Dosimetric Comparison of IMRT Versus 3DCRT for Post-mastectomy Chest Wall Irradiation: An Analytical Observational Study

Purpose: To compare the dose distribution of three-dimensional conformal radiation therapy (3DCRT) with intensity-modulated radiation therapy (IMRT) for post-mastectomy radiotherapy (PMRT) to left chest wall. Materials and Methods: 30 post-MRM female breast cancer patients with histologically confirmed infiltrating ductal carcinoma of unilateral left breast without evidence of distant metastasis or second malignancy were found eligible during January 2017 to December 2021. All patients received 45 Gy in 20 fractions. Planning target volume (PTV) parameters -D2, D98, Dmean, V95, and V107—homogeneity index (HI), and conformity index (CI) were compared. The mean doses of lung and heart, percentage volume of ipsilateral lung receiving 5 Gy (V5), 20 Gy (V20), and 49 Gy (V49) and that of heart receiving 5 Gy (V5), 25 Gy (V25), and 42 Gy (V42) were extracted from dose-volume histograms and compared. Results: PTV parameters were comparable between the two groups. CI was significantly improved with IMRT (1.118 vs. 1.224, p < 0.04) but HI was similar (0.0951 vs. 0.0962, p = 0.125) compared to 3DCRT. IMRT in comparison to 3DCRT significantly reduced the high-dose volumes of lung (V20, 24.52% vs. 29.62%; V49, 3.56% vs. 6.42%; p < 0.001) and heart (V25, 5.89% vs. 8.24%; V42, 1.64% vs. 6.12%; p < 0.001); mean dose of lung and heart (10.21 vs. 11.96 Gy and

3.86 vs. 7.42 Gy, respectively; p < 0.001). Conclusions: For left sided breast cancer, IMRT significantly improves the conformity of plan and reduce the mean dose and high-dose volumes of ipsilateral lung and heart compared to 3DCRT, but 3DCRT is superior in terms of low-dose volume.

 Introduction

Breast cancer is the most common cancer in females, both worldwide and in India [1]. In contrast to Western world, most of the patients here present with advanced stage due to lack of mass screening programmes and awareness; so modified radical mastectomy (MRM) is performed more often than breast conservative surgery (BCS).

Large prospective trials [2] and a meta-analysis [3] have shown that adjuvant radiotherapy of the chest wall improves local control and survival in node positive breast cancer patients after mastectomy. Intensity-modulated radiation therapy (IMRT) has proved to be superior to three-dimensional conformal radiation therapy (3DCRT) in various sites like head and neck, central nervous system, lung, prostate, etc.

In case of chest wall irradiation, lung and heart remain two most important vital organs, irradiation of which always causes concern to radiation oncologists. This becomes even more complicated as most of the chemotherapeutic agents used to treat breast carcinoma like anthracyclines, taxanes and trastuzumab, possess cardiotoxic potential. IMRT directs radiation at the breast tumor and modulates the intensity of the radiation beams with laser accuracy, helping to spare healthy tissue surrounding the breast tumor. IMRT allows each dose of radiation to be custom-tailored according to the exact geometrical shape of the breast tumor [4].

Randomized, retrospective and population based studies have shown that the radiotherapy of the chest wall is associated with a significantly increased risk of cardiac morbidity and mortality [3, 5-16]. Data on the effect of IMRT of the chest wall in post-mastectomy breast cancer patients are scarce in the literature [17-19]. So the present study was carried out at our department to compare the dosimetry in post-MRM patients of left breast with IMRT and 3DCRT.

