tbuckley/cabot-search huggingface dataset:
Opioid safety among high-risk cancer survivors.
Authors: Talya Salz, Akriti A. Mishra, Renee L. Gennarelli, Allison Lipitz-Snyderman, Denise Boudreau, Natalie Moryl, Kathryn Ries Tringale, Deborah Korenstein
Journal: Journal of Clinical Oncology (2020)

e19169 Background: To mitigate risks of opioid-related harms, ASCO’s pain management guidelines for cancer survivors recommend that opioids be used in conjunction with other pharmacologic and non-pharmacologic approaches. The guidelines also recommend caution when prescribing opioids and benzodiazepines concurrently. We evaluated these 2 metrics of safe prescribing as applied to chronic opioid therapy (COT) among older survivors of head and neck cancer (HNC) and lung cancer (LC), two growing populations with high pain burden and prevalent risk factors for opioid-related harms (e.g., opioid use during treatment, history of substance use, distress). Methods: Using SEER-Medicare, we identified opioid-naïve adults diagnosed 2008-2015 with HNC or LC. We restricted analyses to survivors with ≥1 COT episode (≥90 days) occurring ≥1 year after cancer diagnosis and ≤120 days prior to hospice entry or cancer-related death (survivorship period). We report 2 opioid safety metrics during the survivorship period: 1) the proportion of survivors with non-opioid pain management (≥1 dispensing for a non-opioid, non-benzodiazepine pain medication or ≥1 claim for pain management procedure) concurrent with the first 90 days of the first COT episode and 2) the proportion of survivors with 0 dispensings for benzodiazepines within the first 90 days of the first COT episode. Results: Among opioid-naïve HNC (N = 5,500) and LC (N = 21,090) patients, 306 HNC (5.6%) and 927 LC survivors (4.4%) received COT during follow-up. Median duration of first survivorship COT episode was 5.2 and 4.9 months for HNC and LC, respectively. 64% of HNC survivors received non-opioid pain management concurrent with their first COT episode; 55% received an analgesic and 24% underwent a procedure. 75% of LC survivors received non-opioid pain management concurrent with their first COT episode; 67% received an analgesic and 35% underwent a procedure. 79% of HNC and 81% of LC survivors did not receive benzodiazepines during the first COT episode. Conclusions: Among older survivors of LC and HNC, less than 6% receive COT. However, of those, one-half of HNC survivors and more than a third of LC survivors receive guideline-discordant care by using COT without other pain management strategies or while using benzodiazepines. To minimize opioid-related harms, efforts should focus on improving safe COT prescribing practices for survivors. [Table: see text]
Phase Ib dose escalation and cohort expansion study of the novel myeloid differentiating agent MTL-CEBPA in combination with sorafenib in patients with advanced hepatocellular carcinoma (HCC).
Authors: Debashis Sarker, Mikael Sodergren, Elizabeth Ruth Plummer, Bristi Basu, Tim Meyer, Kai-Wen Huang, T.R. Jeffry Evans, Duncan Spalding, Yuk Ting Ma, Daniel H. Palmer, Cheng Ean Chee, David James Pinato, Vikash Reebye, Daniel McVeigh, Nina Raulf, Jenni Vasara, Pinelopi Andrikakou, Robert Habib, David Blakey, Nagy A. Habib
Journal: Journal of Clinical Oncology (2020)

