tbuckley/cabot-search huggingface dataset:
Clinical impact of targetable gene alterations on therapeutic outcomes in stage II/III locally advanced non-small cell lung cancer patients.
Authors: Yoshitaka Zenke, Shingo Matsumoto, Terufumi Kato, Shingo Miyamoto, Takuma Imakita, Tetsuya Mitsudomi, Hiromi Aono, Ryota Ushio, Naoki Furuya, Kazumi Nishino, Saori Takata, Mika Nakao, Satoshi Hara, Motoko Tachihara, Akimasa Sekine, Jun Sakakibara-Konishi, Ryo Toyozawa, Kiyotaka Yoh, Koichi Goto
Journal: Journal of Clinical Oncology (2020)

9038 Background: The clinical significance of genetic alterations in stage II/III non-small cell lung cancer (NSCLC) patients has not yet been clarified. We have prospectively analyzed NSCLC patients for cancer-related gene alterations and have followed up clinical course of the patients, establishing a large-scale clinico-genomic database in our nationwide genome screening project (LC-SCRUM-Japan). Methods: Submitted tumor samples were subjected to a targeted next-generation sequencing (NGS) system, Oncomine™ Comprehensive Assay. Therapeutic and prognostic data were collected and updated every year. Results: Since March 2015 to May 2019, 5166 non-squamous NSCLC patients from 263 institutions had been enrolled in the LC-SCRUM-Japan, and 754 of them were diagnosed as stage II/III. The median age of the 754 patients was 67 years (range, 21-92), and 503 (67%) were male, 595 (79%) smokers and 631 (84%) stage III. Of 640 available samples, 258 (40%) had targetable gene alterations, comprising 106 KRAS mut, 42 EGFR mut, 29 BRAF mut, 20 MET ex14skip/amp, 16 ALK fus, 12 ROS1 fus, 11 ERBB2 ex20ins, 8 RET fus, 7 EGFR ex20ins, 5 AKT1 mut, 1 NRG1 fus, 1 FGFR2/3 fus. In patients who received surgery (n = 159), 3-year disease-free survival rate was worse in patients with targetable gene alterations than in those without (40% vs 58% months; p = 0.03). In patients who received cytotoxic chemo-radiotherapy (n = 148), the response rate was similar in patients with targetable gene alterations and those without (70% vs. 77%); however, 3-year progression-free survival rate tended to be shorter in patients with targetable gene alterations than in those without (19% vs 35%; p = 0.08). Conclusions: In stage II/III NSCLC, the total frequency of targetable gene alterations was similar to that previously evaluated in our stage IV cohort (45%), and the current standard therapies showed early progression in the targetable gene-altered patients. A novel effective multimodality treatment in combination with targeted therapies is needed for this population.
Alternative inflammatory cytokines pathways in prostate cancer: In search of new therapeutic options.
Authors: Marlena Janiczek, Łukasz Szylberg, Paulina Antosik, Andrzej Marszalek
Journal: Journal of Clinical Oncology (2020)

e17504 Background: The inflammatory reaction pathways have impact on tumor cells development or anti-tumor responses. Both by the activity of the innate and acquired immune response signalling pathways. A proper acquired immune response is considered as anti-tumor. While inadequate innate or acquired stimulation of the immune system can cause chronic inflammation that can lead to oncogenesis. Numerous reports have revealed a relationship between chronic prostatitis and prostate cancer (PCa). The aim of the study is to retrospectively assess the histological material of PCa with the Gleason grading score. The histological material evaluated the level of inflammatory factors of pathways initiated by IL-17A and IL-17F. The evaluation of the expression of pro-inflammatory factors such as IL-17A, IL-17F, IL-17RA, IL-17RC, AKT1, EBPbeta, TRAF 6 and NF-kB made it possible to assess the influence of the inflammatory process on the progression of PCa. Methods: Studies were carried out on archival tissue material in the form of paraffin blocks of 40 men with PCa after radical prostatectomy. The control group of 10 men with benign prostatic hyperplasia (BPH). The material was obtained by the transurethral resection of the prostate (TURP). The immunohistochemistry was performed on the material prepared in this way using specific primary antibodies against IL-17A, IL-17F, IL-17RA, IL-17RC, ACT1, TRAF-6, C/EBPbeta and NF-kB. The expression of the antibody to be examined using the light microscopy and the Remmele Stegner score (IRS) in cancer staining were then evaluated. Statistical analysis was performed using the non-parametric Kruskal-Wallis test. Results: In statistical analysis, it was shown that the inflammatory pathway IL17A/IL-17RC/TRAF6/NF-kB occurs in both BPH and PCa. IL-17 RA did not show expression in any group of patients and in the control group. In addition, along with the increase in the grading of Gleason score, a decrease in the expression of the tested inflammatory parameters was demonstrated. Conclusions: The inflammatory process has an impact on the cancer of prostate cancer. There is a correlation between the grades according to Gleason score and the level of expression of inflammation parameters. Activation of the inflammatory pathway through IL17A/IL-17RC/TRAF6/NF-kB cascade could correlate PCa development on the base of BPH. Evaluation of the inflammatory pathway in PCa, the initiated IL-17, may become a starting point for further research on an attempt to use, for example, immunotherapy in PCa.
Feasibility of evidence-based treatment of childhood acute myeloid leukemia in a Sub-Sahara Africa center.
Authors: Irene Nzamu, Joseph Ssenyondwa, Ronald Naitala, Anne Akullo, Siyadora Ankunda, Heronima Kashaigili, Deborah Omeddo, Nana Nakiddu, Ruth Namazzi, Deogratias Munube, Phillip Kasirye, Deogratias Bakulumpagi, Ernest Naturinda, Joseph Lubega, Peter Wasswa
Journal: Journal of Clinical Oncology (2020)

