Purpose: To evaluate and quantify the accuracy using a new custom-made pelvis immobilization device during the course of radiotherapy. Materials and Methods: A new custom-made pelvic immobilization cast had been developed to provide a stable and comfort position of the patients. It consists of a flat and rigid acrylic plate and thermoplastic cast. Eight patients with pelvic cast were evaluated by on line electronic portal imaging during daily radiotherapy treatment for 5 to 8 consecutive days. While another 10 patients without pelvic casts were used as a control. A total of 221 electronic portal imaging (EPI) were reviewed. Under the assistance of image registration software, the geometric errors from the EPI was identified by interactive techniques. The systematic and random setup errors for each patient were determined. Results: Daily set-up variation was markedly improved using the cast. The total directed setup errors for all patients in anterior-posterior (AP), left-right (LR) and inferior-superior (IS) directions were -0.1±2.2 mm, -0.4±1.2 mm and -0.3 ±2.0 mm respectively with cast as compared to -0.4±2.4 mm, 1.2±1.9 mm and -1.1±3.8 mm respectively without cast. The suggested margin, which was calculated according to the total undirected setup error for each patient, in AP/PA and lateral fields for more than 5 mm were found in 14% and 33% of patients with casts as compared to 60% and 89% of patients without immobilization cast. (p value = 0.065 for AP/PA fields and p value = 0.024 for lateral fields) Conclusion: This custom-made pelvic immobilization cast appears to improve the reproducibility of patient setup during radiotherapy for pelvic tumors. In application to 3-D conformal radiotherapy, this type of immobilization is now routinely used in our department and is recommended for all patients receiving pelvic radiotherapy.
IL-3 gene expression within tumors leads to host-cell infiltration, particularly by macrophages, slower tumor growth, and enhanced immunogenicity. Surprisingly, tumor-associated macrophages (TAMs) from within FSAN-JmIL3 tumors had decreased expression of TNF-alpha and iNOS. On short-term culture, TAMs from FSAN-JmIL3 tumors regained their capacity to produce TNF-alpha and NO, indicating that they were primed in vivo. In vitro experiments were unable to demonstrate differences between FSAN-JmIL3 and FSAN tumor cells in their ability to stimulate TNF-alpha production by TAMs. In the absence of evidence that TAM activation was responsible for the slower growth of FSAN-JmIL3 tumors, the response of tumor cells to these effector molecules was studied. TNF-alpha and NO were cytotoxic for FSAN-JmIL3 cells but growth stimulatory for FSAN. These tumor-related phenotypic changes may contribute as much if not more than functional changes in host infiltrating cells to the slower growth of FSAN-JmIL3 tumors in vivo.
In this large-scale, retrospective study, the authors evaluated the diagnostic performances of computed tomography (CT), magnetic resonance (MR) imaging, and (18)F-fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET) in detecting hematogenous bone metastasis in patients with cervical cancer. The associated risk factors also were analyzed.Patients with invasive cervical cancer who had both (18)F-FDG-PET studies and CT or MR imaging studies were selected. Patients who had either International Federation of Gynecology and Obstetrics (FIGO) stage III/IV disease or positive lymph node metastasis at the time of primary staging and patients who had suspected recurrent disease were included in the analyses. The diagnostic performances of PET was compared with the performance of CT and MR imaging by using the area under the receiver-operating-characteristic curve (AUC). Both univariate and multivariate analyses were applied to assess the risk factors for hematogenous bone metastasis at primary staging.PET was more sensitive than CT (P = .004) and was more specific than MR imaging (P = .04). The diagnostic performance of PET was significantly superior to the performance CT (AUC, 0.964 vs 0.662; P < .001) and MR (AUC, 0.966 vs 0.833; P = .033). Both FIGO stage and the extent of lymph node metastases were associated with hematogenous bone metastasis in univariate analysis. However, the extent of lymph node metastases was the only significant risk factor in multivariate analysis (P = .025).The current study demonstrated the superiority of (18)F-FDG-PET over CT and MR imaging for detecting hematogenous bone metastasis in patients with advanced cervical cancer. Hematogenous bone metastasis in cervical cancer was associated with the extent of lymph node metastases rather than with FIGO stage.
Novel technological solutions for the design of positron emission tomography (PET) systems to be used in the in-beam beam-on monitoring of proton tracks within biological tissues represent the frontier of the instrumentation in proton therapy. We report a novel all-digital PET dual heads prototype based on the multivoltage threshold (MVT) technology, able to operate in beam-on modality. We demonstrate in phantom and animal experiments that, by using an event selection based on the energy of singles and on the delay with respect to the radio-frequency period of the proton beam bunches, the monitoring PET system is able to image the induced activity by both pristine and pencil proton beam with energy ranging between 70 and 150 MeV during irradiation.
