Safety of the Breast Cancer Adjuvant Radiotherapy in Ataxia-Telangiectasia Mutated Variant Carriers.

The Ataxia-Telangiectasia Mutated (ATM) gene is implicated in DNA double-strand break repair. Controversies in clinical radiosensitivity remain known for monoallelic carriers of the ATM pathogenic variant (PV). An evaluation of the single-nucleotide polymorphism (SNP) rs1801516 (G-A) showed different results regarding late subcutaneous fibrosis after breast radiation therapy (RT). The main objective of this study was to evaluate acute and late toxicities in carriers of a rare ATM PV or predicted PV and in carriers of minor allele A of rs1801516 facing breast RT. Fifty women with localized breast cancer treated with adjuvant RT between 2000 and 2014 at Institut Curie were selected. Acute and late toxicities in carriers of a rare PV or predicted PV (n= 9), in noncarriers (n = 41) and in carriers of SNP rs1801516 (G-A) (n = 8), were examined. The median age at diagnosis was 53 years old and 82% of patients had an invasive ductal carcinoma and 84% were at clinical stage I-IIB. With a median follow-up of 13 years, no significant difference between carriers and noncarriers was found for acute toxicities (p > 0.05). The same results were observed for late toxicities without an effect from the rs1801516 genotype on toxicities. No significant difference in acute or late toxicities was observed between rare ATM variant carriers and noncarriers after breast RT for localized breast cancer.

Impact of radiation therapy modalities on loco-regional control in inflammatory breast cancer.

INTRODUCTION: In inflammatory breast cancer (IBC), radiotherapy intensification is considered a standard of care by some teams, although the level of evidence remains low. We sought to analyze the impact of radiotherapy modalities on the risk of loco-regional and distant relapse. METHODS: A retrospective multicenter study included patients with localized IBC treated between 2010 and 2017. Standard post-mastectomy radiotherapy consisted of daily fractions to a total dose of 50 Gy equivalent without a boost or bolus, while intensified radiotherapy referred to the use of a boost or bolus. The cumulative incidence curves of loco-regional and distant recurrence were displayed using the competing risk method. RESULTS: Of the 241 included patients, 165 were treated with standard and 76 with intensified radiotherapy. There was significantly more nodal involvement in the intensified group. With a median follow-up of 40 months post-radiotherapy, there was no difference between standard vs intensified radiotherapy regarding the cumulative incidence of loco-regional (p=0.68) or distant recurrence (p=0.29). At 5 years, the risks of loco-regional and distant recurrence were 12.1% (95% CI, 7.5; 17.7) and 29.4% (95% CI, 21.8; 37.3) for patients treated with standard radiotherapy and 10.4% (95% CI, 4.4; 19.3) and 21.4% (95% CI, 12.6; 31.9) for intensified radiotherapy. On multivariate analyses, triple-negative subtype and absence of complete pathological response (pCR) were associated with a higher risk of loco-regional recurrence. Radiotherapy intensification had no significant impact on loco-regional and distant recurrence. For non-pCR patients (n=172, 71.7%), no significant differences were observed between the two groups for loco-regional (p=0.80) and distant recurrence either (p=0.39). Severe toxicity rates were similar in both groups. CONCLUSIONS: Contrary to other important series, this large retrospective multicentric study did not show a loco-regional or distant control benefit of intensified radiotherapy. Pooled prospective studies and meta-analyses of intensified radiotherapy are warranted to endorse this approach.

International Prognostic Score for Nodular Lymphocyte-Predominant Hodgkin Lymphoma.

