Management of intraoral stents for radiotherapy during COVID-19 pandemic

Radiotherapy is being performed in many situations as a curative approach for head and neck cancer instead of surgery due to the current novel coronavirus disease (COVID-19) pandemic. A recent publication reported that even hypofractionation was being conducted in order to reduce the daily exposure of both patients and the medical staff involved in cancer therapies. As a result, dental teams may be requested more frequently than usual to fabricate intraoral stents (IOS). Given that IOS may be a potential source of COVID-19 contagion, the main purpose of the present correspondence is to offer a guide on how health professionals may be safely presented in the room, on the management of the IOS and also how to sanitize the stents.     

Micronuclei and other nuclear anomalies in normal human buccal mucosa cells of oral cancer patients undergoing radiotherapy: a field effect

We evaluated micronuclei and other nuclear anomalies in exfoliated epithelial cells of the oral cavity on the side opposite the lesion targeted by radiotherapy and correlated them with radiation doses. Buccal smears were obtained from oral cancer patients undergoing radiotherapy with a cumulative dose of at least 1000 rad for 3 weeks and from controls matched for age, gender and habits. The exfoliated cells from the mucosa were collected using a cytobrush; smears were prepared, fixed in 80% methanol and stained using the Feulgen plus fast green method. The mean number of micronuclei and other nuclear anomalies/1000 cells was significantly greater in patients undergoing radiotherapy treatment, but the differences were not significant compared to radiation doses. It appears that radiotherapy has a potent clastogenic effect on buccal mucosal cells of oral cancer patients.     

Adjuvant radiotherapy in malignant tumors of parotid. Experience of the Navarra Hospital Complex

BackgroundThe objective of the study was to review the outcome of patients with parotid cancer treated with postoperative radiotherapy at Complejo Hospitalario de Navarra in the last ten years.Materials and methodsWe retrospectively reviewed patients treated with adjuvant radiotherapy between January 2008 and December 2018. We analyzed demographic data, histopathologic findings, local control (LC) and overall survival (OS).ResultsA total of 40 patients received postoperative radiotherapy during the period mentioned. There were 22 men (55%) and 18 women (45%). Median age was 58 years (19–90). By tumor histology, the most common was squamous cell carcinoma (22.5%) followed by ex-pleomorphic adenoma (15%) and adenoid cystic carcinoma (10%). According to Surgery, 19 patients (47.5%) underwent a total parotidectomy, 20 (50%) partial parotidectomy, and 1 (2.5%) a radical parotidectomy. Twenty-one patients (51.2%) underwent cervical dissection, most of them being supraomohyoid (31.7%). Reasons for adjuvant RT were: R1 resection (35% of the patients), high grade tumors (27.5%) and 17.5% because R1 surgery and R1. Radiation was administered using IMRT in most patients to a total dose of 60 Gy in 30 fractions. The 5-year overall survival (OS) (Kaplan-Meier) was 81% (95% CI: 68.5–96.2%), and 10-years — 64%. The 5-year local control (LC) (Kaplan-Meier) was 82.4% (95% CI: 91.46–73.33%) and the 10-year LC — 72.2% (95% CI: 54.9–96%). To date, only 4 patients (10%) have died due to their parotid tumor.ConclusionThe adjuvant radiotherapy added to surgery, significantly reduces the risk of recurrence in high-risk patients with a very acceptable survival rate.     

Role of whole brain radiotherapy in the management of infratentorial metastases from lung and breast cancer

BackgroundBrain metastases (BM) occur in almost one third of patients with systemic malignancies. Only a small number of studies focus on infratentorial location and whole brain radiotherapy (WBRT) as the main non-surgical management. The aim of the study was to compare the prognosis of patients treated with WBRT among patients with supra- or infratentorial lesions.Materials and methodsAt a single center, 263 patients with either breast (BC) or lung (LC) cancer, that had developed BM and received treatment with WBRT, were analyzed during an 8-year period.ResultsA total of 152 patients with BC and 111 with LC were analyzed, median age at the time of BM was 50.7 years, systemic activity other than BM was detected in 91%. Newly diagnosed BM were supratentorial in 40%, infratentorial in 10% and 51% in both locations. Median overall survival was 13 months (95% CI: 11.1–14.8 months), without significant difference between supra- or infratentorial location. WBRT alone was administered in 79% of patients, whereas WBRT with chemtoreapy was provided for 21%.ConclusionIn patients with BM from LC or BC that were not candidates for surgical resection, palliative WBRT appears to be equally effective in those with supra- or infratentorial locations.     

