Comprehensive analysis of stereotactic Radiosurgery outcomes in triple-negative breast cancer patients with brain metastases: The influence of immunotherapy and prognostic factors.

INTRODUCTION: Breast cancer stands as the second most common solid tumors with a propensity for brain metastasis. Among metastatic breast cancer cases, the brain metastasis incidence ranges from 10 % to 30 %, with triple-negative breast cancer (TNBC) displaying a heightened risk and poorer prognosis. SRS has emerged as an effective local treatment modality for brain metastases; however, data on its outcomes specifically in pure triple-negative subtype remain scarce. METHOD: We retrospectively reviewed the electronic medical records of all brain metastasis (BM) TNBC patients treated with SRS. Patient, tumour characteristics and treatment details data were collected. This retrospective cohort study aimed to evaluate local control (LC), distant brain metastasis free survival (DBMFS), and overall survival (OS) outcomes in TNBC patients undergoing SRS for brain metastases while identifying potential prognostic factors. RESULT: Forty-three patients with TNBC and brain metastases treated with SRS between January 2017 and 2023 were included. The study found rates of LC (99 % at 1 year) and DBMFS (76 % at 1 year) after SRS, with brain metastasis count (p = 0,003) and systemic treatment modality (p = 0,001) being significant predictors of DBMFS. The median OS following SRS was 19.5 months, with neurological deficit (p = 0.003) and systemic treatment modality (p = 0.019) identified as significant predictors of OS. CONCLUSION: SRS demonstrates favourable outcomes in terms of local control and distant brain metastasis-free survival in TNBC. Neurological deficit and systemic treatment significantly influence overall survival, emphasizing the importance of personalized treatment approaches and (magnetic resonance imaging) MRI surveillance based on these factors.

Feasibility and tolerability of breath-hold in liver stereotactic body radiotherapy with surface guided radiotherapy.

Purpose: Intrafractional motion constitutes a significant challenge in SBRT (Stereotactic Body Radiotherapy).The breath-hold (BH) technique is employed to mitigate tumor motion; however, ensuring reproducibility and consistency remains critically important. Surface tracking systems, integrated into the treatment process, facilitate motion tracking through three-dimensional camera technology. Surface guidance has been incorporated with Varian EDGE (Varian Medical Systems, Palo Alto, CA, USA) and has been utilized at multiple treatment sites within our department since 2018. Drawing on four years of experience, this study aims to publish patient experience, assess the feasibility, and evaluate the tolerability of breath-hold during SBRT with surface guided radiotherapy (SGRT), particularly focusing on a specific subgroup: patients with liver metastases. Methods: Prospective evaluation was conducted on patients with liver metastases undergoing breath-hold SBRT with SGRT. A two-step survey consisting of seven questions was administered after CT simulation and treatment. Treatment duration and the number of breath-holds were recorded. Additionally, factors potentially influencing SGRT and treatment time were assessed. Results: Between April 2021 and May 2022, a total of 41 patients underwent 171 fractions of treatment. According to the questionnaire, prior training was found to be beneficial, and breath-holding during the procedure was tolerable. Patients reported experiencing slight stress due to their active participation in the treatment. Factors such as Karnofsky Performance Status (KPS), age, lung volume, conditions affecting lung capacity, previous breath-hold history, and being a native speaker showed no correlation with treatment time. Moreover, these factors did not correlate with the tolerability of breath-hold during SGRT. However, female patients showed better breath-holding performance in SGRT treatments compared to male patients (p: 0.02). Conclusions: The application of breath-hold with SGRT procedures is tolerable and feasible in liver SBRT treatments. There exists no specific subgroup that cannot tolerate this method.

Survival outcomes of patients with oligometastatic non-small cell lung cancer who were treated with radical therapy: a multicenter analysis.