PURPOSE: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and large international cooperative efforts are needed to evaluate the significance of clinical risk factors and immunoarchitectural patterns (IAPs) for all stages of pediatric and adult patients with NLPHL. METHODS: Thirty-eight institutions participated in the Global nLPHL One Working Group retrospective study of NLPHL cases from 1992 to 2021. We measured progression-free survival (PFS), overall survival (OS), transformation rate, and lymphoma-specific death rate. We performed uni- and multivariable (MVA) Cox regression stratified by management to select factors for the lymphocyte-predominant international prognostic score (LP-IPS) validated by five-fold cross-validation. RESULTS: We identified 2,243 patients with a median age of 37 years (IQR, 23-51). The median follow-up was 6.3 years (IQR, 3.4-10.8). Most had stage I to II (72.9%) and few B symptoms (9.9%) or splenic involvement (5.4%). IAP was scored for 916 (40.8%). Frontline management included chemotherapy alone (32.4%), combined modality therapy (30.5%), radiotherapy alone (24.0%), observation after excision (4.6%), rituximab alone (4.0%), active surveillance (3.4%), and rituximab and radiotherapy (1.1%). The PFS, OS, transformation, and lymphoma-specific death rates at 10 years were 70.8%, 91.6%, 4.8%, and 3.3%, respectively. On MVA, IAPs were not associated with PFS or OS, but IAP E had higher risk of transformation (hazard ratio [HR], 1.81; P < .05). We developed the LP-IPS with 1 point each for age ≥45 years, stage III-IV, hemoglobin <10.5 g/dL, and splenic involvement. Increasing LP-IPS was significantly associated with worse PFS (HR, 1.52) and OS (HR, 2.31) and increased risk of lymphoma-specific death (HR, 2.63) and transformation (HR, 1.41). CONCLUSION: In this comprehensive study of all ages of patients with NLPHL, we develop the LP-IPS to identify high-risk patients and inform upcoming prospective clinical trials evaluating de-escalation of therapy for patients with low LP-IPS scores (<2).

Tolerance of Concurrent Adjuvant Radiation Therapy and Pembrolizumab for Triple Negative Breast Cancer: Real Life Experience.

Purpose: The current standard-of-care management of locally advanced triple negative breast cancer (TNBC) is based on neoadjuvant chemo-immunotherapy with pembrolizumab, surgery, radiation therapy (RT), and adjuvant pembrolizumab. However, the safety of combining pembrolizumab with adjuvant breast RT has never been evaluated. This study evaluated the tolerance profile of concurrent pembrolizumab with adjuvant RT in patients with locally advanced TNBC. Methods and Materials: This bicentric ambispective study included all the patients with early and locally advanced TNBC who received neoadjuvant chemo-immunotherapy with pembrolizumab and adjuvant RT as part of their treatment. The tolerance profile of adjuvant RT was evaluated and compared in patients who received concurrent pembrolizumab and in patients for whom pembrolizumab was withheld. Results: Fifty-five patients were included between July 2021 and March 2023. Twenty-eight patients received adjuvant RT with concurrent pembrolizumab (RT+P group), and 27 patients had pembrolizumab withheld while receiving adjuvant RT (RT-only group). Two patients developed grade ≥3 toxicity (1 grade 3 pain in the RT+P group and 1 grade 3 radiodermatitis in the RT-only group), and there were no differences in terms of toxicity between the RT-only and the RT+P groups. No cardiac or pulmonary adverse event was reported during RT. With a median follow-up of 12 months (10-26), no patient relapsed. Conclusions: In this study of limited size, the authors did not find a difference between the RT-only and RT+P groups in terms of toxicity. More studies and longer follow-up may add to the strength of this evidence.

Post-mastectomy reirradiation for ipsilateral T3N0M0 breast tumor relapse: a population-based study.

INTRODUCTION: Post-mastectomy radiotherapy is commonly recommended for T3N0M0 breast cancer, particularly in the presence of adverse prognostic factors. However, for T3N0M0 ipsilateral recurrences following breast-conserving surgery and adjuvant radiotherapy, the situation is distinct. Recurrence alone signifies a negative prognostic factor. Moreover, tumor relapses within previously irradiated areas exhibit enhanced radioresistance, and reirradiation of the chest wall carries an escalated risk of radiation-induced toxicity. This study aimed to assess the impact of post-mastectomy reirradiation (PM-reRT) on patient outcomes in cases of ipsilateral T3N0M0 breast tumor recurrence, using data from the SEER database. MATERIALS AND METHODS: We identified all patients who underwent treatment for primary non-metastatic breast cancer with breast-conserving surgery followed by adjuvant radiotherapy in the SEER database; among them, those who later experienced a localized T3N0M0 breast tumor recurrence and underwent total mastectomy were included. The study's goal was to compare overall survival (OS) and cancer-specific survival (CSS) between patients who underwent only mastectomy versus those who had mastectomy followed by adjuvant PM-reRT for their ipsilateral T3N0M0 breast tumor relapse. RESULTS: From 2000 to 2020, the SEER database recorded 44 patients with an ipsilateral T3N0M0 breast tumor recurrence after initial conservative treatment, managed with total mastectomy. No statistically significant differences in OS or CSS were observed between patients undergoing mastectomy (MT) alone versus those receiving MT combined with PM-reRT (p = 0.68 and p = 0.86, respectively). Five-year OS rates for the MT and MT + PM-reRT cohorts were 49.5% [95% CI: 29.9-81.8] and 41.7% [10.0-100.0], respectively, while 5­year CSS rates were 51.6% [12.0-99.5] and 58.3% [15.2-100.0], respectively. CONCLUSION: For patients undergoing total mastectomy after an ipsilateral T3N0M0 breast tumor recurrence, subsequent to initial breast cancer treatment involving breast-conserving surgery and adjuvant radiotherapy, chest wall reirradiation does not enhance survival outcomes. As such, it should not be routinely performed.