The impact of respiratory gating on lung dosimetry in stereotactic body radiotherapy for lung cancer

The purpose of this study was to evaluate the impacts of respiratory gating and different gating windows (GWs) on lung dosimetry in stereotactic body radiotherapy (SBRT) for lung cancer.Gated SBRT plans were developed using the four-dimensional computed tomography data from 17 lung cancer patients treated with SBRT. Using amplitude-based end-exhalation gating, we established 2 fixed GWs with approximate duty cycles of 50% (50% GW) and 25% (25% GW), respectively, for this study.For highly mobile tumors (3D mobility > 10 mm), additional benefits in lung-dose reductions were achieved with the 25% GW, as a result of inadequate mobility and planning target volume reductions obtained with the 50% GW. In these tumors, the absolute differences compared to the non-gated and 50% gated plans, were 0.5 Gy and 0.33 Gy for the mean lung dose and 1.11% and 0.71% for the V20, respectively. Dosimetric benefits were achieved with the 50% GW, compared with the non-gated plan, for tumors with both low mobility and small volume (gross tumor volume ≤ 10 cc). Among the identified predictive factors of dosimetric benefits, the lateral distance from midspinal canal and the motion range in anterior–posterior direction might be stronger factors because of their correlations with many of the lung-dose parameters and greater predictive capacity.The results of the present study might facilitate the selection of appropriate patients and the optimal GW according to the tumor characteristics for gated lung SBRT.     

Gut microbial dysbiosis is associated with development and progression of radiation enteritis during pelvic radiotherapy

Radiation enteritis (RE) is the most common complication of radiotherapy for pelvic irradiation receivers. Herein we investigated the alterations in gut microbial profiles and their association with enteritis in patients undergoing pelvic radiotherapy. Faecal samples were collected from 18 cervical cancer patients during radiotherapy. Microbiota profiles were characterized based on 16S rRNA sequencing using the Illumina HiSeq platform. Epithelial inflammatory response was evaluated using bacterial‐epithelial co‐cultures. Dysbiosis was observed among patients with RE, which was characterized by significantly reduced α‐diversity but increased β‐diversity, relative higher abundance of Proteobacteria and Gammaproteobacteria and lower abundance of Bacteroides. Coprococcus was clearly enriched prior to radiotherapy in patients who later developed RE. Metastat analysis further revealed unique grade‐related microbial features, such as more abundant Virgibacillus and Alcanivorax in patients with mild enteritis. Additionally, using bacterial‐epithelial co‐cultures, RE patient‐derived microbiota induced epithelial inflammation and barrier dysfunction, enhanced TNF‐α and IL‐1β expression compared with control microbiota. Taken together, we define the overall picture of gut microbiota in patients with RE. Our results suggest that dysbiosis of gut microbiota may contribute to development and progression of RE. Gut microbiota can offer a set of biomarkers for prediction, disease activity evaluation and treatment selection in RE.     

A practical methodology to improve the dosimetric accuracy of MR-based radiotherapy simulation for brain tumors

PurposeTo investigate the dosimetric accuracy of synthetic computed tomography (sCT) images generated by a clinically-ready voxel-based MRI simulation package, and to develop a simple and feasible method to improve the accuracy.Methods20 patients with brain tumor were selected to undergo CT and MRI simulation. sCT images were generated by a clinical MRI simulation package. The discrepancy between planning CT and sCT in CT number and body contour were evaluated. To resolve the discrepancies, an sCT specific CT-relative electron density (RED) calibration curve was used, and a layer of pseudo-skin was created on the sCT. The dosimetric impact of these discrepancies, and the improvement brought about by the modifications, were evaluated by a planning study. Volumetric modulated arc therapy (VMAT) treatment plans for each patient were created and optimized on the planning CT, which were then transferred to the original sCT and the modified-sCT for dose re-calculation. Dosimetric comparisons and gamma analysis between the calculated doses in different images were performed.ResultsThe average gamma passing rate with 1%/1 mm criteria was only 70.8% for the comparison of dose distribution between planning CT and original sCT. The mean dose difference between the planning CT and the original sCT were −1.2% for PTV D₉₅ and −1.7% for PTV D_max, while the mean dose difference was within 0.7 Gy for all relevant OARs. After applying the modifications on the sCT, the average gamma passing rate was increased to 92.2%. Mean dose difference in PTV D₉₅ and D_max were reduced to −0.1% and −0.3% respectively. The mean dose difference was within 0.2 Gy for all OAR structures and no statistically significant difference were found.ConclusionsThe modified-sCT demonstrated improved dosimetric agreement with the planning CT. These results indicated the overall dosimetric accuracy and practicality of this improved MR-based treatment planning method.     

