Brachytherapy: An emblematic example of extreme hypofractionated regimen

In order to provide more convenient irradiation regimens for patient comfort, radiation facility organization and health expenses, new hypofractionated protocols have been evaluated. Moderately (dose/fraction: 2.3 to 3 Gy), then ultra (dose/fraction: 5.2 to 6.1 Gy) hypofractionated irradiations were first validated. The current question is: is it possible to go forward using extreme hypofractionated regimens (EHR) based on 1 to 3 fractions. Different irradiation techniques are under investigation. However, brachytherapy remains the smartest way to deliver a high dose in a small volume. We report prospective and retrospective study results which evaluated EHR for breast and prostate brachytherapy. While oncological outcome and toxicity profile appear extremely encouraging for low-risk breast cancer after a 1 to 4 fractions (6.25 to 20 Gy/fraction), the use of a single fraction of 19 to 23 Gy appears debatable for prostate cancer. Brachytherapy represents an emblematic example of EHR but longer follow-up and more mature results are awaited in order to specify the right indications and refine the EQD2 calculation method including new biological and technical factors.     

Efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) created using covered stents of different diameters: A systematic review and meta-analysis

PurposeThe purpose of this study was to make a systematic review and meta-analysis to determine the stent diameter (8 mm vs. 10 mm) that conveys better safety and clinical efficacy for transjugular intrahepatic portosystemic shunt (TIPS).Materials and methodsFour databases were used to identify clinical trials published from inception until March 2020. Data were extracted to estimate and compare one-year and three-year overall survivals, hepatic encephalopathy, variceal rebleeding, and shunt dysfunction rates between patients with 8 mm covered stents and those with 10 mm covered stents.ResultsFive eligible studies were selected, which included 489 patients (316 men, 173 women). The 8 mm covered stent group had higher efficacy regarding one-year or three-year overall survival (odds ratio [OR], 2.88; P = 0.003) and (OR, 1.81; P = 0.04) and lower hepatic encephalopathy (OR, 0.69; P = 0.04) compared with 10 mm covered stent group. There were no significant differences in variceal rebleeding rate (OR 0.80; P = 0.67). However, shunt dysfunction was lower in 10 mm covered stent group (OR, 2.26; P = 0.003).ConclusionsOur results suggest that the use of 8 mm covered stents should be preferred to that of 10 mm covered stents for TIPS placement when portal pressure is frequently monitored.     

The clinical dilemma of JAK inhibitor failure in myelofibrosis: Predictive characteristics and outcomes

Two Janus-associated kinase inhibitors (JAKi) (initially ruxolitinib and, more recently, fedratinib) have been approved as treatment options for patients who have intermediate-risk and high-risk myelofibrosis (MF), with pivotal trials demonstrating improvements in spleen volume, disease symptoms, and quality of life. At the same time, however, clinical trial experiences with JAKi agents in MF have demonstrated a high frequency of discontinuations because of adverse events or progressive disease. In addition, overall survival benefits and clinical and molecular predictors of response have not been established in this population, for which the disease burden is high and treatment options are limited. Consistently poor outcomes have been documented after JAKi discontinuation, with survival durations after ruxolitinib ranging from 11 to 16 months across several studies. To address such a high unmet therapeutic need, various non-JAKi agents are being actively explored (in combination with ruxolitinib in first-line or salvage settings and/or as monotherapy in JAKi-pretreated patients) in phase 3 clinical trials, including pelabresib (a bromodomain and extraterminal domain inhibitor), navitoclax (a B-cell lymphoma 2/B-cell lymphoma 2-xL inhibitor), parsaclisib (a phosphoinositide 3-kinase inhibitor), navtemadlin (formerly KRT-232; a murine double-minute chromosome 2 inhibitor), and imetelstat (a telomerase inhibitor). The breadth of data expected from these trials will provide insight into the ability of non-JAKi treatments to modify the natural history of MF.     

