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ORIGINAL ARTICLE
Year : 2016  |  Volume : 53  |  Issue : 1  |  Page : 147-151
 

Dosimetric comparison of three dimensional conformal radiation therapy versus intensity modulated radiation therapy in accelerated partial breast irradiation


1 Department of Oncology and Haematology, Salmaniya Medical Complex, Kingdom of Bahrain
2 Department of Physics, Acharya Nagarjuna University, Guntur, India

Date of Web Publication28-Apr-2016

Correspondence Address:
S Moorthy
Department of Oncology and Haematology, Salmaniya Medical Complex
Kingdom of Bahrain
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.180833

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 » Abstract 

Aim of Study: Breast conserving surgery (BCS) is the standard treatment for stage I and II breast cancer. Multiple studies have shown that recurrences after lumpectomy occur mainly in or near the tumor bed. Use of accelerated partial breast irradiation (APBI) allows for significant reduction in the overall treatment time that results in increasing patient compliance and decreasing healthcare costs. We conducted a treatment planning study to evaluate the role of intensity modulated radiation therapy (IMRT) with regards to three-dimensional conformal radiation therapy (3DCRT) in APBI. Materials and Methods: Computed tomography planning data sets of 33 patients (20 right sided and 13 left sided) with tumor size less than 3 cm and negative axillary lymph nodes were used for our study. Tumor location was upper outer, upper inner, central, lower inner, and lower outer quadrants in 10, 10, 5, 4 and 4 patients, respectively. Multiple 3DCRT and IMRT plans were created for each patient. Total dose of 38.5 Gy in 10 fractions were planned. Dosimetric analysis was done for the best 3DCRT and IMRT plans. Results: The target coverage has been achieved by both the methods but IMRT provided better coverage (P = 0.04) with improved conformity index (P = 0.01). Maximum doses were well controlled in IMRT to below 108% (P < 0.01). Heart V2 Gy (P < 0.01), lung V5 Gy (P = 0.01), lung V10 Gy (P = 0.02), contralateral breast V1 Gy (P < 0.01), contralateral lung V2 Gy (P < 0.01), and ipsilateral uninvolved breast (P < 0.01) doses were higher with 3DCRT compared to IMRT. Conclusion: Dosimetrically, IMRT–APBI provided best target coverage with less dose to normal tissues compared with 3DCRT-APBI.


Keywords: Accelerated partial breast irradiation, intensity modulated radiation therapy, left anterior descending artery, three-dimensional conformal radiation therapy, whole breast radiotherapy


How to cite this article:
Moorthy S, Elhateer H S, Majumdar S, Mohammed S, Patnaik R, Narayanamurty. Dosimetric comparison of three dimensional conformal radiation therapy versus intensity modulated radiation therapy in accelerated partial breast irradiation. Indian J Cancer 2016;53:147-51

How to cite this URL:
Moorthy S, Elhateer H S, Majumdar S, Mohammed S, Patnaik R, Narayanamurty. Dosimetric comparison of three dimensional conformal radiation therapy versus intensity modulated radiation therapy in accelerated partial breast irradiation. Indian J Cancer [serial online] 2016 [cited 2020 Jul 3];53:147-51. Available from: http://www.indianjcancer.com/text.asp?2016/53/1/147/180833



 » Introduction Top


Breast cancer is the leading cause of cancer-related death in women worldwide.[1] The main treatment is surgery. Modified radical mastectomy and breast conservation therapy (BCT) are the main types of treatment for breast cancer. BCT has been shown to have the same local control and survival rate when compared to modified radical mastectomy for early breast cancer patient.

