Efficacy and Safety of Befotertinib (D-0316) in Patients With EGFR T790M-Mutated NSCLC That Had Progressed After Prior EGFR Tyrosine Kinase Inhibitor Therapy: A Phase 2, Multicenter,Single-Arm,Open-Label Study

IntroductionBefotertinib (D-0316) is a novel, third-generation EGFR tyrosine kinase inhibitor (TKI). This study evaluated befotertinib in patients with locally advanced or metastatic NSCLC who developed an EGFR T790M mutation after progression on first- or second-generation EGFR TKI therapy.MethodsThis was a single-arm, open-label, phase 2 study at 49 hospitals across mainland China. Patients with locally advanced or metastatic NSCLC harboring EGFR T790M mutations with disease progression after prior first- or second-generation EGFR TKI therapy received oral befotertinib of 50 mg (cohort A) or 75 to 100 mg (cohort B) once daily. The primary end point was objective response rate (ORR) assessed by an independent review committee in intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT03861156.ResultsA total of 176 patients and 290 patients were included in cohorts A (50 mg) and B (75–100 mg), respectively. At data cutoff (August 15, 2021), independent review committee–assessed ORR was 67.6% (95% confidence interval [CI]: 61.9%–72.9%) in cohort B. The investigator-assessed ORR was 54.0% (95% CI: 46.3%–61.5%) in cohort A and 65.9% (95% CI: 60.1%–71.3%) in cohort B. The median investigator-assessed progression-free survival was 11.0 (95% CI: 9.6–12.5) months in cohort A and 12.5 (95% CI: 11.1–13.8) months in cohort B. The median independent review committee–assessed progression-free survival in cohort B was 16.6 (95% CI: 15.0–not evaluable [NE]) months. The intracranial ORR was 26.7% (95% CI: 7.8%–55.1%) in cohort A by investigator assessment, while 57.1% (95% CI: 34.0%–78.2%) and 55.9% (95% CI: 37.9%–72.8%) in cohort B by investigator and independent review committee assessment, respectively. The median investigator-assessed intracranial progression-free survival was 16.5 (95% CI: 8.6–NE) months in cohort A, while the median intracranial progression-free survival was not evaluable in cohort B due to immature data regardless of investigator or independent review committee assessment. and NE (95% CI: 13.8–NE) in cohort B. The overall survival was immature. Grade 3 or higher treatment-related adverse events and treatment-related serious adverse events occurred in 20.5% and 11.4% of patients in cohort A and in 29.3% and 10.0% of patients in cohort B, respectively.ConclusionsBefotertinib of 75 to 100 mg has satisfying efficacy and manageable toxicity in patients with locally advanced or metastatic NSCLC harboring T790M mutation with resistance to first- or second-generation EGFR TKIs. A phase 3 randomized trial is underway (NCT04206072).     

Intraoperative Radiation After Pelvic Short Course Radiation-Based Total Neoadjuvant Therapy for Patients With Rectal Adenocarcinoma at High Risk for Local Recurrence

BackgroundShort course radiation-based total neoadjuvant therapy can improve disease-free survival for patients with high-risk locally advanced rectal cancer. Tumors that involve or threaten the circumferential resection margin have a particularly high risk of local recurrence. Intraoperative radiation therapy enables treatment escalation at the threatened or involved margin at the time of surgery.Patients and MethodsPatients with rectal adenocarcinoma treated with preoperative short course radiotherapy-based total neoadjuvant therapy and intraoperative radiation at the time of surgery were identified. All patients had a threatened or involved circumferential resection margin on magnetic resonance imaging at the time of diagnosis. Treatment details, radiation toxicities, postoperative complications and oncologic outcomes were recorded.ResultsTen patients received intraoperative radiation after short course radiation-based total neoadjuvant therapy. All patients had an involved or threatened circumferential resection margin, 60% had extramural venous invasion, and 60% had positive lateral pelvic lymph nodes. Seven patients had negative surgical margins (≥ 2 mm), and 3 patients had an R1 resection with radial margins < 2 mm. The median [IQR] length of hospitalization after surgery was 11 [7-14] days. Three patients required readmission and 2 patients required reoperation due to complications including anastamotic leak and abscess. With a median follow up of 19.5 months postoperatively, no patient developed a pelvic recurrence, and 6 patients developed distant recurrences.ConclusionsThe use of intraoperative radiation after a short course radiotherapy-based neoadjuvant therapy is safe and feasible. Further data are needed to determine whether the addition of intraoperative radiation improves local recurrence rates over preoperative radiation alone.     

