tbuckley/cabot-search huggingface dataset:
Efficacy of ear acupuncture on sleep quality in breast cancer survivors: A randomized controlled trial.
Authors: Melanie Désirée Hoextermann, Katja Buner, Heidemarie Haller, Wiebke Kohl, Mattea Reinisch, Gustav Dobos, Holger Cramer, Petra Voiss
Journal: Journal of Clinical Oncology (2020)

12066 Background: Among females, breast cancer is the most commonly diagnosed cancer worldwide. Sleep problems impair 40 to 70 % of breast cancer survivors. The aim of this randomized controlled trial was to evaluate the effect of ear acupuncture on sleep quality in breast cancer survivors. Methods: Fifty-two female breast cancer survivors (mean age 55.73 ± 8.10) were randomized to either 10 treatments of ear acupuncture within five weeks (N = 26) or to a single session of psycho-education and given an advice booklet concerning insomnia (N = 26). Both interventions were delivered in a group setting. Primary outcome was sleep quality (measured by the Pittsburgh Sleep Quality Index) at week 5 corrected for treatment expectancies. Secondary outcomes were inflammation parameters (interleukin-6) at week 5, sleep quality at week 17, and stress, anxiety, depressive symptoms, quality of life and fatigue 5 weeks and 17 weeks after randomization. Results: Intention-to-treat analysis showed a significantly stronger increase of sleep quality in the ear acupuncture group compared to the psycho-education group ( p= .031; d = 0.64) at week 5. Furthermore, ear acupuncture improved stress ( p= .030; d = 0.64), anxiety ( p = .001; d = 0.97), and fatigue ( p = .012; d = 0.75) at week 5 compared to psycho-education. No significant group difference was found on any outcome at week 17. No serious adverse events occurred during the study period. Conclusions: Group ear acupuncture may be a helpful intervention in tackling sleep problems in breast cancer survivors in the short term and may reduce stress, anxiety and fatigue as well. Long-term effects remain questionable. Clinical trial information: NCT03874598 .
Identification of predicted neoantigen vaccine candidates in follicular lymphoma patients.
Authors: Cody Ramirez, Felix Frenkel, Olga Plotnikova, Vladislav Belousov, Alexander Bagaev, Elena Ocheredko, Susanna Kiwala, Jasreet Hundal, Zach L Skidmore, Marcus Watkins, Michelle Becker-Hapak, Catrina Fronick, Robert Fulton, Robert Schreiber, Nancy L. Bartlett, Brad S. Kahl, Ravshan Ataullakhanov, Malachi Griffith, Obi Griffith, Todd A. Fehniger
Journal: Journal of Clinical Oncology (2020)

8054 Background: Follicular lymphoma (FL) is incurable with conventional therapies and poorly responsive to immune checkpoint blockade. There is a need for new therapies without long-term complications of chemotherapy and with curative potential. We hypothesize that FL contains tumor-specific mutant antigens (TSMAs) that can be targeted by the immune system by vaccination. Recent reports have highlighted the potential for unique immunoglobulin peptides to elicit immune response in lymphomas. We utilized whole exome sequencing (WES) and RNA sequencing (RNA-Seq) of FL patient samples to infer HLA genotype, and predict TSMAs with the goal of designing a personalized cancer vaccine, supported by recent reports of this approach in solid cancers. Methods: DNA and RNA from 58 patients’ FL biopsies underwent WES and RNA-Seq. pVACtools and MiXCR predicted potential somatic and B-cell clonotype neoantigens, which were filtered to identify high quality TSMAs. B-cell oligoclonality was determined by comparison to B-cell receptor (BCR) repertoire profiling of healthy individual lymph nodes. RNA-seq data allowed us to identify expressed TSMAs. Complementary in silico analysis based on mRNA-based peptide reconstruction and custom HLA affinity binding predictions were performed. Results: An average of 52 somatic mutations per patient (range: 2-172) were identified. At least one high quality TSMA was predicted for 57 of 58 patients. Five or more TSMA candidates were identified for 52 (90%) patients with a mean of 17 predicted peptides per patient (range: 0-45). 81% (813/1,004) of the total predicted TSMA peptides arose from missense mutations, 9% (94/1,004) from indels, and 10% (97/1,004) from BCR. 78% (45/58) of patients have both somatic and BCR vaccine candidates, while 21% (12/58) of patients had only somatic vaccine candidates. Predicted TSMAs were identified in multiple genes recurrently mutated in lymphoma (e.g., BCL2). There was a high prediction concordance with the orthogonal BostonGene Vaccine Module V1 pipeline. These pre-clinical results led to a first-in-human pilot trial of personalized TSMA vaccine combined with anti-PD-1 mAb for rel/ref FL patients (NCT03121677), with one response observed within 4 patients evaluable for response to date. Conclusions: TSMA peptides suitable for cancer vaccines were identified for most FL patients via next-generation sequencing, MiXCR and pVACtools. This pre-clinical study suggests that FL patients will be candidates for TSMA vaccine clinical trials and pilot clinical results provide proof of concept for this approach.
National estimates of mental health needs among non-elderly adult cancer survivors.
Authors: Xu Ji, Janet Cummings, Jordan Gilleland Marchak, Xuesong Han, Ann C. Mertens
Journal: Journal of Clinical Oncology (2020)

