-
1.
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.
-
2.
Pharmacological modulation of radiation-induced oral mucosal complications.
Bockel, S, Vallard, A, Lévy, A, François, S, Bourdis, M, Le Gallic, C, Riccobono, D, Annede, P, Drouet, M, Tao, Y, et al
Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique. 2018;(5):429-437
Abstract
Radiation-induced mucositis is a common toxicity, especially in patients with head and neck cancers. Despite recent technological advances in radiation therapy, such as intensity-modulated radiotherapy, radiation-induced mucositis is still causing treatment disruptions, negatively affecting patients' long and short term quality of life, and impacting medical resources use with economic consequences. The objective of this article was to review the latest updates in the management of radiation-induced mucositis, with a focus on pharmaceutical strategies for the prevention or treatment of mucositis. Although numerous studies analysing the prevention and management of oral radiation-induced mucositis have been conducted, there are still few reliable data to guide daily clinical practice. Furthermore, most of the tested drugs have shown no (anti-inflammatory cytokine, growth factors) or limited (palifermin) effect. Therapies for acute oral mucositis are predominantly focused on improving oral hygiene and providing symptoms control. Although low-level laser therapy proved efficient in preventing radiation-induced oral mucositis in patients with head and neck cancer, this intervention requires equipment and trained medical staff, and is therefore insufficiently developed in clinical routine. New effective pharmacological agents able to prevent or reverse radio-induced mucositis are required.
-
3.
Efficacy of the combination neurokinin-1 receptor antagonist, palonosetron, and dexamethasone compared to others for the prophylaxis of chemotherapy-induced nausea and vomiting: a systematic review and meta-analysis of randomized controlled trials.
Chow, R, Tsao, M, Chiu, L, Popovic, M, Milakovic, M, Lam, H, DeAngelis, C
Annals of palliative medicine. 2018;(2):221-233
Abstract
BACKGROUND Chemotherapy-induced nausea and vomiting (CINV), a common side effect of chemotherapy, can substantially impair a patient's quality of life, interfere with a patient's compliance with anticancer therapy, and result in the manifestation of adverse events such as electrolyte imbalance, dehydration and malnutrition. The most recent guidelines published by the Multinational Association of Supportive Care in Cancer (MASCC) and European Society of Medical Oncology (ESMO) recommend the combination of dexamethasone (DEX), a 5-hydroxytrypatmine-3 receptor antagonist (5-HT3RA), preferably palonosetron (PALO), and a neurokinin-1 receptor antagonist (NK1RA) for prophylactic treatment of CINV in patients receiving highly emetogenic chemotherapy (HEC). The aim of this review was to examine the efficacy of triple agent, as reported in randomized controlled trials (RCTs), compared to any other prophylactic treatments. METHODS A literature search was conducted in Ovid MEDLINE(R), Embase Classic & Embase, and the Cochrane Central Register of Controlled Trials. The primary endpoint was the proportion of patients achieving complete response (CR) in the acute, delayed and overall phase. Secondary endpoints included the percentage of patients who achieved complete control (CC), no nausea and no vomiting in the acute, delayed and overall phases. RESULTS A total of 17 RCTs were included in this review, of which 3,146 patients were randomized to receive NK1RA, PALO and DEX, and 2,987 patients to receive other antiemetic treatments. The combination was not superior to other treatments in five endpoints-CC and CR in the acute phase, nausea and emesis control in the delayed phase, and nausea in the overall phase-but was superior in the other 11 endpoints. When looking only at HEC and moderately emetogenic chemotherapy (MEC) studies, the combination was only superior to others in three endpoints (delayed and overall CC, and overall emesis control) in HEC setting, which is less than the nine identified endpoints (delayed and overall CR, delayed and overall CC, acute and overall nausea control, and acute, delayed and overall phases for emesis control) in the MEC setting. CONCLUSIONS The combination of NK1RA, PALO and DEX is superior in the majority of assessed endpoints of this meta-analysis. Further studies should investigate the efficacy and safety of the triple regimen compared to regimens lacking NK1RA, to add to the discussions about whether future CINV prophylaxis guidelines should include NK1RA as a first-line treatment in the MEC setting.
-
4.
