tbuckley/cabot-search huggingface dataset:
Health-related quality of life (HRQoL) in patients with untreated higher-risk myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML) receiving glasdegib + azacitidine (AZA).
Authors: Eunice S. Wang, Timothy Bell, Amer Methqal Zeidan, Helen Bhattacharyya, Art Kudla, Geoffrey Chan, Mikkael A. Sekeres
Journal: Journal of Clinical Oncology (2020)

7527 Background: Glasdegib + AZA showed promising remission rates and overall survival in an analysis of BRIGHT MDS &amp; AML 1012 in patients (pts) with MDS, AML and CMML. Here we assess the impact of glasdegib + AZA on HRQoL in this ongoing Phase Ib study. Methods: Untreated pts with MDS, AML and CMML ineligible for intensive chemotherapy received glasdegib (100 mg QD) + AZA (75 mg/m 2 /D on D1–7 q28D). Pt-reported outcomes (PRO) that characterize HRQoL were measured using the MD Anderson Symptom Inventory (MDASI)-AML/MDS, Pt Global Impression of Severity (PGI-S), and Pt Global Impression of Change (PGIC) tools. PRO were assessed at baseline (BL; except the PGIC), D7 and D15 of cycle (Cyc) 1, D1 of each subsequent Cyc and at end of treatment. Data cutoff: Sept 11, 2019. Results: For the MDS (n=30, including 3 with CMML) and AML (n=30) cohorts, median (range) number of Cyc started was 5 (1–14) and 5 (1–15), respectively. HRQoL over time, as determined by MDASI-AML/MDS, is shown in the Table, with mean scores indicating low symptom burden over time. For the PGI-S, both cohorts showed similar trends in pt’s impression of current leukemia symptoms remaining constant over time (i.e. absent to mild). For the PGIC, pt’s impression of change of leukemia symptoms since starting study medication remained constant over time (i.e. no to minimal change) for the MDS cohort and showed improvement in the AML cohort (i.e. minimal change to much improved). Conclusions: Glasdegib + AZA is a promising first-line treatment option that does not negatively impact the HRQoL of pts with MDS, AML and CMML ineligible for intensive chemotherapy. Clinical trial information: NCT02367456 . [Table: see text]
Tolerability and efficacy of the first-in-class anti-CD47 antibody magrolimab combined with azacitidine in MDS and AML patients: Phase Ib results.
Authors: David Andrew Sallman, Monzr Al Malki, Adam Steven Asch, Daniel Junseung Lee, Suman Kambhampati, William Bruce Donnellan, Terrence James Bradley, Paresh Vyas, Deepa Jeyakumar, Guido Marcucci, Rami S. Komrokji, Joanna Van Elk, Ming Lin, Roy Maute, Jens-Peter Volkmer, Chris H.M. Takimoto, Mark Chao, Naval Guastad Daver
Journal: Journal of Clinical Oncology (2020)

7507 Background: Magrolimab (Hu5F9-G4) is an antibody blocking CD47, a macrophage immune checkpoint and don’t eat me signal on cancers. It induces tumor phagocytosis and eliminates leukemia stem cells. Azacitidine (AZA) synergizes with magrolimab by inducing eat me signals on leukemic cells, enhancing phagocytosis. We report Ph1b data including a potential MDS registration cohort. Methods: Magrolimab+AZA was given to untreated intermediate to very high risk IPSS-R MDS and intensive chemo unfit AML patients. A magrolimab priming/intrapatient dose escalation regimen (1-30 mg/kg QW, Q2W Cycle 3+) was used. AZA was dosed 75mg/m 2 days 1-7. Efficacy was assessed by IWG 2006 (MDS) and ELN 2017 (AML) criteria. Results: 68 patients (39 MDS, 29 AML) with a median age of 72 were treated with magrolimab+AZA. 19% were intermediate cytogenetic risk with 68% poor risk (13% unknown). 27% were TP53 mutant. The combo was well-tolerated with safety similar to AZA alone. Common treatment-related AEs were anemia (38%), fatigue (21%), neutropenia (19%), thrombocytopenia (18%) and infusion reaction (16%). Treatment-related febrile neutropenia was 1.5%. Only 1 patient (1.5%) discontinued due to an AE. In RBC transfusion dependent patients, 58% of MDS and 64% of AML patients became transfusion independent. 30/33 (91%) efficacy evaluable MDS patients had an objective response (42% CR, 24% marrow CR (4/8 also with HI), 3% PR, 21% HI alone, 9% SD). MDS patient responses deepened on study, with a 56% CR rate in patients with ≥ 6 mo follow-up. In AML, 16/25 (64%) responded (40% CR, 16% CRi, 4% PR, 4% MFLS, 32% SD, 4% PD). In 12 TP53 mutant AML patients, 75% had a CR+CRi (42% CR, 33% CRi, 17% SD, 8% PD). Cytogenetic CR was seen in 35% and 50% of responding MDS and AML patients. 22% of MDS and 50% of AML patients with CR/CRi/marrow CR were MRD negative by flow cytometry. Median duration of response is not reached in either MDS or AML, including TP53 mutant AML, with a median follow-up of 5.8, 8.8 and 9.4 mos, respectively (range: 1.9 – 16.8 mos). 91% of MDS and 100% of AML responding patients are in response at 6 mos. The 6 mo overall survival estimate is 100% in MDS and 91% in TP53 mutant AML patients. Conclusions: Magrolimab is a macrophage targeting immunotherapy that with AZA is well tolerated with durable efficacy in MDS, AML, particularly TP53 mutant, a poor prognostic group. A potential registration single arm MDS cohort is ongoing (NCT03248479). ENHANCE, a randomized Ph3 MDS trial is planned. Additional patients/analyses will be reported. Funded by Forty Seven and CIRM. Clinical trial information: NCT03248479 .
Diagnosis and treatment of perimenopausal syndrome
Authors: 陈行
Journal: BMJ (2008)

