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Article

Our Experience and Literature Update Regarding Concomitant Radiotherapy with CDK4/6 Inhibitors and Hormonal Therapy in Metastatic Breast Cancer

by
Laura-Florentina Rebegea
1,2,3,†,
Dorel Firescu
4,
Oana-Gabriela Trifanescu
5,
Roxana-Andreea Rahnea-Nita
5,6,
Liviu Bilteanu
5,
Mihaela Dumitru
1,
Florentina Lacatus
1,* and
Gabriela Rahnea-Nita
6,7,†
1
Radiotherapy Department, Emergency Hospital “Sf. Apostol Andrei” Galați, 800578 Galați, Romania
2
Medical Clinical Department, Faculty of Medicine and Pharmacy, “Dunarea de Jos” University, 800008 Galați, Romania
3
Research Center in the Field of Medical and Pharmaceutical Sciences (ReFORM-UDJ), 800010 Galați, Romania
4
Surgical Clinical Department, Faculty of Medicine and Pharmacy, “Dunarea de Jos” University, 800008 Galați, Romania
5
The Clinical Department, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
6
M Hospital-M Care, 077190 Voluntari, Romania
7
The Clinical Department, The Faculty of Nursing and Midwifery, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
J. Mind Med. Sci. 2025, 12(1), 33; https://doi.org/10.3390/jmms12010033
Submission received: 5 March 2025 / Revised: 30 April 2025 / Accepted: 4 May 2025 / Published: 12 May 2025
Browse Figure
Review Reports Versions Notes

Abstract

:
Background and Objectives: Standard treatment in metastatic breast cancer with positive estrogen receptors and negative HER2neu is represented by CDK4 inhibitors combined with aromatase inhibitors or fulvestrant. Palliative radiotherapy is indicated for symptoms or local–regional control. Multiple preclinical data suggest a potential synergistic effect when CDK4/6 inhibitors and radiotherapy are administered concurrently. We are trying to address some questions and/or to establish correlations within a subgroup of patients with unusual toxicities, the safety of combined treatments, the correlation with radiotherapy techniques and fractionation schemas. Also, we are aware that some organs at risk of a rapid turnover are more vulnerable to the occurrence of acute toxicities. Materials and Methods: This retrospective study includes 20 patients with metastatic breast cancer, treated with CDK4 inhibitors and radiotherapy on 29 disease sites; we followed the compliance and toxicities of combined treatments. Results: Regarding the recorded hematological toxicities, grade 1 associated with CDK4 inhibitors, occurring anterior radiotherapy was recorded; grade 2, leucopenia during radiotherapy presented in three cases without radiotherapy interrupting and leucopenia with neutropenia grade 3 presented in one case after pleural secondary lesion’s irradiation. Non-hematological grade 3 toxicities occurred in two cases: one case with grade 3 enteritis, at 2 weeks from bone metastases irradiation—iliac bone (in field toxicity) and one case with radiodermitis during radiotherapy on the breast and lymph node level, in the second week of external radiotherapy (RTE). Conclusions: In all analyzed cases, we obtained control of irradiated lesions. Secondary toxicities occurred only in irradiated areas. A close monitoring of patients during combined treatment must be considered and we are confident that in the future it will be possible to identify the subgroup of patients with a high risk of unusual toxicities occurring; additionally, we hope that using more conforming radiotherapy techniques minimizes the organ being at risk from radiation doses.