e22508 Background: The proportion of Acute Myeloid Leukemia (AML) among childhood leukemias is putatively higher in Sub-Sahara Africa (SSA) compared to Western experiences. However, the treatment of childhood AML is challenging in SSA settings because of inadequate facilities for supportive care to deliver intensive AML regimens and, hence, high treatment-related mortality (TRM). Many pediatric oncology centers in SSA treat childhood AML with a palliative intent, with or without chemotherapy. At the Mulago National Referral Hospital (MNRH)/Global HOPE Center in Uganda, we treat AML with a curative intent. We distinguish Acute Promyelocytic Leukemia (APL) and AML with Down Syndrome (AML-DS) from other subtypes of AML. We treat APL with Children’s Oncology Group (COG) AAML1331 and AML-DS and other AML with modified reduced intensity regimens. We hereby share our experience of anti-cancer and supportive treatment, TRM, remission rates, and short-term overall survival (OS). Methods: We performed a retrospective cohort analysis of children diagnosed with AML between March 2019 and February 2020. The diagnosis of AML was established by bone marrow or peripheral blood morphology and immunophenotyping by flow cytometry according to WHO criteria. All cases of APL were confirmed by cytogenetics for t(15;17). Children without DS or APL received 2 cycles of Cytarabine 100mg/m 2 12 hourly Days 1-10, Daunorubicin 50mg/m 2 Days 1,3,5 and a single triple intrathecal chemotherapy for induction and 2 cycles of high dose Cytarabine 3000mg/m 2 for consolidation. Supportive care comprised warm saline oral rinses, antiseptic baths, antimicrobial prophylaxis with cotrimoxazole, ciprofloxacin and itraconazole, and blood product support. Results: Of the 74 children diagnosed with leukemia 23 (31%) were AML; 4/23 (17%) of AML were APL and 3/23 (13%) were AML-DS. The mean age at diagnosis of AML was 6.1 (SD 4.3) years and 16/23 (70%) were males. For the 4 cases of APL, TRM 1/4 (25%) due to differentiation syndrome, remission rate 2/4 (50%), 1-year OS 75%; 95% CI 32.5-100. For the 3 cases of AML-DS, TRM 1/3 due to severe sepsis with respiratory failure, remission rate 1/3, and 1 was referred to another treatment center. For the other AML, TRM 2/16 (12.5%) due to severe sepsis, remission rate 9/16 (56%) and 1-year OS 78.6%; 95% CI 57.1-100. Conclusions: It is feasible to treat, manage TRM, and achieve remission in childhood AML in the SSA setting. Although there were several TRMs, a remission rate of 56% in the non-APL non-AML-DS is a promising outcome.
The Death Throes of Mercy — Our Shared Responsibility When Hospitals Close
Authors: Austin S. Kilaru, Kevin B. Mahoney
Journal: New England Journal of Medicine (2020)