Nutritional strategies to prevent gastrointestinal toxicity during pelvic radiotherapy.
Wedlake, LJ
The Proceedings of the Nutrition Society. 2018;(4):357-368
Abstract
Radiotherapy-induced damage to non-cancerous gastrointestinal mucosa has effects on secretory and absorptive functions and can interfere with normal gastrointestinal physiology. Nutrient absorption and digestion may be compromised. Dietary manipulation is an attractive option with sound rationale for intervention. The aim of this review was to synthesise published evidence for the use of elemental formulae, low or modified fat diets, fibre, lactose restriction and probiotics, prebiotics and synbiotics to protect the bowel from gastrointestinal side effects during long-course, radical pelvic radiotherapy. Thirty original studies (recruiting n 3197 patients) were identified comprising twenty-four randomised controlled trials, four cohort studies and two comparator trials. Endpoints varied and included symptom scales (Inflammatory Bowel Disease Questionnaire, Common Technology Criteria for Adverse Events, Radiation Therapy Oncology Group) and Bristol Stool Scale. Dietary and supplement interventions were employed with many studies using a combination of interventions. Evidence from RCT was weak for elemental, low or modified fat and low-lactose interventions and modestly positive for the manipulation of fibre during radiotherapy. Evidence for probiotics as prophylactic interventional agents was more promising with a number of trials reporting positive results but strength and strains of interventions vary, as do methodologies and endpoints making it difficult to arrive at firm conclusions with several studies lacking statistical power. This consolidated review concludes that there is insufficient high-grade evidence to recommend nutritional intervention during pelvic radiotherapy. Total replacement of diet with elemental formula could be effective in severe toxicity but this is unproven. Probiotics offer promise but cannot be introduced into clinical practice without rigorous safety analysis, not least in immunocompromised patients.
-
5.
Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II.
Dietz, A, Wichmann, G, Kuhnt, T, Pfreundner, L, Hagen, R, Scheich, M, Kölbl, O, Hautmann, MG, Strutz, J, Schreiber, F, et al
Annals of oncology : official journal of the European Society for Medical Oncology. 2018;(10):2105-2114
-
-
Free full text
-
Abstract
BACKGROUND The German multicenter randomized phase II larynx organ preservation (LOP) trial DeLOS-II was carried out to prove the hypothesis that cetuximab (E) added to induction chemotherapy (IC) and radiotherapy improves laryngectomy-free survival (LFS; survival with preserved larynx) in locally advanced laryngeal/hypopharyngeal cancer (LHSCC). PATIENTS AND METHODS Treatment-naïve patients with stage III/IV LHSCC amenable to total laryngectomy (TL) were randomized to three cycles IC with TPF [docetaxel (T) and cisplatin (P) 75 mg/m2/day 1, 5-FU (F) 750 mg/m2/day days 1-5] followed by radiotherapy (69.6 Gy) without (A) or with (B) standard dose cetuximab for 16 weeks throughout IC and radiotherapy (TPFE). Response to first IC-cycle (IC-1) with ≥30% endoscopically estimated tumor surface shrinkage (ETSS) was used to define early responders; early salvage TL was recommended to non-responders. The primary objective was 24 months LFS above 35% in arm B. RESULTS Of 180 patients randomized (July 2007 to September 2012), 173 fulfilled eligibility criteria (A/B: larynx 44/42, hypopharynx 41/46). Because of 4 therapy-related deaths among the first 64 randomized patients, 5-FU was omitted from IC in the subsequent 112 patients reducing further fatal toxicities. Thus, IC was TPF in 61 patients and TP in 112 patients, respectively. The primary objective (24 months LFS above 35%) was equally met by arms A (40/85, 47.1%) as well as B (41/88, 46.6%). One hundred and twenty-three early responders completed IC+RT; their overall response rates (TPF/TP) were 94.7%/87.2% in A versus 80%/86.0% in B. The 24 months overall survival (OS) rates were 68.2% and 69.3%. CONCLUSIONS Despite being accompanied by an elevated frequency in adverse events, the IC with TPF/TP plus cetuximab was feasible but showed no superiority to IC with TPF/TP regarding LFS and OS at 24 months. Both early response and 24 months LFS compare very well to previous LOP trials and recommend effective treatment selection and stratification by ETSS. CLINICAL TRIAL INFORMATION NCT00508664.