The longitudinal associations between mental health indicators and digital media use and physical activity during adolescence: A latent class approach

IntroductionEvidence for the relationship between movement behaviors and mental health among adolescents is inconclusive. We aimed to identify profiles of digital media use (including related bedtime delay) and leisure-time physical activity (LTPA) in adolescence, and to examine whether preadolescent mental health predicted later behavior profiles.MethodsThis study included 1285 participants assessed at 11 years of age, and followed-up four years later. Participants completed the Self-Perception Profile for Children (SPPC), Center for Epidemiological Studies Depression Scale for Children (CES-DC) and Screen for Child Anxiety-Related Emotional Disorders (SCARED) at baseline, and reported digital media use (active and passive use, gaming, and related bedtime delays) and LTPA at follow-up. A latent class approach was employed to identify behavior profiles, membership of which was then predicted with mental health and covariates, including baseline digital media use and LTPA.ResultsWe identified four behavior profiles: 1) high digital media use/moderate LTPA (20% of adolescents; 78% boys), 2) moderate digital media use/high LTPA (31%; 28%), 3) high digital media use/high LTPA (26%; 15%), 4) high passive digital media use and gaming/low LTPA (23%; 89%). After adjusting for covariates, higher LTPA and better perception of athletic competence at baseline associated with higher odds of belonging to any other profile than to the unhealthiest profile (4) at follow-up. Symptoms of depression or anxiety did not associate with later behavior profiles.ConclusionsLTPA and related self-esteem seem to be stronger predictors of future digital media use and LTPA behavior during adolescence than mental health symptoms alone.     

Predicting Survival for Chimeric Antigen Receptor T-Cell Therapy: A Validation of Survival Models Using Follow-Up Data From ZUMA-1

ObjectivesSurvival extrapolation for chimeric antigen receptor T-cell therapies is challenging, owing to their unique mechanistic properties that translate to complex hazard functions. Axicabtagene ciloleucel is indicated for the treatment of relapse or refractory diffuse large B-cell lymphoma after 2 or more lines of therapy based on the ZUMA-1 trial. Four data snapshots are available, with minimum follow-up of 12, 24, 36, and 48 months. This analysis explores how survival extrapolations for axicabtagene ciloleucel using ZUMA-1 data can be validated and compared.MethodsThree different parametric modeling approaches were applied: standard parametric, spline-based, and cure-based models. Models were compared using a range of metrics, across the 4 data snapshot, including visual fit, plausibility of long-term estimates, statistical goodness of fit, inspection of hazard plots, point-estimate accuracy, and conditional survival estimates.ResultsStandard and spline-based parametric extrapolations were generally incapable of fitting the ZUMA-1 data well. Cure-based models provided the best fit based on the earliest data snapshot, with extrapolations remaining consistent as data matured. At 48 months, the maximum survival overestimate was 8.3% (Gompertz mixture-cure model) versus the maximum underestimate of 33.5% (Weibull standard parametric model).ConclusionsWhere a plateau in the survival curve is clinically plausible, cure-based models may be helpful in making accurate predictions based on immature data. The ability to reliably extrapolate from maturing data may reduce delays in patient access to potentially lifesaving treatments. Additional research is required to understand how models compare in broader contexts, including different treatments and therapeutic areas.     

北京市某社区15例恢复期精神疾病患者生存压力调查

目的 了解生活在社区的恢复期精神疾病患者在疾病康复过程中的生存压力。方法 2017年8月至2018年1月,选取北京市某社区15例恢复期精神疾病患者,通过半结构式访谈的方式收集资料,以Colaizzi 7步分析法分析资料。结果 得出4个主题:精神疾病症状和药物不良反应等引起的生理性压力;因疾病转归和日常生活角色冲突产生的精神心理性压力;社会歧视、缺乏工作机会和难以获取社会福利资源等带来的社会环境压力;贬低歧视和家庭亲属关系恶化导致的人际交往压力。结论 恢复期精神疾病患者重返家庭和社会后存在明显的生存压力,压力源包括疾病症状、社会歧视、人际关系等多个方面,因此,应注重消除精神疾病患者的自我歧视,完善社会支持与社会福利体系,增加个性化的社区精神康复活动,以减轻患者生存压力,促进其康复。     

