tbuckley/cabot-search huggingface dataset:
Exploring fingerprint ctDNA as a stratifying factor in colorectal cancer.
Authors: Wending Sun, Jianwei Zhang, Jinwang Wei, Chun Dai, Jun Liu, Yanhong Deng
Journal: Journal of Clinical Oncology (2020)

e16101 Background: Colorectal cancer (CRC) ranks near the top in tumor-related deaths. Its standard-of-care is surgical resection plus adjuvant chemotherapy, which can extend patient’s live and disease-free survival for up to several years. However, choosing an appropriate chemotherapy agent is difficult because CRC is a heterogenous disease. It is believed that molecular stratification can help to improve treatment accuracy and this has been proven by the consensus molecular subtypes (CMS) classification. However, the CMS classification relies on expensive and complex gene-expression profiling, and more cumbersomely, is limited to early stage patients without prior chemotherapy, radiation and metastasis. This situation denies many CRC patients from the benefit of CMS classification. Circulating tumor DNA (ctDNA) is a minimally invasive way to monitor disease progression and treatment response in solid tumors but its clinical utility in CRC remains to be validated. We explore the potential of using patient’s fingerprint ctDNA (defined below) as a stratifying factor in CRC patients to assist clinical decision. Methods: WES is performed on tumor and matched blood samples from 149 CRC patients. Based on the WES result, 20-30 tumor specific genes are selected for each patient and form their ctDNA fingerprints. The patients are grouped according to their level of fingerprint ctDNA (high- vs. low-ctDNA). Results: The two groups of patients show significant difference in treatment responses and mutational profiles. The low-ctDNA group in general respond to treatment well and have good prognosis. The high-ctDNA group, in contrast, often experience relapse or recurrence. Interestingly, the low-ctDNA group is dominated by point and small indel mutations in the top mutated genes while the high-ctDNA group is dominated by gene copy variations (CNV). SMAD4 deficit and DCC amplification are well known CNV in CRC, but they only appear in the high-ctDNA group. Similarly, CNV of AGO2, ACTG1, MYC, and BRD3 are only associated with the high-ctDNA group but not the low-ctDNA group. Conclusions: Our result indicates a strong correlation of fingerprint ctDNA level to both tumor mutational profile and prognosis. This suggests fingerprint ctDNA level may be used as an effective stratifying factor in CRC. At the same time, possibly a common molecular cause is driving persistent ctDNA production in CRC patients, including a large portion of them who have received surgical and adjuvant chemotherapy. Further perspective study, however, is needed to test whether fingerprint ctDNA can be a predictive biomarker.
津冀地区变应性鼻炎患病相关因素分析
Authors: 王丽, 林文森, 王泽海, 王小奇, 陈洁, 张振富, 于金珍
Journal: BMJ (2012)

调查天津、河北不同地区内人群变应性鼻炎(AR)患病率,津冀地区AR患病率为9.1％ (139/1524).其中,沿海地区AR患病率均较山区、农村和天津市区低(均P＜0.01).多因素的logistic回归分析显示,AR与工作因素(P =0.002)和变迁因素(P =0.042)有关。
18 FDG PET/CT prediction of treatment outcomes in patients with p16-positive, non-smoking associated, locoregionally advanced oropharyngeal cancer (LA-OPC) receiving deintensified therapy: Results from NRG-HN002.
Authors: Rathan M Subramaniam, Lyudmila Demora, Min Yao, Sue S. Yom, Maura L. Gillison, Jimmy J. Caudell, John Waldron, Ping Xia, Christine H. Chung, Minh-Tam Truong, Louis B Harrison, Jason Chan, Jessica Lyn Geiger, Loren Mell, Samantha A. Seaward, Wade Thorstad, Jonathan Jay Beitler, Khalil Sultanem, Dukagjin Blakaj, Quynh-Thu Le
Journal: Journal of Clinical Oncology (2020)

