Skip to main content

EDITORIAL article

Front. Oncol., 08 January 2024
Sec. Radiation Oncology
This article is part of the Research Topic Advances in Treatment Planning, Optimization and Delivery for Radiotherapy of Breast Cancer View all 14 articles

Editorial: Advances in treatment planning, optimization and delivery for radiotherapy of breast cancer

  • 1Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
  • 2Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, United States
  • 3Department of Radiation Oncology, New York Proton Center, New York, NY, United States

Introduction

Various planning, optimization, delivery, and treatment modalities, as well as their fractionations, are constantly being investigated or updated to improve the therapeutic ratio for breast cancer patient care. Advanced treatment planning and delivery methods, such as volumetric modulated arc therapy (VMAT), have been applied in complex anatomical scenarios where standard 3D conformal planning techniques have failed (1). Although VMAT is useful in these situations, long-term follow-up data on toxicity due to low-dose exposure to VMAT is relatively scarce. Knowledge-based planning (KBP) has been applied to predict optimally achievable dose distributions in a given patient anatomy and to determine if a specific delivery technique is suitable for a patient, minimizing the likelihood of toxicity (2). Moderate hypofractionation decreases the logistic burden and cost to patients and healthcare systems, making it the standard of care for whole breast irradiation (WBI) (35). However, there is a paucity of data on toxicity when using moderate hypofractionation for regional nodal irradiation (RNI). Minimizing treatment volume from whole breast to partial breast irradiation (PBI), in appropriately selected patients, has further helped improve patient outcomes, thus supporting its use (6, 7). However, deploying PBI among a larger patient population that can benefit from it is an area of active investigation in the community. The dosimetric advantages of proton radiation for breast cancer are well established (8), and its use in the postmastectomy radiation therapy (PMRT) setting with either tissue expander or implant reconstruction is increasing. However, more data are needed when it comes to implant safety and toxicity with proton therapy. The potential application of MR-guided radiation therapy (MRgRT) as a neoadjuvant therapy to shrink tumor volume has been discussed for PBI (9). An improved understanding of the quantification and dosimetric impact of the electron stream effect (ESE) will only help increase its use for WBI and PMRT with RNI while simultaneously improving tumor visualization. Our Research Topic titled “Advances in Treatment Planning, Optimization, and Delivery for Radiotherapy of Breast Cancer” is dedicated to featuring original research and review articles addressing some of these topics and the potential paucity of data in these areas.

Topics covered in this editorial

Knowledge-based planning, delivery, and dosimetry for breast cancer: Phurailatpam et al., Quesada et al., Li et al., Prunaretty et al., and Ramos-Mendez et al.

Hypofractionation and axillary nodal irradiation in breast cancer: Chitapanarux et al. and Elumalai et al.

Partial breast radiation: Le et al., Rhome et al., and Galavis et al.

Proton therapy for breast cancer: Chen et al. and Sayan et al.

MRI-guided radiotherapy for breast cancer: Lee et al.

Articles included in this Research Topic

Many patients in low- and middle-income countries (LMICs) present with locally advanced disease, requiring PMRT and RNI as part of their adjuvant treatment. Phurailatpam et al. designed an efficient workflow using VMAT and KBP for moderate and ultra-hypofractionation for these patients. The automated plans were less complex, improving the efficiency of treatment delivery and impacting the workflow in a busy clinic, thus amalgamating KBP in a decreasing treatment planning burden while planning for patients requiring RNI with hypofractionation.

The need to irradiate IMNs increases heart and lung exposure, and VMAT is known to reduce the dose for these while generating more conformal isodose distributions (1, 10). Quesada et al. addressed the feasibility of VMAT in the treatment of bilateral breast with regional nodes. They reported on long-term follow-up concerning the toxicity and safety of VMAT for the largest cohort of patients in this setting.

Deep inspiration breath-hold (DIBH) reduces the extent of low-dose exposure to normal tissue (10). Li et al. investigated tangent-based arcs to further improve dosimetry over partial VMAT using DIBH. This significantly reduced treatment time, making the treatment more clinically viable.

During treatment planning, factoring surrogates that are predictors of late toxicity is essential. Although such surrogates are reliable for cardiac toxicities in conventional planning, their understanding of advanced planning such as VMAT is scarce. Prunaretty et al. investigated this for left-sided breast cancer patients with unfavorable cardiac anatomy requiring IMRT/VMAT for improved sparing, and they concluded that a heart volume receiving dose ≥ 40 Gy is a better surrogate.

