tbuckley/cabot-search huggingface dataset:
Different organ-specific response to nivolumab to determine the survival outcome of patients with advanced hepatocellular carcinoma (aHCC).
Authors: Han Sang Kim, Jung Yong Hong, Jaekyung Cheon, Ilhwan Kim, Chang Gon Kim, Beodeul Kang, Dae Jung Kim, Chan Kim, Hongjae Chon, Hye Jin Choi, Ho Yeong Lim
Journal: Journal of Clinical Oncology (2020)

4584 Background: Previously, two phase III clinical trials of immune checkpoint inhibitors (ICI) failed to meet their primary endpoints, leading to doubts regarding the clinical activity of ICI monotherapy in patients with aHCC. Here, we comprehensively examined clinicopathological factors and estimated their association with survival outcomes in aHCC patients treated with nivolumab. Methods: A total of 261 eligible patients from 5 high-volume centers who were treated with nivolumab between June 9, 2012 and March 14, 2018 and had measurable diseases were reviewed. We reviewed more than 80 clinicopathological factors and categorized them into 6 areas: 1) demographics (n = 16); 2) baseline laboratory values (n = 19); 3) tumor burden (n = 12); 4) previous treatment (n = 12); 5) treatment response (n = 5); 6) toxicity profiles (n = 18). Their association with survival outcomes were evaluated, and organ-specific response evaluation, adapted from RECIST 1.1, was conducted. Results: Of the 261 patients, 218 (84%) had extrahepatic spread. The median follow-up time was 4.5 months. The median progression-free survival (PFS) and overall survival (OS) were 2.3 months (95% CI, 1.8-2.8) and 6.3 months (95% CI, 5.0-8.2). Objective response rate was 15%. Subgroup analyses revealed that compensated liver function (Child-Pugh score A5/6), surrogate markers for low tumor burden (low AFP, low PIVKA, and low LDH level), inflammatory markers (low C-reactive protein [CRP], low erythrocyte sedimentation rate [ESR], low neutrophil-to-lymphocyte ratio [NLR], high lymphocyte-to-monocyte ratio [LMR]), and low intrahepatic tumor burden were significantly associated with longer OS. A total of 456 individual lesions (liver, n = 249; lung, n = 124; lymph node, n = 35; others such as boner soft tissues, n = 48) were examined. Organ-specific response rates (hepatic tumor, 9%; lung, 25%; lymph node, 37%; others metastasis, 15%) were different, of which intrahepatic tumor was the least responsive organ to ICI treatment in aHCC. Conclusions: Underlying liver function, the tumor extent and burden, and the degree of plasma lymphocytes are crucial for determining tumor response to ICI in aHCC. Antitumor immune response to ICI differs in an organ-specific manner. The hepatic tumors of HCC may be less responsive to nivolumab than extrahepatic lesions.
Lebanese experience in treating multiple myeloma: A multicenter retrospective study.
Authors: Fadi Nasr, Lewis Nasr, Ahmad Ghoche, Saada Diab
Journal: Journal of Clinical Oncology (2020)

