tbuckley/cabot-search huggingface dataset:
Open-label pilot study of genetically engineered NY-ESO-1–specific t cells (GSK3377794) alone or in combination with pembrolizumab in relapsed/refractory multiple myeloma.
Authors: Aaron Rapoport, James Edward Hoffman, Jonathan L. Kaufman, Kristin Blouch, Emily Butler, Maurice Phillip Deyoung, Benedetto Farsaci, Aisha N. Hasan, Andrew P. Holmes, Anne Huff, Amit Jain, Michael Jon Chisamore, Taiga Nishihori
Journal: Journal of Clinical Oncology (2020)

TPS8555 Background: Adoptive cellular therapy may be practice-changing in relapsed/refractory multiple myeloma (MM). NY-ESO-1 TCR T (GSK3377794) are autologous polyclonal T cells transduced by a self-inactivating lentiviral vector to express an affinity-enhanced TCR capable of recognizing NY-ESO-1 or LAGE-1a antigenic peptides in complex with HLA-A*02. GSK3377794 has shown clinical activity in synovial sarcoma, melanoma, myxoid/round cell liposarcoma, and MM after autologous stem cell transplant. NY-ESO-1 and LAGE-1a are cancer/testis antigens frequently overexpressed in MM and linked to poor clinical outcome. PD-1 expression on CD8 T cells, which has been observed in MM patients previously treated with GSK3377794 as well as with CD19 CAR T-cell therapy, can limit adaptive immune response. We hypothesize that GSK3377794 alone, or in combination with the anti-PD-1 inhibitor pembrolizumab, may result in an antitumor effect in MM. Methods: This is an open-label, pilot study (NCT03168438) of GSK3377794 in patients with relapsed/refractory MM positive for HLA-A*02:01, HLA-A*02:05, ± HLA-A*02:06 and NY-ESO-1/LAGE-1a. Patients (n = 20) who have received ≥3 prior therapies containing ≥1 immunomodulatory imide, proteasome inhibitor, alkylator, CD38 monoclonal antibody, or glucocorticoid will be assigned to either single-infusion GSK3377794 (Arm 1, n = 10) or single-infusion GSK3377794 + pembrolizumab 200 mg IV every 3 weeks (Arm 2, n = 10). Arm 1 enrollment will be completed first. In Arm 2, pembrolizumab will begin in Week 3 (Week 6 if precluded by toxicity). Patients in both arms will provide cells via leukapheresis to manufacture autologous NY-ESO-1–specific T cells, undergo lymphodepletion (fludarabine + cyclophosphamide), and then receive GSK3377794 infusion (1−8x10 9 transduced T cells). Primary and secondary objectives are to assess safety/tolerability and antitumor activity, respectively, of GSK3377794 (± pembrolizumab). Arm 2 enrollment will pause for a 3-week safety review after 3 patients have received a first dose of pembrolizumab. Efficacy, safety, and biomarkers will be assessed every visit. The treatment phase will last 108 weeks, or until disease progression; follow-up will last ≤15 years. As of January 2020, 3 patients have been treated. Funding: GlaxoSmithKline (208470) Clinical trial information: NCT03168438 .
Final analysis of single-arm confirmatory study of definitive chemoradiotherapy including salvage treatment in patients with clinical stage II/III esophageal carcinoma: JCOG0909.
Authors: Yoshinori Ito, HIROYA TAKEUCHI, Gakuto Ogawa, Ken Kato, Masakatsu Onozawa, Keiko Minashi, Tomonori Yano, Kenichi Nakamura, Takahiro Tsushima, Hiroki Hara, Tatsuya Okuno, Shuichi Hironaka, Isao Nozaki, Takashi Ura, Keisho Chin, Takashi Kojima, Shiko Seki, Katsuyuki Sakanaka, Haruhiko Fukuda, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2020)

