomes after use of LLLT in cancer patients.

Methods: A standard SKH mouse nonmelanoma UV-induced skin cancer model was used after visible squamous cell carcinomas were present, to study the effects of LLLT on tumor growth. The red light group (n=8) received automated full body 670 nm LLLT delivered twice a day at 5 J/cm(2) using an LED source. The control group (n=8) was handled similarly, but did not receive LLLT.

Measurements on 330 tumors were conducted for 37 consecutive days, while the animals received daily LLLT. Results: Daily tumor measurements demonstrated no measurable effect of LLLT on tumor growth.

Conclusions: This experiment suggests that LLLT at these parameters may be safe even when malignant lesions are present. Further studies on the effects of photoirradiation on neoplasms are warranted.

Support Care Cancer.  2012 Mar;20(3):523-9. Epub 2011 Feb 22.

Differential responses of fibroblasts, non-neoplastic epithelial cells, and oral carcinoma cells to low-level laser therapy.

Schartinger VH, Galvan O, Riechelmann H, Dudás J.

Source

Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. volker.schartinger@i-med.ac.at

Abstract

Low-level laser therapy (LLLT) is used in the treatment of chemoradiotherapy- or radiotherapy-induced oropharyngeal mucositis (ORM). In head and neck cancer, tumor cells may lie in the LLLT irradiation field, and LLLT might promote tumor progression. We therefore investigated the effect of LLLT on proliferation, cell cycle distribution, and apoptosis in a human oral carcinoma cell line (SCC-25), non-malignant epithelial cells (BEAS-2B), and fibroblasts in vitro. The cell lines were subjected to LLLT on three consecutive days for 15 min. Cell proliferation was assessed using the MTT assay, cell cycle distribution by flow cytometry and propidium-iodide DNA staining, and apoptosis using an Annexin V-FITC assay. Controls were sham-treated, but not exposed to the laser treatment. LLLT treatment resulted in increased fibroblast proliferation (p < 0.001), whereas decreased cell proliferation was observed after LLLT treatment of BEAS-2B (p = 0.003) and SCC-25 cells (p < 0.001). In SCC-25 cells, an increased percentage of S-phase cells and decreased percentage of G1-phase cells were observed (p < 0.001). Moreover, a proapoptotic effect of LLLT was observed in SCC-25 cells (p = 0.02). LLLT did not exhibit a tumor-promoting effect in this in vitro study.

Acc Chem Res.   2012 Apr 30. [Epub ahead of print]

Detecting and Destroying Cancer Cells in More than One Way with Noble Metals and Different Confinement Properties on the Nanoscale.

Dreaden EC, El-Sayed MA.

Source

Laser Dynamics Laboratory, Department of Chemistry and Biochemistry, Georgia Institute of Technology , Atlanta, Georgia 30332-0400, United States.

Abstract

Today, 1 in 2 males and 1 in 3 females in the United States will develop cancer at some point during their lifetimes, and 1 in 4 males and 1 in 5 females in the United States will die from the disease. New methods for detection and treatment have dramatically improved cancer care in the United States. However, as improved detection and increasing exposure to carcinogens has led to higher rates of cancer incidence, clinicians and researchers have not balanced that increase with a similar decrease in cancer mortality rates. This mismatch highlights a clear and urgent need for increasingly potent and selective methods with which to detect and treat cancers at their earliest stages. Nanotechnology, the use of materials with structural features ranging from 1 to 100 nm in size, has dramatically altered the design, use, and delivery of cancer diagnostic and therapeutic agents. The unique and newly discovered properties of these structures can enhance the specificities with which biomedical agents are delivered, complementing their efficacy or diminishing unintended side effects. Gold (and silver) nanotechnologies afford a particularly unique set of physiological and optical properties which can be leveraged in applications ranging from in vitro/vivo therapeutics and drug delivery to imaging and diagnostics, surgical guidance, and treatment monitoring. Nanoscale diagnostic and therapeutic agents have been in use since the development of micellar nanocarriers and polymer-drug nanoconjugates in the mid-1950s, liposomes by Bangham and Watkins in the mid-1960s, and the introduction of polymeric nanoparticles by Langer and Folkman in 1976. Since then, nanoscale constructs such as dendrimers, protein nanoconjugates, and inorganic nanoparticles have been developed for the systemic delivery of agents to specific disease sites. Today, more than 20 FDA-approved diagnostic or therapeutic nanotechnologies are in clinical use with roughly 250 others in clinical development. The global market for nano-enabled medical technologies is expected to grow to $70-160 billion by 2015, rivaling the current market share of biologics worldwide. In this Account, we explore the emerging applications of noble metal nanotechnologies in cancer diagnostics and therapeutics carried out by our group and by others. Many of the novel biomedical properties associated with gold and silver nanoparticles arise from confinement effects: (i) the confinement of photons within the particle which can lead to dramatic electromagnetic scattering and absorption (useful in sensing and heating applications, respectively); (ii) the confinement of molecules around the nanoparticle (useful in drug delivery); and (iii) the cellular/subcellular confinement of particles within malignant cells (such as selective, nuclear-targeted cytotoxic DNA damage by gold nanoparticles). We then describe how these confinement effects relate to specific aspects of diagnosis and treatment such as (i) laser photothermal therapy, optical scattering microscopy, and spectroscopic detection, (ii) drug targeting and delivery, and (iii) the ability of these structures to act as intrinsic therapeutic agents which can selectively perturb/inhibit cellular functions such as division. We intend to provide the reader with a unique physical and chemical perspective on both the design and application of these technologies in cancer diagnostics and therapeutics. We also suggest a framework for approaching future research in the field.

Photomed Laser Surg.  2011 Jun 30. [Epub ahead of print]

Influence of Laser Phototherapy (?660?nm) on the Outcome of Oral Chemical Carcinogenesis on the Hamster Cheek Pouch Model: Histological Study.

de C Monteiro JS, Pinheiro AL, de Oliveira SC, Aciole GT, Sousa JA, Cangussú MC, Dos Santos JN.

Source

1 Center of Biophotonics, School of Dentistry, Federal University of Bahia , Salvador, Brazil .

Abstract

Abstract Purpose: This study aimed to evaluate, histologically, the effect of low-level laser therapy (LLLT) (?660?nm) on DMBA chemically induced lesions of the oral mucosa of hamsters.

Background data: Squamous cell carcinoma (SCC) is the most common neoplasm of the oral cavity. It is aggressive, highly proliferative, invasive, and metastatic. There is evidence that LLLT similarly affects neoplasic and non-neoplasic cells.

Methods: Cancerous lesions were induced on the cheek pouch of 15 golden Syrian hamsters by using DMBA 3 times a week for 8 weeks. At the end of the cancer induction (8 weeks), animals of G1 were killed and the presence of tumors confirmed. Animals of G3 were irradiated (?660?nm, 30?mW, CW, Ø=3?mm, area: 0.07?cm(2), 424 mW/cm(2), 133?sec, 56.4?J/cm(2), 4?J) at every other day for 4 weeks. G2 received no interventions for the same period. Samples were taken and underwent histological analysis by light microscopy.

Results: GI showed 100% well-differentiated SCC. G2 showed 20% moderately differentiated and 80% well-differentiated SCC. G3 showed 40% well-differentiated, 40% poorly differentiated, and 20% moderately differentiated SCC. Significant differences (p=0.02) in the amount of well-differentiated SCC were seen between G1 and G3 and between G3 and G2 (p=0.04). Significant difference was also seen between G3 and G1 and G2 regarding the number of poorly differentiated tumors (p=0.04).

Conclusions: It is concluded that LLLT, within the parameters specified in the present study, caused a significant progression of the severity of SCC in the oral cavity of hamsters.

Support Care Cancer.  2011 Feb 22. [Epub ahead of print]

Differential responses of fibroblasts, non-neoplastic epithelial cells, and oral carcinoma cells to low-level laser therapy.

Schartinger VH, Galvan O, Riechelmann H, Dudás J.

Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria, volker.schartinger@i-med.ac.at.

Abstract

Low-level laser therapy (LLLT) is used in the treatment of chemoradiotherapy- or radiotherapy-induced oropharyngeal mucositis (ORM). In head and neck cancer, tumor cells may lie in the LLLT irradiation field, and LLLT might promote tumor progression. We therefore investigated the effect of LLLT on proliferation, cell cycle distribution, and apoptosis in a human oral carcinoma cell line (SCC-25), non-malignant epithelial cells (BEAS-2B), and fibroblasts in vitro. The cell lines were subjected to LLLT on three consecutive days for 15 min. Cell proliferation was assessed using the MTT assay, cell cycle distribution by flow cytometry and propidium-iodide DNA staining, and apoptosis using an Annexin V-FITC assay. Controls were sham-treated, but not exposed to the laser treatment. LLLT treatment resulted in increased fibroblast proliferation (p?<?0.001), whereas decreased cell proliferation was observed after LLLT treatment of BEAS-2B (p?=?0.003) and SCC-25 cells (p?<?0.001). In SCC-25 cells, an increased percentage of S-phase cells and decreased percentage of G1-phase cells were observed (p?<?0.001). Moreover, a proapoptotic effect of LLLT was observed in SCC-25 cells (p?=?0.02). LLLT did not exhibit a tumor-promoting effect in this in vitro study.

Curr Opin Oncol. 2010 May;22(3):221-5.

Supportive care in head and neck oncology.

de Castro G Jr, Guindalini RS.

Department of Clinical Oncology, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

Abstract

PURPOSE OF REVIEW: Survival gains were achieved in head and neck cancer patients treated with a multidisciplinary approach, including platinum-based concurrent chemoradiation, with a substantial increase in toxicity. The prompt diagnosis and treatment of these toxicities – the focus of this review – are essential aspects in the daily care of head and neck squamous cell carcinoma patients.

RECENT FINDINGS: Low-level laser is a promising therapy for prevention and treatment of mucositis. Amifostine, as an acute and late xerostomia-preventive agent, may be considered in patients undergoing fractionated radiation therapy alone. The incidence of xerostomia was significantly reduced in patients treated with intensity-modulated radiation therapy. Severe cutaneous reactions can occur when epidermal growth factor receptor-targeting agents are administered concurrently to radiation therapy. Erythropoiesis-stimulating agents should not be administered to head and neck cancer patients under radiation therapy or chemotherapy outside of the context of clinical trials.

SUMMARY: The best outcomes in head and neck squamous cell carcinoma patients treated in the multidisciplinary context can only be achieved with an adequate patient selection, an experienced and motivated team and if the best possible supportive care is offered. Randomized studies on promising supportive therapies must be encouraged.

Photomed Laser Surg. 2010 Feb;28(1):115-23.

The effect of laser irradiation on proliferation of human breast carcinoma, melanoma, and immortalized mammary epithelial cells.

 

Powell K, Low P, McDonnell PA, Laakso EL, Ralph SJ.

School of Medical Science, Griffith University, Gold Coast, Queensland, Australia.

Abstract

OBJECTIVE: This study compared the effects of different doses (J/cm(2)) of laser phototherapy at wavelengths of either 780, 830, or 904 nm on human breast carcinoma, melanoma, and immortalized human mammary epithelial cell lines in vitro. In addition, we examined whether laser irradiation would malignantly transform the murine fibroblast NIH3T3 cell line.

BACKGROUND: Laser phototherapy is used in the clinical treatment of breast cancer-related lymphoedema, despite limited safety information. This study contributes to systematically developing guidelines for the safe use of laser in breast cancer-related lymphoedema. METHODS: Human breast adenocarcinoma (MCF-7), human breast ductal carcinoma with melanomic genotypic traits (MDA-MB-435S), and immortalized human mammary epithelial (SVCT and Bre80hTERT) cell lines were irradiated with a single exposure of laser. MCF-7 cells were further irradiated with two and three exposures of each laser wavelength. Cell proliferation was assessed 24 h after irradiation.