e20526 Background: Multiple myeloma is a clonal plasma cell malignancy that accounts for slightly more than 10% of hematologic cancers. Novel agents and stem-cell transplantation are changing disease prognosis and patient’s survival. Our objective was to do a multicenter retrospective analysis in order to look at the effect of autologous bone marrow transplant on progression free survival (PFS) of multiple myeloma. Methods: 134 myeloma patients from different Lebanese centers were included in a retrospective, observational study. We reviewed disease characteristics of patients that were diagnosed with multiple myeloma between July 2002 and January 2018. Results: 62.7% were males and 33.7% females with a median age of 65.5 years at diagnosis. 37 patients had a Karyotype on diagnosis, of which 21.6% were normal and 78.4% had abnormal cytogenetics including loss of chromosome Y, hypoploidy and tetraploidy. Regarding the M component, we had 52.2% IgG, 17.9% IgA, 1.4% IgM, 11.2% Kappa, 5.2% lambda, and 0.7% had 2 spikes M and G. 53.7% patients had bony lesions on diagnosis, 16.4% didn’t and 29.9% patients were unknown. According to ISS staging, 11.9% patients had an ISS of 1, 11.2% an ISS of 2, and 23.9% an ISS of 3. The majority (40.3%) were transplanted, 24.6% were not and 6.7% were still on induction therapy at the time of data cutoff [31/12/2018]. 28.4% had an unknown transplant status. 6.7% patients were diagnosed based on atypical plasmacytosis, 22.4% had monoclonal spike and 67.8% had multiple diagnostic modalities including immunofixation and urine studies. 29.1% of patients had plasmocytes between 10 and 60% and 9% had more than 60% plasmocytes on bone marrow at diagnosis. VCD was the main induction protocol used (38.8%) followed by VTD (14.2%) and VRD (9%). For the transplant group, 11.7% were in CR, 23.5% in VGPR and 19.6% were in PR before high dose melphalan. No death occurred during induction. 126 patients were still alive and taking treatment at the time of data cutoff. Mean PFS was 49.69 months (± 32.83) and 22.28 months (± 16.36) in the transplant and non-transplant group respectively (p = 0.001). Conclusions: Few previous reports described transplant data in Lebanese myeloma patients. As in the international data, we found a significant progression free survival in the transplanted group compared to the non-transplanted one.
Survivin-responsive conditionally replicating adenovirus for patients with advanced sarcoma demonstrated potent and long-term efficacy and high safety in a phase I clinical trial.
Authors: Satoshi Nagano, Toshitaka Futagawa, Eriko Sumi, Nobuhiro Ijichi, Munekazu Yamaguchi, Masanori Nakajo, Teruto Hashiguchi, Yasuo Takeda, Takashi Yoshiura, Akira Shimizu, Muneo Takatani, Setsuro Komiya, Ken-ichiro Kosai
Journal: Journal of Clinical Oncology (2020)

11512 Background: Whereas one of oncolytic viruses (OVs), inducing selective tumor killing and systemic anti-tumor immunity, was approved by FDA in 2015, the best OV that more safely and efficiently treats intractable cancers has not been successfully developed. By our platform technology to efficiently construct next-generation OVs, i.e., “conditionally replicating adenoviruses (CRAs) that target and/or treat tumor cells with multiple factors” (m-CRAs), we identified that among candidates, survivin-responsive m-CRAs (Surv.m-CRAs) exhibited the most potent antitumor efficacy and cancer selectivity ( i.e., safety) in preclinical studies ( Cancer Res, 2005 et al.). Here we present the data of First-In-Human phase I clinical trial of Surv.m-CRA-1 for musculoskeletal tumors (MST). Methods: This single-arm, open label study included 9 patients with unresectable and advanced MST. Patients underwent a single intratumoral injection of either 1×10^10 viral particle (vp) (low), 1×10^11 vp (mid) or 1×10^12 vp (high). The primary endpoints were safety and tolerability. The secondary endpoints included the local control of treated tumor at one month, defined by RECIST and Choi criteria, analysis of dissemination of Surv.m-CRA-1, serum cytokine and adenoviral antibody. Long-term follow-up was done in some patients. Results: Four patients (44.4%) had grade 3 or higher adverse events, including lymphopenia, leukocytopenia and mildly elevated liver transaminase in 2, 1 and 1 patient, respectively. Virus excretions, including second peak of viremia from viral replication in tumor, were observed in 1, 2 and 3 patients of low, mid and high dose, respectively. Out of 9 patients, 5 PR, 3 SD and 1 PD by Choi, and 8 SD and 1 PD by RECIST were observed. During follow-up, another 1 and 2 patients became PR by Choi and RECIST, respectively. Of note, long-term PR (over 2 years) after a single injection of Surv.m-CRA-1 was achieved in two chordoma cases in low dose. Conclusions: Surv.m-CRA-1 was well tolerated and showed antitumor activity for prolonged periods against advanced MST. We about to start Phase I/II study of multiple injections of Surv.m-CRA-1 for advanced solid tumors in two-arms for musculoskeletal tumors and pancreatic cancer. Clinical trial information: R000026464 .
Prognostic value of baseline complete blood count components in advanced gastric cancer patients: A multicenter retrospective study.
Authors: Shereef Ahmed Elsamany, Ahmed Zeeneldin, Emad Tashkandi, Ayman Ahamd Rasmy, Waleed Abozeed, Gomaa Abdelfatah, Huda Sharif Bukhari, Mernan Sulaimani, Donia Ahmed Firaq
Journal: Journal of Clinical Oncology (2020)

