tbuckley/cabot-search huggingface dataset:
End-of-life care in the immune checkpoint inhibitor era.
Authors: Alyssa Buckenheimer, Andy Shipe Dothard, Gregory Russell, Carl Grey, William J. Petty, Thomas Lycan
Journal: Journal of Clinical Oncology (2020)

e24003 Background: Immune checkpoint inhibitors (ICI) can lead to durable responses in some patients with advanced non-small cell lung cancer (NSCLC) with less toxicity than chemotherapy. However, ICI can cause idiosyncratic adverse effects and radiographic responses can be difficult to interpret, making prognostication difficult and potentially impeding a timely transition to hospice. Our purpose was to explore end of life (EOL) outcomes in NSCLC patients treated with ICI. Methods: Retrospective data were collected on all patients with NSCLC started on ICI at single center (2014-2018) and who died before last known follow-up. EOL outcomes included hospitalizations, ICU admissions, timing/location of hospice referral and death. Charts were reviewed to identify barriers to hospice referrals or enrollment. Outcomes were compared to published data of similar cohort (2008-2010) from same institution treated with chemotherapy. Results: Out of 143 patients who died, 83 (58%) had internal hospice referral by cancer center; 15 (11%) were referred by external provider. Hospitalization frequency was associated with higher likelihood of internal hospice referral (p 0.04). Internal hospice referral was not associated with differences in age, sex, race, ethnicity, smoking history, cancer subtype, treatment response/toxicity, or overall survival. Internal hospice referral was associated with decreased rates of death on the hospital floor (p &lt; 0.001) and the intensive care unit (ICU, p &lt; 0.001). When compared to chemotherapy cohort, there was similar rate of hospice referral (68% vs. 74%, p 0.33) but higher rates of starting new systemic therapy within 30 days of death (17% vs. 6%, p 0.001) and last dose within 14 days of death (13% vs. 5%, p 0.005). Other EOL outcomes (hospitalization frequency, death in ICU) were similar, although ICI cohort trended towards a lower rate of death on the floor than chemotherapy cohort (16% vs. 25%, p 0.06). Barriers to hospice referral were not well documented by providers but lack of family support for home EOL care was a common reason patients declined hospice. Conclusions: ICI was associated with a higher rate of systemic treatment at EOL as compared to a historical chemotherapy cohort, although the rates of hospice referral and other outcomes were similar.
头痛的临床诊断
Authors: 于生元, 董钊
Journal: BMJ (2008)

头痛是神经内科门诊最常见的主诉之一.对不同的头痛进行正确的分类是采取适当治疗手段的前提条件.自1988年国际头痛协会制定第1版头痛分类标准以来,此标准已经成为头痛分类的世界性标准,在我国也得到了推广和应用,但不可否认其应用仍有差距,比如时至今日,相当一部分医生仍在使用神经性头痛、血管性头痛等分类诊断标准中根本不存在的诊断,因此,推广和介绍头痛的国际分类标准显得非常重要。
应高度重视乙型肝炎病毒母婴传递的阻断
Authors: 杨秉辉
Journal: BMJ (2008)

我国是乙型肝炎(乙肝)大国,自乙肝疫苗被列为儿童计划免疫项目并大力推广以来,情况已见转机.以前我国民众HBsAg携带率在10%～15%,但据中华医学会肝病学会与中华医学会传染病学会最近的报告已降至9.09%,是因为已接种乙肝疫苗的儿童,其HBsAg携带率已明显下降。
Phase II randomized trial of carboplatin + pemetrexed + bevacizumab, +/- atezolizumab in stage IV non-squamous non-small lung cancer (NSCLC) patients who harbor a sensitizing EGFR mutation or have never smoked.
Authors: Joseph Nicholas Bodor, Jyoti D. Patel, Eric A. Ross, Samuel Litwin, Margie Clapper, Benjamin Philip Levy, Heather A. Wakelee, Hossein Borghaei, Joseph Treat
Journal: Journal of Clinical Oncology (2020)