1. Introduction

Radiotherapy is a main local control method of neoplasia and approximately half of cases involve radiotherapy [1]. Cisplatin, as a radiation modulator, improves the radio-sensitivity in various types of cancers [2]. Chemotherapeutics increase radiation damage and inhibit DNA repair processes while chemo-radiation therapy increases the radiation toxicity even of normal tissues [1]. CDK4/6 inhibitors represent a category of selective cell cycle therapeutics that block the cell cycle and inhibit the cancer cell multiplication [3,4,5]. Metastatic breast cancer patients often need palliative radiotherapy. There are sparse data about the safety of the combination of CDK4/6 inhibitors and radiotherapy. Preclinical studies suggested CDK4/6 had a radiation-sensitizing effect on human cancer cell lines as they inhibited the repair mechanisms of double DNA strand breaks [6,7,8,9,10,11,12,13,14,15,16,17,18,19]. There is limited evidence in the literature, most of which deals with the toxicity of the combination of CDK4/6 and radiotherapy treatments. Numerous reports submitted suggest good compliance with treatments, but unusual grade 3 toxicity, such as esophagitis, ileitis, and dermatitis during treatments or after the end of radiation therapy, are mentioned.

2. Materials and Methods

We present 20 cases of metastatic breast cancer in treatment with CDK4/6 and aromatase inhibitors or fulvestrant that performed concomitant radiotherapy on symptomatic secondary bone lesions, cerebral, hepatic or locoregional for the mammary gland and regional nodal areas. The CDK4/6 inhibitors administered were Palbociclib, Ribociclib, and Abemaciclib.
In 2020, the starting point of this study, in our radiotherapy clinic, 3DCRT was the only one available; this is the reason for the high percentage of patients (80%) treated with this technique. Since 2022 we have also performed IMRT/VMAT radiotherapy (for 15% of the patients included in this study). Furthermore, we had patients with two or more sites treated in our clinic (re-irradiation or repeat irradiation) with different radiotherapy techniques (e.g., the first irradiation with 3DCRT and the second one with IMRT/VMAT).
All enrolled patients signed the Informed Consent paper containing the patient’s consent to medical teaching and research. Also, this study is covered by the Ethical Committee agreement of the “Sfantul Apostol Andrei” Emergency Clinical Hospital Galati—where this study was performed, between the years 2020 and 2023.

