《新英格兰医学杂志》英文音频和中文摘要

1

                                              

循环肿瘤DNA分析结果指导Ⅱ期结肠癌的辅助治疗

Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer
摘 要

背景

辅助化疗对Ⅱ期结肠癌的作用仍有争议。手术后存在循环肿瘤DNA(ctDNA)预示着无复发生存率很低,而不存在ctDNA则预示着复发风险低。对ctDNA阳性患者采取辅助化疗的获益尚未明确。
Background
The role of adjuvant chemotherapy in stage II colon cancer continues to be debated. The presence of circulating tumor DNA (ctDNA) after surgery predicts very poor recurrence-free survival, whereas its absence predicts a low risk of recurrence. The benefit of adjuvant chemotherapy for ctDNA-positive patients is not well understood.

方法

我们开展了一项试验,旨在评估ctDNA指导的治疗方法可否减少辅助化疗的使用,同时不增加复发风险。Ⅱ期结肠癌患者以2:1的比例被随机分组,两组分别根据ctDNA结果或标准临床病理特征指导治疗决策。在ctDNA指导的治疗组中,如果手术后4或7周时ctDNA结果呈阳性,则采用基于奥沙利铂或氟嘧啶的化疗。ctDNA阴性患者不接受治疗。主要疗效终点是2年无复发生存率。一项关键次要终点是辅助化疗的使用。

Methods
We conducted a trial to assess whether a ctDNA-guided approach could reduce the use of adjuvant chemotherapy without compromising recurrence risk. Patients with stage II colon cancer were randomly assigned in a 2:1 ratio to have treatment decisions guided by either ctDNA results or standard clinicopathological features. For ctDNA-guided management, a ctDNA-positive result at 4 or 7 weeks after surgery prompted oxaliplatin-based or fluoropyrimidine chemotherapy. Patients who were ctDNA-negative were not treated. The primary efficacy end point was recurrence-free survival at 2 years. A key secondary end point was adjuvant chemotherapy use.

结果

在接受随机分组的455例患者中,302例被分配至ctDNA指导的治疗组,153例被分配至标准治疗组。中位随访期为37个月。ctDNA指导组接受辅助化疗的患者比例低于标准治疗组(15% vs. 28%;相对危险度,1.82;95%置信区间[CI],1.25~2.65)。在2年无复发生存率的评估中,ctDNA指导的治疗不劣于标准治疗(分别为93.5%和92.4%;绝对差,1.1个百分点;95% CI,-4.1~6.2[非劣效性界值,-8.5个百分点])。3年无复发生存率如下:接受辅助化疗的ctDNA阳性患者为86.4%,而未接受辅助化疗的ctDNA阴性患者为92.5%。

Result

Of the 455 patients who underwent randomization, 302 were assigned to ctDNA-guided management and 153 to standard management. The median follow-up was 37 months. A lower percentage of patients in the ctDNA-guided group than in the standard-management group received adjuvant chemotherapy (15% vs. 28%; relative risk, 1.82; 95% confidence interval [CI], 1.25 to 2.65). In the evaluation of 2-year recurrence-free survival, ctDNA-guided management was noninferior to standard management (93.5% and 92.4%, respectively; absolute difference, 1.1 percentage points; 95% CI, −4.1 to 6.2 [noninferiority margin, −8.5 percentage points]). Three-year recurrence-free survival was 86.4% among ctDNA-positive patients who received adjuvant chemotherapy and 92.5% among ctDNA-negative patients who did not.

结论

ctDNA指导的Ⅱ期结肠癌治疗减少了辅助化疗的使用,同时未降低无复发生存率。(由澳大利亚国家健康和医学研究委员会[Australian National Health and Medical Research Council]等资助;DYNAMIC在澳大利亚和新西兰临床试验注册系统[Australian New Zealand Clinical Trials Registry]注册号为ACTRN12615000381583。)

Conclusions

A ctDNA-guided approach to the treatment of stage II colon cancer reduced adjuvant chemotherapy use without compromising recurrence-free survival. (Supported by the Australian National Health and Medical Research Council and others; DYNAMIC Australian New Zealand Clinical Trials Registry number, ACTRN12615000381583.)