6563 Background: To determine the negative predictive value (NPV) of 12-14 week post-treatment PET/CT for 2-year progression-free survival (PFS) and 2-year locoregional control (LRC) in NRG-HN002, which is a two-arm phase II trial for patients with low-risk, non-smoking associated p16-positive LA-OPC randomized in a 1:1 ratio to reduced-dose IMRT with or without cisplatin. Methods: PET/CT scans were reviewed both centrally and locally by participating institutions. Tumor response evaluations for primary site, right neck, and left neck were carried out using a 5-point ordinal scale (‘Hopkins Criteria’). Overall scores were then assigned as ‘Negative,’ Positive,’ or ‘Indeterminate.’ Patients who had a ‘Negative’ score for all three evaluation sites were given an overall score of ‘Negative.’ The endpoints were NPV for LRC and PFS at 2 years testing NPV ≤ 90% vs &gt; 90% (1-sided alpha 0.10 and 76% power). Results: There were 316 patients enrolled, of whom 306 were randomized and eligible. Of these, 131 (42.8%) patients consented to a post-therapy PET/CT, and 117 (89.3%) patients were eligible for PET/CT analysis. The median time from end of treatment to PET/CT scan was 94 days (range 52-139). The rates of 2-yr PFS and LRC in the analysis subgroup were 91.3% and 93.8%, respectively. Based on central review, post-treatment scans were negative for residual tumor for 115 patients (98.3%) and positive for 2 patients (1.7%). The NPV for 2-year LRC was 94.5% (90% lower confidence bound [LCB] 90.6%; p = 0.07). NPV for 2-year PFS was 92.0% (90% LCB 87.7%; p = 0.30). Similar NPV results were obtained based on analysis of local reviews. Conclusion: Within the context of deintensification with reduced-dose radiation, the NPV of a 12-14 week post-therapy PET/CT for 2-year LRC is statistically &gt; 90%, similar to that reported for patients receiving standard chemoradiation. However, in this study, there was not enough evidence to conclude that the NPV of a 12-14 week post-therapy PET/CT for 2-year PFS is &gt; 90%. Grant acknowledgement: This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U24CA180803 (IROC), UG1CA189867 (NRG Oncology NCORP) from the National Cancer Institute (NCI). This project is funded, in part, under a Grant with the Pennsylvania Department of Health. The Department specifically disclaims responsibility for any analyses, interpretations or conclusions. Clinical trial information: NCT02254278 .
Randomized Controlled Trials of Electronic Health Record Interventions: Design, Conduct, and Reporting Considerations
Authors: Mark J. Pletcher, Valerie Flaherman, Nader Najafi, Sajan Patel, Robert J. Rushakoff, Ari Hoffman, Andrew Robinson, Russell J. Cucina, Charles E. McCulloch, Ralph Gonzales, Andrew Auerbach
Journal: Annals of Internal Medicine (2020)