3. Results

Of the analyzed cases, 18 (90%) were women and 2 men. The medium age was 59 years, and the age range was 35–76 years. All patients had a stage 4 disease. The BRCA testing was made for patients under 50 years old; there were only two patients under 50 years old for which the BRCA1 tests was negative. The predominant metastatic site was bone (85% of cases), followed by secondary lung lesions (one case) and liver and bone (one case), and brain metastasis oligometastatic (one case), while none of the cases exhibited visceral crisis All patients had indications for radiotherapy for control of the symptoms (brain metastases and pain from bone metastasis) and for tumor control in a progressive disease (liver metastases). CDK4/6 inhibitors were associated with Letrozole in 11 cases (55% of cases), Fulvestrant in 8 cases (40% of cases) and one patient received Exemestane. Of the three inhibitors, Palbociclib was prescribed the most, in 16 cases (80% of cases), followed by Ribociclib in three patients (15%) and Amebaciclib in one case (5% of cases) (Table 1). Most of the patients (75% of cases) received EBRT at the level of secondary bone lesions; one patient underwent palliative whole brain radiation, one patient had radiotherapy for a secondary liver injury, six patients (20% of cases) received local-regional radiotherapy to the mammary gland and regional nodal areas. Most of the sites of secondary bone lesions were in the spine and bone pelvis. The mean duration of the follow-up was 19 months (1–30 months) (Table 1).
In terms of irradiation techniques, 3D conformal radiotherapy (3DCRT) prevailed in 95% of cases, in three irradiated sites; radiation therapy was administered by the IMRT (intensity modulated radiotherapy) technique and SBRT (stereotactic body radiotherapy) was used in another center in case of secondary hepatic determination. Both the secondary bone lesions, cerebral, and the locoregional irradiation of the mammary gland and nodal areas were irradiated using IMRT, 3DCRT, and VMAT (volumetric modulated arc therapy) techniques. The administered doses were DT = 42.56 Gy/16 fr, D/fr = 266 cGy in the mammary and regional nodal areas in two cases (10%), DT = 30 Gy/10 fr, D/fr = 300 cGy whole brain in one patient; doses between 20 and 30 Gy for secondary bone lesions in 14 sites were treated.
In the patients analyzed, radiotherapy was performed between the 2nd and 28th cycle of CDK4/6 inhibitors, with an average of 17 cycles (±6.93 standard deviation, SD).
Regarding metastatic disease status, oligometastatic disease predominated in 75% of cases (Table 2).
Regarding hematological toxicities (evaluated conforming with CTCAE criteria, version 5), these were recorded in grade 1 and 2 toxicities associated with CDK4 inhibitors, occurring anterior radiotherapy; neutropenia grade 2 during radiotherapy was present in five cases and grade 3 neutropenia was encountered in one case. Radiation therapy was not started in grade 2 neutropenia. Grade 1 and 2 neutropenia during radiotherapy was present in nine patients (45%) of the analyzed cases. Grade 1 and 2 thrombocytopenia was noted in six patients (30%), Table 3.
The aim of this study was to analyze the acute hematological and non-hematological toxicities in patients with indication for radiotherapy, during the treatment with CDK4/6 inhibitors, all cases being metastatic patients. Taking into consideration the PALOMA study which interrupted the palbociclib administration 1 day before radiotherapy began and repeated it 1 week after the radiotherapy ended, there is no information regarding the combined therapy, CDK4/6 inhibitors with radiotherapy; our concerns were about the safety of this combination. Additionally, in the Monarch study the patients undergoing radiotherapy were not included.
From our cases which presented toxicity, we observe:
Patient No. 1 performed RTE in the 3DCRT technique, on two metastatic sites in January 2020 on the dorsal spine, which subsequently continued on the right iliac wing in May 2020 at an interval of 4 months and in March 2022 at an interval of 22 months after the last sequence of radiation therapy; undergoes locoregional treatment of the mammary gland and in a hypofractionated regime for lymph node areas, with the appearance of grade 3 radiodermatitis, in week 3 of irradiation and grade 2 esophagitis. Radiation therapy was not discontinued. Assessment of the dose constraints revealed maintenance of dose-volume constriction parameters, i.e., the mean dose to the esophagus was 6.23 Gy (mean dose in QUANTEC < 34 Gy).
In the case of patient No. 3 with breast cancer, with secondary bone and lymphatic mediastinal determinations, in treatment with Palbociclib and fulvestrant, associated with radiotherapy, in the IMRT technique, on the secondary bone lesion in the thoracic spine, T6, shows leukopenia grade 2, neutropenia grade 2 and important hepatic cytolysis with transaminases values of 10× L.N.; this patient temporarily discontinues treatment with Palbociclib. Under liver-protective treatment, transaminases levels show a downward trend and we resumed treatment with Palbociclib with a reduced dose after about 4 weeks. This patient underwent RTE in the VMAT technique.