RESULTS: Although certain doses of laser increased MCF-7 cell proliferation, multiple exposures had either no effect or showed negative dose response relationships. No sign of malignant transformation of cells by laser phototherapy was detected under the conditions applied here.

CONCLUSION: Before a definitive conclusion can be made regarding the safety of laser for breast cancer-related lymphoedema, further in vivo research is required.

Vopr Kurortol Fizioter Lech Fiz Kult. 2009 Nov-Dec;(6):49-52.

Application of low-power visible and near infrared radiation in clinical oncology.

[Article in Russian]

Zimin AA, Zhevago NA, Bu?niakova AI, Samo?lova KA.

Although low-power visible (VIS) and near infrared (nIR) radiation emitted from lasers, photodiodes, and other sources does not cause neoplastic transformation of the tissue, these phototherapeutic techniques are looked at with a great deal of caution for fear of their stimulatory effect on tumour growth. This apprehension arises in the first place from the reports on the possibility that the proliferative activity of tumour cells may increase after their in vitro exposure to light. Much less is known that these phototherapeutic modalities have been successfully used for the prevention and management of complications developing after surgery, chemo- and radiotherapy. The objective of the present review is to summarize the results of applications of low-power visible and near infrared radiation for the treatment of patients with oncological diseases during the last 20-25 years. It should be emphasized that 2-4 year-long follow-up observations have not revealed any increase in the frequency of tumour recurrence and metastasis.

BMC Cancer. 2009 Nov 20;9:404.

The effect of low-level laser irradiation (In-Ga-Al-AsP-660 nm) on melanoma in vitro and in vivo.

Frigo L, Luppi JS, Favero GM, Maria DA, Penna SC, Bjordal JM, Bensadoun RJ, Lopes-Martins RA.

Laboratory of Pharmacology and Phototherapy of Inflammation, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo – São Paulo 05508-900 SP – Brasil. luciofrigo@uol.com.br

BACKGROUND: It has been speculated that the biostimulatory effect of Low Level Laser Therapy could cause undesirable enhancement of tumor growth in neoplastic diseases. The aim of the present study is to analyze the behavior of melanoma cells (B16F10) in vitro and the in vivo development of melanoma in mice after laser irradiation.

METHODS: We performed a controlled in vitro study on B16F10 melanoma cells to investigate cell viability and cell cycle changes by the Tripan Blue, MTT and cell quest histogram tests at 24, 48 and 72 h post irradiation. The in vivo mouse model (male Balb C, n = 21) of melanoma was used to analyze tumor volume and histological characteristics. Laser irradiation was performed three times (once a day for three consecutive days) with a 660 nm 50 mW CW laser, beam spot size 2 mm(2), irradiance 2.5 W/cm(2) and irradiation times of 60s (dose 150 J/cm(2)) and 420s (dose 1050 J/cm(2)) respectively.

RESULTS: There were no statistically significant differences between the in vitro groups, except for an increase in the hypodiploid melanoma cells (8.48 +/- 1.40% and 4.26 +/- 0.60%) at 72 h post-irradiation. This cancer-protective effect was not reproduced in the in vivo experiment where outcome measures for the 150 J/cm(2) dose group were not significantly different from controls. For the 1050 J/cm(2) dose group, there were significant increases in tumor volume, blood vessels and cell abnormalities compared to the other groups.

CONCLUSION: LLLT Irradiation should be avoided over melanomas as the combination of high irradiance (2.5 W/cm(2)) and high dose (1050 J/cm(2)) significantly increases melanoma tumor growth in vivo.

Photomed Laser Surg. 2009 Oct;27(5):763-9.

Managing postmastectomy lymphedema with low-level laser therapy.

Lau RW, Cheing GL.

Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong SAR, China.

OBJECTIVE: We aimed to investigate the effects of low-level laser therapy (LLLT) in managing postmastectomy lymphedema. BACKGROUND DATA: Postmastectomy lymphedema (PML) is a common complication of breast cancer treatment that causes various symptoms, functional impairment, or even psychosocial morbidity. A prospective, single-blinded, controlled clinical trial was conducted to examine the effectiveness of LLLT on managing PML.

METHODS: Twenty-one women suffering from unilateral PML were randomly allocated to receive either 12 sessions of LLLT in 4 wk (the laser group) or no laser irradiation (the control group). Volumetry and tonometry were used to monitor arm volume and tissue resistance; the Disabilities of Arm, Shoulder, and Hand (DASH) questionnaire was used for measuring subjective symptoms. Outcome measures were assessed before and after the treatment period and at the 4 wk follow-up.

RESULTS: Reduction in arm volume and increase in tissue softening was found in the laser group only. At the follow-up session, significant between-group differences (all p < 0.05) were found in arm volume and tissue resistance at the anterior torso and forearm region. The laser group had a 16% reduction in the arm volume at the end of the treatment period, that dropped to 28% in the follow-up. Moreover, the laser group demonstrated a cumulative increase from 15% to 33% in the tonometry readings over the forearm and anterior torso. The DASH score of the laser group showed progressive improvement over time.

CONCLUSION: LLLT was effective in the management of PML, and the effects were maintained to the 4 wk follow-up.

Lasers Med Sci. 2009 Jul;24(4):597-603. Epub 2008 Oct 21.

Effect of drug-light interval on the mode of action of Photofrin photodynamic therapy in a mouse tumor model.

Li LB, Luo RC.

Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China. li_libo2008@yahoo.com.cn

Abstract

Our objective was to examine the effect of time intervals between Photofrin injection and laser irradiation [i.e., drug-light interval (DLI)] on the mode of action of Photofrin photodynamic therapy (PDT). Kunming mice transplanted with sarcoma-180 cells were used as an animal model. The tumor-bearing mice in the control group were given neither photosensitizer nor laser irradiation. PDT groups were given intravenous (i.v.) injection of Photofrin (7.5 mg/kg) prior to being irradiated with a 630 nm laser at 120 J/cm(2) at different DLIs (1 min-48 h). Tumors and overlying skin were visually examined daily. Histopathological and electron microscopic examinations were carried out 48 h after PDT. Survival rates were recorded. The mice in the groups that had experienced short DLIs (<60 min) showed stronger skin reactions than the groups subjected to long DLIs (>6 h). Histological examination showed that antitumor effects were achieved mainly by the destruction of tumor blood vessels and the formation of thrombosis at short DLIs, whereas, at long DLIs, the tumor cells were killed directly by PDT-mediated cytotoxicity. Electron microscopy revealed various degrees of mitochondrial swelling. The survival rate of the mice subjected to long DLIs was slightly higher than that of the mice subjected to short DLIs. Both vascular (e.g., tumor vessel destruction) and cellular (e.g., cytotoxicity) effects contributed to Photofrin PDT-induced tumor ablation.

Clin Rehabil. 2009 Feb;23(2):117-24

Efficacy of pneumatic compression and low-level laser therapy in the treatment of postmastectomy lymphoedema: a randomized controlled trial.

Kozanoglu E, Basaran S, Paydas S, Sarpel T.

Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Cukurova University, Adana, Turkey.

Objective: To compare the long-term efficacy of pneumatic compression and low-level laser therapies in the management of postmastectomy lymphoedema.Design: Randomized controlled trial.Setting: Department of Physical Medicine and Rehabilitation of Cukurova University, Turkey.

Subjects: Forty-seven patients with postmastectomy lymphoedema were enrolled in the study.

Interventions: Patients were randomly allocated to pneumatic compression (group I, n=24) and low-level laser (group II, n=23) groups. Group I received 2 hours of compression therapy and group II received 20 minutes of laser therapy for four weeks. All patients were advised to perform daily limb exercises.Main measures: Demographic features, difference between sum of the circumferences of affected and unaffected limbs (triangle upC), pain with visual analogue scale and grip strength were recorded.

Results: Mean age of the patients was 48.3 (10.4) years. triangle upC decreased significantly at one, three and six months within both groups, and the decrease was still significant at month 12 only in group II (P = 0.004). Improvement of group II was greater than that of group I post treatment (P = 0.04) and at month 12 after 12 months (P = 0.02). Pain was significantly reduced in group I only at posttreatment evaluation, whereas in group II it was significant post treatment and at follow-up visits. No significant difference was detected in pain scores between the two groups. Grip strength was improved in both groups, but the differences between groups were not significant.

Conclusions: Patients in both groups improved after the interventions. Group II had better long-term results than group I. Low-level laser might be a useful modality in the treatment of postmastectomy lymphoedema.

Photomed Laser Surg. 2009 Apr;27(2):371-4

Improvement in quality of life of an oncological patient by laser phototherapy.

Campos L, Simões A, Sá PH, Eduardo Cde P.

Oral Biology Research Center, Department of Biomaterials and Oral Biochemistry, School of Dentistry, University of São Paulo, São Paulo, Brazil.

OBJECTIVE AND BACKGROUND DATA: Common side effects of radiotherapy (RT) to the head and neck include oral mucositis, xerostomia, and severe pain. The aim of this study is to report improvement in the quality of life of an oncological patient by laser phototherapy (LPT).

CLINICAL CASE AND LASER PHOTOTHERAPY PROTOCOL: The patient, a 15-year-old girl diagnosed with mucoepidermoid carcinoma, underwent surgical excision of a tumor of the left palatomaxilla. After that, she was subjected to 35 sessions of RT (2 Gy/d). Clinical examination revealed the spread of severe ulcerations to the jugal mucosa, gums, lips, hard palate, and tongue (WHO mucositis score 3). She had difficulty in moving her tongue and she was unable to eat any solid food. Oral hygiene orientation and LPT were performed throughout all RT sessions. A continuous diode laser, 660 nm, 40 mW, 6 J/cm(2), 0.24 J per point in contact mode, with spot size of 0.04 cm(2) was used in the entire oral cavity. A high-power diode laser at 1 W, 10 sec per cm of mucositis, approximately 10 J/cm(2), was used in defocused mode only on ulcerative lesions. After the first laser irradiation session, decreases in pain and xerostomia were reported; however, a more significant improvement was seen after five sessions. At that point although the mucositis score was still 2, the patient reported that she was free of pain, and consequently a palatine plate could be made to rehabilitate the entire surgical area. Seventeen laser irradiation sessions were necessary to eliminate all oral mucositis lesions.

CONCLUSION: Normal oral function and consequent improvements in the quality of life of this oncologic patient were observed with LPT.

Braz Dent J. 2009;20(3):215-20.

Use of therapeutic laser for prevention and treatment of oral mucositis.

Khouri VY, Stracieri AB, Rodrigues MC, Moraes DA, Pieroni F, Simões BP, Voltarelli JC.

University Hospital, University of São Paulo, Ribeirão Preto, SP, Brazil. vivikhouri@usp.br

Oral mucositis (OM) affects patients who are submitted to hematopoietic stem cell transplantation (HSCT) due to high doses of chemotherapy and/or radiotherapy. The purpose of this investigation was to perform a comparative study of the frequency and evolution of OM among patients subjected to therapeutic laser and to the conventional therapy (use of mouthwash called ‘Mucositis Formula’). The patients were subjected to a myeloablative conditioning regimen before the allogeneic HSCT. Twenty-two patients were selected and divided into 2 groups: group I was irradiated with InGaAlP laser (660 nm) and GaAlAs laser (780 nm), 25 mW potency, 6.3J/cm(2) dose, in 10-s irradiation time, followed to conventional treatment; group II was subjected only to the conventional treatment. Both World Health Organization (WHO) scale and the Oral Mucositis Assessment Scale (OMAS) were used to evaluate the results. Data were analyzed by the non-parametric Wilcoxon test, with p<0.05 considered as statistically significant. Group I presented a lower frequency of OM (p=0.02) and lower mean scores, according to WHO and OMAS scales (p<0.01 and p=0.01, respectively). In conclusion, laser reduced the frequency and severity of OM, suggesting that therapeutic laser can be used both as a new form of prevention and treatment of OM.

