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Dosimetric and radiobiological comparison of simultaneous integrated boost radiotherapy for early stage right side breast cancer between three techniques: IMRT, hybrid IMRT and hybrid VMAT

Dosimetric and radiobiological comparison of simultaneous integrated boost radiotherapy for early... Purpose: This study aimed at evaluating the clinical impact of full intensity-modulated radiotherapy (IMRT ), hybrid IMRT (H-IMRT ) and hybrid volumetric-modulated arc therapy (H-VMAT ) for early-stage breast cancer with simultane- ous integrated boost (SIB), in terms of plan quality and second cancer risk (SCR). Methods: Three different plans were designed in full IMRT, hybrid IMRT, and hybrid VMAT for each of twenty patients with early-stage breast cancer. Target quality, organs at risk (OARs) sparing, and SCR were compared among the three plans for each case. Results: In compared with H-IMRT, IMRT plans showed deterioration in terms of D of SIB, V of ipsilateral lung, and 2% 10 excess absolute risk (EAR) to contralateral lung (C-Lung) and esophagus. D and the homogeneity index (HI) of SIB, 2% V5 of ipsilateral lung (I-Lung), the D of the esophagus, the EAR to C-Lung and the esophagus with hybrid VMAT mean dramatically increased by 0.63%, 10%, 17.99%, 149.27%, 230.41%, and 135.29%, respectively (p = 0.024; 0.025; 0.046; 0.011; 0.000; 0.014). D of the heart, the EAR to contralateral breast (C-Breast) and C-Lung by full IMRT was signifi- mean cantly decreased in comparison to the H-VMAT (4.67%, p = 0.033, 26.76%, p = 0.018; 48.05%, p = 0.036). Conclusion: The results confirmed that H-IMRT could achieve better target quality and OARs sparing than IMRT and H-VMAT for SIB radiotherapy of early-stage right breast cancer. H-IMRT was the best treatment option, while H-VMAT performed the worst among the three plans in terms of SCR to peripheral OARs. Keywords: Breast cancer, Second cancer risk, IMRT, Hybrid IMRT, Hybrid VMAT Introduction Usually diagnosed as early-stage female cancer, the 5-year specific survival rate of breast cancer is up to 98.9% [1]. Whole breast radiotherapy (RT) and a boost to the tumor bed is considered as the adjuvant therapy after *Correspondence: daizt_sinap@163.com breast-conserving surgery for early-stage breast cancer Suyan Bi and Rui Zhu have contributed equally to this work [2, 3]. Studies confirmed that patients benefited from RT National Cancer Center/National Clinical Research Center for Cancer/ Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical and tumor bed boosting [3, 4]. Sciences and Peking Union Medical College, Shenzhen 518116, China Full list of author information is available at the end of the article © The Author(s) 2022. 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The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Bi et al. Radiation Oncology (2022) 17:60 Page 2 of 10 Various RT techniques, such as three-dimensional con- treatment, 3D-CRT technique may result in worse target formal radiation therapy (3D-CRT), intensity-modulated uniformity compared with IMRT and VMAT techniques. radiation therapy (IMRT), and volumetric-modulated arc Therefore, 3D-CRT was usually replaced by modern therapy (VMAT), have been adopted for treating breast intensity modulation technology in SIB treatment for cancer. Utilizing two opposed, wedged, and tangential early stage breast cancer. fields, 3D-CRT treating the whole breast is carried out To pursue an excellent target dose coverage and OARs with multi-leaf collimators (MLCs) to shield the adjacent sparing, and also lower the SCR and radiation toxicity, normal tissue. Many studies [5–7] have been confirmed selecting a reasonable RT modality is critical for treating that tangential field techniques such as dynamic wedge breast cancer. To the best of our knowledge, the clinical and field-in-field techniques are used for whole-breast impact of hybrid VMAT for early stage breast cancer with radiation can improve dose uniformity to the tumour. SIB treatment has not been studied. This study aimed at 3D-CRT has the advantage of improving the local con- assess the plan quality and SCR among three treatment trol, but the toxicities associated with radiation to the modalities (full IMRT, hybrid IMRT, and hybrid VMAT) organs at risk (OARs) are a concern [8]. Dividing each for SIB treatment of early stage breast cancer. beam into smaller beamlets, IMRT delivers a non-uni- form fluence to optimize the dose distribution [8]. VMAT Materials and methods can rotate the angle of gantry and radiate beams contin- Patients preparation uously, and modulate the dose rate (DR) and the shape Twenty females aged between 31 and 64  years old, with of the MLCs simultaneously to achieve a highly confor- early-stage right-sided breast cancer after breast-con- mal dose coverage [9]. IMRT and VMAT were reported serving surgery, were randomly selected. None of the to have incomparable advantages in dose homogeneity patients had contraindications for RT. This study was and coverage compared with 3D-CRT [9, 10]. However, approved by the ethics committee of National Cancer IMRT might be more susceptible to setup error and Center/National Clinical Research Center for Cancer/ shape changes of the breast in whole breast RT [10]. To Cancer Hospital & Shenzhen Hospital, and the informed reduce the effects of the geometrical uncertainties, Naka - consent was acquired from each enrolled patient. mura et al. [11] proposed a method of hybrid IMRT plan All of the patients were positioned with a breast comprised of two opposed tangential open beams and bracket and fixed foam plate on the affected side of the two inverse-planned IMRT beams. And they proved the lower limbs. The computed tomography (CT) scans were hybrid IMRT had excellent performance in target quality acquired on a Philips Brilliance Big Bore CT (Philips, and offsetting the geometrical uncertainties for patients Holland) simulation in 5-mm-thick slices, in the supine who underwent whole breast RT [12]. position with the scan scope from the mandible to the With the advancement of medical technology, systemic thorax. In addition, all of the adjacent normal tissues, therapy and radiation therapy techniques have greatly such as the heart, lung, esophagus, and contralateral lengthened the life span of women with breast cancer. breast, were completely covered. This, however, may increase the likelihood of radiation- induced secondary cancers. RT resulted in inevitably Contouring of target volumes and OARs radiation damage and therapy-related second cancer risk Target volumes and OARs were delineated on the Eclipse (SCR) for normal tissue, which was confirmed by studies treatment planning system (Version 13.6, Varian Medi- [12, 13]. With the improvement of the efficacy and overall cal Systems Inc.). The clinical target volume (CTV) and survival of breast cancer patients, the SCR and radiation the boost region were delineated by the same radiation toxicity caused by RT has gradually become a research oncologist on each CT data set. The CTV was the whole focus. Although IMRT, hybrid IMRT, hybrid VMAT and breast tissue identifiable on the CT scan assisted by wire VMAT have been shown to improve dose conformity markers, which were placed around the palpable breast and reduce dose to organs at risk (OARs) compared with tissue during the simulation. Then the CTV limited 3D-CRT, organ doses to out-of-field regions were greater posteriorly by the intercostal front and retracted 5  mm with IMRT or VMAT than with 3D-CRT, due to the for- from the skin. The boost region encompassed the surgi - mer methods having greater scattering and monitor unit cal bed or seroma. The planning target volume (PTV) (MU) [14–17]. Early studies showed that 3D-CRT pos- was expanded 5  mm based on the CTV, excluding the sesses a lower SCR than IMRT and VMAT for the [18, heart. Then the PTV was retracted 5  mm from the skin 19]. In clinical breast cancer treatment, however, the and limited posteriorly by the intercostal front. The boost uniformity of the target area and the dose of normal tis- region was expanded by 5  mm in all directions to cre- sue should be considered simultaneously. When con- ate the SIB (simultaneous integrated boost) volume. The sidering early stage breast cancer with SIB radiotherapy contoured OARs were the contralateral breast (C-Breast), Bi  et al. Radiation Oncology (2022) 17:60 Page 3 of 10 heart, spinal cord, esophagus, and ipsilateral (I-Lung) and Table 1 Dose targets and constraints for treatment planning contralateral lungs (C-Lung). Before RT planning, we Structure Metrics Objective should also deal with the lead wire marked on the body SIB V (%) ≥ 95% surface during CT positioning and modify its CT values 49.5Gy V (%) < 20% to -1000HU to reduce the impact on dose distribution. In 55Gy D (Gy) < 60 Gy order to avoid the target receiving insufficient radiation max PTV-SIB V (%) ≥ 95% dose because of the target  changes in size due to edema 43.5Gy (%) < 20% during treatment or residual displacement due to breath- 48Gy D (Gy) < 52 Gy ing not properly controlled, a 10  mm artificial expan - max I-Lung V (%) < 60% sion with soft-tissue equivalent HU was added in the 5Gy V (%) < 40% breast region and the PTV contours toward the external 10Gy V (%) < 20% direction. 