Primary ophthalmic natural killer/T-cell lymphoma: A population-based study.

BACKGROUND: Ophthalmic lymphomas, a subgroup of extra-nodal lymphomas, have seen an increase in incidence in recent decades. Of these, the NK/T-cell lymphoma (NKTL) subtype is particularly aggressive. Though prevalent mostly in Asian patients, data on ophthalmic NKTL is still limited, especially in the western population. This study aimed to provide an additional analysis of primary ophthalmic NKTL using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: A retrospective analysis was performed on the SEER database covering records from 2000 to 2020. Patients diagnosed with extranodal NKTL originating primarily from an ophthalmic structure were identified. RESULTS: Out of 4540 ophthalmic lymphomas registered in the SEER database between 2000 and 2020, 9 cases (0.2%) corresponded to ophthalmic NKTL, occurring in patients with a median age of 67 years. The majority of these patients underwent chemotherapy (88.8%) and radiotherapy (66.6%). The 6-month overall survival (OS) and cancer-specific survival (CSS) were both at 50.8%, dropping significantly at the 2-year follow-up. CONCLUSION: Primary orbital NKTL has a notably severe prognosis. An early diagnosis is important due to the aggressive nature of NKTL.

Radiation Exposure of Cardiac Conduction Nodes During Breast Proton Therapy.

Purpose: The exposition of cardiac conduction system during breast radiation therapy has never been studied, despite the increasing use of intensity-modulated radiation therapy, which exposes larger volume to low-dose bath. We evaluated conduction node exposure during breast irradiation with volumetric modulated arc therapy and estimated the potential dosimetric benefit with intensity-modulated proton therapy. Materials and Methods: Atrioventricular (AVN) and sinoatrial (SAN) nodes were retrospectively delineated according to published guidelines on the simulation computed tomography scans of 12 breast cancer patients having undergone conserving surgery and adjuvant locoregional volumetric modulated arc therapy. Intensity-modulated proton therapy treatment was replanned on the simulation computed tomography scans for all breast cancer patients. Mean and maximum doses delivered to the SAN and the AVN were retrieved and compared. Correlation coefficients were calculated between doses to the SAN or the AVN and the whole heart. Results: Average mean doses delivered to the SAN and AVN were 2.8 and 2.3 Gy, respectively, for left-sided irradiation and 9.6 and 3.6 Gy, respectively, for right-sided irradiation. Average maximum doses to the SAN and AVN were 3.5 Gy and 2.8 Gy, respectively, for left-sided irradiation and 13.1 and 4.6 Gy, respectively, for right-sided irradiation. Intensity-modulated proton therapy significantly reduced mean and maximum doses to the SAN and AVN. Correlations between doses to the SAN or AVN and whole heart were usually significant. Conclusion: SAN and AVN can be substantially exposed during breast volumetric modulated arc therapy, especially for right-sided irradiation. Cardiotoxicity studies evaluating conduction node exposure might define dose constraints and criteria for additional cardiac-sparing techniques, such as respiratory techniques or proton therapy, which could benefit patients with underlying rhythmic or conduction disorders.

Large scale experience of two ultrahypofractionated 5 fractions regimes after breast conserving surgery from a single centre.