TPS9629 Background: Stage IV NSCLC patients who are never-smokers or with EGFR-mutated tumors generally do not benefit from single-agent immunotherapy. Retrospective subgroup analyses from recent phase III trials suggest that immunotherapy-chemotherapy +/- VEGF inhibition may overcome resistance to PD-L1 inhibitors in these patients, however prospective research on this is needed. This trial will examine a patient population with stage IV non-squamous disease who either have tumors that possess an EGFR exon 19 or 21 mutation or who are never-smoker wild-types, to determine whether the PD-L1 inhibitor atezolizumab in combination with pemetrexed, carboplatin, and bevacizumab can improve outcomes. Methods: This is a randomized, phase II, multi-center, open-label trial to assess pemetrexed/carboplatin and bevacizumab +/- atezolizumab in 117 subjects with stage IV non-squamous NSCLC. Randomization will be 2:1 favoring the + atezolizumab arm. Patients are stratified by EGFR mutation status (i.e. EGFR exon 19 or 21 vs. never-smoker wild-type). Never-smoker wild-type is defined as smoking &lt; 100 cigarettes in a lifetime and without any EGFR mutation or ALK or ROS1 rearrangement. Patients with EGFR exon 19 or 21 mutated tumors must have progression of disease or intolerance of treatment with one or more prior TKIs. Primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS), overall response rate, duration of response, and time to response. Primary objective is to compare PFS between arms. Secondary objectives include a safety analysis in all treated subjects, and comparisons of PFS and OS between arms for the patient subset with EGFR-mutated tumors. Correlative studies include interrogating flow cytometry-based peripheral blood biomarkers, examining the role of desmoplasia in local tumor immunosuppression, and assessing the contribution of estrogen metabolites to tumorigenesis. This study opened in August 2019 with 2 patients enrolled at the time of submission. Twenty U.S. sites through the NCCN are participating. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Genentech, Inc. Clinical trial information: NCT03786692 .
Correction: Hypoxia-Induced WSB1 Promotes the Metastatic Potential of Osteosarcoma Cells
Authors: Ji Cao, Yijie Wang, Rong Dong, Guanyu Lin, Ning Zhang, Jing Wang, Nengming Lin, Yongchuan Gu, Ling Ding, Meidan Ying, Qiaojun He, Bo Yang
Journal: Cancer Research (2020)

In the original version of [this article][1] ([1][2]), the first and second lanes of the BNIP3 Western blot analysis image in Fig. 1E were inadvertently duplicated in the BNIP3 Western blot analysis image of U2OS cells in Fig. 1C. The authors have provided the correct image for Fig. 1C, and thus the
Propensity score matching analysis of patients with inoperable stage III NSCLC treated with chemoradio- vs. chemoradioimmunotherapy.
Authors: Farkhad Manapov, Julian Taugner, Lukas Käsmann, Chukwuka Eze, Olarn Roengvoraphoj, Claus Belka
Journal: Journal of Clinical Oncology (2020)

e21087 Background: Chemoradiotherapy (CRT) followed by consolidation treatment with the PD-L1 Inhibitor durvalumab is the new standard of care for inoperable stage III NSCLC. The present study compares outcome of patients treated with CRT alone to those treated with additional concurrent and/or sequential immune check-point inhibition (CRT-IO) using propensity-score matching analysis (PSM). Methods: PSM was performed with retro- and prospectively collected data of patients treated with CRT or CRT-IO (consolidation with durvalumab/concurrent and consolidation with nivolumab). Overall survival (OS), progression free survival (PFS) and time to loco-regional recurrence (defined as progression in the mediastinum and ipsilateral lung) were calculated from last day of thoracic irradiation. Results: Sixty-two (37%) of 166 treated patients were successfully matched; 31 received CRT and 31 CRT-IO. 18F-FDG-PET/CT for treatment planning was performed in 97% and cranial contrast enhanced MRI in 81% of patients. PSM was based on age, gender, PTV volume, histology, T- and N-stage. 36 and 51% vs. 42 and 46% of patients had T4- and N3-disease in the CRT and CRT-IO cohorts, respectively. All patients were irradiated to a total dose of at least 60Gy (EQD2). 90% of patients received two cycles of concomitant platinum-based chemotherapy (CRT: 82%, CRT-IO 96%). The median follow-up for 62 patients was 17.3 (range: 1.7-96.0) months. Median PFS was 7.1 (95%CI 2.2-12.1) months in CRT vs. 13.8 (95%CI 13.1-14.5) in CRT-IO patients (p = 0.004). Twelve-month PFS rates were 30% and 55% in the CRT and the CRT-ICI cohort, respectively. Median time to loco-regional recurrence was 15.3 months for CRT vs. not reached for CRT-IO patients (p = 0.050). 12-month loco-regional recurrence rates were 43% vs. 22%; 6- and 12-month brain metastases rates after completion of radiotherapy in the CRT vs. CRT-ICI cohort were 8% and 26% vs. 0% and 20%, respectively. Median OS was 19.1 (8.4-29.8 95%CI) months for CRT and not reached for CRT-IO patients (p &lt; 0.001). 12-month survival rates were 62% and 93% in the CRT and CRT-IO cohort, respectively. Conclusions: The addition of concurrent and/or sequential IO to CRT led to an impressive improvement of loco-regional control, PFS and OS in the matching cohorts.
Efficacy of fluconazole powder in treatment of fungal infection of external auditory canal
Authors: Haoxi Yang
Journal: BMJ (2016)

