tbuckley/cabot-search huggingface dataset:
The role of response as predictor of improved outcome in advanced pancreatic cancer (APC) patients (pts) treated with first-line Gemcitabine plus Nab-paclitaxel (GemNab).
Authors: Maria Bensi, Brunella Di Stefano, Cinzia Bagalà, Alexia Spring, Marta Chiaravalli, Marta Ribelli, Floriana Camarda, Maria Grazia Maratta, Giampaolo Tortora, Lisa Salvatore
Journal: Journal of Clinical Oncology (2020)

e16758 Background: GemNab is one of the first-line standard treatment (tx) of APC. To date, no predictive factors, both clinical and molecular, of benefit from this regimen exist. Two retrospective studies showed that early tumor shrinkage (ETS) can predict an improved outcome in APC pts receiving a first-line tx with FOLFIRINOX or GemNab. However, data regarding GemNab, limited to a small population of only 57 pts, seem to not confirm the association of ETS with a better outcome. Hence, we retrospectively analysed an homogeneous population of APC treated with first-line GemNab at our Institution, investigating the impact of several clinical factors, including response and ETS. Methods: APC pts receiving a first-line tx with GemNab were included in the analysis. The association of RECIST response and ETS with PFS and OS was evaluated. The following variables were collected: gender; age ( &gt; vs ≤ 55 years and ≥ vs &lt; 70 years ); baseline ECOG PS; Ca 19.9 baseline level (≥ vs &lt; 200); anamnesis of diabetes; site of primary tumor (head/uncinate process vs body/tail); locally A vs metastatic (m) PC; synchronous vs metachronous; number of m sites (1 vs &gt; 1); m sites (liver, peritoneum, lung, nodes); number of tx lines (1 vs &gt; 1). Univariate and multivariate analyses for PFS and OS were performed. Results: A total of 184 APC pts receiving first-line GemNab at our Institution from February 2014 to May 2019 were included in the analysis. RR and ETS were assessed in 174 and 168 pts, respectively. RR was 30%, disease control rate (DCR) 63% and ETS was 24%. Responders had a significant better PFS (12.5 vs 5.7 months, p &lt; 0.0001) and OS (25.1 vs 12.1 months, p &lt; 0.0001). ETS was significantly associated with improved PFS (12.3 vs 6.2 months, p &lt; 0.0001) and OS (24.0 vs 12.8 months, p &lt; 0.0001). At the multivariate analysis a significant association with survival parameters was confirmed for RECIST response, but not for ETS. At the multivariate analysis, also metachronous disease and number of tx lines &gt; 1 were independently associated with better OS. Conclusions: Despite its retrospective nature, this is one of the largest series of APC pts treated with first-line GemNab investigating the role of RECIST response and ETS in predicting outcome. On the basis of our results, RECIST response may be considered a positive prognostic factor, whereas ETS does not. In conclusion, achieving tumor shrinkage, not necessarily early, significantly delays PC progression and prolongs survival in pts treated with first-line GemNab.
Gene signature of antigen processing and presentation machinery (APM) as highly predictive of response to checkpoint blockade in lung cancer and melanoma.