PURPOSE: Ultra-hypofractionation breast radiotherapy is a safe alternative to moderate hypofractionation. This study reports the results of two ultrahypofractionated regimens used in clinical practice in a high-volume radiotherapy center in terms of efficacy and of tolerance. METHODS: we included all patients treated in an adjuvant setting with five fractions after breast conserving surgery (BCS), for a histologically-confirmed invasive or in situ breast carcinoma. Radiotherapy regimens after BCS were either a 5-week schedule with 5 weekly fractions of 5,7 Gy or a one-week schedule with 5 daily fractions of 5,2 Gy. Adverse events were recorded and local-relapse free survival (LRFS), locoregional-relapse free survival (LRRFS), metastasis-free survival (MFS), for breast-cancer specific survival (BCSS) and overall survival (OS) were evaluated. RESULTS: Between December 2014 and December 2022, 396 patients (400 breasts) were treated with ultrahypofractionated radiotherapy. Five-year LRFS was 98.8% (95% confidence interval: 97.1%-100%), and 5-year OS was 96.0% (95%CI: 92.6-99.5%). Age was statistically associated with OS in univariate analysis (HR: 1.16, 95%CI: 1.04-1.42, p = .01). Four patients (1.0%) experienced acute grade 3 radiation-induced adverse events, and 8 patients (2.3%) acute grade 2 toxicities. Twenty-three patients (5.8%) experienced late toxicity, all of them being graded as grade 1. The use of the 5.7 Gy-weekly-fraction regimen and the delivery of a tumor bed boost were significantly associated with acute radiodermatitis (p < .01; p = .02; respectively) and late fibrosis (p < .01; p = .049; respectively). CONCLUSIONS: ultrahypofractionated radiotherapy was associated with an excellent tumor control rate in our 'real-life' cohort with low-risk breast cancer patients. However, delivery of a tumor bed boost and using weekly 5.7-Gy fractions were associated with an increased risk of acute and late cutaneous toxicities.

Tolerance and Oncological Outcomes of In-Field Reirradiation for Locally Recurrent Breast Cancer: A Long-Term Single-Center Experience.

BACKGROUND: The management of cancer relapse in previously irradiated tissues is a challenging therapeutic issue. The aim of this work was to report our experience with breast reirradiation for locoregionally recurrent breast cancer. METHODS: All patients who underwent breast or chest wall in-field reirradiation at the Institut Curie, Paris, France, between 2003 and 2019, were identified. Efficacy outcomes and physician-reported toxicities were retrospectively assessed. RESULTS: A total of 21,372 patients underwent breast irradiation in our institution. Of these, 28 received a second course of radiotherapy to the homolateral breast/chest wall. A total of 18 (64%) patients were treated with a curative intent, and 10 (36%) were treated for palliative purposes. Only one acute and one late grade 3 adverse events were reported. One patient with major cardiovascular risk factors died of myocardial infarction 13 months after left breast reirradiation. The 2-year LRFS, OS, DSS, PFS and MFS were 59%, 79%, 82%, 46% and 75%, respectively, in the whole cohort. The 2-year LRFS (72% vs. 31%, p = 0.02), OS (94% vs. 50%, p < 0.01), DSS (94% vs. 56%, p < 0.01) and PFS (61% vs. 20%, p = 0.02) differed significantly between patients treated with curative or palliative intent but not the MFS (78% vs. 69%, p = 0.77). Among the patients, eight (29%) remained relapse-free 5 years after reirradiation. CONCLUSION: Breast/chest wall reirradiation appears to be feasible with good disease control, especially in patients treated with a curative intent, and presents acceptable toxicity rates.

CANTO skin: Evaluation of skin toxicity risk factors in patients treated for breast cancer.

Skin reaction is a common toxicity during oncology management, especially followed during the radiotherapy. Its assessment and understanding of the factors influencing its occurrence, is a major issue in the management of patients treated for an early breast cancer (BC). We evaluated 8561 patients during their overall management for a BC. We focus on specific skin toxicities: erythema, fibrosis, telangiectasia and changes of skin colour. These toxicities were assessed at the baseline defined as 0-3-6 (M0), 12 (M12), 36 (M36) and 60 (M60) months. The prevalence of toxicities of interest varied over time, so at M0, 30.4% of patients had erythema while 17.7% of patients had fibrosis. At M60, the prevalence of erythema was 2%, while fibrosis remained stable at about 19%. After adjustments, at M0, there was a significant association between the onset of cutaneous erythema and obesity, the presence of axillary dissection, the type of surgery and the tumour phenotype RH+/HER2+. Concerning fibrosis, a significant association was found, at M12, with the age of the patient, obesity, Charlson score and type of surgery. Concerning the modification of skin colour at M12, we find a link between the age of the patient, obesity, tobacco consumption and alcohol consumption. The prevention of this toxicity is a major issue for the quality of life. Our results allow us to understand the risk of developing skin toxicity in a patient, depending on her intrinsic, tumour or therapeutic characteristics and to implement adapted means of prevention and monitoring.