Lasers Surg Med. 2009 Apr;41(4):264-70.

Laser phototherapy as topical prophylaxis against head and neck cancer radiotherapy-induced oral mucositis: comparison between low and high/low power lasers.

Simões A, Eduardo FP, Luiz AC, Campos L, Sá PH, Cristófaro M, Marques MM, Eduardo CP.

Centro de Pesquisa em Biologia Oral, Departamento de Materiais Dentários, Faculdade de Odontologia, Universidade de São Paulo (FOUSP), São Paulo 05508-900, Brazil. lysimoes@usp.br

BACKGROUND AND OBJECTIVE: Oral mucositis is a dose-limiting and painful side effect of radiotherapy (RT) and/or chemotherapy in cancer patients. The purpose of the present study was to analyze the effect of different protocols of laser phototherapy (LPT) on the grade of mucositis and degree of pain in patients under RT. PATIENTS AND METHODS: Thirty-nine patients were divided into three groups: G1, where the irradiations were done three times a week using low power laser; G2, where combined high and low power lasers were used three time a week; and G3, where patients received low power laser irradiation once a week. The low power LPT was done using an InGaAlP laser (660 nm/40 mW/6 J cm(-2)/0.24 J per point). In the combined protocol, the high power LPT was done using a GaAlAs laser (808 nm, 1 W/cm(2)). Oral mucositis was assessed at each LPT session in accordance to the oral-mucositis scale of the National Institute of the Cancer-Common Toxicity criteria (NIC-CTC). The patient self-assessed pain was measured by means of the visual analogue scale. RESULTS: All protocols of LPT led to the maintenance of oral mucositis scores in the same levels until the last RT session. Moreover, LPT three times a week also maintained the pain levels. However, the patients submitted to the once a week LPT had significant pain increase; and the association of low/high LPT led to increased healing time. CONCLUSIONS: These findings are desired when dealing with oncologic patients under RT avoiding unplanned radiation treatment breaks and additional hospital costs.

J Pediatr Hematol Oncol. 2009 Jan;31(1):33-7.

Low-level infrared laser therapy in chemotherapy-induced oral mucositis: a randomized placebo-controlled  trial in children.

 

Kuhn A, Porto FA, Miraglia P, Brunetto AL.

Pediatric Oncology Unit, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Brazil. alessandrakuhn@hotmail.com

BACKGROUND: Oral mucositis (OM) is one of the most frequent complications of chemotherapy for which there is no standard therapy; treatment is mostly conservative. This study was conducted to determine whether low-intensity laser therapy (LLLT) can reduce the duration of chemotherapy-induced OM.

PROCEDURE: A placebo-controlled randomized trial was carried out using LLLT or placebo (sham treatment). Children and adolescents with cancer receiving chemotherapy or hematopoietic stem-cell transplantation between October 2005 and May 2006 were eligible as soon as they developed OM. Patients received intervention for 5 days. The LLLT group was treated with laser GaAlAs, wavelength (lambda): 830 nm (infrared), power: 100 mW, dose: 4 J/cm, and placebo group underwent sham treatment. The grade of OM was clinically assessed by the National Cancer Institute, Common Toxicity Criteria scale.

RESULTS: Twenty-one patients developed OM and were evaluable for analysis; 18 (86%) patients had a diagnosis of leukemia or lymphoma and 3(14%) had solid tumors. The mean age was 8.2 (+/-3.1) years. Nine patients were randomized in the laser group and 12 in the placebo-control group. Once OM was diagnosed, the patients had daily OM grading assessments before laser or sham application and thereafter until complete healing of the lesions. On day 7 after OM diagnosis, 1/9 of patients remained with lesions in laser group and 9/12 of patients in the placebo-control group (P=0.029). In the laser group, the mean of OM duration was 5.8+/-2 days and in the placebo group was 8.9+/-2.4 days (P=0.004).

CONCLUSIONS: Our study has shown evidence that laser therapy in addition to oral care can decrease the duration of chemotherapy-induced OM. Our results confirm the promising results observed in adult cancer patients and should encourage pediatric oncologists to use laser therapy as first-line option in children with chemotherapy-induced OM.

Photomed Laser Surg. 2008 Aug;26(4):393-400.

Low-level laser therapy in the prevention and treatment of chemotherapy-induced oral mucositis in young patients.

Abramoff MM, Lopes NN, Lopes LA, Dib LL, Guilherme A, Caran EM, Barreto AD, Lee ML, Petrilli AS.

Private practice, São Paulo, Brazil.

Abstract Objective: A pilot clinical study was conducted to evaluate the efficacy and feasibility of low-level laser therapy (LLLT) in the prevention and treatment of chemotherapy (CT)-induced oral mucositis (OM) in young patients. Background Data: Besides compromising the patient’s nutrition and well-being, oral mucositis represents a portal of entry into the body for microorganisms present in the mouth, which may lead to sepsis if there is hematological involvement. Oncologic treatment tolerance decreases and systemic complications may arise that interfere with the success of cancer treatment. LLLT appears to be an interesting alternative to other approaches to treating OM, due to its trophic, anti-inflammatory, and analgesic properties.

Materials and Methods: Patients undergoing chemotherapy (22 cycles) without mucositis were randomized into a group receiving prophylactic laser-irradiation (group 1), and a group receiving placebo light treatment (group 2). Patients who had already presented with mucositis were placed in a group receiving irradiation for therapeutic purposes (group 3, with 10 cycles of CT). Serum granulocyte levels were taken and compared to the progression of mucositis. Results: In group 1, most patients (73%) presented with mucositis of grade 0 (p = 0.03 when compared with the placebo group), and 18% presented with grade 1. In group 2, 27% had no OM and did not require therapy. In group 3, the patients had marked pain relief (as assessed by a visual analogue scale), and a decrease in the severity of OM, even when they had severe granulocytopenia.

Conclusion: The ease of use of LLLT, high patient acceptance, and the positive results achieved, make this therapy feasible for the prevention and treatment of OM in young patients.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008 Feb;105(2):180-6, 186.e1.

Efficacy of He-Ne Laser in the prevention and treatment of radiotherapy-induced oral mucositis in oral cancer patients.

Arora H, Pai KM, Maiya A, Vidyasagar MS, Rajeev A.

Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Manipal, Karnatka, India. drarora@gmail.com

OBJECTIVE: The objective of this study was to evaluate the efficacy of low-level lasers for the prevention and treatment of radiotherapy-induced oral mucositis in oral cancer patients.

MATERIAL AND METHODS: Twenty-four hospitalized patients with oral cancer, scheduled to undergo radiotherapy at KMC, Manipal, were enrolled in the present study and assigned to laser (Group I)/control group (Group II). They were treated using He-Ne laser (lambda = 632.8nm, output = 10 mW and energy density = 1.8 J/cm(2)). Patients were subjected to treatment using laser scanner for 8 days and subsequently were treated using laser probe at 6 anatomic sites in the oral cavity for 5 minutes each. The patients were evaluated on each day of treatment for pain severity (NRS), functional impairment (FIS), and oral mucositis (RTOG) and were followed until the end of cancer treatment. Statistical analysis was done using SPSS version 10.

RESULTS: Laser therapy applied prophylactically during radiotherapy can reduce the severity of oral mucositis, severity of pain, and functional impairment.

Oral Dis. 2007 Nov;13(6):538-43.

Low-energy laser therapy for prevention of oral mucositis in hematopoietic stem cell transplantation.

Jaguar GC, Prado JD, Nishimoto IN, Pinheiro MC, de Castro DO Jr, da Cruz Perez DE, Alves FA.

Department of Stomatology, Cancer Hospital A.C. Camargo, São Paulo, Brazil.

AIM: To evaluate the clinical effects of laser therapy on the prevention and reduction of oral mucositis in patients who underwent hematopoietic stem cell transplantation (HSCT).

PATIENTS AND METHODS: From January 2003 to September 2004, 24 patients received prophylactic laser therapy (L+ group). The applications started from the beginning of the conditioning regimen up to day +2. The oral assessment was performed daily until day +30. This group was compared with historical controls, namely 25 patients, who did not receive laser therapy (L- group).

RESULTS: All patients developed some grade of mucositis. However, the L- group presented initial mucositis by 4.36 days, whereas the L+ group presented it in 6.12 days (P = 0.01). The maximum mucositis occurred between day +2 and day +6 with healing by day +25 in the L- group and between day +2 and day +7 with healing by day +14 for the L+ group (P = 0.84). Laser therapy also reduced the time of oral pain from 5.64 to 2.45 days (P = 0.04), and decreased the consumption of morphine (P = 0.07).

CONCLUSION: This study suggests that laser therapy can be useful in oral mucositis to HSCT patients and improve the patient’s quality of life. However, controlled randomized trials should be performed to confirm the real efficacy of laser therapy.

Photomed Laser Surg. 2007 Jun;25(3):197-204.

Effect of laser therapy on bone tissue submitted to radiotherapy: experimental study in rats.

Da Cunha SS, Sarmento V, Ramalho LM, De Almeida D, Veeck EB, Da Costa NP, Mattos A, Marques AM, Gerbi M, Freitas AC.

Federal University of Bahia, Salvador, Bahia, Brazil. samanthadacunha@hotmail.com

Abstract

OBJECTIVE: The aim of this study was to investigate the effect of laser therapy (lambda = 780 nm) on bone tissue submitted to ionizing radiation.

BACKGROUND DATA: The biostimulation effect of laser in normal bone tissue has already been demonstrated successfully; however its effect on bone tissue submitted to radiotherapy has not yet been studied.

METHODS: Twenty-two Wistar rats were randomly divided into four groups: group I, control (n = 4), submitted only to radiotherapy; group II, laser starting 1 day prior to radiotherapy (n = 6); group III, laser started immediately after radiotherapy (n = 6); group IV, laser 4 weeks after radiotherapy (n = 6). The source of ionizing radiation used was Cobalt 60, which was applied in a single dose of 3000 cGy on the femur. The laser groups received seven applications with a 48-h interval in four points per session of DE = 4 J/cm(2), P = 40 mW, t = 100 sec, and beam diameter of 0.04 cm(2). All animals were killed 6 weeks after radiotherapy.

RESULTS: Clinical examination revealed cutaneous erosions on experimental groups (II, III, and IV) starting at the 6th week after radiotherapy. The radiographic findings showed higher bone density in groups II and IV (p < 0.05) compared to the control group. The results further showed an increase of bone marrow cells, and number of osteocytes and Haversian canals in experimental groups II and IV (p < 0.05). It was also found an increase of osteoblastic activity, in groups II, III, and IV (p < 0.05).

CONCLUSION: Laser therapy on bone tissue in rats presented a positive biostimulative effect, especially when applied before or 4 weeks after radiotherapy. However, the use of laser in the parameters above should be used with caution due to epithelial erosions.

Ann Oncol. 2007 Apr;18(4):639-46. Epub 2006 Oct 3

A systematic review of common conservative therapies for arm lymphoedema secondary to breast cancer treatment.

Moseley AL, Carati CJ, Piller NB.

School of Nursing & Midwifery, University of South Australia, Adelaide, Australia. amanda.moseley@yahoo.com.au

Secondary arm lymphoedema is a chronic and distressing condition which affects a significant number of women who undergo breast cancer treatment. A number of health professional and patient instigated conservative therapies have been developed to help with this condition, but their comparative benefits are not clearly known. This systematic review undertook a broad investigation of commonly instigated conservative therapies for secondary arm lymphoedema including; complex physical therapy, manual lymphatic drainage, pneumatic pumps, oral pharmaceuticals, low level laser therapy, compression bandaging and garments, limb exercises and limb elevation. It was found that the more intensive and health professional based therapies, such as complex physical therapy, manual lymphatic drainage, pneumatic pump and laser therapy generally yielded the greater volume reductions, whilst self instigated therapies such as compression garment wear, exercises and limb elevation yielded smaller reductions. All conservative therapies produced improvements in subjective arm symptoms and quality of life issues, where these were measured. Despite the identified benefits, there is still the need for large scale, high level clinical trials in this area.

