tbuckley/cabot-search huggingface dataset:
Logistic Regression Classification of Primary Vitreoretinal Lymphoma versus Uveitis by Interleukin 6 and Interleukin 10 Levels
Authors: David E. Kuo, Maggie M. Wei, Jared E. Knickelbein, Karen R. Armbrust, Ian Y.L. Yeung, Aaron Y. Lee, Chi-Chao Chan, H. Nida Sen
Journal: Ophthalmology (2020)
Detection of Circulating Tumor Cells and Their Implications as a Biomarker for Diagnosis, Prognostication, and Therapeutic Monitoring in Hepatocellular Carcinoma
Authors: Joseph C. Ahn, Pai‐Chi Teng, Pin‐Jung Chen, Edwin Posadas, Hsian‐Rong Tseng, Shelly C. Lu, Ju Dong Yang
Journal: Hepatology (2020)

Hepatocellular carcinoma (HCC) is among the leading causes of worldwide cancer-related morbidity and mortality. Poor prognosis of HCC is attributed primarily to tumor presentation at an advanced stage when there is no effective treatment to achieve the long term survival of patients. Currently available tests such as alpha-fetoprotein have limited accuracy as a diagnostic or prognostic biomarker for HCC. Liver biopsy provides tissue that can reveal tumor biology but it is not used routinely due to its invasiveness and risk of tumor seeding, especially in early-stage patients. Liver biopsy is also limited in revealing comprehensive tumor biology due to intratumoral heterogeneity. There is a clear need for new biomarkers to improve HCC detection, prognostication, prediction of treatment response, and disease monitoring with treatment. Liquid biopsy could be an effective method of early detection and management of HCC. Circulating tumor cells (CTCs) are cancer cells in circulation derived from the original tumor or metastatic foci, and their measurement by liquid biopsy represents a great potential in facilitating the implementation of precision medicine in patients with HCC. CTCs can be detected by a simple peripheral blood draw and potentially show global features of tumor characteristics. Various CTC detection platforms using immunoaffinity and biophysical properties have been developed to identify and capture CTCs with high efficiency. Quantitative abundance of CTCs, as well as biological characteristics and genomic heterogeneity among the CTCs, can predict disease prognosis and response to therapy in patients with HCC. This review article will discuss the currently available technologies for CTC detection and isolation, their utility in the clinical management of HCC patients, their limitations, and future directions of research.
Pulse Wave Velocity in Chronic Obstructive Pulmonary Disease and the Impact of Inhaled Therapy (SUMMIT): A Randomized Double-Blind Clinical Trial
Authors: Courtney Crim, Julie A. Anderson, Peter M. A. Calverley, Bartolome R. Celli, Nicholas J. Cowans, Fernando J. Martinez, David E. Newby, Jørgen Vestbo, Julie C. Yates, Robert D. Brook
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
The impact of pancreatic cancer resection in the era of effective systemic treatment.
Authors: Yaacov Richard Lawrence, Ofer Margalit, Galia Jacobson, Liat Hamer, Uri Amit, Naama Halpern, Einat Shacham Shmueli, Ben Boursi, Yuri Goldes, Daniel Azoulay, Talia Golan, Zvi Symon
Journal: Journal of Clinical Oncology (2020)