One hundred and forty patients(165 ears)with fungal infection of external auditory canal were treated in Department of Otolaryngology, Tianjin Fourth Hospital from October 2012 to October 2014. Patients were randomly assigned in two groups: 70 cases (83 ears) received local administration of fluconazole powder (study group) and 70 cases (82 ears) were given local miconazole cream. After 3 weeks of treatment the overall effective rates in study group and control group were 95.18% (79/83) and 73.17% (60/82), respectively (χ2=15.05, P<0.05). Patients were followed up for 6 months the recurrence rates in study and control groups were 6.32% (5/79) and 28.21% (22/78), respectively (χ2=13.19, P<0.05). Results indicate that local administration of fluconazole powder is effective in treatment of fungal infection of external auditory canal with safety and low recurrence rate.


Key words: 
Fluconazole; Ear canal; Fungi; Infection
Radium 223 treatment in metastatic prostate cancer: Exploring use of clinical factors for prognostication in routine practice.
Authors: Salil Vengalil, Paula Bee, Dawn Beetham, Rajanee Bhana, Shibu Joseph, Stephen Dainty, Ian Seedhouse, Loaie El-Helw
Journal: Journal of Clinical Oncology (2020)

e17550 Background: Skeletal metastases are seen in over 90% of metastatic castrate resistant prostate cancer (mCRPC) patients during the course of their disease and is a major cause for significant morbidity and mortality in them. Radium 223 (Ra-223) is a bone seeking calcium mimetic alpha emitter that has demonstrated significant improvement in survival and reduction in skeletal related events (ALSYMPCA trial). Ra-223 treatment was well tolerated and showed benefit before or after chemotherapy. In this study we aimed to assess efficacy of Ra-223 in mCRPC patients treated in our centre and their survival in relation to some common clinical variables that may assist patient selection in routine clinical practice. Methods: We conducted a retrospective audit of mCRPC patients treated with Ra-223 from June 2015 – December 2019. We analysed treatment outcomes and use of Haemoglobin (Hb), Albumin (Alb) and Alkaline Phosphatase (ALP) as potential prognostic factors. Results: There were 46 patients in total with a median age of 76 years (range; 56-90) and 26% were ≥80 years of age. The median follow-up was 10 months (range; 2-38 months). Median baseline PSA was 103.7 (range; 7.2 - 2534) and median baseline ALP was 188 U/L (range; 51 - 2262). Ra-223 was given as 1st or 2nd line treatment in 65% of our patients. Median number of cycles of Ra-223 administered was 4 and 41% of patients completed 6 cycles of treatment. Biochemical response (drop in PSA &gt; 50%) was only seen in 11% of patients but good response in ALP levels (drop in ALP &gt; 50%) was seen in 35%. Median overall survival (OS) was 10 months. Median OS for patients who received Ra-223 as 1st or 2nd line vs subsequent line was 13 and 8.5 months respectively. Median OS for patients with Haemoglobin (Hb) ≥12gm/dl) and lower Hb were 11 and 7 months respectively. Patients with normal albumin at baseline had median OS of 15 months compared to 6 months for those with low albumin. Favourable prognostic group patients (Normal Hb, Normal albumin at baseline and normal ALP after treatment) had a median OS of 31 months compared to 9 months for those in less favourable group. Patients who completed at least 5 cycles had a better survival (13 vs 8.5 months). Fractures were reported in 3 patients (6.5%). Conclusions: Ra-223 treated patients in our centre had a reasonable survival despite having a larger proportion of elderly population compared to the registration trial. Ra-223 treatment seems to be more effective when given at earlier lines in mCRPC setting. Pre-treatment Albumin lower than normal seems to be a predictor for poor overall survival.
Checkmate 77T: A phase III trial of neoadjuvant nivolumab (NIVO) plus chemotherapy (chemo) followed by adjuvant nivo in resectable early-stage NSCLC.
Authors: Tina Cascone, Mariano Provencio, Boris Sepesi, Shun Lu, Nivedita Aanur, Sunney Li, Jonathan Spicer
Journal: Journal of Clinical Oncology (2020)