e19103 Background: As advancements in cancer therapies expand the population of long-term cancer survivors, it is important to understand long-term mental health (MH) outcomes associated with cancer experience. This study used a U.S. nationally-representative sample of adult cancer survivors to assess and compare MH outcomes across age groups. Methods: We used the 2015-2017 National Survey of Drug Use and Health to identify respondents aged 18-64 years who reported a history of cancer (survivors) or never had cancer. MH outcomes were operationalized as events in past year of: major depressive episodes, serious psychological distress, suicidal thoughts, suicidal plans, suicidal attempts, any mental illness, and serious mental illness. We compared these outcomes between survivors and those without cancer in adjusted regression analyses, controlling for respondents’ demographic (gender, race/ethnicity) and socioeconomic (health insurance, employment, education status, marital status) characteristics. All analyses were stratified by age group (18-34, 35-49, and 50-64 years). Results: When comparing 2,656 survivors and 112,952 adults without cancer within each age group, survivors had elevated prevalence of MH problems in in five of the seven domains of adverse MH measures. Among young adults (aged 18-34 years), survivors were more likely than their noncancer counterparts to experience major depressive episodes (18.1% versus 9.6%, p&lt; 0.001), serious psychological distress (34.2% versus 17.9, p&lt; 0.001), suicidal thoughts (10.5% versus 7.0%, p= 0.011), any mental illness (41.1% versus 23.3%, p&lt; 0.001), and serious mental illness (13.2% versus 5.9%, p&lt; 0.001) in the past year. These differences persisted in adjusted analyses ( p-values &lt; 0.01). While similar survivor-comparison differences were observed among older groups, the magnitude of these differences was smaller. When comparing MH outcomes across age groups among survivors, young adult survivors had the highest likelihood of experiencing MH problems across all seven domains of adverse MH measures ( p-values &lt; 0.05). Conclusions: This population-based study shows elevated prevalence of MH problems among adult cancer survivors, as compared to the general noncancer population. We also identified a clear age gradient in the prevalence of MH problems, with young adult survivors exhibiting the highest prevalence of adverse MH outcomes. Our findings highlight the importance of developing strategies to ensure early detection and screening of mental illness and improve access to MH treatment for cancer survivors.
核苷(酸)类抗病毒药物在慢性乙型肝炎中的合理应用
Authors: 段雪飞
Journal: BMJ (2012)

抗病毒治疗是慢性乙型肝炎最重要、最关键的治疗手段.核苷(酸)类药物是临床上应用较广的一类抗病毒药物,具有服用方便、安全性好、不良反应较少的优点,但也存在疗程较长、停药后易复发、长期用药产生耐药变异等不足,基层医生往往在抗病毒时机、治疗疗程以及耐药管理等方面存在误区.本文主要围绕上述常见误区,简要介绍核苷(酸)类抗病毒药物治疗的适应证、停药指征以及耐药监测管理等,指导基层医生合理用药、提高疗效。
Short-term adjuvant versus neoadjuvant hormone therapy in localized prostate cancer: A pooled individual patient analysis of two phase III trials.
Authors: Daniel Eidelberg Spratt, Shawn Malone, Soumyajit Roy, Scott Grimes, Libni Eapen, Scott Carlyle Morgan, Julia Malone, Julia Craig, Robert Timothy Dess, William Jackson, Matthew J Schipper, Jeff M. Michalski, W. Robert Lee, Thomas Michael Pisansky, Felix Y Feng, William U. Shipley, Howard M. Sandler, Mack Roach, Yilun Sun, Colleen Anne Lawton
Journal: Journal of Clinical Oncology (2020)