Authors: Jeffrey C. Thompson, Christiana Davis, Wei-Ting Hwang, Charuhas Deshpande, Seth Jeffries, Corey J. Langer, Steven M. Albelda
Journal: Journal of Clinical Oncology (2020)

3121 Background: Treatment of non-small cell lung cancer (NSCLC) with immune checkpoint blockade (ICB) has resulted in striking clinical responses, but only in a subset of patients (pts), underscoring the need to identify genomic and molecular determinants of immune evasion. Limited data exist on the potential role of alterations in HLA Class I antigen processing and presentation machinery (APM) in mediating response to ICB. Methods: We conducted a retrospective cohort study analyzing transcriptional profiles from pre-treatment tumor samples of chemotherapy-refractory advanced NSCLC pts treated with ICB. RNA was analyzed using the AmpliSeq transcriptomic platform. An APM signature was generated utilizing 8 genes associated with antigen processing ( B2M, CALR, NLRC5, PSMB9, PSME1, PSME3, RFX5, HSP90AB1) and was examined for its association with response to therapy and progression-free and overall survival (PFS, OS). The APM signature was then evaluated in two independent melanoma cohorts treated with ICB. Results: We analyzed pre-treatment tumor samples from 51 advanced NSCLC pts treated with ICB, median age 64 (range 31-92), smokers (n = 43), adenocarcinoma (n = 31). There were 23 responders and 28 non-responders. The APM signature was significantly higher in responders compared to non-responders (average z-score 2.69 vs. -2.49, p = 0.0001). An APM score above the median value for the entire cohort was significantly associated with improved PFS (HR 0.24, 95% CI, 0.12-0.47, log-rank = 0.001) and OS (HR 0.34, 95% CI, 0.18-0.67, log-rank = 0.005). The APM score was significantly correlated with the well-validated T-cell-inflamed resistance gene expression profile (GEP) score (R 2 = 0.32, p &lt; 0.0001). However, the APM score demonstrated improved ability to predict response to ICB relative to the GEP score with AUCs of 0.83 and 0.69, respectively. In an independent cohort of 14 high-risk resectable stage III/IV melanoma pts treated with neoadjuvant anti-PD1 therapy, upregulation of genes involved in antigen processing was associated with improved disease free survival (HR: 0.08, 95% CI, 0.01-0.50, p = 0.0065). In an additional independent melanoma cohort of 28 metastatic pts treated with ICB, a higher APM score was associated with improved overall survival (HR 0.31, 95% CI, 0.09-0.89, log-rank = 0.044). Conclusions: Our data demonstrate that defects in antigen presentation may be an important feature in predicting outcomes to ICB in both lung cancer and melanoma.
A single-center retrospective cohort study evaluating the role of neoadjuvant chemotherapy in malignant peritoneal mesothelioma.
Authors: Xiao Wang, Sharyn I. Katz, Leonid Roshkovan, Suzanne Walker, Sally McNulty, Christine Agnes Ciunci, John Muira, Giorgos Karakousis, Keith A. Cengel, Corey J. Langer, Melina Elpi Marmarelis
Journal: Journal of Clinical Oncology (2020)

e21093 Background: Malignant peritoneal mesothelioma (MPM) is a rare variant of malignant mesothelioma, representing &lt; 30% of cases. Standard of care is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) when feasible. The benefit of systemic chemotherapy (chemo) (Neoadjuvant- N, Adjuvant- A, or 1 st -line metastatic –M) is not well established and some retrospective studies report worse outcomes with N chemo. However, our institution has favored use of N chemo prior to surgery for symptom relief and surgical optimization. We conducted a single-center retrospective cohort study of MPM patients treated at our institution to evaluate the effect of N vs. A chemo on outcomes. Methods: We identified non-papillary MPM patients via ICD9/10 codes seen at our institution between 1/1/2009 and 9/1/2019. Pts were followed until 1/1/2020. Patients without pathologic diagnosis were excluded. We explored the effect of receipt of CRS, type of systemic therapy, and histology on overall survival. Median overall survival (mOS) from diagnosis was estimated from Kaplan-Meier curves. A Cox proportional hazard model computed hazard ratios (HR) to assess the effect of the exposure on OS. Results: We identified 47 patients with non-papillary MPM: median age 62 years, 77% epithelioid histology, 74.5% white, 55.3% known asbestos exposure. CRS was performed in 24 (51%) and 18/24 (75%) received HIPEC. The majority received systemic therapy (34/47 (72%)). Among those that received chemo and surgery, N chemo was more common than A chemo (N:12 (all platinum/pemetrexed), A:7). Median OS was 52.7 months (mo) overall and 77.2 mo with surgery vs 20.2 mo without (log rank p = 0.006). Toxicity from N chemo did not prevent surgery with 8/12 successfully receiving surgery (1 surgery scheduled, 2 lost to follow up). Of the 10 pts with evaluable scans: 5 had radiographic reduction of disease (2 complete responses by RECIST 1.1), 4 stable disease and 1 with disease growth. N chemo reduced ascites in 3 out of 4 pts with baseline ascites. N chemo was not associated with worse mOS compared to A chemo (HR 0.64, 95% CI 0.1-3.0, p = 0.62). Non-epithelioid histology was not associated with a worse OS compared to epithelioid (HR 1.5, 95% CI 0.6-4.1, p = 0.4). Conclusions: N chemo was not associated with worse outcomes compared to A chemo and toxicity from N chemo did not preclude surgery. In addition, N chemo resulted in reduction of disease burden and ascites in pts with MPM.