20Gy V (%) < 15% 30Gy D (Gy) < 15 Gy RT plans mean C-lung V (%) < 20% Figure 1 showed the fields distributions in CT images for 5Gy Heart D (Gy) < 4 Gy the three RT techniques respectively. Three different RT mean C-Breast D (Gy) < 40 Gy plans (full IMRT, hybrid IMRT, and hybrid VMAT) were max created for each case in the Eclipse TPS. Utilizing 6 MV (Gy) < 3 Gy mean photon beams generated by Varian IX linear accelerator, Spinal cord D (Gy) < 45 Gy max dose optimization and calculations were done in Eclipse TPS for all of the plans. The algorithms of Dose-Volume position of jaws of all of the fields were adjusted before Optimizer and Progressive Resolution Optimizer were dose optimization to maximize the protection of the used for IMRT, and VMAT dose optimization, respec- lungs. All of the fields were delivered with dynamic slid - tively, and Anisotropic Analytical Algorithm was adopted ing-window IMRT delivery technique and the fixed DR for final dose calculations [20, 21]. For the purpose of of 600 monitor units (MUs)/min. comparison, all the plans were normalized so that 95% of PTV covered by 43.5 Gy. All the plans were optimized with the same dose constraints [22] as was detailed in Hybrid IMRT Table 1. The hybrid IMRT plans owned two opposed tangential open beams plus three IMRT beams. Two of the three Full IMRT IMRT beams were at the angles of 10° to the two tan- The full IMRT plans contained two opposed tangential gential fields in the direction of outside the body, and fields, and the other four fields that were at the angles the third IMRT beam had an angle of about 30° to 45° of 10° or 20° to the two tangential fields in the direction to the tangential field on the upper side avoiding expo - of outside the body. The angles of the collimator and the sure to the heart and contralateral breast. To maximize Fig. 1 Target volume contouring and field arragement display of three irradiation techniques: a IMRT, b Hybrid IMRT (H-IMRT ) and c Hybrid VMAT (H-VMAT ). The yellow straight lines, red straight lines, and yellow arc represent IMRT beams, tangential beams and partial arc beam, respectively. The green area is the planning target volume (PTV ), and the light blue area is simultaneous integrated boost (SIB) Bi et al. Radiation Oncology (2022) 17:60 Page 4 of 10 the protection of the lungs, the angles of the collimator using HI = (D -D )/D , where D and D are 5% 95% mean 5% 95% of the three IMRT beams were adjusted, and the posi- the minimum dose radiated to 5% and 95% of the SIB, tion of the jaws of the third IMRT beam was adjusted and respectively. PTV-SIB: the D , the D, V and CI of 2% mean 95%, fixed, adapting the shape of the SIB before dose optimi - PTV-SIB were assessed. These indicators were defined as zation and calculation. The adopted delivery technique described above. OARs: the D and D of contralat- max mean and DR were the same as that of the full IMRT plans. The eral breast, heart, spinal cord and esophagus, and the open beams contributed 80% of the total dose, whereas D of contralateral lung were executed for dosimetric mean the inversely optimized IMRT beams contributed to the analysis. The V (the percentage volume receiving 5 Gy), remaining prescription dose. V (the percentage volume receiving 10  Gy), V (the 10 20 percentage of volume receiving 20 Gy), V (the percent- age of volume receiving 30 Gy), and D of the ipsilat- Hybrid VMAT mean eral lung and combined lung were also evaluated. The hybrid VMAT plans owned two opposed tangen - tial open beams and a half arc beam. The gantry of the SCR calculations arc beam rotated from one tangential angle to the other The SCR caused by RT of normal tissues can be assessed tangential angle. The maximum DR of the arc beam was by excess absolute risk (EAR) model, as proposed by Sch- set to 600 MUs/min. The open beams contributed with neider [23, 26]. The EAR to develop a solid cancer after 80% of the total dose, whereas the inversely optimized arc exposure to radiation has been estimated from data of beams contributed to the remaining prescribed dose. the atomic bomb survivors for different kinds of solid For the SIB and PTV-SIB of all of the plans, the pre- cancer and describes the absolute difference in can - scribed doses were 49.50 and 43.50  Gy in 15 fractions, cer rates of persons exposed to a dose d and those not respectively. The prescribed 95% isodose covered no exposed to a dose beyond the natural dose exposion per less than 95% of the target volume [23], and the per- 10,000 person-years per Gy. The Eq. (1) shown below can centage volume of the target volume radiated over 110% be utilized to calculate the SCR of an organ [27, 28]: of the prescribed dose was no more than 2%. The dose constraints for adjacent OARs of contralateral breast, org heart, ipsilateral lung, contralateral lung, spinal cord, and EAR = V (D )β RED(D )μ(x, a) i EAR i (1) esophagus were defined according to published litera - i ture [24]. According to the planning method of Giorgia where V is the total organ volume assessed for second- Nicolini [25], in order to avoid the target receiving insuf- ary carcinogenesis, V (D ) represents the organ volume ficient radiation dose because of the target  changes in receiving the dose D , and the parameter β is the slope i EAR size due to edema during treatment or residual displace- of the dose–response curve in the low dose region. Equa- ment due to breathing not properly controlled, we give tion (2), RED (D ), represents the dose–response mecha- a 10  mm artificial expansion with soft-tissue equivalent nistic model, which describes the fractionation effects HU of the body in the breast region and of the PTV con- and cell killing: tours toward the external direction for the full IMRT and VMAT plans. −α D i ′ e ′ α R 2 α D 2 − D 1−R RED(D ) = 1 − 2R + R e − (1 − R) e α R Treatment plan evaluation (2) The data collected from the Dose-Volume Histogram where R is a parameter that represents the repopulation (DVH) of all of the plans were evaluated in the aspect or repair ability of normal tissues between two dose frac- of target coverage and OARs sparing. SIB: the maxi- tions, and the parameter α′ was calculated by Eq. (3): mum dose (D ), the mean dose (D ), and V of max mean 95% α = α + βd = α + βD /D d SIB were assessed. The D of SIB, also named D , (3) i T T max 2% is defined as the dose received by 2% of the target vol - where D is the prescribed dose of 49.50 Gy to the SIB in ume, and V is defined as the percentage volume 95% this study, and d represents the corresponding fraction- of the target volume receiving 95% of the prescribed ation dose of 3.3  Gy. Given by Eq.  (4), µ (x, a) expresses dose. The conformal index (CI) and homogeneity index the modifying function: (HI) were also evaluated. The CI of SIB is defined as CI = TV /(TV × PIV ) utilizing the Paddick conform- [γ e(x−30)+γ a ln(a/70)] PTV μ(x, a) = e (4) ity index, where the TV was the SIB volume receiving PTV 95% of the prescription dose, the TV is the total volume where γ and γ are both the age modifying parameters. e a of the SIB, and the PIV is the total volume covered by In this study, the EAR has been investigated to the the prescribed 95% isodose. The HI of SIB was assessed organs of contralateral breast, contralateral lung, Bi  et al. Radiation Oncology (2022) 17:60 Page 5 of 10 ipsilateral lung, and esophagus. The assumed value of (99.37 ± 0.51) was better than that of the full IMRT and α/β = 3 Gy for all of the organs needed to evaluate EAR, the hybrid VMAT (98.99 ± 0.42, 99.03 ± 0.67). The find - and all of the other parameters used in EAR calculation ings on SIB and PTV-SIB are listed in Table 3. were taken from previous research [27] and were shown in Table 2. OARs The DVHs of ipsilateral lung (I-Lung), contralateral lung Statistical analysis (C-Lung), heart, contralateral breast (C-Breast), esopha- All the parameters were calculated from the DVHs. Sta- gus, and spinal cord of one representative case are dis- tistical analyses were carried out using IBM SPSS Statis- played in Fig.  4a–f, respectively. The delivered doses to tics version 21 (SPSS Inc.Armonk, NY). A paired t-test the OARs are listed in Table 4. Compared with the hybrid was performed to analyze the difference between three IMRT, V of ipsilateral lung, the Dmean of the esopha- techniques, and a p value < 0.05 was considered to reveal gus with hybrid VMAT increased by 17.99% and149.27%, statistical significance. respectively (p = 0.046; 0.011), the V of ipsilateral lung with full IMRT increased 18.52% (p = 0.013), and the Results Dmean of the heart with hybrid VMAT dramatically Target volume increased by 4.67% compared with the hybrid VMAT The comparison of isodose lines from 500 to 4950  cGy (p = 0.033). for a selected case is illustrated in Fig.  2. The DVHs of SIB and PTV-SIB of one representative case are displayed SCR calculations in Fig.  3a, b, respectively. The parameters of D, D , The EAR of the organs of contralateral breast, contralat - 2% mean V , CI, and HI were compared to evaluate the quality of eral lung, ipsilateral lung, and esophagus with three treat- 95% target dose coverage. For SIB, the hybrid IMRT obtained ment modalities are shown in Table  5. Compared with a lower D than both full IMRT and hybrid VMAT hybrid VMAT, the EAR to the contralateral breast with 2% (p < 0.05) and achieved better HI than the hybrid VMAT full IMRT and hybrid IMRT were decreased by 26.76% (p < 0.05). For the PTV-SIB, the V of the hybrid IMRT and 33.48%, respectively (p = 0.018; 0.031), and the EAR 95% Table 2 Model parameters used in EAR calculation Structure β γ γ α α/β R EAR e a C-Breast 9.2 − 0.037 1.7 0.044 3 0.15 I-Lung 7.5 0.002 4.23 0.042 3 0.83 C-Lung 7.5 0.002 4.23 0.042 3 0.83 Esophagus 0.58 − 0.002 1.9 0.026 3 0.81 Fig. 2 Comparison of planar dose distribution in cGy for a representative patient with three irradiation techniques: a IMRT, b Hybrid IMRT (H-IMRT ) and c Hybrid VMAT (H-VMAT ) Bi et al. Radiation Oncology (2022) 17:60 Page 6 of 10 Fig. 3 DVHs of a SIB and b PTV-SIB for the representative patient with IMRT (red line), Hybrid IMRT (orange line) and Hybrid VMAT (blue line) Table 3 Comparison of dosimetric parameters of SIB and PTV-SIB between IMRT, H-IMRT and H-VMAT Structure Parameters IMRT H-IMRT H-VMAT p value a b c SIB D (Gy) 52.73 ± 0.63 52.35 ± 0.60 52.68 ± 0.48 0.042 0.776 0.024 2% D (Gy) 51.18 ± 0.47 51.18 ± 0.59 51.41 ± 0.38 0.197 0.322 0.181 mean V (%) 99.88 ± 0.33 99.96 ± 0.11 100.00 ± 0.00 0.317 0.225 0.224 95% CI 0.82 ± 0.06 0.84 ± 0.05 0.84 ± 0.04 0.202 0.163 0.747 HI 0.12 ± 0.06 0.12 ± 0.02 0.13 ± 0.02 0.575 0.174 0.025 PTV-SIB D (Gy) 49.40 ± 0.68 49.29 ± 0.45 49.21 ± 0.39 0.581 0.359 0.461 2% D (Gy) 45.69 ± 0.42 45.60 ± 0.23 45.57 ± 0.28 0.438 0.264 0.660 mean V (%) 98.99 ± 0.42 99.37 ± 0.51 99.03 ± 0.67 0.06 0.621 0.076 95% CI 0.63 ± 0.08 0.65 ± 0.10 0.650 ± 0.09 0.38 0.35 0.252 a: IMRT versus H-IMRT; b: IMRT versus H-VMAT; c: H- IMRT versus H-VMAT to the contralateral lung with full IMRT and hybrid clinical options to RT with SIB for early-stage right-sided IMRT were reduced by 48.05%, and 230.41%, respectively breast cancer. (p = 0.036; 0.000). In comparison with the hybrid IMRT, IMRT showed a significant advantage in target dose the EAR to the esophagus with full IMRT and hybrid coverage, and surrounding OARs spring for left-sided VMAT increased 127.94% and 135.29%, respectively breast cancer after breast-conserving surgery [8–10]. (p = 0.030; 0.014) and the EAR to the contralateral lung This could result in better tumor control rate and lower with full IMRT was increased 71.64% (p = 0.048). toxicity, and late effects compared with the conven - tional tangential pair treatment beams. However, IMRT had inherent geometrical uncertainties arising from Discussion and conclusion setup error and target motion, which offset the merits Since studies evaluating the hybrid IMRT and hybrid of IMRT for breast cancer [10, 12, 29]. Combining two VMAT for early-stage breast cancer with SIB are rare, opposed tangential open beams and IMRT beams, the a comparison of the