绝经是每个妇女生命进程中必然发生的生理过程.绝经表示卵巢功能衰退,生殖功能终止.卵巢功能衰退是一个渐进的过程,长期以来人们习惯用更年期(climacteric period)一词来描述这一渐进的变更期,但其确切的定义始终比较含糊。
Trends in colorectal cancer incidence in India.
Authors: Vinay Mathew Thomas, Basil Baby, Kevin Wang, Feitong Lei, Quan Chen, Bin Huang, Aju Mathew
Journal: Journal of Clinical Oncology (2020)

e16084 Background: Colorectal cancer (CRC) accounts for 10% of global cancer deaths yearly. It is postulated that the incidence rates are rising in developing countries like India. We present a comprehensive overview of colorectal cancer incidence in India from various regions from 2004 to 2014. Methods: We obtained data on CRC incidence from the Population Based Cancer Registries (PBCR) of the National Cancer Registry Program. We calculated age-standardized incidence rates (to WHO World Standard Population 2000) for five-year age groups for period of diagnosis (2004-05, 2006-08, 2009-11, and 2012-14). Results: From 2004 to 2014, CRC incidence rates in India increased by 20%. During 2004-2005, the incidence rate of CRC was 5.8 per 100,000 persons. It increased to 6.9 during 2012-2014. Conclusions: CRC rates are rising in India. Even though the absolute rates are low in the Indian population, the rising rates pose a problem in rising cancer morbidity in India. The rising rates can be attributed to changing lifestyles that include consumption of calorie-rich and low fibre diet, excessive use of red meat and processed foods, and physical inactivity. There is a need for cost-effective strategies to enable early diagnosis for colorectal cancer in India. Affordable and equitable treatment will help increase the 5-year survival rates of colorectal cancers. [Table: see text]
Multi-omic single-cell analysis of antigen-presenting compartment reveals a unique functional signature for head and neck squamous cell carcinoma.
Authors: Brittany Barber, Martin Prlic, Florian Mair, Jami Erickson
Journal: Journal of Clinical Oncology (2020)

