tbuckley/cabot-search huggingface dataset:
Real-world hypothesis-generating cohort of pancreatic cancer patients with brain metastases.
Authors: Derek Cridebring, David Hadley, Timothy S Scott, Alex B Vilner, Tammy M Heckman, Kevin Gosselin, Gayle S. Jameson, Susan Haag, Erkut Hasan Borazanci
Journal: Journal of Clinical Oncology (2020)

e16720 Background: Pancreatic cancer (PC) is the third most lethal form of cancer in the United States, and is most often diagnosed having already metastasized, making its 5-year survival rate one of the lowest. Metastatic PC (mPC) is most common at sites such as liver, lymph nodes, and lung while, in contrast, brain metastases from PC are rare. Brain metastases present a major challenge for future oncological research, as they are difficult to treat. If PC patients most likely to develop brain metastases can be identified earlier, there is an opportunity for rapid therapeutic intervention. There is limited research and understanding of the relationship between pancreatic cancer and brain metastases. Methods: We performed a retrospective, non-interventional study using deidentified data. Inteliquet’s data was aggregated from its consortium of 175 US healthcare locations, which includes a variety of source systems at each site. These sources include electronic medical record systems, laboratory information management systems, and other sources. A subset of the adult mPC data originally treated at HonorHealth was identified as an exploratory cohort. Results: 833 patient records were identified with drug treated mPC, 33 (4%) of which had metastasized to the brain. The PC dataset had a median diagnosis age of 65 and was 46% female. The site of the primary tumor within the pancreas was acquired from ICD10 code: 35% were in the head, 14% in the tail, 15% in the body, 5% in overlapping sites, 6% in other parts and 26% where location was unspecified. Metastatic locations came from secondary malignancy ICD10 codes: 63% had liver and 25% had lung metastases, which aligns with prior studies. For patients with brain metastases, the gender distribution was 42% female, while the distribution of primary PC site was: 33% head, 9% tail, 6% body, 6% in overlapping locations, 12% in other parts and 33% with unspecified location. The median age of diagnosis in the brain metastasis group was 67 years. Conclusions: This is the largest study of PC patients with brain metastases that we could find. 33 patients out of 833 had brain metastases compared to a recent review which had 25 cases. Our data suggests that specification of the primary pancreatic site is more difficult, aside from the head of the pancreas. Analyses are underway to explore correlations between other clinical factors and brain metastases, and to calculate the time in between the initial pancreatic cancer diagnosis and detection of the brain metastasis. This hypothesis-generating cohort will be tested in patient data from the rest of the consortium.
Appropriateness of opioid prescribing in cancer patients.
Authors: Robert M. Matera, Christine M. Duffy, James Robbins, Camille Higel-Mcgovern, Ashley Chartier, Don S. Dizon
Journal: Journal of Clinical Oncology (2020)

e24129 Background: The American Cancer Society estimates 48% people with cancer and 34% of cancer survivors report issues with chronic pain and 43 and 10% report taking an opioid, respectively. We sought to further examine the indications for pain medications in people with cancer and whether they were related to cancer, treatment, or neither. Methods: Retrospective chart review was conducted on 122 cancer patients treated at a single American academic cancer center. Authors created criteria to categorize whether patients’ pain was attributable to their malignancy or treatment regimen. Two trained coders reviewed each case with a third to resolve coding differences. Pain due to disease was further subdivided into pre-determined categories (tumor site, fracture, surgery, neuropathy, disease progression). The relationship between demographic, disease and pain type were examined in relation to inappropriate opioid prescribing using Chi-square analysis and Fischer’s exact test. Results: 55% of patients were male, 39% had metastatic disease, and 33% NED. 95% had received chemotherapy 69% radiation and 43% surgery. Factors associated with inappropriate opioid prescribing included increased age and female sex. Appropriateness of opioid prescribing was not associated with a specific cancer type or pain indication subset. Conclusions: As survivorship among cancer patients increases this may result in a cohort of patients in which opioid pain medication may not be indicated and in whom the risks may outweigh the benefits.
Noninvasive identification of lineage-specific circular RNA for ER-positive breast cancer.
Authors: Jason Brown, Palak Shah, Josh Vo, Lanbo Xiao, Yashar Niknafs, Xuhong Cao, Arul Chinnaiyan
Journal: Journal of Clinical Oncology (2020)