target dose coverage, OARs spar- hybrid IMRT plan might solve the geometrical uncer- ing, and SCR among full IMRT, hybrid IMRT, and hybrid tainties of IMRT. Nakamura et al. [12] compared the plan VMAT for treating early-stage breast cancer with SIB quality and robustness of the dose distributions against is extremely relevant. This study aimed at estimate the setup and motion uncertainties among four RT plans. three RT plans, and the expectation was to bring more They confirmed that hybrid IMRT performed better Bi  et al. Radiation Oncology (2022) 17:60 Page 7 of 10 Fig. 4 DVHs of OARs for the representative patient with IMRT (red line), Hybrid IMRT (orange line) and Hybrid VMAT (blue line). a–f are ipsilateral lung (I-Lung), contralateral lung (C-Lung), heart, contralateral breast (C-Breast), esophagus, and spinal cord, respectively Table 4 Comparison of dosimetric parameters of OARs between IMRT, H-IMRT and H-VMAT Structure Parameters IMRT H-IMRT H-VMAT p value a b c I-Lung V (%) 32.78 ± 22.38 35.17 ± 6.05 41.50 ± 9.97 0.672 0.197 0.046 5Gy V (%) 24.19 ± 6.40 20.41 ± 3.75 19.44 ± 5.40 0.013 0.077 0.15 10Gy V (%) 14.84 ± 3.91 13.71 ± 3.14 13.47 ± 3.28 0.245 0.038 0.136 20Gy V (%) 10.38 ± 4.11 10.43 ± 2.79 10.37 ± 2.95 0.193 0.184 0.386 30Gy D (Gy) 11.71 ± 4.04 9.57 ± 4.58 10.36 ± 5.97 0.065 0.169 0.103 mean C-Lung D (Gy) 0.38 ± 0.42 0.34 ± 0.35 0.64 ± 0.43 0.842 0.16 0.068 mean Heart V (%) 5.05 ± 3.43 1.88 ± 2.89 2.78 ± 4.85 0.191 0.14 0.287 5Gy V (%) 0.35 ± 1.21 0.04 ± 0.12 0.07 ± 0.25 0.261 0.22 0.217 10Gy D (Gy) 1.63 ± 0.94 1.32 ± 0.65 1.71 ± 0.63 0.052 0.033 0.728 mean C-Breast D (Gy) 12.59 ± 9.65 12.25 ± 13.09 11.81 ± 12.79 0.838 0.363 0.113 max D (Gy) 0.83 ± 0.55 0.83 ± 0.50 0.99 ± 0.48 0.595 0.17 0.518 mean Esophagus D (Gy) 3.38 ± 3.78 2.06 ± 1.66 3.78 ± 1.14 0.148 0.368 0.111 max D (Gy) 1.10 ± 0.96 0.69 ± 0.47 1.72 ± 0.41 0.053 0.21 0.011 mean Spinal cord D (Gy) 2.87 ± 3.30 2.13 ± 1.83 2.52 ± 0.76 0.362 0.542 0.376 max D (Gy) 0.72 ± 1.32 0.58 ± 0.20 0.70 ± 0.24 0.552 0.485 0.184 mean a: IMRT versus H-IMRT; b: IMRT versus H-VMAT; c: H-IMRT versus H-VMAT Bi et al. Radiation Oncology (2022) 17:60 Page 8 of 10 Table 5 EAR comparison of OARs between IMRT, H-IMRT and H-VMAT Structure IMRT H-IMRT H-VMAT p value a b c C-Breast 4.68 ± 3.39 4.25 ± 3.18 6.39 ± 3.71 0.205 0.018 0.031 I-Lung 109.80 ± 34.42 94.95 ± 39.35 115.53 ± 30.59 0.066 0.094 0.255 C-Lung 9.20 ± 8.06 5.36 ± 5.17 17.71 ± 6.02 0.048 0.036 0.000 Esophagus 1.55 ± 1.20 0.68 ± 0.54 1.60 ± 0.54 0.030 0.215 0.014 a: IMRT versus H-IMRT; b: IMRT versus H-VMAT; c: H-IMRT versus H-VMAT robustness against the uncertainties than full IMRT, and radiation-related risk is the most serious sequelae for it offered superior plan quality. Fogliata et  al. [30] com - breast cancer survivors, which has been confirmed by pared the dosimetric difference for the involved OARs numerous epidemiological cohort studies [31]. The among 3D-CRT plan with field in field technique, and occurrence of secondary cancer is closely related to two VMAT plans (VMAT_full and VMAT_tang, gantry the tissues and organs themselves. Studies have shown rotation partial arc from about 295 to 173° without and that fatal secondary cancer mainly occurs in the stom- with a sector of 0 MU, respectively) for breast cancer. ach, lungs, and colon, and thyroid has a particularly low They proved that full VMAT had an obvious weakness in threshold of SCR (mean dose as low as 0.05  Gy in chil- radiating a higher mean dose to the nearby OARs com- dren and young adults) [31, 32]. In addition, the occur- pared with VMAT_tang. rence of secondary cancer depends on the radiation dose. Considering the excellent characteristics of hybrid Secondary cancer tends to occur in volumes receiving a plans and the lack of studies on hybrid VMAT plan, total dose or near volumes receiving dose from 2 to 50 Gy here, we eagerly studied the clinical dosimetric charac- radiation [31, 33]. Several studies demonstrated that SCR teristics and SCR of full IMRT, hybrid IMRT, and hybrid dramatically increased when receiving a dose reaching a VMAT, and we found that hybrid IMRT was superior certain range in the kidney (from 1 to 15  Gy), stomach to full IMRT and hybrid VMAT in target quality, and and pancreas (from 1 to 45 Gy), and bladder and rectum OARs sparing for early-stage right-sided breast can- (from 1 to 60 Gy) [30, 34]. In our study, seeking the least cer. Adopting the VMAT_tang (partial arcs with a sec- toxic radiation modality for breast cancer, we compared tor of 0 MU) method from Fogliata et  al.’s study, instead the SCR of three modalities for the contralateral breast, of two opposed tangential open beams plus a complete contralateral lung, ipsilateral lung, and esophagus. half arc in our study, the performance of hybrid VMAT Recently, Schneider proposed a calculation model, in protecting peripheral OARs might be improved. How- namely, the EAR model, which can be adopted for SCR ever, different from irradiating the only target PTV as calculation and evaluation utilizing DVH data from the in Fogliata et  al.’s study, the hybrid VMAT in our study RT plan and related radiobiological parameters [25, 28]. delivered a boost dose to the tumor bed, and achieved The EAR model has proved its feasibility to assess the better CI and HI for both the tumor bed and the PTV. SCR for patients with nasal natural killer T-cell lym- u Th s, the hybrid VMAT with a complete half arc beam phoma and breast cancer [28, 30]. Fogliata et  al. [30] might be reasonable in this study. However, the half arc applied the EAR model to compare the SCR among beam delivered only 20% of the total dose by continu- 3D-CRT, VMAT_full, and VMAT_tang for breast cancer. ous rotation 180°, and the dose to the surrounding OARs And they confirmed that VMAT_tang had advantages in inevitably increased. According to previous studies, reducing RT toxicity for the ipsilateral organs compared it can be found that the plan quality for the IMRT and with 3D-CRT with field in field technique when they VMAT techniques depends a lot on the optimization delivered the same SCR to the contralateral organs. process applied and the multiple beam’s angles selected. In this study, we also adopted the EAR model to In this study, in order to reduce the dose to the lung dur- calculate the SCR for right-sided breast cancer, and ing the RT, the direction of 3D-CRT radiation field was our results demonstrated that the hybrid IMRT per- still taken as the basis, and 10 degrees more was given to formed best in target quality, OARs spring, and SCR to the outside and the gantry angle was range of about 200°, peripheral OARs. However, if the half arc had a sector so as to increase the field regulation ability and achieve of 0 MU in hybrid VMAT, the performance of hybrid better uniformity for the target area. VMAT in SCR to adjacent OARs probably approached As a tumor with a better therapeutic effect and or achieved the effect of hybrid IMRT. The percentage longer life expectancy than most other tumors, the of radiated dose and the effective dose delivery angle Bi  et al. Radiation Oncology (2022) 17:60 Page 9 of 10 Funding for the arc beam in the VMAT_tang in Fogliata’s study This work was supported generously by the Basic and the hybrid VMAT in our study was quite different. and Applied Basic Research Foundation of Guangdong Province (Grant No. This could translate into a differentiated radiation dose 2020A1515110335). and SCR to the nearby healthy tissue. Of course, the Availability of data and materials results of the EAR model in predicting SCR depend on Not applicable. the accuracy of commercial TPS system modeling and related biological parameters. Declarations In this study, EAR was used to quantify radiation- Ethics approval and consent to participate induced cancer. However, EAR is originally based on The study was approved by the institutional review board of our hospital. the risk calculations of extremely inhomogeneous dose distributions in the Hodgkin’s cohort from the Japa- Consent for publication The consents for publication of data have been obtained from patients. nese A-bomb survivors [26, 27] but not breast cancer cohort. It is also assumed that the total absolute risk in Competing interests an organ is the volume weighted sum of the risks of the The authors have no conflicts of interest to declare. partial volumes which are irradiated homogeneously. In Author details addition, uncertainties such as out of field low dose cal - National Cancer Center/National Clinical Research Center for Cancer/Can- culation as well as the effect of voxel size selection on cer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China. Depar tment dose calculation inevitably existed in commercial TPS. of Oncology, Yunyang County People’s Hospital, Chongqing 404500, China. Combining the results of previous studies with the results of this study, the following can be concluded: Received: 27 June 2021 Accepted: 13 February 2022 compared with 3D-CRT, IMRT and VMAT improved target uniformity in SIB treatment for early breast can- cer, but increased second cancer risk. Barbara Dobler References et  al. [18, 35] found that compared to techniques with 1. Hoekstra N, Fleury E, Merino Lara TR, van der Baan P, Bahnerth A, Struik a limitation of short arcs or fields around the tangents G, Hoogeman M, Pignol JP. Long-term risks of secondary cancer for for whole breast and SIB treatment, IMRT and VMAT various whole and partial breast irradiation techniques. Radiother Oncol. 2018;128(3):428–33. https:// doi. org/ 10. 1016/j. radonc. 2018. 05. 032. are associated with a higher second cancer risk when 2. Hammer C, Maduro JH, Bantema-Joppe EJ, van der Schaaf A, van der exploiting a larger gantry angle range of around 200°. Laan HP, Langendijk JA, Crijns AP. Radiation-induced fibrosis in the boost This conclusion is consistent with our research results. area after three-dimensional conformal radiotherapy with a simultaneous integrated boost technique for early-stage breast cancer: a multivariable In addition, in our study, hybrid IMRT improved target prediction model. Radiother Oncol. 2017;122(1):45–9. https:// doi. org/ 10. uniformity and also had a lower second cancer com- 1016/j. radonc. 2016. 10. 006. pared with full IMRT and hybrid VMAT at the same 3. Pearson D, Wan J, Bogue J. A novel technique for treating deep seated breast cavity boosts. Med Dosim. 2020;45(2):149–52. https:// doi. org/ 10. gantry angel range. 1016/j. meddos. 2019. 08. 005. Hybrid IMRT combined the advantages of 3D-CRT 4. Baycan D, Karacetin D, Balkanay AY, Barut Y. Field-in-field IMRT versus and IMRT in treating early-stage right-sided breast 3D-CRT of the breast. Cardiac vessels, ipsilateral lung, and contralateral breast absorbed doses in patients with left-sided lumpectomy: a dosi- cancer. Hybrid IMRT was shown to have significant metric comparison. Jpn J Radiol. 