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The effectiveness of a saline mouth rinse regimen and education programme on radiation-induced oral mucositis and quality of life in oral cavity cancer patients: A randomised controlled trial.
Huang, BS, Wu, SC, Lin, CY, Fan, KH, Chang, JT, Chen, SC
European journal of cancer care. 2018;(2):e12819
Abstract
Radiation therapy (RT) and concurrent chemotherapy RT (CCRT) generate radiation-induced oral mucositis (OM) and lower quality of life (QOL). This study assessed the impact of a saline mouth rinse regimen and education programme on radiation-induced OM symptoms, and QOL in oral cavity cancer (OCC) patients receiving RT or CCRT. Ninety-one OCC patients were randomly divided into a group that received saline mouth rinses and an education programme and a control group that received standard care. OM symptoms and QOL were assessed with the WHO Oral Toxicity Scale, MSS-moo and UW-QOL. Data were collected at the first postoperative visit to the radiation department (T0) and at 4 weeks and 8 weeks after beginning RT or CCRT. Patients in both groups had significantly higher levels of physical and social-emotional QOL at 8 weeks after beginning RT or CCRT compared to the first visit. Patients in the saline rinse group had significantly better physical and social-emotional QOL as compared to the standard care group at 8 weeks. Radiation-induced OM symptoms and overall QOL were not different between the groups. We thus conclude the saline rinse and education programme promote better physical and social-emotional QOL in OCC patients receiving RT/CCRT.
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2.
Prevention from radiation damage by natural products.
Fischer, N, Seo, EJ, Efferth, T
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2018;:192-200
Abstract
BACKGROUND Radiotherapy is a mainstay of cancer treatment since decades. Ionizing radiation (IR) is used for destruction of cancer cells and shrinkage of tumors. However, the increase of radioresistance in cancer cells and radiation toxicity to normal tissues are severe concerns. The exposure to radiation generates intracellular reactive oxygen species (ROS), which leads to DNA damage by lipid peroxidation, removal of thiol groups from cellular and membrane proteins, strand breaks and base alterations. HYPOTHESIS Plants have to deal with radiation-induced damage (UV-light of sun, other natural radiation sources). Therefore, it is worth speculating that radioprotective mechanisms have evolved during evolution of life. We hypothesize that natural products from plants may also protect from radiation damage caused as adverse side effects of cancer radiotherapy. METHODS The basis of this systematic review, we searched the relevant literature in the PubMed database. RESULTS Flavonoids, such as genistein, epigallocatechin-3-gallate, epicatechin, apigenin and silibinin mainly act as antioxidant, free radical scavenging and anti-inflammatory compounds, thus, providing cytoprotection in addition to downregulation of several pro-inflammatory cytokines. Comparable effects have been found in phenylpropanoids, especially caffeic acid phenylethylester, curcumin, thymol and zingerone. Besides, resveratrol and quercetin are the most important cytoprotective polyphenols. Their radioprotective effects are mediated by a wide range of mechanisms mainly leading to direct or indirect reduction of cellular stress. Ascorbic acid is broadly used as antioxidant, but it has also shown activity in reducing cellular damage after irradiation mainly due to its antioxidant capabilities. The metal ion chelator, gallic acid, represents another natural product attenuating cellular damage caused by radiation. CONCLUSIONS Some secondary metabolites from plants reveal radioprotective features against cellular damage caused by irradiation. These results warrant further analysis to develop phytochemicals as radioprotectors for clinical use.
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The Microbiome and Radiation Induced-Bowel Injury: Evidence for Potential Mechanistic Role in Disease Pathogenesis.
