Quantifying dose uncertainties resulting from cardiorespiratory motion in intensity-modulated proton therapy for cardiac stereotactic body radiotherapy.

Background: Cardiac stereotactic body radiotherapy (CSBRT) with photons efficaciously and safely treats cardiovascular arrhythmias. Proton therapy, with its unique physical and radiobiological properties, can offer advantages over traditional photon-based therapies in certain clinical scenarios, particularly pediatric tumors and those in anatomically challenging areas. However, dose uncertainties induced by cardiorespiratory motion are unknown. Objective: This study investigated the effect of cardiorespiratory motion on intensity-modulated proton therapy (IMPT) and the effectiveness of motion-encompassing methods. Methods: We retrospectively included 12 patients with refractory arrhythmia who underwent CSBRT with four-dimensional computed tomography (4DCT) and 4D cardiac CT (4DcCT). Proton plans were simulated using an IBA accelerator based on the 4D average CT. The prescription was 25 Gy in a single fraction, with all plans normalized to ensure that 95% of the target volume received the prescribed dose. 4D dose reconstruction was performed to generate 4D accumulated and dynamic doses. Furthermore, dose uncertainties due to the interplay effect of the substrate target and organs at risk (OARs) were assessed. The differences between internal organs at risk volume (IRV) and OARreal (manually contoured on average CT) were compared. In 4D dynamic dose, meeting prescription requirements entails V25 and D95 reaching 95% and 25 Gy, respectively. Results: The 4D dynamic dose significantly differed from the 3D static dose. The mean V25 and D95 were 89.23% and 24.69 Gy, respectively, in 4DCT and 94.35% and 24.99 Gy, respectively, in 4DcCT. Eleven patients in 4DCT and six in 4DcCT failed to meet the prescription requirements. Critical organs showed varying dose increases. All metrics, except for Dmean and D50, significantly changed in 4DCT; in 4DcCT, only D50 remained unchanged with regards to the target dose uncertainties induced by the interplay effect. The interplay effect was only significant for the Dmax values of several OARs. Generally, respiratory motion caused a more pronounced interplay effect than cardiac pulsation. Neither IRV nor OARreal effectively evaluated the dose discrepancies of the OARs. Conclusions: Complex cardiorespiratory motion can introduce dose uncertainties during IMPT. Motion-encompassing techniques may mitigate but cannot entirely compensate for the dose discrepancies. Individualized 4D dose assessments are recommended to verify the effectiveness and safety of CSBRT.

Therapeutic progress and challenges for triple negative breast cancer: targeted therapy and immunotherapy.

Triple negative breast cancer (TNBC) is a subtype of breast cancer, with estrogen receptor, human epidermal growth factor receptor 2 and progesterone receptor negative. TNBC is characterized by high heterogeneity, high rates of metastasis, poor prognosis, and lack of therapeutic targets. Now the treatment of TNBC is still based on surgery and chemotherapy, which is effective only in initial stage but almost useless in advanced stage. And due to the lack of hormone target, hormonal therapies have little beneficial effects. In recent years, signaling pathways and receptor-specific targets have been reported to be effective in TNBC patients under specific clinical conditions. Now targeted therapies have been approved for many other cancers and even other subtypes of breast cancer, but treatment options for TNBC are still limited. Most of TNBC patients showed no response, which may be related to the heterogeneity of TNBC, therefore more effective treatments and predictive biomarkers are needed. In the present review, we summarize potential treatment opinions for TNBC based on the dysregulated receptors and signaling pathways, which play a significant role in multiple stages of TNBC development. We also focus on the application of immunotherapy in TNBC, and summarize the preclinical and clinical trials of therapy for patients with TNBC. We hope to accelerate the research and development of new drugs for TNBC by understanding the relevant mechanisms, and to improve survival.

Hip Arthroscopy for Femoracetabular Impingement in China: A Review and Meta-Analysis.

OBJECTIVE: To explore the development of hip arthroscopy in China through reviewing the change of the application of hip arthroscopy operation on treating femoracetabular impingement (FAI). METHOD: Papers were retrieved from January 1, 2005 to November 1, 2019, from databases CNKI, Wanfang Data, VIP, PubMed, and Embase. The keywords are Hip Impingement, Femoroacetabular impingement, Hip arthroscopy, Arthroscopic operation, Hip Arthroscopy operation, and Arthroscope, etc. The quality of papers was assessed through MINORS , and statistics and meta-analysis were performed by Word, Excel, and Revman 5.3 Zurich, Switzerland. RESULTS: From a total of 8,953 papers, 46 review articles without data and 48 articles with data were involved, and 25 papers were included in the Meta-analysis. The twenty-five papers were selected from 48 papers with data, of which 41 were reported in Chinese, 11 were missing complete Harris scores, five did not mention the number of patients who had lost follow-up, three had minors quality scores below 7, one did not have enough FAI cases, and three did not have standard deviations in Harris scores. Overall, in China, the application of hip arthroscopy regarding FAI has flourished while maintaining a high level of treatment and has reached its peak in the past 2 years. CONCLUSION: With the rapid development of hip arthroscopy in China, hip operation is widely recognized, many reports on its application on FAI have emerged successively, and the scope of application and technical level have been improved.