Radiation therapy for breast cancer: Literature review

Medical Dosimetry 41 (2016) 253–257 Medical Dosimetry journal homepage: www.meddos.org Radiation therapy for breast cancer: Literature review Karunakaran Balaji, M.Sc.,n † Balaji Subramanian, D.N.B.,n Poonam Yadav, Ph.D.,‡ Chandrasekaran Anu Radha, Ph.D.,† and Velayudham Ramasubramanian, Ph.D.† *Department of Radiation Oncology, Global Hospitals, Chennai, India; †School of Advanced Sciences, VIT University, Vellore, India; and ‡Department of Medical Physics and Human Oncology, University of Wisconsin-Madison, WI and Aspirus UW Cancer Center, Wisconsin Rapids, WI A R T I C L E I N F O A B S T R A C T Article history: Received 30 January 2016 Received in revised form 14 May 2016 Accepted 14 June 2016 Concave shape with variable size target volume makes treatment planning for the breast/chest wall a challenge. Conventional techniques used for the breast/chest wall cancer treatment provided better sparing of organs at risk (OARs), with poor conformity and uniformity to the target volume. Advanced technologies such as intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) improve the target coverage at the cost of higher low dose volumes to OARs. Novel hybrid techniques present promising results in breast/chest wall irradiation in terms of target coverage as well as OARs sparing. Several published data compared these technologies for the benefit of the breast/chest wall with or without nodal volumes. The aim of this article is to review relevant data and identify the scope for further research in developing optimal treatment plan for breast/chest wall cancer treatment. & 2016 American Association of Medical Dosimetrists. Keywords: Breast Chest wall VMAT Hybrid IMRT Introduction Breast cancer is the most common cancer in women worldwide.1 Management of breast cancer is multimodal involving surgery, radiotherapy, and chemotherapy/hormones. Radiotherapy is used in early breast cancer after breast conservation surgery and in locally advanced breast cancer patients post mastectomy.2 Meta-analysis of individual patient data by Early Breast Cancer Trialists' Collaborative Group (EBCTCG) on 10,801 breast cancer patients in 17 randomized trials concluded that, radiotherapy, following breast conserving surgery halves the rate at which the disease recurs and also reduces the breast cancer death rate by about one-sixth.3 Overall survival rate is higher for early and locally advanced breast cancer patients (93% and 72%, respectively, survived more than 5 years). Moreover, the European Organization for Research and Treatment of Cancer (EORTC) trial on boost dose vs no boost for stage I and II invasive breast cancer following breast conserving therapy showed that the delivery of 16 Gy additional boost dose reduced the risk of local relapse.4 Radiotherapy planning for breast cancer patients is technically challenging because of varying size and shape of the breast/chest wall as well as setup reproducibility and respiratory motion. In addition priority has to given to spare organs at risk (OARs) Reprint requests to Karunakaran Balaji, M.Sc., Department of Radiation Oncology, Global Hospitals, #439, Cheran Nagar Perumbakkam, Chennai 600100, India. E-mail: [email protected] such as lungs, heart and contralateral breast (CB) to avoid long-term complication and achieve good cosmetic outcomes.5 Radiation therapy techniques like 3-dimensional conformal radiation therapy (3DCRT) with/without wedges or field-in-field (FIF) method, intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), hybrid technique, helical tomotherapy (HT), and Tomo direct have been proposed for the breast cancer patients in the