The aim of this study was to estimate the radiation-related secondary cancer risks in organs during the treatment of breast cancer with different radiotherapy techniques, such as three-dimensional conformal radiotherapy (3D-CRT), intensity modulated radiotherapy (IMRT), and volumetric modulated arc therapy (VMAT). The treatment plans for 26 patients with breast cancer who received whole-breast irradiation at a dose of 50 Gy included tangential field 3D-CRT with hard-wedges (W-TF), tangential field IMRT (2F-IMRT), multiple field IMRT (6F-IMRT), and double partial arcs (VMAT). Patients were divided into three groups according to the distance between the contralateral breast (CB) and the body of the sternum. Setup error was simulated by moving the isocenter, and the dose distribution was then recalculated without changing the field fluency distribution. Based on the linear-exponential, the plateau, and the full mechanistic dose-response models, the organ equivalent dose and excess absolute risk were calculated from dose-volume histograms to estimate the secondary cancer risks in organs. Compared with 3D-CRT, IMRT and VMAT showed excellent results regarding tumor conformity and homogeneity; however, the low dose volume to organs was considerably higher in 6F-IMRT and VMAT. Secondary cancer risks for 2F-IMRT were comparable or slightly lower than for W-TF, but considerably lower than for 6F-IMRT or VMAT. After setup error simulation, there was a small increase in secondary cancer risk for 2F-IMRT and an increase of 159% and 318% for 6F-IMRT and VMAT, respectively, compared with W-TF. Although these results were obtained in most patients, they did not necessarily apply to every individual. The secondary cancer risks in the CB decreased significantly in correlation with increased distance for all alternative techniques, although they were higher in VMAT and lower in 2F-IMRT regardless of the distance. After setup error simulation, the increased changes in secondary cancer risks in the CB were comparable between 2F-IMRT, 6F-IMRT, and VMAT, suggesting that the secondary cancer risks in the CB mainly depend on radiotherapy techniques and distance, although the effect of setup error cannot be ignored. In the contralateral lung (CL), the secondary cancer risks were almost independent from distance and depended mainly on radiotherapy techniques; they were rarely affected by setup error. VMAT was associated with a higher secondary cancer risk in the CL. For the ipsilateral lung (IL), the secondary cancer risks were higher than those in other organs because the IL receives high doses to achieve tumor control, and they were relatively lower in VMAT. This warrants special consideration when estimating the secondary cancer risk to the IL. The study results suggested that the optimal radiotherapy method for breast cancer should be determined on an individual basis and according to the balance between secondary cancer risks related to anatomic diversity and setup error, which can prevent blind selection of techniques.

/pdf/secondary-cancer-risk-after-radiation-therapy-for-breast-4u7lncc2jh.pdf

Secondary cancer risk after radiation therapy for breast cancer with different radiotherapy techniques.

