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Radiotherapy (RT) is an important modality for laryngeal cancer treatment to preserve laryngeal function. During beam delivery, laryngeal motion remains uncontrollable and may compromise tumor-targeting efficacy. We aimed to examine real-time laryngeal motion by developing a surface depth-sensing technique with preliminary testing during RT-based treatment of patients with laryngeal cancer. A surface depth-sensing (SDS) camera was set up and integrated into RT simulation procedures. By recording the natural swallowing of patients, SDS calculation was performed using the Pose Estimation Model and deep neural network technique. Seven male patients with laryngeal cancer were enrolled in this prospective study. The calculated motion distances of the laryngeal prominence (mean ± standard deviation) were 1.6 ± 0.8 mm, 21.4 ± 5.1 mm, 6.4 ± 3.3 mm, and 22.7 ± 4.9 mm in the left–right, cranio–caudal, and anterior–posterior directions and for the spatial displacement, respectively. The calculated differences in the 3D margins for generating the planning tumor volume by senior physicians with and without SDS data were −0.7 ± 1.0 mm (−18%), 11.3 ± 6.8 mm (235%), and 1.8 ± 2.6 mm (45%) in the left–right, cranio–caudal, and anterior–posterior directions, respectively. The SDS technique developed for detecting laryngeal motion during swallowing may be a practical guide for individualized RT design in the treatment of laryngeal cancer. [ABSTRACT FROM AUTHOR]

Background: Radiation-induced bowel damage may compromise nutrient absorption and digestion and affect body composition during pelvic radiotherapy in patients with locally advanced cervical cancer (LACC). This study aimed to evaluate the relationship between bowel radiation dose-volume and body composition changes during pelvic radiotherapy. Methods: Data of 301 LACC patients treated with chemoradiotherapy were analyzed. Changes in skeletal muscle index (SMI) and density (SMD), and total adipose tissue index (TATI) were measured from computed tomography images at the L3 vertebral level. A reduction in SMI, SMD, or TATI of ≥10% was classified as "loss." Bowel V45 indicates the bowel volume (mL) receiving a radiation dose of ≥45 Gy. The relationship between body composition and bowel V45 was analyzed using logistic regression models. Results: After treatment, 61 (20.3%), 81 (26.9%), and 97 (32.2%) patients experienced SMI, SMD, and TATI loss, respectively. Increased bowel V45 was independently associated with increased odds of SMI loss (odds ratio [OR]: 1.012; 95% confidence interval [CI]: 1.007–1.018; p<0.001) and TATI loss (OR: 1.006; 95% CI: 1.001–1.010; p=0.01), but not with SMD loss (OR: 1.005; 95% CI: 1.000–1.009; p=0.054). The cut-off value with the highest accuracy for predicting SMI loss was V45 ≥222 mL; a higher rate of SMI loss was noted in 40.0% of patients with V45 ≥222 mL than in 13.7% of patients with V45 <222 mL (p<0.001). Conclusions: Higher bowel dose-volume was significantly associated with muscle loss during pelvic radiotherapy. Bowel dose-volume consideration is required in individualized nutritional counseling and supportive care in clinical practice. [ABSTRACT FROM AUTHOR]

To evaluate the effect and mechanism of radiotherapy (RT)–sorafenib pharmacokinetics (PK) in different regimens with conventional or high dose irradiation. Between February 2012 and December 2018, 43 patients with portal vein tumor thrombosis treated with sorafenib plus conventional RT (58%) or stereotactic body radiation therapy (SBRT, 42%) were retrospectively reviewed. In vivo and in vitro studies of concurrent and sequential RT with sorafenib were designed. SBRT resulted in a 3-fold increase in complete recanalization compared to conventional RT group (28% vs. 8%, p = 0.014). Compared to the control group, the area under the concentration vs. time curve (AUC) of sorafenib was increased in the concurrent RT2Gy and RT9Gy groups and the sequential RT9Gy group by 132% (p = 0.046), 163% (p = 0.038) and 102% (p = 0.018), respectively; and was decreased by 59% in the sequential RT2Gy group (p = 0.036). Sequential RT2Gy and RT9Gy increased CYP3A4 activity by 82% (p = 0.028) and 203% (p = 0.0004), respectively, compared to that with the corresponding concurrent regimen. SBRT produced better recanalization than conventional RT with sorafenib. The AUC of sorafenib was modulated by RT. P-gp expression was not influenced by RT. The sequential RT regimen increased CYP3A4 activity that may increase the RT-sorafenib synergy effect and overall sorafenib activity. The biodistribution of sorafenib was modulated by local RT with the different regimens. [ABSTRACT FROM AUTHOR]