 Materials and Methods

30 post-MRM female breast cancer patients with histologically confirmed infiltrating ductal carcinoma of unilateral left breast without evidence of distant metastasis or second malignancy were found eligible during January 2017 to December 2021. All patients were immobilized using a thermoplastic mould in supine position over a breast board fixed on the couch with both arms extended above their head onto arm rests, abducted and externally rotated. Scar sites, drain sites and breast borders were marked using lead markers. Patients were simulated using a 16 slice somatom computed tomography (CT) simulator wit 6 MV beam. The 3-mm CT cuts were taken once optimal patient position was confirmed. Supraclavicular fossa (SCF) was irradiated when there was histopathological evidence of 1 or more axillary node metastases, inadequate lymph node dissection (less than 10 nodes examined pathologically) or when neoadjuvant chemotherapy was administered prior to definitive surgery. The clinical target volume (CTV) was contoured according to the Radiation Therapy Oncology Group (RTOG) breast cancer atlas guidelines [20]. The Planning Target Volume (PTV) was then generated by giving 1 cm margin to CTV. Organs at risk (OAR) contoured included heart, lung, spinal cord, esophagus and contralateral breast. 15 patients were treated with 3DCRT and 15 with IMRT with dose of 45 Gy in 20 fractions with 2.25 Gy per fraction, 1 fraction per day for 5 days per week.

<italic id="italic-482871c7d41f7683506109d47611b9fe">Dosimetric Analysis<italic id="italic-2"/></italic>

Planning target volume (PTV) parameters D2, D98, Dmean, V95, and V107, homogeneity index (HI), and conformity index (CI) were compared. The mean doses of lung and heart, percentage volume of ipsilateral lung receiving 5 Gy (V5), 20 Gy (V20), and 49 Gy (V49) and that of heart receiving 5 Gy (V5), 25 Gy (V25), and 42 Gy (V42) were extracted from dose-volume histograms and compared.

HI was defined as the difference between the near-maximum and near-minimum dose normalised to the median dose,

HI=D2-D98/DP

where D2 and D98 are the dose received by 2% and 98% volume of PTV; and Dp is the prescribed dose. The ideal value is zero; an HI value approaching zero indicates a more homogenous dose distribution within the PTV and it increases as homogeneity decreases. CI was defined as the ratio of volume of tissue receiving at least 95% of the prescribed dose divided by the volume of the PTV. The closer the CI to one, the more conformal is the plan.

 <italic id="italic-5bda86c0f4c4a36f467fe5cad259c08b">Statistical Analysis<italic id="italic-a8025c4f68462b85c5c52880451834bc"/></italic>

For statistical analysis, all data were recorded and analysed on Microsoft Excel 2007 and Statistical Package for Social Sciences (SPSS) version 20.0 (IBM Corp., Armonk, New York, USA). The t-test for two independent means was used for quantitative data. The p-value reports were two tailed and an alpha level of 0.05 was used to assess statistical significance.

 Results

Baseline patient and tumor characteristics were found to be comparable between the two groups. PTV parameters are shown in Table 1.

Parameter 3DCRT IMRT P-value
mean sd mean sd
PTV volume (cc) 815 12.2 804 6.8 0.01
D2 (Gy) 47.82 1.09 47.64 1.01 0.18
D98 (Gy) 43.36 0.86 43.24 0.92 0.12
D MEAN 45.56 1.12 45.45 1.06 0.11
V 95 (%) 97.8 1.6 98.1 1.2 0.57
V 107 (%) 2.24 0.98 1.86 0.94 0.29
Homogeneity Index 0.0962 0 0.09 0 0.13
Conformity index 1.224 0 1.118 0 0.04

Values are presented as mean ± 1 standard deviation(sd). PTV, planning target volume; 3DCRT, three-dimensional conformal radiation therapy; IMRT, intensity-modulated radiation therapy; CTV, clinical target volume; D2 and D98, the dose delivered to 2% and 98% of PTV; Dmean, mean dose of PTV; V95 and V107, volume of PTV receiving greater than 95% to 107% of prescribed dose.

It can be seen that although CI was significantly improved with IMRT (1.118 vs. 1.224, p < 0.04) compared to 3DCRT, HI was similar (0.0951 vs. 0.0962, p = 0.125). No significant difference was noted between D2, D98, Dmean, V95 and V107 with the two techniques. Dosimetric parameters for lung and heart are shown in Table 2.

