tbuckley/cabot-search huggingface dataset:
Identifying the distant metastasis genes by next-generation sequencing panel in nasopharyngeal carcinoma.
Authors: Man Hu, Jinming Yu, Zihan Zhou, Peifeng Li, Xianbin Zhang, Limin Zhai, Tingyong Fan, Shiyu Tian, Juan Xu, Xinhua Yang, Jin Xu, Shui Yu, Dongqing Wang, Wei Dong, Xiujuan Cao, Hongjiang Yan, Mingping Sun, Xiuping Ding, Jun Xing, Peng Zhang
Journal: Journal of Clinical Oncology (2020)

e18547 Background: Even though local and regional controls have been substantially improved in nasopharyngeal carcinoma (NPC) in the contemporary era of intensity-modulated radiotherapy with extensive use of combined chemotherapy, the distant metastasis becomes the major cause of treatment failure and cancer-related death. To date, the genes contributed to metastasis of NPC is still unclear. The aim of this study was to identify the genes which lead to distant metastasis. Methods: A total of forty primary nonkeratinizing NPC patients were diagnosed at Shandong Cancer Hospital in this study. The formaldehyde-fixed paraffin embedded (FFPE) taken from primary sites or metastatic lymph nodes were performed next-generation sequencing (NGS) panel (Shanghai OrigiMed Co., Ltd.) to determine variated genes, such as single nucleotide variants (SNV), copy number variants (CNV) and rearrangement. These patients were followed up until Febr. 8, 2020. The genes related to distant metastasis were identified by logistic regression. Moreover, this study compared the frequency of mutated gene between our data and Catalog of Somatic Mutations in Cancer (COSMIC) database by the Chi-square test or Fisher’s exact test. Results: The study included 31 men and 9 women. The median age of the patients at diagnosis was 47 years (range 15–71 years). With the median follow-up of 10.6 months (range 16.8–72.3 months), 7 patients had distant metastasis and 1 undergone recurrent. Notably, EMSY and MCL1 variants were contributed to NPC distant metastasis (OR = 31, P = 0.049). The top eight SNV of genes in our study were CYLD, KMT2D, BAP1, EP300, TP53, ATM, NFKBIA and SPEN. When compared to COSMIC database, the mutant frequencies of CYLD, EP300 and BAP1 in our study were significantly higher than that of COSMIC database. However, the mutant frequencies of IDH2 and KMT2C were significantly lower than COSMIC database. Conclusions: This is the first study which suggests that EMSY and MCL1 variants were involved in the metastasis of NPC. The study identified 5 genes, which mutation frequency is significantly different from the COSMIC database. The study provided a molecular basis for a comprehensive understanding of, and exploring targeted therapies for nasopharyngeal carcinoma.
Efficacy and safety in older patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving cabazitaxel (CBZ) versus abiraterone (ABI) or enzalutamide (ENZ) in the CARD study.
Authors: Cora N. Sternberg, Daniel Castellano, Johann S. De Bono, Karim Fizazi, Bertrand F. Tombal, Christian Wülfing, Gero Kramer, Jean-Christophe Eymard, Aristotelis Bamias, Joan Carles, Roberto Iacovelli, Bohuslav Melichar, Asgerdur Sverrisdottir, Christine Theodore, Susan Feyerabend, Carole Helissey, Elizabeth Poole, Ayse Ozatilgan, Christine Geffriaud-Ricouard, Ronald De Wit
Journal: Journal of Clinical Oncology (2020)

