tbuckley/cabot-search huggingface dataset:
DCE-MRI Evaluation of 10 patients with brain metastases treated with RRx-001, a Myc inhibitor and a CD47 and PD-L1 downregulator, in a phase I/II trial called BRAINSTORM.
Authors: Michelle Miran Kim, Hemant Parmar, Madhava P Aryal, Scott Caroen, Theresa Devasia, Matthew J Schipper, Aki Morikawa, Daniel Eidelberg Spratt, James Hayman, Larry Junck, Theodore Steven Lawrence, Christopher D. Lao, Yue Cao
Journal: Journal of Clinical Oncology (2020)

e14509 Background: In a Phase 1/2 trial called BRAINSTORM (NCT02215512) for brain metastases from any histology, quantitative changes in perfusion MRI after administration of RRx-001, a mic inhibitor and CD47 and PD-L1 downregulator with vascular normalizing properties, were determined and correlated with response. Methods: Ten patients with 64 total lesions evaluable at baseline, 24 hours, and end of radiotherapy (RT) that participated in BRAINSTORM were subjected to a correlative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examination four days prior to the start of whole brain radiotherapy (WBRT) that evaluated Ktrans (capillary permeability) and Vp (plasma volume). The treatment comprised RRx-001 on Day -4, pre-WBRT then twice weekly during WBRT. Four dose levels were administered (5 mg/m 2 , 8.4 mg/m 2 , 16.5 mg/m 2 , and 27.5 mg/m 2 . Results: 10 patients underwent DCE-MRI scans and eight patients with 44 total evaluable lesions had available imaging at 1 month, and 6 patients with 29 total evaluable lesions had imaging at 4 months. On univariate analysis, only a decrease in 24-hour Vp from baseline after a single dose of RRx-001 was marginally associated with absolute tumor volume response 1 month after treatment (p-0.07). In a multivariate model, only Vp prior to therapy and 24-hour change in Vp were retained in the model after stepwise selection. A reduction in Vp 24 hours after RRx-001 (prior to WBRT) was associated with reduced tumor volume at 1 month (Estimate 0.88, 95% CI 0.37-1.40, p = 0.001) and 4 months (Estimate 1.51, 95% CI 0.58-2.43, p = 0.003). Likewise, a lower Vp prior to therapy was associated with reduced tumor volume at 1 month (Estimate 0.73, 95% CI 0.29-1.17, p = 0.002) and 4 months (Estimate 1.8, 95% CI 0.95-2.65, p = 0.0002), suggesting anti-angiogenic activity and early potential vascular normalization after a single dose of RRx-001 predictive of longer-term tumor response. Conclusions: RRx-001 induced a reduction in blood plasma volume, which was associated with tumor response and which suggests a vascular normalizing effect that merits further investigation in future planned studies. Clinical trial information: NCT02215512.
Superior therapy response predictions for patients with myelodysplastic syndrome (MDS) using Cellworks Singula: MyCare-009-02.
Authors: Anthony Selwyn Stein, Drew Watson, Shweta Kapoor, Kunal Ghosh Ghosh Roy, Aftab Alam, Diwyanshu Sahu, Kabya Basu, Annapoorna Prakash, Yashaswini Ullal, Karthik Sundara Raju, Rakhi Purushothaman Suseela, Vishwas Joseph, Sayani Basu, Chandan Kumar, Subrat Mohapatra, Pallavi Kumari, Shivgonda Birajdar, Reshma Gopi, Upasana Mitra, Guido Marcucci
Journal: Journal of Clinical Oncology (2020)

