PURPOSE:This study aimed to evaluate the effects of Chan-Chuang qigong exercise in non-Hodgkin's lymphoma patients who were undergoing chemotherapy on fatigue intensity and sleep quality.

METHODS:The study was a single-centre, controlled randomized study. One hundred and eight subjects were randomly assigned to the qigong group (n = 54) or control group (n = 54). The qigong group received Chan-Chuang qigong exercise 20-min twice daily for 21 days in the course of the chemotherapy treatment, whereas the control group without special exercise intervention. Outcome measures included fatigue and sleep quality.

RESULTS:After the three-week intervention, participants who were in the qigong group had lower fatigue intensity scores than those in the control group. The results of generalized estimating equations (GEE) analyses showed a significant group-by-time interaction effect in average fatigue, worse fatigue, and overall sleep quality (p < 0.001). The average fatigue, worse fatigue, and overall sleep quality significantly decreased over time in the qigong group.

CONCLUSIONS:Chan-Chuang qigong exercise could be regarded as an adjunct measure in clinical practice. This study cannot completely discount the possible influence of placebo effects, and more objective clinical outcome measures are needed to produce our findings with long-term follow-up in a randomized controlled study.

PURPOSE:Many women with ovarian cancer may experience adverse effects from adjuvant chemotherapy after surgery. Non-pharmacological interventions can be used to reduce these side effects. We tested auricular acupressure to reduce treatment side effects in this population.

METHODS:A prospective, quasi-randomized controlled trial was carried out at a publicly-funded hospital in southern Taiwan. Thirty-four women in the intervention group received auricular acupressure at four points (Shenmen, subcortex, endocrine, and heart), three times per day for 3 min per time, for 6 weeks. Thirty-one women in the control group received routine nursing care alone. The M. D. Anderson Symptom Inventory (MDASI) was completed at four time points.

RESULTS:After receiving the third cycle of chemotherapy, side effect severity was elevated among both groups. Auricular acupressure reduced side effects such as disturbed sleep (t = - 11.99; p < .001, eta squared = 0.69), fatigue (t = - 2.57; p < .01, eta squared = 0.10), and lack of appetite (t = - 2.37; p = .024, eta squared = 0.08).

CONCLUSION:Auricular acupressure can reduce adverse side effects of chemotherapy in women with ovarian cancer. Future studies with a larger sample and using some laboratory-based tests (such as C-reactive protein, interleukin-6) are warranted to confirm the results.

PURPOSE:The aim of this study is to compare cryotherapy made only with water and cryotherapy made with chamomile infusion for prevention and reduction of intensity of oral mucositis in patients with cancer receiving 5-fluorouracil and leucovorin.

METHOD:This is a randomized pilot study with two groups: cryotherapy made only with water (control group, n = 18) and cryotherapy made with chamomile infusion (chamomile group, n = 20). Both groups were instructed to swish the ice around in their oral cavity for at least 30 min during chemotherapy. Assessment of oral mucosa occurred on days 8, 15, and 22 after the first day of chemotherapy.

RESULTS:Fifty percent of the patients in the control and 30 % in the chamomile group developed oral mucositis. Mouth pain score was higher in patients in the control group on all evaluations (p = 0.02 for day 8, p = 0.09 for day 15, and p = 0.14 for day 22). Patients in the chamomile group never developed mucositis with grade 2 or higher. Presence of ulceration was statistically significant on day 8 (16 % in the control vs. 0 % in the chamomile group, p = 0.10), but not in days 15 and 22, although 11 % still had ulcerations in the control group and none in the chamomile group.

CONCLUSION:The occurrence of oral mucositis was lower in patients in the chamomile group than in the control group. When compared to the controls, the chamomile group presented less mouth pain and had no ulcerations. Cryotherapy was well tolerated by both groups, and no toxicity related to chamomile was identified.

BACKGROUND:Patients receiving oxaliplatin may experience peripheral neuropathic pain and fatigue. Aromatherapy massage, a nonpharmacological method, may help to control these symptoms.