Electronic health record (EHR) systems can be configured to deliver novel EHR interventions that influence clinical decision making and to support efficient randomized controlled trials (RCTs) designed to evaluate the effectiveness, safety, and costs of those interventions. In designing RCTs of EHR interventions, one should carefully consider the unit of randomization (for example, patient, encounter, clinician, or clinical unit), balancing concerns about contamination of an intervention across randomization units within clusters (for example, patients within clinical units) against the superior control of measured and unmeasured confounders that comes with randomizing a larger number of units. One should also consider whether the key computational assessment components of the EHR intervention, such as a predictive algorithm used to target a subgroup for decision support, should occur before randomization (so that only 1 subgroup is randomized) or after randomization (including all subgroups). When these components are applied after randomization, one must consider expected heterogeneity in the effect of the differential decision support across subgroups, which has implications for overall impact potential, analytic approach, and sample size planning. Trials of EHR interventions should be reviewed by an institutional review board, but may not require patient-level informed consent when the interventions being tested can be considered minimal risk or quality improvement, and when clinical decision making is supported, rather than controlled, by an EHR intervention. Data and safety monitoring for RCTs of EHR interventions should be conducted to guide institutional pragmatic decision making about implementation and ensure that continuing randomization remains justified. Reporting should follow the CONSORT (Consolidated Standards of Reporting Trials) Statement, with extensions for pragmatic trials and cluster RCTs when applicable, and should include detailed materials to enhance reproducibility.
Patterns of progression and subsequent management of patients with <i>BRCA1/2</i> mutated platinum-sensitive recurrent epithelial ovarian cancer (EOC) progressing on olaparib versus placebo: the SOLO2/ENGOT Ov-21 trial (NCT01874353).
Authors: Jean-Sebastien Frenel, Jae-Weon Kim, Dominique Berton, Rebecca Asher, Laura Vidal, Patricia Pautier, Jonathan A. Ledermann, Richard T. Penson, Amit M. Oza, Jacob Korach, Tomasz Huzarski, Sandro Pignata, Nicoletta Colombo, Tjoung-Won Park-Simon, Kenji Tamura, Gabe S. Sonke, Elizabeth S. Lowe, Alison E. Freimund, Chee Khoon Lee, Eric Pujade-Lauraine
Journal: Journal of Clinical Oncology (2020)

6070 Background: Olaparib maintenance is a standard treatment of BRCA1/2 mutated platinum-sensitive recurrent EOC. Despite improvement in PFS, olaparib (O) resistance often occurs and the optimal management of post-olaparib progression remains undefined. Methods: Data of patients who participated in the SOLO-2 trial and progressed were analyzed. Primary objective was to depict the patterns of progression of patients treated with O compared to placebo (P). Secondary objectives include description of post-progression treatments. Results: 106/195 (54%) and 80/99 (81%) patients had a RECIST progression in the O and P arms respectively. As permitted in the protocol, 37 (35%) pts continued O despite a RECIST progression and 10 remained on treatment at the date of data base cut-off of the primary endpoint. Median duration of O post progression was 3.2 months (range: 1 to 19.4). In the placebo arm, only 20% of the patients with progressive disease continued placebo during a median of 1.6 months (range:1.1 to 16.1). Patterns of sites of progressive disease were similar in the O and P arms respectively in terms of liver (21% vs 18%), lung (4% vs 3%), lymph node (20% vs 16%) peritoneal (48% vs 32%) or brain metastases (0% vs 2%). Number of sites of relapsing disease were similar in the O and P arm respectively (1 (68% vs 64), ≥2 (32% vs 36%). A total of 54 (51%) patients in the O arm and 42 (53%) in the P arm received subsequent platinum-based therapy. In both arms, 8% received bevacizumab and 6% received no further treatment. Median PFS with first post-study platinum-based and non platinum-based therapy were 7.1 months and 5.6 months respectively. In the P arm, 18 (23) patients received PARP inhibitors following the first subsequent chemotherapy. Conclusions: Patterns of disease progression and subsequent chemotherapy were similar in patients receiving O or P in the SOLO2 trial. Instead of switching to chemotherapy, continuing O at the time of RECIST progression was an option for 35% of the patients. Clinical trial information: NCT01874353.
Primary efficacy and biomarker analyses from the VISION study of tepotinib in patients (pts) with non-small cell lung cancer (NSCLC) with <i>MET</i>ex14 skipping.
Authors: Xiuning Le, Enriqueta Felip, Remi Veillon, Hiroshi Sakai, Alexis B. Cortot, Marina Chiara Garassino, Julien Mazieres, Santiago Viteri Ramirez, Helene Senellart, Jan Van Meerbeeck, Niels Reinmuth, Pier Franco Conte, Dariusz Kowalski, Byoung Chul Cho, Josef Straub, Jürgen Scheele, Dilafruz Juraeva, Rolf Bruns, John Heymach, Paul K. Paik
Journal: Journal of Clinical Oncology (2020)

