Evaluation of critical organ dosimetry with focus on heart exposure in supine versus prone patient positioning for breast irradiation

Breast cancer (Ca) remains to be the most frequent cancer among females and a leading cause of cancer associated mortality worldwide. Main modalities for management of breast Ca include surgery, Radiation Therapy (RT), and systemic treatments. Diagnosis at earlier stages of breast Ca is increasing with rigorous utilization of screening and raised public awareness. Improvements in therapy contribute to longer life expectancies for patients with breast Ca. In this context, adverse radiation effects are being a more pronounced aspect of breast Ca management recently.

While the adverse effects of irradiation in earlier studies may have led to unfavorable outcomes for some patients with breast Ca, toxicity profile of radiation delivery has been improved with introduction of modernized equipment and contemporary techniques such as Breathing Adapted Radiation Therapy (BART), Image Guided Radiation Therapy (IGRT), Intensity Modulated Radiation Therapy (IMRT) and Adaptive Radiation Therapy (ART). Individualized patient positioning has also been utilized for improved normal tissue sparing while maintaining target coverage. While the conflicting results of cardiac dosimetry among different studies may partly be explained by variations in delineation and treatment techniques between treatment centers, prone positioning may be considered for at least a selected group of breast Ca patients as a viable alternative to supine positioning. Herein, we evaluate critical organ dosimetry with focus on heart exposure in supine versus prone patient positioning for breast irradiation.

Introduction

Breast cancer (Ca) remains to be the most frequent cancer among females and a leading cause of cancer associated mortality worldwide [1-3]. Main modalities for management of breast Ca include surgery, radiation therapy (RT), and systemic treatments. Diagnosis at earlier stages of breast Ca is increasing with rigorous utilization of screening and raised public awareness. Improvements in therapy contribute to longer life expectancies for patients with breast Ca. In this context, adverse radiation effects are being a more pronounced aspect of breast Ca management recently.

RT is typically administered after Breast Conserving Surgery (BCS) or mastectomy particularly for achieving improvement in local control and overall survival in selected patient groups [4-8]. Nevertheless, improvement in overall survival was not achieved in some studies which may partly be explained by radiation induced toxicity particularly in earlier studies [9-11]. An overview of randomized trials of advuvant RT in breast Ca by Cuzick et al. revealed that irradiation could potentially be detrimental in the long term [12]. Cardiac mortality after irradiation was considered to offset the potential benefits of irradiation for some patients suffering from adverse radiation effects [9-14]. While the adverse effects of irradiation in earlier studies may have led to unfavorable outcomes for some patients with breast Ca, toxicity profile of radiation delivery has been improved with introduction of modernized equipment and contemporary techniques such as Breathing Adapted Radiation Therapy (BART), Image Guided Radiation Therapy (IGRT), Intensity Modulated Radiation Therapy (IMRT) and Adaptive Radiation Therapy (ART) [15-22]. Individualized patient positioning has also been utilized for improved normal tissue sparing while maintaining target coverage. Herein, we evaluate critical organ dosimetry with focus on heart exposure in supine versus prone patient positioning for breast irradiation.