literature. Conventional 3DCRT uses tangential beams to avoid low dose region in the ipsilateral lung (IL) and heart. However, it results in poor conformity, homogeneity, and hot spots outside the target volume. On the other hand IMRT and VMAT improve the dose conformity of the target but at the cost of increased low dose spread to contralateral lung (CL) and CB which results in increased risk of secondary cancer.6 Additional advantages of these techniques is their ability to provide differential dose distributions, which allow the simultaneous integrated boost (SIB) delivery.7 Moreover, IMRT plans employ higher monitor units (MU) and hence increases the delivery time by 3-4 folds compared with VMAT and conventional 3DCRT. Increase in treatment time, MU, leakage, scatter radiation in IMRT has implications on tumor cell repair and repopulation.8,9 It has also been reported that these advanced planning techniques consume more planning time depending on the planner's expertise.10 Another problem associated with the breast treatment is target motion due to breathing. Breathing pattern that is difficult to control has a more pronounced effect in IMRT and VMAT compared with 3DCRT.11,12 http://dx.doi.org/10.1016/j.meddos.2016.06.005 0958-3947/Copyright Ó 2016 American Association of Medical Dosimetrists Downloaded from ClinicalKey.com at Ebling Library - University of Wisconsin System August 24, 2016. For personal use only. No other uses without permission. Copyright ©2016. Elsevier Inc. All rights reserved. 254 K. Balaji et al. / Medical Dosimetry 41 (2016) 253–257 Although these advanced techniques provide clinically acceptable treatment, innovative methods are needed for the effective reduction of heart and lung doses.13 To achieve this Mayo et al.5 developed a technique called Hybrid IMRT (H-IMRT), which is a combination of conventional open beam and inverse planned IMRT beam with different weightings. Several researchers have been reported the benefit of H-IMRT technique5,10,14-16 and helical tomotherapy (HT).17,18 The purpose of this article is to review the current available data from different radiation treatment planning techniques and to identify further research direction in breast/chest wall cancer radiation therapy. Literature was reviewed by categorizing the articles into whole breast, whole breast with boost volume (SIB technique), whole breast with nodes and chest wall with nodes target volumes. Also, the clinical studies on cosmetic outcome and secondary cancer have been reviewed. did not include the information related to MU, treatment time, and the effect of breathing on CA dose. Alternatively, Viren et al.13 study included 10 left-sided breast cancer patients. They compared 4 different techniques namely FIF, T-IMRT, T-VMAT, and continuous VMAT (C-VMAT). The whole breast PTV was delineated using RTOG guidelines and prescribed to 50 Gy in 25 fractions. Plans were generated in Monaco TPS and Oncentra TPS (FIF plan only) with 6 and 10 MV photons of Elekta infinity accelerator. The results showed superior target coverage, homogeneity, heart and lung sparing with T-VMAT, C-VMAT compared with FIF and T-IMRT (p o 0.01). IL V20 was 18.1% and 21.6% in T-VMAT and T-IMRT plans, respectively. Heart V30 was 5.7 % and 13.9% in T-VMAT and T-IMRT plans respectively. C-VMAT plan provided increased CL and CB mean dose compared with other techniques (p o 0.05). This study recommends T-VMAT plan for whole breast treatment. HT is another novel technique where the dose is delivered in a continuous spiral.20 Shiau et al.17 compared H-IMRT and HT planning for 30 left-sided early stage breast patients. The whole breast PTV dose prescription is 50.4 Gy in 