The use of neoadjuvant therapy increases the rate of breast conservation in men with locally advanced breast cancer

BackgroundMale breast cancer (MBC) is often diagnosed at a later stage and with a more unfavorable tumor-to-breast ratio compared to women, prompting lower rates of breast conservation (BCT). We sought to assess the practice patterns of neoadjuvant therapy (NT) in MBC patients and the impact on BCT.MethodsMen with nonmetastatic, invasive breast cancer were identified from the National Cancer Database. Patients were categorized as having small (cT1/2) or locally advanced (cT3/4) tumors and by whether they received NT (which included endocrine or chemotherapy). Univariate and multivariable analyses were performed to assess patterns of NT use and rates BCT.ResultsOf 15,151 male patients, 4.8% received NT and 21.6% underwent BCT. NT was more common among males with cT3/4 tumors than those with cT1/2 tumors (8.2 vs. 2.1%, P < .001). Overall, unadjusted rates of BCT were higher for patients receiving NT in the cT3/4 subgroup (19.0 vs. 12.5%, P < .001), a difference which persisted on multivariable analysis. For all patients analyzed, overall survival (OS) did not differ between males who underwent NT and those who did not (110 vs. 122 months, P = .67), but NT was associated with poorer OS in both univariate and multivariate analyses for patients with cT3/4 tumors (both P < .01).ConclusionsMen with invasive breast cancer have an expected low rate of BCT, but NT appears to reduce the use of mastectomy in patients with locally advanced cancers. More work is needed to understand the impacts of BCT on locoregional recurrence and disease-free and overall survival for MBC.     

Relative Incidence of Emergency Department Visits After Treatment for Prostate Cancer With Radiation Therapy or Radical Prostatectomy

PurposeSide effect profiles play an important role in treatment decisions for localized prostate cancer. Emergency department (ED) visits, which may be due to side effects from treatment, can be measured in real-world, structured, electronic health record (EHR) data. The goal of this study was to determine whether treatments for localized prostate cancer are associated with ED visits, as a measure of side effects, using EHR data.Methods and MaterialsWe used a self-controlled case series study design, including patients treated at an urban academic medical center with radiation therapy (RT) or radical prostatectomy (RP) for prostate cancer between 2011 and 2020 who had visits documented for ≥6 months before and after treatment and ≥1 ED visit. We estimated relative incidences (RI) of ED visits, comparing incidence in the exposed and unexposed periods, with the exposed period being between start of treatment and 1 month after completion, and the unexposed period consisting of all other documented time.ResultsAmong men who had at least 1 ED visit and after adjusting for age, there were higher rates of ED visits after RP (RI, 20.4; 95% confidence interval [CI], 15.4-27.0; P < .001), RT overall (RI, 2.4; CI, 1.7-3.4; P < .001), intensity modulated radiation therapy with high dose-rate brachytherapy (RI, 3.4; CI, 1.7-6.8; P < .001) or stereotactic body radiation therapy boost (RI, 7.1; CI, 3.4-14.8; P < .001), and high dose rate brachytherapy alone (RI, 16.3; CI, 7.2-36.9; P < .001) compared with unexposed time. The number needed to harm to result in an ED visit was less for RP (17; CI, 13-23) than RT overall (43; CI, 25-126), but varied by RT modality.ConclusionsIn summary, relative rates of ED visits vary by treatment type, suggesting differing severities of side effects. These data may aid in selecting treatments and demonstrate the feasibility of using the self-controlled case series study design on ED visits in real-world, structured EHR data to better understand side effects of treatment.     

Effects of Tai Chi exercise on cardiovascular disease risk factors and quality of life in adults with essential hypertension: A meta-analysis

BackgroundHypertension is the major attributable risk factor for cardiovascular disease. The effect of Tai Chi on essential hypertension (EH) is contentious.ObjectivesIn this study, we investigated the effects of Tai Chi on the risk factors for cardiovascular disease and quality of life in adults with EH.MethodsUsing data collected from 15 databases up to December 2018, we meta-analyzed randomized controlled trials of the effect of Tai Chi on EH.ResultsTai Chi exercise was associated with lower systolic blood pressure (SBP) (WMD −12.47, 95%CI −16.00 to −8.94, P < 0.001) and diastolic blood pressure (DBP) (WMD −6.46, 95%CI −8.28 to −4.64, P < 0.001); better quality of life (SMD 0.62, 95% CI 0.35 to 0.90, P < 0.001); lower lipid profiles, including total cholesterol (WMD −0.49, 95% CI −0.62 to −0.37, P < 0.001), triglycerides (WMD −0.49, 95% CI −0.92 to −0.07, P = 0.02), and low-density lipoprotein-cholesterol (LDL-C) (WMD −0.86, 95% CI −1.30 to −0.43, P < 0.001); and lower blood glucose (WMD −0.91, 95% CI −1.59 to −0.23, P = 0.009). Tai Chi had no significant effect on high-density lipoprotein–cholesterol (WMD −0.92, 95% CI −2.21 to −0.37, P = 0.16).ConclusionsTai Chi lowers blood pressure, total cholesterol, triglycerides, LDL-C, and blood glucose and significantly increases the quality of life in adults with EH. There is strong evidence for the short-term efficacy of Tai Chi exercises. Larger well-designed RCTs focused on the long-term effect of Tai Chi exercises and patient adherence are needed.     