4545 Background: Definitive chemoradiotherapy (dCRT) consisting of 5-fluorouracil (5-FU) and cisplatin (CDDP) with 60 Gy radiotherapy (RT) for clinical (c) Stage II/III esophageal carcinoma (EC) is a standard treatment for patients (pts) refusing surgery (S) in Japan based on the previous trial (JCOG9906). However, poor survival, high incidence of late toxicities, and severe complications of salvage S are problems. We conducted a single-arm confirmatory study of CRT modifications including salvage treatment (ST) to reduce CRT toxicities and facilitate ST to improve survival. We reported the 3-year survival at 2018 ASCO Annual Meeting. We report the final data after 5-year follow-up. Methods: EC pts with cStage II/III (UICC 6 th , non-T4), PS 0-1, and age 20-75 years were eligible. Chemotherapy (CT) was CDDP (75 mg/m 2 on days 1, 29) and 5-FU (1000 mg/m 2 /d on days 1-4, 29-32). RT was administered to a total dose of 50.4 Gy with elective nodal irradiation of 41.4 Gy. Good responders after dCRT received additional 1-2 cycles of CT. For residual or recurrent disease, salvage endoscopic resection (ER) or S was performed based on the prespecified criteria. Planned sample size was 95, with one-sided alpha of 5% and power of 80%, expected and threshold 3-year overall survival (OS) as 55% and 42%. Key secondary endpoint was ST related toxicity. Final analysis was planned after 5-year follow-up for all pts. Results: From 4/2010 to 8/2014, 96 pts were enrolled, two were ineligible and 94 were included in efficacy analysis (cStage IIA/IIB/III, 22/38/34). Complete response was achieved in 55 pts (59%). Salvage ER and S were performed in 5 (5%) and 27 pts (29%). R0 resection of salvage S was achieved in 23 (85%). With a median follow-up of 5.95 years, 3- and 5-year OS was 74.2% (90% CI 65.9-80.8%) and 64.5% (95% CI 53.9-73.3%). 5-year progression-free survival and esophagectomy-free survival were 48.3% (95% CI 37.9-58.0%) and 54.9% (95% CI 44.3-64.4%). 5-year OS after salvage S was 31.0% and hazard ratio of R1-2 to R0 was 5.635 (95% CI: 1.818-17.467). No complications occurred after salvage ER. Five pts (19%) showed ≥ grade 3 operative complications and 1 treatment related death due to bronchus-pulmonary artery fistula occurred after salvage S. Only 9 pts (9.6%) showed grade 3 late toxicities. And no late operative complications more than grade 3 were observed. Conclusions: This combined modality treatment of dCRT with ST showed acceptable toxicities, favorable 5-year survival, and promising esophageal preservation. Clinical trial information: jRCTs031180110 .
Niraparib exposure-response relationship in patients (pts) with newly diagnosed advanced ovarian cancer (AOC).
Authors: Bradley J. Monk, Ignacio Romero, Whitney Graybill, Cristina Churruca, David M. O'Malley, Bente Lund, Oi Wah S. Yap, Jean-Francois Baurain, Peter Graham Rose, Hannelore denys, Sharad A. Ghamande, Carmela Pisano, Michel Fabbro, Elena Ioana Braicu, Paula Calvert, Amnon Amit, Emily Prendergast, Ashley Milton, Zhi-Yi Zhang, Antonio Gonzalez Martin
Journal: Journal of Clinical Oncology (2020)

