Stereotactic body radiation therapy for primary liver tumors: An effective liver-directed therapy in the toolbox

The use of radiation for primary liver cancers has historically been limited because of the risk of radiation-induced liver disease. Treatment fields have become more conformal because of several technical advances, and this has allowed for dose escalation. Stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy, is now able to safely treat liver tumors to ablative doses while sparing functional liver parenchyma by using highly conformal therapy. Several retrospective and small prospective studies have examined the use of SBRT for liver cancers; however, there is a lack of well-powered randomized studies to definitively guide management in these settings. Recent advances in systemic therapy for primary liver cancers have improved outcomes; however, the optimal selection criteria for SBRT as a local therapy remain unclear among other liver-directed options such as radiofrequency ablation, transarterial chemoembolization, and radioembolization.     

Systemic therapy for hormone receptor-positive/human epidermal growth factor receptor 2-negative early stage and metastatic breast cancer

Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer is defined by the presence of the estrogen receptor and/or the progesterone receptor and the absence of HER2 gene amplification. HR-positive/HER2-negative breast cancer accounts for 65%–70% of all breast cancers, and incidence increases with increasing age. Treatment varies by stage, and endocrine therapy is the mainstay of treatment in both early stage and late-stage disease. Combinations with cyclin-dependent kinase 4/6 inhibitors have reduced distant recurrence in the early stage setting and improved overall survival in the metastatic setting. Chemotherapy is used based on stage and tumor biology in the early stage setting and after endocrine resistance for advanced disease. New therapies, including novel endocrine agents and antibody-drug conjugates, are now changing the treatment landscape. With the availability of new treatment options, it is important to define the optimal sequence of treatment to maximize clinical benefit while minimizing toxicity. In this review, the authors first discuss the pathologic and molecular features of HR-positive/HER2-negative breast cancer and mechanisms of endocrine resistance. Then, they discuss current and emerging therapies for both early stage and metastatic HR-positive/HER2-negative breast cancer, including treatment algorithms based on current data.     

Understanding Hispanic Patient Satisfaction with Telehealth During COVID-19

BackgroundRecent studies have described the use of telehealth for pediatric surgical care during the COVID-19 pandemic. We aimed to evaluate equity in telehealth use by comparing rates of utilization and satisfaction with pediatric surgical telemedicine among Hispanic patients.MethodsWe conducted a retrospective cohort study of patients seen by a surgical subspecialty provider in the outpatient setting at a quaternary pediatric hospital between April 1 and June 30, 2020. Patients evaluated in the same three-month period in 2019 were analyzed as a historic control. Differences in Family Experience Survey (FES) responses based on race and ethnicity and preferred language of care were assessed using univariable and multivariable generalized linear modeling.ResultsThe pandemic cohort included fewer patients of Hispanic ethnicity and fewer Spanish-speakers. After controlling for visit type, comparison of Spanish-speaking and English-speaking patients revealed that Spanish-speaking families had significantly lower scores for FES items that evaluated healthcare provider explaining (IRR 0.74, 95% CI: 0.61–0.90), listening (IRR 0.76, 95% CI: 0.63–0.92), and time spent with the family (IRR 0.73, 95% CI: 0.60–0.89). There were no differences in FES responses based on insurance status or degree of medical complexity.ConclusionsTelehealth services were less commonly used among Hispanic and Spanish-speaking patients. Language may differentially affect family satisfaction with healthcare and telehealth solutions. Strategies to mitigate these inequities are needed and may include strengthening interpreter services and providing language-concordant care.Level of evidenceLevel IV.     

