A. Guido

COMBINED 18F-FDG-PET/CT IMAGING IN RADIOTHERAPY TARGET DELINEATION FOR HEAD-AND-NECK CANCER

PURPOSE To evaluate the effect of the use of (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in radiotherapy target delineation for head-and-neck cancer compared with CT alone. METHODS AND MATERIALS A total of 38 consecutive patients with head-and-neck cancer were included in this study. The primary tumor sites were as follow: 20 oropharyngeal tumors, 4 laryngeal tumors, 2 hypopharyngeal tumors, 2 paranasal sinuses tumors, 9 nasopharyngeal tumors, and 1 parotid gland tumor. The FDG-PET and CT scans were performed with a dedicated PET/CT scanner in one session and then fused. Subsequently, patients underwent treatment planning CT with intravenous contrast enhancement. The radiation oncologist defined all gross tumor volumes (GTVs) using both the PET/CT and CT scans. RESULTS In 35 (92%) of 38 cases, the CT-based GTVs were larger than the PET/CT-based GTVs. The average total GTV from the CT and PET/CT scans was 34.54 cm(3) (range, 3.56-109) and 29.38 cm(3) (range, 2.87-95.02), respectively (p < 0.05). Separate analyses of the difference between the CT- and PET/CT-based GTVs of the primary tumor compared with the GTVs of nodal disease were not statistically significant. The comparison between the PET/CT-based and CT-based boost planning target volumes did not show a statistically significant difference. All patients were alive at the end of the follow-up period (range, 3-38 months). CONCLUSION GTVs, but not planning target volumes, were significantly changed by the implementation of combined PET/CT. Large multicenter studies are needed to ascertain whether combined PET/CT in target delineation can influence the main clinical outcomes.

EFFECTS OF PROBIOTICS FOR THE PREVENTION AND TREATMENT OF RADIATION-INDUCED DIARRHEA

Background and Aims Probiotic supplementation seems to provide beneficial effects in the prevention and treatment of radiation-induced diarrhea. We performed a systematic review and meta-analysis to estimate the efficacy of probiotic supplementation for prevention and treatment of radiation-induced diarrhea. Methods Two reviewers independently searched PubMed, EMBASE, Cochrane Library, Google Scholar and on-line clinical trials registers (up to January 2009) for randomized controlled trials that evaluated the efficacy of probiotic supplementation for the prevention and treatment of radiation-induced diarrhea. Each clinical trial was separately evaluated for study characteristics, methodologic quality and outcomes. Results of the randomized controlled trials were pooled in a meta-analysis. Results Four randomized controlled trials were included. Three clinical trials, with a total of 632 subjects, evaluated the preventive effects of probiotic supplementation and 1 study evaluated the therapeutic role. Random effects meta-analysis of the preventive trials did not show significant differences between probiotic supplementation and control groups (odds ratio 0.47; 95% confidence interval: 0.13-1.67). However, the few available trials and the presence of significant clinical and statistical heterogeneity limited the analysis. Similarly, the therapeutic clinical trial did not show significant differences between active and placebo groups. No major adverse events owing to probiotic supplementation were reported in any study. Conclusions Probiotic supplementation showed beneficial effect in the prevention and treatment of radiation-induced diarrhea in experimental animal studies. Encouraging results have been observed in humans; however, the few available clinical studies do not allow firm conclusions. More well-performed, randomized placebo-controlled studies are needed.