6051 Background: Niraparib improves progression-free survival (PFS) in pts with newly diagnosed AOC after complete or partial response to first-line, platinum-based chemotherapy. In the PRIMA/ENGOT-OV26/GOG-3012 (PRIMA) trial, pts were treated with a fixed starting dose (FSD) of 300 mg QD until a protocol amendment introduced the individualized starting dose (ISD) regimen: 200 mg QD for pts with baseline bodyweight (BW) &lt; 77 kg and/or platelet count (PC) &lt; 150,000/µL, or 300 mg QD for pts with baseline BW ≥77 kg and PC ≥150,000/µL. Here, we developed a population pharmacokinetic (PopPK) model for niraparib and evaluated exposure-response relationships for pts receiving niraparib using safety and efficacy data from PRIMA. Methods: The PopPK model for niraparib was developed based on 7418 plasma samples from 1442 pts from 4 studies: PN001, NOVA, QUADRA, and PRIMA. PRIMA PK samples were collected on cycle 1, day 1 (C1D1), C2D1 pre-dose and 2 h post-dose, C4D1, and C8D1 pre-dose (or EOT if patient discontinued before C8D1). The relationship between PopPK model-based prospective exposure (average concentration [ C ave ] until progression/death) and efficacy (PFS) were evaluated in pts receiving niraparib in both the homologous-recombination deficient (HRd) and overall population. The relationship between model-predicted exposure metrics and incidence of clinically relevant adverse events (AEs) was analyzed using univariate logistic regression in pts receiving niraparib. Results: Of 484 pts receiving niraparib in PRIMA, 480 had PK data and were included in the efficacy and safety analysis. The safety exposure-response showed significant associations ( p≤0.0128) between increasing niraparib exposure and increasing probability of experiencing any-grade and grade ≥3 AEs, except grade ≥3 hypertension. The incidence of AEs, including thrombocytopenia, was lower in pts who received a 200-mg ISD. Efficacy was not compromised in these pts. Conclusions: Niraparib exposure was associated with increased risk of select AEs. However, the ISD regimen decreased AE risk without compromising efficacy. Clinical trial information: NCT02655016.
C-reactive protein (CRP) as a predictive biomarker in lung cancer patients receiving immune checkpoint inhibitors (ICI).
Authors: Aneesha Ananthula, Manojna Konda, Milan Bimali, Ahmad Mazen Safar, Rangaswamy Govindarajan
Journal: Journal of Clinical Oncology (2020)

e21645 Background: C-Reactive Protein (CRP) is an acute phase reactant which is elevated in inflammatory conditions and malignancy. Elevated CRP levels are associated with poor prognosis in many cancers and has been reported in patients with melanoma treated with ICI. We examined the association between CRP levels during therapy with ICI in patients with advanced lung cancer and radiological response. Methods: A retrospective study of patients with metastatic lung cancer (stage IV) who were treated with immunotherapy from 2016 to 2019 was conducted. CRP levels were checked at or soon after initiation of therapy and at frequent intervals thereafter. Association between CRP levels and response was determined. Results: 36 patients had initial (at the beginning of therapy, baseline) and subsequent CRP levels recorded during the first course of immunotherapy. Among the 36 patients, 16 (44%) had radiological response or stable disease, and 20 (55%) had radiological progression. The median age was 69 years (range 50 – 89 years); male/female 35/1, Caucasian/African American/other 26/9/1. There was no significant difference in distribution of initial CRP levels between patients with response vs progression as assessed by Kruskal-Wallis test (P-val: 0.20). Logistic regression modeling was employed to examine the association between final CRP level, the last measurement while on ICI therapy (adjusted for baseline CRP level) and odds of observing a response. A unit increase in final CRP level was associated with 4% decrease in odds of observing a response (Odds Ratio, 95% CI: 0.96, 0.92-1.00, P-val: 0.05). Conclusions: Baseline-adjusted final CRP levels were inversely associated with likelihood of observing a response in advanced lung cancer subjects treated with ICI. Further validation in prospective studies is warranted.
Distribution of oncotype recurrence scores in invasive lobular carcinomas.
Authors: Kelly Suchman, Brittney Shulman Zimmerman, Meng Ru, Krystal Pauline Cascetta, Amy Tiersten
Journal: Journal of Clinical Oncology (2020)