e16528 Background: Gastric cancer (GC) is one of the most prevalent malignant types in the world and an aggressive disease with a poor 5-year survival. Pretreatment CBC-based biomarkers, including blood neutrophil, lymphocyte, monocyte, and platelet counts; hemoglobin (Hb) levels; and their combinations, such as the neutrophil-lymphocyte ratio(NLR), lymphocyte-monocyte ratio (LMR) and platelet-lymphocyte ratio (PLR), have been reported to reflect systemic and local inflammation associated with cancer progression and prognosis. There has been growing interest in using CBC-based measures as biomarkers for GC. Methods: This chart-review study aimed to evaluate the effect of baseline levels of different components of routine CBC examination as well as other patients and disease characteristics on progression free survival (PFS) and overall survival (OS) in metastatic gastric cancer patients. Total 135 metastatic gastric cancer patients who had diagnosed and treated in three oncology centers in Saudi Arabia from 2011 to 2016 were incorporated. Various potential prognostic factors had measured in univariate and multivariate analysis. Results: After a median follow up of 21.4 months, the median OS / PFS were 11.0 and 6.1 months, respectively. Higher albumin level ( &gt; 3g/dl), low neutrophil percentage ≤ 75%, high lymphocyte percentage &gt; 15%, neutrophil /lymphocyte ≤ 2.5, high eosinophil count &gt; 0.4 k/ml, and EOX/EOF chemotherapy vs. doublet chemotherapy were associated with better PFS in univariate analysis. Conversely, in multivariate analysis, only serum albumin and eosinophil levels were related to PFS. In univariate analysis, higher serum albumin (3 g/dl), low neutrophil percentage ≤ 75%, high lymphocyte percentage &gt; 15%, neutrophil/lymphocyte ≤2.5, high eosinophil count &gt; 0.4 k/ml, receiving 1 st line chemotherapy vs. no chemotherapy, receiving &gt; 6 cycles of chemotherapy, receiving EOX/EOF chemotherapy vs. doublet chemotherapy, platelet count ≤450 k/ml, male gender were associated with better OS. In multivariate analysis, lower neutrophil percentage, higher serum albumin, male sex and higher number of chemotherapy cycles were independently associated with OS. Conclusions: Higher eosinophil level was associated with improved PFS while lower neutrophil percentage and higher number of chemotherapy cycles were independent predictors of OS. Higher albumin levels independently predicted better OS and PFS.
桡动脉给药成功抢救重度休克伴呼吸停止一例
Authors: 赵旅, 杨蕊, 卢玉霞, 安亚东, 张勇
Journal: BMJ (2004)

患者女,73岁.6年前接受乳腺癌治疗,有骨转移.半年前开始卧床.1周前肺部感染、呼吸困难,1 d前进行性加重.外院转入时呈深昏迷状态;大动脉搏动微弱,130次/min,测不到血压;呼吸6～8次/min,呼吸道有较多分泌物;双瞳孔扩大,对光反射不明显;颈静脉与四肢浅静脉不可见;睑结膜与口唇黏膜苍白;四肢末梢皮肤冰凉。
Clinical analysis on rheumatoid arthritis treated with glucocorticoids
Authors: 谢雯, 舒荣, 张奉春
Journal: BMJ (2005)