In the case of patient No. 4, the 50-year-old patient, in treatment with Ribociclib with fulvestrant during irradiation of left basal pleural secondary determinations with DT = 40.05 Gy/15 fr, d/fr = 267 cGy, develops leukopenia, grade 3 neutropenia, grade 1 thrombocytopenia and moderate liver damage 2× VN; in the case of this patient, it was decided to continue treatment with Ribociclib but with the dose reduced to 400 mg.
In case No. 7, the patient with breast cancer with multiple secondary bone lesions underwent radiation therapy (3DCRT) in the cervical spine in January 2020 and we identified grade 2 esophagitis during the fourth session; treatment was completed without interruption of CDK4/6 inhibitors and radiotherapy. Analyzing dose constraints in the esophagus, we observed the preservation of dose distribution values in volume, namely the medium dose in the esophagus = 19.27 Gy (according to QUANTEC, Dmed esophagus = 34 Gy). The patient underwent a second radiation therapy sequence at 2 months in the right iliac wing with the development at 2 weeks after completion of radiation therapy of grade 3 radiation-induced enteritis, with inflammatory changes, endoscopically documented. The gastrointestinal symptoms of colic were maintained for 2 weeks and during this period, the patient received antispasmodic and anti-inflammatory treatment. We associate the presence of radiation-induced enteritis with concomitant inhibition + RTE. By checking the dose constraints in the intestine, we identified the preservation of the limits of QUANTEC V35 Gy < 35% and V45 Gy < 195 cubic centimeters (c.c.); in our case, after the EQD2 dose conversion (the conversion dose from hypofractioned regimes into 2 Gy/fr.), the V35 becomes V29, and the value was: V29 = 10.63%; V45 becomes V37.5 and this value was V37.5 Gy = 117.8 c.c. V35 Gy represents the percentage volume of the structure (bowel bag) receiving 35 Gy and V45 Gy represents the volume of the structure, in c.c. receiving 45 Gy. As there was only one patient manifesting this type of toxicity, there was no correlation to be obtained between V35 Gy or V45 in the bowel bag and grade 3 enteritis.
Patient No. 14 undergoing Ribociclib and Letrozole, who underwent re-irradiation in April 2021 on a metastatic lumbar spine lesion, L2 with DT = 21 Gy/7 fr, d/fr = 300 cGy, exhibited leucopenia with grade 2 neutropenia and marked physical asthenia; It was decided to adjust the dose of Ribociclib to 400 mg. RTE was completed without interruption, but the patient died at 6 months post-RTE due SARS-CoV-2 infection. The first irradiation was performed in 2019 and a fractionation scheme was administered at the second reirradiation; on the same site was established conforming to a linear-quadratic model (LQ), taking into consideration the following parameters: normal tissue tolerance (specially the spinal cord radiation tolerance), time between irradiation treatments, repairing cell time, α/β ratio, patient’s performance status, systemic disease, and life expectancy [20].
No patients stopped receiving radiation therapy.
The outcome measures regarding the side effects by type and patient characteristics were: for leucopenia, we administered cortico-therapy, for enteritis-antispastic, sulphalazine drugs and diet. For hepatic cytolysis, we administered hepatoprotector medicines. Knowing that the hematological toxicity is the most important factor involved in reducing CDK4/6 inhibitor doses, in patients with toxicities, we continued CDK4/6 treatment but with reduced doses; for all patients with grade 3 toxicities, the dose of inhibitors was reduced.
In our study, grade 3 toxicities were recorded in four patients; two of these patients received 3DCRT, and two patients underwent radiotherapy using the IMRT/VMAT technique; three of these four patients received Palbociclib and one patient received Ribociclib.
Due to the limited number of patients, we were unable to establish statistically significant correlations between the type of CDK4/6 inhibitors and the radiotherapy technique administered; however, we noted the development of enteritis in only one case, who underwent radiotherapy with the 3D technique at the iliac site.
The grade 3 hepatic cytolysis reported in the patient (no. 3) with Palbociclib, Fulvestrant, and IMRT radiotherapy was not due to the association between the CDK4/6 inhibitor and radiotherapy, the radiotherapy being performed at the T6 vertebra level.
We also analyzed overall survival (OS) in 19 patients; one of them was lost from the follow-up and excluded from the OS analyzed. A Kaplan–Mayer survival curve indicated a 75% OS rate for our patients (Figure 1).

