Highlights from Breast Cancer Radiotherapy Sessions

 

ESTRO 2026 Congress Report

By the ESTRO breast focus group

Breast cancer radiation therapy evolves through technological innovation and the growing body of evidence from clinical trials with increasingly mature follow-up. The ESTRO 2026 annual meeting highlighted several recent advances that have impacted clinical practice, particularly in the areas of treatment optimisation and quality improvement and side effects prevention, apart from technological innovation. We provide here a summary of some major presentations in the field of breast cancer radiation oncology.

 

Recent Publications and Clinical Trial Updates

Particular attention was given to the role of regional-nodal and partial-breast irradiation (PBI).

 

Professors Philip Poortmans and Orit Kaidar-Person presented the results of the last of the three planned primary analyses (at 10, 15 and 20 years) of the European Organisation for Research and Treatment of Cancer (EORTC) 22922/10925 trial, which evaluated the benefit of the use of elective irradiation on the internal mammary and medial supraclavicular lymph node regions in patients with stages I–III breast cancer. After a median follow-up of 22.2 years, 4004 patients from 46 institutions across 13 countries were included in the analysis. No significant benefit was observed in terms of rates of overall survival (OS) (61% vs. 61.8%; hazard ratio (HR)=1, p=0.967), disease-free survival (DFS) (48.2% vs. 49.0%; HR=0.97, p=0.515), or distant metastasis-free survival (58.9% vs. 59.8%; HR=0.97, p=0.578) at 20 years. However, regional-nodal irradiation was associated with a significant reduction in-breast cancer mortality (BCM), corresponding to an absolute benefit of 3.8% (18.6% vs. 22.4%; HR=0.82, p=0.006). This advantage was offset by an absolute increase of 4.6% in non-BCM (20.4% vs. 15.8%; HR=1.26, p=0.002), which became apparent beyond 15 years of follow-up, together with a higher incidence of late cardiopulmonary adverse events. These findings emphasise the importance of very long-term follow-up after treatment for prognostically favourable malignancies, as initial benefits such as local control may be jeopardised by very late treatment-associated adverse events. It should be noted, however, that this study was conducted using conventionally fractionated radiotherapy that had been delivered with 2D- and 3D-conformal radiation therapy (CRT), which probably resulted in cardiac and pulmonary doses that were substantially higher than those that would be achieved with contemporary radiotherapy techniques. These findings highlight the importance of both refined patient selection for regional-nodal irradiation, and of using optimal radiation techniques and quality assurance.

Dr Nielson Anders W. Molby presented the results of the Danish Breast Cancer Group (DBCG) multicentre prospective nationwide population-based cohort study named internal mammary node 1+2 (IMN1+2). IMN2 evaluated the benefit of applying IMN irradiation (IMNI) via 3D-CRT to 4541 patients with node-positive and high-risk breast cancer. After a median follow-up of 13.7 years, the use of IMNI was associated with an absolute improvement in OS of 4.2% (65.0% vs 60.8%, HR=0.85, p=0.0016), a significant reduction in BCM (HR=0.84, p=0.0077), and a reduced risk of distant metastasis (HR=0.87, p=0.026), without an increase in cardiac toxicity (0.2% vs 0.7%). These findings suggest that, when delivered using contemporary radiotherapy techniques and supported by rigorous quality assurance programmes, IMNI can provide a meaningful OS benefit in high-risk breast cancer.

PBI was also highlighted through new data presented by Prof Birgitte Offersen. The phase III randomised controlled DBCG-NATURAL trial evaluated the use of hypofractionated PBI versus omission of radiotherapy in women aged over 60 years who had low-risk breast cancer. At a median follow-up of four years, 41 of 802 patients had a local recurrence, and 39 of them had not had PBI. The estimated local recurrence at five years for those who had received PBI, either alone or combined with endocrine therapy (ET), was below the predefined upper confidence level of 4%, whereas it was 12.2% for patients who had neither radiotherapy nor ET. The only adverse event that significantly increased with PBI was skin pigmentation changes, with depigmentation observed in 7.4% of patients compared with 1% in the non-irradiated group (odds ratio (OR) 0.10, 95% confidence interval (CI) 0.02-0.44, p=0.002). Also, the 15-year results of the Italian accelerated PBI/image-modulated radiotherapy (IMRT) trial were presented by Dr Carlotta Becherini. She reported no differences in rates of locoregional control, distant metastasis, breast cancer-specific survival or OS.

 

These findings support the optimisation of treatment in carefully selected, low-risk patients, and provide additional evidence that facilitates individualised, shared decision-making.