目的 分析糖皮质激素治疗类风湿关节炎(RA)的临床效果及对类风湿关节炎转归的影响,提高对糖皮质激素治疗类风湿关节炎的认识.方法回顾性分析了1999年1月至2003年3月北京协和医院门诊有随访记录的300例类风湿关节炎患者的临床资料,将治疗初期即使用改善病情抗风湿药的227例患者分为糖皮质激素治疗组(89例)和非糖皮质激素治疗组(138例),比较两组患者疾病临床缓解和远期关节X线变化的差异,比较糖皮质激素治疗组中不同剂量间的近期、远期疗效及不同疗程的远期疗效.结果两组近期疗效总有效率分别为86.5%、66.0%(P 0.05).结论糖皮质激素对于活动性类风湿关节炎患者能较快、明显地改善疾病活动程度,但未见对类风湿关节炎骨侵蚀有控制作用.不同初始治疗剂量及疗程对近期改善类风湿关节炎疾病活动度和控制其骨破坏未见差异。
Perioperative MVT-5873, a fully human monoclonal antibody against a CA 19-9 epitope, for operable CA 19-9 producing pancreatic cancers, cholangiocarcinomas, and metastatic colorectal cancers.
Authors: Shreya Gupta, James D McDonald, Reed I Ayabe, Tahsin M Khan, Lauren A Gamble, Alexander J Rossi, Surajit Sinha, Cathleen Hannah, Donna Mabry-Hrones, M. Cecilia Monge B., Andrew M. Blakely, Tim F. Greten, Jeremy L. Davis, Jonathan M Hernandez
Journal: Journal of Clinical Oncology (2020)

TPS4655 Background: Operable hepatopancreatobiliary (HPB) cancers continue to pose significant challenges. Radical resections are rarely curative, and chemotherapy is able to reduce tumor recurrence for only a fraction of patients. Despite the obvious advantages of extirpation of the identifiable tumor(s), the inflammatory milieu that accompanies surgery and the obligate time off cytotoxic agents allows for activation of remote quiescent disseminated tumor cells, leading to metastatic recurrence. We are conducting a study to determine the safety and efficacy of immediate peri-operative MVT-5873, a cytotoxic monoclonal antibody targeting Carbohydrate Antigen 19-9 (CA 19-9), in patients undergoing resections pancreatic cancer, cholangiocarcinoma or metastatic colorectal cancer to the liver. MVT-5873 is a human IgG1 antibody isolated from a patient following immunization with a sLe a -KLH vaccine. MVT-5873 has demonstrated cell surface binding in sLe a positive human tumor lines and has been shown to be potent in complement-dependent cytotoxicity assays and antibody-dependent cell mediated cytotoxicity assays. In patients with CA 19-9-producing cancers, MVT-5873 treatment has been shown to decrease serum CA 19-9 levels and prevent tumor progression. This trial may open the door for investigation of additional and/or synergistic agents in the immediate peri-operative period and usher in a new paradigm in the management of surgically treated cancers. Methods: This is a prospective, Phase II trial designed to determine the efficacy (increase in 1-yr DFS) and safety of peri-operative MVT-5873 for subjects with operable pancreatic, liver and bile duct cancers with elevated CA 19-9 levels. Patients may receive any standard neoadjuvant regimen prior to enrollment at the NIH Clinical Center in Bethesda, Maryland. Eligible patients will receive a pre-operative dose of MVT-5873 three days prior to the planned operation to remove all demonstrable disease. Following the operation, patients will receive a total of four doses of MVT-5873; the first two doses on postoperative days four and ten. The third dose will be administered on the normally scheduled postoperative clinic visit, followed by a final dose one month after discharge from the hospital and prior to the start of adjuvant treatment. Clinical trial information: NCT03801915 .
RTOG 3506 (STEEL): A study of salvage radiotherapy with or without enzalutamide in recurrent prostate cancer following surgery.
Authors: Edwin Melencio Posadas, Hiram Alberto Gay, Stephanie L. Pugh, Todd Matthew Morgan, James B. Yu, Stanislav Lechpammer, Felix Y Feng
Journal: Journal of Clinical Oncology (2020)