TPS9076 Background: Although surgery for early NSCLC is potentially curative, 5-year overall survival (OS) rates for patients with stage IIA–IIIB disease are historically &lt; 50%, representing a population of high unmet need. Conventional neoadjuvant or adjuvant chemo provides only a 5% absolute improvement in OS at 5 years. A rational approach to improve survival in these patients is to eradicate micrometastatic disease and potentially induce anti-tumor immunity to minimize the risk of relapse with peri-operative regimens including NIVO, a fully human anti–programmed death receptor-1 antibody. Early phase trials indicate that NIVO-based regimens have the potential to deepen pathological responses and extend survival in this setting (Reuss JE et al. Poster presentation at ASCO 2019. Abstract 8524; Cascone T et al. Oral presentation at ASCO 2019. Abstract 8504; Provencio M et al. Oral presentation at WCLC 2019. Abstract OA13.05). Data from the phase 2 single-arm NADIM trial (NCT03081689) demonstrated the highly encouraging major pathological response (MPR) rate of 83% with neoadjuvant NIVO plus chemo followed by adjuvant NIVO in patients with resectable stage IIIA NSCLC (Provencio M et al. Oral presentation at WCLC 2019. Abstract OA13.05). These results require validation in a large randomized controlled study. CheckMate 77T (NCT04025879) is a phase 3, randomized, double-blind trial evaluating neoadjuvant NIVO plus chemo followed by adjuvant NIVO in resectable early stage NSCLC. Methods: Approximately 452 patients aged ≥ 18 years with resectable stage IIA–IIIB (T3N2 only) NSCLC, ECOG performance status 0–1, and available lung tumor tissue will be enrolled at 113 sites in North America, South America, Europe, Asia, and Australia. Patients with EGFR/ALK mutations, brain metastasis, prior systemic anti-cancer treatment or radiotherapy, and autoimmune disease are excluded. Patients will be randomized to receive neoadjuvant NIVO plus carboplatin- or cisplatin-based doublet chemo followed by surgery and adjuvant NIVO, or neoadjuvant placebo plus carboplatin- or cisplatin-based doublet chemo followed by surgery and adjuvant placebo. The primary endpoint is event-free survival, assessed by blinded independent central review. Secondary endpoints include OS, pathological complete response and MPR assessed by blind independent pathological review, safety and tolerability. The start date was September 2019. The estimated primary completion date is May 2023. Clinical trial information: NCT04025879.
Discovery of a core-panel of markers for a blood-assay for cancer detection utilizing cfDNA methylation changes.
Authors: Lasika Seneviratne, Steven Evans, Juvairiya Pulicharam, Nadir Arber, Jacob Kuint
Journal: Journal of Clinical Oncology (2020)

1522 Background: Cancer screening is limited to several cancers despite improved outcome A screening test should be acceptable, safe, and relatively inexpensive 1 Tumors shed cfDNA to the blood where abundant tumor-specific methylation changes can be detected 1 https://www.who.int/cancer/detection/variouscancer/en/. Methods: This is a prospective, multicenter, observational study under two protocols NCT04264767, NCT04264754. Plasma was collected from 1,255 subjects: 586 treatment-naïve cancer patients and 639 controls, in 21 sites and biobanks. Training set I (211 cases/99 controls) was used to select the 6 final markers for the core panel, training set II (200 controls) was used to lock the algorithm, and set the threshold to a score yielding specificity of 95%. The validation set (342 cases/310 controls) was performed utilizing the pre-specified algorithm and threshold. Plasma was separated from a single EDTA tube within 4 hours of blood draw. EpiCheck’s reagents and methylation-sensitive enzymes (Nucleix, Israel) were used for DNA extraction, digestion, and amplification in real-time PCR (ABI 7500 Fast Dx, Applied Biosystems). Results: Age was comparable but sex and smoking history were different (more women in cases, more smokers in controls). In the validation cohort twelve cancer types were included, with prominent representation of major cancer types (19% Breast, 14% colorectal and 21% lung) and stages I&amp;II (56%). Specificity and sensitivity were maintained high at 94% and 62%. Highest sensitivity was demonstrated in GI cancers (77% colorectal, 83% esophageal, 100% gastric) and non-solid malignancies (83%). Sensitivity in early stage cancers (stages I, II &amp; IIIA) was 71%, led by Sarcoma (83%) esophageal (76%) and colorectal (61%). Conclusions: This 6-marker blood-based methylation assay is a promising initial component in a future cancer screening test, generating significant signal in early cancers and utilizing simple and inexpensive PCR technology. Clinical trial information: NCT04264767, NCT04264754. [Table: see text]
The effect of longitudinal exercise programming in breast cancer patients.
Authors: Jami Aya Fukui, Shirley Cheng, Shannon Lim, John Shepherd, Paulette Yamada, Cheri Teranishi-Hashimoto
Journal: Journal of Clinical Oncology (2020)