5584 Background: The timing of systemic therapy in relation to radiotherapy (RT) is important in most malignancies. In contrast, androgen deprivation therapy (ADT) has largely been investigated in relation to its duration rather than its sequencing with RT. Herein, we conduct the first combined individual patient analysis of two phase III randomized trials to determine the optimal timing of ADT with RT in localized prostate cancer (PCa). Methods: Individual patient data was obtained from the Malone et al trial (JCO 2019), which randomized patients to receive neoadjuvant/concurrent or concurrent/adjuvant ADT for 6 months with prostate only RT. This was combined with the prostate only RT arms of RTOG 9413 that randomized patients to 4 months of neoadjuvant/concurrent or adjuvant ADT. The neoadjuvant/concurrent arms of both trials were combined into the “neoadjuvant” group, and the concurrent/adjuvant (Malone) and adjuvant arm (RTOG 9413) were combined in the “adjuvant” group. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Cumulative incidence of distant metastasis (DM), PCa-specific mortality (PCSM) and biochemical failure (BF) were calculated using the Fine-Gray method with non-PCa deaths as competing events. Late genitourinary (GU) and gastrointestinal (GI) toxicity are also reported. Results: The median follow-up was 14.9 years (yrs) and 1065 patients were included (n=531 neoadjuvant, 534 adjuvant). Groups were well balanced for all baseline characteristics. Adjuvant ADT was superior to neoadjuvant ADT in terms of BF (15yr: 33% vs 43%, HR: 1.37 (95%CI: 1.12-1.68), p=0.002), DM (15yr: 12% vs 18%, HR: 1.40 (95%CI: 1.00-1.95), p=0.04), and PFS (15yr: 36% vs 29%, HR: 1.25 (95%CI: 1.07-1.47), p=0.01). Adjuvant ADT yielded lower PCSM (15yr: 15% vs 20%, HR: 1.29 (95%CI: 0.95-1.75), p=0.10), but did not reach statistical significance. This approached statistical significance in high risk PCa (HR 1.39 (95%CI 1.00-1.93), p=0.053). OS was not significantly different between arms (15yr: 39% vs 34%, HR: 1.11 (95%CI: 0.95-1.30), p=0.20). There was no significant difference in either late grade ≥3 GI (p=0.21) or GU (p=0.98) toxicity. Conclusions: We demonstrate for the first time that sequencing of ADT with RT significantly impacts long-term oncologic outcomes in localized PCa, favoring an adjuvant rather than neoadjuvant approach, without increasing late toxicity. This data has important implications to ongoing and future clinical trial design. Clinical trial information: NCT00769548 .
7T MRI for neurodegenerative dementias in vivo: a systematic review of the literature
Authors: McKiernan Elizabeth Frances, O'Brien John Tiernan, 周波
Journal: BMJ (2017)

7T磁共振的空间分辨率接近于可发现神经退行性疾病病理改变的水平，例如脑内淀粉样斑块以及皮层内和皮层下神经核团的改变。这一技术将为研究某些神经变性性痴呆带来新的信息，尽管同时我们也将面对伪影增加及不良反应增多等一系列的挑战。本文系统回顾了利用7T磁共振技术在活体研究阿尔茨海默病（AD）、路易小体痴呆、额颞叶痴呆以及亨廷顿病的文献，在纳入分析的19项研究中，15项是针对AD的（主要针对海马亚结构的改变），4项是针对亨廷顿病的。超高的分辨率可以发现很多在低场强磁共振上无法看到的改变，如在轻度认知损害人群中海马亚区的萎缩。得益于敏感度的大幅提升，磁敏感增强铁成像可以更好地观察淀粉样斑块和脑内微出血改变，例如对AD患者脑内的微出血病灶就比以往发现的要更多。涉及影像采集和扫描耐受性等一些理论上的困难在这些研究中并没有被作为问题来报告。相关研究的局限性包括样本量偏小、缺乏针对路易小体痴呆和额颞叶痴呆的研究以及缺乏纵向随访研究等。总的来说，在活体进行7T磁共振研究可能会帮助我们更好的理解疾病进程，同时也许会帮助我们发现新的生物标志物及治疗靶点。作者认为，在AD和亨廷顿病中的研究证据提示：其他神经变性性痴呆的研究未来也必将受益于超高分辨率成像技术的进步。
Epidemiology and outcomes of gastroparesis, as documented in general practice records, in the United Kingdom
Authors: Yizhou Ye, Baoguo Jiang, Sudhakar Manne, Peter L Moses, Cristina Almansa, Dimitri Bennett, Paul Dolin, Alexander C Ford
Journal: Gut (2020)