Kumagai, T, Rahman, F, Smith, AM
Nutrients. 2018;(10)
Abstract
Radiotherapy has played a major role in both the curative and palliative treatment of cancer patients for decades. However, its toxic effect to the surrounding normal healthy tissue remains a major drawback. In cases of intra-abdominal and/or pelvic malignancy, healthy bowel is inevitably included in the radiation field, causing undesirable consequences that subsequently manifest as radiation-induced bowel injury, which is associated with significant morbidity and mortality. The pathophysiology of radiation-induced bowel injury is poorly understood, although we now know that it derives from a complex interplay of epithelial injury and alterations in the enteric immune, nervous, and vascular systems in genetically predisposed individuals. Furthermore, evidence supporting a pivotal role for the gut microbiota in the development of radiation-induced bowel injury has been growing. In this review, we aim to appraise our current understanding of radiation-induced bowel injury and the role of the microbiome in its pathogenesis as well as prevention and treatment. Greater understanding of the relationship between the disease mechanism of radiation-induced bowel injury and gut microbiome might shed light on potential future prevention and treatment strategies through the modification of a patient's gut microbiome.
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4.
Pentoxifylline and vitamin E for treatment or prevention of radiation-induced fibrosis in patients with breast cancer.
Kaidar-Person, O, Marks, LB, Jones, EL
The breast journal. 2018;(5):816-819
Abstract
Radiation therapy (RT) plays an important role in the management of breast cancer. Radiation-induced fibrosis is a side effect of radiation therapy and may occur in up to 13% of the cases in patients (Radiother Oncol, 2009;90:80), fortunately usually is modest/localized and not associated with marked symptoms. However, occasionally, fibrosis can be moderate-to-severe, and cause clinically-meaningful symptoms. The current review summarizes the use of pentoxifylline and vitamin E of treatment or prevention of radiation-induced fibrosis in breast cancer patients. Even though data are limited, this regimen may reduce RT-associated toxicity.
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Randomized control trial of benzydamine HCl versus sodium bicarbonate for prophylaxis of concurrent chemoradiation-induced oral mucositis.
Chitapanarux, I, Tungkasamit, T, Petsuksiri, J, Kannarunimit, D, Katanyoo, K, Chakkabat, C, Setakornnukul, J, Wongsrita, S, Jirawatwarakul, N, Lertbusayanukul, C, et al
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2018;(3):879-886
Abstract
PURPOSE The purpose of the study is to compare the efficacy of benzydamine HCl with sodium bicarbonate in the prevention of concurrent chemoradiation-induced oral mucositis in head and neck cancer patients. METHODS Sixty locally advanced head and neck cancer patients treated with high-dose radiotherapy concurrently with platinum-based chemotherapy were randomly assigned to receive either benzydamine HCl or sodium bicarbonate from the first day of treatment to 2 weeks after the completion of treatment. The total score for mucositis, based on the Oral Mucositis Assessment Scale (OMAS), was used for the assessment, conducted weekly during the treatment period and at the fourth week of the follow-up. Pain score, all prescribed medications, and tube feeding needs were also recorded and compared. RESULTS The median of total OMAS score was statistically significant lower in patients who received benzydamine HCl during concurrent chemo-radiotherapy (CCRT) than in those who received sodium bicarbonate, (p value < 0.001). There was no difference in median pain score, (p value = 0.52). Nineteen percent of patients in sodium bicarbonate arm needed oral antifungal agents whereas none in the benzydamine HCl arm required such medications, (p value = 0.06). Tube feeding needs and the compliance of CCRT were not different between the two study arms. CONCLUSIONS For patients undergoing high-dose radiotherapy concurrently with platinum-based chemotherapy, using benzydamine HCl mouthwash as a preventive approach was superior to basic oral care using sodium bicarbonate mouthwash in terms of reducing the severity of oral mucositis and encouraging trend for the less need of oral antifungal drugs.