Whole breast irradiation (WBI) is the current standard of care after lumpectomy with boost to the tumor bed. WBI is used to eliminate possible areas of occult cancer in remote areas of the breast. However, the biological significance of these areas of occult cancer is unknown, and the necessity to prophylactically treat the entire breast has recently been evaluated. Multiple studies on the pattern of in-breast tumor recurrence (IBTR) after conservative surgery have shown that the majority of recurrences were occurred in patients who did not receive radiotherapy and were mostly at or close to the tumor bed. WBI did not result in improved incidence of new cancer in remote areas of the breast; this was valid for both invasive and non-invasive breast cancer.[2],[3],[4]

On the other hand, accelerated partial breast irradiation (APBI) would provide improved cosmetic outcome as a result of decreased irradiated volume and at the same time, it delivers higher biologically effective doses to the tumor bed that might result in improved local control rates.[5] The other advantages of APBI are significantly shorter over all treatment time compared to WBI (1 week vs. 5-7 weeks), more convenient for the patients, and provides better cost-effective use of the radiation therapy resources.[5]

Different treatment strategies were used for APBI by various trials, external beam radiotherapy (EBRT): Conventional tangential, three-dimensional conformal radiation therapy (3DCRT), intensity modulated radiation therapy (IMRT) and electron beam and proton beam. Same way different brachytherapy (BT) techniques such as Mammosite balloon catheter, strut adjusted volume implant, interstitial implant, and intraoperative radiotherapy were used in different trials. The main advantage of EBRT over BT is non-invasive technique which is easy to implement in clinic with no additional expenses. The main disadvantage is the larger irradiated volume.

Most of the initial studies on APBI used 3DCRT techniques. After introduction of IMRT to breast cancer treatment, it becomes increasingly used in ABPI trials. IMRT has the potential for improved dose conformity to target volume with lower doses to normal tissue which can result in increase in the tumor control probability and reduction of normal tissue complications probability. In this study, we are attempting to examine the dosimetric criteria of planning target volume (PTV) coverage and doses to organs at risk (OAR) associated with the use of IMRT in APBI for patients with early stage breast cancer compared to 3DCRT.


 » Materials and Methods Top


Patients of stage 0, I, and II (tumor size <3 cm) were considered for this retrospective planning study. Computed tomography (CT) simulation data of previously treated 33 patients (13 left sides and 20 right sides) were used. Tumor location was upper outer, upper inner, central, lower inner, and lower outer quadrants in 10, 10, 5, 4, and 4 patients, respectively.

All patients were simulated using four-dimensional CT (Philips Medical Systems-6 slice CT Simulator) with Whole body Vaclok (Civco Medical Solutions, 1401 8th Street SE Orange City, Iowa 51041 USA) immobilization system. Patients were trained before simulation for deep inspirational breath hold (DIBH) technique. Patients were positioned in wide bore CT-simulator couch with the help of lasers and both arms rose above head. Radio opaque markers were placed during the procedure to guide the isocenter shift. CT scan images with slice thickness of 5 mm were obtained from mandible to upper abdomen area with intravenous contrast. Organ motion has been accounted for using real-time position management at the time of CT simulation (RPM Varian, Palo Alto, USA). The reflective markers placed at the position of xiphoid process and the respiration data were registered.

After Planning-CT scan was done, the digital imaging and communications in medicine (DICOM) images were transferred to Eclipse version 10.0.34 (Varian Medical Systems, Inc.

3100, HansenWay, Palo Alto, CA 94304-1038, USA) treatment planning system. Then, PTV and OAR volumes were delineated. The national surgical adjuvant breast and bowel project (NSABP)-B-39-radiation therapy oncology group (RTOG) breast cancer protocol was used as guideline for target delineation.[6] Lumpectomy gross tumor volume (GTV) contour was drawn using clinical and radiographic information including the excision cavity volume, architectural distortion, lumpectomy scar, seroma, and/or extent of surgical clips. Clinical target volume (CTV) was created by 1.5 cm 3D expansion of lumpectomy GTV and was limited posteriorly to anterior surface of the pectoralis major and anterolaterally by 3 mm from skin.

PTV was created using three-dimensional margin of 0.5 cm around CTV except anteriorly toward the skin which was decreased to zero. The OAR structures are delineated according to clinical and radiological data in the CT images taken on breath hold. The OAR structures are contoured such as ipsilateral lung, contra lateral lung, ipsilateral breast, contra lateral breast, heart, left anterior descending (LAD) artery, spinal cord, esophagus, trachea, humerus head, and liver.