Lasers Med Sci. 2006 Jul;21(2):90-4. Epub 2006 May 4.

Low-level laser therapy in management of postmastectomy lymphedema.

Kaviani A, Fateh M, Yousefi Nooraie R, Alinagi-zadeh MR, Ataie-Fashtami L.

Tehran University of Medical Sciences and Iranian Center for Medical Laser Research, Tehran, Iran. akaviani@sina.tims.ac.ir

The aim of this paper was to study the effects of low-level laser therapy (LLLT) in the treatment of postmastectomy lymphedema. Eleven women with unilateral postmastectomy lymphedema were enrolled in a double-blind controlled trial. Patients were randomly assigned to laser and sham groups and received laser or placebo irradiation (Ga-As laser device with a wavelength of 890 nm and fluence of 1.5 J/cm2) over the arm and axillary areas. Changes in patients’ limb circumference, pain score, range of motion, heaviness of the affected limb, and desire to continue the treatment were measured before the treatment and at follow-up sessions (weeks 3, 9, 12, 18, and 22) and were compared to pretreatment values. Results showed that of the 11 enrolled patients, eight completed the treatment sessions. Reduction in limb circumference was detected in both groups, although it was more pronounced in the laser group up to the end of 22nd week. Desire to continue treatment at each session and baseline score in the laser group was greater than in the sham group in all sessions. Pain reduction in the laser group was more than in the sham group except for the weeks 3 and 9. No substantial differences were seen in other two parameters between the two treatment groups. In conclusion, despite our encouraging results, further studies of the effects of LLLT in management of postmastectomy lymphedema should be undertaken to determine the optimal physiological and physical parameters to obtain the most effective clinical response.

Indian J Med Res. 2006 Oct;124(4):399-402.

Effect of low level helium-neon (He-Ne) laser therapy in the prevention & treatment of radiation induced mucositis in head & neck cancer patients.

Arun Maiya G, Sagar MS, Fernandes D.

Departments of Physiotherapy , Manipal College of Allied Health Sciences, Kasturba Medical College, MAHE University, Manipal, India. ajmaiya@yahoo.com

BACKGROUND & OBJECTIVES: Oral mucositis is a common debilitating complication of radiotherapy occurring in about 60 per cent of cancer patients. Considerable buccal toxicity of radiotherapy or chemotherapy in cancer patients to become discouraged and can affect their quality of life. In addition, such toxicity can alter the treatment plan. At present, there is no clinically appropriate prophylaxis efficacious antidote for mucositis. The low level laser (LEL) appears to be a simple, non-traumatic technique for the prevention and treatment of radiation induced mucositis. Therefore the present study was carried out to find out the effect of low-level helium-neon (He-Ne) laser in the prevention and treatment of radiation induced mucositis in head and neck cancer patients.

METHODS: The patients with carcinoma of oral cavity with stages II-IV a being uniformly treated with curative total tumour dose of 66 Gy in 33 fractions over 6 wk were selected for the study. The patients were divided based on computer generated randamosization into laser (study group) and control groups with 25 patients in each group. Both study and control groups were comparable in terms of site of the lesion, stage of the cancer and histology. The study group patients were treated with He-Ne laser (wavelength 632.8 nm and output of 10mW) and control group patients were given oral analgesics, local application of anaesthetics, 0.9 per cent saline and povidine wash during the course of radiotherapy.

RESULTS: All patients tolerated the laser treatment without any adverse effect or reactions. The result showed a significant difference in pain and mucositis (P<0.001) between the two groups. At the end of radiotherapy (after 6 wk) mean pain sure and mucositis grade were significantly lower (P<0.001) in the study group compared to control.

INTERPRETATION & CONCLUSION: The low-level He-Ne laser therapy during the radiotherapy treatment was found to be effective in preventing and treating the mucositis in head and neck cancer patients. Further studies need to be done on a larger sample to find the mechanism.

Int Nurs Rev. 2005 Mar;52(1):68-72

Patients with moderate chemotherapy-induced mucositis: pain therapy using low intensity lasers.

Nes AG, Posso MB.

Buskerud University, Drammen, Norway. s-oddmun@online.no

BACKGROUND: Intensive cancer therapy normally affects malignant and normal cells with high replication rates. Cells in the gastrointestinal tract are therefore commonly affected by cytotoxins. This often results in the development of chemotherapy-induced oral mucositis (COM). COM is the inflammatory response of the oral mucous membrane to the chemotherapy drugs. Low level laser therapy (LLLT) has proved to be effective in treating and repairing biologically damaged tissue and to reduce pain. LLLT has also proven to be an efficient method for the prevention of oral mucositis.

OBJECTIVE: To investigate the effect of LLLT on pain relief among patients who have developed

COM. METHOD: The study was performed as a clinical test with a sample consisting of 13 adult patients receiving oncology treatment. The patients were treated during a 5-day period, and the pain was measured before and after each laser application. The laser used was an AsGaAl, with a wavelength of 830 nm and a potency of 250 mW. The energy given was 35 J cm(-2). ANALYSIS: The results were analysed using the Wilcoxon test.

RESULTS: There was a significant (P = 0.007) 67% decrease in the daily average experience of pain felt before and after each treatment, confirming that LLLT can relieve pain among patients who have developed

COM. STUDY LIMITATIONS: The low number of COM patients at the hospital did not allow a control group to be included in the study, and therefore the results contain a potential placebo effect.

IMPLICATIONS FOR NURSING CARE: The most important benefit the authors consider to be the value for the patients of better and quicker treatment with a drastic reduction in painful mucositis..

Res Commun Mol Pathol Pharmacol. 2004;115-116:185-201.

Effects of diode 808 nm GaAlAs low-power laser irradiation on inhibition of the proliferation of human hepatoma cells in vitro and their possible mechanism.

Liu YH, Cheng CC, Ho CC, Pei RJ, Lee KY, Yeh KT, Chan Y, Lai YS.

Center for Research and Development, Chung-tai Institute of Health Sciences and Technology, Taichung, Taiwan.

Low-power laser irradiation (LPLI) has come into a wide range of use in medical field. Considering basic research, LPLI can enhance DNA synthesis and increases proliferation rate of human cells. But only a few data about the effects of LPLI on human liver or hepatoma cells are available. The cytoskeleton plays important roles in cell function and therefore is implicated in the pathogenesis of many human liver diseases, including malignant tumors. In our previous study, we found the stability of cytokeratin molecules in human hepatocytes was related to the intact microtubule network that was influenced by colchicine. In this study, we are going to search the effect of LPLI on proliferation of human hepatoma cell line HepG2 and J-5 cells. In addition, the stability of cytokeratin and synemin (one of the intermediate filament-associated proteins) were analyzed under the action of LPLI to evaluate the possible mechanism of LPLI effects on proliferation of human hepatoma cells. In experiment, HepG2 and J-5 cells were cultured in 24-well plate for 24 hours. After irradiation by 130 mW diode 808 nm GaAlAs continue wave laser in different time intervals, the cell numbers were counted. Western blot and immunofluorescent staining examined the expression and distribution of PCNA, cytokeratin and synemin. The cell number counting and PCNA expression were evaluated to determine the proliferation. The organization and expression of cytokeratin and synemin were studied to identify the stability of cytoskeleton affected by LPLI. The results revealed that proliferation of HepG2 and J-5 cells was inhibited by LPLI since the cell number and PCNA expression was reduced. Maximal effect was achieved with 90 and 120 seconds of exposure time (of energy density 5.85 J/cm2 and 7.8 J/cm2, respectively) for HepG2 and J-5, respectively. The decreased ratio of cell number by this dose of irradiation was 72% and 66% in HepG2 and J-5 cells, respectively. Besides that, the architecture of intermediate filaments in these cells was disorganized by laser irradiation. The expression of intermediate filament-associated protein, synemin, was also reduced. Two significant findings are raised in this study: (1) Diode 808 nm GaAlAs continuous wave laser has an inhibitory effect on the proliferation of human hepatoma cells line HepG2 and J-5. (2) The mechanism of inhibition might be due to down-regulation of synemin expression and alteration of cytokeratin organization that was caused by laser irradiation.

Med Surg. 2002; 20 (1): 23-26.

 

Effects of low-level laser therapy on malignant cells: In vitro study.

Pinheiro A L, Carneiro Nascimento S, De Barros Vieira A L et al.

The aim of a study by Pinheiro was to assess the effect of 635- and 670-nm laser irradiation on H.Ep.2 cells in vitro using MTT. It was decided to evaluate the effect of increased doses of laser light on these cells. The cells, obtained from SCC of the larynx. The cultures were kept either at 5% or 10% of FBS. Twenty-four hours after transplantation, the cells were irradiated with laser light (5 mW diode lasers; 635 and 670 nm; beam cross section 1 mm at local light doses between 0.04 and 4.8.10(4) J cm2. For 670 nm, significant differences in the proliferation were observed between the two concentrations of FBS and between irradiated cultures and controls. Although the results were not significant, 635-nm irradiated cells also proliferated more than non-irradiated ones. This occurred under both conditions of nutrition. It was concluded, that irradiation with 670 nm laser light applied at doses between 0.04 and 4.8104 J/cm2 could significantly increase proliferation of laryngeal cancer cells.

Int J Mol Med. 2002 Dec;10(6):701-5.

Inhibition of lung metastasis of B16 melanoma cells exposed to blue light in mice.

Ohara M, Kawashima Y, Kitajima S, Mitsuoka C, Watanabe H.

Otsuka Pharmaceutical Factory, Inc., Muya-cho, Naruto, Tokushima 772-8601, Japan. oharams@otsukakj.co.jp

Abstract

The effects of blue light on B16 melanoma cells and on the metastasis of these cells to the lungs were investigated in mice. The exposure of B16 melanoma cells to blue light in two 20-min sessions resulted in marked suppression of cell growth measured at 7 days after exposure. When these cells were harvested, re-inoculated into medium and incubated for a further 7 days, their growth activity returned to almost the same level as that of cultured cells from the non-exposure control group. The melanoma cells harvested after 7 days of incubation were injected intravenously into mice. In the non-exposure group, black nodules developed on the lung surface and the nodules increased in size over time. In the blue-light-exposure group, the development of such black nodules on the lung surface was delayed, and the nodules were smaller. Histopathological examination revealed that blue light suppressed the growth of metastatic tumor cells, and no increase in the number of melanin-containing cells or atypical cells was induced in the metastatic lesions. These results suggest that blue light suppresses the metastasis of B16 melanoma cells.

Cancer J. 2002 May-Jun;8(3):247-54.

 

Pilot study of laser effects on oral mucosits in patients receiving chemotherapy.

Wong SF, Wilder-Smith P.

Western University of Health Sciences, College of Pharmacy, Division of Hematology/Oncology, Pomona, California 91766, USA.

PURPOSE: The purpose of this study was to examine the effectiveness of laser therapy in the prevention and/or healing of chemotherapy-induced oral mucositis lesions. This study also evaluated the ease and feasibility of the laser therapy and the impact of the treatment on improving the patient’s quality of life.

