Evaluation of radiodensity and dimensional stability of polymeric materials used for oral stents during external beam radiotherapy of head and neck carcinomas.

Purpose Intraoral stents protect the healthy tissues from ionizing radiation during external beam radiotherapy reducing mucositis, hyposalivation and osteoradionecrosis. This study investigated the radiodensity and dimensional stability of polymeric materials for suitability in construction of intraoral stents and aimed to provide clinical guidelines. Methods Specimens were fabricated using 4 material types namely, resin composite (ProTemp-PRO), polymethylmethacrylate (PMMA) (Enamel Temp Plus-ETP, Palapress-PAL, TAB 2000-TAB), polycaprolactone (Orfit-ORF) and silicone (Adisil-ADI, Lab Putty-LAB, Memosil2-MEM, Optosil-OPT, President Plus-PRE, Siolaplast A-SIA). They were randomly assigned to measure their radiodensity in Hounsfield Units (HU) (12x12x11mm3) (Nradiodensity = 66; n = 6) using a computer tomograph (CBCT, Toshiba Aquillon LB scanner) at baseline and after 6 weeks. The scanning protocol was applied with and without single energy metal artifact reduction (SEMAR) scans using a slice thickness of 1 and 5 mm. The same materials have been tested for their dimensional stability (µm3) at baseline, 1, 6, 12, 24 h, 3 and 6 weeks (14 × 4 × 2 mm3) (Ndimension = 55; n = 5 per material) using stereolithography (STL) files generated by a lab scanner (L2i, Imetric4D, Courgenay, Switzerland) and analyzed using a matching software (Geomagic ControlX 2020, 3D Systems). Data were analyzed using a paired t-test (alpha = 0.05). Results Radiodensity values (HU) were significantly affected by the material classification (p < 0.05). Polycaprolactone (43.6) presented significantly lower HU values followed by PMMA (91.3-414.9) than those of silicone materials (292.8-874.5). In terms of dimensional stability (µm3), PMMA materials (Δ:1.53-2.68) and resin composite (Δ:2.89) were significantly more dimensionally stable compared to those of silicone materials (Δ:13.64-6.63) and polycaprolactone (Δ:-0.76) and (p < 0.05). Conclusion For fabricating intraoral stents, when reduced radiodensity values are required polycaprolactone could be recommended as it fulfils the requirements for reduced radiodensity and dimensional stability. Among all silicone materials, OPT and MEM can be recommended based on the low HU and dimensional stability

Dental extraction, intensity-modulated radiotherapy of head and neck cancer, and osteoradionecrosis : A systematic review and meta-analysis

Objective: To seek evidence for osteoradionecrosis (ORN) after dental extractions before or after intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC). Methods: Medline/PubMed, Embase, and Cochrane Library were searched from 2000 until 2020. Articles on HNC patients treated with IMRT and dental extractions were analyzed by two independent reviewers. The risk ratios (RR) and odds ratios (OR) for ORN related to extractions were calculated using Fisher's exact test. A one-sample proportion test was used to assess the proportion of pre- versus post-IMRT extractions. Forest plots were used for the pooled RR and OR using a random-effects model. Results: Seven of 630 publications with 875 patients were eligible. A total of 437 (49.9%) patients were treated with extractions before and 92 (10.5%) after IMRT. 28 (3.2%) suffered from ORN after IMRT. ORN was associated with extractions in 15 (53.6%) patients, eight related to extractions prior to and seven cases related to extractions after IMRT. The risk and odds for ORN favored pre-IMRT extractions (RR = 0.18, 95% CI: 0.04-0.74, p = 0.031, I2 = 0%, OR = 0.16, 95% CI: 0.03-0.99, p = 0.049, I2 = 0%). However, the prediction interval of the expected range of 95% of true effects included 1 for RR and OR. Conclusion: Tooth extraction before IMRT is more common than after IMRT, but dental extractions before compared to extractions after IMRT have not been proven to reduce the incidence of ORN. Extractions of teeth before IMRT have to be balanced with any potential delay in initiating cancer therapy. Keywords: Dental care; Dental management; Oropharyngeal cancer; Osteoradionecrosis prevention; Radiation toxicit

Stereotactic or conformal radiotherapy for adrenal metastases: patient characteristics and outcomes in a multicenter analysis