Current treatment of rectal cancer adapted to the individual patient

Preoperative radiochemotherapy and total mesorectal excision surgery is a recommended standard therapy for patients with locally advanced rectal cancer. However, some subgroups of patients benefit more than others from this approach. In order to avoid long-term complications of radiation and chemotherapy, efforts are being made to subdivide T3N0 stage using advanced imaging techniques, and to analyze prognostic factors that help to define subgroup risk patients. Long-course radiochemotherapy has the potential of downsizing the tumor before surgery and may increase the chance of sphincter preservation in some patients. Short-course radiotherapy (SCRT), on the other hand, is a practical schedule that better suits patients with intermediated risk tumors, located far from the anal margin. SCRT is also increasingly being used among patients with disseminated disease, before resection of the rectal tumor. Improvements in radiation technique, such as keeping the irradiation target below S2/S3 junction, and the use of IMRT, can reduce the toxicity associated with radiation, specially long-term small bowel toxicity.     

Changes in lung volume parameters regarding the received dose in the lobes of the lungs after locoregional radiotherapy of breast cancer

AimThe purpose of this study was to evaluate ΔLVP¹ and correlate them with MLD² and V20³ in the lobes of the lung.BackgroundRadiation-induced lung injury after breast irradiation is controversial. The incidence of such an injury could have negative consequences on breast cancer patients.Materials and MethodsTwenty-three women treated with Breast-conserving surgery, chemotherapy, and locoregional RT⁴ underwent body plethysmography pre-RT and 3 and 6 months post-RT. Statistical analysis was used to evaluate ΔLVP over time and relate them with MLD, V20, age, and concurrent hormonal therapy.ResultsLVP decreased after 3 months and then showed a slight improvement by returning partially to their pre-RT values after 6 months. The mean ΔLVP was −0.64% for one Gy increase of MLD and −0.34% for one percent increase of V20 after 3 months. After 6 months, only ΔVC⁵ showed 0.45% reduction with MLD in the upper lobe. Finally, there was no significant correlation between ΔLVP with respect to age and concurrent hormonal therapy.ConclusionsThe results of this study showed that lung volume changes were not a cause for concern in breast cancer patients. There are three reasons to support this conclusion. Lung volume changes and percentage reductions in LVP for each Gy increase of MLD and each percentage increase of V20 in each lobe were small; patients were asymptomatic during the follow-up period; and LVP showed partial improvements after 6 months.     

Shrinkage of the non-malignant prostate gland volume after receiving incidental radiotherapy for rectal cancer

BackgroundThe purpose of this study was to assess the impact of coincidental radiotherapy on the volume of the non-malignant prostate gland in rectal cancer patients treated with neo-adjuvant radiotherapy.Materials and methodsIn this retrospective analysis, thirty male patients with rectal cancer who had neoadjuvant radiotherapy met the inclusion criteria. These patients had pre-treatment magnetic resonance imaging (MRI) and at least one post-treatment MRI of the pelvis and the whole of their prostate volume received the full prescribed radiotherapy dose; 45 Gy in 25 fractions (n = 22), 45 Gy in 20 fractions (n = 4) and 25 Gy in 5 fractions (n = 4).ResultsThe median age of this patient cohort was 66 years (range: 30–87). With a median interval between pre-treatment MRI and first MRI post-treatment of 2 months (range: 1–11), the mean prostate volume reduced from 36.1 cm³ [standard deviation (SD) 14.2] pre-radiotherapy to 31.3 cm³ (SD 13.0) post radiotherapy and this difference was significant (p = 0.0004).ConclusionRadiotherapy may cause shrinkage in volume of normal (non-malignant) prostate. Further research is required in this field, since these results may be of some comfort to men contemplating the consequences of radiotherapy on their quality of life. The authors suggest recording flow-rate and international prostate symptom score (IPSS) during rectal radiotherapy as a next step.     