The management of metastatic patients was also addressed during the congress. The multicentre randomised phase II OLIGOMA trial evaluated the role of ablative stereotactic body radiotherapy (SBRT) that had been directed at all metastatic lesions in 87 patients with oligometastatic breast cancer (≤ 5 metastases). The results were presented by Prof David Krug. All treatment lines and biologic subtypes were eligible. The majority of patients (84%) had hormone-receptor-positive tumours and were treated in the first-line setting. They had between one and three metastatic lesions. Treated lesions were predominantly bone metastases (65%). The study demonstrated that those treated with SBRT showed significant improvement in rates of PFS, with a median PFS of 35.8 months vs. 20.4 months for those not treated with SBRT (HR=0.48, p=0.021). These results were achieved without compromise of their quality of life 12 weeks after randomisation (72.2 points vs. 74.3 points, analysis of covariance -2.1) or increases in the number of treatment-related adverse events (no adverse events in 86.1% vs. 84.1% of patients). These results strengthen the rationale for application of SBRT in selected patients with oligometastatic breast cancer, although further studies are needed to identify optimal candidates to receive this approach.

 

Dr Simona Shaitelman presented the results of a prospective, phase II trial (NCT02945579) of definitive, ablative radiotherapy (ART) with ET and without surgery. In this trial, 20 women aged ≥50 years who had low-risk, hormone-receptor-positive, human epidermal growth-factor-receptor 2 (HER2)-negative, early breast cancer received ET followed by ART, with surgery omitted unless residual disease was detected on biopsy. Among 19 patients who underwent post-treatment biopsy, 53% achieved a pathologic complete response, and after a median follow-up of 37 months, no local tumour progression was observed, resulting in a three-year PFS rate of 92%. Tumour shrinkage during ET was associated with complete response. This finding suggests that the use of imaging and biomarker-based selection may help to identify patients who could safely be removed from surgery lists after ART.

 

Debate: The Future of Ultra-Hypofractionation versus Moderate Hypofractionation in Breast Cancer by 2035

The use of five-fraction schedules is of considerable interest to clinicians, and is leading to changes in practice. This debate session examined the arguments for and against use of this treatment strategy in light of the currently available evidence.

The rationale for use of ultra-hypofractionation is based on radiobiological considerations, particularly the low α/β ratio of breast cancer, which suggests enhanced sensitivity to higher doses per fraction. Ten-year results from the FAST-forward trial confirmed that delivery of 26Gy over five fractions to the whole breast was efficient; this treatment led to a local recurrence rate of below 4% and no detrimental impact on OS, late adverse events, or quality of life. In addition, preliminary findings from the FAST-forward nodal trial were reassuring; there has been no increase in rates of upper-limb lymphoedema or locoregional recurrence after regional-nodal irradiation after five years of follow-up. The main predictor of lymphoedema was axillary surgery, particularly axillary lymph node dissection (OR 3.7, 95% CI 1.61-8.48, p=0.002). Now, the multicentre FAST-forward boost trial is recruiting. It will evaluate the role of a simultaneous integrated boost (SIB) that is delivered within an ultra-hypofractionated schedule. Both local control and treatment-related adverse events will be assessed. The primary results are anticipated in 2034. Beyond its clinical effectiveness, according to Profs Anna Kirby and Icro Meattini, ultra-hypofractionation offers substantial organisational benefits, including shortened treatment courses, reductions in patient travel, lower healthcare costs, and a decreased environmental footprint.

Nevertheless, several concerns were raised by Profs Birgitte Offersen and David Krug. These experts emphasised that from a radiobiological perspective, ultra-hypofractionated regimens delivered a slightly lower biologically effective dose than did moderate hypofractionation, and this could raise concerns regarding tumour control in patients at higher risk of recurrence or who required complex regional-nodal irradiation. They argued that these concerns should be taken into account alongside the possible shortened overall treatment times and the use of higher doses per fraction, which may not be fully accounted for by conventional radiobiological models. The level of evidence for ultra-hypofractionation remains lower than that for moderate hypofractionation for certain indications, such as regional-nodal irradiation or SIB, because there are no mature randomised trials or a formal meta-analysis. However, the FAST-forward trial provides mature, high-quality level 1 evidence in favour of the use of five-fraction breast irradiation.

