Dual Inhibition of CDK4/6 and CDK7 Suppresses Triple-Negative Breast Cancer Progression via Epigenetic Modulation of SREBP1-Regulated Cholesterol Metabolism.

Inhibitors targeting cyclin-dependent kinases 4 and 6 (CDK4/6) to block cell cycle progression have been effective in treating hormone receptor-positive breast cancer, but triple-negative breast cancer (TNBC) remains largely resistant, limiting their clinical applicability. The study reveals that transcription regulator cyclin-dependent kinase7 (CDK7) is a promising target to circumvent TNBC's inherent resistance to CDK4/6 inhibitors. Combining CDK4/6 and CDK7 inhibitors significantly enhances therapeutic effectiveness, leading to a marked decrease in cholesterol biosynthesis within cells.

Clinical outcomes after post-operative radiotherapy for breast cancer patients presenting with ipsilateral supraclavicular metastasis: considerations on the cranial border of irradiation field.

Background: Disease recurrence at lower neck adjacent to ipsilateral supraclavicular (SCV) region represents a concern in locally advanced breast cancer patients presenting with SCV metastasis at diagnosis. This study aims to report the outcomes following post-operative radical radiation therapy and discuss the reasonable cranial border of the irradiation field for N3c patients.

Methods: Between July 2016 and January 2022, a total of 268 patients were eligible for analysis.

CXCR6 expression correlates with radiotherapy response and immune context in triple-negative breast cancer-experimental studies.

Background: The chemokine receptor CXCR6 is critical for sustained tumor control mediated by CD8+ cytotoxic T cells (CTLs) in tumors. Previous studies have shown that ionizing radiation induces an inflamed immune contexture by upregulating CXCR6. However, the clinical significance of CXCR6 expression in triple-negative breast cancer (TNBC) and its correlation with radiotherapy remains unknown.

Hypofractionated radiotherapy with simultaneous tumor bed boost (Hi-RISE) in breast cancer patients receiving upfront breast-conserving surgery: study protocol for a phase III randomized controlled trial.

Background: The effectiveness and safety of moderately hypofractionated radiotherapy (HFRT) in patients undergoing breast-conserving surgery (BCS) has been demonstrated in several pivotal randomized trials. However, the feasibility of applying simultaneous integrated boost (SIB) to the tumor bed and regional node irradiation (RNI) using modern radiotherapy techniques with HFRT needs further evaluation.

Methods: This prospective, multi-center, randomized controlled, non-inferiority phase III trial aims to determine the non-inferiority of HFRT combined with SIB (HFRTsib) compared with conventional fractionated radiotherapy with sequential boost (CFRTseq) in terms of five-year locoregional control rate in breast cancer patients undergoing upfront BCS.

Carbon ion irradiation exerts antitumor activity by inducing cGAS-STING activation and immune response in prostate cancer-bearing mice.

Background And Purpose: As an advanced radiotherapy technique, carbon ion radiotherapy has demonstrated good efficacy and low toxicity for prostate cancer patients, but the radiobiological mechanism of killing tumor cells has not been fully elucidated. This study aims to explore the antitumor effects of carbon ion irradiation (CIR) through investigating the immune response induced by CIR in prostate cancer-bearing mice and the underlying molecular mechanism.

Materials And Methods: We established subcutaneous transplantation tumor models of prostate cancer to evaluate the tumor inhibition effect of CIR.

Adjuvant medial versus entire supraclavicular lymph node irradiation in high-risk early breast cancer (SUCLANODE): a protocol for a multicenter, randomized, open-label, phase 3 trial.

Background: Supraclavicular nodal (SCL) irradiation is commonly used for patients with high-risk breast cancer after breast surgery. The Radiation Therapy Oncology Group (RTOG) and European Society for Radiotherapy and Oncology (ESTRO) breast contouring atlases delineate the medial part of the SCL region, while excluding the posterolateral part. However, recent studies have found that a substantial proportion of SCL failures are located in the posterolateral SCL region, outside of the RTOG/ESTRO-defined SCL target volumes.

Outcomes with and without postmastectomy radiotherapy for pT3N0-1M0 breast cancer: An institutional experience.

Aim: The objective of this study is to comprehensively evaluate the therapeutic efficacy of postmastectomy radiotherapy (PMRT) in treating patients with pT3N0-1M0 breast cancer within the context of modern therapeutic strategies.

Methods: Clinical data from patients with pT3N0-1M0 breast cancer who underwent mastectomy from January 2005 to December 2018 at our institution were retrospectively analyzed.