The importance of image guided radiotherapy in small cell lung cancer: Case report and review of literature

AimDescribe the anatomical changes and tumor displacement due to a rapid response of a patient’s small cell lung cancer (SCLC) during definitive chemoradiotherapy (CRT).BackgroundThe treatment for SCLC is based on CRT. If interfractional changes during RT are incorrectly assessed they might compromise adequate coverage of the tumor or increase dose to organs at risk. Image guided RT with cone-beam computed tomography (CBCT) allows to identify daily treatment variations.Material and methodsDescribe a SCLC case with rapid changes in size, shape and location of the primary tumor during RT.Case reportA 62-year-old woman was diagnosed with SCLC with complete obstruction of the anterior and lingular bronchi and incomplete left thorax expansion due to a 12 × 15 cm mass. During CRT (45 Gy in 1.5 Gy per fraction, twice daily) the patient presented rapid tumor response, leading to resolution of bronchi obstruction and hemithorax expansion. Tumor shifted up to 4 cm from its original position. The identification of variations led to two new simulations and planning in a 3-week treatment course.ConclusionsThe complete radiological response was possible due to systematic monitoring of the tumor during CRT. We recommend frequent on-site image verification. Daily CBCT should be considered with pretreatment tumor obstruction, pleural effusion, atelectasis, large volumes or radiosensitive histology that might resolve early and rapidly and could lead to a miss of the tumor or increased toxicity. Further research should be made in replanning effect in coverage of microscopic disease since it increases uncertainty in this scenario.     

Frequency of whole breast irradiation (WBRT) after intraoperative radiotherapy (IORT) is strongly influenced by institutional protocol qualification criteria

Background

Accelerated partial breast irradiation (APBI) is a promising method of adjuvant radiotherapy for select patients. Intraoperative radiotherapy (IORT) is a form of APBI, and appropriate patient selection is important.

Histological studies on the development of porcine tonsils after birth

Tonsils form the topographically first immune barrier of an organism against the invasion of pathogens. We used histology to study the development of tonsils of pigs after birth. At birth, the tonsils consist of diffuse lymphoid tissue without any lymphoid follicle aggregations. At the age of 7 days, lymphoid follicles appeared in the soft palate tonsil. The lymphoid layer of the nasopharyngeal tonsil, soft palate tonsil, and lingual tonsil became thicker, and lymphoid follicles in the lamina propria were clearly visible at the age of 21 days. Secondary lymphoid follicles were present in the nasopharyngeal tonsil at the age of 50 days, and in the soft palate tonsil at the age of 120 days. Dendritic cells (DCs), CD3⁺ T cells and IgA⁺ B cells in the soft palate tonsil, nasopharyngeal tonsil and lingual tonsil increased continuously, especially during the first 21 days. The results suggested that tonsils have an important role in local immune defense against invading antigens after birth and will be beneficial for understanding the mechanisms of immunity in these animals after nasal and oral vaccination.     

The prognostic value of red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in radiotherapy for oropharyngeal cancer

BackgroundRed cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are known inflammatory indices. Elevated values are found in many cancers and may be associated with a poor prognosis. The article aimed to assess the impact of RDW, NLR, and PLR on overall survival (OS) of patients with oropharyngeal cancer treated with radiotherapy (RT).Materials and methodsThis retrospective study includes 208 patients treated for oropharyngeal cancer with definitive RT or RT combined with neoadjuvant or concurrent systemic therapy, at one institution between 2004 and 2014. The receiver operating characteristic (ROC) method, log-rank testing, and Cox proportional hazards regression model were used for the analysis.ResultsThe OS was significantly higher in RDW ≤ 13.8% (p = 0.001) and NLR ≤ 2.099 (p = 0.016) groups. The RDW index was characterized by the highest discriminatory ability [area under the curve (AUC) = 0.59, 95% confidence interval (CI): 0.51–0.67], closely followed by NLR (AUC = 0.58, 95% CI: 0.50–0.65). In the univariate Cox regression analysis, RDW [hazard ratio (HR): 1.28, 95% CI: 1.12–1.47, p < 0.001] and NLR (HR: 1.11, 95% CI: 1.06–1.18, p < 0.001) were associated with an increased risk of death. In the multivariate analysis, among the analyzed indices, only NLR was significantly associated with survival (HR: 1.16, 95% CI: 1.03–1.29, p = 0.012).ConclusionsIn the study, only NLR proved to be an independent predictor of OS. However, its clinical value is limited due to the relatively low sensitivity and specificity.     