4601 Background: MTL-CEBPA is the first small activating RNA to enter clinical trials and upregulates C/EBPα, a master regulator of myeloid cell differentiation. We previously reported a favourable safety profile of MTL-CEBPA as a single agent in HCC (Sarker D et al, ASCO 2018). After discontinuation of MTL-CEBPA, 3 out of 5 patients (pts) treated with sorafenib off study had a complete response (CR) of 7-18 months duration; 2 pts of which demonstrated resolution of lung metastases for &gt; 1 year. Here we provide new data on pts prospectively treated with MTL-CEBPA + sorafenib. Methods: Primary objective was to assess safety and tolerability of MTL-CEBPA 90-130mg/m 2 QW or BIW in combination with sorafenib 400mg BD administered to HCC patients either concomitantly or sequentially, in cohorts either tyrosine kinase inhibitor (TKI) naive or resistant. Secondary objectives included preliminary assessment of activity by response rate (RECIST v1.1) and immune landscape analysis. Results: As at the cut off date of 1 Feb 2020, 12 pts have been treated with MTL-CEBPA co-administered with sorafenib and 14 pts with MTL-CEBPA followed by sorafenib (23M/3F, median age 65.5years, range 44-83, ECOG PS 0/1: 18/8). The most common treatment-related AEs (all grades/grade 3-4) in these groups include facial flushing (4/0), raised AST (4/2) raised ALT (2/1), fatigue (5/0), raised ALP (2/0), and anaemia (2/2), diarrhoea (3/0), rash (2/0) and anorexia (1/0). Of 14 evaluable pts in the TKI naive cohorts, 2 pts had CR, 3 pts had partial response and 7 had stable disease. 9/10 pts in the TKI resistant cohorts evaluable for efficacy had stable disease. Flow cytometry demonstrated statistically significant decreases in frequency of immature CD66 + CD10 − neutrophils and myeloid derived suppressor cells. IHC demonstrated significant reduction in M2 macrophages in tumour biopsies. Conclusions: MTL-CEBPA + sorafenib is well tolerated with an acceptable safety profile. This study has confirmed signals of objective response to the combination treatment in TKI naïve HCC patients with viral aetiology, warranting expanded development in these patients. Updated efficacy and safety data will be presented. Clinical trial information: NCT02716012. [Table: see text]
Updating the concept and clinical reasoning in diagnosis and treatment of dizziness
Authors: Yi Ju
Journal: BMJ (2020)

头晕/眩晕病因复杂，诊疗涉及多个学科。《头晕/眩晕基层诊疗指南（2019年）》依据近年来国内外头晕/眩晕疾病的最新诊疗指南、专家共识及临床进展编制，以帮助基层医生更新头晕/眩晕理念，澄清既往一些病因诊断及相关疾病认识方面的误区，形成规范的头晕/眩晕疾病的诊疗思维，拓展常见疾病的相关知识，以及适用于基层医疗机构头晕/眩晕诊断的问诊和查体方法，力求满足基层医生对头晕/眩晕疾病的初级诊疗需要，提高基层医生对头晕/眩晕疾病的诊疗水平。
The utility of blood-based molecular tools-the NETest-to monitor and evaluate the efficacy of PRRT in neuroendocrine tumors.
Authors: Lisa Bodei, Mark S. Kidd, Aviral Singh, Ignat A. Drozdov, Anna Malczewska, Richard P. Baum, Eric Krenning, Irvin Mark Modlin
Journal: Journal of Clinical Oncology (2020)

3568 Background: Peptide receptor radionuclide therapy (PRRT) is an effective therapy for metastatic/inoperable neuroendocrine tumors (NETs). Tools to predict and monitor the efficacy of therapy are important adjuncts in the radio-oncology armamentarium. Standard blood biomarkers are not effective by new molecular based assays such as the PRRT Predictive Quotient (PPQ) and NETest are effective as real-time predictors and monitors of therapy. We aimed to prospectively evaluate whether: 1) the NETest functioned as a surrogate biomarker for image-based per RECIST evaluation of PRRT efficacy; 2) there was a correlation between changes in NETest levels during therapy, PPQ prediction and treatment efficacy. Methods: Three independent 177 Lu-PRRT-treated GEP-NET and BPNEN cohorts (Rotterdam, Netherlands: n= 41; Bad-Berka, Germany: n= 44; Meldola, Italy: n= 72). Treatment response: RECIST1.1 [Responder (stable, partial/complete response) vs Non-Responder]. Blood sampling: pre-PRRT, prior to each cycle and 6 months (median) after completion of all cycles. PPQ (positive/negative) and NETest (0-100 score) by PCR. Stable&lt;40; progressive &gt; 40). CgA (ELISA) as comparator. Samples deidentified, measurement and analyses blinded. Kaplan-Meier survival and Mann-Whitney analyses. Results: 122 of 157 were evaluable. RECIST stabilization or response in 67%; 33% progressed. NETest significantly ( p&lt; 0.0001) decreased in RECIST-“responders” (-47±3%); in “non-responders” it elevated (+79±19%, p&lt; 0.0005). NETest monitoring accuracy 98% (119/122). Follow-up levels &gt; 40 (progressive) vs stable (&lt;40) significantly correlated with mPFS (not reached vs. 10 months; HR 0.04, 95%CI: 0.02-0.07). PPQ response prediction was accurate in 118 (97%); 99% accurate positive and 93% accurate negative prediction. NETest significantly ( p&lt; 0.0001) decreased in PPQ-predicted responders (-46±3%) and remained increased in PPQ-predicted non-responders (+75±19%). Follow-up NETest categories stable vs progressive significantly correlated with PPQ prediction and mPFS (not reached vs. 10 months; HR 0.06, 95%CI: 0.03-0.12). In comparison, the standard biomarker, CgA, failed to predict or correlate with response to PRRT ( p= NS). Conclusions: NETest accurately (98%) monitors PRRT response and is an effective surrogate marker for radiological response (image concordance 98%). A NETest decrease identified responders (99%) and correlated ( &gt; 97%) with the pretreatment PPQ response predictor.
牛角顶伤致会阴直肠贯通伤修补成功一例
Authors: 郭婉茹, 张蔚, 李兰玉, 张文婷, 钟亚娟, 周琦, 易跃雄
Journal: BMJ (2011)