Jeanne Tie, Joshua D. Cohen, Kamel Lahouel, Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer. DOI: 10.1056/NEJMoa2200075

2


 

通过治疗肛门高级别鳞状上皮内病变预防肛门癌

Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer

摘 要

背景

人类免疫缺陷病毒(HIV)感染者的肛门癌发病率明显高于一般人群。与宫颈癌类似,肛门癌发生之前也有高级别鳞状上皮内病变(HSIL)。治疗宫颈HSIL可减少向宫颈癌的进展;然而,关于可否通过治疗肛门HSIL来预防肛门癌,目前缺乏前瞻性研究数据。

Background
The incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking.

方法
我们在美国25个研究中心开展了3期试验。年龄≥35岁,活检证实肛门HSIL的HIV感染者被随机分组(1:1),两组分别接受HSIL治疗和主动监测(不接受治疗)。治疗方式包括在诊室实施的消融术,麻醉下的消融术或切除术,或者氟尿嘧啶或咪喹莫特局部给药。主要结局是进展为肛门癌(采用至事件发生时间分析)。治疗组参与者接受的治疗持续至HSIL完全消退。所有参与者均至少每6个月接受一次高分辨率肛门镜检查;此外还对治疗组持续存在的疑似HSIL进行活检,每年对主动监测组进行活检,以及在担心发生癌症时进行活检。
Methods

We conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer.

结果

在接受随机分组的4459名参与者中,4446名(99.7%)被纳入至进展为癌症的时间分析。中位随访时间为25.8个月,治疗组诊断出9例病例(每100,000人-年173例;95%置信区间[CI],90~332),主动监测组诊断出21例(每100,000人-年402例;95% CI,262~616)。治疗组进展为肛门癌的发生率比主动监测组低57%(95% CI,6~80;时序检验P=0.03)。

Result

Of 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P=0.03 by log-rank test).

结论

在活检证实肛门HSIL的参与者中,与主动监测相比,治疗肛门HSIL显著降低了肛门癌风险。(由美国国立癌症研究所[National Cancer Institute]资助;在ClinicalTrials.gov注册号为NCT02135419。)

Conclusions

Among participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.)

Joel M. Palefsky, Jeannette Y. Lee, Naomi Jay, Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer. DOI: 10.1056/NEJMoa2201048

3


 

2019年查帕雷出血热与玻利维亚啮齿动物中的病毒检测

Chapare Hemorrhagic Fever and Virus Detection in Rodents in Bolivia in 2019

摘 要

背景

2019年6月,玻利维亚卫生部(Bolivian Ministry of Health)报道了一组出血热病例,这些病例始于卡拉纳维市(Caranavi),扩散至拉巴斯市(La Paz)。病例的病因不明。
Background
In June 2019, the Bolivian Ministry of Health reported a cluster of cases of hemorrhagic fever that started in the municipality of Caranavi and expanded to La Paz. The cause of these cases was unknown.

方法
我们采集样本并进行二代测序和病毒分离。应用病毒特异性实时定量逆转录酶聚合酶链反应检测法、二代测序和病毒分离法对人和啮齿类动物样本进行了检测。
Methods
We obtained samples for next-generation sequencing and virus isolation. Human and rodent specimens were tested by means of virus-specific real-time quantitative reverse-transcriptase–polymerase-chain-reaction assays, next-generation sequencing, and virus isolation.