To report outcome (freedom from local progression: FFLP, overall survival: OS, and toxicity) after stereotactic, palliative, or highly conformal fractionated (&gt; 12) radiotherapy (SBRT, Pall-RT, 3DCRT/IMRT) for adrenal metastases in a retrospective multicenter cohort within the framework of the German Society for Radiation Oncology (DEGRO). Adrenal metastases treated with SBRT (≤ 12 fractions, biologically effective dose, (BED10) ≥ 50 Gy), 3DCRT/IMRT (&gt; 12 fractions, BED10 ≥ 50 Gy) or Pall-RT (BED10 &lt; 50 Gy) were eligible for this analysis. In addition to unadjusted FFLP (Kaplan-Meier/Log-rank), we calculated the competing-risk-adjusted local recurrence rate (CRA-LRR). 326 patients with 366 metastases were included by 21 centers (median follow-up: 11.7 months). Treatment was SBRT, 3DCRT/IMRT, and Pall-RT in 260, 27, and 79 cases, respectively. Most frequent primary tumors were non-small-cell lung cancer (NSCLC; 52.5%), SCLC (16.3%), and melanoma (6.7%). Unadjusted FFLP was higher after SBRT v. Pall-RT (p&nbsp;=&nbsp;0.026) while numerical differences in CRA-LRR between groups did not reach statistical significance (1-year CRA-LRR: 13.8%, 17.4%, and 27.7%). OS was longer after SBRT v. other groups (p &lt; 0.05) and increased in patients with locally-controlled metastases in a landmark analysis (p &lt; 0.0001). Toxicity was mostly mild; notably, 4 cases of adrenal insufficiency occurred, 2 of which were likely caused by immunotherapy or tumor progression. RT for adrenal metastases was associated with a mild toxicity profile in all groups and a favorable 1-year CRA-LRR after SBRT or 3DCRT/IMRT. 1-year FFLP was associated with longer OS. Dose-response analyses for the dataset are underway

Visualization of the tumor cavity after lumpectomy of breast cancer for postoperative radiotherapy

To visualize the tumor cavity after lumpectomy, the tumor cavity was coated with the liquid tissue marker sucrose acetate isobutyrate (SAIB) with its radiopaque electron dense SAIB analogue (x-SAIB) and assessed for radiotherapy planning. SAIB/x-SAIB enhanced the confidence for target structure definition. Tissue displacement after oncoplasty may be revealed by SAIB/x-SAIB

Hierarchical enhanced non-rigid registration for target volume correction and propagation for adaptive external beam radiotherapy of carcinoma of the prostate

Volumes change during fractionated radiotherapy (RT). We investigate a tool based on the Hierarchical Enhanced Registration Algorithm (HERA) to project a 3D segmentation set of the prostate into the subsequent imaging sets at any time point during RT by using intensity-based image registration techniques. Sequential CT sets during RT at 15, 30, 45, and 60 Gy of two patients were used. Five expert clinicians outlined the prostate in a blinded fashion, defining intraobserver and interobserver variability on a set of 35 and 25 scans, respectively. The observer variability and positioning for manual correction was compared to both affine and elastic image registration-based contour propagation. The overall mean error of the registration-based correction of the planning target volume was comparable to the interobserver variability of manual target volume definition. The correction by affine image fusion was inferior to the results of elastic registration. The maximal deviation for the interobserver segmentation was 15.4 mm, 10.5 mm for the affine and 8.0 mm for the elastic registration. The mean interobserver variability was 1.5 (± 1.4) mm, 2.8 (± 2.3) mm for the affine, and 2.2 (± 1.9) mm for the elastic registration. Intensity-based elastic registration of deformable anatomical structures with HERA is suitable for the assessment of changes of prostate volumes for the purpose of target propagation and adaptive radiotherapy

Vesicular stomatitis virus Indiana glycoprotein as a T-cell-dependent and -independent antigen.