With the increasing use of tissue expanders in the postmastectomy setting, the safety and accuracy of dose calculation in these cases cannot be overemphasized. Ramos-Mendez et al. presented the first comprehensive evaluation of treatment planning strategies accounting for artifacts introduced by tissue expanders and verified it via Monte Carlo calculations, the collapsed cone dose calculation algorithm, and measurement with film. The highest discrepancies in the calculations in their study were noted when artifacts were assumed to have the dosimetric properties of water. These errors could be reduced if the tissue expander geometry and materials were used instead.

Patient eligibility to safely receive PBI is sensitive to when the CT scan is performed for treatment planning. Le et al. first reported the impact of factors other than time post-surgery on the healing of the cavity in the postoperative period, such as body mass index, receipt of neoadjuvant chemotherapy, hypertension, and patient positioning, serving as a reference for safe delivery of PBI.

Triple-negative breast cancer (TNBC) has inferior overall survival, disease-free survival, and local control. The use of PBI can potentially help reduce toxicity over WBI (current standard of care for TNBC) in the concurrent setting while improving logistics. Rhome et al. reported on the outcomes of patients with TNBC treated prospectively with post-lumpectomy PBI and concurrent chemotherapy compared with a matched WBI cohort. The promising results presented in this study are hypothesis generating for prospective clinical trials.

Galavis et al. discussed the PBI delivery technique and the current trends in research to help better define patient selection, treatment delivery, treatment planning dosimetry, and outcomes with respect to toxicity.

There is a relative paucity of data on toxicity profiles for patients receiving regional nodal irradiation (RNI) with hypofractionation and simultaneous integrated boost (SIB). Chitapanarux et al. reported acute toxicities with respect to skin and hematologic function for patients receiving hypofractionation prospectively with helical tomotherapy to the intact breast and regional lymph nodes after BCS and adjuvant chemotherapy. The results were acceptable in both endpoints.

With studies maturing on the use of hypofractionation in the RNI setting, Elumalai et al. presented the latest guidelines and evidence on the management of the axilla with surgery versus radiation.

Chen et al. presented a case study to show the dosimetric impact of a dislocated metallic port of a breast tissue expander while receiving proton therapy and its impact on cumulative dose due to its potential dislocations during treatment.

With the increasing use of proton therapy in post-mastectomy, more data are needed on its use in the reconstruction setting. Sayan et al. presented a retrospective comparison of acute toxicities and reconstructive complications in patients treated with proton-based and photon-based PMRT. They concluded that acute skin toxicity was the most frequent adverse event in PMRT for both modalities. Reconstructive complications were not significantly higher with proton therapy.

Lee et al. quantified the dosimetric impact of the electron stream effect (ESE) during 0.35T MRgRT, along with a discussion on how these excess doses due to ESE can be reduced and the implications for treatment planning after BCS or mastectomy.

Conclusions and future outlook

As results from randomized clinical trials such FABREC are being reported, while the RT CHARM is to arrive within the next year, there are likely to be more and more patients receiving RNI in the PMRT setting, increasing the likelihood of complex anatomies treated with hypofractionation. The need to meet coverage constraints, conformity, and homogeneity while sparing normal tissue from low doses will necessitate deploying these advanced planning, optimization, and delivery methods, such as VMAT and DIBH, while emphasizing new treatment modalities, such as protons. The SHARE trial being made available, which confirms the non-inferiority of APBI to WBI, will also encourage the increased use of the former in the treatment of select patients. With improved image guidance and real-time tumor visualization with MRgRT, the therapeutic ratio is likely to be further enhanced. We hope that through these diverse arrays of topics covering original research and review articles, we have addressed some of the scarcity in the data in a way that could potentially be supplementary and useful in further supporting the safe and efficacious use of these treatments and planning and delivery methods.