28 fractions. H-IMRT, a combination of FIF and 4-fields IMRT (80% to 20%, respectively) was generated using Pinnacle-3 TPS. The HT plans were generated using Hi-ART TPS. The field width, pitch, and modulation factor values were 2.5 cm, 0.287, and 2.8, respectively. Both modalities showed similar target coverage. The CI and HI were improved in HT plan with p o 0.006. The IL V20 was 18.65% and 16.7% in H-IMRT and HT plans, respectively. The heart V25 dose was 8.04% and 1.8% in H-IMRT and HT plans, respectively. Mean dose to CL and CB were similar in both plans. This study suggests HT plan for whole breast treatment. However, there is no data about MU and treatment time in this study, which will play a vital role with HT compared with H-IMRT. Dosimetric comparison data for whole breast PTV plans from these studies are presented in Table 1. Review Whole breast Jin et al.19 conducted a dosimetric study for 20 left-sided breast cancer patients. They compared Tangential Wedge field (TW), FIF technique, Tangential IMRT (T-IMRT), Multifield IMRT (M-IMRT), and VMAT techniques. The whole breast planning target volume (PTV) was delineated as per the ICRU report #83 and the OARs including CB, heart, coronary artery (CA), IL, CL were outlined. All plans were generated in Pinnacle-9.0 (ADAC, Philips) treatment planning system (TPS) with 6 MV photons of Elekta synergy linear accelerator. The PTV was prescribed to 50 Gy in 25 fractions. The study concluded similar PTV coverage for all techniques except VMAT, which had less than 95% of the PTV receiving prescribed dose. The conformity index (CI) significantly improved in M-IMRT and VMAT plans compared with other techniques (p o 0.05). The homogeneity index (HI) is similar in T-IMRT, FIF, and M-IMRT (0.11) and significantly improved (p o 0.05) compared with TW and VMAT plans. The volume of IL, heart, and CA receiving 5, 10, 20 Gy (V5, V10, and V20) showed better results in T-IMRT (p o 0.05) compared with other techniques. The volume of IL, heart, and CA receiving 30, 40 Gy (V30 and V40) were comparable for T-IMRT, M-IMRT, and VMAT. CB mean dose was significantly less in T-IMRT compared with M-IMRT and VMAT (p o 0.05). This study favored T-IMRT technique for whole breast radiation therapy. This study Whole breast with boost volume (SIB technique) Lin et al.21 dosimetrically compared hybrid volumetric modulated arc therapy (H-VMAT), VMAT and M-IMRT plans for 10 leftsided early breast cancer patients. The target volume (whole breast) and boost PTVs were prescribed to 50.4 and 62 Gy, respectively, using SIB technique. All plans were generated using Eclipse V-10 TPS with 6 MV photons of Varian iX linear accelerator. M-IMRT plan included 7 fixed angles and VMAT included 2 partial Table 1 Dosimetric parameters for the different techniques studied in whole breast target volume Study Planning techniques Mean ⫾ SD PTV IL CI HI Heart CA CB Dmean (Gy) Dmean (Gy) Dmean (Gy) Dmean (Gy) 3.7 3.2 2.2 4.4 4.6 ⫾ ⫾ ⫾ ⫾ ⫾ 2.0 1.9 1.0† 1.9 1.7 19.4 15.5 8.9 9.9 11.0 ⫾ ⫾ ⫾ ⫾ ⫾ 10.9 10.2 5.2† 4.7† 4.6 0.4 0.4 0.4 1.6 1.9 ⫾ ⫾ ⫾ ⫾ ⫾ 0.4 0.4 0.3 0.7 1.0 6.3 5.5 9.1 9.1 ⫾ ⫾ ⫾ ⫾ 3.0† 2.9† 3.4 3.5 24.3 20.4 34.4 37.9 ⫾ ⫾ ⫾ ⫾ 8.0† 8.7† 7.0 3.6 1.2 2.6 1.0 1.0 ⫾ ⫾ ⫾ ⫾ 0.3† 1.2 0.4† 0.3† MU Dmean (Gy) V20 (%) 8.6 8.2 6.8 9.3 10.1 ⫾ ⫾ ⫾ ⫾ ⫾ 2.6 2.4 2.0† 3.8 2.5 16.9 15.0 12.9 14.6 16.4 ⫾ ⫾ ⫾ ⫾ ⫾ 5.4 5.0 4.2† 4.5 4.8 NA NA NA NA NA 9.6 8.7 10.9 10.4 ⫾ ⫾ ⫾ ⫾ 2.1 1.7 1.8 1.5 18.1 15.3 21.6 21.4 ⫾ ⫾ ⫾ ⫾ 5.3† 4.6† 4.0 3.7 0.9 1.6 0.7 0.7 Jin et al.19 TW FIF T-IMRT* M-IMRT VMAT 2.0 1.7 1.6 1.3 1.4 ⫾ ⫾ ⫾ ⫾ ⫾ 0.5 0.4 0.3 0.1† 0.2† 0.13 0.11 0.11 0.11 0.14 ⫾ ⫾ ⫾ ⫾ ⫾ 0.002 0.02 0.03 0.02 0.02 NA NA NA NA NA Viren et al.13 T-VMAT* C-VMAT T-IMRT FIF 0.50 