Patients study cases were planned using Clinac 600CD linear accelerator (Varian Medical Systems, USA) which integrated with 120 leaves Millennium Multi Leaf Collimator (MLC). The dynamic MLC leaf width is from the central 20 cm of field has 5 mm leaf width and outer 20 cm of field has 10 mm leaf width. The treatment fields are almost evenly spaced within an arc of 180° on the side of the tumor. Gantry angles ranged from 330 to 150 (clockwise) for left side tumors and from 50 to 210 (counterclockwise) for right side tumors. In Eclipse, the IMRT plans were created with inverse plan optimization and the algorithm used was dose volume optimizer (DVO version 10.0.28). For the dose calculation, pencil beam convolution (PBC version 10.0.28) algorithm was used and leaf motions were calculated with leaf motion calculator (LMC version 10.0.28) algorithm.

For optimization, OAR dose constraints were given as ipsilateral lung V10 <10%, heart V5 10%, maximum dose as low as possible, contralateral breast maximum dose <1 Gy, and LAD maximum dose <7.7 Gy. Prescription dose used was 3.85 Gy in 10 fractions delivered twice daily (at least 6 h interval) to a total dose of 38.5 Gy delivered within 1 week. Out of many treatment plans created, the best plan was reviewed by radiation oncologists and used for analysis.

The target dose uniformity and conformity were calculated and evaluated. The conformity index (CI) as defined in international commission on radiation units and measurements (ICRU) 83[7] is:

CI(ref)= Volume of PTV covered by the reference dose/Volume of PTV

CI = 1.0 is ideal value

The homogeneity index (HI) as defined in ICRU is

HI = D2%–D98%/D50%

HI = 0 (Zero) is ideal value

Where D2%, D98%, and D50% are doses received by 2%, 98%, and 50% volume, respectively.

For 3DCRT plans, using beams eye view, fields were set up to minimize the dose to heart, lung and maximize the target coverage. Five to seven non-coplanar tangential beams were used to produce 95% of the prescribed dose coverage for 95% target volume (PTV). Critical organs were shielded using MLC without compromising PTV coverage. Beam weights were adjusted until the optimum coverage and acceptable hotspots were achieved. In addition to that, the field-in-fields were created to reduce hotspot or better target coverage and to improve homogenous dose distribution.

For IMRT plans, five to seven non-coplanar beams were used to achieve the minimum criteria of 95% of the target volume receives the 95% of the prescribed dose. Multiple plans were created until the dosimetric criteria of RTOG-4139 protocol achieved. The dose constraints to target and critical organs were mentioned in [Table 1]. Heterogeneity correction was done using modified batho method in eclipse. Dose–volume histogram (DVH) was used to analyze the volume receiving 1 Gy, 2 Gy, 5 Gy, 10 Gy, and 20 Gy, mean, maximum, and minimum doses.
Table 1: Modified Child-Pugh classification of the severity of liver disease

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Statistical analyses were performed using the Wilcoxon Signed Rank test. This matched pair t-test was applied to determine the statistical difference between the dose to volume data for IMRT versus 3DCRT. All the values were reported in ranges. The reported P value is two-tailed and P <0.05 were considered significant.


 » Results Top


Most of the planning objectives were met in all cases with both the techniques. 3DCRT plans failed to match our pre-set constraints for target maximum dose, lung V5 Gy, V10 Gy, and LAD doses. DVHs describing the dose volume relationship of the target as well as normal tissues of both the techniques is presented in [Table 2]. DVH shows better normal tissue sparing with IMRT than 3DCRT.
Table 2: Modified Child-Pugh classification of the severity of liver disease