722 Background: Surgical resection is the only curative modality in pancreatic cancer, yet the vast majority of patients undergoing surgery succumb of their disease. No randomized studies have been performed to assess the survival impact of the procedure. We hypothesized that in the era of effective systemic treatments, the survival advantage of surgical resection would be lessened. Methods: A meta-analysis of published phase III clinical trials in pancreatic cancer in both the post resection adjuvant setting and the locally advanced metastatic setting, based upon indirect aggregate data. Data was stratified based upon the systemic agents used. Patients from trials arms for which there were not complementary data sets with/without surgical resection were excluded. Primary endpoint was 3 year overall survival (OS). Results: Trials were published between 1997 and 2018. A total of 2722 patients were included in the data analysis, of whom 1645 underwent tumor resection and 814 were metastatic. Median follow-up was 40 months. Analyses were performed of five systemic options with / without tumor resection. Across the trials averaged 3 yr OS was 0%, 0.8%, 0%, and 3.8% for 5FU, gemcitabine, gemcitabine + capecitabine, &amp; FOLFIRINOX respectively; and 18.1%, 30.0%, 37.9%, 42.5%, and 62.5% for the same systemic treatments delivered following surgical resection. Hence the additive impact of surgical resection on absolute 3 yr OS was only 18.1% in the absence of systemic treatment, but 30.0%, 37.1%, 42.5% and 58.8% in the presence of 5FU, gemcitabine, gemcitabine + capecitabine, FOLFIRINOX respectively. Conclusions: Within the limitations of this analysis, it appears that our hypothesis was incorrect, and that the opposite is true. The introduction of effective systemic therapies has greatly increased the impact of pancreatic surgery on long-term survival in pancreatic cancer. Consequently, every effort should be made to bring patients to curative resection.
CUBIC: an atlas of genetic architecture promises directed maize improvement
Authors: Hai-Jun Liu, Xiaqing Wang, Yingjie Xiao, Jingyun Luo, Feng Qiao, Wenyu Yang, Ruyang Zhang, Yijiang Meng, Jiamin Sun, Shijuan Yan, Yong Peng, Luyao Niu, Liumei Jian, Wei Song, Jiali Yan, Chunhui Li, Yanxin Zhao, Ya Liu, Marilyn L. Warburton, Jiuran Zhao, Jianbing Yan
Journal: Genome biology (2020)

Identifying genotype-phenotype links and causative genes from quantitative trait loci (QTL) is challenging for complex agronomically important traits. To accelerate maize gene discovery and breeding, we present the Complete-diallel design plus Unbalanced Breeding-like Inter-Cross (CUBIC) population, consisting of 1404 individuals created by extensively inter-crossing 24 widely used Chinese maize founders.
The short-term outcomes from TOP-G trial: Ramdomized phase II noninferiority trial comparing gastrectomy with omentectomy and omentum preserving gastrectomy for advanced gastric cancer.
Authors: Takanobu Yamada, Hitoshi Murakami, Masataka Taguri, Shinichi Hasegawa, Takeharu Yamanaka, Yasushi Rino, Hiroyuki Mushiake, Takashi Oshima, Hiroshi Matsukawa, Kazuyuki Tani, Yoshihiro Suzuki, Yukihiro Ozawa, Hiroyasu Tanabe, Tsutomu Sato, Hiroshi Tamagawa, Norio Yukawa, Takaki Yoshikawa, Toshio Imada, Munetaka Masuda, Yuji Yamamoto
Journal: Journal of Clinical Oncology (2020)

