Intensity modulated radiation therapy and oral mucosa sparing in Head and neck cancer patients: A systematic review on behalf of Italian Association of Radiation Oncology - Head and neck working group.

Oral mucositis is a common dose-limiting toxicity during radiotherapy with or without chemotherapy in head and neck cancer patients. This potentially severe complication globally worsens quality of life and negatively impacts local control and survival's outcomes. Several studies have been published on feasibility and/or clinical benefit of intensity modulated radiotherapy (IMRT) mucosa-sparing technique. In 2017, the Italian Association of Radiation Oncology Head and Neck Cancer Working Group organized a study group to perform a systematic review. The aim was to verify if practical indications, including dose-constraints and demonstrated clinical benefit, could be proposed for oral mucosa (OM)-sparing IMRT in order to reduce the incidence of severe acute mucositis. Although dose to OM should be reduced as much as possible without compromising target volumes coverage, it is still tricky to firmly state that OM-sparing procedure should be considered the standard of care, especially due to high subjective variability in OM contour.

Hippocampal sparing in stereotactic radiotherapy for brain metastases: To contour or not contour the hippocampus?

PURPOSE: The aim of our study was to evaluate hippocampal irradiation in patients treated with fractionated stereotactic brain radiotherapy. PATIENTS AND METHODS: Retrospective hippocampal dosimetric analysis performed on 22 patients with one to four brain metastases treated with fractionated stereotactic radiotherapy using volumetric intensity-modulated arc therapy. Original plans did not include hippocampus as avoidance structure in optimization criteria; hippocampus was retrospectively delineated on magnetic resonance coregistered with planning CT and using as reference the RTOG 0933 atlas. Hippocampus was defined both as a single and as pair organ. Constraints analysed were: Dmax<16Gy, D40%<7.3Gy, D100%=Dmin<9Gy. Assuming a α/ß ratio of 2Gy, biologically equivalent dose in 2Gy fractions was calculated. Hippocampal-sparing plans were developed in cases where hippocampal constraints were not respected in the original plan. RESULTS: Among constraints analysed Dmax and D40% have been exceeded in ten out of 22 cases. The constraints were not respected in patients with more than one metastatic lesion and in three patients with only one lesion. Considering all exceeded constraints values in non-hippocampal sparing plans, the 50% of them was respected after replanning. No significant differences were found among conformity and homogeneity index between non-hippocampal sparing and hippocampal sparing plans. CONCLUSION: Volumetric intensity-modulated arc therapy hippocampal sparing plans significantly decreases dose to hippocampus assuring an equal target coverage and organs at risk avoiding.

Effects of Pycnogenol® on endothelial dysfunction in borderline hypertensive, hyperlipidemic, and hyperglycemic individuals: the borderline study.

AIM: This registry study aimed to evaluate the effects of supplementation with pycnogenol on altered endothelial function (EF) in borderline hypertensive, hyperlipidemic and hyperglycemic subjects without atherosclerotic changes in their main arteries and no coronary artery disease. METHODS: Flow mediated dilatation (FMD) and endothelium-independent (EID) dilatation were measured with brachial ultrasound after occlusion. Also, after occlusion, laser Doppler (LDF) flux and distal straingauge flow were measured. Oxidative stress (oxstress) was evaluated at 8 and 12 weeks. 93 subjects with borderline symptoms were enrolled into the study: 32 hypertensives, 31 hyperlipidemics, 30 hyperglycemics. All participants were instructed to follow the best available management to control their symptoms. In addition to best management, half of the subjects in each group used 150 mg/day Pycnogenol(®). 31 normal subjects were included as control. RESULTS: After 12 weeks metabolic values and blood pressure were back to normal in all subjects. Values were slightly better under Pycnogenol(®). FMD increased after 8 weeks from an average 5.3;3.4% to 8.2;2.2% with a further increase to 8.8;3.1% (P<0.05) at 12 weeks. No effects were found in controls and normal subjects. EID of normal subjects was consistently higher with 26%. LDF skin flux increased with Pycnogenol(®) at 8 weeks and 12 weeks. The final flux increase was not different from normal values. In controls flux after occlusion was not improved at 8 weeks; there was a significant but minor increase at 12 weeks. Flux increases were superior in all Pycnogenol(®) subjects. In Pycnogenol(®) subjects, limb flow after occlusion increased at 8 weeks with a further increase at 12 weeks. In controls inclusion flow after occlusion was comparable at 8 and 12 weeks. Oxidative stress was significantly decreased in Pycnogenol(®) subjects at 8 and 12 weeks. Minor differences were observed in controls. CONCLUSION: This open registry study indicates that Pycnogenol(®) improves EF in preclinical, borderline subjects in a macro-microcirculatory model. This observation may suggest an important preventive possibility for borderline hypertensive, hyperglycemic and hyperlipidemic subjects.

Robuvit® (French oak wood extract) in the management of functional, temporary hepatic damage. A registry, pilot study.