Adjuvant radiotherapy is the standard treatment after breast-conserving surgery. According to meta-analyses, adjuvant 3d-conventional irradiation reduces the risk of local recurrence and thereby improves long-term survival by 5–10%. However, there is an unintended exposure of organs such as the heart, lungs and contralateral breast. Irradiation of the left breast has been related to long-term effects like increased rates of coronary events as well as second cancer induction. Modern radiotherapy techniques such as tangential intensity modulated radiotherapy (t-IMRT) and tangential volumetric modulated arc therapy (t-VMAT) and particularly deep inspiration breath hold (DIBH) technique have been developed in order to improve coverage of target volume and to reduce dose to normal tissue. The aim of this study was to compare t-IMRT-plans with t-VMAT-plans in DIBH position for left-sided breast irradiation in terms of normal tissue exposure, i.e. of lungs, heart, left anterior descending coronary artery (LADCA), as well as homogeneity (HI) and conformity index (CI) and excess absolute risk (EAR) for second cancer induction for organs at risk (OAR) after irradiation. Twenty patients, diagnosed with left-sided breast cancer and treated with breast-preserving surgery, were included in this planning study. For each patient DIBH-t-IMRT plan using 5 to 7 beams and t-VMAT plan using four rotations were generated to achieve 95% dose coverage to 95% of the volume. Data were evaluated on the basis of dose-volume histograms: Cardiac dose and LADCA (mean and maximum dose, D25% and D45%), dose to ipsilateral and contralateral lung (mean, D20%, D30%), dose to contralateral breast (mean dose), total monitor units, V5% of total body and normal tissue integral dose (NTID). In addition, homogeneity index and conformity index, as well as the excess absolute risk (EAR) to estimate the risk of second malignancy were calculated. T-IMRT showed a significant reduction in mean cardiac dose of 26% (p = 0.002) compared to t-VMAT, as well as a significant reduction in the mean dose to LADCA of 20% (p = 0.03). Following t-IMRT, mean dose to the left lung was increased by 5% (p = 0.006), whereas no significant difference was found in the mean dose to the right lung and contralateral breast between the two procedures. Monitor units were 31% (p = 0.000004) lower for t-IMRT than for t-VMAT. T-IMRT technique significantly reduced normal tissue integral dose (NTID) by 19% (p = 0.000005) and the V5% of total body by 24% (p = 0.0007). In contrast, t-VMAT improved CI and HI by 2% (p = 0.001) and 0.4% (p = 0.00001), respectively. EAR with t-IMRT was significantly lower, especially for contralateral lung and contralateral breast (2–5/10,000 person years) but not for ipsilateral lung. Compared to t-VMAT, t-IMRT in left-sided breast irradiation significantly reduced dose to organs at risk as well as normal tissue integral dose, and V5% total body. EAR with t-IMRT was significantly lower for contralateral lung and contralateral breast. T-VMAT, however, achieved better homogeneity and conformity. This may be relevant in individual cases where sufficient coverage of medial lymphatic target volumes is warranted.

/pdf/left-breast-irradiation-with-tangential-intensity-modulated-3waxan34vl.pdf

Left breast irradiation with tangential intensity modulated radiotherapy (t-IMRT) versus tangential volumetric modulated arc therapy (t-VMAT): trade-offs between secondary cancer induction risk and optimal target coverage

Purpose Adjuvant radiation therapy (RT) for breast cancer improves outcomes, but prior studies have documented substantive cardiac dose and cardiac risk. We assessed the mean heart dose (MHD) of RT and estimated the risk of RT-associated cardiac toxicity in women undergoing adjuvant RT for breast cancer in contemporary (predominantly) community practice. Methods and materials We identified women with left-sided breast cancer receiving adjuvant RT between 2012 and 2014 from 94 centers across 16 states. We used bivariate analyses and multivariable linear regression to assess associations between RT techniques and MHD. Excess RT-related cardiac risk by age 80 was estimated for women diagnosed at age 60 using the previously reported relationship between MHD and cardiac risk. Results Among 1161 women, 77.3% were treated in community practice and with breast conservation (77.8%). The most common techniques were free-breathing (92.2%), supine (94.8%), and fixed gantry intensity modulated RT (FG-IMRT; 46.9%). The median MHD was 2.76 Gy (interquartile range, 1.47-5.03). In multivariable analyses, the predicted median MHD with deep inspiration breath hold was 2.41 Gy compared with 3.86 Gy with free-breathing ( P P Conclusions MHD varies substantially across patients and is influenced by technique in predominantly community settings. Overall risk of cardiac toxicity is modest.