e13025 Background: Invasive lobular carcinomas (ILC) account for approximately 10-15% of all invasive breast cancers, with the majority of cases presenting as ER/PR positive and HER2 negative. As a result, they often exhibit more robust responses to hormone therapy than adjuvant chemotherapy. Oncotype Recurrence Score (RS) RS is a 21-gene assay used to predict the rate of distant recurrence and response to chemotherapy in women with node-negative, hormone-positive breast cancers. Limited evidence exists regarding oncotype scores for ILC tumors, thus the aim of this study was to examine the distribution and risk stratification of Oncotype RS in ILC tumors. Methods: We analyzed patient and tumor characteristics of 492 patients- 417 (85%) IDC (intraductal carcinoma) and 75 (15%) ILC. Chi-square tests and Wilcoxon rank-sum tests were used to compare categorical and numerical outcomes, respectively. Results: No significant difference was found between IDC and ILC in terms of age and ER/PR positivity. The RS raw scores were also not significantly different between the two groups (both had median scores of 16). ILC patients were significantly more likely to be in the lower RS risk groups using the traditional (Paik) cutoff than ILC patients (61%, 39% and 0% in low, medium and high-risk groups as compared to 57%, 33% and 10% in IDC, p &lt; 0.01). Of 417 patients with IDC, there were 16 recurrences (4%) with a median time from diagnosis to recurrence of 43 months (IQR: 28 Ð 58 months), while 1 in 75 ILC patients had recurrence at 50 months. Conclusions: Oncotype RS scores have the potential to guide treatment decisions in node-negative breast cancers. Though mean RS were similar between ILC and IDC patients, ILC were more likely to be distributed in low-risk groups. Our study was limited by a small sample size and a single ILC recurrence. Further research is needed to determine oncotype RS and recurrence rates. Future studies with longer term follow up can help better elucidate patterns of recurrence scores and recurrence rates based on histologic tumor type. [Table: see text]
Identification of a prognostic immune-related signature for small cell lung cancer.
Authors: JUN WANG, Bicheng Zhang, Jianguo Sun, Jing Liang, Xiaolin Liu, Yan Li, Baocheng Wang
Journal: Journal of Clinical Oncology (2020)

e21041 Background: As a subgroup of lung cancer, small cell lung cancer (SCLC) is characterized by a short tumor doubling time, high rates of early occurred distant cancer spread, and poor outcome. Despite its exquisite sensitivity to chemotherapy and radiotherapy, acquired drug resistance and tumor progression was impossibly avoided. This study aimed to develop a robust signature based on immune-related genes to predict the outcome of patients with SCLC. Methods: The expression data of 77 SCLC patients from George’s cohort were divided into training and testing set, and 1,534 immune-related genes from ImmPort database were used to generate and validate the signature. The Cox proportional hazards model was developed to determine the best gene model and construct the signature. The Kaplan-Meier survival analysis and Cox proportional hazards were used to test the prognostic significance of the signature. Results: A 10-genes model comprising NR3C1, NR1D2, TANK, ARAF, HDGF, INHBE, LRSAM1, PLXNA1, PML and SP1 with the highest frequency after 1,000 interactions, was chosen to construct an immune-related signature. This signature showed robust predictive value for SCLC patients’ survival in both training and testing set. This signature was closely associated with the activation of immune signal pathways, but not TNM stage. Furthermore, patients with high immune risk score presented with poor survival, whereas had high specific tumor-infiltrating immune cells such as NK CD56 bright cells. Conclusions: The present developed immune-related signature could predict the prognosis of SCLC patients, which to some extent reflect individual immune microenvironment phenotype in this highly lethal cancer type.
Outcomes of lung cancer screening among cancer survivors: An NCCN institution experience.
Authors: Bradley Maller, Vani Nath Simmons, Margaret M Byrne, Tawee Tanvetyanon
Journal: Journal of Clinical Oncology (2020)