Objective To generate real-world evidence for the epidemiology of gastroparesis in the UK, we evaluated the prevalence, incidence, patient characteristics and outcomes of gastroparesis in the Clinical Practice Research Datalink (CPRD) database. Design This was a retrospective, cross-sectional study. Prevalence and incidence of gastroparesis were evaluated in the CPRD database, with linkage to Hospital Episodes Statistics Admitted Patient Care and Office for National Statistics mortality data. Prevalence and incidence were age and sex standardised to mid-2017 UK population estimates. Descriptive analyses of demographics, aetiologies, pharmacological therapies and mortality were conducted. Results Standardised prevalence of gastroparesis, as documented in general practice records, was 13.8 (95% CI 12.6 to 15.1) per 100 000 persons in 2016, and standardised incidence of gastroparesis rose from 1.5 (95% CI 1.1 to 1.8) per 100 000 person-years in 2004 to 1.9 (95% CI 1.4 to 2.3) per 100 000 person-years in 2016. The most common disease aetiologies were idiopathic (39.4%) and diabetic gastroparesis (37.5%), with a similar distribution of type 1 and type 2 diabetes among the 90% who had type of diabetes documented. Patients with diabetic gastroparesis had a significantly higher risk of mortality than those with idiopathic gastroparesis after diagnosis (adjusted HR 1.9, 95% CI 1.2 to 3.0). Of those with gastroparesis, 31.6% were not offered any recognised pharmacological therapy after diagnosis. Conclusion This is, to our knowledge, the first population-based study providing data on epidemiology and outcomes of gastroparesis in Europe. Further research is required to fully understand the factors influencing outcomes and survival of patients with gastroparesis.
Study on safe dose of ginseng based on literatures from Tang dynasty to Republic period
Authors: Shengjun Yin, Dexian Jia, Dan Chang, Jieying Liao, Wei Liu, Gang Zhang
Journal: BMJ (2019)

Objective
To study the safe dose of Ginseng (Radix et Rhizoma Ginseng) through analysis of literature from Tang dynasty (618 AD) to Republic period (1949 AD).


Methods
The selection strategy for literature and prescriptions was made to acquire the formulae in need. The authoritative prescription-books from Tang Dynasty to Republic period, or representative books of the renowned doctors who was good at using Ginseng in that period were chosen. From the books above mentioned, prescriptions with Ginseng to tranquilize mind were included, in which insomnia and/or dreaminess were recorded as symptoms or clinical applications. Prescriptions without definite dose or only with dose for children were excluded. All herbal names were standardized according to current TCM terms. Then the maximum, minimum, frequency and 80% confidence interval of dose were studied. The dose range of Ginseng in deferent dosage form was discussed according to above data.


Results
Fourteen classical TCM books were included, from which 85 formulae were studied. In the form of root slices decoction, the applied daily dose of Ginseng ranged from 3.73 g to 18.65 g, while in the formulae with symptom of dreaminess, the dose ranged from 7.46 g to 11.19g. In the form of root powder decoction, the single dose range was 0.07 g to 5.16 g, while in the formulae with symptom of dreaminess, the dose range was 1.03 g to 4.45 g. In the form of pill or powder, the single dose range was 0.68 g to 6.54 g, and 12% to 30% in total dose of the prescription.