Radiation-induced lung injury after breast cancer treatment: incidence in the CANTO-RT cohort and associated clinical and dosimetric risk factors.

Purpose: Radiation-induced lung injury (RILI) is strongly associated with various clinical conditions and dosimetric parameters. Former studies have led to reducing radiotherapy (RT) doses to the lung and have favored the discontinuation of tamoxifen during RT. However, the monocentric design and variability of dosimetric parameters chosen have limited further improvement. The aim of our study was to assess the incidence of RILI in current practice and to determine clinical and dosimetric risk factors associated with RILI occurrence. Material and methods: Data from 3 out of the 10 top recruiting centers in CANTO-RT, a subset of the CANTO prospective longitudinal cohort (NCT01993498), were retrospectively analyzed for RILI occurrence. This cohort, which recruited invasive cT0-3 cN0-3 M0 breast cancer patients from 2012 to 2018, prospectively recorded the occurrence of adverse events by questionnaires and medical visits at the end of, and up to 60 months after treatment. RILI adverse events were defined in all patients by the association of clinical symptoms and compatible medical imaging. Results: RILI was found in 38/1565 (2.4%) patients. Grade II RILI represented 15/38 events (39%) and grade III or IV 2/38 events (6%). There were no grade V events. The most frequently used technique for treatment was 3D conformational RT (96%). In univariable analyses, we confirmed the association of RILI occurrence with pulmonary medical history, absence of cardiovascular disease medical history, high pT and pN, chemotherapy use, nodal RT. All dosimetric parameters were highly correlated and had close predictive value. In the multivariable analysis adjusted for chemotherapy use and nodal involvement, pulmonary medical history (OR=3.05, p<0.01) and high V30 Gy (OR=1.06, p=0.04) remained statistically significant risk factors for RILI occurrence. V30 Gy >15% was significantly associated with RILI occurrence in a multivariable analysis (OR=3.07, p=0.03). Conclusion: Our study confirms the pulmonary safety of breast 3D RT in CANTO-RT. Further analyses with modern radiation therapy techniques such as IMRT are needed. Our results argue in favor of a dose constraint to the ipsilateral lung using V30 Gy not exceeding 15%, especially in patients presenting pulmonary medical history. Pulmonary disease records should be taken into account for RT planning.

Cicaderma® in radiation-related dermatitis of breast cancer: Results from the multicentric randomised phase III CICA-RT.

Background and purpose: To prevent the occurrence of grade ≥ 2 radiodermatitis after post-operative breast irradiation in patients with non metastatic breast cancer. Methods: This prospective randomised open-label multicenter study allocated patients from 3 French institutions, ≥18 years, requiring postoperative radiotherapy for histologically proven, early-stage (non-metastatic) unilateral breast adenocarcinoma or in situ breast cancer, with R0 or R1 post-operative status, to receive hygiene rules, associated with either Cicaderma® (Arm A), or preventive treatment according to the investigator preference (mainly hyaluronic acid (ialuset®), essential oils, or water spray, or no medication (Arm B). The primary outcome was to compare the efficacy of Cicaderma® versus local standard management in preventing the occurrence of grade ≥ 2 radiodermatitis. Main secondary objectives include Cicaderma® impact on radiotherapy discontinuation and on skin toxicity (pruritus), pain, quality of life, satisfaction. Results: The CICA-RT study enrolled from June 2020 to April 2021, 258 women with a median age of 61 (22-91) years in 3 institutions. Patients received either Cicaderma® (A: N = 130) or standard practice (B: N = 128). In the 123 patients who initiated radiotherapy in each arm, 95 (77%, 95%CI 68.8%-84.3%) patients did not develop grade ≥ 2 dermatitis. Sensitivity and per-protocol analyses confirmed the absence of differences between arms. Conclusion: This prospective study did not meet its primary endpoint of superiority of Cicaderma® over routine practice skin care in terms of prevention of acute radioinduced dermatitis of grade 2 or higher. However, Cicaderma® showed a significant decrease in the occurrence of pruritus with less patients reporting at least once grade ≥ 2 pruritus (A: N = 38, 31%; B: N = 58, 47%; p = 0.009).ClinicalTrials.gov identifier NCT04300829.