PATIENTS AND METHODS: Fifteen patients with an episode of prior chemotherapy-induced grade 3 or 4 mucositis with 5-fluorouracil continuous infusion consented to participate in this study. All patients were provided with standardized mouth care instructions at the initiation of chemotherapy treatments. Enrolled patients received laser therapy treatments 24 hours before the chemotherapy and then recommenced weekly with evenly distributed exposure to the standardized designated areas by one operator during the entire cycle of chemotherapy at the same doses until the mucositis resolved or the chemotherapy cycle was completed. lntraoral perfusion was measured by laser Doppler technology. Patients were assessed for response to laser therapy according to standardized mucositis grading criteria by evaluating development of lesions, extent and duration of lesions, and time to healing. The effect of laser therapy on ability to continue planned chemotherapy, the reduction in dose, delays, and ability to maintain planned dose intensity were assessed. The impact of laser therapy on pain control was evaluated using the visual analogue score. A quality-of-life survey was completed by each patient at the initiation of chemotherapy and then weekly throughout the chemotherapy.

RESULTS: Eleven of 15 patients experienced grade 0 mucositis, three patients experienced grade 1 to 2 mucositis, and one patient experienced grade 3 to 4 mucositis. Fourteen patients completed the lasertherapy as planned, and none of the patients withdrew from the laser therapy treatments because of noncompliance. One patient continued to experience grade 4 mucositis that necessitated an interruption in the planned chemotherapy regimen and, consequently, the laser treatment. Patients tolerated the laser therapy very well and did not report any increased discomfort. No significant changes in perfusion were observed as a result of laser therapy.

DISCUSSION: In this pilot study, laser therapy significantly reduced the incidence and the severity of mucositis in chemotherapy patients. The laser therapy does not appear to promote wound healing by affecting the intraoral perfusion, as assessed by Doppler measurements. The mechanisms involved in the mediating of the observed effects remain unknown at this time. Continued research is warranted to determine the optimal laser wavelength and parameters.

Support Care Cancer. 1999 Jul;7(4):244-52.

Low-energy He/Ne laser in the prevention of radiation-induced mucositis. A multicenter phase III randomized study in patients with head and neck cancer.

Bensadoun RJ, Franquin JC, Ciais G, Darcourt V, Schubert MM, Viot M, Dejou J, Tardieu C, Benezery K, Nguyen TD, Laudoyer Y, Dassonville O, Poissonnet G, Vallicioni J, Thyss A, Hamdi M, Chauvel P, Demard F.

External Radiotherapy Unit, Centre Antoine-Lacassagne, Nice, France. rene-jean.bensadoun@cal.nice.fnclcc.fr

Use of the low-energy helium-neon laser (LEL) appears to be a simple atraumatic technique for the prevention and treatment of mucositis of various origins. Preliminary findings, and significant results obtained for chemotherapy-induced mucositis in a previous phase III study, prompted a randomized multicenter double-blind trial to evaluate LEL in the prevention of acute radiation-induced stomatitis. Irradiation by LEL corresponds to local application of a high-photon-density monochromatic light source. Activation of epithelial healing for LEL-treated surfaces, the most commonly recognized effect, has been confirmed by numerous in vitro studies. The mechanism of action at a molecular and enzymatic level is presently being studied. From September 1994 to March 1998, 30 patients were randomized. Technical specification: 60 mW (25 mW at Reims, 1 patient), He-Ne, wavelength 632.8 nm. The trial was open to patients with carcinoma of the oropharynx, hypopharynx and oral cavity, treated by radiotherapy alone (65 Gy at a rate of 2 Gy/fraction, 5 fractions per week) without prior surgery or concomitant chemotherapy. The malignant tumor had to be located outside the tested laser application areas (9 points): posterior third of the internal surfaces of the cheeks, soft palate and anterior tonsillar pillars. Patients were randomized to LEL or placebo light treatment, starting on the first day of radiotherapy and before each session. The treatment time (t) for each application point was given by the equation : t(s)= energy (J/cm2) x surface (cm2)/Power (W). Objective assessment of the degree of mucositis was recorded weekly by a physician blinded to the type of treatment, using the WHO scale for grading of mucositis and a segmented visual analogue scale for pain evaluation. Protocol feasibility and compliance were excellent. Grade 3 mucositis occured with a frequency of 35.2% without LEL and of 7.6% with LEL (P<0.01). The frequency of “severe pain” (grade 3) was 23.8% without LEL, falling to 1.9% with LEL (P<0.05). Pain relief was significantly reduced throughout the treatment period (weeks 2-7). LEL therapy is capable of reducing the severity and duration of oral mucositis associated with radiation therapy. In addition, there is a tremendous potential for using LEL in combined treatment protocols utilizing concomitant chemotherapy and radiotherapy.

Int J Radiat Oncol Biol Phys. 1997 Jul 1;38(4):697-703.

Low energy Helium-Neon laser in the prevention of oral mucositis in patients undergoing bone marrow transplant: results of a double blind randomized trial.

Cowen D, Tardieu C, Schubert M, Peterson D, Resbeut M, Faucher C, Franquin JC.

Department of Radiotherapy, Institut Paoli-Calmettes, Cancer Center, Marseilles, France.

PURPOSE: To evaluate the efficiency of Helium-Neon (He-Ne) laser in the prevention of oral mucositis induced by high dose chemoradiotherapy before autologous bone marrow transplantation (BMT).

METHODS AND MATERIALS: Between 1993 and 1995, 30 consecutive patients receiving an autologous peripheral stem-cell or bone marrow transplant (BMT) after high dose chemoradiotherapy were randomized to possibly receive prophylactic laser to the oral mucosa after giving informed consent. Chemotherapy consisted of cyclophosphamide, 60 mg/kg intravenously (I.V.) on day (d)-5 and d-4 in 27 cases, or melphalan 140 mg/kg I.V. on d-4 in three cases. Total body irradiation (TBI) consisted of 12 Gy midplane dose in six fractions (4 Gy/day for three days). He-Ne laser (632.8 nm wavelength, power 60 mW) applications were performed daily from d-5 to d-1 on five anatomic sites of the oral mucosa. Oral examination was performed daily from d0 to d + 20. Mucositis was scored according to an oral exam guide with a 16 item scale of which four were assessed by the patients themselves. Mean daily self assessment scores for oral pain, ability to swallow and oral dryness were measured. A daily mucositis index (DMI) and a cumulative oral mucositis score (COMS) were established. Requirement for narcotics and parenteral nutrition was recorded.

RESULTS: The COMS was significantly reduced among laser treated (L+) patients (p = 0.04). The improvement of DMI in L+ patients was also statistically significant (p < 0.05) from d + 2 to d + 7. Occurrence and duration of grade III oral mucositis were reduced in L+ patients (p = 0.01). Laser applications reduced oral pain as assessed by patients (p = 0.05) and L+ patients required less morphine (p = 0.05). Xerostomia and ability to swallow were improved among the L+ patients (p = 0.005 and p = 0.01, respectively). Requirement for parenteral nutrition was not reduced (p = NS).

CONCLUSION: Helium-Neon laser treatment was well tolerated, feasible in all cases, and reduced high dose chemoradiotherapy-induced oral mucositis. Optimal laser treatment schedules still needs to be defined.

HeNe laser reduces mucositis

a) Barasch B et al. Helium-neon laser effects on conditioning-induced mucositis in bone marrow transplantation patients. Cancer. 1995; 76 (12): 2550-2556.

Oral mucositis is a common complication of bone marrow transplantation conditioning therapy. Different drugs are given in order to reduce rejection of the implant. These drugs induce an oral mucosits. The mucositis is painful and complicates nutrition. Sometimes the intake of the drug has to be stopped due to complications.  In the study above 20 patients received HeNe to their oral mucosa, either right or left of midline. One side was sham irradiated.  Laser treatment was well-tolerated and reduced the severity of oral mucositis.

b) Cowen D et al. Low energy helium-neon laser in the prevention of oral mucositis in patients undergoing bone marrow transplant: results of a double blind randomized trial. Int J Radiat Oncol Biol Phys. 1997; 38 (4): 697-707. Significant reduction of oral mucositis using a 60 mW HeNe laser.

Eur Arch Otorhinolaryngol. 2001 Nov;258(9):481-7.

Chemotherapy- and radiotherapy-induced mucositis in head and neck cancer patients: new trends in pathophysiology, prevention and treatment.

 

Bensadoun RJ, Magne N, Marcy PY, Demard F.
Department of Radiation Oncology, Centre Antoine Lacassagne, Nice, France. rene-jean.bensadoun@nice.fnclcc.fr

Mucositis is the intensity-limiting toxicity in the management of locally advanced non-resectable head and neck cancer with radiotherapy and chemotherapy. New radiation modalities (hyperfractionation and/or acceleration) as well as combined modality regimens in this situation induce higher rates of acute toxicity. Hyperfractionation, for example, allows higher control rates, with few late toxicities, but it slightly increases acute mucositis. The addition of chemotherapy introduces systemic toxicity and can exacerbate local tissue reactions when used concurrently with radiotherapy. Mucositis is recognized as the principal limiting factor to further treatment intensification. As local regional control and overall survival are related to dose-intensity in this case, further research into the assessment, analysis, prevention and treatment of mucosal toxicity is not only crucial to improvement in quality of life, but certainly also to improved rates of disease control. Several topical and systemic treatments are directed to the decrease and the acceptance of this acute toxicity, but few have shown a significant preventive effect. The efficacy of low-level laser therapy in the management of such toxicity could hence yield important developments with this method in the field of oncology.

Anesteziol Reanimatol. 2001 Sep-Oct;(5):47-50.

 

Validation and approaches to correction of hemorheologic disorders in patients with gastrointestinal cancer.

[Article in Russian]

Karabanov GN, Karimov AI, Ogii II, Gantsev KSh, Khalikov RA, Ishmuratova RSh.

A total of 237 patients were examined: 127 with gastric cancer and 110 with colonic cancer, 99 women and 138 men, mean age 57.5 years. Erythrocyte deformability and aggregation were studied by original methods. Red blood, protein metabolism, and endogenous intoxication parameters were evaluated by routine laboratory tests. Increased aggregation and volume of erythrocytes and decrease of their deformability and hemoglobin content in parallel with hypo- and dysproteinemia and increased level of endogenous intoxication were observed in all patients with gastrointestinal cancer. Correction of these disorders by intravenous laser exposure of the blood essentially improved the erythron status and protein metabolism and decreased endotoxicosis. Infusion/transfusion therapy also notably improved the erythron function and decreased endogenous intoxication. Analysis of the results of surgery showed decreased incidence of complications and lethal outcomes, which was due to methods of corrective therapy.

CHEMO-AND RADIATION-INDUCED MUCOSITIS : RESULTS OF MULTICENTER PHASE III STUDIES.

Rene Jean Bensadoun Centre Antoine-Lacassagne, Nice, France

Considerable buccal toxicity of radiotherapy and/or chemotherapy in patients with cancer can cause patients to become discouraged and can alter their quality of life. In addition, such toxicity often necessitates alterations of treatment planning, with grave consequences in term of tumor response and even survival (concept of dose-intensity). With 5-fluorouracil and head and neck radiotherapy for example, acute mucosal toxic effect is the main limiting factor for which no clinically appropriate prophylaxis or efficacious antidote has been found to date. Management of oral mucositis is currently primarily directed at palliation of the symptoms, and prevention of infections. Low Level Laser Therapy (LLLT) has been reported effective in reducing the severity of oral mucositis lesions in a non-randomized trial, initiated in Nice (France) by Ciais et al. (1). The efficacy of this method in the prevention of chemotherapy induced oral mucositis has been subsequently confirmed in two prospective, double-blind randomized trials, in patients undergoing bone marrow transplant (2 ; 3). These initial findings and the high incidence of radiation-induced mucositis prompted a randomized multicenter trial to evaluate LLLT for the prevention of acute radiation-induced oropharyngeal mucosal lesions. The trial was open to patients with carcinoma of the oropharynx, hypopharynx and oral cavity being treated by external radiotherapy, with a total dose of 65 Gy at a rate of 1 fraction of 2 Gy/day, 5 days a week, from cobalt-60 or linear accelerator photons, without prior surgery or concomitant chemotherapy. Between September 1994 and March 1998, thirty patients entered this double-blind randomized study conforming to the Huriet law. The goal was to determine whether preventive HeNe laser beam applications could reduce or prevent oropharyngeal mucositis caused by radiotherapy.