e15179 Background: Immune studies in head and neck squamous cell carcinoma (HNSCC) are lacking. Studies in the past decade have highlighted the biological significance and the distinct functional properties of immune cell subsets that are resident in non-lymphoid tissues. While tissue-resident memory T cells (T RM ) have been well characterized, much less is known about the human myeloid compartment in HNSCC, which includes professional antigen-presenting cells (APCs) such as dendritic cells (DCs) and macrophages, both of which are critical for shaping the local T cell response. This is particularly relevant in the context of anti-tumor immune responses, which are currently a major focus for therapeutic intervention in HNSCC by either checkpoint inhibitory blockade or adoptive T cell therapy. Methods: A combination of multi-omic single cell RNA sequencing (sc-RNAseq) and 30-parameter fluorescent flow cytometry were used to define the APC compartment in 7 human head and neck squamous cell carcinoma (HNSCC) samples and 4 normal gingival tissue samples as references. Importantly, we performed parallel profiling of the adaptive and innate T cell compartment to elucidate the relationship between APCs and local T RM cells that have been designated as critical players for immune responses in solid tumor tissue. Results: Several novel myeloid phenotypes and an altered composition of the APC compartment in HNSCC relative to normal gingival tissues. APCs expressing pro-inflammatory cytokines such as IL-1b and IL-6 showed reduced abundance, while previously unknown APC subsets defined by the expression of a unique chemokine profile were found to infiltrate HNSCC tissue. Furthermore, our multi-omic approach allowed for profiling of the protein surface phenotype in these transcript-defined clusters, opening up avenues for future therapeutic targeting of tumor-specific antigen-presenting cells. Conclusions: A novel myeloid phenotype and APC compartment were observed in HNSCC when compared to normal gingival tissues. A multi-omic assay identified tumor-specific APCs that may represent future therapeutic targets.
Histiocytic necrotic lymphadenitis: a case report and literature review
Authors: Xiuwen Fei, Chunhua Chi, Na Di, Aimei Dong, Jiatang Zheng, Yuxia Kong
Journal: BMJ (2020)

组织增生坏死性淋巴结炎（HNL）是一种病因不明的非肿瘤性、非特异性淋巴结肿大的自限性疾病。本文报告1例HNL患者资料，并结合文献复习分析其病因及发病机制、临床表现及实验室检查、病理表现和治疗。
Characterizing sites of metastatic involvement in metastatic clear-cell, papillary, and chromophobe renal cell carcinoma.
Authors: Shaan Dudani, Guillermo de Velasco, Connor Wells, Chun Loo Gan, Frede Donskov, Camillo Porta, Anna Fraccon, Felice Pasini, Jae-Lyun Lee, Aaron Richard Hansen, Georg A. Bjarnason, Benoit Beuselinck, Sumanta K. Pal, Takeshi Yuasa, Nils Kroeger, Ravindran Kanesvaran, M. Neil Reaume, Christina M. Canil, Toni K. Choueiri, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2020)

5071 Background: There exists considerable biological and clinical variability between histologic variants of metastatic renal-cell carcinoma (mRCC). Data reporting on sites of metastatic involvement in less common histologies of mRCC are sparse. We sought to characterize the frequency of metastatic site involvement across the three most common histologies of mRCC: clear-cell (ccRCC), papillary (pRCC), and chromophobe (chrRCC). Methods: Using the International mRCC Database Consortium (IMDC) database, patients with mRCC starting systemic therapy between 2002-2019 were identified and sites of metastases at the time of systemic therapy initiation were documented. Patients with multiple sites of metastatic involvement were included in analyses of all groups to which they had metastases. The primary outcomes were prevalence of metastatic site involvement and overall survival (OS). Patients with mixed histology were excluded. Results: 10,105 patients were eligible for analysis. Median age at diagnosis was 60, 72% were male and 79% underwent nephrectomy. 92%, 7% and 2% of patients had ccRCC, pRCC, and chrRCC, respectively. Frequency of metastatic site involvement across the histologic subtypes is shown in Table. Lung, adrenal, brain and pancreatic metastases were more frequent in ccRCC, lymph node involvement was most frequent in pRCC, and liver metastases were most frequent in chrRCC. Median OS for ccRCC varied by site of metastatic involvement, ranging between 16 months (brain/pleura) and 50 months (pancreas). OS by site of metastatic involvement was compared between histologies for the four most common sites of metastases (lung, lymph nodes, bone, liver). As compared to patients with ccRCC, patients with pRCC had lower OS regardless of site of metastasis (p &lt; 0.05). Power was limited and thus differences in OS between ccRCC and chrRCC were not detectable. Conclusions: Sites of metastatic involvement differ based on histology in mRCC. These data highlight the clinical and biologic variability between histologic subtypes of mRCC and constitute the largest cohorts of patients with metastatic pRCC and chrRCC to report on sites of metastases. Sites of Metastatic Involvement by Histology. [Table: see text]
PILGRIM: Phase III clinical trial in evaluating the role of hyperthermic intraperitoneal chemotherapy for locally advanced gastric cancer patients after radical gastrectomy with D2 lymphadenectomy(HIPEC-01).
Authors: Shu-zhong Cui, Han Liang, Yong Li, Yanbing Zhou, Kaixiong Tao, Zhiwei Zhou, Guoxin Li, Peiyu Li, Baojun Zhou, Hongliang Yao, Zheng Peng, Bin Xiong, Minghui Pang, Shirong Cai, Yong Li, Jin Wan, Bin Liang, Ziying Lei, Jiping Wang
Journal: Journal of Clinical Oncology (2020)

