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1.
Acta Gastroenterol Belg ; 85(3): 469-475, 2022.
Article in English | MEDLINE | ID: mdl-35770280

ABSTRACT

Background: Liver metastases may occur during the course of several cancer types and may be associated with significant morbidity and mortality. There is paucity of data regarding the utility of Active Breathing Control (ABC) guided Stereotactic Ablative Body Radiotherapy (SABR) for management of Liver Metastases from Colorectal Cancer (LMCC). Our aim is to investigate the role of ABC guided SABR for management of liver metastases. Patients and methods: 42 liver metastases of 29 patients treated with ABC guided SABR between February 2015 and October 2018 were retrospectively assessed for local control (LC), overall survival (OS), and toxicity outcomes. Primary endpoint was LC. Secondary endpoints were OS and treatment toxicity. Results: At a median follow up duration of 16 months (range: 9-74 months), median OS was 20 months and 3 patients were still alive at last follow up. 1-year OS was 83% and 2-year OS was 28%. LC rates were 92% and 61% at 1 and 2 years, respectively. Comparative analysis of Biological Effective Dose (BED) values revealed that higher BED10 values were associated with higher LC rates (p=0.007). While LC rates for BED10 ≥ 100 Gray (Gy) were 94% and 86% at 1 and 2 years, corresponding LC rates for BED10 < 100 Gy were 89% and 36%, respectively with statistical significance (p=0.007). Assessment of acute and late toxicity outcomes revealed that most common toxicity was fatigue, however, no patients had ≥ grade 3 toxicity. Conclusion: ABC guided SABR is an effective and safe treatment modality for LMCC management.


Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Lung Neoplasms , Radiosurgery , Humans , Liver Neoplasms/radiotherapy , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Lung Neoplasms/pathology , Radiosurgery/adverse effects , Retrospective Studies
2.
Asian Pac J Cancer Prev ; 15(22): 9599-602, 2014.
Article in English | MEDLINE | ID: mdl-25520073

ABSTRACT

BACKGROUND: Postoperative adjuvant radiotherapy (RT) in the management of early stage endometrial cancer (EC) is still controversial. Here we report our institutional experience with patients who received postoperative RT for stage I-II EC over a period of 35 years and assess potential predictors of local recurrence (LR), distant metastasis (DM), and overall survival (OS). MATERIALS AND METHODS: A total of 188 patients undergoing postoperative RT for stage IA-II EC between 1977 and 2012 were evaluated. Some 96 received median 46 Gy whole pelvic radiotherapy (WPRT) (range: 40-60 Gy), 37 were given WPRT with vaginal cuff therapy (VCT), and 55 received only VCT either with brachytherapy (BT) or stereotactic body radiotherapy (SBRT). Chemotherapy was given to 5 patients with uterine papillary serous carcinoma (UPSC). Logistic regression analysis was used to assess the effect of clinicopathological factors on LR, DM, and OS. RESULTS: Median follow-up time was 11 years (range: 1-35 years). At the time of analysis, 34 patients were not alive. Of the 15 patients with LR, 7 (46.7%) recurred in the vaginal stump, 5 (33.3%) in the pelvic region, and 3 (20%) in the paraaortic nodal region, while 12 had distant metastasis. UPSC histology (p=0.027), sole VCT (p=0.041), high histologic grade (p=0.034), and age≥71 (p=0.04) were poor prognostic factors on univariate analysis. CONCLUSIONS: In our patients receiving radiotherapy for early-stage EC, grade III disease and age≥71 were associated with shorter OS whereas UPSC histology was an independent predictor for both LR and DM.