AIM: The aim of this registry study was to evaluate the evolution of moderate functional hepatic failure (MTHF) using a proprietary new oak wood supplement (Robuvit®) extracted from Quercus Robur. Recent studies have indicated the protective effect of oak wood extracts on liver injury. Quercus wood extracts have shown hepatoprotective effect on initial induced liver-injury. METHODS: This registry included a total of 75 patients with MTHF characterized by: decreased albumin levels; increased total bilirubin, altered hepatic functions enzymes, increased oxidative stress, negative viral hepatitis markers. RESULTS: The two groups (best management in comparison with best management+ Robuvit®) were comparable: 32 Robuvit® patients and 29 comparable controls) completed the 12-week registry. At inclusion, the blood parameter values in the two groups were comparable. At the end of the supplementation period, the increase in albumin levels was significantly (P<0.05 at 12 weeks) faster and higher in the Robuvit® group. The decrease in ALT-SGPT and AST-ASAT was significant in the supplement group (P<0.05 at 4 and 12 weeks); the tests were normalized at 4 and 12 weeks. Controls remained out of the normal range for more than 12 weeks. Alkaline phosphatase was normalized at 4 and 12 weeks in Robuvit® patients; they were decreased, but not normalized in controls at 4 weeks (Robuvit® group's values were significantly better; P<0.05). Values were normalized in controls (significantly higher in comparison with Robuvit®; P<0.05) at 12 weeks. Total bilirubin was normalized in Robuvit® subjects at 4 and 12 weeks. Results were significantly better in comparison with controls (P<0.05). Direct bilirubin values increased more in the Robuvit® group at 4 and 12 weeks (P<0.05). Gamma GT values were normalized at 4 and 12 weeks in the Robuvit® group. There was a less important decrease in controls (P<0.05) without normalization at 12 weeks. Plasma free radicals increased at inclusion showed a significant decrease in Robuvit® subject (at 4 and 12 weeks) with normalization at 12 weeks. Persisting, elevated values in controls were observed even at 12 weeks (P<0.05). ESR and CRP decreased in both groups with a more important decrease in the Robuvit® group (P<0.05). Hepatitis markers were negative when repeated at 4 and 12 weeks. CONCLUSION: Data from this pilot, supplement registry study indicate a significant protective activity of Robuvit®, associated with a very good safety profile, in patients with temporary hepatic failure. The activity of Robuvit® seems to be mediated by its anti-inflammatory activity.

Interobserver variability of clinical target volume delineation in soft-tissue sarcomas.

PURPOSE: The present observational study reports the results of a multi-institutional dummy-run designed to estimate the consistency of interobserver variability in clinical target volume delineation in two different cases of soft-tissue sarcomas in which postoperative and preoperative radiotherapy were prescribed, respectively. The purpose of this work was to quantify interobserver variability in routine clinical practice. PATIENTS AND METHODS: Two different cases of soft-tissues sarcomas were chosen: a case of postoperative and a case of preoperative radiation therapy. Participating centres were requested to delineate clinical target volumes according to their experience in both cases. Descriptive statistic was calculated for each variable (volume, diameters) separately for two cases. Box-whiskers plots were used for presentation of clinical target volume. A Shapiro-Wilk's test was performed to evaluate the departures from normality distribution for each variable. The comparison between relative variations of diameters was evaluated using the Student's t test. RESULTS: Several variations affecting both volumes and diameters were observed. Main variations were observed in the craniocaudal and laterolateral diameters. Each case showed similar dispersion, indicating a lack of reproducibility in volumes definition. CONCLUSIONS: This observational study highlighted that, in the absence of specific instructions or guidelines, the interobserver variability can be significant both in postoperative and preoperative radiotherapy of soft-tissue sarcomas.

Diffusion-weighted magnetic resonance for prediction of response after neoadjuvant chemoradiation therapy for locally advanced rectal cancer: preliminary results of a monoinstitutional prospective study.

PURPOSE: To evaluate diffusion-weighted imaging (DWI) for assessment of treatment response in locally advanced rectal cancer (LARC) 8 weeks after neoadjuvant chemoradiotherapy (CRT). METHODS AND MATERIALS: A total of 28 patients with LARC underwent magnetic resonance imaging (MRI) prior to and 8 weeks after CRT. Tumor volume (TV) was calculated on T2-weighted MRI scans as well as the apparent diffusion coefficient (ADC) was calculated using Echo-planar DWI-sequences. All data were correlated to surgical results and histopathologic tumor regression grade (TRG), according to Mandard's classification. Post-treatment difference ADC (%ΔADC) and TV (%ΔTV) changes at 8 weeks were compared complete response (CR; TRG1) and non-complete response tumors (non-CR; TRG2-5). RESULTS: The mean % ADC increase of CR group was significantly higher compared to non-CR group (77.2 ± 54.63% vs. 36.0 ± 29.44%; p = 0.05). Conversely, the mean % TV reduction did not significantly differ in CR group from non-CR group (73.7% vs. 63.77%; p = 0.21). Accordingly, the diagnostic accuracy of the mean % ADC increase to discriminate CR from non-CR group was significantly higher than that of the mean % TV reduction (0.913 vs. 0.658; p = 0.022). No correlation was found between mean % TV reduction and TRG (rho = 0.22; p = 0.3037), whereas a negative correlation between mean % ADC increase and TRG was recorded (r = -0.69; p = 0.006). CONCLUSION: The mean % ADC increase appears to be a reliable tool to differentiate CR from non-CR after CRT in patients with LARC.