Combinatorial effects of radiofrequency hyperthermia and radiotherapy in the presence of magneto-plasmonic nanoparticles on MCF-7 breast cancer cells

Here, the effects of combinatorial cancer therapy including radiotherapy (RT) and radiofrequency (RF) hyperthermia in the presence of gold-coated iron oxide nanoparticles (Au@IONPs), as a thermo-radio-sensitizer, are reported. The level of cell death and the ratio of Bax/Bcl2 genes, involved in the pathway of apoptosis, were measured to evaluate the synergistic effect of Au@IONPs-mediated RF hyperthermia and RT. MCF-7 human breast adenocarcinoma cells were treated with different concentrations of Au@IONPs. After incubation with NPs, the cells were exposed to RF waves (13.56 MHz; 100 W; 15 min). At the same time, thermometry was performed with an infrared (IR) camera. Then, the cells were exposed to 6 MV X-ray at various doses of 2 and 4 Gy. MTT (3-[4,5-dimethylthiazol-2-y1]-2,5-diphenyltetrazolium bromide) assay was performed to evaluate cell viability and quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expression ratio of Bax/Bcl2. Cellular uptake of nanoparticles was confirmed qualitatively and quantitatively. The results obtained from MTT assay and qRT-PCR studies showed that NPs and RF hyperthermia had no significant effect when applied separately, while their combination had synergistic effects on cell viability percentage and the level of apoptosis induction. A synergistic effect was also observed when the cancer cells were treated with a combination of NPs, RF hyperthermia, and RT. On the basis of the obtained results, it may be concluded that the use of magneto-plasmonic NPs in the process of hyperthermia and RT of cancer holds a great promise to develop a new combinatorial cancer therapy strategy.     

Therapy for oral squamous cell carcinoma by tegafur and streptococcal agent OK-432 in combination with radiotherapy: Association of the therapeutic effect with differentiation and apoptosis in the cancer cells

Twenty patients with oral squamous cell carcinoma having mainly stage II or III lesions without distant metastasis, were treated with tegafur and streptococcal agent, OK-432, in combination with radiotherapy. As a consequence, 16 cases among the treated 20 cases showed complete remission by this therapy alone. Especially, we have found that the squamous cell carcinoma arising in non-keratinizing oral epithelium rather than in keratinizing oral epithelium has better response to this therapy. Among the 16 cases with complete remission (CR) by the current therapy, 10 cases were histopathologically diagnosed as well-differentiated squamous cell carcinoma and six cases as moderately differentiated squamous cell carcinoma. When we examined immunohistochemically the expres-sion of various antigens such as proliferating cell nuclear antigen (PCNA), p53 and LeY or the presence of DNA fragmentation by nick-end labelling in the biopsy materials taken at the first visit to our clinic from 20 patients treated with the current therapy, the CR group showed a significantly increased LeY expres-sion level ( p< 0.05) and DNA fragmentation rate ( p< 0.05) as compared with the partial response (PR, n= 3) + no change (NC, n= 1) group. On the other hand, the CR group with respect to PCNA expression level was significantly decreased as compared with the PR + NC group ( p< 0.05). From these findings, it can be considered that the therapy for oral squamous cell carcinoma by UFT and OK-432 in combination with radiotherapy is very effective, which may be associated with differentiation or apoptosis in oral squamous carcinoma cells. In addition, we present the clinical findings and results of immunohistochemical staining for the biopsy materials obtained from four CR cases treated with the current therapeutic method.     

Evaluation of high-grade astrocytoma recurrence patterns after radiotherapy in the era of temozolomide: A single institution experience

Aim

Evaluating the recurrence patterns of high-grade astrocytomas in patients who were treated with radiotherapy (RT) plus temozolomide (TMZ).