e19528 Background: Despite using cytogenetic and molecular-risk stratification and precision medicine, the current overall outcome of MDS patients remains relatively poor. Therapy selection is often based on information considering only cytogenetics and single molecular aberrations and ignoring other patient-specific omics data that could potentially enable more effective treatments. The Cellworks Singula™ report predicts response for physician prescribed therapies (PPT) using the novel Cellworks Omics Biology Model (CBM) to simulate downstream molecular effects of cell signaling, drugs, and radiation on patient-specific in silico diseased cells. We test the hypothesis that Singula is a more accurate predictor of patient-specific therapy response than PPT. Methods: Singula’s ability to predict response was evaluated in an independent, randomly selected, retrospective cohort of 146 MDS patients aged 28 to 89 years (median 69) treated with PPT. Patient omics data was available from PubMed and TCGA. The accuracy of Singula was compared to that of PPT using McNemar’s test to account for the correlation between Singula and PPT. Multivariate logistic regression modeled complete response (CR) as a function of patient age, PPT, and Singula against any non-response (NR). Likelihood ratio tests were performed to further validate if Singula provides predictive information beyond PPT or patient age. Similar analyses were performed for overall survival (OS) using proportional hazards regression. Results: Singula was a better predictor for CR than PPT (McNemar’s χ 2 = 42.0, p-value &lt; 0.0001), with an overall accuracy of 73.3% (Exact 95% CI: 65.3%, 80.2%) compared to 37.7% (95% CI: 30.0%, 46.1%) for PPT. Singula exhibited a sensitivity and specificity of 90.9% (95% CI: 80.0%, 97.0%) and 62.6% (95% CI: 51.8%, 72.6%), respectively. In multivariate regression analysis, Singula (p &lt; 0.0001) remained an independent predictor for CR after adjusting for patient age (p = 0.0759) and PPT (p = 0.0496). Singula provided alternative therapy selections for 17 of 53 true negative detected by Cellworks. Conclusions: Singula is a superior independent predictor for CR compared to PPT in MDS patients. The Singula report can also validate therapy selection, correctly identify non-responders to PPT and further provide alternative therapy selections.
Eucaloric Very-Low-Carbohydrate Ketogenic Diet in Acromegaly Treatment
Authors: Eva C Coopmans, Kirsten A C Berk, Nour El-Sayed, Sebastian J C M M Neggers, Aart J van der Lely
Journal: New England Journal of Medicine (2020)

Eucaloric Low-Carbohydrate Ketogenic Diet in Acromegaly This proof-of-concept study tested whether an adjuvant eucaloric very-low-carbohydrate diet for 2 weeks added to first-generation somatostati...
Tolerance of concurrent CDK inhibitor and radiation therapy in metastatic breast cancer patients.
Authors: Arnaud Beddok, Alexandre Arsene-Henry, Baptiste Porte, Kim Cao, Nathaniel Scher, Joelle Otz, Mathieu Minsat, Francois Clement Bidard, Alain Fourquet, Paul H. Cottu, Youlia Kirova
Journal: Journal of Clinical Oncology (2020)

e12598 Background: Palbociclib, a small-molecule inhibitor of cyclin-dependent kinases (CDK4 and CDK6), combined with letrozole increases progression-free survival among patients with previously untreated ER-positive, HER2 negative advanced breast cancer. The purpose of our study was to retrospectively evaluate the tolerance of the concomitant association of Palbociclib and radiation therapy (RT) at Curie Institute. Methods: Between April 2017 and August 2019, 30 women with ER-positive, HER2 negative metastatic breast cancer received locoregional (LR) and/or symptomatic irradiation at a metastatic site concurrently with Palbociclib at a daily dose of 125 mg, from d1 to d21 every 28 days. Palbociclib was always associated with endocrine therapy: letrozole (with or without an LHRH analogue) or fulvestrant. Thirty-five sites were irradiated: nine patients received post-operative locoregional RT, including the chest wall or breast and lymph node areas, and 26 sites of metastases were irradiated: 17 at the spine, 7 peripheral skeletal lesions, 1 brain lesion and 1 choroidal lesion. The dose prescribed for locoregional mammary radiotherapy was 50 Gy in 25 fractions and varied for the treatment of metastatic sites: 20 Gy in 5 fractions (n = 13), 30 Gy in 10 fractions (n = 10) and 8 Gy in 1 fraction (n = 2). The brain metastasis was stereotactically treated (1 fraction of 18 Gy). The primary endpoint was toxicity scored according to the common terminology criteria for NCI adverse events, version v5.0. Results: Mean number of days of Palbociclib during RT was 8.8 days (range, 1 to 24 days). The most common acute toxicities were dermatitis (12/35, including 2 grade 2) and neutropenia (12/35, including 9 grade 2). Palbociclib had to be stopped during the RT of two patients (2/30): one patient treated locoregionally (bilateral breast and lymph nodes irradiation) developed a grade 3 dermatitis and febrile neutropenia, another treated locoregionally developed grade 2 dysphagia. After a median follow-up since the end of RT of 17 months (6 – 31 months, SD 8), none of the patients have so far exhibited late toxicity. Conclusions: Concomitant administration of palbociclib with RT was reasonably well tolerated in our series of 30 patients. Given this experience, palbociclib should not be discontinued during radiation therapy. Nevertheless, our findings should be confirmed in prospective registration studies collecting larger number of patients.
Compliance to the American Association for the Study of Liver Diseases (AASLD) guidelines and its impact on overall survival in patients with hepatocellular carcinoma.
Authors: Ashish Manne, Madhuri S Mulekar, Daisy E Escobar, Pranitha Prodduturvar, Yazan Fahmawi, Phillip Henderson, Osama Abdul-Rahim, Zeiad Hussain, Spencer Liles, Annabelle Fonseca, John Harrison Howard, Wadad Mneimneh, Robert Gilbert, Sachin Gopalkrishna Pai, Cindy Nelson, Moh'd M. Khushman
Journal: Journal of Clinical Oncology (2020)