TPS5601 Background: Salvage radiotherapy (SRT) is an important intervention for men with prostate cancer (PCa) who experience biochemical recurrence (BCR) after radical prostatectomy (RP). These patients are in need of cure or else they will develop metastatic disease. NRG/RTOG 9601 (WU Shipley, N Eng J Med 2017) identified a survival benefit from the addition of androgen receptor (AR) inhibition to SRT that was most prominent in men with high-risk features. Enzalutamide (Enza) is a non-steroidal anti-androgen that improves survival in castration-resistant and -sensitive PCa. We hypothesized that enhanced AR suppression with Enza would augment the benefit of SRT + androgen deprivation therapy (ADT) in BCR with high risk features. Methods: RTOG 3506 (STEEL, NCT03809000) is a randomized phase II study of SRT in BCR after RP with a serum PSA ≥ 0.2 ng/mL active in the USA and Canada. Patients are stratified by number of high-risk features including Gleason score (8-10), locoregional node involvement at RP, seminal vesicle invasion, persistently elevated PSA after RP, and PSA &gt; 0.7 ng/mL. All patients receive SRT with 2 years of ADT. The experimental arm also receives Enza 160 mg daily for 2 years. Patients are followed by PSA every 3 months. SRT can be highly individualized per treating physician beyond the mandatory treatment of the prostatic fossa. Treatment of the pelvis and/or para-aortic nodes, as well as sequential or concurrent boosts to a prostatic fossa mass and/or suspicious lymph nodes, are allowed options. This permits individualization of radiotherapy guided by CT, MRI, PET, and/or biopsy findings. The primary goal of this study is to determine whether SRT enhanced ADT with Enza, will improve progression-free survival (PFS) compared to SRT with standard ADT. PFS defined as the first occurrence of biochemical failure, clinical failure, or initiation of new anticancer treatment. STEEL is designed to demonstrate a 35% reduction in the risk of progression at 5 years. An accrual goal of 242 patients will provide 80% power with a one-sided alpha = 0.10. Secondary endpoints include disease control rates, acute and late physician- and patient-reported toxicity, and quality of life. This study was activated in February 2019. Site recruitment and activation are underway. Conclusions: There is an unmet and urgent need for individualized strategies to optimize systemic therapy used with SRT for men with BCR. Outcomes from this study will further clarify the approach to systemic therapy for SRT in high-risk BCR patients. Support: Provided by Pfizer. Clinical trial information: NCT03809000 .
CA 15-3 elevation in U.S. women without breast cancer.
Authors: Xiao Hu, Yu Cao
Journal: Journal of Clinical Oncology (2020)

e13609 Background: Cancer antigen 15-3 (CA 15-3) is an epitope of Mucin 1 transmembrane glycoprotein, used to monitor response to therapy in metastatic breast cancer. Elevated CA 15-3 levels have been noted in other malignant and non-malignant conditions. This is the first population-based study examining CA 15-3 elevation in US women without breast cancer. Methods: Women without breast cancer were identified from the National Health and Nutrition Examination Survey 2001-2002 with CA 15-3 measurements via Meso Scale Discovery immunoassay. CA 15-3 levels were dichotomized per previously reported cutoffs of 20, 25, 30, and 40 U/ml, and also logarithmically transformed. Logistic and linear regression models were used to examine associations between CA 15-3 and demographic characteristics, gynecologic/reproductive history, inflammatory markers, non-malignant chronic conditions and non-breast malignancies. Results: Of 2432 women ages 20-85 (mean 48) years old, eighty (3.3%) had CA 15-3 ≥30 U/ml. Based on cutoff ≥30 U/ml, univariate logistic regression showed ages 40-59, uterine fibroids history, and salpingectomy history were associated with normal CA 15-3; Mexican American ethnicity and increasing C-reactive protein were associated with elevated CA 15-3. Multivariate logistic regression confirmed that only ages 40-49 (OR = 0.162, p = 0.0013) and uterine fibroids history (OR = 0.216, p = 0.0373) remained significantly associated. Similar results were found using other cutoffs. Univariate linear regression showed ages 40-59, salpingectomy history, and longer oral contraceptive pill (OCP) use correlated with lower CA 15-3; Black ethnicity, increasing ferritin, endometriosis history, and lung cancer history correlated with higher CA 15-3. Multivariate linear regression revealed significant associations: ages 50-59 (17.1% lower CA 15-3 vs ages &lt; 40, p = 0.028); race other than White, Black, Hispanic, Mexican (32.0% lower CA 15-3 vs White, p = 0.039); longer OCP use (14.0% lower CA 15-3 for 2-5 yrs’ OCP use, p = 0.023; 21.0% lower for &gt; 10 yrs’ OCP use, p = 0.006; vs OCP use &lt; 2 yrs); endometriosis history (22.9% higher CA 15-3 vs no history, p = 0.051). CA 15-3 levels were not significantly associated with chronic liver conditions, coronary artery disease, or metabolic conditions (elevated BMI, diabetes, hyperlipidemia). Conclusions: Perimenopausal women, uterine fibroids history, and longer OCP use were associated with lower CA 15-3 levels, while non-White ethnicity and history of endometriosis were associated with higher CA 15-3. These findings help to elucidate interpretation of CA 15-3 in clinical practice.
Feasibility and effects of home parenteral nutrition (HPN) in cancer patients with or without migrant background.
Authors: Lena Rebekka Schickhaus, Anica Högner, Mario Lorenz, Prisca Sturm, Peter C. Thuss-Patience
Journal: Journal of Clinical Oncology (2020)