Several Danish randomised trials are underway to add to evidence regarding the optimal use of ultra-hypofractionation in specific clinical settings. The low-five trial is investigating the use of ultra-hypofractionated PBI in patients with low-risk disease, whereas the high-five trial is focused on higher-risk patients who require whole breast and/or regional-nodal irradiation. Particular emphasis is being placed on the robustness and consistency of the radiotherapy quality assurance programme.

Overall, ultra-hypofractionation is an effective and well-tolerated treatment option for many patients. Ongoing clinical trials are expected to provide further evidence regarding the role of nodal irradiation and the usefulness of a SIB.

 

Oral Presentations and Poster Discussion
Updates on therapy optimisation strategies

Ways to optimise use of radiotherapy were a major theme at the meeting. The aim is to better tailor treatments to individuals’ recurrence risk in order to reduce the number of adverse events and improve quality of life without compromising oncological efficacy.

Several presentations specifically addressed the role of regional-nodal irradiation and tailoring based on responses to neoadjuvant (primary) systemic therapy (PST). As Dr Fleur Mauritz discusses in an article in this newsletter, she presented results from the Dutch multicentre radiotherapy after chemotherapy (RAPCHEM) study. Among 838 patients with initially cT1-2 cN1 M0 disease, omission of regional-nodal irradiation could be considered in cases of a complete pathological nodal response or low residual disease burden (no more than three positive lymph nodes) after neoadjuvant systemic treatment. Such omission was possible given the very low long-term locoregional recurrence rates that were observed after 10 years without regional-nodal irradiation : 2.9% for those with synchronous distant metastasis (95% CI 1.9-4.2) and 7.8% for those without (95% CI 6.1-9.7), with no significant differences between risk groups. However, the vast majority of patients having undergone axillary lymph node dissection. In the whole group, hormone-negative patients with synchronous distant metastasis had a significantly higher locoregional recurrence rate than did hormone-positive patients. Furthermore, in cases of ypN0, omitting chest-wall irradiation after mastectomy was also associated with reassuringly low 10-year locoregional recurrence rates, in line with the five-year results of the NSABP-B51 trial. However, treatment decisions should not be made solely due to nodal response to PST; tumour biology and baseline disease characteristics may influence residual recurrence risk and should be taken into account when clinicians decide on the best treatment strategy.
 

The indications for tumour bed boost were also discussed. Although it remains recommended in younger patients (≤50 years), several datasets suggest that it could be omitted in selected patients with between zero and two risk factors. These are: patient age ≤40 years; tumours of grade 3 or lower and of triple-negative subtype; indicated systemic therapy not received; and margins ≤4mm. Indeed, Dr Femke Froklage presented the results of a Dutch retrospective study of 33274 patients, which showed that the risk of local breast cancer recurrence remained particularly low for patients with zero to two risk factors; the rate of recurrence of in-breast tumours was only 1.2% at 10 years, with or without boost irradiation. After 10 years, patients with ≥3 risk factors had an in-breast tumour recurrence rate of 2.7% without boost irradiation and 3.3% with. These findings support the growing trend toward individualised, tailored irradiated volumes based on tumour characteristics and risk profile.

 

Data from the multicentre, prospective, randomised HypoG-01 trial, presented by Dr Louis Munschi, showed that triple-negative breast cancers accounted for a substantial proportion of isolated locoregional recurrences (40% of the relapsing population), with no detrimental impact if moderate hypofractionation was applied.
 

Separate from the debate on ultra-fractionation, it was discussed as part of radiotherapy optimisation strategies. The data presented this year continue to support the use of ultra-hypofractionation in early breast cancer. A retrospective-prospective multicentre observational study of more than 2000 patients from Italy, which was presented by Dr Anna Giulia Becchetti, confirmed the non-inferiority of a 26Gy regimen delivered in five fractions over one week (+/− boost) in terms of local control, late adverse events (skin and breast pain), and quality of life at one year. Similarly, the multicentre randomised controlled Indian hypofractionated radiotherapy (HYPORT)-adjuvant trial, presented by Dr Sanjoy Chatterjee, included more than 900 patients, nearly 500 of whom received regional-nodal irradiation. In a post-hoc analysis, no significant difference in quality of life was observed between ultra-hypofractionated and moderately hypofractionated schedules at 18 months of follow-up. After a transient deterioration in quality-of-life scores was observed in the immediate post-treatment period, they stabilised in both groups, as measured through use of the EORTC quality-of-life core 30 and the functional assessment of cancer therapy – breast questionnaires.

These reassuring results support further evaluation of the use of ultra-hypofractionation in populations that require regional-nodal irradiation, and it is hoped that long-term results from the FAST-forward nodal trial will confirm these observations.