4. Discussion and Literature Review

We reviewed the most relevant articles recently published and we selected seven studies with clinical impact, published in the year 2023.
The main updates include safety of radiation therapy combined with CDK 4/6 Inhibitors in the management of advanced breast cancer, recommendations for integrating RT and targeted agents in breast cancer treatment and timing of radiotherapy.
These selected articles are synthesized and listed in Table 4.
CDK4/6 inhibitors substantially changed the treatment modality of Her-positive breast neoplasia cases, restoring additional studies of the combined treatment. The cyclin D-CDK4/6-RB pathway is most often deregulated [28]. Frequently, high values of D-type cyclin and CDK4/6 are noticed [29,30,31]; that is why the inhibitors targeting the cyclin D-CDK4/6-RB are the perfect choice for neoplasia treatments. CDK4/6 inhibitors in combined therapies have good prospects. Palbociclib, Ribociclib, and Abemaciclib have been approved for advanced hormone receptor-positive (HR+) breast cancer patients when combined with aromatases inhibitors such as letrozole or fulvestrant [32].
The combination of CDK4/6i with hormone therapy such as aromatase inhibitors or fulvestrant produces a synergistic effect and cancer cell division is prevented [33,34,35,36,37,38,39]. All three CDK4/6 inhibitors, respectively Palbociclib, Ribociclib, and Abemaciclib, demonstrated improved overall survival in patients with metastatic breast cancer RE (+). European approval based on the PALOMA 2 and 3 trials was granted [40,41,42]. Ribociclib received European approval based on MONALEESA 2 and 3 trials [43,44,45,46]. An improvement in overall survival (OS) was reported from MONALEESA-7 [47]. Abemaciclib received European approval based on MONARCH 2 and MONARCH 3 studies. The update of MONARCH 2 showed an important improvement in OS.
In the course of the evolution of patients with a metastatic disease, radiation therapy is often required for secondary sites in the bone, brain, lymph node or for the control of loco-regional disease in unresectable cases. Metastatic breast cancer patients frequently need palliative radiotherapy. There are sparse data about the safety of the combination of CDK4/6i and radiotherapy. Preclinical studies suggest CDK4/6 had a radiation-sensitizing effect on human cancer cell lines as it inhibited the repair mechanisms of double DNA stand breaks [14,15,16,17,18,19].
CDK4/6i may increase the radiotherapy antitumor effect, controlling cell progression from the G1 phase to the more radioresistant S phase and inhibiting repair mechanisms of the DNA double-strand break [14,15,16,17,18,19]. A careful analysis of all clinical data is required before starting the radiotherapy-CDK4/6 combination. Data about toxicity due to the combination of CDK4/6 with radiotherapy are rare. Radiation treatment schemes are highly heterogeneous and studies on a small number of patients are retrospective.
About therapeutic application of CDK4/6 inhibitors, the combinable strategy presented an important enhancement of progress-free survival with acceptable toxicity in clinical trials.