3543 Background: Non-invasive testing in plasma using RNA biomarkers has been limited by exoribonuclease-mediated degradation of RNA. Circular RNA (circRNA) are covalently closed RNA structures that resist this degradation due to their circular structure. Therefore circRNA are more stable than their linear counterparts. CircRNA are formed by alternative backsplicing of the 3’ end of a downstream exon to the 5’ end of an upstream exon. Here, we propose a novel method for non-invasive identification of circRNA and demonstrate circularized forms of several lineage and cancer specific targets for estrogen receptor-positive breast cancer. Methods: Capture RNA sequencing on cancer tissue was previously performed to determine the relative expression of potential circRNA isoforms in breast cancer patients. These isoforms as well as those predicted by intron length were screened using a quantitative PCR-based assay on ER-positive breast cancer cells. RNA extracted from breast cancer cells are exposed to ribonuclease R to demonstrate stability of circRNA. CircRNA derived from targets with known universal expression are used as positive controls as well as for analysis on plasma. Results: We identify the circRNA isoforms with highest expression for five genes, including ESR1, that are differentially expressed in ER-positive breast cancer compared to other cancers and normal breast tissue. We determine that the circRNA corresponding to all five targets is specifically expressed in breast cancer cell lines with at least 1000-fold higher expression than in non-ER positive breast cancer cell lines. We demonstrate that the highest expressing circRNA isoforms are resistant to degradation by ribonuclease R, whereas corresponding linear mRNA is susceptible. We also demonstrate the presence and stability of positive control circRNA in plasma from patients without cancer. Conclusions: CircRNA are promising biomarkers for early non-invasive detection of cancer due to their stability in plasma. This assay reliably detects ER-positive breast cancer specific circRNA, and exoribonuclease resistance has been validated. Application of this diagnostic assay to plasma from breast cancer patients is underway.
以食管外症状为突出表现的胃食管反流病临床分析
Authors: 刘秋慧, 陈健, 王进
Journal: BMJ (2007)

对经胃镜或24 h食管pH值监测后确诊,并经质子泵抑制剂治疗有效的48例以食管外症状为突出表现的胃食管反流病患者的临床资料进行回顾分析.结果 显示其症状以胸痛最多见,其他依次为咽部异物感、咽喉痛、咳嗽、哮喘等.抗酸反流治疗有效。
Randomized double-blind placebo-controlled trial of primary maintenance vigil immunotherapy (VITAL study) in stage III/IV ovarian cancer: Efficacy assessment in <i>BRCA1/2</i>-wt patients.
Authors: Rodney Paul Rocconi, Elizabeth A. Grosen, Sharad A. Ghamande, John K. Chan, Minal A. Barve, Jonathan Oh, Devansu Tewari, Peter C. Morris, Erin E. Stevens, Justin N. Bottsford-Miller, Min Tang, Phylicia Aaron, Gladice Wallraven, Ernest Bognar, Luisa Manning, John J. Nemunaitis, Brian M. Slomovitz, Thomas J Herzog, Bradley J. Monk, Robert L. Coleman
Journal: Journal of Clinical Oncology (2020)