285 Background: A complete resection of the omentum has been believed as a standard procedure for advanced gastric cancer. However, there was no evidence for survival significance of omentectomy. Therefore, we conduct the Phase II trial (TOP-G trial) comparing gastrectomy with omentectomy and omentum preserving gastrectomy. Here, we present the short-term outcomes which was a secondary endpoint of TOP-G trial. Methods: Enrollment criteria included histologically confirmed cT2-4a and N0-2 gastric adenocarcinoma. The extent of nodal dissection was performed based on the Gastric Cancer Treatment Guidelines in Japan. All procedure was performed through laparotomy. Laparoscopic approach was not accepted. Surgical outcomes morbidity, and mortality were compared between gastrectomy with omentectomy group (group A) and omentum preserving gastrectomy group (group B). Postoperative complication was evaluated with Clavien-Dindo classification. Results: A total of 251 patients were randomly assigned to group A (n = 125) or group B (n = 126) between April 2011 and October 2018. After excluding patients who received bypass or no surgery, 246 patients were analyzed as actual treatment group. There was no difference between two groups in patient characteristics and pathological findings. There was no difference in operation time (median 244 vs 204 min, p = 0.156) and in blood loss (median 260 vs. 210 ml, p = 0.371). Median number of totally retrieved lymph nodes was similar (median 36 vs. 37, p = 0.758). There was no difference in the incidence of any postoperative complication (28.9% vs. 25.8%, p = 0.584). There was no mortality in both groups. Conclusions: Omentum preserving gastrectomy for advanced gastric cancer was similar short-term outcomes with gastrectomy with omentectomy. Clinical trial information: UMIN000005421.
Immune awakening revealed by peripheral T cell dynamics after one cycle of immunotherapy
Authors: Sara Valpione, Elena Galvani, Joshua Tweedy, Piyushkumar A. Mundra, Antonia Banyard, Philippa Middlehurst, Jeff Barry, Sarah Mills, Zena Salih, John Weightman, Avinash Gupta, Gabriela Gremel, Franziska Baenke, Nathalie Dhomen, Paul C. Lorigan, Richard Marais
Journal: Nature Cancer (2020)
Questions on ‘Sequencing of the MHC region defines<i>HLA-DQA</i>1 as the major genetic risk for seropositive rheumatoid arthritis in Han Chinese population’ by Guo<i>et al</i>
Authors: Cristina Regueiro, Antonio Gonzalez
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the paper by Guo et al 1 addressing the HLA association with seropositive rheumatoid arthritis (RA) in Han Chinese. The authors reported that aspartic acid at position 160 of HLA-DQα1 (HLA-DQα1:160D) was the major risk factor. It was accompanied by asparagine at position 37 of HLA-DRβ1 (HLA-DRβ1:37N), which was protective. These results were obtained by targeted sequencing in 961 cases and 1812 controls distributed in discovery and validation stages. The underlying assumption is that sequencing had uncovered new susceptibility HLA alleles. Specifically, HLA-DQα1 has not previously been associated with RA, whereas the most associated HLA alleles and amino acids were those …
Institutional experience with total neoadjuvant therapy for low-lying rectal tumors.
Authors: Jason Sanders, Lauren D. Goldbeck, Donald A. Muller, Sunil W. Dutta, Paul Raymond Kunk, Traci Hedrick, Sook Hoang, Matthew Reilley, Charles Friel, Tri Minh Le, Einsley-Marie Janowski
Journal: Journal of Clinical Oncology (2020)

123 Background: Surgery has traditionally been the primary treatment for rectal cancer with consideration of neoadjuvant and adjuvant therapies based on stage. Recent studies have shown that Total Neoadjuvant Therapy (TNT) may provide excellent outcomes, with a possibility of non-operative management in patients with rectal cancer. This study is an initial report of our institution’s watchful waiting strategy. Methods: Patients with Stage II-III, low rectal adenocarcinomas treated from 2015-2018 with TNT were retrospectively reviewed. Patients were surgical candidates with no planned surgery. All patients received definitive radiation (median dose 54 Gy, range 50-56 Gy, at 1.8-2 Gy/fx) with concurrent Xeloda, with additional chemotherapy delivered either prior to or following chemoradiation. Kaplan-Meier (KM) method was utilized to estimate the 2 year permanent ostomy and surgery free survivals. Univariate and multivariate analysis using binary logistic regression were performed to assess the odds ratio (OR) of the need for surgery, with 95% confidence interval (CI). Results: 28 patients were treated with TNT with a median age of 59 years (range 32-79 yrs) and median follow up of 24 months (range 6-51 mon). Reasons for TNT included: clinical trial (50%, n = 14), patient desire to avoid surgery (43%, n = 12), and history of LDR prostate brachytherapy (7%, n = 2). The majority of patients had Stage III disease (68%, n = 19). Median tumor distance from the anal verge was 3 cm (range 0-7 cm). 75% (n = 21) of patients were initially managed without surgery, with 5 patients requiring LAR and 2 requiring APR for residual disease. 4 patients initially treated without surgery experienced local recurrence (LR) requiring APR, with a median time to LR of 20 months (range 12-27 mon). The KM estimated 2 year permanent ostomy and surgery free survivals were 69% and 56% respectively. Distant metastases occurred in two patients at 2 and 7 months post RT. An incomplete response on post-treatment MRI predicted eventual receipt of surgery (p = 0.012, OR = 19.8, 95% CI 1.9-202, compared to complete responders). Conclusions: These results support the growing evidence that TNT may provide a non-surgical option for select patients with low lying rectal cancer.
Enhancing Chimeric Antigen Receptor T-Cell Efficacy in Solid Tumors
Authors: Giovanni Fucà, Loic Reppel, Elisa Landoni, Barbara Savoldo, Gianpietro Dotti
Journal: Clinical Cancer Research (2020)