Critical Organ Dosimetry with Focus on Heart Exposure in Supine versus Prone Patient Positioning for Breast Irradiation. An overwhelming majority of patients receive RT as part of breast conserving therapy primarily to improve local control rates which has been substantiated by high level evidence from metaanalyses [23-25]. Postmastectomy irradiation may also be considered for selected high risk patients to improve treatment outcomes [4-8]. Nevertheless, radiation induced cardiotoxicity resulting in cardiovascular diseases and even mortality has been addressed in a plethora of studies [26-46]. Considering that patients with breast Ca typically survive longer as a result of increased screening and early detection along with more effective local and systemic therapies, quality of life has been regarded as an endpoint of utmost importance. In this context, efforts have been focused on improving the toxicity profile of radiation delivery. Guidelines suggested contouring of the heart in light of validated consensus recommendations to reduce variations in target and critical organ delineation [47-51]. Positioning of patients and immobilization has gained priority with contemporary image guided treatment strategies with minimized margins around the target volumes to account for setup uncertainties. Immobilization and patient positioning are critical aspects of contemporary breast cancer RT, and repoducibility is an important concern. While supine positioning has been traditionally utilized for breast Ca RT, several studies addressed the prone positioning as a viable alternative in selected patients [52-61]. In the study by Speleers et al.assessing supine or prone crawl photon or proton breast and regional lymph node radiation therapy including the internal mammary chain, mean doses to critical organs were found to be generally lower for prone crawl than for supine positions and for proton than for photon plans [52]. Chung et al. reported the Korean first prospective phase II study on the feasibility of prone position in postoperative whole breast RT [53]. They concluded that prone breast RT could be beneficial for a subset of patients with small breasts since it spares critical structures while maintaining target coverage [53]. Saini et al. evaluated critical organ sparing in supine and prone positions with deep inspiration breath hold for left sided breast cancer patients [54]. Prone free breathing and supine deep inspiration breath hold techniques were found to be advantageous for critical organ sparing [54]. Mulliez et al. assessed prone deep inspiration breath hold for cardiac sparing in left sided breast irradiation, and prone deep inspiration breath hold was found to reduce mean heart doses to less than 2 Gray regardless of breast volume [55]. Mulliez et al. compared prone and supine positioning in a randomized setting of hypofractionated whole breast irradiation in another study which concluded that prone positioning could replace supine positioning in patients with large breasts for intensity modulated breast RT [57]. Lymberis et al. prospectively assessed optimal positioning for breast RT [58]. The authors concluded that prone setup decreased the amount of irradiated cardiac volume in vast majority of patients with left sided breast cancer [58]. Formenti et al. addressed prone versus supine positioning for breast cancer RT and prone positioning was found to reduce the amount of irradiated heart volume in majority of left sided breast cancer patients [59]. The patient typically lies on a platform with an aperture in the prone position, and the target breast is displaced from the thorax due to gravitation [62-64]. Lying in prone position typically results in improved expansion of the lungs, which translates into an increased normal lung volume during RT with decreased mean lung doses. Reduced lung doses may be considered as an important benefit of breast RT in the prone position, however, its effect on cardiac doses is less clear. Prone positioning allows for displacement of the breast parenchyma away from the chestwall thereby enabling designation of the radiation portal to include less heart volume. Increased distance between heart and the chestwall by prone positioning may allow for improved cardiac sparing in selected patients. Reduction of cardiac doses with breast RT in prone positioning has been supported by several studies for at least a selected group of patients, with some studies also focusing on optimized normal tissue sparing and target coverage in prone positioning such as improved dose coverage and homogeneity, reduced volumes of overdosage, lower ipsilateral pulmonary and mean left anterior descending artery doses, decreased moist desquamation with lower incidence of dermatitis, edema, pruritus, and pain [52-61]. While the conflicting results of cardiac dosimetry among different studies may partly be explained by variations in delineation and treatment techniques between treatment centers, prone positioning may be considered for at least a selected group of breast Ca patients as a viable alternative to supine positioning. Reproducibility may be considered as a concern for prone positioning, nevertheless, selected groups of patients such as those with pendulous breasts may substantially benefit from this positioning strategy. In this context, we consider that prone positioning may serve as a viable approach for critical organ sparing for atleast a selected subgroup of patients receiving RT for breast cancer.

Conclusions and future perspectives

Radiation oncology discipline is experiencing ever increasing advances with incorporation of modernized equipment and contemporary strategies such as BART, IGRT, IMRT, ART, and state of the art radiosurgical applications which significantly improve the toxicity profile of radiation delivery in the millennium era [15-22,65-100]. Reflections of these advances have been demonstrated as improved critical organ sparing with optimal therapeutic outcomes for patients with breast Ca. Significant achievements have been made in treatment delivery techniques along with improved therapeutic outcomes with a favorable toxicity profile. Prone positioning appears to be beneficial at least for a selected group of patients with breast Ca. Improved critical organ sparing with contemporary techniques holds promise for optimized management of breast Ca despite the need for further supporting evidence.