BACKGROUND: Oligometastatic disease for nonsmall cell lung cancer (NSCLC) patients is generally thought to represent a better prognosis with a quieter biology, limited number of disease sites and long-term disease control. In this study, we aimed to determine the efficacy of radical treatment options for patients with oligometastatic NSCLC. METHODS: This retrospective trial included totally 134 patients with oligometastatic NSCLC. The presence of oncodriver mutation, tumor stages and nodal status, the number of metastases and involved metastatic site, treatment of primary tumor and oligometastasis, response rate, overall survival (OS) and progression-free survival (PFS) were evaluated. RESULTS: Of 134 patients 66.4% were defined as adenocarcinoma, 26.1% were squamous cell carcinoma and 7.5% of patients were in other histology. Based on the treatment of primary tumor, in 36 patients (26.9%) curative surgery has undergone, in addition, 19 (14.2%) patients were received chemotherapy, 73 (54.5%) were treated with chemoradiotherapy, while immunotherapy and targeted therapy were used in 1 (0.7%) and 2 (1.4%), respectively. The preferred treatment for oligometastatic lesions were SBRT in 72.4% of patients, surgery in 10.5%, and both SBRT and surgery in 17.1% of patients. At the median follow up of 31.3 months (range: 9.5-48.5), the median PFS and OS times were 17 and 24.4 months, respectively. Moreover, OS-2 after progression was also 7.2 months. DISCUSSION: Based on our real-life experience, we demonstrated a significant correlation between good response to first treatment and survival in oligometastatic disease, we also understand that local ablative treatment modalities prolong and also delay both OS and PFS in oligometastatic NSCLC patients OS-2.

Evaluation of clinically involved lymph nodes with deformable registration in breast cancer radiotherapy.

OBJECTIVES: Modern radiotherapy (RT) techniques require careful delineation of the target. There is no particular RT contouring guideline for patients receiving neoadjuvant chemotherapy (NACT). In this study, we examined the distribution of pre-chemotherapy clinically positive nodal metastases. METHODS: We explored the coverage rate of the RTOG breast contouring guideline by deformable fusion of 18-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scan. We retrospectively evaluated neoadjuvant chemotherapy patients. All PET-CT images were imported into the planning software. We combined the planning CT and the CT images of PET-CT with rigid and then a deformable registration. We manually contoured positive lymph nodes on the CT component of the PET-CT data set and transferred them to planning CT after fusion. We evaluated whether previously contoured lymphatic CTVs, according to the RTOG breast atlas, include GTV-LNs. RESULTS: All breast cancer patients between October 2018 and February 2021 were evaluated from the electronic database. There were 142 radiologically defined positive lymph nodes in 31 patients who were irradiated after NACT. Most LNs (70%) were in the level I axilla. Only 71.1% (n:101) of the whole lymph nodes in 10 patients were totally covered, 22.5% (n:32) partially covered and 6.4% %(n:9) totally undercovered. CONCLUSIONS: The extent of regional nodal areas in the RTOG atlas may be insufficient to cover positive lymph nodes adequately. For patients with nodal involvement undergoing neoadjuvant chemotherapy, PET-CT image fusions can be helpful to be sure that positive lymph nodes are in the treatment volume. ADVANCES IN KNOWLEDGE: RTOG contouring atlas may be insufficient to cover all involved lymph nodes after NACT. For patients with nodal involvement undergoing neoadjuvant chemotherapy, PET-CT image fusions may help to be sure that positive lymph nodes are in the treatment volume.

Stereotactic body radiotherapy in patients with adrenal gland metastases of oligometastatic and oliogoprogressive lung cancer.

Objective: To evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) in patients with adrenal gland metastasis (AGM) of oligometastatic lung cancer. Methods: Between June 2013 and May 2021, 44 patients with oligometastatic lung cancer (51 AGMs) were treated with SBRT. Forty-six (90%) lesions received a biological effective dose (BED10, α/ß = 10) of 100 Gy. The primary endpoint was local control (LC). Local control (LC), overall survival (OS), and progression-free survival (PFS) curves were calculated by the Kaplan-Meier method. Results: The median follow-up was 23 months. The most common histology was non-small cell lung cancer (88.6%). The 1- and 2-year LC rates were both 95% and 91%, respectively. Overall survival was better in patients with solitary AGMs in univariate analysis. Conclusion: This study demonstrated that SBRT with higher BED is associated with satisfactory LC and low toxicity rates in patients with AGM of oligometastatic lung cancer.

Treatment outcomes of metastasis-directed treatment using 68Ga-PSMA-PET/CT for oligometastatic or oligorecurrent prostate cancer: Turkish Society for Radiation Oncology group study (TROD 09-002).