1595 Background: In 2013, the USPTF recommended low-dose CT (LDCT) screening for individuals at high risk of lung cancer based on data from the National Lung Screening Trial. However, the trial excluded participants with cancer diagnosis &lt; 5 years except for non-melanoma skin cancer, making it unclear whether the data will be generalizable to cancer survivors. This population, while at increased risk of secondary lung cancer, may be prone to false positive results due to anatomic defects or recurrent cancers. Our NCCN institution serves a large number of cancer survivors. We evaluated the outcomes of LDCT screening and the adherence to annual screening among cancer survivors, compared with individuals without cancer history (IWC). Methods: Prospectively maintained database of LDCT screening participants was analyzed. Eligibility was per NCCN criteria and cancer survivors needing regular chest CT were not offered LDCT. Participants were asked to complete a self-administered questionnaire on risk factors. Positive result was defined as Lung-RADS ≥3, corresponding to nodule ≥6 mm. Adherence to LDCT screening was defined as having T1 screening, excluding those &lt; 18 months from T0 at time of analysis. Predicted risk of lung cancer was calculated per PLCOm2012 model. Results: To date, 454 subjects have undergone LDCT screening. Positive results occurred in 60 subjects (13.2%) at T0; lung cancer was diagnosed in 10 subjects (2.2%); and other cancers were diagnosed in 5 subjects (1.1%). There were 152 cancer survivors, including survivors of breast (52), prostate (26), bladder or kidney (19), lung (14), and head and neck cancer (13). The median time from cancer treatment to LDCT screening was 6 years (range 0-55). Cancer survivors were older than IWC: median age 67.4 vs. 63.5 years ( p&lt; 0.001) and more likely to be active smokers: 37.5% vs. 29.5%, ( p= 0.09). The median predicted risk of lung cancer at 6 year was 5.5% vs. 3.2%, ( p= 0.15). No significant difference in the screening outcomes was found between groups. Among cancer survivors (N = 152), positive screening occurred in 15 (9.9%); lung cancer was diagnosed in 1 (0.7%); and other cancers were diagnosed in 3 subjects (1.9%). Non-adherence to LDCT screening occurred in 31 out of 152 cancer survivors (20.4%), compared with 81 out of 262 (30.9%) IWC, ( p= 0.02). Conclusions: About one-third of LDCT screenings at this NCCN institution occurred among cancer survivors. We found no evidence of increased false positive results. However, a higher rate of adherence to annual screening was observed among cancer survivors than IWC.
Evaluation of a mainstream model of genetic testing for men with prostate cancer.
Authors: Tahlia Scheinberg, Annabel Goodwin, Emilia Ip, Anthony Linton, Blossom Mak, David P Smith, Martin R. Stockler, Madeleine Cornelia Strach, Ben Tran, Alison Luk Young, Alison Yan Zhang, Kate Lynette Mahon, Lisa Horvath
Journal: Journal of Clinical Oncology (2020)

1521 Background: In order to identify the ∼12% with inherited cancer predisposition, it is recommended that all men with metastatic prostate cancer (mPC) be offered testing. This has implications for treatment choices and cancer prevention in family. Limited geneticists/genetic counsellors globally present a major barrier to testing. We tested a potential solution, mainstreaming, where testing is performed by the patient’s oncologist. Methods: Men with mPC at three Australian sites were offered germline genetic testing at their medical oncology appointment. Panel testing ( ATM, BRCA1, BRCA2, BRIP1, CHEK2, EPCAM, FANCA, HOXB13, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, RAD51D and TP53) was performed on saliva/blood (Invitae). Primary outcomes were clinician and patient acceptability (modified Royal Marsden Satisfaction Questionnaires). Secondary outcomes included mutation rates and cost-effectiveness. A sample size of 44 provided 90% power, with a one-sided alpha of 5%, to distinguish a proportion of men happy with mainstreaming of 80% vs. 60% or less. Allowing for 25% drop-out, we aimed to recruit 60 men. Results: Of 66 men offered testing from April to November 2019, 63 (95%) accepted. Four pathogenic variants were identified (2 BRCA2, 1 NBN, 1 MSH6). 48 patients and eight clinicians completed questionnaires. Acceptability was high. All (48/48) patients were happy to have been tested, and 45/48 (94%) were happy to have been tested at their oncology appointment. All were happy to receive their results from their oncologist. All clinicians were satisfied mainstreaming and 88% (7/8) felt confident doing so. Mainstreaming was cost-effective, requiring 87% fewer genetic consultations than traditional genetic counselling. Conclusions: This study shows that mainstreaming of men with mPC is feasible, resource efficient and acceptable to both clinicians and patients. Widespread implementation as a new standard of care would facilitate timely access to genetic testing for men with mPC.
宫腹腔镜联合盆腔灌注在盆腔粘连致不孕症中的应用
Authors: 高善霞, 郝俊秀
Journal: BMJ (2007)

对197例经腹腔镜确诊的慢性盆腔炎、盆腔粘连所致不孕的病例,采用盆腔连续灌注替硝唑和左氧氟沙星注射液抗炎,宫腹腔镜联合输卵管插管疏通术治疗.术后妊娠109例,妊娠率55.3%(109/197),异位妊娠率4.1%(8/197),妊娠流产率6.4%(7/109),校正妊娠率47.7%(94/197).说明盆腔连续灌注联合宫腹腔镜手术是治疗慢性盆腔炎盆腔粘连所致不孕症的一种有效方法。
Magnetic resonance imaging and radiological findings of familial sacral agenesis: a report of 6 cases
Authors: Tongtong Tian, Haitao Wu, Shouan Wang, Wenxin Chen, Xiaohua Hu, Lianqi Yan
Journal: BMJ (2014)