Evaluating the influence of the Siemens IGRT carbon fibre tabletop in head and neck IMRT

BACKGROUND AND PURPOSE To investigate the impact of a commercial IMRT/IGRT carbon-fibre tabletop in radiotherapy planning optimization and clinical dose distribution. MATERIALS AND METHODS In this investigation the Siemens IGRT carbon fibre tabletop, routinely used for IMRT treatments in our Centre, has been incorporated into the CT volume of 6 IMRT patients. This was done by CT scanning the tabletop and by adding the obtained volume to the clinical dataset, acquired using the standard couch available in our CT scanner. This procedure was tested and validated for the purpose of this study. The radiotherapy plans have been optimized using both the original CT volume and the modified CT volume. RESULTS IMRT optimization with the tabletop included in the clinical volume produced significantly different deliverable plans compared to standard optimized plans which did not include the treatment couch. Differences up to 6%/7% in terms of total number of MU were found in half of the clinical cases. Differences up to 37% in the number of MU per beam were also found. The number of iterations needed to reach an optimal solution also varied between -18% and +25%. Although the DVH analysis produced similar results, due to the fulfilment of the optimization objectives, differences higher than 10% were found in the dose calculated to superficial regions of the body. CONCLUSIONS The results of this investigation show that the presence of the carbon fibre tabletop significantly affects the outcome of the beam parameters optimization. We suggest including carbon fibre tabletops into patient treatment planning dose calculation and optimization.

Gamma rays induce a p53-independent mitochondrial biogenesis that is counter-regulated by HIF1α

Mitochondrial biogenesis is an orchestrated process that presides to the regulation of the organelles homeostasis within a cell. We show that γ-rays, at doses commonly used in the radiation therapy for cancer treatment, induce an increase in mitochondrial mass and function, in response to a genotoxic stress that pushes cells into senescence, in the presence of a functional p53. Although the main effector of the response to γ-rays is the p53-p21 axis, we demonstrated that mitochondrial biogenesis is only indirectly regulated by p53, whose activation triggers a murine double minute 2 (MDM2)-mediated hypoxia-inducible factor 1α (HIF1α) degradation, leading to the release of peroxisome-proliferator activated receptor gamma co-activator 1β inhibition by HIF1α, thus promoting mitochondrial biogenesis. Mimicking hypoxia by HIF1α stabilization, in fact, blunts the mitochondrial response to γ-rays as well as the induction of p21-mediated cell senescence, indicating prevalence of the hypoxic over the genotoxic response. Finally, we also show in vivo that post-radiotherapy mitochondrial DNA copy number increase well correlates with lack of HIF1α increase in the tissue, concluding this may be a useful molecular tool to infer the trigger of a hypoxic response during radiotherapy, which may lead to failure of activation of cell senescence.

Randomised clinical trial: preventive treatment with topical rectal beclomethasone dipropionate reduces post‐radiation risk of bleeding in patients irradiated for prostate cancer

Aliment Pharmacol Ther 2011; 34: 628–637

Volumetric modulated arc therapy for treatment of solid tumors: current insights

Aim This article discusses the current use of volumetric modulated arc therapy (VMAT) techniques in clinical practice and reviews the available data from clinical outcome studies in different clinical settings. An overview of available literature about clinical outcomes with VMAT stereotactic/radiosurgical treatment is also reported. Materials and methods All published manuscripts reporting the use of VMAT in a clinical setting from 2009 to November 2016 were identified. The search was carried out in December 2016 using the National Library of Medicine (PubMed/Medline). The following words were searched: “volumetric arc therapy”[All Fields] OR “vmat”[All Fields] OR “rapidarc”[All Fields], AND “radiotherapy”[All Fields] AND “Clinical Trial”[All Fields]. Results Overall, 37 studies (21 prospective and 16 retrospective) fulfilling inclusion criteria and thus included in the review evaluated 2,029 patients treated with VMAT; of these patients, ~30.8% had genitourinary (GU) tumors (81% prostate, 19% endometrial), 26.2% head-and-neck cancer (H&NC), 13.9% oligometastases, 11.2% had anorectal cancer, 10.6% thoracic neoplasms (81% breast, 19% lung), and 7.0% brain metastases (BMs). Six different clinical scenarios for VMAT use were identified: 1) BMs, 2) H&NC, 3) thoracic neoplasms, 4) GU cancer, 5) anorectal tumor, and 6) stereotactic body radiation therapy (SBRT) performed by VMAT technique in the oligometastatic patient setting. Conclusion The literature addressing the clinical appropriateness of VMAT is scarce. Current literature suggests that VMAT, especially when used as simultaneous integrated boost or SBRT strategy, is an effective safe modality for all cancer types.