6017 Background: Vigil is an autologous tumor cell vaccine constructed from autologous harvested tumor tissue transfected with a DNA plasmid encoding GMCSF and bi-shRNA-furin thereby creating TGFβ expression control. Methods: A randomized double-blind placebo-controlled trial of Vigil vs. placebo was performed in advanced stage frontline OC patients. Relapse-free survival (RFS) and safety were endpoints. Patients who achieved complete clinical response were randomized [1:1 to placebo (control group, CG) or Vigil (Vigil group, VG)] after completion of frontline surgery and chemotherapy. All patients received 1 x 10e7 cells/ml of Vigil or placebo intradermally once a month for up to 12 doses. Results: Ninety-two patients were randomized with 91 patients in the per-protocol population (PP), (VG n=46; CG n=45). 62 patients were tested for BRCA1/2 status. VG showed no added overall toxicity compared to CG and no grade 4/5 toxicities were observed. Grade 2/3 toxic events were observed in 18% of CG patients (most common bone pain, fatigue) compared to 8% of VG patients (most common nausea, musculoskeletal pain). From time of randomization median RFS for all 91 patients was favorable in the VG (HR 0.69, one-sided p 0.088).Stratified by BRCA status, an advantage in RFS was seen in the BRCA1/2-wt patients in VG (19.4 mo) compared to CG (8 mo) (HR 0.51, 90% CI 0.26 – 1.01, one-sided p 0.050) from time of randomization and HR of 0.49 (90% CI 0.25 – 0.97, one-sided p 0.038) from time of surgery. Median time from surgery to randomization was 208.5 days (6.9 mo) in VG vs. 200 days (6.6 mo) in CG. 37.5% BRCA1/2-wt Vigil treated patients relapsed compared to 71% of placebo at time of data snap for analysis (HR 0.51, one-sided p 0.05), (median follow-up of 34.3 mo for all n=91 subjects). Germline and somatic BRCA1/2 molecular testing via central third party is underway on all 91 patients under continued blinded conditions to validate activity in BRCA1/2-wt. Conclusions: Vigil immunotherapy as frontline maintenance in Stage III/IV ovarian cancer is well tolerated and showed RFS clinical benefit, particularly in BRCA1/2-wt disease. Clinical trial information: NCT02346747. [Table: see text]
Association of body mass index (BMI) with clinical efficacy of immune checkpoint inhibitors (ICI) in advanced cancer patients: A retrospective analysis.
Authors: Raphael Brandao Moreira, Mauricio Fernandes, Mariana Ribeiro Monteiro, Francine Luiz, Erika Simplicio, Perla de Mello Andrade, Mayara Batista, Letycia Lima, Astrid Silva, Juliana Nunez, Daniele Freitas, Luiz H. Araujo, Pedro Nazareth Aguiar
Journal: Journal of Clinical Oncology (2020)

e15066 Background: Obesity is linked to an increased risk of cancer development. The excess of body fatness seems to be associated with alterations in hormonal, metabolic and inflammatory pathways, that may lead to activation of the carcinogenesis process. Previous studies suggested this obesity pro-inflammatory state could improve ICI clinical efficacy. Methods: Baseline characteristics and clinical outcomes were retrospectively collected from advanced cancer patients of any primary site, and treated with ICI in our institution. The BMI was determined for all pts and categorized into 2 groups: obese (BMI≥30) and non-obese (BMI &lt; 30). Primary outcomes were the association of BMI category with overall survival (OS) and progression free survival (PFS) assessed by log-rank statistic, and both were stratified by sex, age, treatment agent and primary tumor site using the Cox-regression. Secondary outcome was the association of BMI with objective response rate (ORR). Results: We collected data from 448 advanced cancer pts - 192 (43%) as normal weight, 159 (36%) as overweight, 78 (17%) as obese and 19 (4%) as underweight. A total of 370 pts (83%) were included in the non-obese group (BMI &lt; 30) and 78 (17%) patients in the obese group (BMI≥30). The majority of pts (387 - 84%) received anti-PD-1/anti-PD-L1; 128 pts (28%) were treated at 1st line and 200 pts (44%) at 2nd line. The obese group experienced longer mOS than the non-obese group - 21.8 months (95% CI NR - NR) vs. 14.9 months (95% CI 8.3 -21.5); HR = 0.82, (95% CI 0.57-1.18, P = 0.28). However, this was not statistically significant and even after stratification. The obese group had an inferior mPFS than the non-obese group - 4.7 months (95% CI 3.8- 5.7) vs. 5.3 months (95% CI 3.45-7.15); - HR = 0.99, (95% CI 0.76 -1.30), P = 0.95. There was no significative difference in mPFS and ORR according to BMI. Conclusions: Although study did not report an improved OS among high BMI pts treated with ICI, our results suggested a trend in survival benefit. The BMI should be explored as a stratification variable in the design of prospective trials with advanced cancer pts and ICI treatment.
Phase I trial of lorlatinib in patients with ALK-driven refractory or relapsed neuroblastoma: A New Approaches to Neuroblastoma Consortium study.
Authors: Kelly C. Goldsmith, Kimberly Kayser, Susan G. Groshen, Marc Chioda, Holger C. Thurm, Joseph Chen, Gerson Peltz, Meaghan Granger, John Maris, Katherine K. Matthay, Suzy Ghazarian, Julie R. Park, Esther Berko, Araz Marachelian, Yael P. Mosse
Journal: Journal of Clinical Oncology (2020)