e16609 Background: The Barcelona-Clinic Liver Cancer (BCLC) staging based management proposed by AASLD depends on baseline liver function and performance status of the patient in addition to tumor characteristics. Low adherence to AASLD guidelines, especially in advanced staged tumors, can be ascribed to suboptimal revision/updates of the guidelines reflecting the advancements in hepatocellular carcinoma (HCC) management. Here, in addition to the adherence rate, we explored the overall survival of patients with HCC according to first-line treatment modality compliance to AASLD guidelines. Methods: This is a retrospective study conducted at the University of South Alabama/Mitchell Cancer Institute. Between 2017 and 2019, 148 unique treatment-naïve patients with HCC were identified. Patients were staged according to the BCLC staging system and their compliance with suggested first-line treatment modality according to AASLD guidelines was noted. Overall survival was explored and differences between overall survival rates of compliant and non-complaint patients were compared using the log-rank Wilcoxon test. Results: In our cohort, the median age was 72.5 years (range 38-90). Males represented 80%. Caucasians, African Americans, and other ethnicities (e.g. Asians) represented 68%, 30% and 2% respectively. The overall adherence rate was 83%. The adherence rate according to BCLC stage 0, A, B, C and D was 100%, 97%, 77%, 77% and 38% respectively. Compliance vs. non-compliance to AASLD guidelines showed no significant difference in overall survival of patients with BCLC stage 0-A, B and C. In patients with BCLC stage D (N = 13), compared to patients treated in compliance to AASLD guidelines (N = 5), patients treated in non-compliance (N = 8) had better overall survival (2.2 vs. 5.2 months, p = 0.0012). Conclusions: In our cohort, the adherence rate to AASLD treatment guidelines in patients with BCLC stage D was very low at 38%. Lack of adherence in this group of patients translated into better overall survival. The current AASLD guidelines for the management of HCC have several limitations, especially for advanced stages. In the last few years, the FDA approved several tyrosine kinase inhibitors, immune checkpoint inhibitors and the monoclonal antibody, ramucirumab. This expansion generated the need for periodic updates/revisions of consensus guidelines.
以咽部不适为首发症状的心肌梗死二例
Authors: 杨秀山
Journal: BMJ (2008)

疼痛常是心肌梗死最先出现的症状,但有的患者疼痛部位和性质不典型,有的为上腹部疼痛,常被误诊为胃溃疡穿孔或急性胰腺炎等急腹症[1];少数位于下颌或颈部,易被误认为是咽部不适而就诊于耳鼻咽喉科门诊[2-4]。
Real-world survival data of palbociclib in advanced and metastatic breast cancer: A multicenter experience in Lebanon.
Authors: Lewis Nasr, Ahmad Ghoche, Saada Diab, Fadi Nasr
Journal: Journal of Clinical Oncology (2020)

e13054 Background: Approximately 70% of all breast cancer cases are hormone receptor (HR) positive. One of the most important treatment strategies for HR positive, human epidermal growth factor receptor 2 (HER2) negative subtype was endocrine treatment monotherapy by targeting estrogen receptor or aromatization and thus reducing estrogen level. However, resistance to this treatment and disease progression is universal. In the past few years, palbociclib, an oral inhibitor of cyclin dependent kinase 4 and 6 have been approved by the FDA, as a new standard of care in the metastatic or locally advanced setting either as front line therapy or after progression. The aim of our study is to describe the real world experience with palbociclib. Methods: Eligible patients had histologically confirmed metastatic breast cancer estrogen and progesterone receptors positive and HER2 receptor negative. Palbociclib was given 125 mg orally for 21 consecutive days of a 28 day cycle. Patients were followed over one year. Primary objective was progression free survival (PFS). Tumor response and treatment tolerability were defined as secondary objectives. Results: From 2002 to 2018, we identified a total of 44 breast cancer patients. All patients were females. The median age at diagnosis was 57 years. Among all the patients, 33.3% had visceral metastasis, 35.9% had non visceral metastasis and 30.8% had the two types of metastasis. 64.1% were de novo metastatic and 35.9% were not de novo metastatic. 82.5% had less than 3 sites of metastasis. 47% of the study patients had received both chemotherapy and endocrine therapy during treatment course, and 13 % had only received prior adjuvant endocrine therapy. 28.26% took only prior systemic therapy for breast cancer. By the cutoff date for the final analysis (1/11/2018), a total of 8 events of disease progression occurred, no death events happened. The median progression free survival was 262.6 months for palbociclib combined with letrozole as first line. Conclusions: no data was published before on palbociclib in Lebanon. We are the first to describe these characteristics. Our result (PFS 26 2.6 months) is in conformity with the PFS obtain with PALOMA-2 (24 months).
Adaptations to the British Society of Gastroenterology guidelines on the management of acute severe UC in the context of the COVID-19 pandemic: a RAND appropriateness panel
Authors: Shahida Din, Alexandra Kent, Richard C Pollok, Susanna Meade, Nicholas A Kennedy, Ian Arnott, R Mark Beattie, Felix Chua, Rachel Cooney, Robin J Dart, James Galloway, Daniel R Gaya, Subrata Ghosh, Mark Griffiths, Laura Hancock, Richard Hansen, Ailsa Hart, Christopher Andrew Lamb, Charlie W Lees, Jimmy K Limdi, James O Lindsay, Kamal Patel, Nick Powell, Charles D Murray, Chris Probert, Tim Raine, Christian Selinger, Shaji Sebastian, Philip J Smith, Phil Tozer, Andrew Ustianowski, Lisa Younge, Mark A Samaan, Peter M Irving
Journal: Gut (2020)

