Comparison of Dose Distribution in Regional Lymph Nodes in Whole-Breast Radiotherapy vs. Whole-Breast Plus Regional Lymph Node Irradiation: An In Silico Planning Study in Participating Institutions of the Phase III Randomized Trial (KROG 1701)
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. General Information
2.2. Comparisons of RLN and OAR Dose between the Treatment Arms
3. Discussion
4. Materials and Methods
4.1. Cases
4.2. Data Analysis
4.3. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
- Early Breast Cancer Trialists’ Collaborative Group; Darby, S.; McGale, P.; Correa, C.; Taylor, C.; Arriagada, R.; Clarke, M.; Cutter, D.; Davies, C.; Ewertz, M.; et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: Meta-analysis of individual patient data for 10, 801 women in 17 randomised trials. Lancet 2011, 378, 1707–1716. [Google Scholar]
- Poortmans, P.M.P.; Coles, C.; Bernier, J. Treatment of Regional Lymph Nodes in Breast Cancer—Evidence in Favor of Radiation TherapyTreatment of Regional Lymph Nodes in Breast CancerTreatment of Regional Lymph Nodes in Breast Cancer. JAMA Oncol. 2016, 2, 989–990. [Google Scholar] [CrossRef] [PubMed]
- The National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology, Breast Cancer, Version 1.2019. Available online: https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. (accessed on 19 May 2019).
- Harris, J.R. Treatment of Regional Lymph Nodes in Breast Cancer—Not Recommended for All Patients With 1 to 3 Positive Auxiliary Nodes. JAMA Oncol. 2016, 2, 991–992. [Google Scholar] [PubMed]
- Poortmans, P.M.; Collette, S.; Kirkove, C.; Van Limbergen, E.; Budach, V.; Struikmans, H.; Collette, L.; Fourquet, A.; Maingon, P.; Valli, M.; et al. Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer. N. Engl. J. Med. 2015, 373, 317–327. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Whelan, T.J.; Olivotto, I.A.; Parulekar, W.R.; Ackerman, I.; Chua, B.H.; Nabid, A.; Vallis, K.A.; White, J.R.; Rousseau, P.; Fortin, A.; et al. Regional Nodal Irradiation in Early-Stage Breast Cancer. N. Engl. J. Med. 2015, 373, 307–316. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, H.; Park, W.; Choi, D.; Ahn, S.; Kim, S.; Kim, E.; Lee, J.; Lee, K.; Kim, J.; Lee, H.-S.; et al. Abstract OT2-04-02: A phase 3 study of post-lumpectomy radiotherapy to whole breast + regional lymph nodes vs whole breast alone for patients with pN1 breast cancer treated with taxane-based chemotherapy (KROG 1701): Trial in progress. In Proceedings of the 2018 San Antonio Breast Cancer Symposium, San Antonio, TX, USA, 4–8 December 2019. [Google Scholar] [CrossRef]
- Xie, L.; Higginson, D.S.; Marks, L.B. Elective regional nodal irradiation in patients with early-stage breast cancer. Semin. Radiat. Oncol. 2011, 21, 66–78. [Google Scholar] [CrossRef] [PubMed]
- Piccart-Gebhart, M.; Holmes, E.; Baselga, J.; de Azambuja, E.; Dueck, A.C.; Viale, G.; Zujewski, J.A.; Goldhirsch, A.; Armour, A.; Pritchard, K.I.; et al. Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial. J. Clin. Oncol. 2016, 34, 1034–1042. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gingras, I.; Holmes, E.; De Azambuja, E.; Nguyen, D.H.; Izquierdo, M.; Anne Zujewski, J.; Inbar, M.; Naume, B.; Tomasello, G.; Gralow, J.R.; et al. Regional Nodal Irradiation After Breast Conserving Surgery for Early HER2-Positive Breast Cancer: Results of a Subanalysis From the ALTTO Trial. J. Natl. Cancer Inst. 2017, 109, djw331. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Poortmans, P.M.; Venselaar, J.L.; Struikmans, H.; Hurkmans, C.W.; Davis, J.B.; Huyskens, D.; van Tienhoven, G.; Vlaun, V.; Lagendijk, J.J.; Mijnheer, B.J.; et al. The potential impact of treatment variations on the results of radiotherapy of the internal mammary lymph node chain: A quality-assurance report on the dummy run of EORTC Phase III randomized trial 22922/10925 in Stage I–III breast cancer(1). Int. J. Radiat. Oncol. Biol. Phys. 2001, 49, 1399–1408. [Google Scholar] [CrossRef]