Chimeric antigen receptor (CAR) T-cell therapy has been acclaimed as a revolution in cancer treatment following the impressive results in hematologic malignancies. Unfortunately, in patients with solid tumors, objectives responses to CAR T cells are still anecdotal, and important issues are driven by on-target but off-tumor activity of CAR T cells and by the extremely complex biology of solid tumors. Here, we will review the recent attempts to challenge the therapeutic impediments to CAR T-cell therapy in solid tumors. We will focus on the most promising strategies of antigen targeting to improve tumor specificity and address the tumor heterogeneity, efforts to circumvent the physical barriers of the tumor architecture such as subverted tumor vasculature, impediments of CAR T-cell trafficking and immune suppressive microenvironment.
More evidence for dolutegravir as first-line ART for all
Authors: Janne Estill, Barbara Bertisch
Journal: The Lancet HIV (2020)

In The Lancet HIV, Andrew Phillips and colleagues 1 Phillips AN Bansi-Mataru L Venter F et al. Updated assessment of risks and benefits of dolutegravir versus efavirenz in new antiretroviral treatment initiators in sub-Saharan Africa: modelling to inform treatment guidelines. Lancet HIV. 2020; (published online Feb 5)https://doi.org/10.1016/S2352-3018(19)30400-X Scopus (13) Google Scholar present the results of a mathematical modelling study comparing first-line regimens in people initiating antiretroviral therapy (ART). They balance the risks and benefits of a dolutegravir-based regimen for all adults versus a dolutegravir-based regimen for all adults except women wanting (more) children, who will be treated with efavirenz. 1 Phillips AN Bansi-Mataru L Venter F et al. Updated assessment of risks and benefits of dolutegravir versus efavirenz in new antiretroviral treatment initiators in sub-Saharan Africa: modelling to inform treatment guidelines. Lancet HIV. 2020; (published online Feb 5)https://doi.org/10.1016/S2352-3018(19)30400-X Scopus (13) Google Scholar Updated assessment of risks and benefits of dolutegravir versus efavirenz in new antiretroviral treatment initiators in sub-Saharan Africa: modelling to inform treatment guidelinesIn the context of a range of modelled setting scenarios in sub-Saharan Africa, we found that a policy of ART initiation with a dolutegravir-based regimen, including in women intending pregnancy, was predicted to bring population health benefits and be cost-effective, supporting WHO's strong recommendation for dolutegravir as a preferred drug for ART initiators. Full-Text PDF Open Access
Muscle-specific SMN reduction reveals motor neuron–independent disease in spinal muscular atrophy models
Authors: Jeong-Ki Kim, Narendra N. Jha, Zhihua Feng, Michelle R. Faleiro, Claudia A. Chiriboga, Lan Wei-Lapierre, Robert T. Dirksen, Chien-Ping Ko, Umrao R. Monani
Journal: Journal of Clinical Investigation (2020)