Radiation dose and cardiac risk in breast cancer treatment: An analysis of modern radiation therapy including community settings

Background Breast radiotherapy is an established adjuvant treatment after breast conserving surgery. One of the important individual factors affecting the final cosmetic outcome after radiation is breast size. The purpose of this review is to summarise the clinical toxicity profile of adjuvant radiotherapy in women with breasts of various sizes, and to evaluate the treatment planning studies comparing target coverage and dose to thoracic organs at risk in relation to breast size. Conclusions Inhomogeneity and excessive radiation dose (hot spots) in the planning of target volume as well as large volume of the breast per se, all contribute to a higher rate of acute adverse events and suboptimal final cosmetic outcome in adjuvant breast cancer radiotherapy, regardless of the fractionation schedule. Improved homogeneity leads to a lower rate of ≥ grade 2 toxicity and can be achieved with three-dimensional conformal or modulated radiotherapy techniques. There may be an association between body habitus (higher body mass index, bigger breast size, pendulous breast, and large chest wall separation) and a higher mean dose to the ipsilateral lung and whole heart. A combination of the technical innovations (i.e. the breath-hold technique, prone position with or without holding breath, lateral decubitus position, and thermoplastic bra), dose prescription (i.e. moderate hypofractionation), and irradiated volume (i.e. partial breast irradiation) should be tailored to every single patient in clinical practice to mitigate the risk of radiation adverse effects.

/pdf/breast-size-impact-on-adjuvant-radiotherapy-adverse-effects-czl7smi9yx.pdf

Breast size impact on adjuvant radiotherapy adverse effects and dose parameters in treatment planning

Objective To compare 3-dimensional conformal radiotherapy (3D-CRT) and intensity modulated radiotherapy (IMRT) techniques on the target tissue and critical organ doses in terms of dosimetry, during treatment planning of patient's post-mastectomy radiotherapy (PMRT) to the left chest wall. Materials and Methods Twenty breast cancer patients with left-sided post-mastectomy have selected for PMRT both 3D-CRT and IMRT techniques. Dosimetric calculation of dose simulation in Eclipse treatment planning system have been performed. Organs at risk with the maximum dose, minimum dose, mean dose, D95, conformity and homogeneity indexes and total monitor unit for the Planning Target Volume were compared in terms of the critical organ doses. Results There was no significant difference between the two treatment planning techniques in terms of maximum, minimum, mean dose and heterogeneity index (p>0.05). At low doses, the dose received at the heart was significantly lower with the 3D-CRT technique, but there was no statistically significant difference between the two techniques at the maximum and average doses in the high dose regions. Conclusion For PMRT to the left chest wall, IMRT significantly improves the conformity of plan and reduce the high-dose volumes of ipsilateral lung and heart compared to 3D-CRT, but 3D-CRT is superior in terms of low-dose volume.

/pdf/dosimetric-comparison-of-three-dimensional-conformal-319ymjce78.pdf

Dosimetric Comparison of Three-Dimensional Conformal Radiotherapy (3D-CRT) and Intensity Modulated Radiotherapy Techniques (IMRT) with Radiotherapy Dose Simulations for Left-Sided Mastectomy Patients.

Purpose The ICRU/GEC-ESTRO released the ICRU Report No. 89, which introduced the concept of four-dimensional brachytherapy and ushered in a new era of brachytherapy for cervical cancer. The purpose of this study was to evaluate the local control and late toxicity of four-dimensional brachytherapy in cervical cancer through a systematic review and to reveal the dose-response relationship between the volumetric dose paraments and the local control rate via a probit model. Material and Methods We identified studies that reported the HR-CTV D90 and local control probabilities by searching the PubMed Database, the Web of Science Core Collection and the Cochrane Library Database through February 1st, 2022. Regression analyses were performed between the HR-CTV D90 and the local control probability using a probit model. Results Nineteen studies enrolling 3,616 patients were included. The probit model showed a significant relationship between the HR-CTV D90 value and IR-CTV D90 Vs. the local control probability, P < 0.001 and P = 0.003, respectively. The D90 for HR-CTV and IR-CTV corresponding to a probability of 90% local control was 79.1 GyEQD2,10 (95% CI:69.8 – 83.7 GyEQD2,10) and 66.5 GyEQD2,10 (95% CI: 62.8 - 67.9 GyEQD2,10), respectively. The limits for the prescribed dose of 85 GyEQD2,10 for HR-CTV D90 theoretically warranted a 92.1% (95% CI: 90.2% - 95.3%) local control rate, and 87.2% (95% CI: 82.4% - 91.8%) local control probability was expected for 65 GyEQD2,10 to IR-CTV D90. The probit model showed no significant relationship between the D2cc to organs at risk and the probability of grade 3 and above gastrointestinal or genitourinary toxicity. Conclusions Four-dimensional brachytherapy takes into account uncertain factors such as tumour regression, internal organ motion and organ filling, and provides a more accurate and more therapeutic ratio delivery through adaptive delineation and replanning, replacement of the applicator, and the addition of interstitial needles. The dose volume effect relationship of four-dimensional brachytherapy between the HR-CTV D90 and the local control rate provides an objective planning aim dose.