Patients characteristics: There were 26 men and 4 women. Mean age was 60.4 years (range 36 – 78). Oral examination and preventive dental management were performed prior to radiotherapy. Daily oral hygiene (cleaning of the teeth and dental prosthesis) during treatment was recommended. Patients were assigned to either laser treatment (L+) or sham-treatment (L-) by computer blocked randomization. The protocol called for the inclusion of 30 patients, 15 in each arm. No associated anti-inflammatory or other treatment was authorized. Analgesics could be prescribed, but not during the 2 days preceding each week evaluation. Patients received HeNe laser applications daily for five consecutive days (Monday to Friday) each week, during the seven weeks of radiotherapy. The malignant tumor had to be located outside the areas selected for randomized preventive LLL application. Laser was delivered to the tissues by a straight optical fiber with a 1.2 mm spot size. The 9 treatment areas included : posterior third of buccal mucosa, soft palate and anterior tonsillar pillars. Laser illumination consisted of a continuous beam (wavelength: 632.8 nm; power: 60 mW), calibrated at the end of the optical fiber every day. The treatment time (t) for each application point was given by the equation : t (sec) = energy (J/cm2) x surface (cm2)/ Power (W). The average energy density delivered to the treatment areas was 2 J/cm2, and was applied on these nine points, equally distributed on the treated surfaces, for 33 s per point (each specific LLL session lasted approximately 5 minutes). The 60 mW lasers were designed and produced by Fradama S.A. (Geneva, Switzerland). All laser illuminations were performed by the same individual in each center. This operator was the only person to know whether or not the patient was sham-treated, and did not participate in the evaluation and scoring mucositis. During the sessions, patients wore wavelength-specific dark glasses and were instructed to keep their eyes closed, to assure that they did not know whether they were sham-treated or whether they received laser applications. The laser made the same noises, and the probe was held in the mouth exactly the same way, when treating control subjects and when treating laser patients. The whole irradiation field, the oral cavity and the visible oropharynx were inspected weekly during seven weeks by the same physician (head and neck surgeon, or radiation oncologist), blinded to the result of randomization. The evaluation of mucositis and pain was performed on the oropharyngeal areas (9 points). Criteria for evaluation were the standard WHO scale for mucositis in the oropharynx; and a segmented visual analogic scale for pain (patient self evaluation). In this phase III study, no adverse effect was noted with the use of a 60-mW HeNe laser, though it is important to emphasize the importance of preventing retinal damage by the use of wavelength-specific goggles. This is consistent with previous reports. Laser applications delayed time of onset, attenuated the peak severity and shortened the duration of oral mucositis. The difference between L+ and L- patients was statistically significant from week 4 to week 7. With the total delivered dose of 65Gy, conventionally fractionated, all L- patients developed mucositis at week 2, with a peak at week 5 (13 with grade 3 mucositis, and 2 with grade 2 mucositis). All L+ patients also had mucositis at week 2, with a peak at week 5 (5 with grade 3 mucositis, 9 with grade 2, 1 with grade 1). During the 7 weeks of treatment, the mean grade of mucositis in L+ patients was significantly lower (p=0.01) than the mean grade in L- patients. Results on decrease in pain intensity were also quite convincing. Laser applications reduced the incidence and duration of morphine administration. Ability to swallow was also improved. These results confirm previous data collected with this method, especially for patients undergoing bone marrow transplant (BMT). In a prospective study, Barasch et al. (2) used a 25- mW laser on one side of the mouth only and reported a statistically significant reduction in oral mucositis on that side, according to the scoring system they used. In the Barasch study, each patient was his or her own control, which could be of importance, since mucosal damage on the sham-treated side could have benefited also from a distant systemic laser effect. Cowen et al. (3), using a 60 mW HeNe laser, performed a double-blind randomized phase III trial, in which laser was administered to the treatment group during conditioning, prior to the day of transplant. This study showed a 33% reduction of grades 3 and 4 mucositis in L+ patients. In this trial, mucositis was scored according to an oral examination guide, with a 16 items scale, of which 4 were assessed by the patients themselves. Daily mucositis index was significantly lower in L+ patients (p < 0.05) from d+2 to d+7 after BMT. The duration of grade 3 stomatitis was also reduced in L+ patients (p = 0.01). Oral pain was lower (p = 0.05), and L+ patients required less morphinomimetics (p = 0.05). Finally, xerostomia and ability to swallow were improved among L+ patients (p = 0.05, and p = 0.01, respectively). All these results were in keeping with previous observations, suggesting the efficacy of the method (1, 4). Schubert et al. for example (4), identified a trend towards lower oral mucositis scores, on all examination days, in an interim results report of a phase I/II study, in which laser application was performed prophylactically during conditioning before BMT.

In conclusion, LLLT seems to be a safe and efficient method for the prevention of chemo- and radiation-induced mucositis, with a tremendous potential interest for combined modality treatment. The concomitant use of chemo- and radiotherapy is becoming the new standard of care in advanced head and neck cancer, with very encouraging results, even in nonresectable cases. Since the main limiting factor of these combined protocols is the acute mucositis, this complementary treatment option with low level HeNe laser could be important in enhancing the feasibility of such regimens, and especially in the conservation of dose-intensity effect. At Nice, where the method is now used routinely during head and neck radiation, we project a new study testing LLL in patients being treated with concomitant chemo- and radiotherapy for advanced head and neck cancer. Even more than the improvement of patient comfort, the therapeutic index of combined specific treatment should be increased by the use of LLLT, besides standard supportive care, oral care and enteral nutrition (5). During this study, other laser wavelengths and powers could be tested, and compared to 60-mW HeNe laser.
Ref :
1. CIAIS G., NAMER M., SCHNEIDER M., DEMARD F., POURREAU-SCHNEIDER N., MARTIN P.M., SOUDRY M., FRANQUIN J.C., ZATTARA H. La laserthérapie dans la prévention et le traitement des mucites liées à la chimiothérapie anticancéreuse. Bull. Cancer 79 : 183-191, 1992.
2. BARASCH A., PETERSON D., TANZER J.M., D’AMBROSIO J.A., NUKI K., SCHUBERT M., FRANQUIN J.C., CLIVE J., TUTSCHKA P. Helium-Neon laser effects on conditioning-induced oral mucositis in bone marrow transplantation patients. Cancer 76:2550-2556, 1995.
3. COWEN D., TARDIEU C., SCHUBERT M., PETERSON D., RESBEUT M., FAUCHER C., FRANQUIN J.C. Low energy helium-neon laser in the prevention of oral mucositis in patients undergoing bone marrow transplant : results of a double blind randomized trial. Int. J. Radiat Oncology Biol. Phys. 38 (4):697-703, 1997.
4 . SCHUBERT M.M., FRANQUIN J.C., NICCOLI-FILHO F., MARCIAL F., LLOID M., KELLY J. Effects of low-energy laser on oral mucositis : a phase I/II pilot study. Cancer Researcher Weekly 7:14, 1997.
5 . R. J. BENSADOUN, J. C. FRANQUIN, G. CIAIS, V. DARCOURT, M. M. SCHUBERT, M. VIOT, J. DEJOU, C. TARDIEU, K. BENEZERY, T. D. NGUYEN, Y. LAUDOYER, O. DASSONVILLE, G. POISSONNET, J. VALLICIONI, A. THYSS, M. HAMDI, P. CHAUVEL, F. DEMARD. Low-energy He/Ne laser in the prevention of radiation-induced mucositis. A multicenter phase III randomized study in patients with head and neck cancer. Support Care Cancer 7(4):244-252, 1999.

Klin Khir. 1999;(5):27-9.

 

Intravascular laser irradiation of the blood in complex treatment of the patient with esophageal cancer.

[Article in Ukrainian]

Hanul VL, Zaitsev SL, Kirkilevs’kyi SI, Fil’chakov FV.

Complex treatment of 41 patients with intrathoracic esophageal cancer using intravascular laser irradiation of the blood was done. The immunorehabilitating method application had promoted the postoperative complications rate lowering, the mortality reduction, the three-year survival rate indexes improvement.

Vopr Onkol. 1998;44(6):672-5.

 

Microcirculation in gastrointestinal cancer and some possibilities of its correction.

[Article in Russian]

Karabanov GN, Ogiij II, Reshetova LA.

Bashkir Republican Oncological Dispensary, Ufa.

Microcirculation and blood rheology were studied in 348 patients with tumors of the gastrointestinal tract. Such disorders as increased blood and plasma viscosity, aggregates of erythrocytes and their increased stability of shape were recorded in conjunction with hypo- and dysproteinemia, endogenous intoxication syndrome and microvascular disturbances. Microcirculation significantly improved and endoxemia was alleviated following photomodification of the blood by use of helium-neon laser radiation and application of an original procedure of infusion.

Klin Khir. 1998;(3):40-1.

 

Results of the clinical use of laser therapy in malignant tumors.

[Article in Ukrainian]

Dryzhak VI, Halaichuk II, Dombrovich MI, Oleksii OP, Zahurs’ka NO.

The raise of natural antitumoral resistance level, the reduction of intoxication severity, the raise of an organism tolerance to irradiation and polychemotherapy were permitted by adjuvant low-energy laser therapy absorption in the complex of treatment of 27 patients with colonic cancer in early postoperative period, 16–cervix uteri cancer while irradiation therapy conduction, and 14–with cutaneous melanoma during polychemotherapy.

J Photochem Photobiol B: Biology. 1997; (40): 253-257

 

Biomodulation of normal and tumor cells.

In a study by Schaffer et al. various cells were irradiated by 805 nm laser light.  The cells were (1) murine skeletal myotubes, (2) normal urothelial cells, (3) human squamous carcinoma cells of the gingival mucosa and (4) urothelial carcinoma cells. Mitotic index for 1, 2 and 4 increased at fluences of 4 J/cm2 while irradiation at 20 J/cm2 resulted in a slight decrease. The no 3 cells showed a decrease of the mitotic index with both fluences. The most interesting observation is the different reaction of the two carcinoma cells.

Abstract Volume 13 Issue 3 (1998) pp 214-218

Biological Effect of Helium-Neon (He-Ne) Laser Irradiation on Mouse Myeloma (Sp2-Ag14) Cell Line in Vitro.

J.M. Ocaña-Quero (1), J. Perez de la Lastra (1), R. Gomez-Villamandos (2), M. Moreno-Millán (1)(1) Departamento de Genética(2) Departamento de Patología Animal, Facultad de Veterinaria de Córdoba, Spain

Received for publication 22 July 1997; accepted following revision 6 February 1998.

We examined the effect of helium-neon (He-Ne) laser irradiation with a wavelength of 632.8 nm on cell cycle synchronisation of monolayer growing mouse myeloma (Sp2-Ag14) cell line. The monolayer cultures were exposed to repeated doses of different energy densities (4-64 J&sol;cm2). The nuclear DNA content has been studied by flow cytometry to obtain the cell percentage in each cell cycle phase. Results showed that the He-Ne laser irradiation at energy densities of 8-64 J&sol;cm2 produced a significative and different effect on the G0-G1 and S phases of cell cycle over control. In contrast, no significant effect in G2-M phase was produced by He-Ne laser irradiation at any energy density compared with non-treated control. These results support previous observations suggesting that He-Ne laser irradiation of low energy density interferes with cell cycling and may inhibit cell proliferation when irradiation is performed at doses of 8 J&sol;cm2 or more.