Paucity of the survival motor neuron (SMN) protein triggers the oft-fatal infantile-onset motor neuron disorder, spinal muscular atrophy (SMA). Augmenting the protein is one means of treating SMA and recently led to FDA approval of an intrathecally delivered SMN-enhancing oligonucleotide currently in use. Notwithstanding the advent of this and other therapies for SMA, it is unclear whether the paralysis associated with the disease derives solely from dysfunctional motor neurons that may be efficiently targeted by restricted delivery of SMN-enhancing agents to the nervous system, or stems from broader defects of the motor unit, arguing for systemic SMN repletion. We investigated the disease-contributing effects of low SMN in one relevant peripheral organ — skeletal muscle — by selectively depleting the protein in only this tissue. We found that muscle deprived of SMN was profoundly damaged. Although a disease phenotype was not immediately obvious, persistent low levels of the protein eventually resulted in muscle fiber defects, neuromuscular junction abnormalities, compromised motor performance, and premature death. Importantly, restoring SMN after the onset of muscle pathology reversed disease. Our results provide the most compelling evidence yet for a direct contributing role of muscle in SMA and argue that an optimal therapy for the disease must be designed to treat this aspect of the dysfunctional motor unit.
A global phase II trial-in-progress with bavituximab plus pembrolizumab in patients with advanced gastric or gastroesophageal cancer.
Authors: Jeeyun Lee, Kerry Culm-Merdek, Jessicca Martin Rege, Andrew William Pippas, Johanna C. Bendell, Ian Chau
Journal: Journal of Clinical Oncology (2020)

TPS459 Background: The majority of gastric cancer (GC) patients fail to derive sufficient benefit from currently available therapies. Pembrolizumab received accelerated approval in 2017 as a third-line therapy in PD-L1 positive GC patients with an ORR of 13.3%. Further studies in second- and third-line GC patients showed comparable outcomes when pembrolizumab was combined with chemotherapy. Bavituximab, an investigational, chimeric monoclonal antibody designed to inhibit the immunosuppressive effects of phosphatidylserine (PS), is being evaluated in combination with pembrolizumab in patients with advanced gastric and gastroesophageal junction (GEJ) cancer. Bavituximab binds in a high-affinity complex with β2-glycoprotein and PS to reverse immunological non-responsiveness and activate multiple immune cell receptors, including TIMS and TAMS. Data from the Phase III Sunrise second-line lung cancer study indicated that patients who progressed on study treatment with bavituximab plus docetaxel and continued with a checkpoint inhibitor showed significantly improved overall survival. Cumulative data suggest that bavituximab may potentiate pembrolizumab-mediated checkpoint inhibition, potentially increasing overall clinical benefit. Methods: This phase 2, multicenter, open-label, single-arm global study is designed to assess the safety, tolerability and efficacy of the bavituximab-pembrolizumab combination in advanced gastric or GEJ adenocarcinoma patients, regardless of PD-L1 status, who have progressed on or after at least one prior standard therapy. Patients must be treatment naïve for checkpoint inhibitors. The study, started in August 2019, consists of an initial 3+3 de-escalation safety cohort to confirm the expansion cohort dose. A total of 80 patients will be enrolled. Primary endpoints will assess antitumor activity of the treatment combination on objective response rate using RECIST1.1, safety and tolerability. Secondary endpoints will evaluate antitumor characteristics, pharmacokinetics, and immunogenicity. Exploratory objectives include the evaluation of a novel biomarker signature panel and its relationship to efficacy outcomes.
Wild-type APC and prognosis in metastatic colorectal cancer.
Authors: Chongkai Wang, Ching Ouyang, Jaideep Singh Sandhu, Michael Kahn, Marwan Fakih
Journal: Journal of Clinical Oncology (2020)