Author contributions

VD: Writing – original draft, Writing – review & editing. NO: Writing – review & editing. JC: Writing – review & editing. AC: Writing – review & editing. HL: Writing – review & editing.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

1. Kuo L, Ballangrud AM, Ho AY, Mechalakos JG, Li G, Hong L. A VMAT planning technique for locally advanced breast cancer patients with expander or implant reconstructions requiring comprehensive postmastectomy radiation therapy. Med Dosim (2019) 44:150–4. doi: 10.1016/j.meddos.2018.04.006

PubMed Abstract | CrossRef Full Text | Google Scholar

2. Rice A, Zoller I, Kocos K, Weller D, DiCostanzo D, Hunzeker A, et al. The implementation of RapidPlan in predicting deep inspiration breath-hold candidates with left-sided breast cancer. Med Dosim (2019) 44:210–8. doi: 10.1016/j.meddos.2018.06.007

PubMed Abstract | CrossRef Full Text | Google Scholar

3. Whelan TJ, Pignol JP, Levine MN, Julian JA, MacKenzie R, Parparia S, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med (2010) 362:513–20. doi: 10.1056/NEJMoa0906260

PubMed Abstract | CrossRef Full Text | Google Scholar

4. Haviland JS, Owen JR, Dewar JA, Agrawal RK, Barrett J, Barrett-Lee PJ, et al. The UK standardization of breast radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomized controlled trials. Lancet Oncol (2013) 14:1086–94. doi: 10.1016/S1470-2045(13)70386-3

PubMed Abstract | CrossRef Full Text | Google Scholar

5. Smith BD, Bellon JR, Blitzblau R, Freedman G, Haffty B, Hahn C, et al. Radiation therapy for the whole breast: Executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based guideline. Pract Radiat Oncol (2018) 8:145–52. doi: 10.1016/j.prro.2018.01.012

PubMed Abstract | CrossRef Full Text | Google Scholar

6. Coles CE, Griffin CL, Kirby AM, Titley J, Agrawal RK, Alhasso A, et al. Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicenter, randomized, controlled, phase 3, non-inferiority trial. Lancet (2017) 390:1048–60. doi: 10.1016/S0140-6736(17)31145-5

PubMed Abstract | CrossRef Full Text | Google Scholar

7. Correa C, Harris EE, Leonardi MC, Smith BD, Taghian AG, Thompson AM, et al. Accelerated partial breast irradiation: Executive summary for update of an ASTRO evidence-based consensus statement. Pract Radiat Oncol (2017) 7:73–9. doi: 10.1016/j.prro.2016.09.007

PubMed Abstract | CrossRef Full Text | Google Scholar

8. Bekelman JE, Lu H, Pugh S, Baker K, Berg CD, Berrington de Gonzalez A, et al. Pragmatic randomized clinical trial of proton versus photon therapy for patients with non-metastatic breast cancer: the radiotherapy comparative effectiveness (RADCOMP) consortium trial protocol. Br J Radiol (2019) 9:1–10. doi: 10.1136/bmjopen-2018-025556

CrossRef Full Text | Google Scholar

9. Koerkamp MLG, Vasmel JE, Russell NS, Shaitelman SF, Anandadas CN, Currey A, et al. Optimizing MR-guided radiotherapy for breast cancer patients. Fron Oncol (2020) 10:1107–20. doi: 10.3389/fonc.2020.01107

CrossRef Full Text | Google Scholar

10. Dumane VA, Saksornchai K, Zhou Y, Hong L, Powell S, Ho AY. Reduction in low-dose to normal tissue with the addition of deep inspiration breath hold (DIBH) to volumetric modulated arc therapy (VMAT) in breast cancer patients with implant reconstruction receiving regional nodal irradiation. Radiat Oncol (2018) 13:187–94. doi: 10.1186/s13014-018-1132-9

PubMed Abstract | CrossRef Full Text | Google Scholar

Keywords: breast cancer, hypo-fractionation, partial breast irradiation, post-mastectomy radiation therapy, deep inspiration breath-hold, knowledge-based planning, volumetric modulated arc therapy, proton therapy

Citation: Dumane V, Ohri N, Choi JI, Chhabra A and Lin H (2024) Editorial: Advances in treatment planning, optimization and delivery for radiotherapy of breast cancer. Front. Oncol. 13:1354731. doi: 10.3389/fonc.2023.1354731

Received: 12 December 2023; Accepted: 19 December 2023;
Published: 08 January 2024.

Edited and Reviewed by:

Timothy James Kinsella, Brown University, United States

Copyright © 2024 Dumane, Ohri, Choi, Chhabra and Lin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Vishruta Dumane, dmlzaHJ1dGEuZHVtYW5lQG1vdW50c2luYWkub3Jn

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.