Impact of axillary lymph node dissection (ALND) on survival in patients with ypN1 breast cancer that receive regional nodal irradiation (RNI): A national cancer database (NCDB) analysis.
Authors: Michael Kharouta, Nicholas Damico, Eleanor Elizabeth Harris, Janice A. Lyons
Journal: Journal of Clinical Oncology (2020)

572 Background: The innovation of sentinel lymph node biopsy (SLNB) has allowed many patients with invasive breast cancer to forego ALND. However, the benefit of ALND is unclear in patients with pathologic N1 disease detected on SLNB following neoadjuvant chemotherapy, particularly in patients who receive adjuvant regional nodal irradiation. Methods: The National Cancer Database (NCDB) was queried for women ages 18-75 with cT1-3N1, and ypT0-T3N1M0 invasive breast cancer who underwent definitive surgical resection with axillary staging and also received adjuvant RNI. Patients treated from 2012 – 2015 were included to allow for appropriate coding of extent of axillary surgery. Overall survival (OS) was estimated using the Kaplan-Meier method and compared between patients who received SLNB alone and ALND with or without SLNB utilizing log rank testing. Propensity matching was performed to reduce the impact of potential confounders and balance sample bias. Cox proportional hazards regression was used to identify predictors of overall survival. Results: A total of 1411 women were identified who met inclusion criteria. The median age was 52 (23-75) years. 206 (15%) women had SLNB alone and 1205 (85%) had ALND with or without SLNB. Five year OS was 73% in patients who underwent ALND compared to 76% in those who had SLNB alone (p =0.39). Following propensity matching by age, race, Charlson Deyo Comorbid Condition score, pT stage, grade, ER status, and HER2 status, 5 year OS was 79% in patients who underwent SLNB alone vs. 69% in patients who had ALND performed (p = 0.33). On Cox regression analysis, none of the variables predicted for 5 year OS. Conclusions: ALND in addition to RNI did not improve survival in patients with cT1-3N1M0 and ypT0-3N1M0 breast cancer compared to SLNB and RNI. We await results of the Alliance 011202 randomized trial for prospective validation of ALND omission in a similar subset of patients. [Table: see text]
Type of prior genotoxic insult determines the genomic characteristics of therapy-related acute myeloid leukemia.