2012;30(10):819–23. https:// doi. org/ 10. advantages in target dose coverage, OARs sparing, and 1007/ s11604- 012- 0126-z. SCR to nearby normal tissues. Hybrid IMRT is worthy 5. Herrick JS, Neill CJ, Rosser PF. A comprehensive clinical 3-dimen- sional dosimetric analysis of forward planned IMRT and conventional of clinical application and promotion. wedge planned techniques for intact breast radiotherapy. Med Dosim. 2008;33(1):62–70. https:// doi. org/ 10. 1016/j. meddos. 2007. 06. 001. 6. Furuya T, Sugimoto S, Kurokawa C, Ozawa S, Karasawa K, Sasai K. The Abbreviations dosimetric impact of respiratory breast movement and daily setup IMRT: Intensity-modulated radiotherapy; VMAT: Volumetric-modulated arc error on tangential whole breast irradiation using conventional wedge, therapy; SCR: Second cancer risk; OAR: Organs at risk; SIB: Simultaneous field-in-field and irregular surface compensator techniques. J Radiat Res. integrated boost; EAR: Excess absolute risk; HI: Homogeneity index; RT: Radio- 2013;54(1):157–65. https:// doi. org/ 10. 1093/ jrr/ rrs064. therapy; 3D-CRT : 3-Dimensional conformal radiation therapy; MLC: Multi-leaf 7. Lai Y, Chen Y, Wu S, Shi L, Fu L, Ha H, Lin Q. Modified volumetric modu- collimator; DR: Dose rate; CT: Computed tomography; TPS: Treatment plan- lated arc therapy in left sided breast cancer after radical mastectomy ning system; CTV: Clinical target volume; PTV: Planning target volume; MUs: with flattening filter free versus flattened beams. Medicine (Baltimore). Monitor units; DVH: Dose-volume histogram; CI: Conformal index. 2016;95(14): e3295. https:// doi. org/ 10. 1097/ MD. 00000 00000 003295. 8. Michalski A, Atyeo J, Cox J, Rinks M, Morgia M, Lamoury G. A dosimetric Acknowledgements comparison of 3D-CRT, IMRT, and static tomotherapy with an SIB for large The authors thank Prof. Xianfeng Liu for helpful discussion. and small breast volumes. Med Dosim. 2014;39(2):163–8. https:// doi. org/ 10. 1016/j. meddos. 2013. 12. 003. Authors’ contributions 9. Mo JC, Huang J, Gu WD, Gao M, Ning ZH, Mu JM, Li QL, Pei HL. A dosi- All authors carried out the study. Suyan Bi, Rui Zhu, Zhitao Dai draft the manu- metric comparison of double-arc volumetric arc therapy, step-shoot script. All authors read and approved the final manuscript. intensity modulated radiotherapy and 3D-CRT for left-sided breast Bi et al. Radiation Oncology (2022) 17:60 Page 10 of 10 cancer radiotherapy after breast-conserving surgery. Technol Health Care. 27. Schneider U, Sumila M, Robotka J. Site-specific dose-response relation- 2017;25(5):851–8. https:// doi. org/ 10. 3233/ THC- 160746. ships for cancer induction from the combined Japanese A-bomb and 10. Liu H, Chen X, He Z, Li J. Evaluation of 3D-CRT, IMRT and VMAT radio- Hodgkin cohorts for doses relevant to radiotherapy. Theor Biol Med therapy plans for left breast cancer based on clinical dosimetric study. Model. 2011;8:27. https:// doi. org/ 10. 1186/ 1742- 4682-8- 27. Comput Med Imaging Graph. 2016;54:1–5. https:// doi. org/ 10. 1016/j. 28. Liu X, Wu F, Guo Q, Wang Y, He Y, Luo H, Li Q, Zhong M, Li C, Yang H, Zhou compm edimag. 2016. 10. 001. J, Jin F. Estimation of radiotherapy modalities for patients with stage I-II 11. Nakamura N, Takahashi O, Kamo M, Hatanaka S, Endo H, Mizuno N, nasal natural killer T-Cell lymphoma. Cancer Manag Res. 2019;11:7219–29. Shikama N, Ogita M, Sekiguchi K. Eec ff ts of geometrical uncertainties on https:// doi. org/ 10. 2147/ CMAR. S2015 14. whole breast radiotherapy: a comparison of four different techniques. J 29. van Mourik A, van Kranen S, den Hollander S, Sonke JJ, van Herk M, van Breast Cancer. 2014;17(2):157–60. https:// doi. org/ 10. 4048/ jbc. 2014. 17.2. Vliet-Vroegindeweij C. Eec ff ts of setup errors and shape changes on 157. breast radiotherapy. Int J Radiat Oncol Biol Phys. 2011;79(5):1557–64. 12. Deasy JO, Moiseenko V, Marks L, Chao KS, Nam J, Eisbruch A. Radiother-https:// doi. org/ 10. 1016/j. ijrobp. 2010. 07. 032. apy dose-volume effects on salivary gland function. Int J Radiat Oncol 30. Fogliata A, De Rose F, Franceschini D, Stravato A, Seppälä J, Scorsetti M, Biol Phys. 2010;76(3 Suppl):S58-63. https:// doi. org/ 10. 1016/j. ijrobp. 2009. Cozzi L. Critical appraisal of the risk of secondary cancer induction from 06. 090. breast radiation therapy with volumetric modulated arc therapy relative 13. Toda K, Shibuya H, Hayashi K, Ayukawa F. Radiation-induced cancer to 3D conformal therapy. Int J Radiat Oncol Biol Phys. 2018;100(3):785–93. after radiotherapy for non-Hodgkin’s lymphoma of the head and neck: https:// doi. org/ 10. 1016/j. ijrobp. 2017. 10. 040. a retrospective study. Radiat Oncol. 2009;4:21. https:// doi. org/ 10. 1186/ 31. Jin F, Luo HL, Zhou J, He YN, Liu XF, Zhong MS, Yang H, Li C, Li QC, Huang 1748- 717X-4- 21. X, Tian XM, Qiu D, He GL, Yin L, Wang Y. Cancer risk assessment in modern 14. Becker SJ, Elliston C, Dewyngaert K, Jozsef G, Brenner D, Formenti radiotherapy workflow with medical big data. Cancer Manag Res. S. Breast radiotherapy in the prone position primarily reduces the 2018;10:1665–75. https:// doi. org/ 10. 2147/ CMAR. S1649 80. maximum out-of-field measured dose to the ipsilateral lung. Med Phys. 32. Cardis E, Howe G, Ron E, Bebeshko V, Bogdanova T, Bouville A, Carr Z, 2012;39(5):2417–23. https:// doi. org/ 10. 1118/1. 37004 02. Chumak V, Davis S, Demidchik Y, Drozdovitch V, Gentner N, Gudzenko 15. Kourinou KM, Mazonakis M, Lyraraki E, Stratakis J, Damilakis J. Scattered N, Hatch M, Ivanov V, Jacob P, Kapitonova E, Kenigsberg Y, Kesminiene dose to radiosensitive organs and associated risk for cancer develop- A, Kopecky KJ, Kryuchkov V, Loos A, Pinchera A, Reiners C, Repacholi ment from head and neck radiotherapy in pediatric patients. Phys Med. M, Shibata Y, Shore RE, Thomas G, Tirmarche M, Yamashita S, Zvonova I. 2013;29(6):650–5. https:// doi. org/ 10. 1016/j. ejmp. 2012. 08. 001. Cancer consequences of the Chernobyl accident: 20 years on. J Radiol 16. Kry SF, Salehpour M, Followill DS, Stovall M, Kuban DA, White RA, Rosen Prot. 2006;26(2):127–40. https:// doi. org/ 10. 1088/ 0952- 4746/ 26/2/ 001. II. Out-of-field photon and neutron dose equivalents from step-and- 33. Berrington de Gonzalez A, Gilbert E, Curtis R, Inskip P, Kleinerman R, Mor- shoot intensity-modulated radiation therapy. Int J Radiat Oncol Biol Phys. ton L, Rajaraman P, Little MP. Second solid cancers after radiation therapy: 2005;62(4):1204–16. https:// doi. org/ 10. 1016/j. ijrobp. 2004. 12. 091. a systematic review of the epidemiologic studies of the radiation dose- 17. Lee B, Lee S, Sung J, Yoon M. Radiotherapy-induced secondary cancer response relationship. Int J Radiat Oncol Biol Phys. 2013;86(2):224–33. risk for breast cancer: 3D conformal therapy versus IMRT versus VMAT. J https:// doi. org/ 10. 1016/j. ijrobp. 2012. 09. 001. Radiol Prot. 2014;34(2):325–31. https:// doi. org/ 10. 1088/ 0952- 4746/ 34/2/ 34. Suit H, Goldberg S, Niemierko A, Ancukiewicz M, Hall E, Goitein M, Wong 325. W, Paganetti H. Secondary carcinogenesis in patients treated with 18. Abo-Madyan Y, Aziz MH, Aly MM, Schneider F, Sperk E, Clausen S, radiation: a review of data on radiation-induced cancers in human, non- Giordano FA, Herskind C, Steil V, Wenz F, Glatting G. Second cancer human primate, canine and rodent subjects. Radiat Res. 2007;167(1):12– risk after 3D-CRT, IMRT and VMAT for breast cancer. Radiother Oncol. 42. https:// doi. org/ 10. 1667/ RR0527.1. 2014;110(3):471–6. https:// doi. org/ 10. 1016/j. radonc. 2013. 12. 002. 35. Dobler B, Maier J, Knott B, Maerz M, Loeschel R, Koelbl O. Second 19. Corradini S, Ballhausen H, Weingandt H, Freislederer P, Schönecker S, Cancer Risk after simultaneous integrated boost radiation therapy of Niyazi M, Simonetto C, Eidemüller M, Ganswindt U, Belka C. Left-sided right sided breast cancer with and without flattening filter. Strahlen- breast cancer and risks of secondary lung cancer and ischemic heart ther Onkol. 2016;192(10):687–95. English. https:// doi. org/ 10. 1007/ disease: effects of modern radiotherapy techniques. Strahlenther Onkol. s00066- 016- 1025-5. 2018;194(3):196–205. https:// doi. org/ 10. 1007/ s00066- 017- 1213-y. 20. Zhuang M, Zhang T, Chen Z, Lin Z, Li D, Peng X, Qiu Q, Wu R. Advanced Publisher’s Note nasopharyngeal carcinoma radiotherapy with volumetric modulated Springer Nature remains neutral with regard to jurisdictional claims in pub- arcs and the potential role of flattening filter-free beams. Radiat Oncol. lished maps and institutional affiliations. 2013;8:120. https:// doi. org/ 10. 1186/ 1748- 717X-8- 120. 21. Bragg CM, Wingate K, Conway J. Clinical implications of the anisotropic analytical algorithm for IMRT treatment planning and verification. Radio - ther Oncol. 2008;86(2):276–84. https:// doi. org/ 10. 1016/j. radonc. 2008. 01. 22. Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Brønnum D, Correa C, Cutter D, Gagliardi G, Gigante B, Jensen MB, Nisbet A, Peto R, Rahimi K, Taylor C, Hall P. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013;368(11):987–98. https:// doi. org/ 10. 1056/ NEJMo a1209 825. Re Read ady y to to submit y submit your our re researc search h ? Choose BMC and benefit fr ? Choose BMC and benefit from om: : 23. Peters S, Schiefer H, Plasswilm L. A treatment planning study comparing Elekta VMAT and fixed field IMRT using the varian treatment planning fast, convenient online submission system eclipse. Radiat Oncol. 2014;9:153. https:// doi. org/ 10. 1186/ thorough peer review by experienced researchers in your field 1748- 717X-9- 153. 24. Giorgia N, Antonella F, Alessandro C, Eugenio V, Luca C. Planning rapid publication on acceptance strategies in volumetric modulated arc therapy for breast. Med Phys. support for research data, including large and complex data types 2011;38(7):4025–31. https:// doi. org/ 10. 1118/1. 35984 42. • gold Open Access which fosters wider collaboration and increased citations 25. Schneider U. Modeling the risk of secondary malignancies after radio- therapy. Genes (Basel). 2011;2(4):1033–49. https:// doi. org/ 10. 3390/ genes maximum visibility for your research: over 100M website views per year 20410 33. 26. Schneider U. Mechanistic model of radiation-induced cancer after At BMC, research is always in progress. fractionated radiotherapy using the linear-quadratic formula. Med Phys. Learn more biomedcentral.com/submissions 2009;36(4):1138–43. https:// doi. org/ 10. 1118/1. 30897 92. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Radiation Oncology Springer Journals