H ospital closures disrupt com- munities.They also demand that we clarify our goals: Do we come together to support endangered hospitals, or do we support the patients and communities relying on them?Sometimes the second requires the first, but not always.For 245 years, the Philadelphia General Hospital served the city as a public institution.It closed in 1977, when the city could no longer afford escalating operating costs and capital expenses.The creation of Medicare and Medicaid also made it easier for private hospitals to care for the poor and the elderly.Together, private hospitals assumed responsibility for vulnerable patients and crafted a new safety net.Many of those hospitals have since closed.Last year, the bankruptcy of Hahnemann University Hospital drew national attention and was portrayed by some observers as a tale of corporate greed endangering the health of vulnerable patients. 1 The closure complicated access to care for Hahnemann's patients, nearly all of whom had public insurance or were uninsured.More than 2500 people lost their jobs, including 575 physicians-in-training.Less than a year later, another Philadelphia institution, Mercy Philadelphia Hospital, has announced that it will close.Although Mercy has made noble efforts to remain open, including expanding its emergency department (ED), the hospital is in its death throes.Hospitals are failing in communities throughout the United
Intrathoracic versus cervical anastomosis after minimally invasive esophagectomy for esophageal cancer: A randomized controlled trial.
Authors: Moniek Verstegen, Frans van Workum, Bastiaan Klarenbeek, Suzanne Gisbertz, Gerjon Hannink, Jan Willem Haveman, Joos Heisterkamp, Ewout Kouwenhoven, Jan Van Lanschot, Grard Nieuwenhuijzen, Donald Van der Peet, Fatih Polat, Maroeska Rovers, Camiel Rosman
Journal: Journal of Clinical Oncology (2020)

4509 Background: Robust evidence is lacking whether Ivor Lewis minimally invasive esophagectomy (MIE) or McKeown MIE should be preferred for patients with mid to distal esophageal or gastro-esophageal junction Siewert I-II (GEJ) cancer. Methods: In this multicenter randomized controlled trial, patients with esophageal (below the level of the carina) or GEJ cancer planned for curative resection were recruited. Eligible patients were randomly assigned (1:1) to either Ivor Lewis MIE or McKeown MIE. The primary endpoint was anastomotic leakage (AL) requiring endoscopic, radiologic or surgical intervention. Secondary outcome parameters were overall AL rate, postoperative complications, length of stay and mortality. Results: A total of 262 patients were randomly assigned to Ivor Lewis MIE (n = 130) or McKeown MIE (n = 132). Seventeen patients were excluded from the trial due to not meeting inclusion criteria (n = 2), physical unfitness for surgery (n = 3), patients’ choice (n = 3), interval metastases (n = 5) or peroperative metastases (n = 4). AL necessitating reintervention occurred in 15 (12.3%) of 122 patients after Ivor Lewis MIE and in 39 (31.7%) of 123 patients after McKeown MIE (relative risk 0.39, 95% CI 0.22-0.65; risk difference 19.4%, 95% CI 7.9%-31.8%). Overall AL rate was 12.3% after Ivor Lewis MIE and 34.1% after McKeown MIE. Severe complications (Clavien-Dindo ≥ 3b) were observed in 10.7% after Ivor Lewis MIE and in 22.0% after McKeown MIE. Pleural effusion requiring drainage occurred in 9.8% of patients after Ivor Lewis MIE and 21.1% of patients after McKeown MIE. RLN palsy rate was 0% after Ivor Lewis MIE and 7.3% after McKeown MIE. Median length of hospital stay was 10 days (IQR 8 – 15 days) after Ivor Lewis MIE and 12 days (IQR 9 – 18 days) after McKeown MIE. ICU length of stay and mortality rates were comparable between groups. Conclusions: These findings provide evidence for a lower rate of AL requiring reintervention after Ivor Lewis MIE compared to McKeown MIE for patients with mid to distal esophageal or GEJ cancer. Clinical trial information: NTR4333 .
短程心理治疗法治疗心理创伤一例
Authors: 孙燕玲
Journal: BMJ (2008)

患者女,17岁,入伍10个月.班长代诉:停经3个月,伴胸口堵闷、烦躁.患者被动就诊,表情冷漠,情绪低落,少语,无笑容.多次询问诱导后,自诉3个月前其外祖母突然去世,外祖父昏迷抢救,母亲着急病倒住院,得知消息时,自己悲痛万分,感天崩地裂,白天黑夜不分,只知道哭泣,走路一脚高一脚低,但因工作没能回去帮助料理家事。
Diagnostic and surgical treatment of carotid body tumor: a report of 21 cases
Authors: Rongwei Xu, Zhidong Ye, Xueqiang Fan, Jianbin Zhang, Qian Wang
Journal: BMJ (2015)