10504 Background: Lorlatinib, a potent ALK inhibitor, exerts unprecedented activity against neuroblastoma (NB) derived xenografts harboring common crizotinib-resistant ALK mutations, leading to a first in child phase I study. Methods: R/R NB patients (pts) &gt; 12 months, with ALK mutations/amplification and prior ALK inhibitor (ALKi) treatment were eligible. Lorlatinib was administered in 28-day courses (C). For pts &lt; 18 years, 5 dose levels (DL) (45, 60, 75, 95, 115 mg/m 2 /day) were assessed. DL5 (115 mg/m 2 /day) expansion is enrolling (cohort A1). For patients &gt; 18 years, two DL (DL3a the adult RP2D of 100 mg/day and DL4a at 150mg/day) were assessed (cohort A2). Primary endpoint was dose-limiting toxicity (DLT) during C1 and neurocognitive toxicity through C2. Blood samples for circulating tumor DNA (ctDNA) were matched to radiologic restaging. Results: From 9/2017 to 1/2019, 33 eligible patients enrolled (13 with prior ALKi therapy), with median age (range) 5.5 years (2-17) on A1, 21.5 years (15-50) on A2. In A1, 3 pts each enrolled onto DL1-3, with no DLT’s. 5/10 pts enrolled on DL4, with no DLT’s. 1/3 on DL5 had a DLT of grade 3 diarrhea, with expansion ongoing. In cohort A2, 5 patients enrolled at 100 mg/day with no DLT’s; 6 enrolled at 150 mg/day, with one DLT (grade 4 reversible psychosis). Most common treatment-related adverse events were weight gain (90%, grade 1-3), hyperlipidemia (90%, grade 1-3), concentration/memory impairment (23%, grade 1-2), peripheral neuropathy (13%; grade 1-2, A2 only), and peripheral edema (10%; grade 1, A2 only). Lorlatinib steady state exposure at DL3 and DL4 was in the range of exposures seen in adult lung cancer patients at the 100 mg and 200 mg DLs. In A1, 1/18 had partial response (PR), 3/18 had minor responses (MR), and 4/18 had stable disease (SD). Of pts with MR, 2/3 had PR of soft tissue and 1/3 had complete response (CR) by MIBG. In A2 pts, 1/10 had CR, 3/10 PR, and 3/10 MR; Notably, 2/3 with PR had CR by MIBG. Of the pts with MR, one had PR and one CR by MIBG. Responses occurred across dose levels, ALK mutations, and in ALKi pre-treated pts with median courses of 2 (1-24) on A1 and 10.5 (2-28) on A2. Serial ctDNA results showed mutant ALK variant allele frequency trajectories that correlated with clinical response and emergence of novel ALK mutations in cis that corresponded with disease progression. Conclusions: Inhibition of ALK-driven NB with lorlatinib occurs with manageable toxicity and objective anti-tumor activity. Prospective ctDNA allows for monitoring of disease and evolution of resistance. Clinical trial information: NCT03107988.
Combination of western and Chinese traditional medicine in treatment of chronic obstructive pulmonary disease with acute exacerbation
Authors: Guang Li
Journal: BMJ (2008)