Dosimetric and radiobiological comparison of simultaneous integrated boost radiotherapy for early stage right side breast cancer between three techniques: IMRT, hybrid IMRT and hybrid VMAT

Radiation Oncology , Volume 17 (1) – Mar 28, 2022

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Abstract

Purpose: This study aimed at evaluating the clinical impact of full intensity-modulated radiotherapy (IMRT ), hybrid IMRT (H-IMRT ) and hybrid volumetric-modulated arc therapy (H-VMAT ) for early-stage breast cancer with simultane- ous integrated boost (SIB), in terms of plan quality and second cancer risk (SCR). Methods: Three different plans were designed in full IMRT, hybrid IMRT, and hybrid VMAT for each of twenty patients with early-stage breast cancer. Target quality, organs at risk (OARs) sparing, and SCR were compared among the three plans for each case. Results: In compared with H-IMRT, IMRT plans showed deterioration in terms of D of SIB, V of ipsilateral lung, and 2% 10 excess absolute risk (EAR) to contralateral lung (C-Lung) and esophagus. D and the homogeneity index (HI) of SIB, 2% V5 of ipsilateral lung (I-Lung), the D of the esophagus, the EAR to C-Lung and the esophagus with hybrid VMAT mean dramatically increased by 0.63%, 10%, 17.99%, 149.27%, 230.41%, and 135.29%, respectively (p = 0.024; 0.025; 0.046; 0.011; 0.000; 0.014). D of the heart, the EAR to contralateral breast (C-Breast) and C-Lung by full IMRT was signifi- mean cantly decreased in comparison to the H-VMAT (4.67%, p = 0.033, 26.76%, p = 0.018; 48.05%, p = 0.036). Conclusion: The results confirmed that H-IMRT could achieve better target quality and OARs sparing than IMRT and H-VMAT for SIB radiotherapy of early-stage right breast cancer. H-IMRT was the best treatment option, while H-VMAT performed the worst among the three plans in terms of SCR to peripheral OARs. Keywords: Breast cancer, Second cancer risk, IMRT, Hybrid IMRT, Hybrid VMAT Introduction Usually diagnosed as early-stage female cancer, the 5-year specific survival rate of breast cancer is up to 98.9% [1]. Whole breast radiotherapy (RT) and a boost to the tumor bed is considered as the adjuvant therapy after *Correspondence: daizt_sinap@163.com breast-conserving surgery for early-stage breast cancer Suyan Bi and Rui Zhu have contributed equally to this work [2, 3]. Studies confirmed that patients benefited from RT National Cancer Center/National Clinical Research Center for Cancer/ Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical and tumor bed boosting [3, 4]. Sciences and Peking Union Medical College, Shenzhen 518116, China Full list of author information is available at the end of the article © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Bi et al. Radiation Oncology (2022) 17:60 Page 2 of 10 Various RT techniques, such as three-dimensional con- treatment, 3D-CRT technique may result in worse target formal radiation therapy (3D-CRT), intensity-modulated uniformity compared with IMRT and VMAT techniques. radiation therapy (IMRT), and volumetric-modulated arc Therefore, 3D-CRT was usually replaced by modern therapy (VMAT), have been adopted for treating breast intensity modulation technology in SIB treatment for cancer. Utilizing two opposed, wedged, and tangential early stage breast cancer. fields, 3D-CRT treating the whole breast is carried out To pursue an excellent target dose coverage and OARs with multi-leaf collimators (MLCs) to shield the adjacent sparing, and also lower the SCR and radiation toxicity, normal tissue. Many studies [5–7] have been confirmed selecting a reasonable RT modality is critical for treating that tangential field techniques such as dynamic wedge breast cancer. To the best of our knowledge, the clinical and field-in-field techniques are used for whole-breast impact of hybrid VMAT for early stage breast cancer with radiation can improve dose uniformity to the tumour. SIB treatment has not been studied. This study aimed at 3D-CRT has the advantage of improving the local con- assess the plan quality and SCR among three treatment trol, but the toxicities associated with radiation to the modalities (full IMRT, hybrid IMRT, and hybrid VMAT) organs at risk (OARs) are a concern [8]. Dividing each for SIB treatment of early stage breast cancer. beam into smaller beamlets, IMRT delivers a non-uni- form fluence to optimize the dose distribution [8]. VMAT Materials and methods can rotate the angle of gantry and radiate beams contin- Patients preparation uously, and modulate the dose rate (DR) and the shape Twenty females aged between 31 and 64  years old, with of the MLCs simultaneously to achieve a highly confor- early-stage right-sided breast cancer after breast-con- mal dose coverage [9]. IMRT and VMAT were reported serving surgery, were randomly selected. None of the to have incomparable advantages in dose homogeneity patients had contraindications for RT. This study was and coverage compared with 3D-CRT [9, 10]. However, approved by the ethics committee of National Cancer IMRT might be more susceptible to setup error and Center/National Clinical Research Center for Cancer/ shape changes of the breast in whole breast RT [10]. To Cancer Hospital & Shenzhen Hospital, and the informed reduce the effects of the geometrical uncertainties, Naka - consent was acquired from each enrolled patient. mura et al. [11] proposed a method of hybrid IMRT plan All of the patients were positioned with a breast comprised of two opposed tangential open beams and bracket and fixed foam plate on the affected side of the two inverse-planned IMRT beams. And they proved the lower limbs. The computed tomography (CT) scans were hybrid IMRT had excellent performance in target quality acquired on a Philips Brilliance Big Bore CT (Philips, and offsetting the geometrical uncertainties for patients Holland) simulation in 5-mm-thick slices, in the supine who underwent whole breast RT [12]. position with the scan scope from the mandible to the With the advancement of medical technology, systemic thorax. In addition, all of the adjacent normal tissues, therapy and radiation therapy techniques have greatly such as the heart, lung, esophagus, and contralateral lengthened the life span of women with breast cancer. breast, were completely covered. This, however, may increase the likelihood of radiation- induced secondary cancers. RT resulted in inevitably Contouring of target volumes and OARs radiation damage and therapy-related second cancer risk Target volumes and OARs were delineated on the Eclipse (SCR) for normal tissue, which was confirmed by studies treatment planning system (Version 13.6, Varian Medi- [12, 13]. With the improvement of the efficacy and overall cal Systems Inc.). The clinical target volume (CTV) and survival of breast cancer patients, the SCR and radiation the boost region were delineated by the same radiation toxicity caused by RT has gradually become a research oncologist on each CT data set. The CTV was the whole focus. Although IMRT, hybrid IMRT, hybrid VMAT and breast tissue identifiable on the CT scan assisted by wire VMAT have been shown to improve dose conformity markers, which were placed around the palpable breast and reduce dose to organs at risk (OARs) compared with tissue during the simulation. Then the CTV limited 3D-CRT, organ doses to out-of-field regions were greater posteriorly by the intercostal front and retracted 5  mm with IMRT or VMAT than with 3D-CRT, due to the for- from the skin. The boost region encompassed the surgi - mer methods having greater scattering and monitor unit cal bed or seroma. The planning target volume (PTV) (MU) [14–17]. Early studies showed that 3D-CRT pos- was expanded 5  mm based on the CTV, excluding the sesses a lower SCR than IMRT and VMAT for the [18, heart. Then the PTV was retracted 5  mm from the skin 19]. In clinical breast cancer treatment, however, the and limited posteriorly by the intercostal front. The boost uniformity of the target area and the dose of normal tis- region was expanded by 5  mm in all directions to cre- sue should be considered simultaneously. When con- ate the SIB (simultaneous integrated boost) volume. The sidering early stage breast cancer with SIB radiotherapy contoured OARs were the contralateral breast (C-Breast), Bi  et al. Radiation Oncology (2022) 17:60 Page 3 of 10 heart, spinal cord, esophagus, and ipsilateral (I-Lung) and Table 1 Dose targets and constraints for treatment planning contralateral lungs (C-Lung). Before RT planning, we Structure Metrics Objective should also deal with the lead wire marked on the body SIB V (%) ≥ 95% surface during CT positioning and modify its CT values 49.5Gy V (%) < 20% to -1000HU to reduce the impact on dose distribution. In 55Gy D (Gy) < 60 Gy order to avoid the target receiving insufficient radiation max PTV-SIB V (%) ≥ 95% dose because of the target  changes in size due to edema 43.5Gy (%) < 20% during treatment or residual displacement due to breath- 48Gy D (Gy) < 52 Gy ing not properly controlled, a 10  mm artificial expan - max I-Lung V (%) < 60% sion with soft-tissue equivalent HU was added in the 5Gy V (%) < 40% breast region and the PTV contours toward the external 10Gy V (%) < 20% direction. 