TPS12124 Background: Obesity and weight gain are significant concerns for breast cancer survivors. Obesity at diagnosis is an established negative prognostic factor and studies suggest that post-diagnosis weight gain may increase risk for recurrence and decrease disease free survival. Various interventions such as dietary modification, physical activity, individualized counseling, cognitive behavioral therapy, and combinations of these interventions have been studied in order to identify strategies for weight loss in breast cancer survivors. However, one of the main challenges have been to show sustainability in these interventions. Given the adverse consequences of weight gain after diagnosis, continued efforts to identify appropriate weight management interventions aimed at promoting overall health and long term survivorship are needed. Methods: We have opened an investigator initiated Breast Cancer Exercise Study that provides a tailored exercise program and body health assessments for breast cancer patients along their treatment journey. We are enrolling women diagnosed with breast cancer up to 2 years after their diagnosis into a two 12-week exercise program. Participants’ biometrics and physical assessments will be assessed at baseline to determine the appropriate exercise intensity to implement. Women will attend private 1:1, 90min sessions, 3 days/week. At the end of the initial 12-week program, biometric assessments are again performed and participants are then randomized to either: a) continue with individual exercise classes, 2 days/week or b) continue with group exercise classes, 2 days/week. The study follows their long term outcomes including cancer recurrence, exercise adherence as well as quality of life symptoms. The functional health assessment and subsequent personalized exercise program utilizes kinesiology students from University of Hawaii-Manoa during their clinical practicum and is based at our community partner facility the Rehabilitation Hospital of the Pacific. Body assessments and other biomarkers are evaluated through expertise at University of Hawaii Cancer Center. Collectively, our study exemplifies our partnership with community facilities, utilizes cutting edge research and incorporates local students, to provide an important health program for cancer patients all the while enriching our understanding of the unique patient population. The results of this project may help to develop standardized exercise protocols for breast cancer survivors and provide insights to other important health concerns. Clinical trial information: NCT04013568 .
Effectiveness of nivolumab versus regorafenib in hepatocellular carcinoma patients who failed sorafenib treatment
Authors: Cheol-Hyung Lee, Yun Bin Lee, Minseok Albert Kim, Heejoon Jang, Hyunwoo Oh, Sun Woong Kim, Eun Ju Cho, Kyung-Hun Lee, Jeong-Hoon Lee, Su Jong Yu, Jung-Hwan Yoon, Tae-You Kim, Yoon Jun Kim
Journal: Clinical and Molecular Hepatology (2020)

Background/Aims: Several treatment options are currently available for patients with hepatocellular carcinoma (HCC) failing previous sorafenib treatment. We aimed to compare the effectiveness of regorafenib and nivolumab in these patients.Methods: Consecutive HCC patients who received regorafenib or nivolumab after failure of sorafenib treatment were included. Primary endpoint was overall survival (OS) and secondary endpoints were time to progression, tumor response rate, and adverse events. Inverse probability of treatment weighting (IPTW) using the propensity score was conducted to reduce treatment selection bias.Results: Among 150 study patients, 102 patients received regorafenib and 48 patients received nivolumab. Median OS was 6.9 (95% confidence interval [CI], 3.0–10.8) months for regorafenib and 5.9 (95% CI, 3.7–8.1) months for nivolumab (P=0.77 by log-rank test). In multivariable analysis, nivolumab was associated with prolonged OS (vs. regorafenib: adjusted hazard ratio [aHR], 0.54; 95% CI, 0.30–0.96; P=0.04). Time to progression was not significantly different between groups (nivolumab vs. regorafenib: aHR, 0.82; 95% CI, 0.51–1.30; P=0.48). HRs were maintained after IPTW. Objective response rates were 5.9% and 16.7% in patients treated with regorafenib and nivolumab, respectively (P=0.04).Conclusions: After sorafenib failure, the use of nivolumab may be associated with improved OS and better objective response rate as compared to using regorafenib.