The clinical characteristics and radiological data of 6 cases of sacral agenesis in one single family were analyzed and a literature review was performed. On magnetic resonance imaging (MRI), all of them presented with a partial absence of sacral vertebra, including associations with lumbar abnormalities (n=2) and sacral agenesis (n=2). One case presented with fourth/fifth lumbar vertebra bone fusion and fifth lumbar/first sacral vertebra bone fusion. On radiology, 4 cases had concurrent scoliosis. None of them had tethered cord, diastematomyelia or meningocele. The understanding of sacral agenesis may be improved after reviewing and summarizing clinical features and radiological findings.


Key words: 
Dysostoses, sacrum; Magnetic resonance imaging
The ethics of neuro-oncology in the era of COVID-19: lessons to be learned
Authors: Sunit Das
Journal: Neuro-Oncology (2020)

Additional criteria apply.Please refer to protocol 14379-201 for full inclusion and exclusion criteria.† Patients can participate if they had some skin cancers, superficial bladder cancer (cancer that was only on the surface of the lining of the bladder), or carcinoma in situ (cancer that had not spread) of the cervix or breast that had been cured.
触摸与心理疏导对硬膜外麻醉手术患者的效果观察
Authors: 李玲, 单秀萍, 汤金荣, 李键铃, 刘伟
Journal: BMJ (2005)

手术作为一种应激源,常可导致手术患者产生不同程度的生理与心理应激反应,这些反应如果过于强烈,不仅会对神经、内分泌及循环系统产生影响,而且会干扰手术和麻醉的顺利实施,影响治疗效果[1].特别是硬膜外麻醉手术的患者,他们在术中神志仍保持清醒,因此紧张和恐惧情绪尤为严重,心理压力也较大,而触摸则可以舒缓患者的紧张情绪,减轻其心理痛苦.2001年1月至2003年12月,我们对772例硬膜外麻醉手术患者在术中适当应用触摸手段结合心理疏导,效果满意,现报告如下。
Relationship between serum brain natriuretic peptide level and short-term prognosis in patients with acute myocardial infarction
Authors: Xu-bo Wang, Hong-tao Pan, Do-zhi Shi, Dong-qing Zhang, Jun Zhao
Journal: BMJ (2010)

Objective To investigate relationship between serum level of brain natriuretic peptide (BNP)and short-term prognosis in patients with acute myocardial infarction(AMI).Methods Ninetynine patients with AMl with elevated S-T segment in electrocardiogram admitted to the department of cardiology,the Fourth Hospital of Jilin University,Changchun during January to December 2008 were divided into two groups.one with percutaneous transluminal coronary angioplasty(PTCA)or pereutaneous coronary intervention(PCI)(61 eases)and the other without PTCA(38 cases)as controls.Their serum levels of BNP were measured at admission, and one day and seven days after admission,respectively,and their main adverse cardiac events(MACE)were followed-up and recorded for 30 days.Results No significant differenee in serum BNP level between the patients at admission and one day after admission was found(P＜0.01).Seven days after admission,serum BNP level in PCI group was significantly lower than that in controls(P＜0.01),and occurrence of MACE was significantly lower in PCI group than that in controls(P＜0.05).Logistic regression analysis indicated that serum BNP level in PCI group seven days after admission was the uppermost predictor for MACE in patients with AMI in one month after onset(OR=1.026,95%CI 1.014-1.038,P＜0.01).Serum BNP level was significantly higher in patients with MACE seven days after admission than that in those without it(P＜0.01)during 30-day followup.Conclusion Serum level of BNP seven days after admission is associated with their short-term prognosisfor patients with AMI.

Key words: 
Myocardial infarction;  Natriuretie peptide,brain;  Angioplasty,transluminal,pereutaneous coronary