Voprosy onkologii. 2000; 46 (4): 459-461.

Nizkointensivnaia lasernaia terapiia v detskoi onkologii

Balakirev S A, Gusev L I, Kazanova M B et al.

The study by Balakirev suggests that the application of laser therapy makes it possible to reduce the time needed for the management of radiation injury and chemotherapy complications in pediatric patients 1.5-2-fold. It was shown that exposure to laser caused mononuclear levels of donors’ blood to rise, which in turn led to release, in higher concentrations, of IL-1 and FNO cytokins, major factors of immune response development.

Vestn Ross Akad Med Nauk. 2000; (6): 24-27.

Low-intensity lasers in pediatric oncology.

Durnov L A, Gusev L I, Balakirev S A et al

The study by Durnov outlines the outcomes of treatment for complications associated with chemo- and radiation therapy in children with malignant neoplasms by using low-intensity laser radiation. The use of this therapy may reduce the duration of treatment of these complications by 1.5-2 times. The use of low-intensity laser radiation in the treatment of other complications that are common in pediatric oncological care is briefly described.

Vopr Kurortol Fizioter Lech Fiz Kult. 2000; (3): 3-4.

The correction of the subcellular postradiation changes in the hypothalamus and parathyroid gland by using low-intensity laser radiation.  An experimental study.

Korolev Iu N, Panova L N, Geniatulina M S

The study by Korolev showed that exposure of the rat adrenals 30 days after radiation (1 Gy) to infrared laser radiation arrested the development of ultrastructural disorders in the cells of the hypothalamus and the parathyroid gland and enhanced subcellular manifestations of adaptation and rehabilitation processes.

USE OF LOW-LEVEL LASER THERAPY (LLLT) FOR TREATMENT OF THE PATIENTS WITH A CANCER OF A ESOPHAGUS T3NoMX

V.A.Mikhailov,* I.B.Sudakov,** I.N.Denisov,*** V.L.Osin Moscow scientific-practical center on laser therapy,*Oncologic hospital, Rjasan, **Moscow medical academy named after Setchenov,***Medical Center at business management of the President of Russian Federation

In this part of work at 20 patients received the laser therapy (LLLT) in a combination with external radial therapy under the radical program (1group), 15 patients (2 groups) received only one laser therapy , the control group consist of 18 men receiving only external radial therapy on the radical program (3 groups), 10 patients received only symptomatic therapy (4 groups). The stage of disease T3N0MX and spent treatment in skilled and control groups was identical. Radial therapy carried out on kettles “Lutch-1? and “Agat- ?” on a procedure from three fields (1 parasternal, 2 and 3 – juxtaspinal under an angle of 40 degrees to a backbone) with a single dose till 90 % on doses by a curve 1,8 Gr and cooperative dose 64-66 Gr. The irradiation was carried out 5 days per one week with a break 2 days. A GaAs semiconductor laser (wavelength 890 nm., pulsed mode, pulse power 5-10 W.) was used for laser therapy. Laser therapy carried out after leading to a tumor of a dose 15-20 Gr. The sessions LLLT carried out 3 times per one week in day. A cooperative dose – 5,8 J/cm2 The analysis of lifespan of the patients in group receiving LLLT with radial therapy and in control group has shown, that use of laser therapy increases lifespan of the patients: 1 group – up to 10,28 ±2,03 months, in 2 groups up to 11,4 ±3,02 months, in 3 groups it makes 7,35 ±2,4 months, in 4 groups – 6,3 ± 1,94 months. Use LLLT allows to reduce quantity of occurrence of complications after radiation therapy in 2,9 times.

Cancer. 1995; 76 (12): 2550-2556.

HeNe laser reduces mucositis

 

 

a) Barasch B et al. Helium-neon laser effects on conditioning-induced mucositis in bone marrow transplantation patients. Oral mucositis is a common complication of bone marrow transplantation conditioning therapy. Different drugs are given in order to reduce rejection of the implant. These drugs induce an oral mucosits. The mucositis is painful and complicates nutrition. Sometimes the intake of the drug has to be stopped due to complications.  In the study above 20 patients received HeNe to their oral mucosa, either right or left of midline. One side was sham irradiated.  Laser treatment was well-tolerated and reduced the severity of oral mucositis.

b) Cowen D et al. Low energy helium-neon laser in the prevention of oral mucositis in patients undergoing bone marrow transplant: results of a double blind randomized trial. Int J Radiat Oncol Biol Phys. 1997; 38 (4): 697-707. Significant reduction of oral mucositis using a 60 mW HeNe laser

CHEMO-AND RADIATION-INDUCED MUCOSITIS: RESULTS OF MULTICENTER PHASE III STUDIES.

Rene Jean Bensadoun Centre Antoine-Lacassagne, Nice, France

Considerable buccal toxicity of radiotherapy and/or chemotherapy in patients with cancer can cause patients to become discouraged and can alter their quality of life. In addition, such toxicity often necessitates alterations of treatment planning, with grave consequences in term of tumor response and even survival (concept of dose-intensity). With 5-fluorouracil and head and neck radiotherapy for example, acute mucosal toxic effect is the main limiting factor for which no clinically appropriate prophylaxis or efficacious antidote has been found to date. Management of oral mucositis is currently primarily directed at palliation of the symptoms, and prevention of infections. Low Level Laser Therapy (LLLT) has been reported effective in reducing the severity of oral mucositis lesions in a non-randomized trial, initiated in Nice (France) by Ciais et al. (1). The efficacy of this method in the prevention of chemotherapy induced oral mucositis has been subsequently confirmed in two prospective, double-blind randomized trials, in patients undergoing bone marrow transplant (2 ; 3). These initial findings and the high incidence of radiation-induced mucositis prompted a randomized multicenter trial to evaluate LLLT for the prevention of acute radiation-induced oropharyngeal mucosal lesions. The trial was open to patients with carcinoma of the oropharynx, hypopharynx and oral cavity being treated by external radiotherapy, with a total dose of 65 Gy at a rate of 1 fraction of 2 Gy/day, 5 days a week, from cobalt-60 or linear accelerator photons, without prior surgery or concomitant chemotherapy. Between September 1994 and March 1998, thirty patients entered this double-blind randomized study conforming to the Huriet law. The goal was to determine whether preventive HeNe laser beam applications could reduce or prevent oropharyngeal mucositis caused by radiotherapy.

Patients characteristics: There were 26 men and 4 women. Mean age was 60.4 years (range 36 – 78). Oral examination and preventive dental management were performed prior to radiotherapy. Daily oral hygiene (cleaning of the teeth and dental prosthesis) during treatment was recommended. Patients were assigned to either laser treatment (L+) or sham-treatment (L-) by computer blocked randomization. The protocol called for the inclusion of 30 patients, 15 in each arm. No associated anti-inflammatory or other treatment was authorized. Analgesics could be prescribed, but not during the 2 days preceding each week evaluation. Patients received HeNe laser applications daily for five consecutive days (Monday to Friday) each week, during the seven weeks of radiotherapy. The malignant tumor had to be located outside the areas selected for randomized preventive LLL application. Laser was delivered to the tissues by a straight optical fiber with a 1.2 mm spot size. The 9 treatment areas included : posterior third of buccal mucosa, soft palate and anterior tonsillar pillars. Laser illumination consisted of a continuous beam (wavelength: 632.8 nm; power: 60 mW), calibrated at the end of the optical fiber every day. The treatment time (t) for each application point was given by the equation : t (sec) = energy (J/cm2) x surface (cm2)/ Power (W). The average energy density delivered to the treatment areas was 2 J/cm2, and was applied on these nine points, equally distributed on the treated surfaces, for 33 s per point (each specific LLL session lasted approximately 5 minutes). The 60 mW lasers were designed and produced by Fradama S.A. (Geneva, Switzerland). All laser illuminations were performed by the same individual in each center. This operator was the only person to know whether or not the patient was sham-treated, and did not participate in the evaluation and scoring mucositis. During the sessions, patients wore wavelength-specific dark glasses and were instructed to keep their eyes closed, to assure that they did not know whether they were sham-treated or whether they received laser applications. The laser made the same noises, and the probe was held in the mouth exactly the same way, when treating control subjects and when treating laser patients. The whole irradiation field, the oral cavity and the visible oropharynx were inspected weekly during seven weeks by the same physician (head and neck surgeon, or radiation oncologist), blinded to the result of randomization. The evaluation of mucositis and pain was performed on the oropharyngeal areas (9 points). Criteria for evaluation were the standard WHO scale for mucositis in the oropharynx; and a segmented visual analogic scale for pain (patient self evaluation). In this phase III study, no adverse effect was noted with the use of a 60-mW HeNe laser, though it is important to emphasize the importance of preventing retinal damage by the use of wavelength-specific goggles. This is consistent with previous reports. Laser applications delayed time of onset, attenuated the peak severity and shortened the duration of oral mucositis. The difference between L+ and L- patients was statistically significant from week 4 to week 7. With the total delivered dose of 65Gy, conventionally fractionated, all L- patients developed mucositis at week 2, with a peak at week 5 (13 with grade 3 mucositis, and 2 with grade 2 mucositis). All L+ patients also had mucositis at week 2, with a peak at week 5 (5 with grade 3 mucositis, 9 with grade 2, 1 with grade 1). During the 7 weeks of treatment, the mean grade of mucositis in L+ patients was significantly lower (p=0.01) than the mean grade in L- patients. Results on decrease in pain intensity were also quite convincing. Laser applications reduced the incidence and duration of morphine administration. Ability to swallow was also improved. These results confirm previous data collected with this method, especially for patients undergoing bone marrow transplant (BMT). In a prospective study, Barasch et al. (2) used a 25- mW laser on one side of the mouth only and reported a statistically significant reduction in oral mucositis on that side, according to the scoring system they used. In the Barasch study, each patient was his or her own control, which could be of importance, since mucosal damage on the sham-treated side could have benefited also from a distant systemic laser effect. Cowen et al. (3), using a 60 mW HeNe laser, performed a double-blind randomized phase III trial, in which laser was administered to the treatment group during conditioning, prior to the day of transplant. This study showed a 33% reduction of grades 3 and 4 mucositis in L+ patients. In this trial, mucositis was scored according to an oral examination guide, with a 16 items scale, of which 4 were assessed by the patients themselves. Daily mucositis index was significantly lower in L+ patients (p < 0.05) from d+2 to d+7 after BMT. The duration of grade 3 stomatitis was also reduced in L+ patients (p = 0.01). Oral pain was lower (p = 0.05), and L+ patients required less morphinomimetics (p = 0.05). Finally, xerostomia and ability to swallow were improved among L+ patients (p = 0.05, and p = 0.01, respectively). All these results were in keeping with previous observations, suggesting the efficacy of the method (1, 4). Schubert et al. for example (4), identified a trend towards lower oral mucositis scores, on all examination days, in an interim results report of a phase I/II study, in which laser application was performed prophylactically during conditioning before BMT.