20Gy V (%) < 15% 30Gy D (Gy) < 15 Gy RT plans mean C-lung V (%) < 20% Figure 1 showed the fields distributions in CT images for 5Gy Heart D (Gy) < 4 Gy the three RT techniques respectively. Three different RT mean C-Breast D (Gy) < 40 Gy plans (full IMRT, hybrid IMRT, and hybrid VMAT) were max created for each case in the Eclipse TPS. Utilizing 6 MV (Gy) < 3 Gy mean photon beams generated by Varian IX linear accelerator, Spinal cord D (Gy) < 45 Gy max dose optimization and calculations were done in Eclipse TPS for all of the plans. The algorithms of Dose-Volume position of jaws of all of the fields were adjusted before Optimizer and Progressive Resolution Optimizer were dose optimization to maximize the protection of the used for IMRT, and VMAT dose optimization, respec- lungs. All of the fields were delivered with dynamic slid - tively, and Anisotropic Analytical Algorithm was adopted ing-window IMRT delivery technique and the fixed DR for final dose calculations [20, 21]. For the purpose of of 600 monitor units (MUs)/min. comparison, all the plans were normalized so that 95% of PTV covered by 43.5 Gy. All the plans were optimized with the same dose constraints [22] as was detailed in Hybrid IMRT Table 1. The hybrid IMRT plans owned two opposed tangential open beams plus three IMRT beams. Two of the three Full IMRT IMRT beams were at the angles of 10° to the two tan- The full IMRT plans contained two opposed tangential gential fields in the direction of outside the body, and fields, and the other four fields that were at the angles the third IMRT beam had an angle of about 30° to 45° of 10° or 20° to the two tangential fields in the direction to the tangential field on the upper side avoiding expo - of outside the body. The angles of the collimator and the sure to the heart and contralateral breast. To maximize Fig. 1 Target volume contouring and field arragement display of three irradiation techniques: a IMRT, b Hybrid IMRT (H-IMRT ) and c Hybrid VMAT (H-VMAT ). The yellow straight lines, red straight lines, and yellow arc represent IMRT beams, tangential beams and partial arc beam, respectively. The green area is the planning target volume (PTV ), and the light blue area is simultaneous integrated boost (SIB) Bi et al. Radiation Oncology (2022) 17:60 Page 4 of 10 the protection of the lungs, the angles of the collimator using HI = (D -D )/D , where D and D are 5% 95% mean 5% 95% of the three IMRT beams were adjusted, and the posi- the minimum dose radiated to 5% and 95% of the SIB, tion of the jaws of the third IMRT beam was adjusted and respectively. PTV-SIB: the D , the D, V and CI of 2% mean 95%, fixed, adapting the shape of the SIB before dose optimi - PTV-SIB were assessed. These indicators were defined as zation and calculation. The adopted delivery technique described above. OARs: the D and D of contralat- max mean and DR were the same as that of the full IMRT plans. The eral breast, heart, spinal cord and esophagus, and the open beams contributed 80% of the total dose, whereas D of contralateral lung were executed for dosimetric mean the inversely optimized IMRT beams contributed to the analysis. The V (the percentage volume receiving 5 Gy), remaining prescription dose. V (the percentage volume receiving 10  Gy), V (the 10 20 percentage of volume receiving 20 Gy), V (the percent- age of volume receiving 30 Gy), and D of the ipsilat- Hybrid VMAT mean eral lung and combined lung were also evaluated. The hybrid VMAT plans owned two opposed tangen - tial open beams and a half arc beam. The gantry of the SCR calculations arc beam rotated from one tangential angle to the other The SCR caused by RT of normal tissues can be assessed tangential angle. The maximum DR of the arc beam was by excess absolute risk (EAR) model, as proposed by Sch- set to 600 MUs/min. The open beams contributed with neider [23, 26]. The EAR to develop a solid cancer after 80% of the total dose, whereas the inversely optimized arc exposure to radiation has been estimated from data of beams contributed to the remaining prescribed dose. the atomic bomb survivors for different kinds of solid For the SIB and PTV-SIB of all of the plans, the pre- cancer and describes the absolute difference in can - scribed doses were 49.50 and 43.50  Gy in 15 fractions, cer rates of persons exposed to a dose d and those not respectively. The prescribed 95% isodose covered no exposed to a dose beyond the natural dose exposion per less than 95% of the target volume [23], and the per- 10,000 person-years per Gy. The Eq. (1) shown below can centage volume of the target volume radiated over 110% be utilized to calculate the SCR of an organ [27, 28]: of the prescribed dose was no more than 2%. The dose constraints for adjacent OARs of contralateral breast, org heart, ipsilateral lung, contralateral lung, spinal cord, and EAR = V (D )β RED(D )μ(x, a) i EAR i (1) esophagus were defined according to published litera - i ture [24]. According to the planning method of Giorgia where V is the total organ volume assessed for second- Nicolini [25], in order to avoid the target receiving insuf- ary carcinogenesis, V (D ) represents the organ volume ficient radiation dose because of the target  changes in receiving the dose D , and the parameter β is the slope i EAR size due to edema during treatment or residual displace- of the dose–response curve in the low dose region. Equa- ment due to breathing not properly controlled, we give tion (2), RED (D ), represents the dose–response mecha- a 10  mm artificial expansion with soft-tissue equivalent nistic model, which describes the fractionation effects HU of the body in the breast region and of the PTV con- and cell killing: tours toward the external direction for the full IMRT and VMAT plans. −α D i ′ e ′ α R 2 α D 2 − D 1−R RED(D ) = 1 − 2R + R e − (1 − R) e α R Treatment plan evaluation (2) The data collected from the Dose-Volume Histogram where R is a parameter that represents the repopulation (DVH) of all of the plans were evaluated in the aspect or repair ability of normal tissues between two dose frac- of target coverage and OARs sparing. SIB: the maxi- tions, and the parameter α′ was calculated by Eq. (3): mum dose (D ), the mean dose (D ), and V of max mean 95% α = α + βd = α + βD /D d SIB were assessed. The D of SIB, also named D , (3) i T T max 2% is defined as the dose received by 2% of the target vol - where D is the prescribed dose of 49.50 Gy to the SIB in ume, and V is defined as the percentage volume 95% this study, and d represents the corresponding fraction- of the target volume receiving 95% of the prescribed ation dose of 3.3  Gy. Given by Eq.  (4), µ (x, a) expresses dose. The conformal index (CI) and homogeneity index the modifying function: (HI) were also evaluated. The CI of SIB is defined as CI = TV /(TV × PIV ) utilizing the Paddick conform- [γ e(x−30)+γ a ln(a/70)] PTV μ(x, a) = e (4) ity index, where the TV was the SIB volume receiving PTV 95% of the prescription dose, the TV is the total volume where γ and γ are both the age modifying parameters. e a of the SIB, and the PIV is the total volume covered by In this study, the EAR has been investigated to the the prescribed 95% isodose. The HI of SIB was assessed organs of contralateral breast, contralateral lung, Bi  et al. Radiation Oncology (2022) 17:60 Page 5 of 10 ipsilateral lung, and esophagus. The assumed value of (99.37 ± 0.51) was better than that of the full IMRT and α/β = 3 Gy for all of the organs needed to evaluate EAR, the hybrid VMAT (98.99 ± 0.42, 99.03 ± 0.67). The find - and all of the other parameters used in EAR calculation ings on SIB and PTV-SIB are listed in Table 3. were taken from previous research [27] and were shown in Table 2. OARs The DVHs of ipsilateral lung (I-Lung), contralateral lung Statistical analysis (C-Lung), heart, contralateral breast (C-Breast), esopha- All the parameters were calculated from the DVHs. Sta- gus, and spinal cord of one representative case are dis- tistical analyses were carried out using IBM SPSS Statis- played in Fig.  4a–f, respectively. The delivered doses to tics version 21 (SPSS Inc.Armonk, NY). A paired t-test the OARs are listed in Table 4. Compared with the hybrid was performed to analyze the difference between three IMRT, V of ipsilateral lung, the Dmean of the esopha- techniques, and a p value < 0.05 was considered to reveal gus with hybrid VMAT increased by 17.99% and149.27%, statistical significance. respectively (p = 0.046; 0.011), the V of ipsilateral lung with full IMRT increased 18.52% (p = 0.013), and the Results Dmean of the heart with hybrid VMAT dramatically Target volume increased by 4.67% compared with the hybrid VMAT The comparison of isodose lines from 500 to 4950  cGy (p = 0.033). for a selected case is illustrated in Fig.  2. The DVHs of SIB and PTV-SIB of one representative case are displayed SCR calculations in Fig.  3a, b, respectively. The parameters of D, D , The EAR of the organs of contralateral breast, contralat - 2% mean V , CI, and HI were compared to evaluate the quality of eral lung, ipsilateral lung, and esophagus with three treat- 95% target dose coverage. For SIB, the hybrid IMRT obtained ment modalities are shown in Table  5. Compared with a lower D than both full IMRT and hybrid VMAT hybrid VMAT, the EAR to the contralateral breast with 2% (p < 0.05) and achieved better HI than the hybrid VMAT full IMRT and hybrid IMRT were decreased by 26.76% (p < 0.05). For the PTV-SIB, the V of the hybrid IMRT and 33.48%, respectively (p = 0.018; 0.031), and the EAR 95% Table 2 Model parameters used in EAR calculation Structure β γ γ α α/β R EAR e a C-Breast 9.2 − 0.037 1.7 0.044 3 0.15 I-Lung 7.5 0.002 4.23 0.042 3 0.83 C-Lung 7.5 0.002 4.23 0.042 3 0.83 Esophagus 0.58 − 0.002 1.9 0.026 3 0.81 Fig. 2 Comparison of planar dose distribution in cGy for a representative patient with three irradiation techniques: a IMRT, b Hybrid IMRT (H-IMRT ) and c Hybrid VMAT (H-VMAT ) Bi et al. Radiation Oncology (2022) 17:60 Page 6 of 10 Fig. 3 DVHs of a SIB and b PTV-SIB for the representative patient with IMRT (red line), Hybrid IMRT (orange line) and Hybrid VMAT (blue line) Table 3 Comparison of dosimetric parameters of SIB and PTV-SIB between IMRT, H-IMRT and H-VMAT Structure Parameters IMRT H-IMRT H-VMAT p value a b c SIB D (Gy) 52.73 ± 0.63 52.35 ± 0.60 52.68 ± 0.48 0.042 0.776 0.024 2% D (Gy) 51.18 ± 0.47 51.18 ± 0.59 51.41 ± 0.38 0.197 0.322 0.181 mean V (%) 99.88 ± 0.33 99.96 ± 0.11 100.00 ± 0.00 0.317 0.225 0.224 95% CI 0.82 ± 0.06 0.84 ± 0.05 0.84 ± 0.04 0.202 0.163 0.747 HI 0.12 ± 0.06 0.12 ± 0.02 0.13 ± 0.02 0.575 0.174 0.025 PTV-SIB D (Gy) 49.40 ± 0.68 49.29 ± 0.45 49.21 ± 0.39 0.581 0.359 0.461 2% D (Gy) 45.69 ± 0.42 45.60 ± 0.23 45.57 ± 0.28 0.438 0.264 0.660 mean V (%) 98.99 ± 0.42 99.37 ± 0.51 99.03 ± 0.67 0.06 0.621 0.076 95% CI 0.63 ± 0.08 0.65 ± 0.10 0.650 ± 0.09 0.38 0.35 0.252 a: IMRT versus H-IMRT; b: IMRT versus H-VMAT; c: H- IMRT versus H-VMAT to the contralateral lung with full IMRT and hybrid clinical options to RT with SIB for early-stage right-sided IMRT were reduced by 48.05%, and 230.41%, respectively breast cancer. (p = 0.036; 0.000). In comparison with the hybrid IMRT, IMRT showed a significant advantage in target dose the EAR to the esophagus with full IMRT and hybrid coverage, and surrounding OARs spring for left-sided VMAT increased 127.94% and 135.29%, respectively breast cancer after breast-conserving surgery [8–10]. (p = 0.030; 0.014) and the EAR to the contralateral lung This could result in better tumor control rate and lower with full IMRT was increased 71.64% (p = 0.048). toxicity, and late effects compared with the conven - tional tangential pair treatment beams. However, IMRT had inherent geometrical uncertainties arising from Discussion and conclusion setup error and target motion, which offset the merits Since studies evaluating the hybrid IMRT and hybrid of IMRT for breast cancer [10, 12, 29]. Combining two VMAT for early-stage breast cancer with SIB are rare, opposed tangential open beams and IMRT beams, the a comparison of the target dose coverage, OARs spar- hybrid IMRT plan might solve the geometrical uncer- ing, and SCR among full IMRT, hybrid