OBJECTIVE:The aim of this open-label, parallel-group, quasi-randomized controlled pilot study was to investigate the effect of aromatherapy massage on chemotherapy-induced peripheral neuropathic pain and fatigue in patients receiving oxaliplatin.

METHODS:Stratified randomization was used to allocate 46 patients to 2 groups: intervention (n = 22) and control (n = 24). Between week 1 and week 6, participants in the intervention group (IG) received aromatherapy massage 3 times a week. There was no intervention in weeks 7 and 8. The control group (CG) received routine care. Neuropathic pain was identified using the Douleur Neuropathique 4 Questions; severity of painful paresthesia was assessed with the numerical rating scale; fatigue severity was identified with the Piper Fatigue Scale.

RESULTS:At week 6, the rate of neuropathic pain was significantly lower in the IG, when compared with the CG. The severity of painful paresthesia based on numerical rating scale in the IG was significantly lower than that in the CG at weeks 2, 4, and 6. At week 8, fatigue severity in the IG was significantly lower when compared with CG (P<.05).

CONCLUSION:Aromatherapy massage may be useful in the management of chemotherapy-induced peripheral neuropathic pain and fatigue.

IMPLICATIONS FOR PRACTICE:This pilot study suggests that aromatherapy massage may be useful to relieve neuropathic pain and fatigue. However, there is a need for further clinical trials to validate the results of this study.

PURPOSE:There are reports that elemental diet (ED) ameliorates oral mucositis caused by antineoplastic chemotherapy. Although this effectiveness may be partly due to high nutrient absorption, the effects of chemotherapy on mucosal defense mechanisms remain unclear. We investigated the effects of oral supplementation with ED on mucin in 5-fluorouracil (5-FU)-induced intestinal mucositis.

METHODS:5-FU was administered to rats orally once daily, and ED was supplied orally twice daily for 5 days. The severity of mucositis was assessed by length, dry tissue weight, and villus height of the intestinal tract. Using anti-mucin monoclonal antibody, we compared the immunoreactivity in the gastrointestinal (GI) tract and mucin content by histological and biochemical examinations.

RESULTS:Oral supplementation with ED reduced histological damage and loss of length, dry tissue weight, and villus height induced by 5-FU administration. ED markedly altered PGM34 antibody immunoreactivity and mucin contents in the small intestine of rats with 5-FU-induced mucositis.

CONCLUSIONS:ED may possibly be more effective for the prevention of antineoplastic chemotherapy-induced mucositis through the activation of GI mucus cells.

OBJECTIVE:To evaluate the efficacy of hyperbaric oxygen therapy (HBO) in the treatment of post-radiation haematuria (PRH) and to identify the predictive factors for a successful outcome.

MATERIALS AND METHODS:We conducted a retrospective study and included all patients treated with HBO for PRH in a university hospital centre between January 2003 and December 2013. We studied the patients' clinical characteristics, radiotherapy indication, treatments preceding HBO, the grade of haematuria diagnosed based on the CTCAE classification v 4.03 and the efficacy of HBO. The success of HBO was defined as the total or partial resolution of haematuria.

RESULTS:We included 71 patients with a median age of 72 (39-87) years. PRHs were severe (grade≥3) in 50 (70.4%) of the cases. Radiotherapy was indicated in the treatment of prostate cancer in 61 (85.9%) patients. The median length of time between haematuria and HBO was 8 (1-154) months. Prior to HBO, 46 (64.8%) patients underwent electrocoagulation of the bladder. HBO sessions were compounded by 9 cases of barotraumatic otitis, 5 cases of transient visual disturbance, and one case of finger paresthesia. On average, 29 (3-50) sessions were carried out. Treatment was effective in 46 (64.8%) patients, 37 (52.1%) of whom were completely cured. A haematuria grade of less than 3 was a predictive factor in successful treatment (p=0.027). Median follow-up was 15 (1-132) months.

CONCLUSION:Hyperbaric oxygen therapy completely resolves post-radiation haematuria in 52.1% of cases. Prolonged patient follow-up is required in order to confirm the efficacy of this treatment.