Subject(s)
Carcinoma, Papillary/drug therapy , Endometrial Neoplasms/mortality , Endometrial Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Carcinoma, Papillary/complications , Disease-Free Survival , Endometrial Neoplasms/surgery , Female , Humans , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local , Neoplasm Staging , Radiotherapy, Adjuvant , Retrospective Studies , Treatment Outcome
3.
J BUON ; 18(3): 717-22, 2013.
Article in English | MEDLINE | ID: mdl-24065489

ABSTRACT

PURPOSE: Stereotactic radiosurgery (SRS) has emerged as a viable alternative to surgery in the management of meningioma through exploiting the advantage of being minimally invasive with few complications and acceptable local control rates. The aim of this study was to evaluate the efficiency of linear accelerator (LINAC)-based SRS in the management of meningiomas and to report our experience using this sophisticated technique. METHODS: Between July 1998 and March 2012, 79 patients (42 female, 37 male) were treated using LINAC-based SRS in the Department of Radiation Oncology, Gulhane Military Medical Academy. Median dose was 13 Gy (range 10- 16) prescribed to the 80-95% isodose line encompassing the target. RESULTS: Median follow-up time was 53 months (range 9-112). Median tumor volume was 3.43 cc (range 0.3-14.1). Local tumor control was 89.7% in the 68 patients with adequate follow-up. CONCLUSION: LINAC-based SRS offers a safe and effective treatment alternative to surgery in intracranial meningiomas with high local control rates and low morbidity.


Subject(s)
Meningeal Neoplasms/surgery , Meningioma/surgery , Radiosurgery , Adult , Aged , Female , Follow-Up Studies , Humans , Imaging, Three-Dimensional , Male , Meningeal Neoplasms/pathology , Meningioma/pathology , Middle Aged , Neoplasm Grading , Prognosis , Tomography, X-Ray Computed
4.
Neoplasma ; 60(3): 322-7, 2013.
Article in English | MEDLINE | ID: mdl-23374003

ABSTRACT

The purpose of this study is to evaluate the use of linear accelerator (LINAC)-based stereotactic body radiotherapy (SBRT) boost with multileaf collimator technique after pelvic radiotherapy (RT) in patients with endometrial cancer. Consecutive patients with endometrial cancer treated using LINAC-based SBRT boost after pelvic RT were enrolled in the study. All patients had undergone surgery including total abdominal hysterectomy and bilateral salpingo-oophorectomy ± pelvic/paraortic lymphadenectomy before RT. Prescribed external pelvic RT dose was 45 Gray (Gy) in 1.8 Gy daily fractions. All patients were treated with SBRT boost after pelvic RT. The prescribed SBRT boost dose to the upper two thirds of the vagina including the vaginal vault was 18 Gy delivered in 3 fractions with 1-week intervals. Gastrointestinal and genitourinary toxicity was assessed using the Common Terminology Criteria for Adverse Events version 3 (CTCAE v3).Between April 2010 and May 2011, 18 patients with stage I-III endometrial cancer were treated with LINAC-based SBRT boost after pelvic RT. At a median follow-up of 24 (8-26) months with magnetic resonance imaging (MRI) and gynecological examination, local control rate of the study group was 100 % with negligible acute and late toxicity.LINAC-based SBRT boost to the vaginal cuff is a feasible gynecological cancer treatment modality with excellent local control and minimal toxicity that may replace traditional brachytherapy boost in the management of endometrial cancer.


Subject(s)
Endometrial Neoplasms/surgery , Neoplasm Recurrence, Local/surgery , Radiosurgery , Aged , Disease Management , Endometrial Neoplasms/pathology , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Grading , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis
5.
Neoplasma ; 59(3): 333-40, 2012.
Article in English | MEDLINE | ID: mdl-22296503