CDK4/6 Inhibitors and Tumor Radiosensitization

The mechanism of CDK4/6 inhibitors as radio-sensitizers is the blocking of DNA repair mechanisms. DNA damage plays a critical role in the radiosensitisation associated with CDK4/6 inhibitors in human cell lines. It generates cytotoxic damage on the DNA molecule which determines single or double strand breaks [48]. The major causes of radiation-induced cell death are the DNA double-strand breaks that remain unrepaired or incorrectly repaired [49].
The most common sites in our study are metastatic bone sites followed by breast-related locoregional treatment, similar to the published data. In our study, we observe a single case (5% of cases) with grade 3 neutropenia, but also grade 1 thrombocytopenia and hepatic cytolysis when performing EBRT on pleural lesions. Many scientific papers sustain this option that CDK4/6 inhibitors manifested radio-sensitivity by developing unrepaired DSBs and determining the late repair kinetics of DSBs [49]. There are also many studies that discuss the improved efficiency of concomitant CDK4/6 inhibitors and radiation therapy. There is still a need for future studies regarding the safety and efficiency of these strategies. The first outcomes of this study indicate that there are not significantly more side effects; thus, the concurrent therapy is promising [50,51,52,53]. The predominant toxicities found in our study were similar for grade 1 and 2 to that of Chowdhary et al. [52] who reported that concurrent therapy with Palbociclib and radiotherapy determined grade 1 or 2 toxicity and important pain decrease. Ippolito et al. [50] showed that neutropenia was the most frequent toxicity. In general, 60% of cases manifested grade 3 or more neutropenia before combined therapy, showing that reoccurrence prevention must be evaluated with care. Also, the study reported first grade and second skin toxicities. Only one patient performed whole brain radiotherapy without notable post-treatment toxicities and currently under regular monitoring, the last evaluation was in May 2022 is without any signs of relapse, but we cannot conclude based on a single case.
Figura et al. [51] analyzed 15 brain MBC patients in retrospect that had 42 lesions and noticed 2 cases with radiation necrosis occurring after performing 4 RTE fractions. A conclusion after these studies is that the patients are compliant even if the severe side toxicities can be a concern. Several case studies draw attention to unusual toxicity to such associations, so Messer [53] describes in one case with grade 3 esophagitis induced by radiation and dermatitis after Palbociclib administration are reported at breast cancer cases with supraclavicular lymph node metastases and who performed a total dose of 40 Gy in 20 fractions to the left neck [53] and Kawamota draws attention to the development of grade 3 enteritis in a patient undergoing radiation therapy on the iliac bone with DT = 30 Gy/10 fr which might be related to the over-sensitization after Palbociclib administration [17]. Analyzing our treatment plan of case no. 7, we do not notice any exceeding on dose constraints according to QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic).
Another case was a breast cancer patient with bone metastases at the left iliac bone and first sacral vertebrae. This patient had grade 3 enteritis enteritis post-administration of Palbociclib and RTE, TD = 30 Gy/10 fractions (3DCRT) that might be correlated with administration of Palbociclib treatment confirming with Kawamoto’s study [17]. The combined treatment of CDK4/6 inhibitors and radiation therapy must be administered with caution and the patient’s condition should be closely evaluated [17].
Regarding esophageal toxicity, we had two cases and 10% respectively had grade 2 toxicity; both underwent 3DCRT.
In our study, grade 3 toxicities were recorded in four patients; two of these patients received 3DCRT, and two patients underwent radiotherapy using the IMRT/VMAT technique; three of these four patients received Palbociclib and one patient received Ribociclib.
We do recommend, in cases of simultaneous treatment—CDK4/6 inhibitors and radiotherapy—to use IMRT or VMAT techniques in the localized pelvic or abdominal sites to obtain the lowest dose in the organs in the respective risk bowel bag, but with good coverage—95% of the PTV to receive 98% of the prescribed dose.
A combination of radiotherapy and CDK4/6 should be used cautiously until more data are available and the patient’s condition should be thoroughly evaluated and treated individually before the utilization of combination regimens. The management of treatment must be multimodal, requiring a multidisciplinary team, and a differentiation based on the primary tumor location and staging of the tumor [54,55,56,57,58,59].
Kubeczko M et al. published their largest single-center experience (100 patients) in the year 2023, and confirmed the acceptable safety profile of the CDK4/6i and RT combination [21].
Franco R et al., in the year 2023, in a review of the literature, demonstrate limited toxicities with the combination of radiotherapy with CDK4/6 inhibitors [22].
Becherini C et al., in the year 2023, conducted a systematic review to evaluate the safety profile of the combination of radiotherapy with CDK4/6 inhibitors [23].
Other studies concluded, also, that CDK4/6 inhibitor therapy combined with radiotherapy is safe [24,25,26,27].
Our study is limited by the small number of patients and the heterogeneity of fractionation schedules.
Neutropenia in our patients was similar to other studies in the literature.
No correlations were found between V35 parameters and grade 3 enteritis, nor between the average dose at the esophageal level and the presence of radicular esophagitis.
The observed toxicity patterns are aligned with prior studies, especially in terms of rare or unexpected adverse events.
The rare or unexpected adverse event was grade 3 enteritis.
There were no recorded grade 4 toxicities.
Long-term toxicities are fibrosis and the risk of secondary tumors, but we did not follow them for a long time.
There are sparse data in currently prospective clinical studies about CDK4/6i and radiotherapy. Additional safety data should be reported in open and ongoing clinical trials testing CDK4/6i-radiotherapy. The ongoing prospective phase 2 ASPIRE trial is assessing radiotherapy combined with Palbociclib and hormone therapy for bone metastases in breast cancer patients whereas a PALATINE prospective trial will assess local breast treatment (surgery and/or radiotherapy) in advanced breast cancer [59].