5559 Background: In the CARD (NCT02485691) study, radiographic PFS (rPFS), PFS and OS were significantly improved with CBZ vs. androgen-signaling-targeted agents (ARTA; ABI or ENZ) in pts with mCRPC who had received docetaxel (DOC) and progressed within 12 months (mo) on an alternative ARTA. This analysis evaluated the impact of age (&lt; 70 vs. ≥ 70 years) on the efficacy and safety of CBZ and ARTAs in CARD. Methods: 255 pts with mCRPC were randomized 1:1 to CBZ (25 mg/m 2 IV Q3W + prednisone [P] + G-CSF) vs. ABI (1000 mg PO + P) or ENZ (160 mg PO) until disease progression, unacceptable toxicity or pt request. Pts were eligible if they had received ≥ 3 cycles of DOC and progressed ≤ 12 mo on the previous alternative ARTA. Primary endpoint was rPFS. Subgroup analysis of older (≥ 70 years; n = 135) and younger (&lt; 70 years; n = 120) pts was pre-specified for rPFS; others were post hoc. Results: rPFS was significantly improved vs. ARTA in both older (median 8.2 vs. 4.5 mo; HR 0.58; 95% CI 0.38–0.89) and younger pts (median 7.4 vs. 3.2 mo; HR 0.47; 95% CI 0.30–0.74). Median OS for CBZ vs. ARTA was 13.9 vs. 9.4 mo (HR 0.66; 95% CI 0.41–1.06) in older pts and 13.6 vs. 11.8 mo (HR 0.66; 95% CI 0.41–1.08) in younger pts. PFS, tumor, PSA and pain responses also favored CBZ, regardless of age. Grade ≥ 3 adverse events (AEs) occurred in 57.8% vs. 49.3% of older pts receiving CBZ vs. ARTA and 48.4% vs. 42.1% in younger pts. AEs leading to death were more frequent with ARTA, mainly due to disease progression. Conclusions: CBZ had improved efficacy outcomes vs. ARTA in pts with mCRPC previously treated with DOC and the alternative ARTA, regardless of age. Grade ≥ 3 cardiac AEs were more frequent in older pts treated with ARTA. A higher rate of AEs was reported in older vs. younger pts, for ARTA and CBZ. CBZ and ARTA had different safety profiles in older compared with younger pts. Clinical trial information: NCT02485691 . Funding: Sanofi. [Table: see text]
AFT-16: Phase II trial of atezolizumab before and after definitive chemoradiation (CRT) for unresectable stage III non-small cell lung cancer (NSCLC).
Authors: Helen J. Ross, David E. Kozono, James John Urbanic, Terence Marques Williams, Carter Dufrane, Ilze Bara, Mayank Gandhi, Katja Schulze, JaneMichelle Michelle Brockman, Xiaofei F. Wang, Junheng Gao, Everett E. Vokes, Tom Stinchcombe
Journal: Journal of Clinical Oncology (2020)

9045 Background: A minority of the &gt; 40,000 patients (pts) diagnosed with stage III NSCLC annually in the US are cured by CRT, more recently followed by adjuvant immune checkpoint inhibitors (ICI). PD-L1 blockade with CRT may attenuate tumor-related immunosuppression via depletion of regulatory T cells and clonal expansion of effector T cells. Further, CRT may expose otherwise hidden antigens that present additional targets to the reconstituting immune system. Adjuvant ICI has improved survival. Whether ICI before CRT will further improve outcomes is unknown. Methods: This Alliance Foundation Trials (AFT) study evaluated safety and efficacy of atezolizumab before and after CRT. 4 cycles of atezolizumab 1200 mg IV q 21 days with restaging after cycles 2 and 4 were followed by carboplatin and paclitaxel (C/P) weekly with 60 Gy radiation and C/P consolidation followed by atezolizumab for 1 year of therapy. Primary endpoint is disease control rate (DCR) (complete response + partial response (PR) + stable disease (SD)) at 12 weeks (wks). Secondary endpoints include overall response rate, progression-free survival, overall survival, safety and quality of life assessed by EORTC QLQ-30. Correlatives include PD-L1 and tumor mutation burden as predictive biomarkers. Tumor tissue was obtained at study entry; plasma and immune cells were isolated at multiple timepoints. Results: 64 pts with stage III NSCLC, performance status (PS) 0-1, no active autoimmune disease or significant organ dysfunction enrolled at 13 Alliance sites from 11/2017 to 7/2019. 62 pts received ≥ 1 dose of atezolizumab and are included in the primary analysis; median age 63.9 years (38.1-86.5), 51.6% female, 77.4% white, 61.3% former smokers, 56.5% PS 0. DCR at 12 wks was 77.4% (80% confidence interval 69.2-84.3%) (30.7% PR, 46.8% SD). 54 pts reported adverse events (AEs) during induction, mostly grade (gr) 1. There were 13 serious AEs, most unrelated to study treatment; 1 gr 3 anaphylactic reaction, 1 gr 3 colitis, and 1 gr 4 Guillain-Barre syndrome were attributable to atezolizumab. Baseline PD-L1 status was available for 49 pts. DCR was 82.4% for pts with PD-L1 negative and 90.9% for pts with PD-L1 positive tumors. Conclusions: Atezolizumab prior to and following CRT for stage III unresectable NSCLC was well tolerated with an encouraging 12-wk DCR. Analysis of secondary endpoints is ongoing. Further study of induction ICI therapy is warranted in patients with unresectable stage III NSCLC. Support: AFT, Genentech; Clinical trial information: NCT03102242.
小儿股骨干骨折98例
Authors: 王勇, 王兆阳, 王淑霞, 房群, 吴延平, 李爱武
Journal: BMJ (2005)