Parameter 3DCRT IMRT P-value
mean sd mean sd
V5 (%) 52.09 6.12 58.42 4.28 0.002
V20 (%) 29.62 2.52 24.52 1.68 0.001
V49 (%) 6.42 1.12 3.56 1.24 0.001
D MEAN (Gy) 11.96 1.86 10.21 1.94 0.017
HEART
V5 (%) 21.62 1.89 26.54 4.2 0.003
V25 (%) 8.24 0.75 5.89 0.91 0.001
V42 (%) 6.12 0.94 1.64 0.35 0.001
D MEAN(Gy) 7.42 0.98 3.86 0.89 0.001

Values are presented as mean ± 1 standard deviation. 3DCRT, three-dimensional conformal radiation therapy; IMRT, intensity-modulated radiation therapy; Vx, volume of tissue receiving x Gy; Dmean, mean dose

For lung, IMRT in comparison to 3DCRT significantly reduced the high-dose volumes (V20, 24.52% vs. 29.62%; V49, 3.56% vs. 6.42%; p < 0.001) and the mean dose (10.21 Gy vs. 11.96 Gy, p < 0.001). Similarly for heart also, IMRT in comparison to 3DCRT significantly reduced the high-dose volumes (V25, 5.89% vs. 8.24%; V42, 1.64% vs. 6.12%; p < 0.001) and the mean dose (3.86 Gy vs. 7.42 Gy, p < 0.001). However, 3DCRT proved to be superior to IMRT in terms of low-dose volume for both the lung (V5, 52.09% vs. 58.42%; p < 0.001) and the heart (V5, 21.62% vs. 26.54%; p < 0.001).

 Discussion

Data about the impact of IMRT on the adjuvant radiotherapy of the chest wall in postmastectomy patients are scarce in the literature. This study was undertaken to evaluate the dose distribution of IMRT of the chest wall compared to 3D-CRT in postmastectomy breast cancer patients. Fiorentino et al. [21] compared 3DCRT and 4-fields IMRT treatment plans, in terms of target dose coverage, integral dose and dose to organs at risk (OARs) in early breast cancer and concluded 4-fields IMRT technique significantly reduced the dose to OARs and normal tissue, with a better target coverage compared to 3DCRT.

All our plans had the PTV95% coverage values of >95% of prescription dose. In literature [22,23], various planning studies have shown the PTV95% coverage values ranging from 90% to 97%. Hong et al. have showed that the use of equally spaced gantry angles not only improves HI and CI but also reduces the volume of critical normal tissues [24]. In the present study, statistically significant improvement was noted in CI with IMRT compared to 3DCRT (1.127 vs. 1.254, p < 0.001) [25,26]. However, no significant difference was noted in HI (0.094 vs. 0.096, p = 0.83). Similar results have been reported by Moorthy et al. [26] (CI,0.14vs.0.18,p=0.01;HI,1.01vs.1.03,p=0.45)andRudat etal.[26](CI, 0.32vs. 0.25,p=0.03; HI, 0.73vs. 0.77,p>0.05).

However, Li et al. [27] concluded that IMRT neither significantly improved CI (1.42 vs. 1.41, p = 0.13) nor HI (0.13 for both groups, p = 1.0); whereas Beckham et al. [28] concluded that IMRT significantly improved not only CI (0.91 vs. 0.48, p < 0.05) but also HI (0.95 vs. 0.74, p < 0.05).

Moorthy et al. [25] concluded that IMRT in comparison to 3DCRT had significantly lower V40 heart (2.13% vs. 7.5%) and Dmax left anterior descending artery (29.17 Gy vs. 39.5 Gy, p < 0.05). Rudat et al. [26] concluded that tangential beam IMRT statistically significantly reduced the V55 by an average of 43% (5.7% vs. 10.6%) and the mean heart dose by an average of 20% (7.04 Gy vs. 8.77 Gy, p = 0.03). Beckham et al. [28] concluded that IMRT significantly reduced volume of the heart receiving more than 30 Gy (V30 heart, 1.7% vs. 12.5%).

In conclusion, IMRT for the irradiation of the chest wall in post-mastectomy left sided breast cancer patients offers the potential to significantly reduce the mean dose and high-dose volumes of the ipsilateral lung and heart compared to 3DCRT (p < 0.001). IMRT significantly improves the conformity of the plan (p < 0.001) but the homogeneity remains similar with the two techniques (p = 0.83).