In conclusion, LLLT seems to be a safe and efficient method for the prevention of chemo- and radiation-induced mucositis, with a tremendous potential interest for combined modality treatment. The concomitant use of chemo- and radiotherapy is becoming the new standard of care in advanced head and neck cancer, with very encouraging results, even in nonresectable cases. Since the main limiting factor of these combined protocols is the acute mucositis, this complementary treatment option with low level HeNe laser could be important in enhancing the feasibility of such regimens, and especially in the conservation of dose-intensity effect. At Nice, where the method is now used routinely during head and neck radiation, we project a new study testing LLL in patients being treated with concomitant chemo- and radiotherapy for advanced head and neck cancer. Even more than the improvement of patient comfort, the therapeutic index of combined specific treatment should be increased by the use of LLLT, besides standard supportive care, oral care and enteral nutrition (5). During this study, other laser wavelengths and powers could be tested, and compared to 60-mW HeNe laser.
Ref :
1. CIAIS G., NAMER M., SCHNEIDER M., DEMARD F., POURREAU-SCHNEIDER N., MARTIN P.M., SOUDRY M., FRANQUIN J.C., ZATTARA H. La laserthérapie dans la prévention et le traitement des mucites liées à la chimiothérapie anticancéreuse. Bull. Cancer 79 : 183-191, 1992.
2. BARASCH A., PETERSON D., TANZER J.M., D’AMBROSIO J.A., NUKI K., SCHUBERT M., FRANQUIN J.C., CLIVE J., TUTSCHKA P. Helium-Neon laser effects on conditioning-induced oral mucositis in bone marrow transplantation patients. Cancer 76:2550-2556, 1995.
3. COWEN D., TARDIEU C., SCHUBERT M., PETERSON D., RESBEUT M., FAUCHER C., FRANQUIN J.C. Low energy helium-neon laser in the prevention of oral mucositis in patients undergoing bone marrow transplant : results of a double blind randomized trial. Int. J. Radiat Oncology Biol. Phys. 38 (4):697-703, 1997.
4 . SCHUBERT M.M., FRANQUIN J.C., NICCOLI-FILHO F., MARCIAL F., LLOID M., KELLY J. Effects of low-energy laser on oral mucositis : a phase I/II pilot study. Cancer Researcher Weekly 7:14, 1997.
5 . R. J. BENSADOUN, J. C. FRANQUIN, G. CIAIS, V. DARCOURT, M. M. SCHUBERT, M. VIOT, J. DEJOU, C. TARDIEU, K. BENEZERY, T. D. NGUYEN, Y. LAUDOYER, O. DASSONVILLE, G. POISSONNET, J. VALLICIONI, A. THYSS, M. HAMDI, P. CHAUVEL, F. DEMARD. Low-energy He/Ne laser in the prevention of radiation-induced mucositis. A multicenter phase III randomized study in patients with head and neck cancer. Support Care Cancer 7(4):244-252, 1999.

J Clin Laser Med Surg. 2002 Feb;20(1):23-6

Effects of low-level laser therapy on malignant cells: in vitro study.

Barbosa P, Carneiro NS, de B, Brugnera A Jr, Zanin FA, Barros RA, Soriano D.

School of Dentistry, Universidade Federal da Bahia, Salvador, BA, Brazil. albp@ufba.br

The aim of this study was to assess the effect of 635- and 670-nm laser irradiation on H.Ep.2 cells in vitro using MTT. In addition to our previous report on the effects of LLLT on the proliferation of laryngeal carcinoma cells in which it was found that irradiaton H.Ep.2 cells with 670-nm laser results in increased cell proliferation, it was decided to evaluate the effect of increased doses of laser light on these cells. The cells, obtained from SCC of the larynx, were routinely processed from defrost to the experimental condition. The cultures were kept either at 5% or 10% of FBS. Twenty-four hours after transplantation, the cells were irradiated with laser light (5-mW diode lasers; 635 and 670-nm; beam cross section approximately 1 mm) at local light doses between 0.04 and 4.8.10(4) Jm(-2). For 670 nm, significant differences in the proliferation were observed between the two concentrations of FBS (p = 0.002) and between irradiated cultures and controls (p = 0.000). Although the results were not significant, 635-nm irradiated cells also proliferated more than nonirradiated ones. This occurred under both conditions of nutrition. It is concluded, that irradiation with 670-nm laser light applied at doses between 0.04 and 4.810(4) Jm(-2) could significantly increase proliferation of laryngeal cancer cells.

J Photochem Photobiol B. 2000 Dec;59(1-3):1-8.

 

Magnetic resonance imaging (MRI) controlled outcome of side effects caused by ionizing radiation, treated with 780 nm-diode laser –preliminary results.

Schaffer M, Bonel H, Sroka R, Schaffer PM, Busch M, Sittek H, Reiser M, Duhmke E.
Department of Radiation Therapy, University of Munich, Germany.

sroka@life.med.uni-muenchen.de

BACKGROUND and OBJECTIVE: Ionizing radiation therapy by way of various beams such as electron, photon and neutron is an established method in tumor treatment. The side effects caused by this treatment such as ulcer, painful mastitis and delay of wound healing are well known, too. Biomodulation by low level laser therapy (LLLT) has become popular as a therapeutic modality for the acceleration of wound healing and the treatment of inflammation. Evidence for this kind of application, however, is not fully understood yet. This study intends to demonstrate the response of biomodulative laser treatment on the side effects caused by ionizing radiation by means of magnetic resonance imaging (MRI). STUDY DESIGN/PATIENTS and METHODS: Six female patients suffering from painful mastitis after breast ionizing irradiation and one man suffering from radiogenic ulcer were treated with lambda=780 nm diode laser irradiation at a fluence rate of 5 J/cm2. LLLT was performed for a period of 4-6 weeks (mean sessions: 25 per patient, range 19-35). The tissue response was determined by means of MRI after laser treatment in comparison to MRI prior to the beginning of the LLLT. RESULTS: All patients showed complete clinical remission. The time-dependent contrast enhancement curve obtained by the evaluation of MR images demonstrated a significant decrease of enhancement features typical for inflammation in the affected area. CONCLUSION: Biomodulation by LLLT seems to be a promising treatment modality for side effects induced by ionizing radiation.

Lasers Med Sci. 2003;18(2):100-3.

 

Low-level 809 nm GaAlAs laser irradiation increases the proliferation rate of human laryngeal carcinoma cells in vitro.

Kreisler M, Christoffers AB, Willershausen B, d’Hoedt B.

Poliklinik fur Zahnarztliche Chirurgie, Johannes Gutenberg-University, Mainz, Germany. matthiaskreisler@web.de

The aim of the study was to investigate the effect of low-level 809 nm laser irradiation on the proliferation rate of human larynx carcinoma cells in vitro. Epithelial tumor cells were obtained from a laryngeal carcinoma and cultured under standard conditions. For laser treatment the cells were spread on 96-well tissue culture plates. Sixty-six cell cultures were irradiated with an 809 nm GaAlAs laser. Another 66 served as controls. Power output was 10 mW(cw) and the time of exposure 75-300 s per well, corresponding to an energy fluence of 1.96-7.84 J/cm2. Subsequent to laser treatment, the cultures were incubated for 72 h. The proliferation rate was determined by means of fluorescence activity of a redox indicator (Alamar Blue Assay) added to the cultures immediately after the respective treatment. The indicator is reduced by metabolic activity related to cellular growth. Proliferation was determined up to 72 h after laser application. The irradiated cells revealed a considerably higher proliferation activity. The differences were highly significant up to 72 h after irradiation (Mann-Whitney U test, p < 0.001). A cellular responsiveness of human laryngeal carcinoma cells to low-level laser irradiation is obvious. The cell line is therefore suitable for basic research investigations concerning the biological mechanisms of LLLT on cells.

Braz Dent J. 2002;13(2):109-12.

 

Does LLLT stimulate laryngeal carcinoma cells?  An in vitro study.

Pinheiro AL, do Nascliento SC, de Vieira AL, Rolim AB, da Silva PS, Brugnera A Jr.

Faculty of Dentistry, Federal University of Bahia, Salvador, BA, Brazil. albp@ufba.br

Low level laser therapy (LLLT) has been used successfully in biomedicine and some of the results are thought to be related to cell proliferation. The effects of LLLT on cell proliferation is debatable because studies have found both an increase and a decrease in proliferation of cell cultures. Cell culture is an excellent method to assess both effects and dose of treatment. The aim of this study was to assess the effect of 635nm and 670 nm laser irradiation of H.Ep.2 cells in vitro using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). The cells were obtained from squamous cell carcinoma (SCC) of the larynx and were routinely processed from defrost to the experimental condition. Twenty-four hours after transplantation the cells were irradiated with doses ranging from 0.04 to 0.48J/cm2 for seven consecutive days (5 mW diode lasers: 635nm or 670 nm, beam cross-section approximately 1 mm) at local light doses between 0.04 and 0.48 J/cm2. The results showed that 635nm laser light did not significantly stimulate the proliferation of H.Ep.2 cells at doses of 0.04 J/cm2 to 0.48 J/cm2, However, 670nm laser irradiation led to an increased cell proliferation when compared to both control and 635nm irradiated cells. The best cell proliferation was found with 670nm laser irradiated cultures exposed to doses of doses of 0.04 to 0.48 J/cm2. We conclude that both dose and wavelength are factors that may affect cell proliferation of H.Ep.2 cells.

ANZ J Surg. 2002 Feb;72(2):95-9.

 

Combined endoscopic laser and radiotherapy palliation of advanced rectal cancer.

Chapuis PH, Yuile P, Dent OF, Sinclair G, Low L, Aggarwal G.

Department of Colon and Rectal Surgery, The University of Sydney at Concord Hospital, New South Wales, Australia. pchapuis@mail.usyd.edu.au

BACKGROUND: In the palliative treatment of patients with advanced, inoperable rectal cancer, combined endoscopic laser and radiotherapy have been claimed to be more effective than laser therapy alone. The number of laser treatments, laser energy used, relapse rate, treatment of relapse, morbidity and survival in consecutive patients who were treated either by laser therapy alone or laser plus radiotherapy was compared.

METHODS: Prospective data were analysed with regard to number of treatments, laser energy used, relapse rate, morbidity and survival for 56 consecutive patients.

RESULTS: The crude relapse rate was significantly higher in the laser only group than in the laser plus radiotherapy group (58 and 15%, respectively; P = 0.002). There was no difference between the groups in the median total number of laser treatments or the mean total laser energy used. In patients experiencing a relapse, there was no difference in the median number of relapses, the number of laser treatments post-relapse or the total energy used post-relapse. Survival did not differ between the groups and there were no treatment-related deaths.

CONCLUSIONS: These findings demonstrate a clear reduction in relapse after using combined laser and radiotherapy to palliate patients with advanced rectal cancer with no appreciable additional morbidity and have encouraged continuing use of this treatment.

LASER THERAPY IN CLINICAL ONCOLOGY

R. Kabisov, V. Chissov, V. Sokolov

Moscow Gertsen Cancer Research Institute, Moscow, Russia

The methodological basis for the treatment of malignant tumors will remain multivariant combinations of surgical, radiation and medicinal methods in the next century just like in this century. Such approach undoubtedly provides some results although the effectiveness of the treatment, rehabilitation indices and the existing standards of oncological patients do not meet requirements of society, physicians and patients. It is for the first time that system of Low Intensity Laser Therapy (LILT) has been used. From the position of the system approach LILT technologies with oncological patients represent complicated biotechnical processes and at its application specific features of the system, i.e. “tumor-organism”, technology of the irradiation as well as professional experience of the operator (i.e. physician) play a very important role and should be taken into account. LILT has been applied for 1000 patients with oncologic pathology of major localizations, different clinical states and morphological forms, independent of sex, age, psychosomatic features and other standard factors. The main trends of LILT in the treatment of oncological patient were: protective action during the antitumorogenic and radiation therapy (hemo-clinical correction); stimulation of growth-inhibiting factors and increase of the tumor sensivity to special and other additional means of treatment; preventive measures and treatment of complications after surgical operations; improvement of the results and quality of rehabilitation therapy and palliative treatment; treatment of opportunist pathologies with oncological patients; provides elimination of reaction for radiation therapy in 93,6% of cases; elimination of surgical complications in 89,4%. Effectiveness of the palliative LILT is 68,4%. Absolute contraindications of LILT have not been revealed. The analysis of immediate and long- term results reveals a complete absence of oncostimulating influence of LILT. Thus, it is possible to say that LILT is a new mean, improving the quality and results of a combined treatment of patients with malignant tumors.