Results: The study involved a total of 222 participants, with 112 individuals undergoing PMRT and 110 individuals not receiving it.

Brain Radiotherapy With Pyrotinib and Capecitabine in Patients With ERBB2-Positive Advanced Breast Cancer and Brain Metastases: A Nonrandomized Phase 2 Trial.

Importance: The potential benefit of combining intracranial effective systemic therapy with radiotherapy for patients with breast cancer with brain metastases remains unclear.

Objective: To assess the activity and safety of combining radiotherapy with pyrotinib and capecitabine in patients with ERBB2-positive breast cancer and brain metastases.

Design, Setting, And Participants: This was a single-arm, single-center, phase 2 nonrandomized clinical trial with a safety run-in phase.

Biological and clinical significance of radiomics features obtained from magnetic resonance imaging preceding pre-carbon ion radiotherapy in prostate cancer based on radiometabolomics.

Introduction: We aimed to investigate the feasibility of metabolomics to explain the underlying biological implications of radiomics features obtained from magnetic resonance imaging (MRI) preceding carbon ion radiotherapy (CIRT) in patients with prostate cancer and to further explore the clinical significance of radiomics features on the prognosis of patients, based on their biochemical recurrence (BCR) status.

Methods: Metabolomic results obtained using high-performance liquid chromatography coupled with tandem mass spectrometry of urine samples, combined with pre-RT radiomic features extracted from MRI images, were evaluated to investigate their biological significance. Receiver operating characteristic (ROC) curve analysis was subsequently conducted to examine the correlation between these biological implications and clinical BCR status.

The metabolic repression effect of carbon-ion radiotherapy in synchronous hormone-sensitive oligometastatic prostate cancer.

Background: Metastatic prostate cancer (PCa) poses a significant public health concern. While radiation therapy (RT) is commonly utilized in the treatment of synchronous oligometastatic hormone sensitive prostate cancer (OM-HSPC), the occurrence of biochemical recurrence still remains. To deepen our understanding and optimize the outcome of OM-HSPC, we conducted this study to investigate the characteristics of PCa progression and explore potential synergistic mechanisms involving carbon-ion radiotherapy (CIRT) and neoadjuvant androgen deprivation treatment (naADT) in OM-HSPC.

Favorable prognosis of breast cancer brain metastases patients with limited intracranial and extracranial metastatic lesions.

Background: Breast cancer brain metastases (BCBM) are highly heterogenous with widely differing survival. The prognosis of the oligometastatic breast cancer (BC) patients with brain metastases (BM) has not been well studied. We aimed to investigate the prognosis of BCBM patients with limited intracranial and extracranial metastatic lesions.

Combined Aurora Kinase A and CHK1 Inhibition Enhances Radiosensitivity of Triple-Negative Breast Cancer Through Induction of Apoptosis and Mitotic Catastrophe Associated With Excessive DNA Damage.

Purpose: There is an urgent need for biomarkers and new actionable targets to improve radiosensitivity of triple-negative breast cancer (TNBC) tumors. We characterized the radiosensitizing effects and underlying mechanisms of combined Aurora kinase A (AURKA) and CHK1 inhibition in TNBC.

Methods And Materials: Different TNBC cell lines were treated with AURKA inhibitor (AURKAi, MLN8237) and CHK1 inhibitor (CHK1i, MK8776).

A retrospective study of adjuvant proton radiotherapy for breast cancer after lumpectomy: a comparison of conventional-dose and hypofractionated dose.

Purpose: This study aimed to compare the adverse reactions of conventional-dose and hypofractionated dose of proton therapy for breast cancer.

Materials And Methods: Breast cancer patients treated with proton radiotherapy in conventional-dose or hypofractionated dose were studied retrospectively.

Result: From January 2017 to December 2019, our center treated 50 patients following lumpectomy with proton radiotherapy.

The Role of Radiotherapy for Patients with Unresectable Locally Advanced Breast Cancer following Neoadjuvant Systemic Therapy.

Background: For locally advanced breast cancer (LABC) patients who remained unresectable after neoadjuvant systemic therapy (NST), radiotherapy (RT) is considered as an approach for tumor downstaging. In this study, we attempted to discuss the value of RT for patients with unresectable or progressive disease in the breast and/or regional nodes following NST.

Methods: Between January 2013 and November 2020, the data for 71 patients with chemo-refractory LABC or de novo bone-only metastasis stage IV BC who received locoregional RT with or without surgical resection were retrospectively analyzed.