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74. Sager O, Beyzadeoglu M, Dincoglan F, Uysal B, Gamsiz H, et al. (2014) Evaluation of linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) for cerebral cavernous malformations: A 15-year single-center experience. Ann Saudi Med 34: 54-58. Link: https://bit.ly/3i1lpGs  
75. Demiral S, Beyzadeoglu M, Sager O, Dincoglan F, Gamsiz H, et al. (2014) Evaluation of linear accelerator (linac)-based stereotactic radiosurgery (srs) for the treatment of craniopharyngiomas. UHOD - Uluslararasi Hematoloji-Onkoloji Dergisi 24: 123-129.  
76. Dincoglan F, Sager O, Gamsiz H, Uysal B, Demiral S, et al. (2014) Management of patients with ≥ 4 brain metastases using stereotactic radiosurgery boost after whole brain irradiation. Tumori 100: 302-306. Link: https://bit.ly/382aDLp  
77. Gamsiz H, Beyzadeoglu M, Sager O, Dincoglan F, Demiral S, et al. (2014) Management of pulmonary oligometastases by stereotactic body radiotherapy. Tumori 100: 179-183. Link: https://bit.ly/31h8b28  
78. Sager O, Dincoglan F, Beyzadeoglu M (2015) Stereotactic radiosurgery of glomus jugulare tumors: Current concepts, recent advances and future perspectives. CNS Oncol 4: 105-114. Link: https://bit.ly/2VjVaRF  
79. Dincoglan F, Beyzadeoglu M, Sager O, Demiral S, Gamsiz H, et al. (2015) Management of patients with recurrent glioblastoma using hypofractionated stereotactic radiotherapy. Tumori 101: 179-184. Link: https://bit.ly/2YzAOGi  
80. Gamsiz H, Beyzadeoglu M, Sager O, Demiral S, Dincoglan F, et al. (2015) Evaluation of stereotactic body radiation therapy in the management of adrenal metastases from non-small cell lung cancer. Tumori 101: 98-103. Link: https://bit.ly/3fZ4e6w  
81. Demiral S, Dincoglan F, Sager O, Gamsiz H, Uysal B, et al. (2016) Hypofractionated stereotactic radiotherapy (HFSRT) for who grade I anterior clinoid meningiomas (ACM). Jpn J Radiol 34: 730-737. Link: https://bit.ly/3fUj9yI  
82. Dincoglan F, Sager O, Demiral S, Uysal B, Gamsiz H, et al. (2017) Radiosurgery for recurrent glioblastoma: A review article. Neurol Disord Therap 1: 1-5. Link: https://bit.ly/3eAiIJD  
83. Demiral S, Dincoglan F, Sager O, Uysal B, Gamsiz H, et al. (2018) Contemporary Management of Meningiomas with Radiosurgery. Int J Radiol Imaging Technol 80: 187-190. Link: https://bit.ly/2Nvq2uk  
84. Demiral S, Sager O, Dincoglan F, Uysal B, Gamsiz H, et al.  (2018) Evaluation of Target Volume Determination for Single Session Stereotactic Radiosurgery (SRS) of Brain Metastases. Canc Therapy  Oncol Int J 12: 555848. Link: https://bit.ly/3i0DO67  
85. Sager O, Dincoglan F, Demiral S, Gamsiz H, Uysal B, et al. (2019) Evaluation of the Impact of Magnetic Resonance Imaging (MRI) on Gross Tumor Volume (GTV) Definition for Radiation Treatment Planning (RTP) of Inoperable High Grade Gliomas (HGGs). Concepts in Magnetic Resonance Part A 2019: 4282754. Link: https://bit.ly/2VhvmFT  
86. Demiral S, Sager O, Dincoglan F, Beyzadeoglu M (2019) Assessment of target definition based on Multimodality imaging for radiosurgical Management of glomus jugulare tumors (GJTs). Canc Therapy  Oncol Int J 15: 555909. Link: https://bit.ly/3eBeZvi  
87. Dincoglan F, Sager O, Demiral S, Beyzadeoglu M (2019) Multimodality Imaging for Radiosurgical Management of Arteriovenous Malformations. Asian Journal of Pharmacy, Nursing and Medical Sciences 7: 7-12. Link: https://bit.ly/2BAAzlh  