小儿股骨干骨折分为保守治疗和手术治疗.近年来,随着固定技术和抗生素的发展,手术治疗有增多的趋势.但无论保守或手术治疗,其目的均是尽量缩短骨折愈合时间,减少并发症及治疗费用.我院自1991年9月至2003年9月收治小儿股骨干骨折98例,现报告如下。
Reassessing the net health benefit (NHB) of FDA approved cancer drugs with evolution of evidence using the American Society of Clinical Oncology Value Framework (ASCO-VF).
Authors: Seanthel Delos Santos, Noah Witzke, Vanessa Sarah Arciero, Amanda Putri Rahmadian, Louis Everest, Kelvin K. Chan
Journal: Journal of Clinical Oncology (2020)

7011 Background: Regulatory approval of oncology drugs are often based on data presented in the primary publication of clinical trials (CT). However, clinically relevant data, such as long-term overall survival (OS) and quality of life (QOL), are often reported in subsequent publications. Therefore, this study aimed to evaluate the ASCO-VF NHB at the time of drug approval and over time as further evidence is published. Methods: All FDA approved oncology drug indications from 01/06-12/16 were reviewed to identify CTs that were scorable using the ASCO-VF version 2. Subsequent publications of included CTs relevant for scoring were identified from Web of Science with a follow-up time of 3 years from approval. Using ASCO-defined threshold scores of ≤40 for low benefit and ≥45 for substantial benefit, changes in classification of benefit were assessed at 3-years post-FDA approval. Results: We identified 57 FDA approved indications (40.4% OS, 59.6% progression-free survival (PFS) as primary endpoints) with scorable ASCO-VF CTs. Among those 57 indications, 36.8% at the time of FDA approval demonstrated substantial benefit, 10.5% demonstrated intermediate benefit, and 52.6% demonstrated low benefit. We then identified 96 subsequent publications relevant to scoring within 3-years of FDA approval, consisting of primary endpoint updates (29.2%; 14.6% OS, 12.5% PFS), secondary endpoint updates (44.8%; 16.7% OS, 7.3% PFS), new reporting of secondary endpoint (4.2% OS), safety updates (28.1%), and QOL reporting (43.8%). Upon reassessment of the NHB in subsequent publications, there was an overall change from initial classification of benefit in 36.8% of trials (17.5% became substantial, 8.8% became low, and 10.5% became intermediate). Changes in scores were mainly the result of an updated hazard ratio (35.1%), change in scoring endpoints from PFS to OS as per ASCO-VF endpoint hierarchy (8.8%), toxicity updates (57.9%), new tail of the curve bonus (12.3%), palliation bonus (14.0%), or QOL bonus (22.8%). Overall, at reassessment at 3 years post-FDA approval, 42.1% were substantial, 10.5% were intermediate, and 47.3% were low benefit. Conclusions: Only a modest proportion of FDA approved drugs have demonstrated substantial NHB at time of approval. As further evidence was published, a substantial proportion of indications have a change in classification of NHB, resulting in a small increase in the overall proportion of indications being deemed to have substantial benefit at 3 years post-approval.
Immune related adverse effects (IRAEs) in patients with cancer who received immune checkpoint inhibitors (ICIs): A single center experience from rural Maine.
Authors: Anannya Patwari, Vineel Bhatlapenumarthi, Antoine Joseph Harb, Adam Curtis
Journal: Journal of Clinical Oncology (2020)