- Chung, Y.; Kim, J.W.; Shin, K.H.; Kim, S.S.; Ahn, S.J.; Park, W.; Lee, H.S.; Kim, D.W.; Lee, K.C.; Suh, H.S.; et al. Dummy run of quality assurance program in a phase 3 randomized trial investigating the role of internal mammary lymph node irradiation in breast cancer patients: Korean Radiation Oncology Group 08-06 study. Int. J. Radiat. Oncol. Biol. Phys. 2015, 91, 419–426. [Google Scholar] [CrossRef] [PubMed]
- Kim, H.; Park, W.; Yu, J.I.; Choi, D.H.; Huh, S.J.; Kim, Y.J.; Lee, E.S.; Lee, K.S.; Kang, H.S.; Park, I.H.; et al. Prognostic Impact of Elective Supraclavicular Nodal Irradiation for Patients with N1 Breast Cancer after Lumpectomy and Anthracycline Plus Taxane-Based Chemotherapy (KROG 1418): A Multicenter Case-Controlled Study. Cancer Res. Treat. 2017, 49, 970–980. [Google Scholar] [CrossRef] [PubMed]
- Taylor, C.; Correa, C.; Duane, F.K.; Aznar, M.C.; Anderson, S.J.; Bergh, J.; Dodwell, D.; Ewertz, M.; Gray, R.; Jagsi, R.; et al. Estimating the Risks of Breast Cancer Radiotherapy: Evidence From Modern Radiation Doses to the Lungs and Heart and From Previous Randomized Trials. J. Clin. Oncol. 2017, 35, 1641–1649. [Google Scholar] [CrossRef] [PubMed]
- Dess, R.T.; Liss, A.L.; Griffith, K.A.; Marsh, R.B.; Moran, J.M.; Mayo, C.; Koelling, T.M.; Jagsi, R.; Hayman, J.A.; Pierce, L.J. Ischemic Cardiac Events Following Treatment of the Internal Mammary Nodal Region Using Contemporary Radiation Planning Techniques. Int. J. Radiat. Oncol. Biol. Phys. 2017, 99, 1146–1153. [Google Scholar] [CrossRef] [PubMed]
- Deasy, J.O.; Blanco, A.I.; Clark, V.H. CERR: A computational environment for radiotherapy research. Med. Phys. 2003, 30, 979–985. [Google Scholar] [CrossRef] [PubMed]
- Allozi, R.; Li, X.A.; White, J.; Apte, A.; Tai, A.; Michalski, J.M.; Bosch, W.R.; El Naqa, I. Tools for consensus analysis of experts’ contours for radiotherapy structure definitions. Radiother. Oncol. 2010, 97, 572–578. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fedorov, A.; Beichel, R.; Kalpathy-Cramer, J.; Finet, J.; Fillion-Robin, J.C.; Pujol, S.; Bauer, C.; Jennings, D.; Fennessy, F.; Sonka, M.; et al. 3D Slicer as an image computing platform for the Quantitative Imaging Network. Magn. Reason. Imaging 2012, 30, 1323–1341. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Offersen, B.V.; Boersma, L.J.; Kirkove, C.; Hol, S.; Aznar, M.C.; Biete Sola, A.; Kirova, Y.M.; Pignol, J.P.; Remouchamps, V.; Verhoeven, K.; et al. ESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage breast cancer. Radiother. Oncol. 2015, 114, 3–10. [Google Scholar] [CrossRef] [PubMed]
- Zeman, E.M.; Schreiber, E.C.; Tepper, J.E. 27—Basics of Radiation Therapy. In Abeloff’s Clinical Oncology, 6th ed.; Niederhuber, J.E., Armitage, J.O., Kastan, M.B., Doroshow, J.H., Tepper, J.E., Eds.; Content Repository Only; Elsevier: Philadelphia, PA, USA, 2020; pp. 431–460. ISBN 978-0-323-47674-4. [Google Scholar]
- Rucker, G.; Schimek-Jasch, T.; Nestle, U. Measuring inter-observer agreement in contour delineation of medical imaging in a dummy run using Fleiss’ kappa. Methods Inf. Med. 2012, 51, 489–494. [Google Scholar] [PubMed] [Green Version]
- Landis, J.R.; Koch, G.G. The measurement of observer agreement for categorical data. Biometrics 1977, 33, 159–174. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Contour90% iso * | Dice Similarity Coefficient † | |||
---|---|---|---|---|
Case | Median Volume (Range) | Kappa | Median (Range) | |
Case A | WBI | 511 cc (307–721 cc) | 0.77 | 0.80 (0.51–0.89) |
WBI+RNI | 766 cc (469–1184 cc) | 0.68 | 0.77 (0.58–0.90) | |