患者女,63岁.因6 h前被牛角顶伤会阴部至撕裂伤,同时伴有大量出血及剧烈疼痛感,于2010年7月27日在当地医院简单压迫止血后立即转往本院.伤后未解大便,小便正常.体检:体温37.4℃,脉搏67次/min,血压122/67mm Hg(1 mm Hg=0.133 kPa),呼吸19次/min.神志清楚,一般情况好,皮肤黏膜无苍白.心肺未见明显异常.腹平软,下腹部见一约10 cm长纵行手术瘢痕,无明显压痛及反跳痛,肝脾肋下未及,双肾区无叩击痛,双下肢无浮肿.妇科检查:外阴后联合处一约6 cm长撕裂伤,会阴体仪残留小部分薄层筋膜;阴道后壁完整,轻度膨出,可见一小血肿,其下方一约3 cm深裂隙;肛门括约肌完全断裂,直肠前壁距肛门约6 cm处可见一约8 cm长的裂伤,黏膜外翻.入院诊断:会阴直肠贯通伤.遂于持续硬膜外麻醉下行急诊手术治疗。
Obstructive sleep apnea hyperpnoea syndrome and carotid artery arthrosclerosis
Authors: Ying Wang, Zhi-ling Zhang, Mei Yan
Journal: BMJ (2009)

Eighty-eight patients with obstructive sleep apnea hyperpnoea syndrome (OSHAS) were assigned to the mild (n =21 ), moderate (n =30), or severe group (n =37) according to apnea-hypopnea index( AHI ). Twenty-five healthy individuals were selected as normal controls. Color Doppler ultrasonography was used to measure the intimae-media thickness of the carotid coteries and the occurrence of sclerosis plagues. Our data found that increased severity of OSHAS led to the elevated intimae-media thickness of the carotid coteries and more sclerosis plagues, which suggests OSHAS may influence the development of the carotid artery arthrosclerosis.

Key words: 
Sleep apnea, obstructive;  Carotid artery diseases
Uncovering the immune-modulating role of anti-RANKL therapy for cervical cancer: Preliminary results.
Authors: Peter Van Dam, Yannick Verhoeven, Jorrit De Waele, Julie Jacobs, Pieter-Jan Van Dam, Mark Kockx, Koen Van de Vijver, Martin Lammens, An Wouters, Evelien Smits, Filip Lardon, Xuan Bich Trinh
Journal: Journal of Clinical Oncology (2020)