ABSTRACT

The purpose of this study is to evaluate the effect of Active Breathing Control-moderate deep inspiration breath-hold (ABC-mDIBH) on tumor motion and critical organ doses in non-small cell lung cancer (NSCLC) radiotherapy. 23 patients with locally advanced NSCLC were included in the study. All patients were scanned at free breathing and ABC-mDIBH for radiation treatment planning. 3 separate treatment plans were generated for each patient including one plan with ABC-mDIBH and uniform margins, one plan with free breathing and uniform margins, and one plan with free breathing and 3-dimensional non-uniform margins determined by Cone Beam Computed Tomography (CBCT) and XVI Motion View (X-ray Volume Imaging, Elekta, UK). Critical organ dose-volumes and physical lung parameters were comparatively evaluated on 3 separate dose-volume histograms of each patient acquired from planning software. Individual tumor motion of each patient with and without ABC-mDIBH was documented and compared. Use of ABC-mDIBH resulted in statistically significant improvement in physical lung parameters of V20 (lung volume receiving ≥ 20 Gy) and mean lung dose (MLD) which are predictors of radiation pneumonitis (p<0.001). Reduction in spinal cord dose and tumor motion with ABC-mDIBH was also statistically significant (p<0.001). ABC-mDIBH increases normal lung tissue sparing in definitive NSCLC radiotherapy by improving physical lung parameters along with spinal cord dose reduction through exact tumor immobilization. The incorporation of ABC-mDIBH into NSCLC radiotherapy may have implications for potential margin reduction and dose escalation to improve treatment outcomes.


Subject(s)
Adenocarcinoma/radiotherapy , Breathing Exercises , Carcinoma, Large Cell/radiotherapy , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Squamous Cell/radiotherapy , Immobilization , Lung Neoplasms/radiotherapy , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathology , Aged , Carcinoma, Large Cell/diagnostic imaging , Carcinoma, Large Cell/pathology , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/pathology , Dose Fractionation, Radiation , Female , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Male , Middle Aged , Prognosis , Radiotherapy Planning, Computer-Assisted , Tomography, X-Ray Computed
6.
Acta Chir Belg ; 106(1): 73-6, 2006.
Article in English | MEDLINE | ID: mdl-16612919

ABSTRACT

AIM: This study was undertaken to assess the effect of intra-operative radiotherapy on intestinal wound healing and prevention of its side effects by retinoic acid. MATERIALS AND METHODS: Thirty Spraque-Dawley rats were divided into 3 groups of (n = 10). All the groups had laparatomies and terminal ileum exteriorization. Group I was the control group with no irradiation and no anastomosis; group II had both irradiation and anastomosis and group III rats had peroral retinoic acid conditioning and irradiation + anastomosis. On the seventh postoperative day, tensile strength and intestinal elongation measurements were to evaluate the effect of retinoic acid on wound healing. RESULTS: Compared to the non-retinoic acid conditioned group, the retinoic acid conditioned group had statistically significant higher tensile strength and lower intestinal elongation values, revealing better wound healing. CONCLUSION: Peroral retinoic acid supplement administration has a preventive effect on radiation-induced wound-healing inhibition in intra-operative abdominopelvic irradiation and anastomoses.


Subject(s)
Intestines/surgery , Premedication , Radiation Injuries/prevention & control , Radiation-Protective Agents/therapeutic use , Radiotherapy/adverse effects , Tretinoin/therapeutic use , Wound Healing/drug effects , Anastomosis, Surgical , Animals , Combined Modality Therapy , Intestines/drug effects , Intestines/radiation effects , Male , Radiation Injuries/etiology , Radiation-Protective Agents/pharmacology , Rats , Rats, Sprague-Dawley , Tensile Strength , Tretinoin/pharmacology , Wound Healing/radiation effects
7.
Dentomaxillofac Radiol ; 35(1): 14-7, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16421258

ABSTRACT

OBJECTIVES: In this study, quantification of backscatter doses between scattering titanium dental implant and the thermoluminescent dosimeter (TLD(100)) radiation detector at axial beam irradiation-angle range of 0-90 degrees in head and neck radiotherapy is done to evaluate irradiation angle dependency of dose enhancement contributing to osteoradionecrosis. METHODS: A cylindrical titanium dental implant with diameter of 4 mm and length of 9 mm was implanted into a specially-designed human mandible phantom with a TLD100 chip placed on the buccal site and irradiated with 6 MV X, 25 MV X and Co-60 gamma sources at 19 different irradiation angles. RESULTS: Dose enhancement on a buccal site of the titanium implant depends on the incident beam angle. At angles of 65 degrees, 60 degrees and 40 degrees the maximum detected scatter doses over the titanium implant are 36%, 32% and 23% for Co-60 gamma, 6 MV X-ray and 25 MV X-ray, respectively. The dose enhancement at different beam angles was less pronounced in 25 MV X and more pronounced in Co-60 gamma irradiation. CONCLUSIONS: For the different radiation beams studied, the irradiation angle between scattering titanium dental implants and the central axis does not significantly affect the total dose that may lead to osteoradionecrosis of the mandible.