The clinical data of 21 patients with carotid body tumor (CBT) were analyzed retrospectively. The lesions were unilateral (n=20) and bilateral (n=1). Among 20 surgical cases, the procedures included tumor resection alone (n=11), tumor resection along with external carotid artery (n=6) and vascular reconstruction of carotid artery after resection of tumor body (n=3). No mortality occurred during perioperative period. CBT was confirmed by pathologic examination in all cases and 1 case was malignant. Follow-up period ranged from 3 months to 7 years and the follow-up rate was 85%. Five cases of cranial nerve impairment recovered completely over 3 months. One case of bilateral CBT underwent contralateral tumor resection at another hospital 1 year later and 1 case with malignant tumor died from metastases 3 years later. The remainder survived recurrence-free. CBT tends to be misdiagnosed. Therefore ultrasonography, digital subtraction angiography (DSA), CT angiography (CTA) or magnetic resonance angiography (MRA) are important for preoperative diagnosis and evaluation. Surgical resection is a first choice for CBT.


Key words: 
Carotid body tumor; Diagnosis; Surgical procedures, operative
Phase II neoadjuvant (N-) gemcitabine (G) and pembrolizumab (P) for locally advanced urothelial cancer (laUC): Interim results from the cisplatin (C)-ineligible cohort of GU14-188.
Authors: Hristos Z. Kaimakliotis, Nabil Adra, William Kevin Kelly, Edouard John Trabulsi, Richard C. Lauer, Joel Picus, Zachary L Smith, Radhika Walling, Timothy A. Masterson, Adam C Calaway, Michael O. Koch, Elizabeth Sonderman, Pingfu Fu, Gordon Goolamier, Cheryl Eitman, Lee Evan Ponsky, Christopher J. Hoimes
Journal: Journal of Clinical Oncology (2020)

5019 Background: Patients (pts) with laUC who are C-ineligible have inferior survival compared to counterparts who receive C based N-therapy and have a pathologic response at radical cystectomy (RC). Cohort 2 (C2) of the GU14-188 trial is designed to assess the tolerability and efficacy of N- G and P in laUC pts who are C-ineligible. Methods: Eligible pts for C2 were surgical candidates and C-ineligible with cT2-4aN0M0 bladder UC or mixed histology. Enrollment followed a Simon 2-stage design for H 0 of interval futility which was rejected at stage 1, and fully enrolled. Pts were treated with N- G (1000mg/m 2 ) on days 1, 8, and 15 of a 28 day cycle (cy) for a total of 3 cy, and overlapped with P 200mg every 3wks starting on cy 1 day 8 x 5 doses. Minimum criteria for evaluation of safety: 1 dose of P, and for efficacy: 2 doses P and RC. The primary endpoint of pathologic muscle invasive response rate (PaIR, ≤pT1N0) was assessed at RC and designed for 86% power, 4% significance to detect PaIR difference from 18 to 40%. Molecular subtyping is planned. Results: 37 pts were enrolled to C2 with a median (mdn) age of 72, 70% male, 55% &gt; cT2. C-ineligibility was due to renal function (49%), hearing (30%), neuropathy (12%). Mdn per-pt doses given (intended) for P:5(5) and G:9(9). The PaIR was 51.6% (95%CI 0.35, 0.68), P0 (ypT0N0) rate of 45.2%, and neither correlated with baseline PD-L1 score. Downstage to PaIR occurred in 57% of pts with cT2, and 47% of &gt; cT2. Mdn time to RC from last dose was 5.6wks. Six were not included in the primary analysis: 3 (8.1%) did not have RC due to progression (RFS censored), 2 did not receive required protocol therapy, and 1 withdrew consent. At mdn follow up of 10.8mo (4-24), the estimated 12mo RFS, OS, and DSS is 74.9%, 93.8%, and 100%, respectively. Treatment related AE included grade (gr) 3/4 neutropenia (24%), anemia (13%), and platelets (5%). There were no gr 4 non-heme AE, and of 14 (36%) pts with gr 3, 12 did not preclude RC. Of these, there were 4 gr 3 investigator assessed immune related adverse events (IAirAE) of pneumonitis (5%), colitis (3%), and AST elevation (3%). Though IAirAE improved, protocol therapy was discontinued in 3 pts: 2 did not have RC due to progression. Conclusion: N- G with P in C-ineligible pts with laUC is feasible with manageable toxicity, and has a pathologic downstage rate comparable to standard of care in the C-eligible population. G and P warrants further study with component contribution as a C- free N- option in laUC. Clinical trial information: NCT02365766 .
Current treatment efficacy for metastatic soft tissue sarcoma: A targeted literature review.
Authors: Heide Stirnadel-Farrant, Anadi Mahajan, Navdeep Dhillon, Nashita Patel, Shibani Pokras
Journal: Journal of Clinical Oncology (2020)