 

Radiation-associated adverse events

Reducing the number of treatment-induced adverse events remains a major challenge in the management of patients with breast cancer, especially given their increasing life expectancies and the increasing numbers of early diagnoses. Several studies presented at this meeting have helped to improve the management of side effects associated with modern radiotherapy techniques.

Results of the Italian prospective, non-randomised (single arm), phase II DEBoRa trial (NCT070021846) of 93 patients were presented by Dr Salvatore Minuti. It evaluated a moderately hypofractionated breast irradiation regimen (40Gy over 15 fractions given in three weeks) combined with a high-dose SIB (52.5Gy similarly given in 15 fractions over three weeks) in patients aged 50 years or younger who had high-risk but early-stage breast cancer. Preliminary results are reassuring; there have been no severe acute adverse events of grades ≥3, whether cutaneous, breast, cardiac, or pulmonary. Longer follow-up will nevertheless be required to assess the late effects of this strategy. These findings are consistent with those of the multicentre phase III randomised controlled non-inferiority UK intensity-modulation and partial-organ radiotherapy (IMPORT) high trial presented by Prof Charlotte Coles. In this trial, dose-escalated whole-breast irradiation using IMRT with SIB strategies was evaluated in 2617 patients (pT1-3 pN0-3a M0). This trial demonstrated low ipsilateral breast-tumour relapse rates with no difference between treatment groups: 2% in the control group (40Gy/15f followed by a sequential 16 Gy boost) vs. 1.9% in the SIB group (48Gy/15f) at five years, and 3.7% vs. 3.5% at 10 years, respectively. Excellent local-regional control was achieved (HR=1.02), with similar time to any moderate or marked clinician-assessed breast normal tissue effect (46.4% vs. 47.9%, respectively) at 10 years.

Several presentations were focused specifically on effects of radiation on organs of interest, which might significantly affect the quality of patients’ lives. Thyroid dysfunction after breast and nodal irradiation was analysed in a substudy of the HypoG-01 trial presented by Dr Lisa Ciaptacz. After a median follow-up of 4.8 years in 1059 patients, the cumulative incidence of thyroid dysfunction was approximately 2.2%, with no obvious difference between fractionation schedules (40Gy/15f/3wk versus 50Gy/25f/5wk).
No thyroid dosimetric parameter (mean dose, volume, the percentage of the volume receiving at least 5-50 Gy (V5-V50), the minimum dose received by the hottest 2% and 5% of the volume (D2%, D5%)) was associated with the risk of thyroid dysfunction when the recommended thyroid dose constraints were respected (mean dose <30Gy). In contrast, patients who developed thyroid dysfunction were more frequently observed to have a higher body mass index (28.9 vs. 26.1kg/m², p=0.023) and were treated through the use of IMRT compared with 3D-CRT (18 patients treated with IMRT vs. 5 with 3D-CRT, p=0.01).

These findings indicate that the thyroid gland should be routinely contoured, particularly in the setting of nodal irradiation and/or the presence of risk factors, to ensure compliance with recommended dosimetric constraints and thereby limit the incidence of thyroid adverse events.
 

Adverse cardiac events also featured prominently in the discussions. Several studies suggest that mean dose to the heart alone may not be used to estimate long-term cardiovascular risk accurately, and that dosimetric analysis of cardiac substructures may provide more clinically relevant information. Results of a study on a Chinese multicentre cohort of 633 patients who were treated between 2011 and 2013 and underwent a median follow-up after 12 years were presented by Dr Chun Hin Chan, and it was found that the left anterior descending coronary artery (LAD) V40 was the main dosimetric predictor of major cardiovascular events (HR=1.023), alongside age (HR=1.086, p<0.001) and a history of cardiovascular disease (HR=5.421, p=0.001). These findings support the need to plan treatment with consideration of cardiac substructures, and particularly to optimise LAD V40 according to patient age.
 

In this context, the results of the prospective randomised trial of the use of respiratory training and relaxation techniques to improve adjuvant radiation therapy in deep-inspiration breath-hold (DIBH) in breast cancer (B-REST) are relevant. They were presented by Dr Rebecca Moser. The trial involved 100 patients and highlighted the key role of DIBH, which significantly reduces radiation exposure to the heart (−34%), the LAD (−50%), and the cardiac ventricles (−49% for the right ventricle and −45% for the left ventricle), thereby potentially decreasing the number of cardiac adverse events. Furthermore, programmes that combined respiratory training with relaxation techniques were shown to improve the quality of DIBH execution and enhance cardiac (p<0.0001) and pulmonary (p<0.0001) sparing.