Functional imaging-guided carbon ion irradiation with simultaneous integrated boost for localized prostate cancer: study protocol for a phase II randomized controlled clinical trial.

Background: Due to the physical dose distribution characteristic of "Bragg peak" and the biological effect as a kind of high linear energy transfer ray, heavy ion therapy has advantages over conventional photon therapy in both efficacy and safety. Based on the evidence that prostate cancer lesions before treatment are the most common sites of tumor residual or recurrence after treatment, simultaneous integrated boost radiation therapy for prostate cancer has been proven to have the advantage of improving efficacy without increasing toxicities.

Methods: This study is a prospective phase II randomized controlled clinical trial evaluating the efficacy and safety of functional imaging-guided carbon ion irradiation with simultaneous integrated boost for localized prostate cancer.

Immunomodulatory effects of carbon ion radiotherapy in patients with localized prostate cancer.

Purpose: Radiotherapy is one of the main local treatment modalities for prostate cancer, while immunosuppressive effect induced by radiotherapy is an important factor of radiation resistance and treatment failure. Carbon ion radiotherapy (CIRT) is a novel radiotherapy technique and the immunomodulatory effect of CIRT provides the possibility of overcoming radioresistance and improving efficacy. The aim of this study was to assess the immune response evoked by CIRT in localized prostate cancer patients.

Carbon Ion Radiotherapy Induce Metabolic Inhibition After Functional Imaging-Guided Simultaneous Integrated Boost for Prostate Cancer.

Purpose: As local recurrence remains a challenge and the advantages of the simultaneous integrated boost (SIB) technique have been validated in photon radiotherapy, we applied the SIB technique to CIRT. The aim was to investigate the metabolomic changes of the CIRT with concurrent androgen deprivation therapy (ADT) in localized prostate cancer (PCa) and the unique metabolic effect of the SIB technique.

Material And Methods: This study enrolled 24 pathologically confirmed PCa patients.

A randomized phase 3 trial of Gemcitabine or Nab-paclitaxel combined with cisPlatin as first-line treatment in patients with metastatic triple-negative breast cancer.

Platinum is recommended in combination with gemcitabine in the treatment of metastatic triple-negative breast cancer (mTNBC). We conduct a randomized phase 3, controlled, open-label trial to compare nab-paclitaxel/cisplatin (AP) with gemcitabine/cisplatin (GP) in mTNBC patients (ClinicalTrials.gov NCT02546934).

Entire Versus Medial Supraclavicular Nodal Irradiation for Patients With High-Risk Node-Positive Breast Cancer.

Purpose: We aimed to examine whether elective inclusion of the posterolateral supraclavicular node (SCL) region to the standard medial SCL target volume improves SCL control and survival outcomes in patients with high-risk node-positive breast cancer undergoing regional nodal irradiation (RNI).

Methods And Materials: We retrospectively reviewed 544 consecutive women with high-risk breast cancer treated with postoperative chest wall/breast and RNI in our center from January 2015 to December 2016. High-risk features were defined as clinical or pathologic stage N2-3b disease.

Molecular subtypes predict second breast events of ductal carcinoma in situ after breast-conserving surgery.

Purpose: Currently, the prognostic value of molecular subtypes in ductal carcinoma in situ (DCIS) remains unclear. In this study, we explored whether molecular subtypes could predict second breast events (SBEs) in patients after breast-conserving surgery (BCS).

Methods: From January 2008 to December 2016, 291 DCIS patients treated with BCS were retrospectively analyzed.

Combined angiogenesis and PD-1 inhibition for immunomodulatory TNBC: concept exploration and biomarker analysis in the FUTURE-C-Plus trial.

Background: Immune checkpoint inhibitors had a great effect in triple-negative breast cancer (TNBC); however, they benefited only a subset of patients, underscoring the need to co-target alternative pathways and select optimal patients. Herein, we investigated patient subpopulations more likely to benefit from immunotherapy and inform more effective combination regimens for TNBC patients.

Methods: We conducted exploratory analyses in the FUSCC cohort to characterize a novel patient selection method and actionable targets for TNBC immunotherapy.

Radiomics predicts the prognosis of patients with locally advanced breast cancer by reflecting the heterogeneity of tumor cells and the tumor microenvironment.

Background: This study investigated the efficacy of radiomics to predict survival outcome for locally advanced breast cancer (LABC) patients and the association of radiomics with tumor heterogeneity and microenvironment.

Methods: Patients with LABC from 2010 to 2015 were retrospectively reviewed. Radiomics features were extracted from enhanced MRI.