e18028 Background: Conventional treatments for cervical cancer (CC) have reached a plateau and only limited progress for targeted therapy has been made over the last decades, resulting in a meager five-year survival rate of only 17% for the advanced stages. To improve long-term benefits for the patient, a promising hot field of research in oncology that opens new perspectives is immunotherapy. Even though CC has shown to be immunogenic, only a minority of patients respond to this type of treatment. In recent years, the RANKL/RANK signaling pathway has been implicated as a key immune modulating factor in the tumor microenvironment, allowing the cancer cells to evade the immune response by disrupting the immune-intrinsic crosstalk. Both RANKL and RANK are highly co-expressed in CC, which correlates with inferior clinicopathological parameters and an increased risk of death. Targeting this pathway may therefore be of great value in the treatment of CC and the quest to release the brakes on the immune system, thereby reinvigorating the tumors’ susceptibility to immunotherapy. Hence, we aim to elucidate the effects of anti-RANKL therapy on the tumor-immune microenvironment in CC. Methods: Two cervical biopsies were taken before and after anti-RANKL therapy in CC patients. One fresh biopsy was immediately processed to a single cell suspension for flow cytometry (FCM) using enzymatic digestion, while the other was formalin-fixed and paraffin-embedded for immunohistochemistry (IHC) and RNA sequencing. For FCM and IHC, the samples were stained with different markers for RANK/L signaling, the immune infiltrate and immune checkpoints. FCM was performed on a BD FACSAria IIä cytometer and analyzed with FlowJo. IHC staining was performed on a Ventana Benchmark Ultra and Ventana Discovery Ultra and scored by a pathologist or by HistoScientist using Visiopharm, while RNA sequencing was performed with the Truseq RNA exome panel on the NextSeq 500 system. Results: Our preliminary results show a relative increase of the CD8+ population, while a trend is observed in increased lymphocyte activation after anti-RANKL therapy. Updated results will be presented in more detail at the conference, including RNA sequencing data. Conclusions: Preliminary findings indicate that anti-RANKL therapy modifies the tumor-immune microenvironment in CC. Higher patient accrual will allow to dissect targets for combination therapy with anti-RANKL to further optimize this treatment strategy.
Immunomodulation by HDAC inhibition: Results from a phase I study with entinostat in combination with atezolizumab and bevacizumab in metastatic renal cell carcinoma patients.
Authors: Roberto Pili, Nabil Adra, Nur Damayanti, Theodore F. Logan, Vivek Narayan, Paul Monk, S Dropcho, Lina M Sego, Hao Liu, Sandra K. Althouse, Naomi B. Haas
Journal: Journal of Clinical Oncology (2020)

5064 Background: Immunosuppressive regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) limit the efficacy of immunotherapies. We have previously reported that the HDAC inhibitor entinostat has synergistic antitumor effect in combination with immunotherapies in preclinical models by inhibiting Tregs and MDSCs function. The combination of atezolizumab (PD-L1 inhibitor) and bevacizumab (VEGF inhibitor) is active in renal cell carcinoma (RCC). Thus, we have conducted a Phase I study with entinostat, atezolizumab and bevacizumab in patients (pts) with metastatic RCC. Methods: The primary objective was to evaluate safety and tolerability. The phase I portion included 3 dose levels of entinostat (1 mg, 3 mg or 5 mg, PO weekly) and fixed, standard doses of atezolizumab (1200 mg IV every 21 days) and bevacizumab (15 mg/Kg IV every 21 days). Pts with any histological type and prior therapies were included. Results: Dose levels were completed with up to 1 DLT/dose level. 5 mg was the Phase II recommended dose for entinostat. DLTs included hypertension, encephalopathy, hyponatremia and pruritus. The most common resolved grade 3/4 toxicities were hypophosphatemia (33%), hypertension (17%), and pneumonitis (11%). We have enrolled 18 pts (17 evaluable for ORR by RECIST). 5 pts continue on treatment. 3 pts discontinued treatment because of adverse events, 9 pts for disease progression, and one pt for physician decision. Good risk and intermediate risk pts were 61% and 39%, respectively. Overall ORR was 47.1% (95% CI 23.0-72.2) and median PFS was 7.6 months (95% CI 1.6-16.3). In pts with no prior therapies (12) the ORR was 58.3% (95% CI 27.7-84.8) and median PFS was 13.4 months (95% CI 1.5-28.9). One additional PR was observed by ir-RC but was not confirmed within the data cut-off date of 11/11/19. In pts with prior immune checkpoint inhibitors (ICIs) (5) ORR was 20% (95% CI 0.5-71.6) and median PFS was 7.6 months (95% CI 1.3-NR). Preliminary data show a statistically significant lower % of circulating monocytic MDSC (HLADR − 1CD11b + CD33 high CD14 + CD15 − ) and exhausted T cells (CD45 + CD3 + CD8 + TIM3 + ) following treatment in pts (4) with objective responses as compared to pts (4) with progressive disease. Conclusions: The results from this phase I suggest that the combination of entinostat, atezolizumab and bevacizumab is relatively well tolerated and is active in renal cell carcinoma patients, in both ICIs naïve and resistant disease. A phase II portion of this study is currently accruing patients. Clinical trial information: NCT03024437 .
Recurrence score (RS) differences between primary and second-primary breast cancer (BC): Exploratory analysis of the Clalit Health Services (CHS) registry.
Authors: Shlomit Shachar, Shulamith Rizel, Georgeta Fried, Michelle Leviov, Rinat Yerushalmi, Noa Ben-Baruch, Margarita Tokar, Lior Soussan-Gutman, Addie Dvir, Avital Bareket-Samish, Tamar Yablonski-Peretz, Amir Sonnenblick, Bella Kaufman, Ariel Hammerman, Nicky Liebermann, Salomon M. Stemmer
Journal: Journal of Clinical Oncology (2020)