Tuberculosis during lung cancer treatment-A case series

This study aimed to clarify the characteristics of patients with lung cancer undergoing treatment until the onset of tuberculosis. Between 2005 and 2019, patients who were admitted to Tokyo National Hospital due to tuberculosis during lung cancer treatment were examined retrospectively. There were 42 patients, and detailed medical information was obtained in 39 patients. The median age of the 39 patients were 75 years (range: 47–92 years), of which 33 were males and 36 were Japanese Baby Boomers or older. Regarding risk factors for developing tuberculosis, smoking was noted in 34 cases, oral corticosteroid use in 13, and previous tuberculosis in six. Thirty-seven patients had one risk factor and 19 had two or more risk factors, but diagnosis of latent tuberculosis infection (LTBI) was obtained in only one patients, and none had received LTBI treatment. The first-line treatment for lung cancer was resection in 13 cases, chemoradiotherapy in 6, chemotherapy in 10, radiation therapy in 3, laser therapy in 1, and best supportive care (BSC) alone in 6. At tuberculosis onset, BSC accounted for 17 cases, but other situations were considerably existed such as anticancer medication (12 cases), and observation after lung cancer treatment (10 cases). Tuberculosis occurred in various situations in elderly patients with lung cancer. It is critical to actively evaluate the risk of tuberculosis and consider LTBI screening and treatment.     

基于iTRAQ技术探讨人胃癌细胞乙酰肝素酶调控的信号通路北大核心

目的:探讨人胃癌细胞中乙酰肝素酶(HPSE)调控的差异蛋白和信号通路,为以HPSE为靶点防治胃癌提供依据。方法:利用siRNA干扰技术,在乙酰肝素酶(HPSE)基因高表达的SGC7901细胞中转入干扰HPSE的慢病毒载体(LV-HPSE-RNAi),通过嘌呤霉素筛选出稳定株,利用qPCR和Western blot分别检测HPSE mRNA和蛋白表达;利用细胞划痕实验和Transwell侵袭实验测定细胞的迁移和侵袭能力;利用同位素标记的相对和绝对定量(iTRAQ)联合二维液相色谱串联质谱(2DLC-MS/MS)技术筛查差异蛋白,并进行生物信息学分析,对差异蛋白PKCa应用Western blot进一步验证。结果:人胃癌SGC7901细胞和沉默HPSE表达的ZSGC7901细胞对比检测出98个差异蛋白,并且富集在157条信号通路上。与肿瘤发生发展关系密切的有6条:细胞外基质和受体相互作用、局灶性黏附、PI3K-Akt信号通路、癌途径、癌中microRNAs、Wnt信号通路。且上调的FAK、ITGA、PKCa等蛋白和下调的PKA、CDK6等蛋白在通路中处于重要的位置。Western blot结果证明PKCa在沉默HPSE的ZSGC7901细胞中表现为上调,差异具有统计学意义(P<0.05),与蛋白质组学筛选结果一致。结论:HPSE在人胃癌细胞中调控的蛋白,参与细胞重要生物学过程、参与重要分子功能及重要信号途径,有望可以成为防治胃癌的新靶点。     

A systematic review of axillary nodal irradiation for the management of the axilla in patients with early-stage breast cancer

BackgroundGiven numerous publications and clinical trials regarding axillary management in breast cancer, we sought to summarize this complex literature to help clarify this field for clinicians. This systematic review focuses on the role of irradiation of the axillary nodes (locoregional nodal irradiation [LRNI]) in the management of the axilla in patients with early-stage breast cancer in various clinical settings.MethodsWe searched MEDLINE and EMBASE databases, the Cochrane library, the proceedings of the ASCO, the ASTRO, the ESMO, the ESTRO, and the San Antonio Breast Cancer Symposium (2016–2019) meetings. The quality of the studies was assessed with design-specific tools. The study was registered in PROSPERO.ResultsWe included one systematic review, one individual patient data (IPD) meta-analysis, and five randomized controlled trials (RCTs). After axillary lymph node dissection (ALND), LRNI resulted in small benefits in breast cancer specific mortality, locoregional recurrence, and distant metastases-free survival but not overall survival. After a positive sentinel node biopsy (SLNB), LRNI may provide equivalent locoregional control and disease-free survival (DFS) compared to ALND with a lower risk of lymphedema. No randomized data is available for the neoadjuvant setting.ConclusionsThe summary of the role of radiation, is relevant to radiation oncologists for choosing the correct cohort of patient requiring LRNI and to surgeons making clinical decisions regarding the timing and type of breast reconstruction offered to patients.     