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Pharmacological interventions for the prevention of insufficiency fractures and avascular necrosis associated with pelvic radiotherapy in adults.
van den Blink, QU, Garcez, K, Henson, CC, Davidson, SE, Higham, CE
The Cochrane database of systematic reviews. 2018;(4):CD010604
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Abstract
BACKGROUND Pelvic radiotherapy is a treatment delivered to an estimated 150,000 to 300,000 people annually across high-income countries. Fractures due to normal stresses on weakened bone due to radiotherapy are termed insufficiency fractures. Pelvic radiotherapy-related interruption of the blood supply to the hip is termed avascular necrosis and is another recognised complication. The reported incidences of insufficiency fractures are 2.7% to 89% and risk of developing avascular necrosis is 0.5%. These complications lead to significant morbidity in terms of pain, immobility and consequently risk of infections, pressure sores and mortality. OBJECTIVES To assess the effects of pharmacological interventions for preventing insufficiency fractures and avascular necrosis in adults over 18 years of age undergoing pelvic radiotherapy. SEARCH METHODS We performed electronic literature searches in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and DARE to 19 April 2017. We also searched trial registries. Further relevant studies were identified through handsearching of citation lists of included studies. SELECTION CRITERIA Randomised controlled trials (RCTs) or non RCTs with concurrent comparison groups including quasi-RCTs, cluster RCTs, prospective cohort studies and case series of 30 or more participants were screened. We included studies assessing the effect of pharmacological interventions in adults over 18 years of age undergoing radical pelvic radiotherapy as part of anticancer treatment for a primary pelvic malignancy. We excluded studies involving radiotherapy for bone metastases. We assessed use of pharmacological interventions at any stage before or during pelvic radiotherapy. Interventions included calcium or vitamin D (or both) supplementation, bisphosphonates, selective oestrogen receptor modulators, hormone replacement therapy (oestrogen or testosterone), denosumab and calcitonin. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trial quality and extracted data. We contacted study authors to obtain missing data. Data were to be pooled using the random-effects model if study comparisons were similar, otherwise results were to be reported narratively. MAIN RESULTS We included two RCTs (1167 participants). The first RCT compared zoledronic acid with placebo in 96 men undergoing pelvic radiotherapy for non-metastatic prostate cancer.The second RCT had four treatment arms, two of which evaluated zoledronic acid plus adjuvant androgen suppression compared with androgen suppression only in 1071 men undergoing pelvic radiotherapy for non-metastatic prostate cancer.Both studies were at a moderate to high risk of bias and all evidence was judged to be of very low certainty.The studies provided no evidence on the primary outcomes of the review and provided limited data in relation to secondary outcomes, such that meta-analyses were not possible. Both studies focused on interventions to improve bone health in relation to androgen deprivation rather than radiation-related insufficiency fractures and avascular necrosis. Few fractures were described in each study and those described were not specific to insufficiency fractures secondary to radiotherapy. Both studies reported that zoledronic acid in addition to androgen deprivation and pelvic radiotherapy led to improvements in BMD; however, the changes in BMD were measured and reported differently. There was no available evidence regarding adverse effects. AUTHORS' CONCLUSIONS The evidence relating to interventions to prevent insufficiency fractures and avascular necrosis associated with pelvic radiotherapy in adults is of very low certainty. This review highlights the need for prospective clinical trials using interventions prior to and during radiotherapy to prevent radiation-related bone morbidity, insufficiency fractures and avascular necrosis. Future trials could involve prospective assessment of bone health including BMD and bone turnover markers prior to pelvic radiotherapy. The interventions for investigation could begin as radiotherapy commences and remain ongoing for 12 to 24 months. Bone turnover markers and BMD could be used as surrogate markers for bone health in addition to radiographic imaging to report on presence of insufficiency fractures and development of avascular necrosis. Clinical assessments and patient reported outcomes would help to identify any associated adverse effects of treatment and quality of life outcomes.
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Radiation-induced acute toxicities after image-guided intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy for patients with spinal metastases (IRON-1 trial) : First results of a randomized controlled trial.