Purpose: Sonic hedgehog (Shh) signaling is critical to embryogenesis and resistance to chemotherapy. We aimed to examine the role of Shh signaling in the response to radiation of human hepatocellular carcinoma (HCC) cells. Methods and Materials: Response to ionizing radiation therapy (RT) was evaluated by clonogenic assay. Quantitative RT—polymerase chain reaction for patched-1 (PTCH-1) expression was performed. Cytosolic accumulation of Shh and nuclear translocation of Gli-1 were assessed by immunofluorescence. Gli-1 knockdown was done by RNA interference (RNAi). Immunoprecipitation was performed to detect Shh ligand in conditioned medium. Immunofluorescent stain for γ-H2AX was used as an index of DNA double strand breaks (DSB). Expression of proteins related to DNA damage repair was assessed by Western blotting. Results: We found that Shh ligand could protect human HCC HA22T and Sk-Hep1 cells against RT. In HA22T cells, Shh ligand activated the Shh signaling with upregulation of Shh, PTCH-1, and Gli-1 expression. The nuclear translocation of Gli-1 further supports the activation of Gli-1. The radioprotection by Shh ligand was partly blocked by Shh antibody neutralization and was abolished by Gli-1 RNAi, suggesting a critical role of Shh signaling in radiation resistance. Furthermore, we noted that soluble factors secreted into conditioned medium, either constitutively or responding to radiation, by HA22T or Sk-Hep1 cells protected subsequent culturing cells against RT. Immunoprecipitation shows the presence of Shh peptide in conditioned medium. Intriguingly, antibody neutralization of Shh ligand or knockdown of Gli-1 reversed the radioprotective effect of conditioned medium. Furthermore, Shh ligand reduced the RT-induced phosphorylation of checkpoint kinase 1 and impaired the repair of DNA DSB. Conclusions: Activation of Shh signaling protects HCC cells against ionizing radiation in an autocrine manner. Impairment of DNA damage repair might involve mechanism of Shh-induced radioresistance. Targeting Shh signaling pathway may be a novel strategy to enhance the radioresponse of human HCC cells. [Copyright &y& Elsevier]

Esophageal cancer prognosis remains poor in current clinical practice. We previously reported that moscatilin can induce apoptosis and mitotic catastrophe in esophageal cancer cells, accompanied by upregulation of polo-like kinase 1 (Plk1) expression. We aimed to validate in vitro activity and Plk1 expression in vivo following moscatilin treatment and to examine the treatment's radiosensitizing effect. Human esophageal cancer cells were implanted in nude mice. Moscatilin was intraperitoneally (i.p.) injected into the mice. Tumor size, body weight, white blood cell counts, and liver and renal function were measured. Aberrant mitosis and Plk1 expression were assessed. Colony formation was used to measure survival fraction after radiation. Moscatilin significantly suppressed tumor growth in mice bearing human esophageal xenografts without affecting body weight, white blood cell counts, or liver and renal function. Moscatilin also induced aberrant mitosis and apoptosis. Plk1 expression was markedly upregulated in vivo. Moreover, moscatilin pretreatment enhanced CE81T/VGH and BE3 cell radioresponse in vitro. Moscatilin may inhibit growth of human esophageal tumors and sensitize esophageal cancer cells to radiation therapy. [ABSTRACT FROM AUTHOR]