223 Background: Somatic mutations at adenomatous polyposis coli ( APC) gene, found in ~75% of colorectal cancers (CRC), are under-represented in microsatellite instable (MSI-H) tumors. While several studies have suggested worse outcomes for CRC patients (pts) with wild-type APC ( APC-WT), the prognostic implication of this genomic alteration in metastatic CRC (mCRC) is not well defined. Methods: APC prognostic value was evaluated in 331 stage IV microsatellite stable (MSS) CRC pts treated in our institution. Next-generation genomic analysis (FoundationOne) was used to characterize the molecular characteristics of APC-WT and mutant APC ( APC-MT) pts. Findings were validated on a public database of stage IV colon cancer from MSKCC. Results: APC-WT was present in 26% of mCRC patients. In comparison to APC-MT population (n = 244), APC-WT pts (n = 87) tended to be younger (median age: 49 vs. 58 years), right-sided (44% vs. 24%), BRAF-V600E mutated (25% vs. 5%), p53 WT (38% vs. 21%) and RAS WT (66% vs. 53%). APC-WT tumors were associated with other Wnt activating alterations ( CTNNB1, FBXW7, RNF43, ARID1A and SOX9). Among those, RNF43 and CTNNB1 were more significantly represented in the APC-WT vs APC-MT population (12% vs 1% and 11% vs 3%, respectively). APC-WT pts had a worse overall survival (OS) than APC-MT pts (30 vs 48 months, HR = 1.809, 95% CI 1.260-2.596, p &lt; 0.0001). Using a multivariate model correcting for primary tumor location, RAS and BRAF status, APC-WT was predictive of poor survival (HR = 1.7, p = 0.001) in our data set. The prognostic implication of APC-WT on OS were confirmed further in a similar multivariate model of 433 stage IV pts from MSKCC public database (HR = 1.6, P = 0.01). Conclusions: APC-WT is associated with poor OS in MSS mCRC regardless of RAS, BRAF status. Compared with APC-MT mCRC tumors, APC-WT tumors were associated with other activating alterations of Wnt pathway, including RNF43 and CTNBB1.
The impact of early palliative care on the quality of life of patients with advanced pancreatic cancer: The IMPERATIVE study.
Authors: Stephanie Lelond, Harvey Chochinov, Paul Joseph Daeninck, Benjamin Adam Goldenberg, Lisa Lix, Susan McClement, Christina Kim
Journal: Journal of Clinical Oncology (2020)

TPS777 Background: Pancreatic cancer is lethal. Chemotherapy can improve survival by months; however, many patients experience an overwhelming burden of cancer-associated symptoms and poor quality of life (QOL). Early palliative care (EPC) alongside standard oncologic care results in improved QOL and survival in patients with lung cancer. Although international guidelines recommend EPC for patients with advanced pancreatic cancer (PANC), the benefit is not known. Objectives: The primary objective is to test for change in QOL between baseline (BL) and 16 weeks (wk). Secondary objectives are to test for change between BL and 16 wk in (a) symptom control; and (b) depression and anxiety. Methods: This prospective case-crossover study of patients with PANC provides EPC plus standard oncologic care. Primary oncology clinics refer patients to an EPC team led by a palliative care physician and a clinical nurse specialist. BL questionnaires are completed prior to initial EPC assessment, then every 4 wk until wk 16. EPC visits are every 2 wk for the first month, every 4 wk until wk 16, and then as needed. QOL, symptom control, anxiety and depression are measured using the FACT-Hep tool, ESAS-r, HADS and PHQ-9, respectively. A generalized linear model will test for statistically significant change in scores between BL and 16 wk; chemotherapy (yes/no) is included as a confounding covariate; model fit will be assessed. A sample size of 20 patients provides 80% power after controlling for covariate effects. 40 patients will be enrolled to account for missing data. To date, 28 patients have enrolled and 17 have completed the intervention. Significance: The benefit of EPC for patients with PANC is not known, however, EPC is increasingly recognized internationally by patients and stakeholders as a critical intervention which may improve both QOL and satisfaction with care. The Canadian Partnership Against Cancer’s report on the patient experience states “the best possible patient experience means all people with cancer have equitable access to high-quality person-centered palliative care”. This study offers access to EPC and provides an environment in which the benefit of an integrated approach is evaluated.