e12587 Background: In the phase 3 TAILORx study, the first invasive disease-free survival event (in all arms) was often opposite BC or other second primary cancer. Our goal was to investigate differences in the 21-gene RS results between the primary BC and a second primary BC, as well as the association with clinicopathological characteristics. Methods: This analysis of the prospectively-designed CHS registry included all CHS pts with estrogen receptor (ER)+ HER2-negative BC who underwent RS testing between 1/2006 and 6/2019 and for whom ≥2 RS results were identified which were &gt; 1 year apart. Results: Of the 10,244 RS assays ordered in this time frame, 371 involved pts for whom the assay was performed at least twice. Our analysis focused on the 42 pts for whom the assays were performed &gt; 1 year apart. All pts were females; 76% were initially diagnosed with node-negative BC; median (interquartile range [IQR]) age at first diagnosis was 56 (43-64) yrs. Tumor characteristics for the first and subsequent primary BC are presented (Table). The median time (IQR) between the first and latest RS assay was 4.5 (2.9-6.4) yrs. In 28 pts (67%), the latest primary BC was ipsilateral and in 14 (33%) it was contralateral. The median (IQR) difference between the first and latest RS value was 7 (1-12). The second/third primary BC had higher RS than the first BC in the majority (76%) of pts. Higher RS in the latest primary BC (compared to the first primary BC) was more common when the latest primary BC was ipsilateral than when it was contralateral (86% vs 57%, P= 0.04). Conclusions: In ER+ HER2-negative BC pts, second/third primary BC is generally associated with higher RS result (compared to the first primary BC), particularly if the later primary BC is ipsilateral. [Table: see text]
儿童肺炎肺不张的治疗
Authors: 吴明昌
Journal: BMJ (2009)

肺炎是儿童的常见病,炎症产生的黏液、渗出物可阻塞小气道引起肺不张.多数情况下随肺炎治愈,肺不张也会消失.但有的肺不张会持续存在,导致反复继发感染,甚至发展为支气管扩张等永久性损害.因此,肺炎合并肺不张时,应重视其治疗.现举3例如下. 一位4岁患儿,女,因发热、咳喘2天就诊,听诊肺部有湿啰音,右上肺为主,诊断肺炎,治疗1周好转.5个月后又患肺炎,部位同前.其母称其自2岁半患肺炎后,已反复多次发生肺炎.查阅既往住院病历,胸片有肺炎合并肺不张,与本次胸片比较,肺不张是同一部位,乃嘱作支气管镜检查.经镜检取出黏液栓塞后,肺不张消失,此后未再患肺炎。
Cardiovascular Health in American Indians and Alaska Natives: A Scientific Statement From the American Heart Association
Authors: Khadijah Breathett, Mario Sims, Marie Gross, Elizabeth A. Jackson, Emily J. Jones, Ana Navas-Acien, Herman Taylor, Kevin L. Thomas, Barbara V. Howard
Journal: Circulation (2020)

Background: Cardiovascular disease (CVD) is the leading cause of death among American Indians and Alaska Natives. Over the past 50 years, the prevalence of CVD has been rising among American Indians and Alaska Natives. The objective of this statement is to summarize population-level risk factors and management techniques tailored for the American Indian and Alaska Native populations. Methods: PubMed/MEDLINE, the Centers for Disease Control and Prevention, and the annual Heart Disease and Stroke Statistics report from the American Heart Association were used to identify risk factors and interventions specific to American Indians and Alaska Natives. Results: Diabetes mellitus is a major contributor to disproportionately higher rates of coronary heart disease among American Indians and Alaska Natives compared with other racial and ethnic groups. Additional risk factors for CVD include low-density lipoprotein cholesterol levels, hypertension, renal disease, age, and sex. Smoking and exposure to toxic metals are risk factors for some subpopulations. A quarter of American Indians live below the federal poverty line, and thus, low socioeconomic status is an important social determinant of cardiovascular health. Community-based interventions have reduced CVD risk in American Indians and Alaska Natives. Underreporting of American Indian and Alaska Native race could underestimate the extent of CVD in this population. Conclusions: Prevention and treatment of CVD in American Indians and Alaska Natives should focus on control of risk factors and community-based interventions that address social determinants of health, particularly among individuals with diabetes mellitus. Accurate reporting of race/ethnicity is encouraged to address race-specific risk factors.
临床上主要的鼓膜检查方法
Authors: 刘博
Journal: BMJ (2012)