IMRT, and hybrid tainties of IMRT. Nakamura et al. [12] compared the plan VMAT for treating early-stage breast cancer with SIB quality and robustness of the dose distributions against is extremely relevant. This study aimed at estimate the setup and motion uncertainties among four RT plans. three RT plans, and the expectation was to bring more They confirmed that hybrid IMRT performed better Bi  et al. Radiation Oncology (2022) 17:60 Page 7 of 10 Fig. 4 DVHs of OARs for the representative patient with IMRT (red line), Hybrid IMRT (orange line) and Hybrid VMAT (blue line). a–f are ipsilateral lung (I-Lung), contralateral lung (C-Lung), heart, contralateral breast (C-Breast), esophagus, and spinal cord, respectively Table 4 Comparison of dosimetric parameters of OARs between IMRT, H-IMRT and H-VMAT Structure Parameters IMRT H-IMRT H-VMAT p value a b c I-Lung V (%) 32.78 ± 22.38 35.17 ± 6.05 41.50 ± 9.97 0.672 0.197 0.046 5Gy V (%) 24.19 ± 6.40 20.41 ± 3.75 19.44 ± 5.40 0.013 0.077 0.15 10Gy V (%) 14.84 ± 3.91 13.71 ± 3.14 13.47 ± 3.28 0.245 0.038 0.136 20Gy V (%) 10.38 ± 4.11 10.43 ± 2.79 10.37 ± 2.95 0.193 0.184 0.386 30Gy D (Gy) 11.71 ± 4.04 9.57 ± 4.58 10.36 ± 5.97 0.065 0.169 0.103 mean C-Lung D (Gy) 0.38 ± 0.42 0.34 ± 0.35 0.64 ± 0.43 0.842 0.16 0.068 mean Heart V (%) 5.05 ± 3.43 1.88 ± 2.89 2.78 ± 4.85 0.191 0.14 0.287 5Gy V (%) 0.35 ± 1.21 0.04 ± 0.12 0.07 ± 0.25 0.261 0.22 0.217 10Gy D (Gy) 1.63 ± 0.94 1.32 ± 0.65 1.71 ± 0.63 0.052 0.033 0.728 mean C-Breast D (Gy) 12.59 ± 9.65 12.25 ± 13.09 11.81 ± 12.79 0.838 0.363 0.113 max D (Gy) 0.83 ± 0.55 0.83 ± 0.50 0.99 ± 0.48 0.595 0.17 0.518 mean Esophagus D (Gy) 3.38 ± 3.78 2.06 ± 1.66 3.78 ± 1.14 0.148 0.368 0.111 max D (Gy) 1.10 ± 0.96 0.69 ± 0.47 1.72 ± 0.41 0.053 0.21 0.011 mean Spinal cord D (Gy) 2.87 ± 3.30 2.13 ± 1.83 2.52 ± 0.76 0.362 0.542 0.376 max D (Gy) 0.72 ± 1.32 0.58 ± 0.20 0.70 ± 0.24 0.552 0.485 0.184 mean a: IMRT versus H-IMRT; b: IMRT versus H-VMAT; c: H-IMRT versus H-VMAT Bi et al. Radiation Oncology (2022) 17:60 Page 8 of 10 Table 5 EAR comparison of OARs between IMRT, H-IMRT and H-VMAT Structure IMRT H-IMRT H-VMAT p value a b c C-Breast 4.68 ± 3.39 4.25 ± 3.18 6.39 ± 3.71 0.205 0.018 0.031 I-Lung 109.80 ± 34.42 94.95 ± 39.35 115.53 ± 30.59 0.066 0.094 0.255 C-Lung 9.20 ± 8.06 5.36 ± 5.17 17.71 ± 6.02 0.048 0.036 0.000 Esophagus 1.55 ± 1.20 0.68 ± 0.54 1.60 ± 0.54 0.030 0.215 0.014 a: IMRT versus H-IMRT; b: IMRT versus H-VMAT; c: H-IMRT versus H-VMAT robustness against the uncertainties than full IMRT, and radiation-related risk is the most serious sequelae for it offered superior plan quality. Fogliata et  al. [30] com - breast cancer survivors, which has been confirmed by pared the dosimetric difference for the involved OARs numerous epidemiological cohort studies [31]. The among 3D-CRT plan with field in field technique, and occurrence of secondary cancer is closely related to two VMAT plans (VMAT_full and VMAT_tang, gantry the tissues and organs themselves. Studies have shown rotation partial arc from about 295 to 173° without and that fatal secondary cancer mainly occurs in the stom- with a sector of 0 MU, respectively) for breast cancer. ach, lungs, and colon, and thyroid has a particularly low They proved that full VMAT had an obvious weakness in threshold of SCR (mean dose as low as 0.05  Gy in chil- radiating a higher mean dose to the nearby OARs com- dren and young adults) [31, 32]. In addition, the occur- pared with VMAT_tang. rence of secondary cancer depends on the radiation dose. Considering the excellent characteristics of hybrid Secondary cancer tends to occur in volumes receiving a plans and the lack of studies on hybrid VMAT plan, total dose or near volumes receiving dose from 2 to 50 Gy here, we eagerly studied the clinical dosimetric charac- radiation [31, 33]. Several studies demonstrated that SCR teristics and SCR of full IMRT, hybrid IMRT, and hybrid dramatically increased when receiving a dose reaching a VMAT, and we found that hybrid IMRT was superior certain range in the kidney (from 1 to 15  Gy), stomach to full IMRT and hybrid VMAT in target quality, and and pancreas (from 1 to 45 Gy), and bladder and rectum OARs sparing for early-stage right-sided breast can- (from 1 to 60 Gy) [30, 34]. In our study, seeking the least cer. Adopting the VMAT_tang (partial arcs with a sec- toxic radiation modality for breast cancer, we compared tor of 0 MU) method from Fogliata et  al.’s study, instead the SCR of three modalities for the contralateral breast, of two opposed tangential open beams plus a complete contralateral lung, ipsilateral lung, and esophagus. half arc in our study, the performance of hybrid VMAT Recently, Schneider proposed a calculation model, in protecting peripheral OARs might be improved. How- namely, the EAR model, which can be adopted for SCR ever, different from irradiating the only target PTV as calculation and evaluation utilizing DVH data from the in Fogliata et  al.’s study, the hybrid VMAT in our study RT plan and related radiobiological parameters [25, 28]. delivered a boost dose to the tumor bed, and achieved The EAR model has proved its feasibility to assess the better CI and HI for both the tumor bed and the PTV. SCR for patients with nasal natural killer T-cell lym- u Th s, the hybrid VMAT with a complete half arc beam phoma and breast cancer [28, 30]. Fogliata et  al. [30] might be reasonable in this study. However, the half arc applied the EAR model to compare the SCR among beam delivered only 20% of the total dose by continu- 3D-CRT, VMAT_full, and VMAT_tang for breast cancer. ous rotation 180°, and the dose to the surrounding OARs And they confirmed that VMAT_tang had advantages in inevitably increased. According to previous studies, reducing RT toxicity for the ipsilateral organs compared it can be found that the plan quality for the IMRT and with 3D-CRT with field in field technique when they VMAT techniques depends a lot on the optimization delivered the same SCR to the contralateral organs. process applied and the multiple beam’s angles selected. In this study, we also adopted the EAR model to In this study, in order to reduce the dose to the lung dur- calculate the SCR for right-sided breast cancer, and ing the RT, the direction of 3D-CRT radiation field was our results demonstrated that the hybrid IMRT per- still taken as the basis, and 10 degrees more was given to formed best in target quality, OARs spring, and SCR to the outside and the gantry angle was range of about 200°, peripheral OARs. However, if the half arc had a sector so as to increase the field regulation ability and achieve of 0 MU in hybrid VMAT, the performance of hybrid better uniformity for the target area. VMAT in SCR to adjacent OARs probably approached As a tumor with a better therapeutic effect and or achieved the effect of hybrid IMRT. The percentage longer life expectancy than most other tumors, the of radiated dose and the effective dose delivery angle Bi  et al. Radiation Oncology (2022) 17:60 Page 9 of 10 Funding for the arc beam in the VMAT_tang in Fogliata’s study This work was supported generously by the Basic and the hybrid VMAT in our study was quite different. and Applied Basic Research Foundation of Guangdong Province (Grant No. This could translate into a differentiated radiation dose 2020A1515110335). and SCR to the nearby healthy tissue. Of course, the Availability of data and materials results of the EAR model in predicting SCR depend on Not applicable. the accuracy of commercial TPS system modeling and related biological parameters. Declarations In this study, EAR was used to quantify radiation- Ethics approval and consent to participate induced cancer. However, EAR is originally based on The study was approved by the institutional review board of our hospital. the risk calculations of extremely inhomogeneous dose distributions in the Hodgkin’s cohort from the Japa- Consent for publication The consents for publication of data have been obtained from patients. nese A-bomb survivors [26, 27] but not breast cancer cohort. It is also assumed that the total absolute risk in Competing interests an organ is the volume weighted sum of the risks of the The authors have no conflicts of interest to declare. partial volumes which are irradiated homogeneously. In Author details addition, uncertainties such as out of field low dose cal - National Cancer Center/National Clinical Research Center for Cancer/Can- culation as well as the effect of voxel size selection on cer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China. Depar tment dose calculation inevitably existed in commercial TPS. of Oncology, Yunyang County People’s Hospital, Chongqing 404500, China. Combining the results of previous studies with the results of this study, the following can be concluded: Received: 27 June 2021 Accepted: 13 February 2022 compared with 3D-CRT, IMRT and VMAT improved target uniformity in SIB treatment for early breast can- cer, but increased second cancer risk. Barbara Dobler References et  al. [18, 35] found that compared to techniques with 1. Hoekstra N, Fleury E, Merino Lara TR, van der Baan P, Bahnerth A, Struik a limitation of short arcs or fields around the tangents G, Hoogeman M, Pignol JP. Long-term risks of secondary cancer for for whole breast and SIB treatment, IMRT and VMAT various whole and partial breast irradiation techniques. Radiother Oncol. 2018;128(3):428–33. https:// doi. org/ 10. 1016/j. radonc. 2018. 05. 032. are associated with a higher second cancer risk when 2. Hammer C, Maduro JH, Bantema-Joppe EJ, van der Schaaf A, van der exploiting a larger gantry angle range of around 200°. Laan HP, Langendijk JA, Crijns AP. Radiation-induced fibrosis in the boost This conclusion is consistent with our research results. area after three-dimensional conformal radiotherapy with a simultaneous integrated boost technique for early-stage breast cancer: a multivariable In addition, in our study, hybrid IMRT improved target prediction model. Radiother Oncol. 2017;122(1):45–9. https:// doi. org/ 10. uniformity and also had a lower second cancer com- 1016/j. radonc. 2016. 10. 006. pared with full IMRT and hybrid VMAT at the same 3. Pearson D, Wan J, Bogue J. A novel technique for treating deep seated breast cavity boosts. Med Dosim. 2020;45(2):149–52. https:// doi. org/ 10. gantry angel range. 1016/j. meddos. 2019. 08. 005. Hybrid IMRT combined the advantages of 3D-CRT 4. Baycan D, Karacetin D, Balkanay AY, Barut Y. Field-in-field IMRT versus and IMRT in treating early-stage right-sided breast 3D-CRT of the breast. Cardiac vessels, ipsilateral lung, and contralateral breast absorbed doses in patients with left-sided lumpectomy: a dosi- cancer. Hybrid IMRT was shown to have significant metric comparison. Jpn J Radiol. 