e24137 Background: Parenteral nutrition is used in cancer patients (pts) requiring intensive nutrition support due to insufficient dietary intake and consuming tumor disease. As there is no data of HPN in pts with migrant background (MB), this observational study examined viability of HPN, influence on QoL and nutrition status of cancer pts with and without MB. Methods: Eligibility included ECOG ≥ 1, life expectancy ≥ 4 weeks, first time HPN for at least 28 days and written informed consent. Migrant background status and patient characteristics were assessed at baseline. At day 1 (baseline), day 14 and day 28 validated questionnaires assessed QoL, nutrition status (EORTC-QLQ-C15-PAL, Subjective global assessment (SGA)), as well as feasibility and complications of HPN. Additionally, bioimpedance analysis, BMI and weight were measured to evaluate response of HPN. Results: Between Mai 2015 and November 2019, 68 pts were included, 17 of them with MB. Tumor entities were gastric (n = 41), esophageal (n = 20) and other (n = 7), treated in a curative (n = 14) or palliative (n = 54) concept. Overall, 40 pts were able to continue HPN until day 14, 26 pts until day 28. 42 pts left study due to death (1 with MB/8 overall), worsening of general condition (3/15), dietary improvement (1/2), change of supplier (1/5), informed consent withdrawal (0/1) and lost to follow up (2/11). Global QoL in all pts was stable from baseline to d14 (n = 36; 36.6 to 40.3), whereas QoL in pts with MB deteriorated (n = 9; 37.0 to 27.8). From baseline to d28, QoL in all pts improved (n = 23; 38.4 to 47.8) and in pts with MB QoL was stable (n = 7; 40.5 to 42.9). Medical problems associated with HPN occurred in 4/11 pts with MB (36%) and 11/37 pts without MB (30%), respectively. The majority of pts reported about HPN-associated organizational complications, whereas there is no significant difference of pts with MB (6/10) and without MB (20/38). SGA improvement was observed in all pts regardless of MB. During the course of HPN, there was no significant change in body weight and BMI in all pts, independent from MB. Conclusions: Overall, 59% of pts received HPN for 14 days, only 38% of pts for 28 days. Discontinuation was mainly due to disease progression. Feasibility and organizational problems did not affect duration of HPN. Assessing HPN prospectively shows, that defining the ideal point to start HPN appears to be essential for response to HPN. In our study, migrant background is not associated with a major difference in incidence of complications, viability, benefit or duration of HPN.
Expressions of miRNA141 and miRNA375 in serum samples from prostate cancer
Authors: Qipeng Xie, Jian Yu, Xiaoqing Chen
Journal: BMJ (2015)

To explore the diagnostic values of miRNA141 and miRNA375 for prostate cancer. The expressions of miRNA141 and miRNA375 in serum samples from 30 prostate cancer (PCA) patients, 40 benign prostatic hyperplasia patients and 50 normal controls were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression of miRNA141 in tissue samples from prostate cancer was 13.4±7.2 folds of that from benign prostatic hyperplasia while the expression of miRNA375 in tissue samples from prostate cancer was 28.4±10.3 folds of that from benign prostatic hyperplasia. The differential expression of miRNA141 and miRNA375 in sera of prostate cancer suggested that miRNA141 and miRNA375 might be potential tumor markers in clinical practice.


Key words: 
Prostatic neoplasms; Laboratory techniques and procedures
树立全科医学的人文精神
Authors: 杨秉辉
Journal: BMJ (2012)

人文一词源于拉丁文humanists,即人性与教养.它包括了人的文化、知识、宗教、信仰、道德、法律、文学、艺术等等,可以说凡属人类精神活动的内容皆可包括其中.如今人们追求的是生命价值的提高,“人文”成了当今社会发展的主题。