PURPOSE:Whether the benefits of exercise during chemotherapy continue into survivorship is not well-known. Here, the aim was to examine the effects of two exercise interventions on self-reported health-related and objectively measured physiological outcomes 12 months following commencement of chemotherapy.

METHODS:Two hundred and forty women with breast cancer stage I-IIIa were randomized to 16 weeks of high-intensity aerobic interval training combined with either resistance training (RT-HIIT), or moderate-intensity aerobic training (AT-HIIT), or to usual care (UC).

PRIMARY OUTCOME:cancer-related fatigue (CRF); secondary outcomes: quality of life (QoL), symptom burden, muscle strength, cardiorespiratory-fitness, body mass, and return to work.

RESULTS:Compared to UC, both RT-HIIT and AT-HIIT significantly counteracted increases in total CRF (ES = - 0.34; ES = - 0.10), daily life CRF (ES=-0.76; ES=-0.50, and affective CRF (ES=-0.60; ES=-0.39). Both RT-HIIT and AT-HIIT reported significantly lower total symptoms (ES = - 0.46, ES = - 0.46), and displayed gains in lower limb (ES = 0.73; ES = 1.03) and handgripmuscle strength (surgery side ES = 0.70, ES = 0.71; non-surgery side ES = 0.57, ES = 0.59). AT-HIIT displayed significant reductions in body mass (ES = - 0.24), improved QoL: role (ES = 0.33) and emotional functioning (ES = 0.40), and a larger proportion had returned towork (p = 0.02) vs UC.

CONCLUSION:These findings emphasize the beneficial effects of supervised high-intensity exercise during chemotherapy to improve the health and to reduce societal costs associated with prolonged sick leave for patients with breast cancer several months following chemotherapy.

IMPLICATIONS FOR CANCER SURVIVORS:These findings provide important information with substantial positive consequences for breast cancer survivorship. High-intensity exercise programs during chemotherapy and support to maintain physical activity can be a powerful strategy to manage or prevent many of the short- and long-term adverse effects of treatment for the increasing cohort of cancer survivors.

BACKGROUND:Radiation therapy is performed as an adjuvant therapy when indicated following surgical resection of malignant tumors. However, radiation exposure induces acute or chronic dermatitis, depending on the radiation dose, interval, tissue volume, or irradiated area of the body. Radiation-induced skin ulcers and osteomyelitis of the underlying bone are intractable late-stage complications of radiation therapy, and often require reconstructive surgery to cover exposed tissue. Hyperbaric oxygen therapy has been suggested as a treatment for delayed radiation injury with soft tissue and bony necrosis.

CASE PRESENTATION:A 74-year-old Japanese female underwent left radical mastectomy for breast cancer (T3N3M0, stage IIIB) in 1987. Radiation therapy was initiated 6 weeks after the surgery. She received telecobalt-60 in a total dose of 50 Gy with 25 fractions to the left supraclavicular, parasternal and left axillary regions, and electron treatment (9 MeV) in a total dose of 50 Gy in 25 fractions to the left chest wall. After irradiation, her skin became thinner and more fragile on the left chest wall, but no severe infections were observed. She noticed a small ulcer that repeatedly healed and recurred in 2000. She visited the hospital where she received radiation therapy and was treated for a skin ulcer on the left chest wall in December 2012. A fistula developed and then pus was discharged in January 2013. She was referred to the hyperbaric medical center in February 2013, and the fistula (1.5× 3 cm) with pus discharge was observed. She was diagnosed with a late-onset radiation-induced skin ulcer that developed 25 years after radical mastectomy. HBO2 (2.5 atmospheres absolute with 100% oxygen for 60 minutes) was indicated for the refractory ulcer and osteomyelitis of the ribs. The patient was treated with HBO2 a total of 101 times over the course of 1 year and completely recovered.

CONCLUSIONS:Hyperbaric oxygen therapy can be performed safely for even more than 100 sessions in patients with radiation-induced skin ulcers and osteomyelitis. Hyperbaric oxygen therapy can be considered as an alternative, conservative treatment when surgical resection for late-onset, radiation-induced skin ulcers is not indicated because of fragile skin in the irradiated areas.