Accelerated subsequent lung cancer after post-operative radiotherapy for breast cancer.

BACKGROUND: Post-operative whole breast radiotherapy for breast cancer (BC) may increase the risk of subsequent lung cancer (LC). The impact of radiotherapy intensification (boost) has not been specifically explored in this context. We investigated the role of radiation modalities on the development of subsequent LC among our patients treated by radiotherapy for localized BC. METHODS: All patients with a diagnosis of LC between 2000 and 2020 with a history of prior localized BC treated by surgery and post-operative radiotherapy were retrospectively reviewed. Primary endpoint was time to first diagnosis of LC after BC treatment with radiotherapy (RT). RESULTS: From 98 patients who developed subsequent LC after primary BC treated with post-operative RT, 38% of patients (n = 37) received an additional RT boost, and 46% (n = 45) received hormonal treatment post radiation. A total of 61% (n = 60) were smokers. With regards to LC characteristics, adenocarcinoma was the most frequent histology (68%, n = 66); 36% (n = 35) harbored at least 1 molecular alteration, 57% (n = 20) of them being amenable to targeted therapy. Median time to first diagnosis of LC was 6 years [1.7-28.4 yrs] in the whole cohort. In the subgroup of patients treated with boost this time was reduced to 4 years [1.8-20.8 years] compared to 8 years for patients without boost [1.7-28.4 yrs] (p = 0.007). Boost, smoking usage, endocrine therapy, and age <50 yrs old at BC radiation remained independent factors associated with shorter time to first diagnosis of LC after BC treatment. DISCUSSION: We report for the first time the potential impact of boost -part of BC radiation treatment- for BC on the risk of subsequent LC. The impact of low dose radiation on lung parenchyma could explain this phenomenon, but the underlying physiopathology is still under investigation. This work highlights the need for clinicians to identify patients at risk of developing faster subsequent thoracic malignancy after BC radiation, for implementing personalized surveillance.

Breast Cancer and Mediastinal Hodgkin's Lymphomas: Multidisciplinary Discussion.

Treatment for Hodgkin's lymphoma (HL) has evolved, with modern treatments combining less toxic chemotherapy and radiation, leading to improved long-term disease-free survival. However, there is a higher chance of second cancer, especially breast cancer, following effective HL treatment. The impact of reduced radiation doses and volumes, as well as the use of advanced irradiation techniques, on the risk of second malignancy is not clear. According to medical organizations, the history of chest irradiation is a relative contraindication to breast preservation therapy for women with initial breast cancer, leading to a paradigm of mastectomy. This article proposes a discussion between radiation oncologists and surgeons to review major trials and recent developments on the prevalence of breast cancer following HL therapy, the risk of contralateral cancer, the feasibility of breast conserving surgery (BCS), as well as breast reconstruction modalities.

Preoperative Radiation Therapy for Chemorefractory Localized Inflammatory Breast Cancer.

PURPOSE: Inflammatory breast cancer (IBC) is a rare breast cancer subtype. Chemorefractory nonmetastatic IBC, defined by locoregional progression under neoadjuvant chemotherapy, is a rare situation with few therapeutic options. Owing to the rarity of this clinical presentation and the lack of specific data, no specific management guidelines exist. We evaluated whether preoperative radiation therapy/chemoradiotherapy could achieve locoregional control after first-line neoadjuvant chemotherapy in patients with IBC. METHODS AND MATERIALS: Patients with chemorefractory disease receiving preoperative radiation therapy were identified from a retrospective multicenter cohort of consecutive patients with IBC diagnosed between 2010 and 2017 at 7 oncology centers in France. RESULTS: Overall, 18 patients among the 364 patients (5%) treated for IBC had progressive disease during neoadjuvant chemotherapy. These patients had aggressive tumors with lymph node involvement at diagnosis (n = 17; 94.4%), triple-negative subtype (n = 11; 61.1%), Scarff Bloom and Richardson grade 3 (n = 10; 55.6%), and high Ki67 (median, 56.0%). After preoperative radiation therapy, all patients had a complete (n = 1; 5.6%) or partial (n = 17; 94.4%) locoregional response. One patient (5.6%) experienced acute grade 3 dermatitis. Twelve (66.7%) patients underwent surgery as planned. The estimated median follow-up was 31 months. The median overall survival, disease-free survival, distant metastases-free survival, and locoregional recurrence-free survival were 19 months, 4.5 months, 5 months, and 6 months, respectively. Ultimate locoregional control was obtained for 11 patients (61.1%), and 13 patients (72.2%) experienced metastatic progression. Triple-negative subtype (hazard ratio [HR], 15.54; P = .011) and surgery (HR, 0.23; P = .030) were significantly associated with overall survival in the univariate analysis. In multivariate analyses, the triple-negative subtype remained a significant prognostic factor (HR, 13.04; P = .021) for overall survival. CONCLUSIONS: Preoperative radiation therapy is a feasible approach with acceptable toxicities. It allowed surgery and ultimate locoregional control in a majority of patients. The lack of translation into better survival has been a challenge, in part owing to the metastatic propensity of patients with chemorefractory IBC, especially in the overrepresented triple-negative population in this series.