结果

我们发现了9例出血热,其中4例死亡。鉴定出病原体属于哺乳类沙粒病毒属(Mammarenavirus),具体为引起查帕雷出血热(CHHF)的查帕雷哺乳类沙粒病毒或称查帕雷病毒(CHAPV)。我们发现医护人员间可能发生了院内传播。一些CHHF患者有神经系统表现,存活患者的恢复期漫长。我们在人体多种体液(包括血液;尿液;鼻咽、口咽和支气管肺泡灌洗液;结膜;以及精液),以及在从捕获的小耳侏儒稻大鼠(small-eared pygmy rice rat)(小耳小啸鼠[Oligoryzomys microtis])采集的样本中检出CHAPV RNA。在存活的CHHF患者中,截至症状出现后170天仍可检出病毒RNA;在症状出现后86天采集的一份精液样本中分离出了CHAPV。

Result

Nine cases of hemorrhagic fever were identified; four of the patients with this illness died. The etiologic agent was identified as Mammarenavirus Chapare mammarenavirus, or Chapare virus (CHAPV), which causes Chapare hemorrhagic fever (CHHF). Probable nosocomial transmission among health care workers was identified. Some patients with CHHF had neurologic manifestations, and those who survived had a prolonged recovery period. CHAPV RNA was detected in a variety of human body fluids (including blood; urine; nasopharyngeal, oropharyngeal, and bronchoalveolar-lavage fluid; conjunctiva; and semen) and in specimens obtained from captured small-eared pygmy rice rats (Oligoryzomys microtis). In survivors of CHHF, viral RNA was detected up to 170 days after symptom onset; CHAPV was isolated from a semen sample obtained 86 days after symptom onset.

结论

我们鉴定出查帕雷哺乳类沙粒病毒是CHHF的病原体。研究发现该疾病发生了动物传人事件,并且可能发生了人际传播。我们在啮齿类动物小耳小啸鼠中检出该病毒。(由玻利维亚卫生部[Bolivian Ministry of Health]等资助。)

Conclusions

M. Chapare mammarenavirus was identified as the etiologic agent of CHHF. Both spillover from a zoonotic reservoir and possible person-to-person transmission were identified. This virus was detected in a rodent species, O. microtis. (Funded by the Bolivian Ministry of Health and others.)

Roxana Loayza Mafayle, Maria E. Morales-Betoulle, Carla Romero, Chapare Hemorrhagic Fever and Virus Detection in Rodents in Bolivia in 2019. DOI: 10.1056/NEJMoa2110339

4


 

干细胞-肾脏序贯移植治疗Schimke免疫-骨发育不良

Sequential Stem Cell–Kidney Transplantation in Schimke Immuno-osseous Dysplasia

摘 要
肾移植后的移植肾存活需要终生免疫抑制,但不能最终防止慢性排斥反应导致的移植肾丢失。我们开发了一种方法,试图消除三例同时患有T细胞免疫缺陷和肾衰竭的Schimke免疫-骨发育不良患者的免疫排斥和移植后免疫抑制的需要。每名患者都接受了来自相同供者的αβ T细胞耗竭和CD19 B细胞耗竭的单倍体造血干细胞移植和肾脏的序贯移植。在肾移植后22~34个月,患者实现了全供者造血嵌合和功能性的体外T细胞耐受,在没有接受免疫抑制治疗的情况下,肾功能持续正常。(由Kruzn for a Kure基金会资助。)
 
Lifelong immunosuppression is required for allograft survival after kidney transplantation but may not ultimately prevent allograft loss resulting from chronic rejection. We developed an approach that attempts to abrogate immune rejection and the need for post-transplantation immunosuppression in three patients with Schimke immuno-osseous dysplasia who had both T-cell immunodeficiency and renal failure. Each patient received sequential transplants of αβ T-cell–depleted and CD19 B-cell–depleted haploidentical hematopoietic stem cells and a kidney from the same donor. Full donor hematopoietic chimerism and functional ex vivo T-cell tolerance was achieved, and the patients continued to have normal renal function without immunosuppression at 22 to 34 months after kidney transplantation. (Funded by the Kruzn for a Kure Foundation.)
Alice Bertaina, Paul C. Grimm, Kenneth Weinberg, Sequential Stem Cell–Kidney Transplantation in Schimke Immuno-osseous Dysplasia. DOI: 10.1056/NEJMoa21170

原文始发于微信公众号(NEJM医学前沿):2022年6月16日 |《新英格兰医学杂志》英文音频和中文摘要

相关文章

发表回复

您的电子邮箱地址不会被公开。 必填项已用*标注