-
6.
The effect of the use of thyme honey in minimizing radiation - induced oral mucositis in head and neck cancer patients: A randomized controlled trial.
Charalambous, M, Raftopoulos, V, Paikousis, L, Katodritis, N, Lambrinou, E, Vomvas, D, Georgiou, M, Charalambous, A
European journal of oncology nursing : the official journal of European Oncology Nursing Society. 2018;:89-97
Abstract
PURPOSE Radiation-induced oral mucositis is one of the main side effects during and after the treatment of head and neck cancer patients. The study was designed to provide evidence on the effectiveness of thyme honey on oral mucositis management. METHODS This was a randomised controlled trial (RCT) with 72 head and neck cancer patients who were divided either to the intervention group (thyme honey rinses) or to the control group (saline rinses). Oral mucositis was assessed according to the Radiation Therapy Oncology Group (RTOC criteria), and assessments were performed weekly starting at the 4th week of the radiotherapy for seven weeks and repeated once 6 months later. Additionally, the Oral Mucositis Weekly Questionnaire (OMWQ) was given at 4th week of radiotherapy, 1 month after the completion of radiotherapy and 6 months later. The ClinicalTrials.gov Identifier for this study is NCT01465308. This paper reports on the findings regarding thyme honey's effectiveness on oral mucositis. RESULTS Generalized estimating equations revealed that patients in the intervention group were graded lower in the objective assessment of oral mucositis (p < 0,001), maintained their body weight (p < 0,001) and showed an improvement in their global health (p = 0.001) compared to the control group. Quality of life of the patients in the same group was also statistically significantly higher than that of the patients of the control group (p < 0,001). CONCLUSION The study provided evidence on the positive effect of thyme honey on the management of radiation-induced oral mucositis and quality of life in head and neck cancer patients.
-
7.
Union of light ion therapy centers in Europe (ULICE EC FP7) - Objectives and achievements of joint research activities.
Pötter, R, Balosso, J, Baumann, M, Bert, C, Davies, J, Enghardt, W, Fossati, P, Harris, S, Jones, B, Krämer, M, et al
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 2018;(1):83-100
Abstract
Under the umbrella of the European Network for Light Ion Therapy (ENLIGHT), the project on Union of Light Ion Centers in Europe (ULICE), which was funded by the European Commission (EC/FP7), was carried out from 2009 to 2014. Besides the two pillars on Transnational Access (TNA) and Networking Activities (NA), six work packages formed the pillar on Joint Research Activities (JRA). The current manuscript focuses on the objectives and results achieved within these research work packages: "Clinical Research Infrastructure", "Biologically Based Expert System for Individualized Patient Allocation", "Ion Therapy for Intra-Fractional Moving Targets", "Adaptive Treatment Planning for Ion Radiotherapy", "Carbon Ion Gantry", "Common Database and Grid Infrastructures for Improving Access to Research Infrastructures". The objectives and main achievements are summarized. References to either publications or open access deliverables from the five year project work are given. Overall, carbon ion radiotherapy is still not as mature as photon or proton radiotherapy. Achieved results and open questions are reflected and discussed in the context of the current status of carbon ion therapy and particle and photon beam therapy. Most research topics covered in the ULICE JRA pillar are topical. Future research activities can build upon these ULICE results. Together with the continuous increase in the number of particle therapy centers in the last years ULICE results and proposals may contribute to the further growth of the overall particle therapy field as foreseen with ENLIGHT and new joint initiatives such as the European Particle Therapy Network (EPTN) within the overall radiotherapy community.
-
8.
Randomized Trial Comparing Resection of Primary Tumor with No Surgery in Stage IV Breast Cancer at Presentation: Protocol MF07-01.