Prognostic factor analysis of irreversible electroporation for locally advanced pancreatic cancer – A multi-institutional clinical study in Asia

IntroductionIrreversible electroporation (IRE) is a modality that utilizes high electric voltage to cause cell apoptosis. IRE has been used to treat locally advanced pancreatic cancer (LAPC). However, studies of IRE via surgical approaches for LAPC are limited. This study aims to analyse the outcomes and related prognostic factors of IRE for Asian patients with LAPC.Materials and methodsFrom 2012 to 2017, this prospective trial for using IRE through surgical approaches for LAPC was conducted in 11 medical centres in Asia. All related and treatment outcomes were analysed from a prospective database.ResultsSeventy-four patients were enrolled. Thirty complications occurred in thirteen (17.6%) patients without mortality. The electrode placement direction (anteroposterior vs. craniocaudal, HR = 14.2, p < 0.01) and gastrointestinal invasion (HR = 15.7, p < 0.01) were significant factors for complications. The progression-free survival (PFS) rate in one year, three years, and five years were 69.1%, 48.7%, and 28.8%, and the overall survival (OS) rate in one year, three years, and five years were 97.2%, 53%, and 31.2%. In univariate analysis, the chemotherapy regimen, local tumour recurrence, axial tumour length, tumour volume, and serum carbohydrate antigen 19-9 levels were all significantly associated with PFS and OS. In multivariate analysis, the chemotherapy regimen was the only significant factor associated with PFS and OS. TS-1 (Tegafur, gimeracil, and oteracil) group has superior survival outcome than gemcitabine group.ConclusionThis study showed that combined induction chemotherapy and surgical IRE for LAPC is safe. For well-selected patients, IRE can achieve encouraging survival outcomes.     

头颈部鳞癌患者HPV DNA、E6/E7 mRNA的分布及其在预后中的作用

摘 要：［目的］ 检测头颈部鳞癌组织标本人乳头瘤病毒(HPV)DNA、E6/E7 mRNA感染情况,并分析HPV感染对预后的影响。［方法］ 收集2016—2018年头颈部鳞癌手术标本121例,采用MassARRAY?誖HPV基因分型技术和RT-qPCR方法分别进行HPV DNA和HPV E6/E7 mRNA检测,比较不同肿瘤部位检出率差异。采用多因素Cox比例风险回归模型分析HPV E6/E7 mRNA对头颈部鳞癌预后的影响,计算HR值及其95%可信区间。［结果］ 121例头颈部鳞癌患者HPV阳性率为66.94%（81/121）,其中口腔癌阳性率为70.37%（19/27）,喉癌为65.79%（50/76）,口咽癌为66.67%（12/18）,HPV DNA阳性率在不同肿瘤部位无统计学差异（P>0.05）。HPV16阳性率为4.13%（5/121）,HPV18阳性率为6.61%（8/121）。头颈部鳞癌HPV E6/E7 mRNA阳性率为28.93%（35/121）,HPV E6/E7 mRNA阳性率在不同肿瘤部位中无统计学差异（P>0.05）。多因素分析结果显示,与HPV E6/E7 mRNA阴性组相比,HPV E6/E7 mRNA阳性组预后较好（HR=0.13,95%CI：0.04~0.46）。［结论］ 头颈部鳞癌患者HPV DNA阳性率高,但HPV E6/E7 mRNA阳性率明显降低。HPV感染为头颈部鳞癌独立的预后因素。     

温肾散结法联合西药治疗乳腺癌骨转移疼痛临床研究

目的：观察温肾散结法联合化疗、双磷酸盐治疗乳腺癌骨转移疼痛的效果。方法：31例乳腺癌骨转移伴有疼痛患者按随机数字表法分成对照组和治疗组。对照组应用双磷酸盐和化疗,治疗组在对照组的基础上加用温肾散结方药,对照组仅用唑来膦酸和TP方案化疗。治疗2周期进行疗效评价。结果：治疗组镇痛效果、生活质量评分及体质量增加稳定率优于对照组（P〈0.05）。治疗组治疗后外周血WBC、Hb、PLT稍降低（P〉0.05）,对照组治疗后上述指标明显下降（P〈0.05）。结论：温肾散结方药联合化疗、双磷酸盐治疗乳腺癌骨转移疼痛止痛效果良好,可以改善患者生活质量,减轻化疗的毒副作用。     

COMPASS三维验证系统在食管癌容积旋转调强放疗中的应用

目的 探讨COMPASS三维验证系统在食管癌容积旋转调强剂量验证中的可行性。方法 选取37例食管癌初治患者在Oncentra计划系统上进行容积旋转调强（VMAT）计划设计,然后将治疗计划传送至COMPASS验证系统和加速器上。比较计划系统中的计算结果和COMPASS验证系统中实际测量结果之间的差异。分析靶区的平均剂量（Dmean）、95%体积受照射的剂量（D95）和γ值,危及器官比较双肺V20、V30剂量值。结果 计算结果和测量结果在靶区上的γ通过率均>92%,靶区D95的平均值偏差<3%,Dmean标准偏差平均值<1%。测量结果与计划结果中双肺V20、V30分别为（19.86±2.18）%、（20.03±2.21）%和（12.35±2.61）%、12.40±2.52）%,明显看出测量的结果V20、V30比计算结果小。结论 COMPASS三维验证系统能准确快速的分析出结果,保证食管癌治疗的安全。