e23577 Background: Soft tissue sarcoma (STS) is a rare malignancy with an annual incidence rate of &lt; 5 cases per 100,000 persons; outcomes for metastatic STS (mSTS) are poor. A targeted literature review was conducted to quantify the efficacy/effectiveness of current mSTS therapies. Methods: A structured search based on the population, intervention, comparator, outcome, study type (PICOS) framework was performed on articles (2009–2019) in MEDLINE, Embase, and Cochrane Central. Limited congress searches (ESMO, AACR, ASCO 2016–2018/2019) were also conducted. Clinical trials (CT) and observational studies (Obs) involving patients (pts, any age) with advanced mSTS receiving any pharmacological intervention were included. After screening, selected efficacy (CT) or effectiveness (Obs) endpoints (including progression-free survival [PFS], overall survival [OS], overall response rate, and duration of response) stratified by line of treatment (LOT, if available) were extracted. Results: Overall, 85 studies (56 CT, 29 Obs) met inclusion criteria; study size was 20–4,274 pts. PFS and OS (from 70 studies) were reported for pts with mSTS treated with a wide range of interventions including doxorubicin, trabectedin, pazopanib, and gemcitabine. Across any LOT, median PFS ranged 1.5–9.3 months in CT and 2.1–11.0 months in Obs; ranges were 5.7─28.8 months and 7.0─38.6 months, respectively, for OS. Median PFS and OS were generally lower with later (vs initial) LOT; few studies assessed ≥4 LOT (Table). Outcome data (any LOT) for trabectedin and pazopanib (the only approved targeted mSTS treatments) are shown in Table. Conclusions: This review of the efficacy/effectiveness of current treatments highlights the unmet clinical need for therapies that improve survival outcomes in pts with mSTS. Results may be influenced by small sample size, pt population, and care improvements over the period studied. [Table: see text]
A novel method for enrichment and detection of the six major subtypes of EGFR exon 19 deletions simultaneously by capturing mutant-alleles.
Authors: Yue Pu, Rui Lin, Tao Wang
Journal: Journal of Clinical Oncology (2020)

e15539 Background: EGFR exon 19 deletions (19DELs) are important precision therapy targets for NSCLC patients. Due to over twenty subtypes of 19DEL mutations, it is usually challenging for detecting different deletion forms in one assay using limited DNA preparation from plasma sample. Methods: Previously we had developed a high sensitivity detection method, namely PEAC, to detect single somatic mutation in one assay. The method used locked¨Cnucleic acid modified short DNA probe to capture mutant fragment under an optimized temperature. In the present study, we have established a multiplexing PEAC approach for simultaneous enrichment and high sensitivity detection of six major subtypes of EGFR 19DELs.The six subtypes overall account for &gt;86% EGFR exon 19 deletions in the patient population. Results: Genomic DNA of EGFR wild-type was mixed with DNA samples of known EGFR 19DEL mutations. The mutation allele fractions of 5%, 1%, and 0.1% for the six 19del subtypes were constructed, which included c.2235-2249del15 p.E746_A750del, c.2236-2250del15 p.E746_A750del, c.2237-2255delinsT p.E746_A752delinsV, c.2235-2249delinsC p.L747_A750delinsP, c.2240-2254del15 p.L747_T751del, and c.2240-2257del18 p.L747_P753delinsS. The mixed DNA samples were sonicated to mimic the fragment distribution of circulating-free DNA (cfDNA) and PCR amplified for exon 19 regions. Multiplexing enrichment using the six specific probes targeted to the 19DEL subtypes were performed to the amplified DNA fragments under the optimal binding conditions. Sanger sequencing all showed detectable variants in the enriched samples starting with 5%, 1%, or 0.1% mutants, which indicated the capacity and high sensitivity of multiplexing PEAC technology. To explore the potential of multiplexing with other EGFR mutants, the 0.1% mixed mutants of 19DEL were PCR amplified for EGFR exon 20 and exon 21 in addition to exon 19, and followed with enrichment and detection of the six 19DEL variants. Sanger sequencing can detect all the six subtypes of 19DELs. Our method is superior to ddPCR in some aspects such as high throughput and low starting DNA amounts. Conclusions: Multiplexing PEAC technology can simultaneously enrich and detect the six major subtypes of EGFR 19 deletions with high sensitivity. It also has potential to multiplex with other EGFR driver mutations such as in exons 18-21. The technology may serve as an attractive method for detecting mutations in liquid biopsies in clinical practice.