Sprave, T, Verma, V, Förster, R, Schlampp, I, Bruckner, T, Bostel, T, Welte, SE, Tonndorf-Martini, E, El Shafie, R, Nicolay, NH, et al
Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]. 2018;(10):911-920
Abstract
PURPOSE Radiation therapy (RT) provides an important treatment approach in the palliative care of vertebral metastases, but radiation-induced toxicities in patients with advanced disease and low performance status can have substantial implications for quality of life. Herein, we prospectively compared toxicity profiles of intensity-modulated radiotherapy (IMRT) vs. conventional three-dimensional conformal radiotherapy (3DCRT). METHODS This was a prospective randomized monocentric explorative pilot trial to compare radiation-induced toxicity between IMRT and 3DCRT for patients with spinal metastases. A total of 60 patients were randomized between November 2016 and May 2017. In both cohorts, RT was delivered in 10 fractions of 3 Gy each. The primary endpoint was radiation-induced toxicity at 3 months. RESULTS Median follow-up was 4.3 months. Two patients suffered from grade 3 acute toxicities in the IMRT arm, along with 1 patient in the 3DCRT group. At 12 weeks after treatment (t2), 1 patient reported grade 3 toxicity in the IMRT arm vs. 4 patients in the 3DCRT group. No grade 4 or 5 adverse events occurred in either group. In the IMRT arm, the most common side effects by the end of irradiation (t1) were grade 1-2 xerostomia and nausea in 8 patients each (29.6%), and dyspnea in 7 patients (25.9%). In the 3DCRT group, the most frequent adverse events (t1) were similar: grade 1-2 xerostomia (n = 10, 35.7%), esophagitis (n = 10, 35.8%), nausea (n = 10, 35.8%), and dyspnea (n = 5, 17.9%). CONCLUSION This is the first randomized trial to evaluate radiation-induced toxicities after IMRT versus 3DCRT in patients with vertebral metastases. This trial demonstrated an additional improvement for IMRT in terms of acute side effects, although longer follow-up is required to further ascertain other endpoints.
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Safety and Efficacy of Mesenchymal Stem Cells for Radiation-Induced Xerostomia: A Randomized, Placebo-Controlled Phase 1/2 Trial (MESRIX).
Grønhøj, C, Jensen, DH, Vester-Glowinski, P, Jensen, SB, Bardow, A, Oliveri, RS, Fog, LM, Specht, L, Thomsen, C, Darkner, S, et al
International journal of radiation oncology, biology, physics. 2018;(3):581-592
Abstract
BACKGROUND Salivary gland hypofunction and xerostomia are major complications to head and neck radiotherapy. This trial assessed the safety and efficacy of adipose tissue-derived mesenchymal stem cell (ASC) therapy for radiation-induced xerostomia. PATIENT AND METHODS This randomized, placebo-controlled phase 1/2 trial included 30 patients, randomized in a 1:1 ratio to receive ultrasound-guided transplantation of ASCs or placebo to the submandibular glands. Patients had previously received radiotherapy for a T1-2, N0-2A, human papillomavirus-positive, oropharyngeal squamous cell carcinoma. The primary outcome was the change in unstimulated whole salivary flow rate, measured before and after the intervention. All assessments were performed one month prior (baseline) and one and four months following ASC or placebo administration. RESULTS No adverse events were detected. Unstimulated whole salivary flow rates significantly increased in the ASC-arm at one (33%; P = .048) and four months (50%; P = .003), but not in the placebo-arm (P = .6 and P = .8), compared to baseline. The ASC-arm symptom scores significantly decreased on the xerostomia and VAS questionnaires, in the domains of thirst (-22%, P = .035) and difficulties in eating solid foods (-2%, P = .008) after four months compared to baseline. The ASC-arm showed significantly improved salivary gland functions of inorganic element secretion and absorption, at baseline and four months, compared to the placebo-arm. Core-needle biopsies showed increases in serous gland tissue and decreases in adipose and connective tissues in the ASC-arm compared to the placebo-arm (P = .04 and P = .02, respectively). MRIs showed no significant differences between groups in gland size or intensity (P < .05). CONCLUSIONS ASC therapy for radiation-induced hypofunction and xerostomia was safe and significantly improved salivary gland functions and patient-reported outcomes. These results should encourage further exploratory and confirmatory trials.