e19265 Background: ICIs are used for a variety of malignancies and have shown to improve survival, but they are associated with IRAEs. We aim to identify the frequency and severity of new IRAEs and flares of preexisting autoimmune (AI) disorders excluding thyroid disorders in cancer patients treated with ICIs at our institution. Methods: We conducted a retrospective chart review analysis of all cancer patients who received ICIs: nivolumab, pembrolizumab, atezolizumab and durvalumab at the Northern Light Cancer Institute from June 2015 to March 2019. We excluded patients who received ipilimumab. We then studied those who developed IRAEs. Results: Out of 465 who received ICIs, 115(24.7%) developed IRAEs. 83 out of 298 (27.9%) nivolumab recipients, 20/121 (15.7%) pembrolizumab recipients, 5/26 (19.2%) atezolizumab and 7/20 (35%) durvalumab recipients developed IRAEs. Some patients had multiple toxicities. Median age at cancer diagnosis was 66 years, evenly split among males and females. Majority (63%) were treated for Lung cancer, followed by melanoma (20%) and genitourinary cancers (12%). Summary of new IRAEs are as noted in the table below. In patients with new IRAEs treatment was held in 29(6%) for a median duration of 7.2 wks. Upon rechallenge with the same ICI in 27 patients, 20(74%) tolerated and 7 did not leading to permanent discontinuation. Majority were treated with steroids and some required immunomodulators. Interestingly 39(8%) patients with underlying AI condition received ICIs. Of these 11(28.2%) developed flares, resulting in permanent discontinuation of drug in 4. The majority tolerated the treatment well. Treatment was permanently discontinued in 70(15%), 26(6%) required hospital admission for IRAEs. Pneumonitis was the most common toxicity necessitating treatment discontinuation and hospital stay. Conclusions: In real world setting the frequency and severity of IRAEs was more than the reported literature data, leading to higher rates of permanent discontinuation of treatment. [Table: see text]
Risk of chronic opioid use after radiation for head and neck cancer: A systematic review and meta-analysis.
Authors: Sondos Zayed, Cindy Lin, Gabriel Boldt, Nancy Read, Lucas Mendez, Varagur Venkatesan, Jinka Sathya, Dwight Moulin, David A. Palma
Journal: Journal of Clinical Oncology (2020)

6579 Background: Opioid overuse is a major international public health concern. The prevalence and risk factors for chronic opioid use (COU) in radiation-induced head and neck pain are poorly understood. The aim of this study was to estimate the rates of COU and to identify risk factors for COU in head and neck cancer (HNC) patients undergoing curative-intent radiotherapy (RT) or chemoradiotherapy (CRT). Methods: We performed a systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, using the PubMed (Medline), EMBASE, and Cochrane library databases, queried from dates of inception until present. COU was defined as persistent opioid use ≥3 months after treatment completion. Studies in the English language that reported on COU in HNC patients who received RT/CRT were included. Meta-analyses were performed using random effects models. Heterogeneity was assessed using the I 2 value. Results: A total of 134 studies were identified, with 7 retrospective studies (reporting on 1841 patients) meeting inclusion criteria. Median age was 59.4 years (range 56.0-62.0) with 1343 (72.9%) men and 498 (27.1%) women. Primary tumour locations included oropharynx (891, 48.4%), oral cavity (533, 29.0%), larynx (93, 5.1%), hypopharynx (32, 1.7%), and nasopharynx (29, 1.6%). 846 (46.0%) patients had stage I/II disease and 926 (50.3%) had stage III-IV disease. 301 (16.3%) patients had RT alone, 738 (40.1%) received CRT, and 594 (32.3%) underwent surgery followed by adjuvant RT/CRT. The proportion of HNC patients who received radiotherapy and developed COU was 40.7% at 3 months (95% CI 22.6%-61.7%, I 2 = 97.1%), 15.5% at 6 months (95% CI 7.3%-29.7%, I 2 = 94.3%) and 7.0% at 1 year. There were significant differences in COU based on primary tumor sites (P &lt; 0.0001), with the highest rate (46.6%) in oropharyngeal malignancies. Other factors associated with COU included history of psychiatric disorder (61.7%), former/current alcohol abuse (53.9%), and start of opioids prior to radiation treatment (51.6%). There was no significant difference in the proportion of COU by gender (P = 0.683), disease stage (I/II vs III/IV; P = 0.443), or treatment received (RT, CRT, or adjuvant RT/CRT; P = 0.711). Conclusions: A significant proportion of patients who undergo radiotherapy for head and neck cancer suffer from COU. High-risk factors for COU include an oropharyngeal primary tumour, history of psychiatric disorder, former/current alcohol abuse, and pre-treatment opioid use. New strategies to mitigate opioid use are needed.
Indication for surgical treatment of polypoid lesion of gallbladder
Authors: Yuan-zhi Liu, Abuduwaili, Guo-bin Wang, Bo Yang
Journal: BMJ (2009)

This study was to investigate the indication for surgical treatment of polypoid lesion of gallbladder (PLG). Clinical and pathological data from 121 PLG patients undergoing laparoscopic cholecysteotomy were retrospectively analyzed. Asymptomatic or moderate symptomatic PLG was seen in 67. Pathology test-confirmed cholesterol, hyperplasia, and adenomatous polyps were found in 111 (91.7%), 8 (6. 6%), and 2 (1.7%), respectively. Our data suggest that most PLG might be benign and have non-neoplasm nature. Over-operation may be unnecessary, and the indication for surgical procedure should be prudently controlled.