Conflict of interest

Nil

Funding

Nil

References Available from: http://www.ncdirindia.org/NCRP/ALL_NCRP_REPORTS/PBCR_REPORT_2012_2014/index.htm National Cancer Registry Programme . Bangalore, India: National Centre for Disease Informatics and Research; c2016. Three-year report of Population Based Cancer Registries 2012-2014 [Internet] [cited 2018 Mar 1] 3 03 247-253 82 2007 10.1016/j.radonc.2007.02.001 Overgaard M Nielsen HM Overgaard J Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology Is the benefit of postmastectomy irradiation limited to patients with four or more positive nodes, as recommended in international consensus reports? A subgroup analysis of the DBCG 82 b&c randomized trials 17 9503 12 2087-2106 366 2005 10.1016/S0140-6736(05)67887-7 Clarke M. Collins R. Darby S. Davies C. Elphinstone P. Evans V. Godwin J. Gray R. Hicks C. James S. MacKinnon E. McGale P. McHugh T. Peto R. Taylor C. Wang Y. Lancet (London, England) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials Available from: https://www.cancercenter.com/breast-cancer/imrt Cancer Treatment Centers of America . Boca Raton, FL: Cancer Treatment Centers of America; c2018. IMRT for breast cancer [Internet] [cited 2018 Mar 1] 16 6 03 419-424 97 2005 10.1093/jnci/dji067 Giordano SH Kuo Y Freeman JL Buchholz TA Hortobagyi GN Goodwin JS Journal of the National Cancer Institute Risk of cardiac death after adjuvant radiotherapy for breast cancer 8 08 557-565 6 2005 10.1016/S1470-2045(05)70251-5 Darby SC McGale P Taylor CW Peto R The Lancet. Oncology Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women in US SEER cancer registries 01 7383 02 256-257 326 2003 10.1136/bmj.326.7383.256 Darby S McGale P Peto R Granath F Hall P Ekbom A BMJ (Clinical research ed.) Mortality from cardiovascular disease more than 10 years after radiotherapy for breast cancer: nationwide cohort study of 90 000 Swedish women 3 03 447-453 12 1994 10.1200/JCO.1994.12.3.447 Cuzick J. Stewart H. Rutqvist L. Houghton J. Edwards R. Redmond C. Peto R. Baum M. Fisher B. Host H. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology Cause-specific mortality in long-term survivors of breast cancer who participated in trials of radiotherapy 5 887-896 22 1992 10.1016/0360-3016(92)90784-f Rutqvist L. E. Lax I. Fornander T. Johansson H. International Journal of Radiation Oncology, Biology, Physics Cardiovascular mortality in a randomized trial of adjuvant radiation therapy versus surgery alone in primary breast cancer 5 05 727-732 12 1986 10.1016/0360-3016(86)90029-5 Høst H. Brennhovd I. O. Loeb M. International Journal of Radiation Oncology, Biology, Physics Postoperative radiotherapy in breast cancer--long-term results from the Oslo study 17 6688 06 1611-1614 298 1989 Haybittle J. L. Brinkley D. Houghton J. A'Hern R. P. Baum M. BMJ : British Medical Journal Postoperative radiotherapy and late mortality: evidence from the Cancer Research Campaign trial for early breast cancer. 2 03 204-208 40 1989 10.1016/s0009-9260(89)80099-6 Jones J. M. Ribeiro G. G. Clinical Radiology Mortality patterns over 34 years of breast cancer patients in a clinical trial of post-operative radiotherapy 01 4 03 755-762 43 1999 10.1016/s0360-3016(98)00412-x Paszat L. F. Mackillop W. J. Groome P. A. Schulze K. Holowaty E. International Journal of Radiation Oncology, Biology, Physics Mortality from myocardial infarction following postlumpectomy radiotherapy for breast cancer: a population-based study in Ontario, Canada 23 9188 10 1425-1430 354 1999 10.1016/s0140-6736(99)02245-x Højris I. Overgaard M. Christensen J. J. Overgaard J. Lancet (London, England) Morbidity and mortality of ischaemic heart disease in high-risk breast-cancer patients after adjuvant postmastectomy systemic treatment with or without radiotherapy: analysis of DBCG 82b and 82c randomised trials. Radiotherapy Committee of the Danish Breast Cancer Cooperative