DHS和PFNA固定治疗老年股骨粗隆间骨折的疗效

目的对比动力髋螺钉(dynamic hip screw,DHS)治疗和股骨近端抗旋髓内钉(proximal femoral nail anti-rotation,PFNA)固定治疗老年股骨粗隆间骨折疗效。方法纳入本院收治的45例采用PFNA固定治疗的老年股骨粗隆间骨折患者作为研究组,研究时间为2017年11月-2018年11月;回顾性分析2016年11月-2017年11月在我院采用DHS治疗的45例老年股骨粗隆间骨折患者的临床资料,作为对照组。记录两组的相关手术指标,观察手术并发症情况。结果研究组的手术时间和骨折愈合时间均短于对照组,术中出血量明显少于对照组,术后疼痛VAS评分均明显低于对照组(P<0.05)。对照组的并发症发生率高于研究组(P<0.05)。结论PFNA固定治疗比DHS治疗老年股骨粗隆间骨折更加安全有效,值得临床借鉴和应用。     

Abdominal lymph node recurrence from colorectal cancer: Resection should be considered as a curative treatment in patients with controlled disease

BackgroundLymph node recurrences (LNR) from colorectal cancer (CRC) still represent a therapeutic challenge, as standardized recommendations have yet to be established. The aim of this study was to analyze short- and long-term oncological outcomes following resection of LNR from CRC.MethodsAll patients with previously resected CRC who underwent histopathologically confirmed LNR resection in 3 tertiary referral centers between 2010 and 2017 were reviewed. Short- and long-term outcomes were analyzed, mainly recurrence-free and overall survival. Further recurrences following LNR resection were also analyzed.ResultsOverall, 18 patients were included. Primary CRC was left-sided in 16 (89%) patients, staged T3-4 in 15 (83%), N+ in 14 (78%) and presented with synchronous metastases in 8 (43%). Median time interval between primary CRC and LNR resections was 31 months. Performed lymphadenectomies were aortocaval (n = 10), pelvic (n = 7), in hepatic pedicle (n = 3) and mesenteric (n = 1). Four patients had associated liver metastases resection. Three (17%) presented with postoperative complications, of which one Clavien-Dindo 3. Fourteen (78%) patients presented with further recurrences after a mean delay of 9 months, with 36% of patients presenting with early (<6 months) recurrence. Five (36%) patients could undergo secondary recurrence resection and 3 (21%) patients radiotherapy. Median overall survival following LNR resection reached 44 months.ConclusionsCurrent results suggest that LNR resection is feasible and associated with improved survival, in selected patients. Longer time interval between primary CRC resection and LNR occurrence appeared to be a favorable prognostic factor whereas multisite recurrence appeared to be associated with impaired long-term survival.     

肝癌组织LncRNA TINCR表达水平对术后长期生存的影响

目的 探讨肝癌组织中LncRNA TINCR 表达水平对术后长期生存的影响。方法 回顾性分析2013 年4 月～2016 年2 月间在本院接受手术治疗的157 例肝细胞肝癌患者的临床资料。RT-PCR 法检测肝癌标本内LncRNA TINCR 表达水平，采用ROC 曲线和Kaplan-Meier 法分析LncRNA TINCR 表达水平对肝癌术后长期生存的影响。结果 肝癌组织LncRNA TINCR 表达水平对术后长期生存预测的曲线下面积（AUC）为0.812，特异度为73.77%，灵敏度为79.17%，最佳判读值为1.89（P＜0.0001）。根据ROC 曲线分析结果，将肝癌组织LncRNA TINCR 相对表达水平大于1.89 的93 例（59.24%）患者纳入高表达组，而肝癌组织LncRNA TINCR 相对表达水平小于或等于1.89的64 例（40.76%）患者纳入低表达组。Kaplan－Meier 法生存分析发现高表达组术后3 年内有76 例患者死亡，3 年总生存率为18.28%（17/93）；低表达组术后3 年内有20 例患者死亡，3 年总生存率为68.75%（44/64），低表达组3 年总生存率明显优于高表达组（P＜0.0001，两组间死亡风险比为3.7534，95%可信区间为2.5158～5.6000）。结论 肝癌组织LncRNA TINCR 表达水平与肝癌术后长期生存显著相关，LncRNA TINCR 表达水平升高则预示着预后不佳。