Eighty patients with acute exacerbation of chronic obstructive pulmonary disease(COPD)complicated by pulmonary artery hypertention(PAH)were recruited in the study. All patients took conventional western medicine, among them 40 also received injection of Chinese herb medicine Shenxiong(study group)for 14 days. Mean pulmonary artery pressure(mPAP), plasma platelet alphagranule membrane protein(GMP-140), thromboxane B2(TXB2)and 6-keto-prostaglandin F1α(6-K-PGF1α)were measured before and after treatment in both groups. Compared with pretreatment levels and levels in control group mPAP, GMP-140 and TXB2 levels in study group were significantly decreased, while the levels of 6-K-PGF1α were significantly increased. The results indicate that Shenxiong injection may inhibit platelet activation and reduce mPAP. 

Key words: 
Lung disease,obstructive; Anticoagulants(TCD)
Identifying genomic alterations in small cell lung cancer using the liquid biopsy of bronchial washing fluid.
Authors: Jinfang Zhai, Songyan Han, Qinxiang Guo, Binbin Shan, Jing Wang, Yanrong Guo, Guoping Tong, Chang Zhao, Yuan Li, Qiao Han, Xiaoqin An, Ruiqing Yue, Li Wang, Tingting Guo, Weihua Yang
Journal: Journal of Clinical Oncology (2020)

e21098 Background: With the rapid development of cancer genomics, the precision medicine of small cell lung cancer (SCLC) is emerging. However, there are limitations to the clinical use of tumor tissue and peripheral blood biopsies. The main purpose of this study was to evaluate the potential use of bronchial washing fluid (BWF) in the liquid biopsy of SCLC. Methods: Twenty-one SCLC patients diagnosed in 2019 were enrolled in this study. BWF (separated as supernatant and precipitate), treatment-naive plasma and tumor tissue samples were collected from all of patients and subjected to next-generation sequencing (NGS) using a 1021-gene panel. The concordance rates of genomic profiling using NGS in these four types of samples were evaluated. Results: Of these 21 patients, 20 BWF supernatant (BWFs) samples, 21 BWF precipitate (BWFp) samples, 21 tumor tissue samples and 20 plasma samples were successfully tested. The detectability of somatic mutations was 100% for BWFs, BWFp and tumor tissues, and only one plasma was absent with any mutation. Matched tumor tissue, BWFs, BWFp and plasma samples were subsistent for 19 patients. For these patients, 204 genomic alterations were identified in tissue samples, of which 189 (92.6%), 175 (85.5%) and 163 (79.9%) alterations were detected in the matched BWFs, BWFp and plasma samples, respectively. Moreover, tumor mutation burden (TMB) was also calculated. Compared with the proportion of TMB-H samples in tissue samples counting 61.9% (13/21), 60% (12/20) of BWFs samples and 52.38 % (11/21) of BWFp samples were TMB-H (defined as more than or equal to 9 mutations per megabase), which was a molecular biomarker that can be used in immunotherapy efficacy prediction. The TMBs of BWFs, BWFp and treatment-naive plasma samples all had strong correlation with that of tissue samples. The TMB of BWFs had the strongest correlation (Pearson r = 0.9512, p &lt; 0.0001), and the TMB of treatment-naive plasma had relatively lower correlation (Pearson r = 0.8782, p &lt; 0.0001) compared with those of BWFs (Pearson r = 0.936, p &lt; 0.0001) and BWFp (Pearson r = 0.8782, p &lt; 0.0001). Conclusions: For SCLC patients, the liquid biopsy of BWF showed high potential to identify DNA alterations and calculate TMB grades, which suggested that genomic analysis of BWF liquid biopsy may have clinical value in predicting the effectiveness of targeted therapy and immunotherapy. It can be widely used in routine clinical practice.
Application of ultrasound-guided transversus abdominis plane block for operations of inguinal region in infants
Authors: Yongsheng Qiu, Defu Zhang, Yingping Jia, Qing Xu
Journal: BMJ (2014)