Subject(s)
Cranial Irradiation/adverse effects , Dental Implants , Osteoradionecrosis/etiology , Titanium , Dose-Response Relationship, Radiation , Head and Neck Neoplasms/radiotherapy , Humans , Mandible/radiation effects , Phantoms, Imaging , Radiotherapy Dosage , Radiotherapy, High-Energy/adverse effects , Scattering, Radiation , Thermoluminescent Dosimetry
8.
Exp Oncol ; 26(3): 236-9, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15494694

ABSTRACT

OBJECTIVE: The aim of this study is to evaluate the efficacy of electronic portal imaging (EPI) to measure the set-up errors for four different sites of irradiation caused by patient positioning. METHODS: A total number of 95 portal images of 11 patients (3 pelvic, 1 total cranium, 3 mantle and 4 tangential fields for breast) were collected during the course of study. The first portal images after a correction of set-up errors according to the simulation films were accepted as the reference images for the subsequent sessions. By matching each portal image with the reference image, the deviations in lateral (x) and superior-inferior (y) axis for all and additionally in antero-posterior (z) axis for pelvis, and standard deviations were calculated. RESULTS: The set-up errors caused by patient's positioning are completely abolished in 15 mm planning target volume (PTV) margins for all studied cases. CONCLUSION: Standard PTV margins usually completely cover the set-up errors caused by patient's positioning.


Subject(s)
Neoplasms/radiotherapy , Radiotherapy Planning, Computer-Assisted/methods , Adenocarcinoma/pathology , Adenocarcinoma/radiotherapy , Adenocarcinoma/surgery , Brain Neoplasms/pathology , Brain Neoplasms/radiotherapy , Breast Neoplasms/pathology , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/radiotherapy , Carcinoma, Ductal, Breast/surgery , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Combined Modality Therapy , Electronics, Medical , Endometrial Neoplasms/pathology , Endometrial Neoplasms/radiotherapy , Feasibility Studies , Female , Hodgkin Disease/pathology , Hodgkin Disease/radiotherapy , Humans , Lymphatic Metastasis/radiotherapy , Neoplasms/pathology , Organ Specificity , Radiotherapy, Adjuvant , Rectal Neoplasms/pathology , Rectal Neoplasms/radiotherapy , Rectal Neoplasms/surgery
9.
Neoplasma ; 51(5): 390-4, 2004.
Article in English | MEDLINE | ID: mdl-15640945

ABSTRACT

There has been a number of approaches in the literature for therapeutic malignant and benign orbital irradiation. All techniques intend to deliver a homogenous dose to the orbital and retroorbital target volume while sparing the lens of excessive dose. In this experimental lens-sparing study, 4 MeV and 12 MeV anterior electron irradiation has been used with cerrobend shielding circular blocks of varying diameter and thickness placed on a thin Mylar at the distal tip of the electron applicator to spare the lens. The first phase of the study in water phantom has been designed to determine the shield thickness and diameter constant for 4 MeV and 12 MeV electron beams. After optimizing the lens dose by water phantom, the second phase of our study has been designed to measure doses at lens and other specific localizations in randophantom under same conditions with 4 MeV and 12 MeV electron beams. By this technique lens accumulated 18.56% of prescribed dose and lateral aspects of the lens received 44.59% of the prescribed dose in 4 MeV electron irradiation, whereas this was 13.86% and 44.80%, respectively in 12 MeV electron irradiation. The technique used is found to be an extremely simple and effective technique allowing an easier setup with excellent dose distribution characteristics with lens sparing applicable to orbital irradiation practice.