9556 Background: Preliminary tepotinib data showed durable activity in pts with NSCLC with METex14 skipping prospectively identified by liquid (L+) or tissue (T+) biopsy. Having met target enrollment of ≥60 L+ pts &amp; ≥60 T+ pts, we report primary data. Methods: VISION Cohort A enrolled pts with advanced EGFR/ALK wt, METex14 skipping NSCLC (asymptomatic brain metastases [BM] allowed), who received oral tepotinib 500 mg QD. On-study treatment decisions were based on investigator assessment (INV) of response. Primary endpoint was objective response rate (ORR) by independent review committee (IRC) analyzed in 3 primary ITT sets: L+ and/or T+, L+, T+. 2ary endpoints included ORR by INV, duration of response (DOR), disease control rate (DCR), PFS, OS, &amp; safety. Preplanned analyses were performed in pts with BM at baseline (BL). BL/on-treatment ctDNA plasma samples (L+) were analyzed using a 73-gene NGS panel (Guardant360). Deep molecular responses (MR), defined as &gt; 75% depletion of METex14, were compared with objective responses (OR). Results: By data cut-off (1 Oct 19) 151 pts received tepotinib (safety set); 99 L+/T+, 66 L+, 60 T+ pts comprised the 3 ITT sets with ≥6-month [m] follow-up. Across treatment lines (n = 44 1L, n = 55 ≥2L), primary ORR &amp; mPFS [95% CI] in 99 L+/T+ pts were 43% [34–54] &amp; 8.6 m [6.9–11.0] by IRC and 56% [45–66] &amp; 9.5 m [6.7–13.5] by INV. ORR was similar in L+ or T+ pts (table) or in T+L− pts (n = 25): 40% [21–61] by IRC and 48% [28–69] by INV. Only 2 pts were T−L+. Outcomes were also comparable in pts with BM (n = 11): IRC ORR 55% [23–83] &amp; mPFS 10.9 m [8.0–ne]. 34/51 pts (67%) with matched BL/on-treatment L+ samples had deep MR strongly associated with clinical response: 32/34 pts (94%) with MR had disease control (INV), including 29/34 pts (85%) with OR; 2/34 pts had progressive disease. Further biomarker data will be presented. Grade ≥3 treatment-related adverse events (TRAEs) were reported by 37/151 pts (25%). 13 pts (9%) discontinued due to TRAEs. Conclusions: Tepotinib is a promising targeted therapy with durable clinical activity and manageable toxicity in pts with METex14 skipping NSCLC L+ or T+, including pts with BM. High ORR &amp; DCR in pts with ctDNA molecular responses support that MET inhibition in METex14+ tumor cells can lead to clinical benefit. Clinical trial information: NCT02864992 . [Table: see text]
Diagnosis and treatment of Roux and Y space hernia after Roux-en-Y gastric bypass surgery for gastric cancer patients: a clinical analysis of 12 cases
Authors: Guoqiang Zhang, Chengjiang Xiang, Ping Wang, Dongming Zhao, Jiangang Tang, Yuanwei Zhang, Maohe Jin
Journal: BMJ (2019)

Clinical data of 12 patients with gastric cancer, in whom the Roux and Y space hernia developed after gastrectomy with Roux-en-Y anastomosis in our hospital from June 2010 to December 2018, were retrospectively analyzed. The clinical symptoms of patients were abdominal pain, distension and ileus. The main CT findings were torsion of mesentery with whirlpool sign, intestinal obstruction and exudants around the small bowels. During the operation it was found that small bowels herniated into the Roux and Y space in all 12 patients, the necrotic small intestines were resected in 4 patients. Ten patients were recovered, and 2 died. No recurrence was observed in all 10 patients during 3 month-follow up. The postoperative Roux and Y space hernia is a internal hernia and difficult to be diagnosed. The CT scan is valuable for diagnosis of Roux and Y space hernia; the main CT signs were swirled appearance of mesentery and small bowel obstruction. Once diagnosis is made the emergency operation is necessary.