Conclusion
For the root slices decoction, the favorable dose range of Ginseng is between 7 g and 11 g, but not more than 18.00 g per day. For the root power decoction, the favorable dose range is from 1 g to 4.00 g, and the maximum single dose is 5.00 g. For pill or powder form, the maximum dose is 6.00 g, taking 12% to 30% in total prescription.


Key words: 
Panax; Clinical safe dose; Data mining
ENGOT-EN6/NSGO-RUBY: A phase III, randomized, double-blind, multicenter study of dostarlimab + carboplatin-paclitaxel versus placebo + carboplatin-paclitaxel in recurrent or primary advanced endometrial cancer (EC).
Authors: Mansoor Raza Mirza, Robert L. Coleman, Lars Christian Hanker, Brian M. Slomovitz, Giorgio Valabrega, Ellie Im, Monica Walker, Wei Guo, Matthew A. Powell
Journal: Journal of Clinical Oncology (2020)

TPS6107 Background: Carboplatin-paclitaxel is considered standard systemic anticancer therapy for recurrent or advanced EC for which surgery and/or radiation are not curative. Dostarlimab (TSR-042) is an anti-programmed cell death (PD)-1 humanized monoclonal antibody that has demonstrated antitumor activity and an acceptable safety profile in patients (pts) with recurrent or advanced EC in the GARNET trial. The RUBY trial was designed to evaluate the efficacy and safety of dostarlimab in combination with carboplatin-paclitaxel in recurrent or primary advanced EC compared with carboplatin-paclitaxel alone. Methods: This is a global, randomized, double-blind, multicenter, placebo-controlled study. Eligible pts must have first recurrent or primary stage III or stage IV EC with a low potential for cure by radiation therapy or surgery alone or in combination. Pts with carcinosarcoma are eligible for enrollment. 470 pts will be enrolled from approximately 160 sites in the ENGOT countries, United States, and Canada. Stratification factors are microsatellite instability (MSI) status (MSI-high [MSI-H] or microsatellite stable [MSS]), prior external pelvic radiotherapy (yes or no), and disease status (recurrent, primary stage III, or primary stage IV). Pts will be randomized 1:1 to receive combination dostarlimab 500 mg or placebo + carboplatin AUC 5 + paclitaxel 175 mg/m 2 every 3 weeks for 6 cycles followed by dostarlimab 1000 mg or placebo monotherapy every 6 weeks for up to 3 years in the absence of progressive disease, death, unacceptable toxicity, or patient/physician decision to withdraw from the study. The primary endpoint is progression-free survival (PFS) as assessed by the investigator in the all-comers population and the MSI-H population per RECIST version 1.1. Secondary efficacy endpoints are PFS assessed by blinded independent central review per RECIST version 1.1, overall survival, objective response rate, duration of response, disease control rate, safety and tolerability, and patient-reported outcomes. Clinical trial information: NCT03981796.
Initial safety and tumor control results from a phase I prospective trial evaluating a novel alpha-emitting radionuclide for the treatment of locally advanced recurrent squamous cell carcinomas of the skin and head and neck.
Authors: Aron Popovtzer
Journal: Journal of Clinical Oncology (2020)