Background and purpose The left anterior descending coronary artery (LAD) and diagonal branches (DBs) are blurred on computed tomography (CT). We aimed to define the LAD region (LADR) with adequate inclusion of the LAD and DBs and contouring consistency. Methods and materials The LADR was defined using coronary CT angiograms. The inclusion ratio was used to assess the LAD and DBs inclusion by the LADR. Four radiation oncologists delineated the LAD and LADR, using contrast-enhanced CT of 15 patients undergoing left breast radiotherapy. The Sørensen–Dice similarity index (DSI), Jaccard similarity index (JSI), and Hausdorff distance (HD) were calculated to assess similarity. The mean dose ( D mean ) and maximum dose ( D max ) to the LAD and LADR were calculated to compare consistency. Correlations were evaluated using Pearson’s correlation coefficient. Results The inclusion ratio of the LAD by the LADR was 96%. The mean DSI, JSI, and HD values were respectively 27.9%, 16.7%, and 0.42 mm for the LAD, and 83.1%, 73.0%, and 0.18 mm for the LADR. The D mean between the LAD and LADR were strongly correlated ( r = 0.93). Conclusion Delineation of the LADR significantly improved contouring similarity and consistency for dose reporting. This could optimize dose estimation for breast radiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Increasing the sensitivity of tumor cells to radiation is a major goal of radiotherapy. The present study investigated the radiosensitizing effects of andrographolide and examined the molecular mechanisms of andrographolide-mediated radiosensitization. Methods and Materials: An H-ras-transformed rat kidney epithelial (RK3E) cell line was used to measure the radiosensitizing effects of andrographolide in clonogenic assays, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide assays, and a xenograft tumor growth model. The mechanism of andrographolide-sensitized cell death was analyzed using annexin V staining, caspase 3 activity assays, and terminal transferase uridyl nick end labeling assays. The roles of nuclear factor kappa B (NF-κB) and Akt in andrographolide-mediated sensitization were examined using reporter assays, electrophoretic mobility shift assays, and Western blotting. Results: Concurrent andrographolide treatment (10 μM, 3 h) sensitized Ras-transformed cells to radiation in vitro (sensitizer enhancement ratio, 1.73). Andrographolide plus radiation (one dose of 300 mg/kg peritumor andrographolide and one dose of 6 Gy radiation) resulted in significant tumor growth delay (27 ± 2.5 days) compared with radiation alone (22 ± 1.5 days; p <.05). Radiation induced apoptotic markers (e.g., caspase-3, membrane reversion, DNA fragmentation), and andrographolide treatment did not promote radiation-induced apoptosis. However, the protein level of activated Akt was significantly reduced by andrographolide. NF-κB activity was elevated in irradiated Ras-transformed cells, and andrographolide treatment significantly reduced radiation-induced NF-κB activity. Conclusion: Andrographolide sensitized Ras-transformed cells to radiation both in vitro and in vivo. Andrographolide-mediated radiosensitization was associated with downregulation of Akt and NF-κB activity. These observations indicate that andrographolide is a novel radiosensitizing agent with potential application in cancer radiotherapy. [Copyright &y& Elsevier]

Purpose: To review the experience with and evaluate the treatment plan for helical tomotherapy for the treatment of oropharyngeal cancer. Methods and Materials: Between November 1, 2006 and January 31, 2009, 10 histologically confirmed oropharyngeal cancer patients were enrolled. All patients received definitive concurrent chemoradiation with helical tomotherapy. The prescription dose to the gross tumor planning target volume, the high-risk subclinical area, and the low-risk subclinical area was 70Gy, 63Gy, and 56Gy, respectively. During radiotherapy, all patients were treated with cisplatin, 30mg/m2, plus 5-fluorouracil (425mg/m2)/leucovorin (30mg/m2) intravenously weekly. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events, version 3.0. Several parameters, including maximal or median dose to critical organs, uniformity index, and conformal index, were evaluated from dose–volume histograms. Results: The mean survival was 18 months (range, 7–22 months). The actuarial overall survival, disease-free survival, locoregional control, and distant metastasis-free rates at 18 months were 67%, 70%, 80%, and 100%, respectively. The average for uniformity index and conformal index was 1.05 and 1.26, respectively. The mean of median dose for right side and left side parotid glands was 23.5 and 23.9Gy, respectively. No Grade 3 toxicity for dermatitis and body weight loss and only one instance of Grade 3 mucositis were noted. Conclusion: Helical tomotherapy achieved encouraging clinical outcomes in patients with oropharyngeal carcinoma. Treatment toxicity was acceptable, even in the setting of concurrent chemotherapy. Long-term follow-up is needed to confirm these preliminary findings. [Copyright &y& Elsevier]

Purpose: Point A, used for dose specification for intracavitary brachytherapy for cervical cancer, is the point at which the uterine artery and ureter cross. This study assessed compatibility of commonly used traditional point A (TPA) and actual anatomic point A (APA). Methods and Materials: We visualized and placed radiopaque clips at the APA during pelvic and paraaortic lymphadenectomy in 11 patients with cervical carcinoma. Orthogonal and oblique radiographs were obtained after insertion of brachytherapy applicators. We measured the distance between the TPA and APA and estimated the brachytherapy dose to each of the two points. Results: A total of 64 brachytherapy treatments were performed. The mean distances between the TPA and APA were 5.2 +/- 1.0 cm on the right and 5.4 +/- 1.1 cm on the left. The estimated brachytherapy doses delivered to the APA as a percentage of the presumed 500-cGy fraction size to the TPA were 35.2% (176.6 +/- 59.0 cGy) on the right and 30.0% (150.2 +/- 42.9 cGy) on the left. The marked discrepancy in the position of the two points was not related to individual kinetic variations during brachytherapy treatment, tumor size, or bladder filling. Conclusions: The conventional TPA does not provide an accurate estimate of the APA determined during lymphadenectomy, indicating a need to reevaluate the current practice for determining the brachytherapy prescription for cervical cancer. (ClinicalTrials.gov Identifier, NCT00319462). [ABSTRACT FROM AUTHOR]