2012;30(10):819–23. https:// doi. org/ 10. advantages in target dose coverage, OARs sparing, and 1007/ s11604- 012- 0126-z. SCR to nearby normal tissues. Hybrid IMRT is worthy 5. Herrick JS, Neill CJ, Rosser PF. A comprehensive clinical 3-dimen- sional dosimetric analysis of forward planned IMRT and conventional of clinical application and promotion. wedge planned techniques for intact breast radiotherapy. Med Dosim. 2008;33(1):62–70. https:// doi. org/ 10. 1016/j. meddos. 2007. 06. 001. 6. Furuya T, Sugimoto S, Kurokawa C, Ozawa S, Karasawa K, Sasai K. The Abbreviations dosimetric impact of respiratory breast movement and daily setup IMRT: Intensity-modulated radiotherapy; VMAT: Volumetric-modulated arc error on tangential whole breast irradiation using conventional wedge, therapy; SCR: Second cancer risk; OAR: Organs at risk; SIB: Simultaneous field-in-field and irregular surface compensator techniques. J Radiat Res. integrated boost; EAR: Excess absolute risk; HI: Homogeneity index; RT: Radio- 2013;54(1):157–65. https:// doi. org/ 10. 1093/ jrr/ rrs064. therapy; 3D-CRT : 3-Dimensional conformal radiation therapy; MLC: Multi-leaf 7. Lai Y, Chen Y, Wu S, Shi L, Fu L, Ha H, Lin Q. Modified volumetric modu- collimator; DR: Dose rate; CT: Computed tomography; TPS: Treatment plan- lated arc therapy in left sided breast cancer after radical mastectomy ning system; CTV: Clinical target volume; PTV: Planning target volume; MUs: with flattening filter free versus flattened beams. Medicine (Baltimore). Monitor units; DVH: Dose-volume histogram; CI: Conformal index. 2016;95(14): e3295. https:// doi. org/ 10. 1097/ MD. 00000 00000 003295. 8. Michalski A, Atyeo J, Cox J, Rinks M, Morgia M, Lamoury G. A dosimetric Acknowledgements comparison of 3D-CRT, IMRT, and static tomotherapy with an SIB for large The authors thank Prof. Xianfeng Liu for helpful discussion. and small breast volumes. Med Dosim. 2014;39(2):163–8. https:// doi. org/ 10. 1016/j. meddos. 2013. 12. 003. Authors’ contributions 9. Mo JC, Huang J, Gu WD, Gao M, Ning ZH, Mu JM, Li QL, Pei HL. A dosi- All authors carried out the study. Suyan Bi, Rui Zhu, Zhitao Dai draft the manu- metric comparison of double-arc volumetric arc therapy, step-shoot script. All authors read and approved the final manuscript. intensity modulated radiotherapy and 3D-CRT for left-sided breast Bi et al. Radiation Oncology (2022) 17:60 Page 10 of 10 cancer radiotherapy after breast-conserving surgery. Technol Health Care. 27. Schneider U, Sumila M, Robotka J. Site-specific dose-response relation- 2017;25(5):851–8. https:// doi. org/ 10. 3233/ THC- 160746. ships for cancer induction from the combined Japanese A-bomb and 10. Liu H, Chen X, He Z, Li J. Evaluation of 3D-CRT, IMRT and VMAT radio- Hodgkin cohorts for doses relevant to radiotherapy. Theor Biol Med therapy plans for left breast cancer based on clinical dosimetric study. Model. 2011;8:27. https:// doi. org/ 10. 1186/ 1742- 4682-8- 27. Comput Med Imaging Graph. 2016;54:1–5. https:// doi. org/ 10. 1016/j. 28. Liu X, Wu F, Guo Q, Wang Y, He Y, Luo H, Li Q, Zhong M, Li C, Yang H, Zhou compm edimag. 2016. 10. 001. J, Jin F. Estimation of radiotherapy modalities for patients with stage I-II 11. Nakamura N, Takahashi O, Kamo M, Hatanaka S, Endo H, Mizuno N, nasal natural killer T-Cell lymphoma. Cancer Manag Res. 2019;11:7219–29. Shikama N, Ogita M, Sekiguchi K. Eec ff ts of geometrical uncertainties on https:// doi. org/ 10. 2147/ CMAR. S2015 14. whole breast radiotherapy: a comparison of four different techniques. J 29. van Mourik A, van Kranen S, den Hollander S, Sonke JJ, van Herk M, van Breast Cancer. 2014;17(2):157–60. https:// doi. org/ 10. 4048/ jbc. 2014. 17.2. Vliet-Vroegindeweij C. Eec ff ts of setup errors and shape changes on 157. breast radiotherapy. Int J Radiat Oncol Biol Phys. 2011;79(5):1557–64. 12. Deasy JO, Moiseenko V, Marks L, Chao KS, Nam J, Eisbruch A. Radiother-https:// doi. org/ 10. 1016/j. ijrobp. 2010. 07. 032. apy dose-volume effects on salivary gland function. Int J Radiat Oncol 30. Fogliata A, De Rose F, Franceschini D, Stravato A, Seppälä J, Scorsetti M, Biol Phys. 2010;76(3 Suppl):S58-63. https:// doi. org/ 10. 1016/j. ijrobp. 2009. Cozzi L. Critical appraisal of the risk of secondary cancer induction from 06. 090. breast radiation therapy with volumetric modulated arc therapy relative 13. Toda K, Shibuya H, Hayashi K, Ayukawa F. Radiation-induced cancer to 3D conformal therapy. Int J Radiat Oncol Biol Phys. 2018;100(3):785–93. after radiotherapy for non-Hodgkin’s lymphoma of the head and neck: https:// doi. org/ 10. 1016/j. ijrobp. 2017. 10. 040. a retrospective study. Radiat Oncol. 2009;4:21. https:// doi. org/ 10. 1186/ 31. Jin F, Luo HL, Zhou J, He YN, Liu XF, Zhong MS, Yang H, Li C, Li QC, Huang 1748- 717X-4- 21. X, Tian XM, Qiu D, He GL, Yin L, Wang Y. Cancer risk assessment in modern 14. Becker SJ, Elliston C, Dewyngaert K, Jozsef G, Brenner D, Formenti radiotherapy workflow with medical big data. Cancer Manag Res. S. Breast radiotherapy in the prone position primarily reduces the 2018;10:1665–75. https:// doi. org/ 10. 2147/ CMAR. S1649 80. maximum out-of-field measured dose to the ipsilateral lung. Med Phys. 32. Cardis E, Howe G, Ron E, Bebeshko V, Bogdanova T, Bouville A, Carr Z, 2012;39(5):2417–23. https:// doi. org/ 10. 1118/1. 37004 02. Chumak V, Davis S, Demidchik Y, Drozdovitch V, Gentner N, Gudzenko 15. Kourinou KM, Mazonakis M, Lyraraki E, Stratakis J, Damilakis J. Scattered N, Hatch M, Ivanov V, Jacob P, Kapitonova E, Kenigsberg Y, Kesminiene dose to radiosensitive organs and associated risk for cancer develop- A, Kopecky KJ, Kryuchkov V, Loos A, Pinchera A, Reiners C, Repacholi ment from head and neck radiotherapy in pediatric patients. Phys Med. M, Shibata Y, Shore RE, Thomas G, Tirmarche M, Yamashita S, Zvonova I. 2013;29(6):650–5. https:// doi. org/ 10. 1016/j. ejmp. 2012. 08. 001. Cancer consequences of the Chernobyl accident: 20 years on. J Radiol 16. Kry SF, Salehpour M, Followill DS, Stovall M, Kuban DA, White RA, Rosen Prot. 2006;26(2):127–40. https:// doi. org/ 10. 1088/ 0952- 4746/ 26/2/ 001. II. Out-of-field photon and neutron dose equivalents from step-and- 33. Berrington de Gonzalez A, Gilbert E, Curtis R, Inskip P, Kleinerman R, Mor- shoot intensity-modulated radiation therapy. Int J Radiat Oncol Biol Phys. ton L, Rajaraman P, Little MP. Second solid cancers after radiation therapy: 2005;62(4):1204–16. https:// doi. org/ 10. 1016/j. ijrobp. 2004. 12. 091. a systematic review of the epidemiologic studies of the radiation dose- 17. Lee B, Lee S, Sung J, Yoon M. Radiotherapy-induced secondary cancer response relationship. Int J Radiat Oncol Biol Phys. 2013;86(2):224–33. risk for breast cancer: 3D conformal therapy versus IMRT versus VMAT. J https:// doi. org/ 10. 1016/j. ijrobp. 2012. 09. 001. Radiol Prot. 2014;34(2):325–31. https:// doi. org/ 10. 1088/ 0952- 4746/ 34/2/ 34. Suit H, Goldberg S, Niemierko A, Ancukiewicz M, Hall E, Goitein M, Wong 325. W, Paganetti H. Secondary carcinogenesis in patients treated with 18. Abo-Madyan Y, Aziz MH, Aly MM, Schneider F, Sperk E, Clausen S, radiation: a review of data on radiation-induced cancers in human, non- Giordano FA, Herskind C, Steil V, Wenz F, Glatting G. Second cancer human primate, canine and rodent subjects. Radiat Res. 2007;167(1):12– risk after 3D-CRT, IMRT and VMAT for breast cancer. Radiother Oncol. 42. https:// doi. org/ 10. 1667/ RR0527.1. 2014;110(3):471–6. https:// doi. org/ 10. 1016/j. radonc. 2013. 12. 002. 35. Dobler B, Maier J, Knott B, Maerz M, Loeschel R, Koelbl O. Second 19. Corradini S, Ballhausen H, Weingandt H, Freislederer P, Schönecker S, Cancer Risk after simultaneous integrated boost radiation therapy of Niyazi M, Simonetto C, Eidemüller M, Ganswindt U, Belka C. Left-sided right sided breast cancer with and without flattening filter. Strahlen- breast cancer and risks of secondary lung cancer and ischemic heart ther Onkol. 2016;192(10):687–95. English. https:// doi. org/ 10. 1007/ disease: effects of modern radiotherapy techniques. Strahlenther Onkol. s00066- 016- 1025-5. 2018;194(3):196–205. https:// doi. org/ 10. 1007/ s00066- 017- 1213-y. 20. Zhuang M, Zhang T, Chen Z, Lin Z, Li D, Peng X, Qiu Q, Wu R. Advanced Publisher’s Note nasopharyngeal carcinoma radiotherapy with volumetric modulated Springer Nature remains neutral with regard to jurisdictional claims in pub- arcs and the potential role of flattening filter-free beams. Radiat Oncol. lished maps and institutional affiliations. 2013;8:120. https:// doi. org/ 10. 1186/ 1748- 717X-8- 120. 21. Bragg CM, Wingate K, Conway J. Clinical implications of the anisotropic analytical algorithm for IMRT treatment planning and verification. Radio - ther Oncol. 2008;86(2):276–84. https:// doi. org/ 10. 1016/j. radonc. 2008. 01. 22. Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Brønnum D, Correa C, Cutter D, Gagliardi G, Gigante B, Jensen MB, Nisbet A, Peto R, Rahimi K, Taylor C, Hall P. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013;368(11):987–98. https:// doi. org/ 10. 1056/ NEJMo a1209 825. Re Read ady y to to submit y submit your our re researc search h ? Choose BMC and benefit fr ? Choose BMC and benefit from om: : 23. Peters S, Schiefer H, Plasswilm L. A treatment planning study comparing Elekta VMAT and fixed field IMRT using the varian treatment planning fast, convenient online submission system eclipse. Radiat Oncol. 2014;9:153. https:// doi. org/ 10. 1186/ thorough peer review by experienced researchers in your field 1748- 717X-9- 153. 24. Giorgia N, Antonella F, Alessandro C, Eugenio V, Luca C. Planning rapid publication on acceptance strategies in volumetric modulated arc therapy for breast. Med Phys. support for research data, including large and complex data types 2011;38(7):4025–31. https:// doi. org/ 10. 1118/1. 35984 42. • gold Open Access which fosters wider collaboration and increased citations 25. Schneider U. Modeling the risk of secondary malignancies after radio- therapy. Genes (Basel). 2011;2(4):1033–49. https:// doi. org/ 10. 3390/ genes maximum visibility for your research: over 100M website views per year 20410 33. 26. Schneider U. Mechanistic model of radiation-induced cancer after At BMC, research is always in progress. fractionated radiotherapy using the linear-quadratic formula. Med Phys. Learn more biomedcentral.com/submissions 2009;36(4):1138–43. https:// doi. org/ 10. 1118/1. 30897 92.

Journal

Radiation OncologySpringer Journals

Published: Mar 28, 2022

Keywords: Breast cancer; Second cancer risk; IMRT; Hybrid IMRT; Hybrid VMAT

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