Key words: 
Stomach neoplasms; Hernia, abdominal; Anastomosis, Roux-en-Y
Is there a role of functional endoscopic evaluation of swallowing (FEES) in aiding tracheotomy decannulation post oral cancer surgery?
Authors: Vibhu Ranjan Sahni, Shamit Chopra, Anubha Bharthuar
Journal: Journal of Clinical Oncology (2020)

e18523 Background: A significant proportion of patients with oral cancer require perioperative tracheotomy. The altered oral anatomy post surgery significantly impairs the first and second stages of swallowing, resulting in swallowing dysfunction and potential aspiration. There is no priordata on utilization of FEES or other objective tools to predict successful tracheotomy decannulation in patients with oral cancer. Methods: This constituted a retrospective analysis of 237 patients with oral cancer treated at our institution between Feb 2017 and Dec 2019. Seventy two (30.4%)patients underwent perioperative tracheotomy. Post surgery,after excluding patients who were not considered candidates for early decannulation, 48 (65.7%) underwent FEES with the endpoint of tracheotomy decannulation. The number of FEES procedures required for decannulation was correlated with patient and disease-specific variables utilizing Chi square analysis. Results: The rate of successful decannulation was 100%. The mean number of days from tracheotomy to decannulation was 24.9. Thirty two (66.7%) patients underwent decannulation post the first FEES, notablyupon documentation of no penetration or aspiration to three bolus consistencies. However, 33.3% patients needed swallowing therapy followed by a second (18.8%) or a third (14.6%) FEES before they could be decannulated (late decannulation). No patients required a repeat tracheotomy. A significantly higher proportion of individuals at or younger than median age were decannulated earlier, compared with individuals above median age ( p= 0.01). There was no statistically significant difference between early (T1/2) and advanced (T3/4) primary lesions and timing of decannulation ( p= 0.83). The presence of comorbid diabetes mellitus did not correlate with decannulation timing ( p= 0.81). Conclusions: FEES constitutes a reliable, minimally invasive and cost-effective tool to aid successful decannulation across all stages of oral cancer. It may be indicated especially in older individuals. It helps guide swallowing therapy, and thus potentially augments quality of life by tailoring serial evaluations to aid early decannulation.
Circulating tumor DNA dynamics to predict cancer recurrence/metastasis in Chinese pathologic stage I lung adenocarcinoma.
Authors: Chao Cheng, Weixiong Yang, Na You, Minghan Jia, Sai-Ching Yeung, Man Yu, Yinguang Wang, Xiayu Fu, Zhenguo Liu, Bo Zeng, Qiuxiang Ou, Xue Wu, Yang Shao, Siyu Wang
Journal: Journal of Clinical Oncology (2020)

3537 Background: Pathologic(p)stage I lung adenocarcinoma (LUAD) patients exhibit high levels of genetic heterogeneity and the association between the genomic characteristics of (p)stage I LUADs and tumor recurrence remains poorly understood. Circulating tumor DNA (ctDNA) monitoring after resection represents a useful tool to predict response to therapy and tumor recurrence but its application in (p)stage I LUAD patients remains controversial. In addition, it is of great clinical interest to decipher the difference of genetic features between ground-glass opacity (GGO) and solid nodules (non-GGO) subgroups. Methods: Tumor tissues and matched post-operative plasma samples were collected from a total of 86 Chinese (p)stage I LUAD patients who were enrolled in a clinical study (NCT03172156). Comprehensive genomic profiling was performed using capture-based hybrid next generation sequencing by targeting 422 cancer relevant genes. Results: EGFR and TP53 represent commonly mutated genes in this cohort of (p)stage I lung adenocarcinoma, followed by alterations in ALK, PIK3CA, STK11and MYC. For a median follow up period of 21.54 months after surgical resection, we observed that ctDNA positivity significantly correlated with an increased probability of early tumor recurrence or metastasis ( P= 0.03, HR = 7.9), and in particular, the EGFR mutation status of ctDNA samples rather than that of primary tumor samples significantly correlated with shorter disease-free survival (DFS). Further comparison between GGO and non-GGO subgroups indicated that the frequency of TP53 mutations in non-GGO was markedly higher than that in GGO (48% vs 20%, P&lt; 0.05). In addition, pathway analysis showed that the epigenetic regulation pathway was more frequently affected in the GGO subgroup, while impaired apoptosis/cell cycle pathway was more enriched in the non-GGO LUADs. Conclusions: Our data show that ctDNA positivity, including the EGFR mutation status, significantly correlated with early relapse or metastasis after surgery, representing a useful tool to predict treatment response and tumor relapse in (p)stage I LUAD patients. Mutated TP53 was more abundant in non-GGO comparing to GGO (p)stage I LUADs that may act as potential oncogenic driver in LUAD development and/or disease progression. Clinical trial information: NCT03172156 .
泪囊恶性黑色素瘤一例
Authors: 张庆, 王俊东, 黄天纳
Journal: BMJ (2005)