BACKGROUND:Cancer is a significant global health problem. Radiotherapy is a treatment for many cancers and about 50% of people having radiotherapy will be long-term survivors. Some will experience late radiation tissue injury (LRTI) developing months or years later. Hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for LRTI based upon the ability to improve the blood supply to these tissues. It is postulated that HBOT may result in both healing of tissues and the prevention of problems following surgery.

OBJECTIVES:To assess the benefits and harms of HBOT for treating or preventing LRTI.

SEARCH METHODS:We updated the searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 11), MEDLINE, EMBASE, DORCTIHM and reference lists of articles in December 2015. We also searched for ongoing trials at clinicaltrials.gov.

SELECTION CRITERIA:Randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing.

DATA COLLECTION AND ANALYSIS:Three review authors independently evaluated the quality of the relevant trials using the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions and extracted the data from the included trials.

MAIN RESULTS:Fourteen trials contributed to this review (753 participants). There was some moderate quality evidence that HBOT was more likely to achieve mucosal coverage with osteoradionecrosis (ORN) (risk ratio (RR) 1.3; 95% confidence interval (CI) 1.1 to 1.6, P value = 0.003, number needed to treat for an additional beneficial outcome (NNTB) 5; 246 participants, 3 studies). There was also moderate quality evidence of a significantly improved chance of wound breakdown without HBOT following operative treatment for ORN (RR 4.2; 95% CI 1.1 to 16.8, P value = 0.04, NNTB 4; 264 participants, 2 studies). From single studies there was a significantly increased chance of improvement or cure following HBOT for radiation proctitis (RR 1.72; 95% CI 1.0 to 2.9, P value = 0.04, NNTB 5), and following both surgical flaps (RR 8.7; 95% CI 2.7 to 27.5, P value = 0.0002, NNTB 4) and hemimandibulectomy (RR 1.4; 95% CI 1.1 to 1.8, P value = 0.001, NNTB 5). There was also a significantly improved probability of healing irradiated tooth sockets following dental extraction (RR 1.4; 95% CI 1.1 to 1.7, P value = 0.009, NNTB 4).There was no evidence of benefit in clinical outcomes with established radiation injury to neural tissue, and no randomised data reported on the use of HBOT to treat other manifestations of LRTI. These trials did not report adverse events.

AUTHORS' CONCLUSIONS:These small trials suggest that for people with LRTI affecting tissues of the head, neck, anus and rectum, HBOT is associated with improved outcome. HBOT also appears to reduce the chance of ORN following tooth extraction in an irradiated field. There was no such evidence of any important clinical effect on neurological tissues. The application of HBOT to selected participants and tissues may be justified. Further research is required to establish the optimum participant selection and timing of any therapy. An economic evaluation should be undertaken.

INTRODUCTION:This study examines patient reported outcome measures of women undergoing hyperbaric oxygen treatment (HBOT) after breast-conserving therapy.

METHOD:Included were 57 women treated with HBOT for late radiation-induced tissue toxicity (LRITT) referred in the period January 2014-December 2015. HBOT consisted of (on average) 47 sessions. In total, 80 min of 100 % O2 was administered under increased pressure of 2.4 ATA. Quality of life was assessed before and after treatment using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR23, and a NRS pain score.

RESULTS:Fifty-seven women were available for evaluation before and after treatment. Before HBOT, patients had severe complaints of pain in the arm/shoulder (46 %), swollen arm/hand (14 %), difficulty to raise arm or move it sideways (45 %), pain in the area of the affected breast (67 %), swollen area of the affected breast (45 %), oversensitivity of the affected breast (54 %), and skin problems on/in the area of the affected breast (32 %); post HBOT, severe complaints were still experienced in 17, 7, 22, 15, 13, 15, and 11 % of the women, respectively. Differences were all significant. The NRS pain score improved at least 1 point (range 0-10) in 81 % of the patients (p < 0.05).