One hundred and fifty ASA Ⅰ-Ⅱ infants scheduled to undergo surgery on unilateral inguinal region, were randomly assigned to 3 groups with 50 in each group. In groups Ⅰ and Ⅱ puncture was performed at traversus abdominis plane under ultrasound-guidance, 0.4 or 0.5/kg of 0.25% ropivacaine was injected respectively. In group Ⅲ the triangle of Petit was positioned through palpating and then 0.5 ml/kg of 0.25% ropivacaine was injected. HR, RR, SpO2, PETCO2, expired sevoflurane concentration and BIS value at the time of entering the operation room (T1), incision of skin (T2), pulling hernia sac (T3), ending the surgery (T4), waking (T5), the number of pressing the analgesia pump after operation were recorded. The results showed that HR at T2 and T3 of groups Ⅰ and Ⅱ was lower than group Ⅲ (P<0.05). The were significant differences in case numbers of insufficient intraoperative analgesia among 3 groups(χ2=10.500, P=0.005). The CHEOPS scores and the number of pressing analgesia pump after operation in groups Ⅰ and Ⅱ were lower than those in group Ⅲ (χ2=7.230, P=0.027). Results indicate that ultrasound-guided transversus abdominis plane block is safer and more effective than conventional method for operations of inguinal region in infants; it may reduce dose of local anesthetics and postoperative use of analgesics.


Key words: 
Nerve block; Infant
Phase II study of pembrolizumab plus SurVaxM for glioblastoma at first recurrence.
Authors: Manmeet Singh Ahluwalia, David M. Peereboom, Marci Ciolfi, Cathy Schilero, Brian Hobbs, Michael J Ciesielski, Robert Alan Fenstermaker
Journal: Journal of Clinical Oncology (2020)

TPS2581 Background: Glioblastoma is the most common primary malignant brain tumor with median survival of approximately 15-16 months. Following first recurrence, progression free survival at six months ~15%. There is no therapy in recurrent glioblastoma associated with any survival benefit and there is an urgent need for better therapeutic options. Immunotherapy is one promising option for patients with cancer. This is being explored in glioblastoma and a number of forms of active specific vaccination and immune checkpoint based approaches have been devised and are being investigated in glioblastoma. Methods: Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD-1) receptor. Survivin is a 16.5 kDa intracellular protein that belongs to the inhibitor of apoptosis protein (IAP) family. SurVaxM is a 15 amino acid antigenic peptide that targets surviving capable of binding several human MHC class I molecules. Primary Objective is to assess clinical activity of Pembrolizumab and SurVaxM in patients with recurrent glioblastoma using progression free survival at 6 months (PFS-6) as determined using RANO criteria. Secondary Objective(s) includes safety and tolerability of combination, response rates, progression free survival and overall survival. Exploratory Objective include measuring cellular and humoral immune responses during concurrent administration of Pembrolizumab and SurVaxM. This is a phase II study of two arms in patients with recurrent glioblastoma. Arm A is patients with first recurrence of glioblastoma who have failed prior chemotherapy and radiation but have not received any immunotherapy. Arm B is an exploratory arm of glioblastoma patients who have failed prior anti-PD1 therapy. This clinical trial will enroll 41 patients with glioblastoma at first recurrence (bevacizumab naïve) in arm 1.This will include a 6-patient toxicity/safety run-in. There will an exploratory cohort of 10 patients who have failed prior PD1 blockade for a total of 51 patients in 2 arms. Key inclusion criteria include diagnosis of glioblastoma, Age ≥18 years old, Previous first line treatment with at least radiotherapy with or without temozolomide and Documented first recurrence of GBM and Karnofsky performance status of 70 and normal organ function. Key exclusion criteria include more than one recurrence of GBM, presence of extracranial metastatic or leptomeningeal disease, patients with &gt; 1 cm midline shift on imaging. Patients must not require &gt; 10 mg daily of prednisone equivalent. Clinical trial information: NCT04013672 .