5. Conclusions

CDK4/6 inhibitors represent a change in the therapeutic management of HR-positive breast neoplasia, increasing the need for further studies for this combined therapy. Several clinical studies have reported well-tolerated toxicity and promising efficacy for combination therapy. Radiation therapy is performed as a palliative treatment in clinical studies and most cases have already undergone radiotherapy at other timepoints. Radiation therapy can also be performed as a post-surgical adjuvant approach with CDK4/6 inhibitors.
CDK4/6i has a synergistic radio sensitizing effect. Most severe toxicities occur in radiation fields. The results of future prospective clinical trials about the combination of CDK4/6i and radiotherapy are expected to bring additional answers about its safe use.
Patients tolerated the treatment well, except for one case of grade III acute enteritis. Most of the reactions were grade I and II. CDK4/6 inhibitors have a radio-sensibility effect, but more studies are needed.
Further studies will bring data about the safety of the administration of a combined treatment and the evaluation of late toxicities. We are recommending IMRT/VMAT or an SBRT radiotherapy technique, but if these are not available when we use the 3DCRT technique, the CDK4/6 inhibitors treatment must be interrupted and repeated after 7 days from the end of radiotherapy. Also, the CDK4/6 inhibitors must be interrupted if the patient presents neutropenia, grade 2 or 3.

Author Contributions

Conceptualization, L.-F.R.; methodology, L.-F.R.; software, M.D. and F.L.; validation, L.-F.R. and D.F.; formal analysis, M.D., F.L. and R.-A.R.-N.; investigation, D.F. and O.-G.T.; resources, M.D. and D.F.; data curation, G.R.-N. and R.-A.R.-N.; writing—original draft preparation, R.-A.R.-N.; writing—review and editing, O.-G.T., G.R.-N. and L.B.; visualization, D.F., L.B. and O.-G.T.; supervision, L.-F.R.; project administration, L.-F.R. and G.R.-N. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of “Saint Apostle Andrei” County Emergency Clinical Hospital in Galati (approval code: no. 11776 and date for the approval: 30 May 2023).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

All the data were collected from the medical files of all patients. Due to this fact, all information is private and is available according to the institutional rules of “Saint Apostle Andrei” County Emergency Clinical Hospital in Galati.

Conflicts of Interest

The authors declare no conflicts of interest.