Authors: Michael Ozga, James Stewart Blachly, Nicole Renee Grieselhuber, Karilyn T.M. Larkin, Alison R. Walker, Bhavana Bhatnagar, Gregory Behbehani, Meixiao Long, Tamanna Zohra Haque, Sumithira Vasu, Weiqiang Zhao, Daniel Jones, John C. Byrd, Alice S. Mims, Caner Saygin
Journal: Journal of Clinical Oncology (2020)

7515 Background: Therapy-related AML (tAML) is a long-term complication of cytotoxic cancer therapy. It is characterized by adverse genetics and inferior survival outcomes when compared to de novo AML. A proposed mechanism in tAML pathogenesis includes treatment-induced selection of clones harboring pre-existing mutations (i.e. clonal hematopoiesis, CH). We hypothesize that genotoxic therapies used to treat prior malignancy drive leukemogenesis through different mechanisms leading to unique clonal compositions. Methods: AML patients (pts) treated at The Ohio State University between 2015-2018 were included. Genetic profiling was performed using Miseq Illumina platform with a 49-gene targeted sequencing panel at our clinical laboratory. Results: We studied 337 AML pts (Table), of whom 53% had smoking history. Mutations involving ASXL1 were more common in smokers vs non-smokers (14% vs 5.8%, p= .001), while JAK2 mutations were more common in non-smokers (8% vs 1.2%, p= .003). Regarding specific genotoxic therapies and mutations in tAML, we investigated common CH-associated mutations including DNMT3A, TET2, and ASXL1 (DTA mutations). In tAML pts, those exposed to radiotherapy experienced a higher frequency of DTA (52% vs 27%, p= .05), NPM1 (21% vs 0%, p= .002), and SRSF2 (15% vs 0%, p= .01) mutations, and conversely, a lower incidence of TP53 mutations (21% vs 46%, p= .04). Pts with history of cytotoxic chemotherapy had a lower incidence of DTA mutations, including those who received platinum agents (8% vs 49%, p= .005) and taxanes (7% vs 52%, p&lt; .001), but had a higher incidence of TP53 mutations (75% vs 25%, p&lt; .001 for platinum; 53% vs 25%, p= .04 for taxanes). Similarly, alkylators and anthracyclines were associated with lower incidence of DNMT3A (0% vs 20%, p= .009) and ASXL1 (0% vs 12.5%, p= .04) mutations. Conclusions: Different genotoxic agents demonstrate unique effects in leukemia development. Our data suggest that CH clones with DTA mutations may be enriched with smoking and radiotherapy, while cytotoxic chemotherapy may confer a higher incidence of TP53 mutations. Given the adverse prognosis of TP53 mutated AML, identification of pre-existing CH clones might influence treatment selection in solid tumor pts receiving anticancer therapy. [Table: see text]
Effect of accreditation best practice systems on time to treatment delays: Three-year review of a South African internationally accredited site.
Authors: Carol Benn, Bernardo Leon Rapoport, Dominic van Loggerenberg
Journal: Journal of Clinical Oncology (2020)

e14009 Background: The Netcare Breast Care Centre has been an operational multi-disciplinary centre since 2000. It was proposed that formalised accreditation would improve patient services thus three years of patient time to treatment data were analysed comparing the pre-accreditation average to the mid accreditation and post accreditation. Methods: Patients for this comparison met the following criteria: The treating physicians were members of the unit, no arm of the care was external; they underwent a combination therapy of surgery; systemic treatment (neo-adjuvant or post-operative); The patients fell within a clearly defined treatment time frame. The time to treatment was judged from date of diagnosis to date starting first treatment whether surgery or systemic. patients who delayed treatment for longer than 100 days beyond the reasonable allowance within the centre’s Standard operating procedure were excluded. Results: Pre accreditation time to treatment was an average of 36.5 days from the date of initial diagnosis,. An even split of primary surgery (48%) to systemic (52%). During the implementation of new accredited systems, the time to treatment average saw a reduction of 20%, down to 29 days from the date of diagnosis. An even split of primary surgery (47%) to systemic (53%) remained. After full implementation of the new systems and full international accreditation being achieved the time to treatment saw a further 20% improvement (41% from initial value) of 21 days from diagnosis to treatment. Case mix was now heavily weighted towards the systemic treatment of 71% and primary surgery 29%. Conclusions: The implementation of accredited systems and optimization of the MDM environment saw a dramatic improvement to the service provided to patients. Over the course of the accreditation period, the systems allowed for a two-week reduction in time to treatment (40% improvement) from a previous 5-week standard.