Prevention of pelvic radiation disease

Pelvic cancers are among the most frequently diagnosed cancers worldwide. Treatment of patients requires a multidisciplinary approach that frequently includes radiotherapy. Gastrointestinal (GI) radiation-induced toxicity is a major complication and the transient or long-term problems, ranging from mild to very severe, arising in non-cancerous tissues resulting from radiation treatment to a tumor of pelvic origin, are actually called as pelvic radiation disease. The incidence of pelvic radiation disease changes according to the radiation technique, the length of follow up, the assessment method, the type and stage of cancer and several other variables. Notably, even with the most recent radiation techniques, i.e., intensity-modulated radiotherapy, the incidence of radiation-induced GI side effects is overall reduced but still not negligible. In addition, radiation-induced GI side effects can develop even after several decades; therefore, the improvement of patient life expectancy will unavoidably increase the risk of developing radiation-induced complications. Once developed, the management of pelvic radiation disease may be challenging. Therefore, the prevention of radiation-induced toxicity represents a reasonable way to avoid a dramatic drop of the quality of life of these patients. In the current manuscript we provide an updated and practical review on the best available evidences in the field of the prevention of pelvic radiation disease.

EUS-guided gold fiducial placement and migration rate

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Management of Radiation-Induced Rectal Bleeding

Pelvic radiation disease is one of the major complication after radiotherapy for pelvic cancers. The most commonly reported symptom is rectal bleeding which affects patients’ quality of life. Therapeutic strategies for rectal bleeding are generally ignored and include medical, endoscopic, and hyperbaric oxygen treatments. Most cases of radiation-induced bleeding are mild and self-limiting, and treatment is normally not indicated. In cases of clinically significant bleeding (i.e. anaemia), medical therapies, including stool softeners, sucralfate enemas, and metronidazole, should be considered as first-line treatment options. In cases of failure, endoscopic therapy, mainly represented by argon plasma coagulation and hyperbaric oxygen treatments, are valid and complementary second-line treatment strategies. Although current treatment options are not always supported by high-quality studies, patients should be reassured that treatment options exist and success is achieved in most cases if the patient is referred to a dedicated centre.

Brachytherapy for the palliation of dysphagia owing to esophageal cancer: A systematic review and meta-analysis of prospective studies

BACKGROUND The management of dysphagia owing to esophageal cancer is challenging. Brachytherapy has been proposed as an alternative option to stent placement. We performed a systematic review to examine its efficacy and safety in the resolution of dysphagia. METHODS Prospective studies recruiting at least 20 patients with malignant dysphagia and published up to April 2016 were eligible. The dysphagia-free survival (DFS) and adverse event rates were pooled by means of a random effect model. RESULTS Six studies for a total of 9 treatment arms (623 patients) were eligible for inclusion. After 1month since treatment, the DFS rate was 86.9% [95%CI: 76.0-93.3%]; after 3months, it was 67.2% [95%CI: 56.1-76.7%]; after 6months, it was 47.4% [95%CI: 38.5-56.5%]; after 9months, it was 37.6% [95%CI:30.0-45.9%]; and, finally, after 12months, it was 29.4% [95%CI: 21.6-38.7%]. The heterogeneity between studies was high at 1-, 3- and 6-month assessment; the values of I2 were 86.3%, 80.0% and 57.8%, respectively. The meta-regression analysis showed total radiation dose and number of fractions as the only positively influencing factors. Severe adverse event rate was 22.6% (95%CI 19.4-26.3). The main reported adverse events were brachytherapy-related stenosis (12.2%) and fistula development (8.3%). Two cases (0.3%) of deaths were reported due to esophageal perforation. CONCLUSION Brachytherapy is a highly effective and relatively safe treatment option therefore its underuse is no longer justified. Further studies should investigate the optimal radiation dose and number of fractions able to achieve the highest DFS rates.