Evaluation of Simplified Lymphatic Microsurgical Preventing Healing Approach (SLYMPHA) for the prevention of breast cancer-related lymphedema after axillary lymph node dissection using bioimpedance spectroscopy

BackgroundLymphedema is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 20%. Simplified Lymphatic Microsurgical Preventing Healing Approach (SLYMPHA) is a safe and relatively simple method, which decreases incidence of lymphedema dramatically. Our initial study showed an 88% decrease in clinical lymphedema rate. In the initial study, we used arm circumference measurement for the diagnosis of lymphedema and median follow up was 15 months. The aim of this study was to confirm these results after a long-term follow up period and by using bioimpedance spectroscopy (L-Dex) technology in detecting lymphedema.Study designAll patients, undergoing ALND with or without SLYMPHA between January 2014 and November 2020 were included in the study. Patients with no postoperative L-Dex measurements were excluded. A L-Dex score outside the normal range (±10 L-Dex unit) or ≥10 L-Dex unit increase above patient's baseline was considered as lymphedema. The incidence of lymphedema was compared between patients with and without SLYMPHA.Results194 patients were included in the study. 57% of cohort underwent SLYMPHA. Mean follow-up time was 47 ± 37 months. Patients, who underwent SLYMPHA, had a significantly lower rate of lymphedema (16% vs 32%; p = 0.01; OR 0.4 [0.2–0.8]).ConclusionSLYMPHA is a safe and relatively simple method, which continued its efficacy after a long-term follow up period. It should be considered as an adjunct procedure to ALND for all patients during initial surgery.     

Metastasis-directed Therapy in Prostate Cancer: Prognostic Significance of the ESTRO/EORTC Classification in Oligometastatic Bone Disease

AimsOligometastatic disease (OMD) represents a spectrum of clinical scenarios and various classification systems have been proposed. Bone-only OMD can occur in patients with advanced prostate cancer and validated decision-making tools are needed to assist patient selection for metastasis-directed therapy. The aim of the present study was to determine the prognostic utility of a classification system for OMD.Materials and methodsA retrospective review was conducted of all patients with bone-only oligometastatic prostate cancer treated with stereotactic body radiotherapy (SBRT) since November 2011. SBRT was delivered using CyberKnife® and gantry-based linear accelerator platforms. All patients were classified into oligometastatic states based on the European Society for Radiotherapy and Oncology/European Organisation for Research and Treatment of Cancer (ESTRO/EORTC) classification system. Kaplan–Meier and Cox regression analyses were carried out to determine the prognostic utility of this classification system.ResultsIn total, 105 patients with 145 osseous metastases were treated over 119 sessions. The median follow-up after SBRT was 23 months (interquartile range 10–39.8). Twelve patients had died after a median time of 31 months. The 3-year metastatic progression-free survival was 23% (95% confidence interval 13–32) and the 3-year overall survival was 88% (95% confidence interval 80–96). Patients in a metachronous oligometastatic state were 4.50 (95% confidence interval 1.19–17.10, P = 0.03) times more likely to experience metastatic progression compared with those with synchronous oligometastases, and 6.69 (95% confidence interval 1.05–42.50, P = 0.04) times more likely to experience any failure. Hazard ratio magnitudes increased for patients in a repeat oligometastatic state. The multivariate model for both metastatic progression-free survival and failure-free survival found prostate-specific antigen doubling time <4 months (P = 0.002; P = 0.05) to independently predict for progression.ConclusionThe ESTRO/EORTC classification of OMD predicts for progression in patients treated with SBRT for bone-only oligometastatic prostate cancer at our institution. Further validation in prospective series over multiple tumour sites is needed. These characterisation factors should be assessed in patients considered for metastasis-directed therapy together with established prognostic features.