Outcomes and toxicity of concurrent CDK4/6 inhibitor and locoregional radiotherapy for patients with de novo metastatic breast cancer.

The objective of the present study was to assess the outcomes and toxicity of patients treated with concurrent administration of CDK4/6 inhibitors (CDK4/6i) and locoregional radiation therapy (RT), including the breast with a boost or the thoracic wall after mastectomy and the regional lymph node areas. We retrospectively analyzed data from 27 patients with hormone receptor-positive, HER2-negative de novo metastatic breast cancer treated with CDK4/6i and concomitant locoregional RT in 2017/2022. Survival rates were calculated by Kaplan-Meier method. Prognostic factors were tested with log-rank test. CDK4/6i was used as the first systemic metastatic treatment for all the patients, and the median overall treatment time was 26 months. The median time from initiation of CDK4/6i to the start of RT was 10 months (IQR: 7-14 months). The median duration of concomitant CDK4/6i and RT administration was 21 days (IQR: 14.5-23 days). After a median follow-up of 19 months (IQR: 14-36 months), 1 patient died, 11/27 had distant metastases and 1 patient had local recurrence, respectively. The 1- and 3-years progression-free survival (PFS) were 61.4% (95% CI: 45.1%-83.7%) and 53.7% (35.8%-80.5%), respectively. The acute toxicities most observed during RT were neutropenia (44%) and dermatitis (37%). Dermatitis was significantly more frequent in patients with large target volumes (CTV > 911 cc and PTV > 1285 cc). CDK4/6i had to be discontinued in five patients during RT (due to toxicity in three cases and disease progression in two cases). One patient has developed grade 2 late pulmonary fibrosis. Finally, our study demonstrated that concurrent administration of locoregional RT and CDK4/6i did not induce severe late toxicity for most patients.

CANTO-RT: One of the Largest Prospective Multicenter Cohort of Early Breast Cancer Patients Treated with Radiotherapy including Full DICOM RT Data.

This article describes the methodology used and provides a characterization of the study population in CANTO-RT (CANcer TOxicities RadioTherapy). CANTO (NCT01993498) is a prospective clinical cohort study including patients with stage I-III BC from 26 French cancer centers. Patients matching all CANTO inclusion and exclusion criteria who received RT in one of the 10 top recruiting CANTO centers were selected. Individual full DICOM RT files were collected, pseudo-anonymized, structured and analyzed on the CANTO-RT/UNITRAD web platform. CANTO-RT included 3875 BC patients with a median follow-up of 64 months. Among the 3797 patients with unilateral RT, 3065 (80.4%) had breast-conserving surgery, and 2712 (71.5%) had sentinel node surgery. Tumor bed boost was delivered in 2658 patients (68.5%) and lymph node RT in 1356 patients (35%), including internal mammary chain in 844 patients (21.8%). Most patients (3691 (95.3%)) were treated with 3D conformal RT. Target volumes, organs at risk contours and dose/volume histograms were extracted after quality-control procedures. CANTO-RT is one of the largest early BC prospective cohorts with full individual clinical, biological, imaging and DICOM RT data available. It is a valuable resource for the identification and validation of clinical and dosimetric predictive factors of RT and multimodal treatment-related toxicities.