Subject(s)
Eye Neoplasms/diagnostic imaging , Lens, Crystalline/diagnostic imaging , Phantoms, Imaging , Electrons/therapeutic use , Humans , Radiography , Radiotherapy/adverse effects , Water
10.
Neoplasma ; 50(5): 372-6, 2003.
Article in English | MEDLINE | ID: mdl-14628091

ABSTRACT

The purpose of this study is to report on the dose homogeneity in total body irradiated patients undergoing Bone Marrow Transplantation (BMT), and carcinogenic risk in surviving patients. Between 1987 and 2001, 105 patients received hyperfractionated (6 fractions in 3 days) 12 Gy Total Body Irradiation (TBI) in our institution with lateral opposed fields. All the patients had measurements with thermoluminiscence dosimetry (TLD100) placed on seven bilateral body sites in vivo, controlled by the randophantom measurements to verify reasonable dose homogeneity achievement. The comorbid effects in the whole TBI conditioning group with at least three months post BMT follow-up were noted and surviving patients who had a minimum 5-year and maximum 14-year follow-up (median 7.8 years) have been evaluated for carcinogenic radiation risk on the basis of tissue weighting factors as defined by ICRP 60. Reasonable dose homogeneity by lateral opposed beam TBI has been obtained in all 105 patients in whom lateral TLD100 measurement means were within +5% of the planned doses. Calculated carcinogenesis risk factor was 11.34% for males and 12.40% for females, and no second-cancer has been detected whilst radiation-induced 5 cataracts and 10 interstitial pneumonia comorbidities were noted. Dose homogenization can be well achieved for hyperfractionated lateral-beam TBI with acceptable comorbidities and estimated second-cancer risk is significant but relatively low compared to the risk from the clinical indications for TBI.


Subject(s)
Bone Marrow Transplantation/immunology , Neoplasms, Radiation-Induced/epidemiology , Radiation Injuries/epidemiology , Whole-Body Irradiation/adverse effects , Burkitt Lymphoma/epidemiology , Burkitt Lymphoma/etiology , Cataract/epidemiology , Dose Fractionation, Radiation , Dose-Response Relationship, Radiation , Follow-Up Studies , Humans , Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/etiology , Radiation Injuries/classification , Retrospective Studies , Risk Factors , Time Factors
11.
Neoplasma ; 49(5): 338-41, 2002.
Article in English | MEDLINE | ID: mdl-12458334

ABSTRACT

The purpose of this study is to report carcinogenesis risk factor evaluation in vertebral hemangioma patients treated by radiotherapy. Between 1975 and 1995, 29 patients received 20-30 Gy total irradiation dose using conventional fractionation scheme. All the patients had measurements with thermoluminescent dosimeters (TLD 100 ), placed on multiple randophantom sites in vivo within the irradiated volume, to verify irradiation accuracy and calculate carcinogenesis risk factor. Twenty nine still-alive patients who had a minimum 6-year and maximum 26-year follow-up (median 14.34 years) have been evaluated by carcinogenic radiation risk factor on the basis of tissue weighting factors as defined by International Commission on Radiological Protection Publication 60. Reasonable pain relief has been obtained in all 29 patients. Calculated mean carcinogenesis risk factor is 0.6% for single irradiation portals and 0.9% for double irradiation portals in the whole group, whilst no secondary cancer has been detected. Radiotherapy is an effective treatment modality in relieving pain of vertebral hemangioma patients. Estimated secondary cancer risk factor for this benign neoplasm irradiation is not as high as can be feared.


Subject(s)
Hemangioma/radiotherapy , Neoplasms, Radiation-Induced/etiology , Spinal Neoplasms/etiology , Spinal Neoplasms/radiotherapy , Adult , Aged , Disease-Free Survival , Dose-Response Relationship, Radiation , Female , Hemangioma/diagnosis , Humans , Male , Middle Aged , Neoplasms, Radiation-Induced/prevention & control , Phantoms, Imaging , Radiometry , Risk Factors , Spinal Neoplasms/diagnosis , Spinal Neoplasms/prevention & control , Temperature , Time Factors , Tissue Distribution
12.
Int J Radiat Oncol Biol Phys ; 40(4): 923-7, 1998 Mar 01.
Article in English | MEDLINE | ID: mdl-9531378