0.50 0.45 0.47 ⫾ ⫾ ⫾ ⫾ 0.003 0.004 0.05 0.09 0.10 0.10 0.12 0.14 ⫾ ⫾ ⫾ ⫾ 0.01† 0.01† 0.02 0.01 629 678 283 233 Shiau et al.17 H-IMRT HT* 0.73 ⫾ 0.04† 0.75 ⫾ 0.04 0.92 ⫾ 0.04† 0.99 ⫾ 0.01 CL NA NA ⫾ ⫾ ⫾ ⫾ 93 98 37† 5† 10.0 ⫾ 2.5 6.5 ⫾ 1.4† 18.6 ⫾ 5.6 10.7 ⫾ 3.4† ⫾ ⫾ ⫾ ⫾ 0.1† 0.7 0.1† 0.1† 0.9 ⫾ 0.3 0.5 ⫾ 0.2† 6.1 ⫾ 2.7 2.8 ⫾ 1.2† NA ¼ parameter not analyzed; SD ¼ standard deviation. n † Favorable technique. Values significantly differ from other techniques (p o 0.05). Downloaded from ClinicalKey.com at Ebling Library - University of Wisconsin System August 24, 2016. For personal use only. No other uses without permission. Copyright ©2016. Elsevier Inc. All rights reserved. NA NA 1.3 ⫾ 0.8 1.3 ⫾ 0.7 K. Balaji et al. / Medical Dosimetry 41 (2016) 253–257 255 Table 2 Dosimetric parameters for the different techniques studied in whole breast with boost target volume (SIB technique) Study Planning techniques Mean þ SD PTV Lin et al. 21 Jeulink et al.22 IL CI HI M-IMRT VMAT H-VMAT† 0.786 ⫾ 0.035 0.840 ⫾ 0.024 0.841 ⫾ 0.028n 9.55 ⫾ 1.78 10.52 ⫾ 1.22 7.56 ⫾ 1.44n H-IMRT† M-IMRT 2ARC 6ARC NA NA NA NA NA NA NA NA MU 958.6 ⫾ 108.2 539.1 ⫾ 31.5n 490.6 ⫾ 69.8n 698.1 1546.9 729.5 902.8 ⫾ ⫾ ⫾ ⫾ 98.7n 320.0 62.9 86.6 CL Heart CB Dmean (Gy) V20 (%) Dmean (Gy) Dmean (Gy) Dmean (Gy) 11.55 ⫾ 0.8 11.52 ⫾ 0.6 10.17 ⫾ 0.9n 15.2 ⫾ 1.8 15.9 ⫾ 1.6 14.5 ⫾ 1.8n 5.25 ⫾ 0.31 5.87 ⫾ 0.46 2.45 ⫾ 0.56n 15.09 ⫾ 1.11 14.85 ⫾ 2.51 7.15 ⫾ 1.25n 4.84 ⫾ 0.50 5.95 ⫾ 0.89 2.05 ⫾ 0.34n 6.5 6.1 7.1 5.1 ⫾ ⫾ ⫾ ⫾ 2.3 1.3 1.5 0.8n 11.7 7.0 9.1 6.0 ⫾ ⫾ ⫾ ⫾ 5.5 2.0 3.4 2.2n 0.5 1.2 1.7 1.8 ⫾ ⫾ ⫾ ⫾ 0.3n 0.3 0.8 0.7 3.8 4.8 5.0 3.9 ⫾ ⫾ ⫾ ⫾ 1.8n 1.9 1.5 1.9n 0.6 1.6 2.4 2.4 ⫾ ⫾ ⫾ ⫾ 0.3n 0.2 0.4 0.4 NA ¼ parameter not analyzed; SD ¼ standard deviation. n † Values significantly differ from other techniques (p o 0.05). Favorable technique. arcs. For the H-VMAT plan, 2 T-IMRT fields and 2 conformal arcs were integrated. The H-VMAT plan provided better target coverage, CI and HI compared with other techniques (p o 0.0002). Moreover, H-VMAT plan generated less mean dose to IL, heart, CL and CB (p o 0.0001). The V5 of IL and CL were 72.4, 74.2, 48.6% and 42.9, 49.7, 5.0% for the M-IMRT, VMAT and H-VMAT plans respectively (p o 0.0001). The MU was 958.6, 539.1, and 490.6 for the M-IMRT, VMAT, and H-VMAT plans, respectively (p o 0.0001). Study concluded that H-VMAT plan is feasible for whole breast irradiation. Jeulink et al.22 conducted a planning comparison study using H-IMRT, M-IMRT, VMAT 2 partial arcs (2ARC) and 6 partial arcs (6ARC) under max inspiration breath hold (MIBH) and free breath conditions. And 10 left-sided breast patients were planned with whole breast PTV and PTV boost. The dose prescriptions were 40.05 Gy (15 fractions of 2.67 Gy) and 50.25 Gy (15 fractions of 3.35 Gy) to the breast and boost PTV, respectively. All plans were generated using Eclipse V-10 TPS with 6 MV photons. In the results, H-IMRT provided improved mean and low dose volume to OARs sparing and PTV coverage, homogeneity. 6ARC had shown better intermediate high dose sparing, but with the cost of more dose to CL and CB. The MU was less with H-IMRT (698) than 2ARC (729), 6ARC (903), and M-IMRT (1547) plans. This study concluded that H-IMRT offers better plan for breast treatment under free breath as well as MIBH condition. Dosimetric comparison data for whole breast with boost PTV plans from these studies are presented in Table 2. Whole breast with nodes Amoush et al.16 compared single-isocenter H-IMRT and 2isocenter conventional 3D plans. Overall, 15 (8 right and 7 left) breast patients were selected for this study. The PTV included whole breast and supraclavicular nodes and was prescribed to 50 Gy in 25 fractions. All