为方便鼓膜检查,受检查者应侧对检查者,并通过以下几种方式将外耳道变成一条直线,在充足的光源下进行观察.一、徒手检查法1.双手检查法:检查者应一手将耳廓向后、上、外方轻轻牵拉,使外耳道变直,另外一只手的手食指将耳屏向前推压,使外耳道口扩大,以便看清外耳道及鼓膜.由于婴幼儿外耳道的方向为向内、向前、向下,因此在检查鼓膜时应将耳廓向下拉,同时将耳屏向前方牵引,方能使外耳道变直.2.单手检查法:检查者以左手牵拉耳廓,右手进行操作如拭洗脓液,钳取耵聍、异物等.检查左耳时,左手从耳廓下方以拇指和中指夹持耳廓并向后、上外方牵拉.同时以食指推压耳屏向前,检查右耳时,左手则从耳廓上方以拇指和中指牵拉耳廓,食指推压耳屏。
激素疗法的临床共识和用药原则
Authors: 孙爱军
Journal: BMJ (2004)

在妇女健康倡议研究(WHI)[1]与百万妇女研究(MWS)[2]结果发表后,中华医学会妇产科学分会绝经学组基于目前对激素疗法(hormone therapy,HT)研究现状制定了 [3](以下简称指南),以指导中国的医生正确实施HT,同时纠正因部分媒体理解偏倚造成限制HT应用的负面影响。
Quality of life of adults and children with TRK fusion cancer treated with larotrectinib compared to the general population.
Authors: Shivaani Kummar, Cornelis M. Van Tilburg, Catherine M. Albert, Jordan Berlin, Anna F. Farago, Raymond S. McDermott, Stefan S. Bielack, Francois P. Doz, Steven G. DuBois, Ulrik Niels Lassen, Serge Leyvraz, Leo Mascarenhas, Ramamoorthy Nagasubramanian, Karen N Keating, Costel Chirila, Barrett H. Childs, Theodore Willis Laetsch, Alexander E. Drilon, David S. Hong
Journal: Journal of Clinical Oncology (2020)

3614 Background: NTRK gene fusions occur in diverse tumor types in adults and children. The selective TRK inhibitor, larotrectinib, has shown high response rates, durable disease control, and a favorable safety profile in patients (pts) with TRK fusion cancer. We report an expanded quality of life (QoL) analysis for pts treated with larotrectinib. Methods: QoL data were collected in two trials of larotrectinib in pts with TRK fusion cancer using EORTC QLQ-C30 (adults) and PedsQL (children) questionnaires, and were analyzed descriptively and longitudinally. EORTC QLQ-C30 global health scores (GHS) and PedsQL total scores range from 0 to 100, with higher scores indicating better QoL. We calculated the proportion of pts with normal/above and below normal QoL scores compared to values in the literature for the US general population. Results: By July 2019, 126 pts with TRK fusion cancer (74 adults, 24 children ≥2 yrs, and 28 infants &lt;2 yrs) had received larotrectinib and completed baseline (BL) and ≥1 post-BL questionnaire. Most pts had clinically meaningful QoL improvements that reached or exceeded the minimally important difference (Table); a positive change from BL was also seen in infants: mean best change of 12.0 (SD 13.8). Of 52 adults with BL EORTC QLQ-C30 GHS at or above the population norm, 51 remained in this category on treatment and 1 moved into the below normal category. Of 22 adults with BL scores below the population norm, 20 moved into the normal/above normal category. All 9 children aged ≥2 yrs with BL PedsQL scores at or above the population norm remained in this category on treatment. Of 15 children with BL scores below the population norm, 10 moved into the normal/above normal category. Sustained QoL improvements (change from BL ≥0) occurred by 2 months of treatment in 69% of adults and 75% of children. Median duration of sustained improvement in EORTC QLQ-C30 GHS and PedsQL total score was 12.0 months (range 1.7–20.3) and not estimable (range 1.1–23.0), respectively. Conclusions: Adults and children with TRK fusion cancer treated with larotrectinib had rapid, clinically meaningful, and sustained improvements in QoL. Clinical trial information: NCT02576431, NCT02637687 . [Table: see text]