CONCLUSION:In these breast cancer patients treated with HBOT for LRITT, the patient-reported outcomes were positive and improvements were observed. HBOT was a well-tolerated treatment for LRITT and its side-effects were both minimal and reversible.

OBJECTIVES:To analyze the efficacy of hyperbaric oxygen for the treatment of radiation-induced hemorrhagic cystitis and to identify factors associated with successful treatment.

METHODS:Clinical records from 176 patients with refractory radiation-induced hemorrhagic cystitis treated at the Portuguese Navy Center for Underwater and Hyperbaric Medicine, during a 15-year period, were retrospectively analyzed. Evolution of macroscopic hematuria was used to analyze treatment efficacy and correlated with other external variables.

RESULTS:From a total of 176 treated patients, 23.9% evidenced other radiation-induced soft tissue lesions. After an average on 37 sessions, 89.8% of patients showed resolution of hematuria, with only 1.7% of adverse events. In our sample, hematuria resolution after treatment with hyperbaric oxygen was statistically associated to the need for transfusion therapy (P = 0.026) and the number of sessions of hyperbaric oxygen (P = 0.042). No relationship was found with the remaining variables.

CONCLUSIONS:Refractory radiation-induced hemorrhagic cystitis can be successfully and safely treated with hyperbaric oxygen. Treatment effectiveness seems to be correlated with the need for transfusion therapy and the number of sessions performed.

OBJECTIVE:Radiation-induced xerostomia is one of the most common morbidities of radiation therapy in patients with head and neck cancer. However, in spite of its high rate of occurrence, there are few effective therapies available for its management. The aim of this study was to assess the efficacy of hyperbaric oxygen on the treatment of radiation-induced xerostomia and xerostomia-related quality of life.

STUDY DESIGN:PubMed, Google Scholar, and the Cochrane Library were searched for retrospective or prospective trials assessing subjective xerostomia, objective xerostomia, or xerostomia-related quality of life. To be included, patients had to have received radiation therapy for head and neck cancer, but not hyperbaric oxygen therapy (HBOT).

RESULTS:The systematic review initially identified 293 potential articles. Seven studies, comprising 246 patients, qualified for inclusion. Of the included studies, 6 of 7 were prospective in nature, and 1 was a retrospective study; and 2 of the 7 were controlled studies.

CONCLUSIONS:HBOT may have utility for treating radiation-induced xerostomia refractory to other therapies. Additionally, HBOT may induce long-term improvement in subjective assessments of xerostomia, whereas other therapies currently available only provide short-term relief. The strength of these conclusions is limited by the lack of randomized controlled clinical trials.

PURPOSE:Radiotherapy is effective in the treatment of tumors in the pelvic area but is associated with side effects such as cystitis and proctitis. Hyperbaric Oxygen Therapy (HBOT) has emerged as a treatment modality for radiation-induced side effects. In a rat model for radiation cystitis, we studied the effects of HBOT on oxidative stress and pro-fibrotic factors.

MATERIALS AND METHODS:Sedated Sprague-Dawley rats underwent bladder irradiation of 20Gy with and without 20 sessions of HBOT during a fortnight. Control animals were treated with and without HBOT. All four groups of animals were euthanized 28 days later. Histopathological examinations, immunohistochemistry and quantitative polymerase chain reaction (qPCR) were used to analyze changes in oxidative stress (8-OHdG), anti-oxidative responses (SOD-1, SOD2, HO-1 and NRFα) and a panel of Th1-type and Th2-type cytokines (IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, TNF-α, TGF-β, IFN-γ) in the urinary bladder.

RESULTS:Bladder irradiation increased the expression of 8-OHdG, SOD2, HO-1, NRFα, IL-10, TNF-α and tended to increase TGF-β. These changes were completely reversed by HBOT while HBOT in control animals had no effects on the studied markers for oxidative stress, anti-oxidative responses and Th1-type and Th2-type cytokines.

CONCLUSIONS:Radiation induced a significant elevation of oxidative stress, antioxidants and pro-fibrotic factors in our animal model for radiation cystitis that were completely reversed and normalized by HBOT. Our findings indicate that HBOT may prevent radiation-induced changes by affecting oxidative stress and inflammatory cascades induced by radiation.