plans were generated in Pinnacle TPS with 6 and 10 MV photons of Siemens ARTISTE linear accelerator. The results favored both the techniques in terms of dose coverage and HI. The total lung V20 and heart V30 was 13.6% vs 14.3% (p ¼ 0.03) and 1.25% vs. 1.2% (p ¼ 0.62) respectively. No significant difference is seen in CB dose. The MU was less in 3D plan (270.3 þ 92.7) compared with H-IMRT (324.1 þ 99.1). This study shows dosimetric equivalency of H-IMRT and 3D plans, but the author suggested single-isocenter H-IMRT as it reduce the treatment time as well as treatment uncertainties due to couch and collimator rotations. Meanwhile there was no discussion about the optimal weight between 3D and IMRT to create H-IMRT plans. Dosimetric comparison data for whole breast with nodal PTV plans from this study are presented in Table 3. Chest wall with nodes Internal mammary nodes (IMN) irradiation along with chest wall is performed in high-risk breast patients. Planning chest wall with IMN is more challenging. Because of the wider target, there is a concern of IL and heart dose. Johansen et al.23 published a work which compares FIF, IMRT, rapid arc (RA) planning techniques on 8 (5 right and 3 left) patients with stage II to III breast cancer. The PTV includes chest wall, infraclavicular, axillary nodes, and IMN and other OARs were delineated. This study also predicts the excess relative risk (ERR) for induced cancer in CB using linear and nonlinear models. FIF plans were generated in Oncentra TPS with 6 MV photons of Varian clinic 2100CD with multileaf collimator (MLC) 80 leaves. IMRT and RA plans were produced in Eclipse TPS with 6 MV photons of Varian 6EX with MLC 120 leaves. The PTV was prescribed to 50 Gy in 25 fractions. All plans were normalized to PTV mean dose. The results revealed improved HI and CI with Table 3 Dosimetric parameters for the different techniques studied in whole breast with nodal target volume Study Planning techniques Mean ⫾ SD PTV Amoush et al.16 H-IMRT* 3DCRT Total Lung CB Heart HI MU V20 (%) V1 (%) V30 (%) 0.91 ⫾ 0.01 0.91 ⫾ 0.02 324.1 ⫾ 99.1 270.3 ⫾ 92.7† 14.3 ⫾ 6.5 13.6 ⫾ 5.8† 1.07 ⫾ 1.7 0.7 ⫾ 1.2 1.22 ⫾ 2.2 1.25 ⫾ 2.2 NA ¼ parameter not analyzed; SD ¼ standard deviation. n † Favorable technique. Values significantly differ from other techniques (p o 0.05). Downloaded from ClinicalKey.com at Ebling Library - University of Wisconsin System August 24, 2016. For personal use only. No other uses without permission. Copyright ©2016. Elsevier Inc. All rights reserved. 256 K. Balaji et al. / Medical Dosimetry 41 (2016) 253–257 Table 4 Dosimetric parameters for the different techniques studied in chest wall with nodal target volume Study Planning techniques Mean ⫾ SD PTV CI Johansen et al. 23 Dumane et al.24 IL HI CL Dmean (Gy) V20 (%) Heart Dmean (Gy) n CB Dmean (Gy) n Dmean (Gy) FIF M-IMRT RA† 2.0 ⫾ 0.2 1.2 ⫾ 0.2n 1.3 ⫾ 0.0 NA NA NA 18.0 ⫾ 1.0 13.6 ⫾ 1.8n 14.3 ⫾ 0.9n 41.5 ⫾ 2.7 18.6 ⫾ 3.8n 24.0 ⫾ 3.3 1.4 ⫾ 0.3 2.9 ⫾ 0.4 2.9 ⫾ 0.4 2.6 ⫾ 1.6 5.5 ⫾ 1.3 4.6 ⫾ 2.4 2.2 ⫾ 1.0 2.9 ⫾ 0.8 2.0 ⫾ 0.4 VMAT† M-IMRT 3DCRT 1.13 1.11 1.39 1.17 1.11 1.16 13.57 15.83 20.68 20.24 22.33 39.05 2.83 3.46 0.55 6.64 6.17 3.14 1.88 2.02 0.29 NA ¼ parameter not analyzed; SD¼ standard deviation. n † Values significantly differ from other techniques (p o 0.05). Favorable technique. RA plans. IMRT and RA plans spare IL better, whereas FIF spare CL and heart better. The mean and maximum dose to CB was lowest for RA plans. The mean predicted ERR by linear model was lower in FIF and RA than IMRT plans. This work observed no detriment in FIF and RA plans while showed higher risk in CB with IMRT plan. Similar study was done by Dumane et al.24 by comparing VMAT, IMRT, and 3DCRT plans in right sided chest wall and nodal regions. 