 

Quality and safety considerations

Improving treatment quality and safety was a major focus of this congress. As moderate hypofractionation has become the standard-of-care when nodal irradiation is needed, and ultra-hypofractionation has become the standard for whole-breast irradiation, the harmonisation of clinical practice has become a key issue. For example, the Swedish national quality registry for radiotherapy (SKvaRT), presented by Dr Caroline Olsson, shows that 62.1% of patients treated in Sweden in 2025 received an ultra-hypofractionated regimen.

 

In this context, speakers emphasised the importance of using quality indicators (QIs) to ensure the consistent, reproducible, and safe delivery of treatment across institutions. An international ESTRO-endorsed Delphi consensus presented by Dr Mouhamadou Bachir Ba established a set of clinical and dosimetric QIs that were applicable to both hypofractionated and ultra-hypofractionated breast radiotherapy. The high level of agreement achieved (minimum median consensus threshold of 85%) and the feasibility/usability of all indicators (greater than 80%) suggest that these metrics could provide a robust framework for quality assessment and continuous improvement of breast radiotherapy across different centres. However, the study also revealed inter-centre dosimetric heterogeneity, highlighting opportunities for quality improvement.

 

An international implementation survey is underway to evaluate routine clinical practice using these QIs. This is particularly important, as the prospective UK national dosimetry audit study over 26000 patients, presented by Dr Imogen Locke, demonstrated the feasibility of the large-scale collection and evaluation of real-world dosimetric data.

Technological innovations

Novel irradiation modalities were also highlighted at this year’s ESTRO meeting, with particular attention given to proton therapy and carbon ion radiotherapy.
 

The results of a substudy of the randomised controlled phase III DBCG proton trial presented by Dr Kristine Wiborg Hogsbjerg provided important data on the early adverse events caused by proton therapy in early breast cancer. Although proton therapy theoretically offers superior sparing of organs of interest, particularly the heart and lungs, it was associated with a significantly higher incidence of grades 2–3 skin adverse events (71% vs. 20%, p<0.001) and breast pain (17% vs. 4%, p=0.015) compared with conventional hypofractionated photon radiotherapy. These events peaked at week five after the radiotherapy and then returned to baseline levels at weeks 11-13. In contrast, no differences were observed in the number of fatigue or pulmonary adverse events. These findings demonstrate a significantly higher incidence of acute skin-related adverse events with proton therapy; however, these are transient.

A substudy of the multicentre randomised phase III proton-beam therapy in patients with breast cancer: evaluating early and late effects (PARABLE) trial was presented by Prof Anna Kirby. This substudy, which involved 74 patients, investigated factors that influenced patient participation in a breast proton therapy clinical trial. It examined the determinants of enrolment in a study comparing proton therapy with optimised photon radiotherapy. The main barrier to participation was the need to travel to, or temporarily stay near, a proton therapy centre that was far from home. Logistical constraints, separation from family, and disruption of daily life were the most commonly cited reasons for declining participation. Conversely, trust in the healthcare team, interest in an innovative treatment modality, and willingness to participate in a clinical trial were the principal factors encouraging enrolment.

These findings underscore the importance of considering organisation and logistics in the development of proton therapy trials. The implementation of logistical and financial support measures, together with clear patient information and streamlined care pathways, appears essential to ensure equitable access to these innovative treatments and to improve the representativeness of patient populations enrolled in future clinical studies.
 

Carbon ion radiotherapy, which is as yet underdeveloped in the treatment of breast cancer, was the subject of a presentation by Dr Noriyuki Okonogi. A single-centre prospective phase I/II study (jRCTs032180153) evaluated this approach in patients older than 60 years with untreated stage I early breast cancer (cT1 N0 M0) that was oestrogen-receptor-positive and HER2-negative. Following dose escalation up to 60Gy delivered in four fractions, the reported results demonstrated excellent local tumour control, with an OS rate of 100% and a DFS rate of 84.7% after a median follow-up of seven years in a cohort of 12 patients. Observed adverse events were limited, consisting mainly of low-grade (grade 1) skin reactions.
 

Although preliminary and based on a small patient cohort, these findings illustrate the potential of particle therapy techniques in selected clinical situations. Further studies will nevertheless be required to better define their role relative to modern photon-based radiotherapy techniques, which are now widely standardised and established in routine clinical practice.