SUMMARY:Radiotherapy may cause the development of chronic inflammation and fibrosis, significantly impairing organ function. We hypothesized that bladder irradiation induces an oxidative stress reaction, thereby triggering the redox system and thus initiating an inflammatory and pro-fibrotic response. We aimed to assess whether these changes would be reversed by hyperbaric oxygen using an animal model for radiation cystitis. Our study show that hyperbaric oxygen therapy may reverse oxidative stress and pro-inflammatory factors induced by radiation.

Late effects of radiotherapy for head and neck cancer treatment have been increasingly investigated due to its impact on patients' quality of life. The purpose of this study was to evaluate the effect of low-level laser therapy on hyposalivation, low salivary pH, and quality of life in head and neck cancer patients post-radiotherapy. Twenty-nine patients with radiation-induced xerostomia received laser sessions twice a week, during 3 months (24 sessions). For this, a continuous wave Indium-Gallium-Aluminium-Phosphorus diode laser device was used punctually on the major salivary glands (808 nm, 0.75 W/cm(2), 30 mW, illuminated area 0.04 cm(2), 7.5 J/cm(2), 10 s, 0.3 J). Six extraoral points were illuminated on each parotid gland and three on each submandibular gland, as well as two intraoral points on each sublingual gland. Stimulated and unstimulated salivary flow rate, pH (two scales with different gradations), and quality of life (University Of Washington Quality of Life Questionnaire for Patients with Head andNeck Cancer) were assessed at baseline and at the end of the treatment. There were significant increases in both mean salivary flow rates (unstimulated: p = 0.0012; stimulated: p < 0.0001), mean pH values (p = 0.0002 and p = 0.0004), and mean score from the quality of life questionnaire (p < 0.0001). Low-level laser therapy seems to be effective to mitigate salivary hypofunction and increase salivary pH of patients submitted to radiotherapy for head and neck cancer, thereby leading to an improvement in quality of life.

Vitamin C or ascorbic acid (AA) is implicated in many biological processes and has been proposed as a supplement for various conditions, including cancer. In this review, we discuss the effects of AA on the development and function of lymphocytes. This is important in the light of cancer treatment, as the immune system needs to regenerate following chemotherapy or stem cell transplantation, while cancer patients are often AA-deficient. We focus on lymphocytes, as these white blood cells are the slowest to restore, rendering patients susceptible to often lethal infections. T lymphocytes mediate cellular immunity and have been most extensively studied in the context of AA biology. In vitro studies demonstrate that T cell development requires AA, while AA also enhances T cell proliferation and may influence T cell function. There are limited and opposing data on the effects of AA on B lymphocytes that mediate humoral immunity. However, AA enhances the proliferation of NK cells, a group of cytotoxic innate lymphocytes. The influence of AA on natural killer (NK) cell function is less clear. In summary, an increasing body of evidence indicates that AA positively influences lymphocyte development and function. Since AA is a safe and cheap nutritional supplement, it is worthwhile to further explore its potential benefits for immune reconstitution of cancer patients treated with immunotoxic drugs.

PURPOSE:This paper aims to evaluate the effects of laser (660 nm) and light-emitting diode (LED) (670 nm) irradiation in the cheek pouch mucosa of hamsters with oral mucositis (OM) induced by chemotherapy (Che) with 5-fluorouracil (5-FU).

MATERIALS AND METHODS:In the preventive groups, the photobiomodulation was started 1 day before the drug administration and was performed every 48 h (Ia, IIa, Ib, and IIb). In the therapeutic groups (IIIa, IIIb, IVa, and IVb), the irradiations were started on the third day after the Che d(0) and was performed every 48 h. In both groups, animals were sacrificed 7 or 14 days after Che. In the positive control groups, the hamsters were subjected to Che but did not receive irradiation, and they were sacrificed in 7 days (Va) or 14 days (Vb). In the negative control groups, no procedures were done and the animals were sacrificed 7 days (Vc) or 14 days (Vd) after the experiment started.