3DCRT plan used both photon and electron beams together. The VMAT plan contains 2 continuous partial arcs and the IMRT plan used nine equally spaced static fields. The dose prescription was 50.4 Gy to the PTV that includes chest wall, supraclavicular, axillary nodes, and IMN. The Eclipse V-10 TPS was used to create plans with 6 MV photons and 12 MeV electrons. The results demonstrated comparable target coverage from all plans. However, VMAT showed improved CI, HI over 3DCRT by 18.75% and 2%, respectively. The IL V20 from VMAT, IMRT, and 3DCRT were 20.24%, 22.33%, and 39.05%, respectively. The mean dose to the heart, CL and CB were reduced with 3DCRT compared with VMAT and IMRT. The MU and treatment time were reduced with VMAT compared with IMRT by 30% and 10%, respectively. This study recommends VMAT plans superior to the IMRT and 3DCRT. However, this study results were concluded from single patient data and might not be considered reliable. Dosimetric comparison data for cheat wall with nodal PTV plans from these studies are presented in Table 4. Clinical study Pignol et al.25 reported a clinical study that compared 3D with wedge compensation and IMRT plans. A total of 358 whole breast patients were randomized to receive either IMRT or 3D. The dose prescription was 50 Gy to whole breast and with or without electron boost of 16 Gy to tumor bed. They assessed skin toxicity weekly during the treatment and up to 6 weeks post-treatment. They found that IMRT compared with 3D provided reduced moist desquamation in all breast quadrants (31% vs 48%, p ¼ 0.0019) and in the inframammary fold (26% vs 43%, p ¼ 0.0012). IMRT treatment significantly reduced the grade 3 to 4 skin toxicity in inframammary fold (p o 0.05), whereas no significant results were found in all breast quadrants (p ¼ 0.2). They reported that the increased skin toxicity during the treatment course has also been depended the breast volume of patients. This clinical study should have also included the advanced chest wall patients, where the likelihood of skin toxicity is more. Further long-term follow up is needed to predict the risk of secondary malignancies.26 Abo-Madyan et al.27 estimated the secondary cancer risk after radiotherapy for breast cancer using organ equivalent dose and excess absolute risk (EAR) concepts. They compared 3DCRT, T-IMRT, M-IMRT, VMAT plans in 10 (5 right and 5 left) patients. The whole breast PTV was prescribed to 50 Gy in 25 fractions. The organs of interest for the calculation of organ equivalent dose are both lungs and CB. The second cancer risk was estimated using linear, linear-exponential and plateau models. The cumulative (Both lungs þ CB) EAR for 3DCRT is 29 ⫾ 7, 70þ24 and 27 ⫾ 6 for the linear-exponential, linear and plateau model respectively. Compared with 3DCRT, EAR value for T-IMRT, M-IMRT, and VMAT are increased by 2% ⫾ 15%, 131% ⫾ 85%, 123 ⫾ 66% for linear-exponential model, 9% ⫾ 22%, 82 ⫾ 96%, 71% ⫾ 82% for linear model, and 3% ⫾ 14%, 123% ⫾ 78%, 113% ⫾ 61% for plateau model, respectively. Second cancer risk after 3DCRT or T-IMRT is lower than M-IMRT or VMAT by about 34% for linear model and 50% for the linear-exponential and plateau models, respectively. Discussions The recommended technique for whole breast radiotherapy is varied as evident in this review. For whole breast target Jin et al.19 recommended T-IMRT, whereas Viren et al.13 favored T-VMAT and Shiau et al.17 preferred HT over H-IMRT. Further data comparing T-IMRT, T-VMAT and HT techniques is needed to decide upon the dosimetric superiority of one technique over the others. Similarly, for whole breast