 

Brachytherapy and Accelerated PBI

Interstitial brachytherapy was one of the highlights of this year’s ESTRO meeting. This technique enables the use of very accelerated PBI (vAPBI) by targeting only the tumour bed, based on the observation that most ipsilateral breast recurrences occur immediately around the original tumour site.
 

The GEC-ESTRO group presented the five-year results of a study by Prof Jean-Michel Hannoun-Levi of a large (579-patient) multicentre cohort with low-risk breast cancer who had been treated with pre- or post-operation interstitial brachytherapy. One of three ultra-short fractionation schedules was used: 1×16-18Gy in one day; or 3×7.45Gy or 4×6.2Gy over two consecutive days. After a median follow-up of 64 months, outcomes were particularly encouraging, with a local recurrence rate of only 2% at five years, with no differences observed between treatment schedules. These findings were consistent with those of the phase III randomised GEC-ESTRO APBI trial, which reported a local recurrence rate of 1.4%, compared with 0.92% after conventionally fractionated whole-breast irradiation. The OS rate was 93%, breast cancer-specific survival 98%, and DFS 91%. Late adverse events mainly consisted of low-grade skin and subcutaneous fibrosis (61%), with fewer than 1% grade 3 events and no differences between fractionation regimens.
 

Longer-term outcomes were also reported through the 10-year update of the phase II single-fraction elderly breast irradiation (SiFEBI) trial, presented by Dr Laura Haas and explained in an article by her in this edition of the newsletter. This study evaluated single-fraction PBI using 16Gy interstitial brachytherapy in patients aged 70 years or older who had low-risk early breast cancer and who had undergone lumpectomy (negative margins, tumour ≤2cm, node-negative disease). Among the 26 enrolled patients and after a median follow-up exceeding 11 years, the local recurrence rate remained low at 5% at 10 years, with a DFS of 73% and an OS of 81%. No breast cancer-related deaths or distant metastases were observed. Cosmetic outcomes were rated as excellent or good by the majority of patients, and the reported adverse events were limited to mild-to-moderate breast fibrosis (grades 1-2 in 35% of patients).
 

These data strengthen the evidence for the use of interstitial brachytherapy as an alternative to conventional whole-breast irradiation in carefully selected patients with low-risk breast cancer.

To further define its place within treatment de-escalation strategies, the GEC-ESTRO group launched the multicentre phase II single-fraction sfVAPBI trial in 2025. This study is evaluating the feasibility, efficacy, and five-year safety profile of the use of single-fraction 16Gy PBI, delivered by interstitial brachytherapy in patients with low-risk invasive or in situ breast carcinoma.

 

Radiotherapy and Immune Response

The interaction between radiotherapy and the immune system is attracting growing interest, particularly since the integration of immunotherapy into the treatment of triple-negative breast cancer. Several studies presented at the congress explored the biological impact of nodal irradiation on the tumour immune microenvironment.

Analyses that had been conducted in the neoadjuvant setting across several trial datasets (PRADA NCT02771938, Neo-RT NCT03818100) were presented by Dr Matthew Fenton (Somaiah lab). They suggest that nodal irradiation induces profound remodelling of lymph nodes, and this is characterised by increased fibrosis and alterations in cellular composition. In irradiated fibrotic regions, an accumulation of non-lymphoid cells was observed alongside depletion of B-cells and relative enrichment in CD8+ T-lymphocytes, at the expense of the original tumour-involved areas. These changes were accompanied by sustained activation of inflammatory pathways, cellular stress responses, and apoptosis both within tumour-bearing nodes and in tumour-free lymph nodes. It has been suggested that nodal irradiation could influence the efficacy of combined radiotherapy and immunotherapy strategies by modulating the overall immune response.
 

The immune microenvironment may also play a central role in treatment response. As reported by Prof Marco Lucarelli in the phase I/II CRYSTAL (NCT04679454) trial evaluating molecular features associated with single-fraction stereotactic radiotherapy, preliminary transcriptomic analyses performed in a cohort of 13 patients showed that non-responding tumours were characterised by the downregulation of several immune-related genes. These findings suggest the presence of an immunologically ‘cold’ tumour microenvironment and support the hypothesis that impaired antitumour immune activation may contribute to resistance to preoperative radiotherapy. Although these findings are exploratory, they open promising avenues for research aimed at optimising the integration of locoregional and systemic therapies in patients with high-risk breast cancer.

 

Lisa Ciaptacz, MD

Department of Radiotherapy

CHU Dupuytren

Limoges, France

lisa.ciaptacz@gmail.com

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Member of the ESTRO Breast Focus Group