Case S | WBI | 745 cc (418–1211 cc) | 0.78 | 0.83 (0.71–0.94) |
WBI+RNI | 1048 cc (468–1557 cc) | 0.71 | 0.80 (0.68–0.89) |
Case A (Rt, ALND) | Case S (Lt, SLNBx) | |||||
---|---|---|---|---|---|---|
Regions | WBI | WBI+RNI | p-Value | WBI | WBI+RNI | p-Value |
Axillary level I | 0.64 (0.14–1.05) | 1.05 (0.68–1.17) | <0.01 | 0.61 (0.09–0.98) | 1.03 (0.52–1.19) | <0.01 |
Axillary level II | 0.27 (0.02–0.68) | 1.08 (0.97–1.15) | <0.01 | 0.51 (0.01–0.89) | 1.07 (0.34–1.15) | <0.01 |
Axillary level III | 0.02 (0.01–0.33) | 1.12 (0.93–1.18) | <0.01 | 0.05 (0.00–0.52) | 1.11 (0.14–1.22) | <0.01 |
SCN | 0.01 (0.00–0.09) | 1.12 (0.69–1.20) | <0.01 | 0.02 (0.00–0.11) | 1.11 (0.18–1.24) | <0.01 |
IMN | 0.54 (0.05–0.81) | 0.82 (0.02–1.15) | <0.01 | 0.49 (0.01–0.86) | 0.72 (0.29–1.18) | <0.01 |
Case A (Rt. Breast, ALND) | Case S (Lt. Breast, SLNBx) | |||||
---|---|---|---|---|---|---|
Parameters | WBI | WBI+RNI | p-Value | WBI | WBI+RNI | p-Value |
Ipsilateral lung | ||||||
V5 Gy (%) | 30.2 (15.1–77.6) | 46.8 (31.6–99.7) | <0.01 | 28.3 (11.8–81.5) | 48.1 (27.8–99.9) | <0.01 |
V10 Gy (%) | 20.5 (10.1–44.1) | 34.9 (19.2–97.4) | <0.01 | 20.7 (7.4–57.8) | 36.7 (17.5–99.9) | <0.01 |
V20 Gy (%) | 14.3 (6.1–26.1) | 28.2 (7.1–76.5) | <0.01 | 16.3 (3.9–29.0) | 28.8 (7.2–74.0) | <0.01 |
V30 Gy (%) | 11.6 (2.1–20.5) | 20.1 (1.5–38.4) | <0.01 | 12.9 (1.1–23.1) | 20.2 (2.7–48.6) | <0.01 |
Mean dose (Gy) | 8.8 (4.7–15.3) | 13.9 (5.6–27.2) | <0.01 | 8.3 (3.0–16.8) | 14.2 (5.4–29.3) | <0.01 |
Heart | ||||||
Mean dose (Gy) | 0.5 (0.1–5.0) | 0.9 (0.3–6.8) | 0.07 | 3.7 (0.8–8.9) | 4.4 (1.5–10.6) | 0.09 |
Case | Description |
---|---|
Case A | 43 years old. She received partial mastectomy and sentinel lymph node biopsy for right breast cancer. Intraoperative frozen sections of sentinel lymph nodes revealed metastatic carcinoma in 2 out of 3 sentinel lymph nodes. Complete axillary lymph node dissection was performed. The pathology showed a 2.5-cm-sized invasive ductal carcinoma of the breast. In the specimen of axillary lymph node dissection, there was no metastatic carcinoma in the lymph nodes. |
Case S | 40 years old. She received partial mastectomy and sentinel lymph node biopsy for cT1N0 cancer in the left breast. Intraoperative frozen sections of sentinel lymph nodes revealed metastatic carcinoma in 1 out of 4 sentinel lymph nodes. Axillary lymph node dissection was not performed. Pathology showed a 1.2-cm-sized invasive ductal carcinoma of the breast. |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Kim, H.; Kim, H.; Park, W.; Baek, J.Y.; Ahn, S.J.; Kim, M.Y.; Park, S.-H.; Lee, I.J.; Ha, I.; Kim, J.H.; et al. Comparison of Dose Distribution in Regional Lymph Nodes in Whole-Breast Radiotherapy vs. Whole-Breast Plus Regional Lymph Node Irradiation: An In Silico Planning Study in Participating Institutions of the Phase III Randomized Trial (KROG 1701). Cancers 2020, 12, 3261. https://doi.org/10.3390/cancers12113261
Kim H, Kim H, Park W, Baek JY, Ahn SJ, Kim MY, Park S-H, Lee IJ, Ha I, Kim JH, et al. Comparison of Dose Distribution in Regional Lymph Nodes in Whole-Breast Radiotherapy vs. Whole-Breast Plus Regional Lymph Node Irradiation: An In Silico Planning Study in Participating Institutions of the Phase III Randomized Trial (KROG 1701). Cancers. 2020; 12(11):3261. https://doi.org/10.3390/cancers12113261
Chicago/Turabian StyleKim, Haeyoung, Heejung Kim, Won Park, Jong Yun Baek, Sung Ja Ahn, Mi Young Kim, Shin-Hyung Park, Ik Jae Lee, Inbong Ha, Jin Hee Kim, and et al. 2020. "Comparison of Dose Distribution in Regional Lymph Nodes in Whole-Breast Radiotherapy vs. Whole-Breast Plus Regional Lymph Node Irradiation: An In Silico Planning Study in Participating Institutions of the Phase III Randomized Trial (KROG 1701)" Cancers 12, no. 11: 3261. https://doi.org/10.3390/cancers12113261