宫腔镜与B超联合诊断陈旧性子宫壁损伤11例
Authors: 谢青贞, 杨菁, 徐望明, 程丹
Journal: BMJ (2007)

回顾性分析2001年6月至2006年6月采用B超联合宫腔镜对11例陈旧性子宫壁损伤患者的检查结果,评价B超联合宫腔镜检查诊断陈旧性子宫壁损伤的安全性和有效性.11例患者中有8例为部分子宫壁陈旧性损伤,3例为子宫壁全层损伤.子宫壁损伤在宫腔镜下可见到异常孔穴,孔穴周围围绕着白色机化纤维结缔组织.B超联合宫腔镜检查有助于陈旧性子宫壁损伤的诊断,可以对陈旧性损伤的部位、大小及有无组织嵌顿等做出准确的判断。
Development and Validation of a Deep Learning Model for Non–Small Cell Lung Cancer Survival
Authors: Yunlang She, Zhuochen Jin, Junqi Wu, Jiajun Deng, Lei Zhang, Hang Su, Gening Jiang, Haipeng Liu, Dong Xie, Nan Cao, Yijiu Ren, Chang Chen
Journal: JAMA Network Open (2020)

<h3>Importance</h3> There is a lack of studies exploring the performance of a deep learning survival neural network in non–small cell lung cancer (NSCLC). <h3>Objectives</h3> To compare the performances of DeepSurv, a deep learning survival neural network with a tumor, node, and metastasis staging system in the prediction of survival and test the reliability of individual treatment recommendations provided by the deep learning survival neural network. <h3>Design, Setting, and Participants</h3> In this population-based cohort study, a deep learning–based algorithm was developed and validated using consecutive cases of newly diagnosed stages I to IV NSCLC between January 2010 and December 2015 in a Surveillance, Epidemiology, and End Results database. A total of 127 features, including patient characteristics, tumor stage, and treatment strategies, were assessed for analysis. The algorithm was externally validated on an independent test cohort, comprising 1182 patients with stage I to III NSCLC diagnosed between January 2009 and December 2013 in Shanghai Pulmonary Hospital. Analysis began January 2018 and ended June 2019. <h3>Main Outcomes and Measures</h3> The deep learning survival neural network model was compared with the tumor, node, and metastasis staging system for lung cancer–specific survival. The C statistic was used to assess the performance of models. A user-friendly interface was provided to facilitate the survival predictions and treatment recommendations of the deep learning survival neural network model. <h3>Results</h3> Of 17 322 patients with NSCLC included in the study, 13 361 (77.1%) were white and the median (interquartile range) age was 68 (61-74) years. The majority of tumors were stage I disease (10 273 [59.3%]) and adenocarcinoma (11 985 [69.2%]). The median (interquartile range) follow-up time was 24 (10-43) months. There were 3119 patients who had lung cancer–related death during the follow-up period. The deep learning survival neural network model showed more promising results in the prediction of lung cancer–specific survival than the tumor, node, and metastasis stage on the test data set (C statistic = 0.739 vs 0.706). The population who received the recommended treatments had superior survival rates than those who received treatments not recommended (hazard ratio, 2.99; 95% CI, 2.49-3.59;<i>P</i> &lt; .001), which was verified by propensity score–matched groups. The deep learning survival neural network model visualization was realized by a user-friendly graphic interface. <h3>Conclusions and Relevance</h3> The deep learning survival neural network model shows potential benefits in prognostic evaluation and treatment recommendation with respect to lung cancer–specific survival. This novel analytical approach may provide reliable individual survival information and treatment recommendations.
Screening strategies and methods for colorectal cancer
Authors: Yong Lin
Journal: BMJ (2017)

我国结直肠癌发病率、死亡率居高不下，且呈逐年上升趋势。有效的筛查方式可以提高结直肠癌及癌前病变的早期诊断，进行有效的干预治疗，改变其自然病程和预后。文章总结最新结直肠癌筛查的共识和进展，旨在提高大家对结直肠癌筛查模式与方法的认识，以期降低结直肠癌的发病率和死亡率。
Multiple myeloma (MM) vaccination (influenza, FV and pneumococcal, PV) rates worldwide and impact on infection, hospitalization, and death.