Objective Management of acute severe UC (ASUC) during the novel COVID-19 pandemic presents significant dilemmas. We aimed to provide COVID-19-specific guidance using current British Society of Gastroenterology (BSG) guidelines as a reference point. Design We convened a RAND appropriateness panel comprising 14 gastroenterologists and an IBD nurse consultant supplemented by surgical and COVID-19 experts. Panellists rated the appropriateness of interventions for ASUC in the context of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Median scores and disagreement index (DI) were calculated. Results were discussed at a moderated meeting prior to a second survey. Results Panellists recommended that patients with ASUC should be isolated throughout their hospital stay and should have a SARS-CoV-2 swab performed on admission. Patients with a positive swab should be discussed with COVID-19 specialists. As per BSG guidance, intravenous hydrocortisone was considered appropriate as initial management; only in patients with COVID-19 pneumonia was its use deemed uncertain. In patients requiring rescue therapy, infliximab with continuing steroids was recommended. Delaying colectomy because of COVID-19 was deemed inappropriate. Steroid tapering as per BSG guidance was deemed appropriate for all patients apart from those with COVID-19 pneumonia in whom a 4–6 week taper was preferred. Post-ASUC maintenance therapy was dependent on SARS-CoV-2 status but, in general, biologics were more likely to be deemed appropriate than azathioprine or tofacitinib. Panellists deemed prophylactic anticoagulation postdischarge to be appropriate in patients with a positive SARS-CoV-2 swab. Conclusion We have suggested COVID-19-specific adaptations to the BSG ASUC guideline using a RAND panel.
Olaparib as salvage treatment for advanced germ cell tumors after chemotherapy failure: Results of the open-label, single-arm, IGG-02 phase II trial.
Authors: Ugo De Giorgi, Giuseppe Schepisi, Giorgia Gurioli, Carmela Pisano, Umberto Basso, Cristian Lolli, Elisabetta Petracci, Chiara Casadei, Sabrina Chiara Cecere, Laura Attademo, Alberto Clemente, Valentina Zampiga, Valentina Galla, Ilaria Cangini, Marilena Di Napoli, Linda Valmorri, Sandro Pignata
Journal: Journal of Clinical Oncology (2020)