Soran, A, Ozmen, V, Ozbas, S, Karanlik, H, Muslumanoglu, M, Igci, A, Canturk, Z, Utkan, Z, Ozaslan, C, Evrensel, T, et al
Annals of surgical oncology. 2018;(11):3141-3149
Abstract
BACKGROUND The MF07-01 trial is a multicenter, phase III, randomized, controlled study comparing locoregional treatment (LRT) followed by systemic therapy (ST) with ST alone for treatment-naïve stage IV breast cancer (BC) patients. METHODS At initial diagnosis, patients were randomized 1:1 to either the LRT or ST group. All the patients were given ST either immediately after randomization or after surgical resection of the intact primary tumor. RESULTS The trial enrolled 274 patients: 138 in the LRT group and 136 in the ST group. Hazard of death was 34% lower in the LRT group than in the ST group (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.49-0.88; p = 0.005). Unplanned subgroup analyses showed that the risk of death was statistically lower in the LRT group than in the ST group with respect to estrogen receptor (ER)/progesterone receptor (PR)(+) (HR 0.64; 95% CI 0.46-0.91; p = 0.01), human epidermal growth factor 2 (HER2)/neu(-) (HR 0.64; 95% CI 0.45-0.91; p = 0.01), patients younger than 55 years (HR 0.57; 95% CI 0.38-0.86; p = 0.007), and patients with solitary bone-only metastases (HR 0.47; 95% CI 0.23-0.98; p = 0.04). CONCLUSION In the current trial, improvement in 36-month survival was not observed with upfront surgery for stage IV breast cancer patients. However, a longer follow-up study (median, 40 months) showed statistically significant improvement in median survival. When locoregional treatment in de novo stage IV BC is discussed with the patient as an option, practitioners must consider age, performance status, comorbidities, tumor type, and metastatic disease burden.
-
9.
A Perspective on the Evolving Story of PSMA Biology, PSMA-Based Imaging, and Endoradiotherapeutic Strategies.
O'Keefe, DS, Bacich, DJ, Huang, SS, Heston, WDW
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2018;(7):1007-1013
Abstract
In this review, we cover the evolution of knowledge on the biology of prostate-specific membrane antigen (PSMA) and its translation to therapy. The usual key to discovery is a realistic model for experimentation and for testing a hypothesis. A realistic model is especially needed in the case of the human prostate, which differs significantly from the prostate of species often used as research models. We will emphasize the genetic characterization of PSMA, the nature of the PSMA protein, and its role as a carboxypeptidase, with differing important substrates and products in different tissues. We give special prominence to the importance of PSMA as a target for imaging and therapy in prostate cancer and its underdeveloped role for imaging and targeting the neovasculature of tumors other than prostate cancer. Lastly, we bring attention to its importance in other nonprostatic tissues.
-
10.
The role of adjuvant probiotics to attenuate intestinal inflammatory responses due to cancer treatments.
Thomsen, M, Clarke, S, Vitetta, L
Beneficial microbes. 2018;(6):899-916
Abstract
Chemotherapy and radiotherapy treatment regimens for gastrointestinal, peritoneal and pelvic tumours can disrupt the intestinal microbiome and intestinal epithelia. Such disturbances can provoke symptoms such as diarrhoea, nausea and vomiting. Chemotherapy and radiotherapy induced gastrointestinal toxicity aggravating intestinal microbiome dysbiosis is postulated to adversely alter the intestinal microbiome, with a consequent induced pro-inflammatory effect that disrupts the intestinal microbiome-epithelia-mucosal immunity axis. Although not widely recognised, the intestinal mucosa is the largest and most densely and dynamically populated immune-environment. Cancer treatment adverse effects that affect intestinal and mucosal cells inadvertently target and disrupt resident intestinal macrophages, the cells that marshal immune activity in the intestinal mucosa by shaping pro-inflammatory and anti-inflammatory activities to control and eradicate infectious insults and maintain local homeostasis. Pathobionts (bacteria capable of pathogenic pro-inflammatory activity) and noxious environmental and bacterial antigens use the intestinal epithelia and gap junctions as a point of entry into the systemic circulation. This translocation movement promotes toxic sequelae that obstruct intestinal macrophage functions resulting in uncontrolled local and systemic pro-inflammatory activity, loss of phagocytic function and loss of expression of tight junction proteins. Probiotic bacteria as an adjunctive treatment shows efficacy in ameliorating enteropathies such as mucositis/diarrhoea resulting from chemotherapy or radiotherapy regimens. As such we posit that an important benefit that warrants a further focused research effort is the administration of adjuvant probiotics to help reduce the incidence of febrile neutropenia.