患者男,83岁.因右眼溢泪半年、血泪1个月,于2003年9月27日收住解放军总医院.患者于2003年3月出现右眼溢泪,无其他不适,8月右眼出现血性分泌物,到当地医院就诊,给予泪道冲洗及抗感染治疗,效果不佳.后行CT检查发现右眼泪囊区肿物,即转来解放军总医院。
Complications of high-dose methotrexate (HDMTX) in lymphoma patients.
Authors: Darragh O'Donoghue, Huong Truong, Heidi Diann Finnes, Jennifer McDonald, Stephen M. Ansell, Nelson Leung
Journal: Journal of Clinical Oncology (2020)

e20035 Background: HDMTX is a vital treatment of lymphoma secondary to central nervous system penetrance. MTX is nephrotoxic and may cause acute kidney injury (AKI). AKI results in delayed MTX elimination, increased hospital length of stay (LOS) and intensive care unit (ICU) stays. Our aim was to characterise the complications and associated 48-hour MTX levels in lymphoma patients undergoing HDMTX. Methods: A retrospective review of the electronic medical record was conducted to identify lymphoma patients who received HDMTX from 1/1/2002 to 12/31/18. We assessed the incidence of AKI using AKIN criteria, ICU admission, and LOS across 48 hour MTX levels per the table. Results: 2704 cycles of HDMTX were identified. The mean age was 64 years, 54% were male and 72.2% received high dose (≥8g/m 2 ). A significant increase in AKI severity (p &lt; 0.0001) and LOS (p &lt; 0.01) occurred with increasing 48 hour MTX levels, (p &lt; 0.001, Table). All 7 patients requiring dialysis had MTX levels &gt; 10. ROC curve analysis for AKI grade ≥ 2 demonstrated a 48 hour MTX level threshold of 1.28 (AUC 0.79) with relative risk of 7.6 (95% CI 5.3-11) and odds ratio of 8.8 (95% CI 5.9-13.1). A significant increase occurred in LOS across escalating 48 hour MTX level subgroups (p &lt; 0.01, Table). A significant rise in ICU admissions occurred with increasing MTX levels ( &lt; 0.01% for MTX &lt; 2 compared to 15% with MTX &gt; 5). Conclusions: Complications of HDMTX are significantly increased with elevated 48 hour MTX levels, particularly with levels &gt; 1 μmol/L. [Table: see text]
直肠Dieulafoy病二例
Authors: 李曙晖, 王梅, 柴同海, 张爱琴
Journal: BMJ (2005)

例1 男,64岁,因便血,伴头晕、心悸、出冷汗3 h入我院外科.便血为鲜血,量约1 000 g.平时大便正常.体格检查:体温36.5℃,脉搏126次/min,血压75/50 mm Hg(1 mm Hg=0.133 kPa),神志清楚,精神差,贫血貌,皮肤黏膜无黄染,浅表淋巴结未触及,心肺腹无异常,四肢稍凉。