/pdf/four-dimensional-image-guided-adaptive-brachytherapy-for-2ftit4q4.pdf

Four-Dimensional Image-Guided Adaptive Brachytherapy for Cervical Cancer: A Systematic Review and Meta-Regression Analysis

Purpose To investigate the role of transrectal ultrasound guidance in interstitial brachytherapy for cervical cancer. Material and methods Forty-eight patients who underwent interstitial brachytherapy treatment for cervical cancer between January 2017 and January 2018 were enrolled in the study. The distances between each inserted needle and the lesion were measured at seven sites by ultrasound (D1-D7) and compared to the corresponding distances (M1-M7) when visualised with nuclear magnetic resonance imaging (MRI). Measurements were paired on the basis of the observation sites, e.g. D1 and M1, D2 and M2. The statistical differences, intraclass correlation coefficients (ICCs), and linear relationships for the paired measurements were calculated. Results No significant differences were found between the paired M and D measurements, with all ICCs showing high levels of concordance (0.81-0.93). Conclusions Transrectal ultrasound showed strong agreement with MRI results in determining the position of the inserted needles. Transrectal ultrasound is a useful tool for guided interstitial brachytherapy and is appropriate for widespread use in the treatment of locally advanced cervical cancer.

https://www.termedia.pl/Journal/-54/pdf-41569-10?filename=Application of transrectal.pdf

Application of transrectal ultrasound in guiding interstitial brachytherapy for advanced cervical cancer.

Background For brachytherapy of cervical cancer, applicator shifts can not be avoided. The present investigation concerned Utrecht interstitial applicator shifts and their effects on organ movement and DVH parameters during 3D CT-based HDR brachytherapy of cervical cancer. Materials and methods After the applicator being implanted, CT imaging was achieved for oncologist contouring CTVhr, CTVir, and OAR, including bladder, rectum, sigmoid colon and small intestines. After the treatment, CT imaging was repeated to determine applicator shifts and OARs movements. Two CT images were matched by pelvic structures. In both imaging results, we defined the tandem by the tip and the base as the marker point, and evaluated applicator shift, including X, Y and Z. Based on the repeated CT imaging, oncologist contoured the target volume and OARs again. We combined the treatment plan with the repeated CT imaging and evaluated the change range for the doses of CTVhr D90, D2cc of OARs. Results The average applicator shift was -0.16 mm to 0.10 mm for X, 1.49 mm to 2.14 mm for Y, and 1.9 mm to 2.3 mm for Z. The change of average physical doses and EQD2 values in Gyα/β range for CTVhr D90 decreased by 2.55 % and 3.5 %, bladder D2cc decreased by 5.94 % and 8.77 %, rectum D2cc decreased by 2.94 % and 4 %, sigmoid colon D2cc decreased by 3.38 % and 3.72 %, and small intestines D2cc increased by 3.72 % and 10.94 %. Conclusions Applicator shifts and DVH parameter changes induced the total dose inaccurately and could not be ignored. The doses of target volume and OARs varied inevitably.

/pdf/utrecht-interstitial-applicator-shifts-and-dvh-parameter-2fae0ld7je.pdf

Utrecht Interstitial Applicator Shifts and DVH Parameter Changes in 3D CT-based HDR Brachytherapy of Cervical Cancer.