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In 3DCRT plan, 95% volume of the PTV received by (mean) 95.7% of the prescription dose (36.84 Gy) but IMRT plan significantly (P = 0.04) covered PTV with (mean) 98.5% of the prescription dose (37.93 Gy). The mean dose was insignificant but maximum dose significantly better with IMRT (mean) 41.72 Gy (P < 0.01). HI was not significant but CI for IMRT (mean-1.15) is better than 3DCRT (mean-1.19) (P = 0.01). The dose distribution in axial sections is shown in [Figure 1a] and [Figure 1b]. These axial sections show that PTV conformity and exclusion of LAD of both techniques were presented [Figure 1a] and [Figure 1b].
Figure 1a: The target coverage, target conformity, maximum dose and non-sparing of left anterior descending artery by three dimensional conformal radiation therapy method

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Figure 1b: The better target coverage, target conformity, maximum dose and sparing of left anterior descending artery by intensity modulated radiation therapy method

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Ipsilateral lung V5 Gy and V10 Gy were significantly lower with IMRT (P = 0.01) and (P = 0.02). Ipsilateral lung mean doses were insignificant but maximum doses were significant with IMRT (P ≤ 0.01). Contralateral lung V2 Gy for 3DCRT was not better than IMRT (P < 0.01). Heart maximum doses were controlled with IMRT (P = 0.04) and also heart V2 Gy (P < 0.01) and mean doses were significant (P = 0.02). LAD maximum dose (mean) was 11.88 Gy for 3DCRT and 6.76 Gy for IMRT (P < 0.01). Thyroid doses were less than 0.5 Gy for both methods [Figure 2].
Figure 2: Dose–volume histogram shows better normal tissue sparing with intensity modulated radiation therapy than three dimensional conformal radiation therapy

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Contralateral breast V1 Gy was significantly lower with IMRT (P < 0.01). Uninvolved breast V9.5 Gy (25% of the prescription dose) received by 52.8% of the volume (mean) with 3DCRT and 45.18% of the volume with IMRT (P < 0.01). Also V19 Gy (50% of the prescription dose), V29 Gy (75% of the prescription dose), and V38.5 Gy (100% of the prescription dose) of the uninvolved breast volume were analyzed and all favored IMRT.


 » Discussions Top


The pattern of failure near or within the lumpectomy site in the ipsilateral breast after BCT has made to introduce the concept of APBI. Multiple studies with follow-up of more than 5 years for patients received WBI after conservative surgery reported that most of recurrences were in or near the tumor bed and the recurrence rate in remote areas within the ipsilateral breast matched that of the contralateral breast which infers that WBI benefits little.[8],[9],[10],[11],[12],[13] Based on this supportive statement, many APBI modalities were evolved using BT [14],[15],[16] and EBRT.[17],[18],[19],[20]

BT–APBI methods like interstitial, mammosite has long history of follow-up, the main disadvantages of BT are invasive procedure with risk of infection and the need of operative skills. On the other hand, EBRT techniques such as 3DCRT and IMRT are non-invasive; enable the use of existing resources, possibility of irradiated volume comparison with other institutions, and dose homogeneity. Direct comparison of EBRT dosimetric outcome with BT modalities is difficult due to fractionated delivery and variation in irradiated volume.

In our study, we attempted to analyze the dosimetric criteria of IMRT compared to 3DCRT in APBI for early breast cancer patients. IMRT is sophisticated technology capable to reduce normal tissue dose along with improved conformity and currently is used in many centers.[21]

Inverse planning optimization in IMRT uses non-uniform beamlets to improve the OAR and PTV doses to achieve required dosimetric criteria. IMRT is able to produce concave, convex, island type of dose distributions, and to reduce dose to adjacent organs like LAD. Also it has been proved effective and safe in different tumor types including head and neck, and prostate cancers where the target volume is in close proximity to OAR.[22],[23]

Taghian et al. reported 50% of the prescribed dose received by 40% of the uninvolved breast volume with 3DCRT.[24] In our study, 50% of the prescribed dose received by 42% by 3DCRT and 30% by IMRT. Also the mean volume of uninvolved breast receiving 25%, 50%, 75%, and 100% of the prescribed dose was reduced to 14%, 15%, 29%, and 42%, respectively, with IMRT compared to 3DCRT which was comparable to results from other studies.[25],[26]