88. Demiral S, Sager O, Dincoglan F, Beyzadeoglu M (2019) Assessment of Computed Tomography (CT) And Magnetic Resonance Imaging (MRI) Based Radiosurgery Treatment Planning for Pituitary Adenomas. Canc Therapy  Oncol Int J 13: 555857. Link: https://bit.ly/3fWmZHB  
89. Sager O, Dincoglan F, Demiral S, Beyzadeoglu M (2019) Evaluation of Radiosurgery Target Volume Determination for Meningiomas Based on Computed Tomography (CT) And Magnetic Resonance Imaging (MRI). Cancer Sci Res Open Access 5: 1-4. Link: https://bit.ly/2BA4FoS  
90. Beyzadeoglu M, Sager O, Dincoglan F, Demiral S (2019) Evaluation of Target Definition for Stereotactic Reirradiation of Recurrent Glioblastoma. Arch Can Res 7: 3. Link: https://bit.ly/2Nvtp4c  
91. Dincoglan F, Sager O, Demiral S, Beyzadeoglu M (2019) Incorporation of Multimodality Imaging in Radiosurgery Planning for Craniopharyngiomas: An Original Article. SAJ Cancer Sci 6: 103. Link: https://bit.ly/2Vi5k5m  
92. Dincoglan F, Sager O, Demiral S, Gamsiz H, Uysal B, et al. (2019) Fractionated stereotactic radiosurgery for locally recurrent brain metastases after failed stereotactic radiosurgery. Indian J Cancer 56: 151-156. Link: https://bit.ly/3i1iw8A  
93. Dincoglan F, Sager O, Uysal B, Demiral S, Gamsiz H, et al. (2019) Evaluation of hypofractionated stereotactic radiotherapy (HFSRT) to the resection cavity after surgical resection of brain metastases: A single center experience. Indian J Cancer 56: 202-206. Link: https://bit.ly/3fUhyJl  
94. Sager O, Dincoglan F, Demiral S, Gamsiz H, Uysal B, et al. (2019) Utility of Magnetic Resonance Imaging (Imaging) in Target Volume Definition for Radiosurgery of Acoustic Neuromas. Int J Cancer Clin Res 6: 119. Link: https://bit.ly/2NvDwGu  
95. Demiral S, Beyzadeoglu M, Dincoglan F, Sager O (2020) Assessment of Target Volume Definition for Radiosurgery of Atypical Meningiomas with Multimodality Imaging. J Hematol Oncol 3: 14-21. Link: https://bit.ly/3ewDh9O  
96. Beyzadeoglu M, Dincoglan F, Demiral S, Sager O (2020) Target Volume Determination for Precise Radiation Therapy (RT) of Central Neurocytoma: An Original Article. International Journal of Research Studies in Medical and Health Sciences 5: 29-34. Link: https://bit.ly/2B8KzSN  
97. Dincoglan F, Demiral S, Sager O, Beyzadeoglu M (2020) Utility of Multimodality Imaging Based Target Volume Definition for Radiosurgery of Trigeminal Neuralgia: An Original Article. Biomed J Sci  Tech Res 26: 19728-19732. Link: https://bit.ly/2ZbkUAG  
98. Sager O, Demiral S, Dincoglan F, Beyzadeoglu M (2020) Target Volume Definition for Stereotactic Radiosurgery (SRS) Of Cerebral Cavernous Malformations (CCMs). Canc Therapy  Oncol Int J 15: 555917. Link: https://bit.ly/2YxbVuT  
99. Dincoglan F, Beyzadeoglu M, Sager O, Demiral S, Uysal B, et al. (2020) A Concise Review of Irradiation for Temporal Bone Chemodectomas (TBC). Arch Otolaryngol Rhinol 6: 016-020. Link: https://bit.ly/3eyy5Cd  
100. Sager O, Dincoglan F, Demiral S, Beyzadeoglu M (2020) Radiosurgery Treatment Volume Determination for Brain Lymphomas with and without Incorporation of Multimodality Imaging. Journal of Medical Pharmaceutical and Allied Sciences 9: 2398-2404.  Link: https://bit.ly/3dy7Ryv