Use of an orthovoltage X-ray treatment unit as a radiation research system in a small-animal cancer model

BackgroundWe explore the use of a clinical orthovoltage X-ray treatment unit as a small-animal radiation therapy system in a tumoral model of cervical cancer.MethodsNude mice were subcutaneously inoculated with 5 × 106 HeLa cells in both lower limbs. When tumor volume approximated 200 mm3 treatment was initiated. Animals received four 2 mg/kg intraperitoneal cycles (1/week) of cisplatin and/or 6.25 mg/kg of gemcitabine, concomitant with radiotherapy. Tumors were exposed to 2.5 Gy/day nominal surface doses (20 days) of 150 kV X-rays. Lead collimators with circular apertures (0.5 to 1.5 cm diameter) were manufactured and mounted on the applicator cone to restrict the X-ray beam onto tumors. X-ray penetration and conformality were evaluated by measuring dose at the surface and behind the tumor lobe by using HS GafChromic film. Relative changes in tumor volume (RTV) and a clonogenic assay were used to evaluate the therapeutic response of the tumor, and relative weight loss was used to assess toxicity of the treatments.ResultsNo measurable dose was delivered outside of the collimator apertures. The analysis suggests that dose inhomogeneities in the tumor reach up to ± 11.5% around the mean tumor dose value, which was estimated as 2.2 Gy/day. Evaluation of the RTV showed a significant reduction of the tumor volume as consequence of the chemoradiotherapy treatment; results also show that toxicity was well tolerated by the animals.ConclusionResults and procedures described in the present work have shown the usefulness and convenience of the orthovoltage X-ray system for animal model radiotherapy protocols.

[1]  S. Webb,et al.  A proof that uniform dose gives the greatest TCP for fixed integral dose in the planning target volume. , 1994, Physics in medicine and biology.

[2]  R. Weichselbaum,et al.  Concomitant chemoradiotherapy: rationale and clinical experience in patients with solid tumors. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  Jane Fridlyand,et al.  Bioinformatics Original Paper a Comparison Study: Applying Segmentation to Array Cgh Data for Downstream Analyses , 2022 .

[4]  F. H. Attix Introduction to Radiological Physics and Radiation Dosimetry , 1991 .

[5]  Frank Herbert Attix,et al.  Introduction to Radiological Physics and Radiation Dosimetry: Attix/Introduction , 2007 .

[6]  J. Galvin,et al.  Radiochromic film dosimetry: recommendations of AAPM Radiation Therapy Committee Task Group 55. American Association of Physicists in Medicine. , 1998, Medical physics.

[7]  M. Gasco,et al.  Gemcitabine and cisplatin in a concomitant alternating chemoradiotherapy program for locally advanced head-and-neck cancer: a pharmacology-guided schedule. , 2006, International journal of radiation oncology, biology, physics.

[8]  H. Mercado-Uribe,et al.  The use of a reflective scanner to study radiochromic film response. , 2002, Physics in medicine and biology.

[9]  N. Olea,et al.  MCF‐7 breast cancer cells grown as multicellular spheroids in vitro: Effect of 17β‐estradiol , 1992, International journal of cancer.

[10]  Peter Kazanzides,et al.  Small Animal Radiation Research Platform: Imaging, Mechanics, Control and Calibration , 2007, MICCAI.

[11]  S. Santillana,et al.  Concurrent cisplatin/gemcitabine chemotherapy along with radiotherapy in locally advanced cervical carcinoma: a phase II trial. , 2006, Gynecologic oncology.

[12]  Erik Tryggestad,et al.  The small-animal radiation research platform (SARRP): dosimetry of a focused lens system , 2007, Physics in medicine and biology.

[13]  M. Mcentee,et al.  Principles and applications of radiation therapy. , 2003, Clinical techniques in small animal practice.

[14]  P. Rose Chemoradiotherapy for cervical cancer. , 2002, European journal of cancer.

[15]  F. Khan The physics of radiation therapy , 1985 .

[16]  Wilfried De Backer,et al.  Body surface area in normal-weight, overweight, and obese adults. A comparison study. , 2006, Metabolism: clinical and experimental.

[17]  Sasa Mutic,et al.  Progress toward a microradiation therapy small animal conformal irradiator. , 2006, Medical physics.

[18]  Guido Bocci,et al.  Drug distribution in tumors: Mechanisms, role in drug resistance, and methods for modification , 2007, Current oncology reports.

[19]  D. Bouchier-Hayes,et al.  Improvement in efficacy of chemoradiotherapy by addition of an antiangiogenic agent in a murine tumor model. , 2004, The Journal of surgical research.

[20]  H. Hamada,et al.  Local tumour irradiation enhances the anti‐tumour effect of a double‐suicide gene therapy system in a murine glioma model , 2003, The journal of gene medicine.

[21]  S. Fisher,et al.  A murine model for the effects of pelvic radiation and cisplatin chemotherapy on human papillomavirus vaccine efficacy. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[22]  S. Rockwell,et al.  Applicability of animal tumor data to cancer therapy in humans. , 1988, International journal of radiation oncology, biology, physics.

[23]  S Mutic,et al.  MicroRT-small animal conformal irradiator. , 2007, Medical physics.

[24]  A. Mohar,et al.  Pathologic response and toxicity assessment of chemoradiotherapy with cisplatin versus cisplatin plus gemcitabine in cervical cancer: a randomized Phase II study. , 2005, International journal of radiation oncology, biology, physics.

[25]  O. Fodstad,et al.  A human tumor lung metastasis model in athymic nude rats. , 1989, Cancer research.