OBJECTIVES To evaluate the accuracy of ultrasound (US) in determining the positions of parametrial implants by comparing US with magnetic resonance imaging (MRI) for advanced cervical cancer. METHODS Patients undergoing brachytherapy with parametrial implantation for cervical cancer from February 2017 to February 2019 were involved in the study. The transverse section of the cervix (surface S1 ) and the transverse section 1 cm above the external cervix (surface S2 ) were selected from MRI and US images as the observation planes. In the MRI observation plane, the distances between the uterine titanium needles and the uterine tube/implanter were set as M1 to M4 ; in the US observation plane, the distances between the uterine titanium needles and the uterine tube/implanter were set as D1 to D4 . The differences and consistency in M and D of each group were then compared. RESULTS There were no significant differences between M and D in each group (P = .058; P = .821; P = .870; and P = .936, respectively). The intraclass correlation coefficients of M and D in each group were 0.970, 0.968, 0.952, and 0.956. A regression analysis showed that the relationships between M and D in each group were as follows: M1 = 0.9449D1  + 0.1812; M2 = 0.9463D2  + 0.0965; M3 = 0.9176D3  + 0.1233; and M4 = 0.9253D4  + 0.1224. CONCLUSIONS In parametrial brachytherapy for cervical cancer, US can accurately determine the positions of parametrial implantation needles, which is already applicable on MRI, and can provide assistance in parametrial brachytherapy for advanced cervical cancer.

Clinical Application of Ultrasound Guidance for Parametrial Treatment of Advanced Cervical Cancer

Objective
To compare target volume and dosimetry between computed tomography(CT)-and magnetic resonance imaging(MRI)-guided three-dimensional(3D)conformal brachytherapy for locally advanced cervical cancer, and to provide evidence for optimization of the image-guided approach and improvement of treatment regimen.


Methods
Thirteen patients with locally advanced cervical cancer who were treated with radical radiotherapy in our hospital in 2014 were enrolled as subjects. All patients received MRI-guided 3D conformal intracavitary/interstitial brachytherapy. All patients received MRI and CT scans for each brachytherapy fraction, based on which the target volume delineation, intracavitary/interstitial regimen design, and intracavitary-only treatment regimen design were performed. Comparison of data between MRI and CT scans was performed using paired t test.


Results
The width and volume of the high-risk clinical target volume(HR-CTV)were significantly smaller in the MRI simulation than in the CT simulation((38.0±9.4)mm vs.(45.1±8.7)mm, P=0. 000; (34.2±15. 3)cm3vs.(42.9±20.4)cm3, P = 0. 002), and the width, thickness, and volume of the intermediate-risk clinical target volume(IR-CTV)were also significantly smaller in the MRI simulation than in the CT simulation((58.8±9. 4)mm vs.(65.4±10. 3)mm, P=0.000;(34.8±6.3)mm vs.(37.5±6.3)mm, P=0. 001;(90.9±28. 5)cm3vs.(109.0±36.4)cm3, P = 0. 000). The D90 values for HR-CTV and IR-CTV were significantly higher in the MRI simulation than in the CT simulation(87. 6 Gy vs. 85. 8 Gy, P=0. 013;67. 7 Gy vs. 66. 3 Gy, P=0. 005), while the average D2 cm3 values for the bladder and rectum were significantly lower in the MRI simulation than in the CT simulation(73. 1 Gy vs. 75. 5 Gy , P= 0.011 ; 61. 0 Gy vs. 65. 7 Gy , P= 0. 000).


Conclusions
Compared with the MRI simulation, the CT simulation overestimates the width of target volume. MRI has substantial advantages in dosimetry for target volume and normal tissues. The intracavitary/interstitial treatment can make up the reduced dose for the target volume resulting from the CT simulation.


Key words: 
Cervical neoplasms; Image guided brachytherapy; Target volume delineation; Dosimetry

A comparative study of CT-and MRI-based three-dimensional conformal brachytherapy for locally advanced cervical cancer

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