Group 20 30 10 7475-7482 23 2005 10.1200/JCO.2005.13.755 Patt DA Goodwin JS Kuo Y Freeman JL Zhang DD Buchholz TA Hortobagyi GN Giordano SH Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology Cardiac morbidity of adjuvant radiotherapy for breast cancer 20 21 07 3031-3037 25 2007 10.1200/JCO.2006.08.6595 Correa CR Litt HI Hwang W Ferrari VA Solin LJ Harris EE Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology Coronary artery findings after left-sided compared with right-sided radiation treatment for early-stage breast cancer 2 107-116 30 2005 10.1016/j.meddos.2005.02.002 Cavey ML Bayouth JE Endres EJ Pena JM Colman M M Hatch S Medical Dosimetry: Official Journal of the American Association of Medical Dosimetrists Dosimetric comparison of conventional and forward-planned intensity-modulated techniques for comprehensive locoregional irradiation of post-mastectomy left breast cancers 3 03 313-318 94 2010 10.1016/j.radonc.2009.12.037 Gauer T Engel K Kiesel A Albers D Rades D Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology Comparison of electron IMRT to helical photon IMRT and conventional photon irradiation for treatment of breast and chest wall tumours 2 02 235-240 94 2010 10.1016/j.radonc.2009.12.015 Laan HP Korevaar EW Dolsma WV MaduroJH Langendijk JA Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology Minimising contralateral breast dose in post-mastectomy intensity-modulated radiotherapy by incorporating conformal electron irradiation Available from: https://www.rtog.org/CoreLab/ContouringAtlases/BreastCancerAtlas.aspx RTOG Foundation . Philadelphia, PA: RTOG Foundation; c2018. Breast cancer atlas [Internet] [cited 2018 Mar 1] 2 02 146-153 122 2017 10.1007/s11547-016-0700-z Fiorentino A Ruggieri R Giaj-Levra N Sicignano G Di Paola G Naccarato S Fersino S Mazzola R Tebano U Ricchetti F Alongi F La Radiologia Medica Three-dimensional conformal versus intensity modulated radiotherapy in breast cancer treatment: is necessary a medical reversal? 2 02 86-92 184 2008 10.1007/s00066-008-1730-9 Abo-Madyan Y Polednik M Rahn A Schneider F Dobler B Wenz F Lohr F Strahlentherapie Und Onkologie: Organ Der Deutschen Rontgengesellschaft ... [et Al] Improving dose homogeneity in large breasts by IMRT: efficacy and dosimetric accuracy of different techniques 1 07 34-41 92 2009 10.1016/j.radonc.2009.03.003 Barnett GC Wilkinson J Moody AM Wilson CB Sharma R Klager S Hoole ACF Twyman N Burnet NG Coles CE Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology A randomised controlled trial of forward-planned radiotherapy (IMRT) for early breast cancer: baseline characteristics and dosimetry results 15 5 07 1155-1164 44 1999 10.1016/s0360-3016(99)00132-7 Hong L. Hunt M. Chui C. Spirou S. Forster K. Lee H. Yahalom J. Kutcher G. J. McCormick B. International Journal of Radiation Oncology, Biology, Physics Intensity-modulated tangential beam irradiation of the intact breast 10 10 1 2013 10.14319/ijcto.0101.10 Moorthy S Sakr H Hasan S Al-Janahi S Murthy N International Journal of Cancer Therapy and Oncology Dosimetric study of SIB-IMRT versus SIB-3DCRT for breast cancer with breath-hold gated technique 21 03 26 6 2011 10.1186/1748-717X-6-26 Rudat V Alaradi AA Mohamed A Ai-Yahya K Altuwaijri S Radiation Oncology (London, England) Tangential beam IMRT versus tangential beam 3D-CRT of the chest wall in postmastectomy breast cancer patients: a dosimetric comparison 22331 22337 9 2016 Li W Wang J Cheng H Yu H Ma J Int J Clin Exp Med IMRT versus 3D-CRT for post-mastectomy irradiation of chest wall and regional nodes: a population-based comparison of normal lung dose and radiation pneumonitis 01 3 11 918-924 69 2007 10.1016/j.ijrobp.2007.06.060 Beckham WA Popescu CC Patenaude VV Wai ES Olivotto IA International Journal of Radiation Oncology, Biology, Physics Is multibeam IMRT better than standard treatment for patients with left-sided breast cancer?