Authors: Michael A. Thompson, Caitlin Costello, Jesus G. Berdeja, Faith Davies, Jeffrey A. Zonder, Hans Chulhee Lee, Jim Omel, Andrew Spencer, Evangelos Terpos, Vania Hungria, Noemi Puig, Cheng-Cheng Fu, Tomas Skacel, Renda H. Ferrari, Kaili Ren, Dawn Marie Stull, Ajai Chari
Journal: Journal of Clinical Oncology (2020)

8528 Background: MM is a cancer of the immune system. Infections are common reasons for hospitalization and death in MM. As MM patients (pts) are living longer, with prolonged exposure to systemic therapy, there is a need to vaccinate pts and to determine the effectiveness of these vaccines. Vaccination in MM pts is underutilized, based on a study of vaccination patterns in a large health system (Alemu JPCRR 2017) and data collected via a pt self-report online portal (Thompson ASCO 2020). We analyzed FV and PV patterns and associated outcomes in INSIGHT MM, the largest global, prospective, observational study in MM to date. Methods: INSIGHT MM aims to understand MM pt and disease characteristics at diagnosis and relapse, treatment patterns, clinical outcomes, and treatment-associated tolerability, effectiveness, quality of life, and healthcare resource utilization. INSIGHT MM has enrolled 4318 MM pts from 15 countries worldwide; pts are being followed up prospectively for ≥5 yrs. Vaccine status is collected at study entry and yearly. We analyzed FV and PV patterns and associated outcomes of pts enrolled in July 2016–2019. Results: At data cutoff (Sep 1, 2019), 2562/2523 pts had study entry data on FV/PV status. Overall vaccination rates were low (FV 40%, PV 30%) and varied by region: FV 56%/38%/27%/4% and PV 43%/28%/21%/5% in US/Europe/Latin America/Asia. In evaluable pts, lack of vaccination was associated with higher infection and hospitalization rates for FV, and with increased risk of death (univariate analysis) for both FV and PV (Table; multivariate analysis underway). Infections, including influenza and pneumonia, were the cause of death in 19% (43/226) / 8% (9/108) (P = 0.018) of pts who did not receive FV / received it in the past 2 yrs and 19% (46/236) / 9% (9/100) (P = 0.027) of pts who did not receive PV / received it in the past 5 yrs, and in 7%/15%/20%/40% of pts who died in US/ Europe/Latin America/Asia (P &lt; 0.0001). Conclusions: Global vaccination rates in MM pts were low and varied by region. Lack of vaccination correlated with rates of infection (FV), hospitalization (FV), and death (FV and PV). Further MM datasets should be analyzed to confirm the findings. Vaccination data should be collected in prospective clinical trials as it may affect survival. Vaccination is important in MM and should be encouraged. Clinical trial information: NCT02761187 . [Table: see text]
A circadian rhythm-gated subcortical pathway for nighttime-light-induced depressive-like behaviors in mice
Authors: Kai An, Huan Zhao, Ying Miao, Qi Xu, Yu-Fei Li, Yu-Qian Ma, Yi-Ming Shi, Jia-Wei Shen, Jian-Jun Meng, Yong-Gang Yao, Zhi Zhang, Ju-Tao Chen, Jin Bao, Mei Zhang, Tian Xue
Journal: Nature Neuroscience (2020)
Systematic mapping of genetic interactions for de novo fatty acid synthesis identifies C12orf49 as a regulator of lipid metabolism
Authors: Michael Aregger, Keith A. Lawson, Maximillian Billmann, Michael Costanzo, Amy H. Y. Tong, Katherine Chan, Mahfuzur Rahman, Kevin R. Brown, Catherine Ross, Matej Usaj, Lucy Nedyalkova, Olga Sizova, Andrea Habsid, Judy Pawling, Zhen-Yuan Lin, Hala Abdouni, Cassandra J. Wong, Alexander Weiss, Patricia Mero, James W. Dennis, Anne-Claude Gingras, Chad L. Myers, Brenda J. Andrews, Charles Boone, Jason Moffat
Journal: Nature Metabolism (2020)