e18509 Background: The purpose of this study is to report on the feasibility and safety of Diffusing Alpha-emitters Radiation Therapy (DaRT), including interstitial implantation of a novel alpha-emitting brachytherapy source, to treat locally advanced and recurrent squamous cell carcinomas (SCC) of the skin and head and neck. Methods: This prospective, first-in-human Phase I multicenter study included 28 eligible patients with 31 lesions. The primary endpoint was the feasibility and safety of the DaRT treatment approach. The secondary endpoint was initial tumor response and local progression-free survival (PFS) outcomes. Eligibility criteria included biopsy-proven SCC of the skin and head neck with either recurrent or previously-treated disease with either surgery or prior external beam radiotherapy. Toxicity was evaluated according to the Common Terminology Criteria for Adverse Events (Version 4.03). Tumor response was assessed at follow-up (30-45 days following treatment) using the Response Evaluation Criteria in Solid Tumors (Version 1.1). Results: Acute toxicity events included mostly erythema and swelling at the implantation site followed by pain and mild skin ulceration. Pain and Grade 2 skin ulcerations resolved in most patients within 3-5 weeks. Complete response (CR) to the Ra-224 DaRT treatment was observed in 22 lesions (22/28; 78.6%); seven lesions (6/28; 21.4%) manifested a partial response ( &gt; 30% tumor reduction). Among the 22 lesions with a CR, 5 (22%) developed a subsequent local relapse at the site of DaRT implantation at a median of 4.9 months (range: 2.43-5.52 months). The one-year local PFS probability at the implanted site was 60% (95% Confidence Interval, CI: -28.61-81.35%) for complete responders. Overall survival (OS) at 12 months post-DaRT implantation was 75% (95% CI: 46.14-89.99%); among complete responders, OS was 93% (95% CI: 59.08-98.96%). Conclusions: Alpha-emitter brachytherapy using DaRT achieved significant tumor responses without Grade 3 or higher toxicities. Longer follow-up observations and larger studies are underway to validate these findings. Clinical trial information: NCT03015883 NCT03353077.
I-SABR phase II randomized study of nivolumab immunotherapy and stereotactic ablative radiotherapy in early stage NSCLC: Interim analysis adverse effects.
Authors: Joe Y. Chang, Steven H. Lin, Luyang Yao, Saumil Gandhi, Zhongxing X. Liao, Stephen G. Chun, Melenda Jeter, James William Welsh, Percy Lee, Mara Antonoff, Lei Feng, J. Jack Lee, John Heymach
Journal: Journal of Clinical Oncology (2020)

9035 Background: Stereotactic Ablative Radiotherapy (SABR) provides &gt; 95% local control and has become standard care of medically inoperable stage I NSCLC. However, cumulatively about 40% of patients develop recurrence in the regional lymph nodes, distant organs, or secondary lung cancer. Combined immunotherapy and SABR (I-SABR) may reduce these recurrences by stimulating stronger cancer specific immune response. Methods: This is an ongoing phase II randomized study (SABR vs. I-SABR) to evaluate the efficacy and toxicity of I-SABR in medically inoperable, early stage (T1-T3: &lt; 7 cm, including multi-primary tumors), isolated recurrence NSCLC without lymph node or distant metastasis. The primary objective is event-free survival (any recurrence and/or death). Secondary objectives include rates of ≥Grade 2 toxicity. 4-D CT image guided SABR (50 Gy in 4 fractions or 70 Gy in 10 fractions) was delivered to all patients. Patients randomized to I-SABR received additional concurrent Nivolumab (240 mg, every two weeks for total of 7 doses or 480 mg every four weeks for total of 4 doses). 140 patients are anticipated to enroll. We report here interim analysis of toxicity. Results: 92 patients (median age: 72, range: 57 to 90) were enrolled and randomized (47 to SABR; 45 to I-SABR). With median follow up of 14.5 months (range 2 to 28 months), there were no treatment-related grade 4/5 adverse events. For the I-SABR arm, there was one case of possible related grade 3 dyspnea, skin rash and 2 cases of probable grade 3 fatigue. There were possible/probable treatment related 2 cases of grade 2 pneumonitis, fatigue, pruritus and 1 case of grade 2 hyperthyroidism and arthralgia. No patients discontinued treatment due to adverse effects. For the SABR arm, there were possible treatment related 1 case of grade 2 fatigue and pneumonitis. All symptoms resolved with or without treatment. Conclusions: Combined Nivolumab immunotherapy and SABR (I-SABR) appear to be well-tolerated in this fragile patient population with no grade 4/5 toxicity. All toxicities were tolerable and resolved. The major barrier for patient enrollment and/or randomization is patient’s perception of potential toxicities and additional clinic visits. Continued enrollment and additional follow up are needed to validate these findings. Clinical trial information: NCT03110978.
Salvage Therapy with Sofosbuvir, Elbasvir, Grazoprevir and Ribavirin for Daa Non-Responders - High Efficacy in GT3 and GT1/4 HCV Infection
Authors: Tim Papaluca, Susanne Glasgow, Kate New, Anne Craigie, Lucy McDonald, Lisa Stothers, David Iser, Paul Desmond, Sally Bell, Barbara Demediuk, Kumar Visvanathan, Marno Ryan, Jessica Howell, Thai Hong, Catherine Croagh, Marie Sinclair, Peter W Angus, Niranjan Arachchi, Jacinta O'Keefe, Scott Bowden, Alexander Thompson
Journal: Hepatology (2018)