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Diagnostic Accuracy of Amino Acid and FDG-PET in Differentiating Brain Metastasis Recurrence from Radionecrosis after Radiotherapy: A Systematic Review and Meta-Analysis.
Li, H, Deng, L, Bai, HX, Sun, J, Cao, Y, Tao, Y, States, LJ, Farwell, MD, Zhang, P, Xiao, B, et al
AJNR. American journal of neuroradiology. 2018;(2):280-288
Abstract
BACKGROUND Current studies that analyze the usefulness of amino acid and FDG-PET in distinguishing brain metastasis recurrence and radionecrosis after radiation therapy are limited by small cohort size. PURPOSE Our aim was to assess the diagnostic accuracy of amino acid and FDG-PET in differentiating brain metastasis recurrence from radionecrosis after radiation therapy. DATA SOURCES Studies were retrieved from PubMed, Embase, and the Cochrane Library. STUDY SELECTION Fifteen studies were included from the literature. Each study used PET to differentiate radiation necrosis from tumor recurrence in contrast-enhancing lesions on follow-up brain MR imaging after treating brain metastasis with radiation therapy. DATA ANALYSIS Data were analyzed with a bivariate random-effects model. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were pooled, and a summary receiver operating characteristic curve was fit to the data. DATA SYNTHESIS The overall pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of PET were 0.85, 0.88, 7.0, 0.17, and 40, respectively. The area under the receiver operating characteristic curve was 0.93. On subgroup analysis of different tracers, amino acid and FDG-PET had similar diagnostic accuracy. Meta-regression analysis demonstrated that the method of quantification based on patient, lesion, or PET scan (based on lesion versus not, P = .07) contributed to the heterogeneity. LIMITATIONS Our study was limited by small sample size, and 60% of the included studies were of retrospective design. CONCLUSIONS Amino acid and FDG-PET had good diagnostic accuracy in differentiating brain metastasis recurrence from radionecrosis after radiation therapy.
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Nutrient Recommendations for Cancer Patients Treated with Pelvic Radiotherapy, with or without Comorbidities.
Castro-Eguiluz, D, Leyva-Islas, JA, Luvian-Morales, J, Martínez-Roque, V, Sánchez-López, M, Trejo-Durán, G, Jiménez-Lima, R, Leyva-Rendón, FJ
Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion. 2018;(3):130-135
Abstract
Radiotherapy is one of the main treatment options used in pelvic cancers. Ionizing radiation induces damage to surrounding tissues, resulting in disruption of normal physiological functions and symptoms such as diarrhea, tenesmus, incontinence, and rectal bleeding, which can all significantly alter the patient's quality of life. These patients are at increased risk of developing protein-calorie malnutrition and micronutrient deficiencies. Therefore, designing a proper nutritional intervention plan, with an optimal proportion of protein, fat, and carbohydrates, is required to reduce or even reverse the patients' poor nutritional status, increase their tolerance and response to oncology treatment, decrease the rate of complications and improve their quality of life. The aim of this review was to establish a nutritional plan that includes recommendations on macronutrient proportions and micronutrient intake in patients receiving pelvic radiotherapy. The following nutritional plan has been recommended in the literature: Energy: 28-31 kcal/kg/day, using the Harris-Benedict formula adjusted for body weight in obese patients; protein: 20-30%; fat: 30-40%; and carbohydrates: 40-50%. The maintenance of adequate levels of Vitamin D, Vitamin E, Vitamin A, calcium, magnesium, thiamin, riboflavin, and niacin must be emphasized. Physical activity must also be increased to maintain muscle mass. Nutrient requirements must be established in an integral manner, considering the patient's age, nutritional status, and the presence of comorbidities. Unnecessary dietary restrictions should be avoided to ensure an adequate nutritional status.