5058 Background: Therapeutic options for patients with advanced germ cell tumors (GCTs) after multiple relapses or resistant disease are limited. Olaparib is an inhibitor of poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair. We aimed to evaluate olaparib activity in patients with refractory GCT. Methods: In this proof-of principle open-label, single-arm, phase II trial of olaparib 300 mg twice daily in patients with relapsed/refractory metastatic germ cell cancer IGG-02 study (NCT02533765), patient eligibility included failure after high-dose chemotherapy or after at least 2 different cisplatin-based regimens. Measurements of serum tumor markers and computed tomography were carried out at baseline and every 6 weeks of olaparib treatment. The study primary endpoint was the overall response rate, the study planned to recruit initially 18 patients and not continue further recruitment until one or more responses were observed. Results: Between September 2015 and February 2019, 18 patients, median age 39 years (range, 22-61) were enrolled. The number of prior chemotherapy regimens was: 2 for 3 patients (16.7%), 3 for 5 patients (27.8%), &gt;3 for 10 patients (55.6%). Sixteen cases (89.9%) received prior high-dose chemotherapy with support of hematopoietic progenitor cells. Grade 3-4 adverse events were observed in 5 patients (27.7%). There were no partial responses, 5 cases (27.8%) with stable disease (SD) lasting 3, 4, 4, 7 and 7+ months and 13 (72.2%) progressive disease. The 12-week progression-free survival probability was 27.8% [95% confidence interval (CI): 10.1%-48.9%]. The 12-month overall survival probability was 27.8% (95% CI: 10.1%-48.9%). A germline DNA repair profile panel showed only a BRCA1 mutated case associated with a SD lasted 4 months. Conclusions: Olaparib as a single agent has marginal activity in heavily pretreated GCT patients, however, an anecdotic 4-month SD in the only BRCA mutated patient has been reported. Plans for future studies with olaparib are suggested in combination or following salvage chemotherapy in less pretreated and more selected GCT patients. The Study has been conducted with AstraZeneca contribution. Clinical trial information: NCT02533765 .
对乳腺增生症与乳腺癌前期病变的认识与临床处理
Authors: 邹强
Journal: BMJ (2009)

乳腺增生症与乳腺癌前期病变(precursor lesions)是临床常见病症,了解其概念与命名原则、发病机制、病理改变,对于临床准确判断病情,采取恰当的临床处理措施,避免因恐癌而扩大手术指征,具有重要意义。
Comprehensive next-generation profiling of clonal hematopoiesis in cancer patients using paired tumor-blood sequencing for guiding personalized therapies.
Authors: Ziyang Li, Wensou Huang, Jiani Yin, Chenglong Na, Xue Wu, Yang Shao, Huaxin Ding, Jinming Li
Journal: Journal of Clinical Oncology (2020)

e13662 Background: Clonal hematopoiesis (CH) is commonly observed during genomic profiling of cancer patients. However, the relevance of CH in Chinese patients has yet to be characterized. Methods: We analyzed next-generation sequencing (NGS) data from blood and matched solid tumors of 4,544 cancer patients. For delineating the impact of CH on panel-based estimation of tumor mutational burden (TMB), its correlation with whole-exome-based TMB calculation was analyzed in an independent cohort of 175 patients. Results: A total of 1,749 CH mutations in 237 genes were identified in the blood of 1,301 (28.6%) patients, among which 26% carried more than one CH mutations. DMNT3A (35.8%), TET2 (13.2%), NOTCH1 (4.8%), ASXL1 (3.8%) and TP53 (3.7%) were among the top altered CH genes, while the prevalence of several other known CH genes, including JAK2 and SF3B1, were below 1%. The predominant hot-spot mutation in DNMT3A at R882 showed varying frequencies of different amino acid changes. An age-associated accumulation of CH events was observed, with alterations in DNMT3A, TET2, ASXL1 and TP53 showing evidence of early changes. A large proportion (74.1%, 1296 mutations) of CH was detectable in the matched tumors. Of these, 453 (25.9%) were functionally annotated as oncogenic or likely oncogenic, including two EGFR kinase domain mutations (V742I and R776H), one KRAS mutation (F156L) and a loss-of-function BRCA2 mutation. With respect to immunotherapy, while CH was not associated with microsatellite instability, it had a negative impact on accurate TMB determination. Consequently, we developed a novel panel-based TMB estimation algorithm with CH filters that showed optimal concordance with exome sequencing in an independent cohort of 175 patients. Conclusions: Our findings highlight the clinical significance of CH in fulfilling the promise of precision medicine and emphasize the need for matched tumor-blood sequencing.
Clinicopathologic features of primary gastrointestinal non-Hodgkin's lymphoma
Authors: Yi Cheng, He-sheng Luo
Journal: BMJ (2012)

The clinical data of 26 cases with pathologically confirmed primary gastrointestinal nonHodgkin's lymphoma (PGINHL) admitted to our hospital from January 2001 to December 2010 were retrospectively analyzed.Among 26 patients,12 cases occurred in stomach,9 cases in small intestine,4 cases in colon and 1 case in multiple sites.The most common symptoms were abdominal pain (73％),followed by gastrointestinal bleeding (23％) and abdominal mass (15％).The main pathological types were MALT lymphoma (35％),diffuse large B-cell lymphoma (35％),and enteropathy-type T-cell lymphoma ( 15％ ).There were 14 patients in stage Ⅰ,6 in stage Ⅱ,1 in stage Ⅲ and 5 in stage ⅣV.Radical surgery and/or chemotherapy was the main therapy for PGINHL.

Key words: 
Lymphoma; Non-Hodgkin;  Retrospective study