ABSTRACT

PURPOSE: This study was performed to determine the toxicity and efficacy of external-beam radiotherapy in patients with age-related subfoveal neovascularization. METHODS AND MATERIALS: Between January 1996 and September 1996, 25 patients with a mean age of 70.5 (60-84) years were enrolled. All patients underwent fluorescein angiographic evaluation and documentation of their neovascular disease prior to irradiation. A total of 25 patients were treated with a total dose of 12 Gy in 6 fractions over 8 days. We used a lens-sparing technique and patients were treated with a single lateral 6-MV photon beam. To assess the risk of radiation carcinogenesis after treatment of age-related subfoveal neovascularization, we estimated the effective dose for a standard patient on the basis of tissue-weighting factors as defined by the International Commission on Radiological Protection (ICRP). The calculations were made with TLD on a male randophantom. The lens dose was found to be 0.217 Gy per fraction. RESULTS: No significant acute morbidity was noted. Visual acuity was maintained or improved in 76% and 80% of treated patients at their 1- and 3-month follow-up examinations, respectively. On angiographic imaging, there was stabilization of subfoveal neovascular membranes in 23 patients (92%) at 3 months after irradiation. CONCLUSION: Our observations on these 25 patients in this study indicate that many patients will have improved or stable vision after radiotherapy treatment with low-dose irradiation.


Subject(s)
Macular Degeneration/radiotherapy , Aged , Aged, 80 and over , Female , Fluorescein Angiography , Humans , Male , Middle Aged , Radiometry , Radiotherapy Dosage
13.
Radiat Med ; 15(1): 1-5, 1997.
Article in English | MEDLINE | ID: mdl-9134577

ABSTRACT

The objective of this study was to examine the influence of vitamin A on the development of early radiation-induced reactions in the rat small intestine. The early effects of intraoperative gamma-radiation on the small bowel utilizing the terminal ileum of Sprague-Dawley rats and the protective effect of supplemental vitamin A on acute radiation injury were investigated. Three groups were included in the study: group I (10 rats) was the surgical control group; group II (13 rats) underwent only intraoperative irradiation; and group III (10 rats) was the vitamin A plus irradiation group. Exteriorized terminal ileal segments of groups II and III were exposed to a single fraction of 20 Gy of intraoperative gamma-irradiation. On the seventh postoperative day, terminal ileal segments of all rats were resected and histopathologically evaluated for ulceration, enteritis cystica profunda, atypical epithelial regeneration, fibrosis, vascular sclerosis, and inflammatory process. Although none of the above findings were present in the surgical control group, group III rats experienced less severe effects than group II rats. The results suggest the early side effects of radiation may be prevented by vitamin A supplementation.


Subject(s)
Ileum/radiation effects , Radiation Injuries, Experimental/prevention & control , Vitamin A/pharmacology , Acute Disease , Animals , Gamma Rays , Ileum/pathology , Intraoperative Period , Radiation Injuries, Experimental/pathology , Rats , Rats, Sprague-Dawley
14.
Radiat Med ; 14(5): 293-6, 1996.
Article in English | MEDLINE | ID: mdl-8988512

ABSTRACT

Multileaf collimation (MLC) is a crucial component dynamic conformal radiotherapy and can be used as a replacement for conventional blocks. The most appropriate volumetric approach for the lesion's shape is achieved by MLC by conforming the prescribed dose to the critical structure or normal tissue dose. In this study, the edge effects of dose profiles on an irregular radiation field obtained by MLC and shield alloy blocks drawn by a water-phantom system were compared. We used a SL25 linac machine with MLC consisting of 40 pairs of opposing leaves and conventional alloy block shielding on a water phantom system. We found no significant edge effect difference between MLC and conventional shielding, but MLC showed clear advantages over conventional blocks in terms of time-saving, repeatability, and reliability.


Subject(s)
Radiation Protection/instrumentation , Radiotherapy/methods , Humans , Particle Accelerators , Phantoms, Imaging , Radiation Effects , Radiotherapy/instrumentation , Radiotherapy Dosage , Reproducibility of Results , Water
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