RESULTS:The results indicated loss of body mass, xerostomia, and alopecia in the animals subjected to Che and the healing of OM to different degrees after the photobiomodulation treatment. Histologically, the positive control and experimental groups showed inflammation, predominately with lymphocytes and plasma cells, which tended to diminish with time. Epithelial atrophy, hyperemia, fibroblast proliferation, and vascular congestion were also observed at those intervals.

CONCLUSIONS:The best results were obtained from the preventive laser and LED photobiomodulation groups; both treatments were effective in diminishing the OM lesions.

CLINICAL RELEVANCE:A noninvasive and effective method with sparse side effects of OM would be desirable for use in cancer centers around the world.

PURPOSE:This paper aims to evaluate the effects of laser (660 nm) and light-emitting diode (LED) (670 nm) irradiation in the cheek pouch mucosa of hamsters with oral mucositis (OM) induced by chemotherapy (Che) with 5-fluorouracil (5-FU).

MATERIALS AND METHODS:In the preventive groups, the photobiomodulation was started 1 day before the drug administration and was performed every 48 h (Ia, IIa, Ib, and IIb). In the therapeutic groups (IIIa, IIIb, IVa, and IVb), the irradiations were started on the third day after the Che d(0) and was performed every 48 h. In both groups, animals were sacrificed 7 or 14 days after Che. In the positive control groups, the hamsters were subjected to Che but did not receive irradiation, and they were sacrificed in 7 days (Va) or 14 days (Vb). In the negative control groups, no procedures were done and the animals were sacrificed 7 days (Vc) or 14 days (Vd) after the experiment started.

RESULTS:The results indicated loss of body mass, xerostomia, and alopecia in the animals subjected to Che and the healing of OM to different degrees after the photobiomodulation treatment. Histologically, the positive control and experimental groups showed inflammation, predominately with lymphocytes and plasma cells, which tended to diminish with time. Epithelial atrophy, hyperemia, fibroblast proliferation, and vascular congestion were also observed at those intervals.

CONCLUSIONS:The best results were obtained from the preventive laser and LED photobiomodulation groups; both treatments were effective in diminishing the OM lesions.

CLINICAL RELEVANCE:A noninvasive and effective method with sparse side effects of OM would be desirable for use in cancer centers around the world.

PURPOSE:There is a large body of evidence supporting the efficacy of low-level laser therapy (LLLT), more recently termed photobiomodulation (PBM) for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved and dosimetric parameters may lead to the management of a broader range of complications associated with HNC treatment. This could enhance patient adherence to cancer therapy, and improve quality of life and treatment outcomes. The mechanisms of action, dosimetric, and safety considerations for PBM have been reviewed in part 1. Part 2 discusses the head and neck treatment side effects for which PBM may prove to be effective. In addition, PBM parameters for each of these complications are suggested and future research directions are discussed.

METHODS:Narrative review and presentation of PBM parameters are based on current evidence and expert opinion.

RESULTS:PBM may have potential applications in the management of a broad range of side effects of (chemo)radiation therapy (CRT) in patients being treated for HNC. For OM management, optimal PBM parameters identified were as follows: wavelength, typically between 633 and 685 nm or 780-830 nm; energy density, laser or light-emitting diode (LED) output between 10 and 150 mW; dose, 2-3 J (J/cm(2)), and no more than 6 J/cm(2) on the tissue surface treated; treatment schedule, two to three times a week up to daily; emission type, pulsed (<100 Hz); and route of delivery, intraorally and/or transcutaneously. To facilitate further studies, we propose potentially effective PBM parameters for prophylactic and therapeutic use in supportive care for dermatitis, dysphagia, dry mouth, dysgeusia, trismus, necrosis, lymphedema, and voice/speech alterations.

CONCLUSION:PBM may have a role in supportive care for a broad range of complications associated with the treatment of HNC with CRT. The suggested PBM irradiation and dosimetric parameters, which are potentially effective for these complications, are intended to provide guidance for well-designed future studies. It is imperative that such studies include elucidating the effects of PBM on oncology treatment outcomes.