with boost volume target Lin et al.21 recommended H-VMAT and Jeulink et al.22 favored H-IMRT. Amoush et al.16 work suggested H-IMRT for whole breast with nodal PTV. This scenario also requires further research comparing H-VMAT and H-IMRT techniques. Early diagnosis through screening in developed nations has led to more focus on early stage patients undergoing whole breast radiotherapy with or without nodal irradiation. On the other hand, the dosimetric comparison data on chest wall with nodal volumes are sparse. Unlike whole breast treatment, chest wall irradiation is more challenging in terms of thin target volume along lung interface. For chest wall with nodal irradiation, both Johansen et al.23 and Dumane et al.24 favored VMAT in their comparison study. In Abo-Madyan et al.27 clinical study, they calculated the second cancer risk after 3DCRT or T-IMRT using predictive models and found that it was lower than M-IMRT or VMAT. This leads further investigation on hybrid treatment technique which provides dosimetric and clinical benefit while having less low dose spillage. Hybrid is a combination of techniques that would further improve the treatment of breast as well as chest wall. Detailed research is required among different hybrid techniques to explore its benefit. An important area of concern in breast/chest wall irradiation has been the effect of organ motion. Michalski et al.28 provided the details of breathing magnitude during breast irradiation. The Downloaded from ClinicalKey.com at Ebling Library - University of Wisconsin System August 24, 2016. For personal use only. No other uses without permission. Copyright ©2016. Elsevier Inc. All rights reserved. K. Balaji et al. / Medical Dosimetry 41 (2016) 253–257 magnitudes of intrafraction motion are 1.19, 1.26, 1.82 mm in central lung distance, central beam edge to skin distance, and in craniocaudal distance, respectively. For inter-fraction motions, the magnitudes are 2.21, 1.9, 2.2, 2.6 and 3.18 in central lung distance, central irradiated width , central beam edge to skin distance, craniocaudal distance and central breast distance, respectively.28 Jain et al.29 also investigated the organ motion effect during whole breast IMRT delivery. They conducted a daily cone beam computed tomography imaging study to quantify3D organ motion. They concluded that the IMRT dose homogeneity remained stable throughout the treatment course irrespective of target motion. More studies needs to be done using in-vivo dosimetric measurements for different planning techniques to reveal the actual dose effect due to target motion. Conclusions Planning breast radiation therapy is always a challenging task. Improvements in radiotherapy planning and imaging techniques have helped in overcoming this challenge to some extent. Most of the articles reviewed here favored hybrid planning technique. Detailed research and analysis is further required among various hybrid techniques for improvisation. Eventually studies reviewed here belonged to different clinical scenario like patients, volume of irradiation, techniques, treatment planning systems and planners. Considering the uniqueness of every patient more research on planning techniques is required to recommend a particular technique for a particular kind of patient/target. As there is paucity in number of robust clinical outcome studies with long-term follow up in patients treated with these advanced techniques, prospective clinical studies are the need of the hour. References 1. Bray, F.; Ren, J.S.; Masuyer, E.; et al. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int. J. Cancer 132(5):1133–45; 2013. 2. 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