Pulsed Radiotherapy Research Articles

Mathematical models and dynamic behaviors of cancer treatment by continuous and pulsed radiotherapy

Mathematical models and dynamic behaviors of cancer treatment by continuous and pulsed radiotherapy

Effect of Irradiation on Tumor Microenvironment and Bone Marrow Cell Migration in a Preclinical Tumor Model

To characterize the tumor microenvironment after standard radiation therapy (SRT) and pulsed radiation therapy (PRT) in Lewis lung carcinoma (LLC) allografts. Subcutaneous LLC tumors were established in C57BL/6 mice. Standard RT or PRT was given at 2Gy/d for a total dose of 20Gy using a 5days on, 2days off schedule to mimic clinical delivery. Radiation-induced tumor microenvironment changes were examined after treatment using flow cytometry and antibody-specific histopathology. Normal tissue effects were measured using noninvasive (18)F-fluorodeoxyglucose positron emission tomography/computed tomography after naïve animals were given whole-lung irradiation to 40Gy in 4weeks using the same 2-Gy/d regimens. Over the 2weeks of therapy, PRT was more effective than SRT at reducing tumor growth rate (0.31±0.02mm(3)/d and 0.55±0.04mm(3)/d, respectively; P<.007). Histopathology showed a significant comparative reduction in the levels of Ki-67 (14.5%±3%), hypoxia (10%±3.5%), vascular endothelial growth factor (2.3%±1%), and stromal-derived factor-1α (2.5%±1.4%), as well as a concomitant decrease in CD45(+) bone marrow-derived cell (BMDC) migration (7.8%±2.2%) after PRT. The addition of AMD3100 also decreased CD45(+) BMDC migration in treated tumors (0.6%±0.1%). Higher vessel density was observed in treated tumors. No differences were observed in normal lung tissue after PRT or SRT. Pulsed RT-treated tumors exhibited slower growth and reduced hypoxia. Pulsed RT eliminated initiation of supportive mechanisms utilized by tumors in low oxygen microenvironments, including angiogenesis and recruitment of BMDCs.

OC-0048: Tumor microenvironment response and bone marrow cell migration after pulsed radiotherapy

OC-0048: Tumor microenvironment response and bone marrow cell migration after pulsed radiotherapy

Dynamic analysis of an antitumor model and investigation of the therapeutic effects for different treatment regimens

In this paper, to explore the therapeutic effects for different treatment regimens, we propose an antitumor model with pulsed radiotherapy and immunotherapy. Using Floquent theorem and small-amplitude perturbation skills, the sufficient condition for the global stability of the tumor-free periodic solution is derived at first. Furthermore, the fixed-point approach is applied to investigate the existence and stability of the nontrivial periodic solution. Moreover, by comparing different therapeutic regimens, we achieve the conditions that determine which therapeutic regimen is more effective in diminishing the basic reproduce number. Finally, we perform numerical simulations to illustrate and justify our theoretical findings and design a combined treatment regimen with reference value and guidance significance.

The Effects of Pulsed Radiation Therapy on Tumor Oxygenation in 2 Murine Models of Head and Neck Squamous Cell Carcinoma

To evaluate the efficacy of low-dose pulsed radiation therapy (PRT) in 2 head and neck squamous cell carcinoma (HNSCC) xenografts and to investigate the mechanism of action of PRT compared with standard radiation therapy (SRT). Subcutaneous radiosensitive UT-SCC-14 and radioresistant UT-SCC-15 xenografts were established in athymic NIH III HO female mice. Tumors were irradiated with 2 Gy/day by continuous standard delivery (SRT: 2 Gy) or discontinuous low-dose pulsed delivery (PRT: 0.2 Gy × 10 with 3-min pulse interval) to total doses of 20 Gy (UT14) or 40 Gy (UT15) using a clinical 5-day on/2-day off schedule. Treatment response was assessed by changes in tumor volume, (18)F-fluorodeoxyglucose (FDG) (tumor metabolism), and (18)F-fluoromisonidazole (FMISO) (hypoxia) positron emission tomography (PET) imaging before, at midpoint, and after treatment. Tumor hypoxia using pimonidazole staining and vascular density (CD34 staining) were assessed by quantitative histopathology. UT15 and UT14 tumors responded similarly in terms of growth delay to either SRT or PRT. When compared with UT14 tumors, UT15 tumors demonstrated significantly lower uptake of FDG at all time points after irradiation. UT14 tumors demonstrated higher levels of tumor hypoxia after SRT when compared with PRT as measured by (18)F-FMISO PET. By contrast, no differences were seen in (18)F-FMISO PET imaging between SRT and PRT for UT15 tumors. Histologic analysis of pimonidazole staining mimicked the (18)F-FMISO PET imaging data, showing an increase in hypoxia in SRT-treated UT14 tumors but not PRT-treated tumors. Differences in (18)F-FMISO uptake for UT14 tumors after radiation therapy between PRT and SRT were measurable despite the similar tumor growth delay responses. In UT15 tumors, both SRT and PRT were equally effective at reducing tumor hypoxia to a significant level as measured by (18)F-FMISO and pimonidazole.

Pulsed Radiation Therapy Maintains Tumor Oxygenation in a Murine Model of Head and Neck Squamous Cell Carcinoma

Despite multimodal therapy, local recurrence for advanced head and neck squamous cell carcinoma (HNSCC) remains high with overall 5-year survival of about 50%. Tumor hypoxia has been identified as a significant source of radioresistance and is associated with poor clinical outcomes. The aim of this study was to determine if tumor response and radiation-induced hypoxia are altered following fractionated standard radiation therapy (SRT) or pulsed radiation therapy (PRT) in murine xenograft model of HNSCC.