PURPOSE: The aim of this study was to evaluate the outcomes of 68Ga prostate-specific membrane antigen (68Ga-PSMA) positron-emission tomography (PET)/CT-based metastasis-directed treatment (MDT) for oligometastatic prostate cancer (PC). METHODS: In this multi-institutional study, clinical data of 176 PC patients with 353 lesions receiving MDT between 2014 and 2019 were retrospectively evaluated. All patients had biopsy proven PC with ≤5 metastases detected with 68Ga-PSMA-PET/CT. MDT was delivered with conventional fractionation or stereotactic body radiotherapy (SBRT) techniques. CTCAE v4.0 was used for acute and RTOG/EORTC Late Radiation Morbidity Scoring Schema was used for late toxicity evaluation. RESULTS: At the time of MDT, 59 patients (33.5%) had synchronous and 117 patients (66.5%) had metachronous metastases. Median number of metastases was one and the MDT technique was SBRT in 73.3% patients. The 2­year overall survival (OS) and progression-free survival (PFS) rates were 87.6% and 63.1%, respectively. With a median follow-up of 22.9 months, 9 patients had local recurrence at the irradiated site. The 2­year local control rate at the treated oligometastatic site per patient was 93.2%. In multivariate analysis, an increased number of oligometastases and untreated primary PC were negative predictors for OS; advanced clinical tumor stage, untreated primary PC, BED3 value of ≤108 Gy, and MDT with conventional fractionation were negative predictors for PFS. No patient experienced grade ≥3 acute toxicity, but one patient had a late grade 3 toxicity of compression fracture after spinal SBRT. CONCLUSION: 68Ga-PSMA-PET/CT-based MDT is an efficient and safe treatment for oligometastatic PC patients. Proper patient selection might improve treatment outcomes.

Concordance of PD-L1 expression and CD8+ TIL intensity between NSCLC and synchronous brain metastases.

Programmed death-ligand 1 (PD-L1) is suggested to be a predictive biomarker in non-small-cell lung carcinoma (NSCLC). However, the differential expression of PD-L1 in primary lung tumor vs. synchronous metastases, especially brain metastasis (BM), remains unclear. This study assessed the concordance of PD-L1 expression on tumor cells and tumor-infiltrating lymphocytes (TILs) and CD8+ TIL intensity between primary lung tumors and synchronous BMs from 24 NSCLC patients. PD-L1, CD3, and CD8 positivity was determined by immunohistochemistry (IHC). PD-L1 scoring was based on the proportion of tumor cells with membranous expression of PD-L1 and the cutoff values <1%, 1-49%, and ≥50%. CD3 and CD8 positivity in TILs was evaluated semi-quantitatively and the proportion of CD3+/CD8+ TILs was determined. PD-L1 expression on tumor cells and TILs was evaluated in relation to CD3+/CD8+ TIL proportions and the intensity of CD8+ TILs between the paired primary lung and BM tissues. In the primary lung tumors, PD-L1 positivity was observed in 25%, 37.5%, and 37.5% cases for the cutoff values <1%, 1-49%, and ≥50%, respectively. PD-L1 expression on tumor cells was strongly correlated between the paired primary lung and BM tissues, in all cutoff groups. However, PD-L1 expression on TILs and the proportion of CD3+/CD8+ TILs were not strongly correlated in all three groups between the paired primary lung tumors and BMs. The intensity of CD8+ TILs was concordant in only 54.16% of the paired primary lung tumors and BMs. This study showed a high concordance of PD-L1 expression in neoplastic cells between primary NSCLC and synchronous BMs.

Biological Subtypes and Distant Relapse Pattern in Breast Cancer Patients After Curative Surgery (Study of Anatolian Society of Medical Oncology).

PURPOSE: The aim of the study was to investigate the association between the molecular subtypes and patterns of relapse in breast cancer patients who had undergone curative surgery. METHODS: We retrospectively evaluated 1,350 breast cancer patients with relapses after curative surgery between 1998 and 2012 from referral centers in Turkey. Patients were divided into 4 biological subtypes according to immunohistochemistry and grade: triple negative, HER2 overexpressing, luminal A and luminal B. RESULTS: The percentages of patients with luminal A, luminal B, HER2-overexpressing, and triple-negative breast cancer were 32.9% (n = 444), 34.9% (n = 471), 12.0% (n = 162), and 20.2% (n = 273), respectively. The distribution of metastases differed among the subgroups: bone (66.2% and 53.9% in luminal A and B vs. 38.9% in HER2-overexpressing and 45.1% in triple negative, p < 0.001), liver (40.1% in HER2-overexpressing vs. 24.5% in luminal A, 33.5% in luminal B, and 27.5% in triple negative, p < 0.001), lung (41.4% in triple negative and 35.2% in HER2-overexpressing vs. 30.2% and 30.6% in luminal A and B, p = 0.008) and brain (25.3% in HER2-overexpressing and 23.1% in triple negative vs. 10.1% and 15.1% in luminal A and B, p < 0.001). CONCLUSIONS: Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer should be considered.