The neutralizing immunoglobulin M (IgM) response to vesicular stomatitis virus (VSV) has been shown to be largely T-cell independent in several T-cell-deficient models of mice. By using different antigen froms of VSV, VSV antigen doses could be graded in vivo (infectious > > UV inactivated > formalin inactivated). The present study reveals a T-cell-dependent component of the neutralizing IgM response in nude mice given intravenous injections of low doses of noninfectious UV-inactivated VSV serotype Indiana (VSV-IND) only if the mice are transfused with VSV-IND-specific helper T cells. Instead, nude mice immunized with infectious VSV, which leads to greater antigen doses in vivo, were able to mount an IgM response in the absence of T cells. These results indicate that the IgM response to low doses of VSV-IND glycoprotein (G) is T-cell dependent. Nude mice immunized with infectious VSV also made a variable but low VSV-IND-neutralizing IgG response. A VSV-IND matrix (M)-specific helper T-cell line rendered this response more consistent, much higher, and longer lasting. Thus (i) VSV-G induces a mostly T-cell-independent but partially T-cell-dependent IgM (the latter can be visualized best at low doses of antigen) and (ii) the antibody response to VSV in nude mice proceeds through steps, i.e., IgM and IgG, that are dose dependent. The results suggest that the predominant role of helper T cells may be to expand and maintain the individual steps of differentiating B cells

G2/M cell cycle checkpoint is functional in cervical cancer patients after initiation of external beam radiotherapy

PURPOSE: To investigate changes in cancer of the uterine cervix during radiotherapy (RT) with respect to G2/M transition in relation to tumor cell apoptosis and changes in the tumor vasculature in cervical carcinoma. METHODS AND MATERIALS: A total of 40 consecutive patients with Stage IIA-IIIB cervical cancer underwent RT without any chemotherapy. Tumor biopsy was obtained before RT and after five fractions of 1.8 Gy. The tumor samples were stained for cyclin B1, cdc2, and Ki-67, the apoptotic index, using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining. The tumor vasculature density was assessed. In 38 cases, the tissue samples were informative. RESULTS: Cyclin B1 was positive in all biopsies before and after initiation of RT, and staining for cdc2 was positive in 35 (92%) of 38 biopsies before and 33 (87%) of 38 after 1 week of RT. Nuclear staining for cyclin B1 was observed in 92% of patients, staining an average of 15% of cells before RT. After initiating RT, 73% of patients showed positive staining on about 5% of tumor cells (p < 0.01). Nuclear staining for cdc2 was detected in 89% of patients, staining an average of 21% of cells before RT. After initiating RT, 79% of patients showed positive staining on 9% of cells (p < 0.01). The apoptotic index of the tumor cells increased after initiating RT, and a slight decrease in the vascular density after 1 week of RT was noted (p = 0.08). Changes in G2/M were associated with the clinical response, but changes in apoptosis or tumor vasculature were not. CONCLUSION: RT leads to significant changes in the cell cycle in cervical cancer indicating intact G2/M checkpoint function. Targeting G2/M with compounds interfering with G2/M transition may further enhance the effect of RT in cervical cancer patients

Intensity-modulated radiotherapy and volumetric-modulated arc therapy for malignant pleural mesothelioma after extrapleural pleuropneumonectomy

Radiotherapy reduces the local relapse rate after pleuropneumonectomy of malignant pleural mesothelioma (MPM). The optimal treatment technique with photons remains undefined. Comparative planning for intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) was performed. Six MPM patients with significant postoperative intrathoracic air cavities were planned with IMRT and VMAT. A dose comparison for the targets and organ at risks (OAR) was performed. Robustness was assessed in respect to the variation of target dose with change in volume of air cavities. VMAT reduced the dose to the contralateral lung by reducing the volume covered by 13 Gy and 20 Gy by a factor 1.8 and 2.8, in respect to IMRT (p = 0.02). Dose distribution with VMAT was the most stable technique in regard to postsurgical air cavity variation. For IMRT, V90, V95, and the minimal target dose decreased by 40%, 64%, and 12% compared to 29%, 47%, and 7% with VMAT when air cavity decreased. Two arcs compared to one arc decreased the dose to all the organs at risk (OAR) while leaving PTV dose coverage unchanged. Increasing the number of arcs from two to three did not reduce the dose to the OAR further, but increased the beam-on time by 50%. Using partial arcs decreased the beam-on time by 43%. VMAT allows a lower lung dose and is less affected by the air cavity variation than IMRT. The best VMAT plans were obtained with two partial arcs. VMAT seems currently the most suitable technique for the treatment of MPM patients when air cavities are remaining and no adaptive radiotherapy is performed