The use of 3DCRT for ABPI is associated with multiple dosimetric challenges that made many authors tried to improve on its dosimetric quality. El Nemr et al. used mixed photon/electron for 3DCRT complex cases where photon was unable to fulfill dosimetric constraint.[27] Prone position treatment method was also used for APBI. Patel et al. used prone positioning to reduce doses to the heart.[28] Formenti et al. also used prone breast technique for 3DCRT and they reported decreased acute toxicity along with better sparing of the heart and the lungs.[29]

IMRT was introduced to overcome the limitations of 3DCRT for treatment of complex shape target volumes. In one of the earliest APBI-IMRT studies, Jagsi et al. reported unexpected poor cosmetic results that led to early closure of the trial.[30] On the other hand, several investigators have analyzed the different delivery methods of APBI to evaluate its safety and efficacy and they reported improved cosmetic outcome especially for patients with challenging anatomy of breast and/or larger breast size.[17],[31],[32],[33]

In this study, we used DIBH respiratory gating to decrease infraction movement and the electronic portal imaging device (EPID) for daily set up verification to decrease inter-fraction set up errors. In general; all plans met dosimetric criteria of NSABP B39, in addition to that better coverage and OAR sparing with use of IMRT. Some of the dosimetric criteria were not met by 3DCRT. For the 3DCRT arm, the heart V2 Gy (mean 10%) and lung V5 Gy (mean 16%), and V10 Gy (mean 11%) were comparable to Vicini et al.[34] and slightly higher when compared to Formenti et al. and Taghian et al. The former authors used total dose of 32 Gy and patient selection criteria of tumor size is 2 cm. Analysis of dosimetric data of IMRT arm compared to 3DCRT in our study showed that the CI improved with IMRT (P = 0.01) in comparison with the results from Lorenzo et al.[35]

Although the 95% of PTV coverage for IMRT was higher (98.5%) compared to 3DCRT (95.7% with a P value of 0.04), it appeared to be less than the results from Moran et al.[36] This may be due to larger PTV volume among our patients (309 cc vs. 185 cc). The doses to contralateral breast V1 Gy and ipsilateral lung V5 Gy were 1.05%, 9% with IMRT which were significantly lower (1.1% and 16%, respectively) when compared to 3DCRT and were comparable to the results from Lorenzi et al.(0.3% and 9.7%, respectively).[35]

Apart from RTOG dose criteria fulfillment, we did analysis on tumor location. Out of five quadrants, dosimetric results were better in the order of lower outer quadrant, upper outer quadrant, central quadrant, lower inner quadrant, and upper inner quadrant. Inner quadrants tumor coverage was difficult because of heart, LAD, and ipsilateral lung situated closer to target for both methods. Outer quadrants tumor planning was better with IMRT. Clinical studies with IMRT are limited. Lorenzo et al. clinically used IMRT and concluded that acute toxicity was considerably low. IBTR recurrences were 5% for APBI versus 4% for WBRT.[37]

Qiu et al. used volumetric modulated arc therapy for APBI and showed capability of significant reduction in ipsilateral lung and breast doses with low monitor units.[38] Using IMRT, doses to uninvolved breast, lungs, heart, and contralateral breast reduced better along with optimal coverage to PTV than compared to 3DCRT. So, long-term clinical data are needed to provide strong support of proper modality, dose, and fractionation schemes to use APBI effectively. EBRT-PBI methods are easily adoptable and executable by institutions with existing resources.


 » Conclusions Top


IMRT–APBI is technically and dosimetrically feasible. It provides better target coverage with less dose to normal tissues compared with 3DCRT-APBI. More clinical studies with long-term follow-up are needed to further assess its clinical outcomes.

 
 » References Top

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    Figures

  [Figure 1a], [Figure 1b], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]

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