Abstract Recent studies indicate that sunitinib, a tyrosine kinase inhibitor, could decease accumulation of myeloid-derived suppressor cells (MDSC) in tumors and also in peripheral blood. This study aims to investigate the behavior and dynamic profile of myeloid-derived suppressor cells in tumor tissues and peripheral blood of sunitinib-treated mice bearing prostate adenocarcinoma TRAMP-C1 tumors. To this end, 3×106 TRAMP-C1 tumor cells were inoculated at shank muscle of C57BL6/J mouse and sunitinib was administered by intraperitoneal injection of a daily dose of 20mg/kg into mice bearing 4 mm diameter tumor. Comparing to tumors in untreated group, sunitinib administration slightly delayed tumor growth delay for 2 days, but significantly decreased micro-vascular density and induced chronic hypoxia in tumors, resulting in the specific accumulation of CD11b+Gr-1+ MDSCs at the tumor necrotic region within CA-IX positive chronic hypoxic area. Flow cytometry was used to analyze the change of CD11b+ myeloid cells within tumor tissues and peripheral blood. Results showed that sunitinib treatment decreased the percentage of CD11b+Ly6G-LyC- tumor-associated macrophages (TAMs), but increased the percentage of CD11b+Ly6G-Ly6C+ monocytic MDSCs (M-MDSCs) while had no effect on CD11b+Ly6G+Ly6C+ neutrophilic MDSCs (N-MDSCs) within tumor tissues. In contrast, both the percentage of N-MDSCs and M-MDSC were expanded in peripheral blood of sunitinib-treated mice. Multiplex immunoassay showed significant increase of CCL2, CCL3, CCL5, CXCL5, IL-17a, GM-CSF, G-CSF and VEGF-A in tumor tissues, but only CXCL5, IL-á, IL-6 and G-CSF in the peripheral blood of sunitinib-treated mice were affected. In conclusion, this study shows that sunitinib has anti-vascular effect and could disrupt the recruitment of CD11b+Ly6G-Ly6C- TAMs into tumors. We also propose that sunitinib might exert different effects on tumor microenvironment and peripheral blood. Citation Format: Fang-Hsin Chen, Sheng-Yung Fu, Chun-Chieh Wang, Chi-Shiun Chiang, Ji-Hong Hong. Sunitinib has opposite roles to regulate the myeloid-derived suppressor cells in tumors and peripheral blood. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 759.
Abstract Immunotherapy such as anti-PD-1/PD-L1 is effective in several types of tumors, but in general the response rate is less than 30%. Systemic administration of cytokine such as IL-12 could create anti-tumor immunity but has unacceptable side effects. This study is to test our hypothesis that combination of high-dose local radiotherapy (RT) and local production of IL-12 inside tumors within short period could have potent anti-tumor effects but low systemic toxicity. TRAMP-C1 tumors derived from a murine prostate cancer were either no treatment, or irradiated with 25 Gy, or intra-tumorally injected with Ad-sc-IL12 virus (1×10sup8 pfu), or treated with both modalities at the tumor size of 4mm. RT alone and Ad-sc-IL12 alone could not shrink tumors and only caused tumor growth delay around 7 and 12 days, respectively. The combination of RT with Ad-sc-IL12 virus could shrink the tumors to the sizes of < 2mm and further extended the tumor growth delay more than 20 days. The percentage of lymphocytes and IFN-γproduction were evaluated by flow cytometry and ELISA. The percentages of CD4 cells in tumors were too low to be reliably measured in all groups, but the percentages of CD8 cells were increased in Ad-sc-IL12 virus-treated groups and even much higher in those combined with RT. For mice treated with Ad-sc-IL12 virus injection, the serum IL-12 levels were around 4.5 times increase at day7, but those combined with with RT had significantly lower levels than those treated with virus alone. The serum IFN-γ(Th1 response) levels were around 12 times higher in Ad-sc-IL12 groups at day7 as compared to control or RT only group, but had no significant differences between those treated with combined modality and with Ad-sc-IL12 virus alone. Liver damage is an index for IL-12 toxicity and the levels of GOT and GTP were also lower in those treated IL-12 combined with RT than those treated with IL-12 alone. This study supported our hypothesis and showed that combination of local IL-12 production and local RT are effective in increasing CD8 cells, exerting Th1 response, and enhancing tumor growth delay. The most important is that this combination has less systemic toxicity than local IL-12 production alone. This study provides evidence to develop new strategy for producing a strong anti-tumor and low toxicity for radioresistant tumors by combining RT and IL-12 immunotherapy. Citation Format: Ji-Hong Hong, Ching-Fang Yu, Fang-Hsin Chen, Chi-Shiun Chiang. Combination of high-dose irradiation and local interleukin-12 treatment enhance tumor killing and have less toxicities than either treatment alone. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4014.
Background: This retrospective study was conducted to evaluate the safety of radiotherapy for kidney transplant recipients (KTRs) with urothelial carcinoma (UC).
To investigate how single or fractionated doses of radiation change the microenvironment in transgenic adenocarcinoma of the mouse prostate (TRAMP)-C1 tumors with respect to vascularity, hypoxia, and macrophage infiltrates.Murine prostate TRAMP-C1 tumors were grown in C57BL/6J mice to 4 mm tumor diameter and were irradiated with either 25 Gy in a single dose or 60 Gy in 15 fractions. Changes in vascularity, hypoxia, and macrophage infiltrates were assessed by immunohistochemistry and molecular assays.Tumor growth was delayed for 1 week after both radiation schedules. Tumor microvascular density (MVD) progressively decreased over a 3-week period to nadirs of 25% and 40% of unirradiated tumors for single or fractionated treatment, respectively. In accord with the decrease in MVDs, mRNA levels of endothelial markers, such as CD31, endoglin, and TIE, decreased over the same time period after irradiation. Central dilated vessels developed surrounded by avascularized hypoxic regions that became infiltrated with aggregates of CD68+ tumor-associated macrophages, reaching a maximum at 3 weeks after irradiation. Necrotic regions decreased and were more dispersed.Irradiation of TRAMP-C1 tumors with either single or fractionated doses decreases MVD, leading to the development of disperse chronic hypoxic regions, which are infiltrated with CD68+ tumor-associated macrophages. Approaches to interfere in the development of these effects are promising strategies to enhance the efficacy of cancer radiotherapy.
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