Key words: 
Gallbladder disease;  Cholecystectomy, laparoscopic
Relationship between systemic lupus erythematosus and autoimmune thyroid disease
Authors: Qin Song, Yujing Mao, Jian Li
Journal: BMJ (2014)

Objective
To evaluate the incidence of autoimmune thyroid disease (AITD) in systemic lupus erythematosus (SLE) and examine the correlation between AITD and SLE activity.


Methods
The study group included 220 SLE patients with the screening of thyroid function (FT3, FT4, TSH) and anti-thyroid autoantibodies (TgAb, TPOAb) were hospitalized into Affiliated Hospital, Jining Medical College between July 2009 and October 2013.The control group included 160 healthy subjects.We compared the prevalence of AITD between SLE patients and normal controls and also the positive rate of anti-thyroid autoantibodies was observed.We also compared the positive rate of anti-thyroid autoantibodies between AITD in SLE and simple SLE group and also analyzed the correlation between two groups of patients and SLE activity (evaluated by the titer of anti-dsDNA, C3, C4, CH50, SLEDAI score).


Results
Among them, 45 patients suffered from AITD (20.5%). There were hyperthyroidism (n=6, 13.3%) and hypothyroidism (including subclinical hypothyroidism) (n=26, 57.8%), Hashimoto's thyroiditis (n=13, 28.9%). And 74 SLE cases were positive for anti-thyroid autoantibodies.The prevalence of AITD and the positive rate of anti-thyroid autoantibodies in SLE patients (20.5%, 33.6%) were higher than that in normal controls (3.13%, 7.50%)(P 0.05).


Conclusions
The SLE patients have a great prevalence of AITD and a positive rate of anti-thyroid autoantibodies.Those with anti-thyroid autoantibodies have a higher incidence of AITD and it has nothing to do with SLE activity.It is essential to monitor thyroid function and thyroid autoantibodies during the follow-ups.


Key words: 
Lupus erythematosus, systemic; Thyroiditis autoimmune; Autoantibodies
Five day accelerated partial breast irradiation (APBI) using stereotactic body radiation therapy (SBRT) in stage 0-II breast cancer: A report of 135 cases with up to two-year follow-up.
Authors: Rufus J. Mark, Valerie Gorman, Steven McCullough
Journal: Journal of Clinical Oncology (2020)

e12596 Background: Randomized trials in stage 0-II breast cancer have proven that APBI given via HDR implant in 5 days is equivalent to whole breast External Radiation Therapy (XRT) given in 5-6 weeks in regard to breast tumor local recurrence (LR). However, complications have been significant. Recently APBI using non-invasive IMRT given in 5 fractions has been shown in another randomized trial to be equivalent to XRT in 6 weeks, with respect to LR. IMRT was superior in regard to acute effects, late effects, and cosmesis. In the randomized clinical trial of APBI IMRT, the Clinical Target Volume (CTV) was defined by the injection of individual fiducial markers bordering the surgical cavity. At our institution, we have used the Biozorb fiducial system to localize the CTV for IMRT. We sought to confirm the APBI IMRT results with this simpler less labor intensive fiducial placement system. Methods: Between 2017 and 2020, 135 patients have undergone SBRT targeted to a Biozorb defined CTV with the walls of the surgical cavity sewn to the Biozorb device. Eligible patients were older than age 40, had tumor sizes &lt; 3 cm, negative surgical margins, and negative sentinel node dissections. SBRT dose was 30 Gy given in 5 fractions. Dose Constraints were as follows: V-30 Gy &lt; 105%, Ipsilateral Breast V-15 Gy &lt; 50%, Ipsilateral Lung V-10 Gy &lt; 20%, Contralateral Lung V-5 Gy &lt; 10%, Heart V-3 Gy &lt; 20%, Contralateral Breast Dmax &lt; 2 Gy and Skin Dmax &lt; 27 Gy. The Planning Target Volume (PTV) ranged from 27 to 355 cc with a median of 80 cc. PTV = CTV + 1-2 cm. Results: Follow-up ranged from 1-26 months with a median of 12 months. LR has been 0% (0/135). There have been no skin reactions or seromas. Infection has occurred in one patient (0.7%). Three (2.2%) patients developed pain around the Biozorb site. This resolved within 2 days on a short course of steroids in all cases. Cosmetic results as rated by the Surgeon, Radiation Oncologist, and Nurse, were rated excellent in 98.5% (133/135) of cases. Conclusions: Non-invasive APBI with SBRT given qd over 5 days targeted to Biozorb has resulted in LR, complications, and cosmetic results which compare favorably to invasive APBI given bid with HDR implant. At last follow-up, there have been no LR, skin reactions, or significant complications. Cosmesis has been excellent in 98.5% of patients.