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Jmms 12 00033 g001
Figure 1. Overall survival at 30 months of follow-up.
Figure 1. Overall survival at 30 months of follow-up.
Jmms 12 00033 g001
Table 1. Clinical and therapeutical parameters.
Table 1. Clinical and therapeutical parameters.
ParametersNo. of Patients (%) n = 20
Median age (range) (years) 59 (34–76)
Sex
Male2 (10)
Female 18 (90)
Histology
IDC (invasive ductal carcinoma)19 (95)
Lobular carcinoma1 (5)
Metastatic situs
Bone17 (85)
Bone + visceral1 (5)
M1 metastatic at diagnostic2 (10)
Type CDK4/6 administered
Palbociclib16 (80)
Ribociclib3 (15)
Abemaciclib1 (5)
HT
Letrozol11 (55)
Fulvestrant 8 (45)
Exemestan1 (5)
RT technique
3DCRT16 (80)
IMRT/VMAT3 (15)
SBRT1 (5)
Radiotherapy schema
30 Gy/10 fr5 (25)
20 Gy/5 fr16 (80)
42.56 Gy/16 fr2 (10)
40.05 Gy/15 fr1 (5)
50 Gy/25 fr1 (5)
54 Gy/6 fr1 (5)
Treated sites (n = 29)
Breast4 (13.79)
Spine10 (34.48)
Extremities4 (13.79)
Pelvis bones8 (27.59)
Left basal pleural1 (3.45)
Sternum1 (3.45)
Brain1 (3.45)
Table 2. Distribution of patients’ function of CDK4/6 inhibitors, hormonal therapy, radiotherapy technique, and occurred toxicities.
Table 2. Distribution of patients’ function of CDK4/6 inhibitors, hormonal therapy, radiotherapy technique, and occurred toxicities.
No. of Treated PatientsPalbociclib
n = 16		Ribociclib
n = 3		Abemaciclib
n = 1
Irradiated sites2441
Concomitance HT
  • Letrozol
101-
  • Fulvestrant
62-
  • Exemestan
--1
RTE technique
  • 3DCRT
151-
  • IMRT/VMAT
111
  • SBRT
-1-
Toxicities ≥ 3
  • hematologic (neutropenia)
-1-
  • digestive—enteritis
1--
  • skin
1
  • hepatic cytolysis
1
Metastatic state
  • oligometastatic
1311
  • pluri-metastatic
32-
Table 3. Distribution of toxicities.
Table 3. Distribution of toxicities.
Toxicities Grade 1Grade 2Grade 3Grade 4
Hematological
thrombocytopenia42
leucopenia45
neutropenia451
anemia41
Skin
Radiodermatitis131
Digestive
enteritis 1
Others
Esophagitis 2
Hepatic cytolysis 11
Table 4. Selected articles regarding safety of radiation therapy combined with CDK4/6 inhibitors in the management of advanced breast cancer.
Table 4. Selected articles regarding safety of radiation therapy combined with CDK4/6 inhibitors in the management of advanced breast cancer.
No.Author–YearSubjectReference No.
1Kubeczko M–2023Safety and feasibility[21]
2Franco R–2023Review of the literature[22]
3Becherini C–2023Review of the literature[23]
4Tornyi I–2023Timing of radiotherapy[24]
5Camps Maléa A–2023Benefit from the potentiation of local treatment[25]
6Beddok A–2023Biological, preclinical, and clinical aspects[26]
7Chauhan K–2023Safety of radiotherapy[27]
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Rebegea, L.-F.; Firescu, D.; Trifanescu, O.-G.; Rahnea-Nita, R.-A.; Bilteanu, L.; Dumitru, M.; Lacatus, F.; Rahnea-Nita, G. Our Experience and Literature Update Regarding Concomitant Radiotherapy with CDK4/6 Inhibitors and Hormonal Therapy in Metastatic Breast Cancer. J. Mind Med. Sci. 2025, 12, 33. https://doi.org/10.3390/jmms12010033

AMA Style

Rebegea L-F, Firescu D, Trifanescu O-G, Rahnea-Nita R-A, Bilteanu L, Dumitru M, Lacatus F, Rahnea-Nita G. Our Experience and Literature Update Regarding Concomitant Radiotherapy with CDK4/6 Inhibitors and Hormonal Therapy in Metastatic Breast Cancer. Journal of Mind and Medical Sciences. 2025; 12(1):33. https://doi.org/10.3390/jmms12010033

Chicago/Turabian Style

Rebegea, Laura-Florentina, Dorel Firescu, Oana-Gabriela Trifanescu, Roxana-Andreea Rahnea-Nita, Liviu Bilteanu, Mihaela Dumitru, Florentina Lacatus, and Gabriela Rahnea-Nita. 2025. "Our Experience and Literature Update Regarding Concomitant Radiotherapy with CDK4/6 Inhibitors and Hormonal Therapy in Metastatic Breast Cancer" Journal of Mind and Medical Sciences 12, no. 1: 33. https://doi.org/10.3390/jmms12010033

APA Style

Rebegea, L.-F., Firescu, D., Trifanescu, O.-G., Rahnea-Nita, R.-A., Bilteanu, L., Dumitru, M., Lacatus, F., & Rahnea-Nita, G. (2025). Our Experience and Literature Update Regarding Concomitant Radiotherapy with CDK4/6 Inhibitors and Hormonal Therapy in Metastatic Breast Cancer. Journal of Mind and Medical Sciences, 12(1), 33. https://doi.org/10.3390/jmms12010033

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