4538 Background: Gastric cancer remains the 3rd leading cancer related death worldwide due to early disease recurrence. We hypothesize that hyperthermic intraperitoneal chemotherapy (HIPEC) may effectively prevent local regional recurrence for locally advanced gastric cancer patients who received curative intent surgery. Methods: Pathology proven gastric cancer patients with clinical T3/T4NxM0 disease are eligible for the study and will be randomized to either control group, who will receive standard radical gastrectomy and D2 lymph node dissection or HIPEC group, who will receive the same surgery and HIPEC with paclitaxel x 2 within the first week after surgery. All patients will receive either XELOX or SOX adjuvant chemotherapy. The primary end point is overall survival. Results: 648 patients from 16 high volume gastric medical centers were enrolled between May, 2015 and March, 2019. 331 and 317 patients were randomized to control and HIPEC groups respectively. The median follow-up time is 12.1 months. The common grade 3/4 toxicities ( &gt; 5%) in control and HIPEC groups are anemia 6% vs. 4.1%, intraabdominal infection 5.4% vs. 3.8%, pneumonia 9.7% vs. 9.8%, fever 10.6% vs. 11.4% and hypoalbunemia 15.1% vs. 16.7% respectively. All three perioperative death (within 30 days after surgery) occurred in control group. One patient died from duodenum stump leak which led to multiple organ failure. One patient died from anastomotic led to intraabdominal infection and shock. The 3rd death was suicide caused by severe depression. At the time of this report, the number of event has not reached for final efficacy analysis. Conclusions: It is safe to administer HIPEC to patients received radical gastrectomy with D2 lymph node dissection within one week of surgery. The primary analysis will be expected in one year. Clinical trial information: NCT02356276 .
Role of intratumoral NK cells in triple-negative breast cancer in the FinXX trial and Mayo Clinic cohort.
Authors: Saranya Chumsri, Jodi M Carter, Yaohua Ma, Douglas Hinerfeld, Heather Ann Brauer, Sarah Warren, Torsten O Nielsen, Karama Asleh, Heikki Joensuu, Edith A. Perez, Roberto Antonio Leon-Ferre, David W. Hillman, Judy Caroline Boughey, Minetta C. Liu, James N. Ingle, Krishna R. Kalari, Fergus Couch, Keith L. Knutson, Matthew P. Goetz, E Aubrey Thompson
Journal: Journal of Clinical Oncology (2020)

510 Background: Several studies have established the critical role of preexisting immune response in triple negative breast cancer (TNBC). Most studies evaluated the tumor infiltrating lymphocytes in stroma. However, limited data are available with regards to the importance of specific subtypes and spatial distribution of these immune infiltrates. Methods: NanoString IO360 gene expression analysis and Digital Spatial Profiling (DSP) were used. DSP was used to quantify 39 immune-related proteins in stromal and tumor-enriched segments from 44 TNBC samples from the FinXX trial (NCT00114816) and 335 samples from the Mayo Clinic (MC) cohort of centrally reviewed TNBC (Leon-Ferre BCRT 2018). In FinXX trial, 22 patients with recurrence and 22 patients without recurrence were included. In MC cohort, 217/335 patients received adjuvant chemotherapy while 118 patients had surgery only without adjuvant chemotherapy. Regions were segmented based on pancytokeratin staining. The general linear model was used for statistical analysis of differential expression with recurrence free survival (RFS) as a categorical variable (recur yes or no). Kaplan-Meier estimates and Cox regression models were also used for analysis. Results: In the FinXX trial, using global gene expression analysis with IO360, there was no signature significantly associated with RFS. However, using DSP, high protein expression of CD56 in the tumor-enriched segments was associated with significant improvement in RFS (HR 0.26, 95%CI 0.09-0.78, p 0.01). Nevertheless, CD56 expression in the stroma (HR 0.66, 95%CI 0.29-1.53, p 0.33) and all segments (HR 0.53, 95%CI 0.23-1.25, p 0.14) was not significantly associated with improved outcome. We further validated these findings in the MC TNBC cohort where intratumoral CD56 expression was associated with a significant improvement in RFS (HR 0.23, p 0.002) but not stromal CD56 (p 0.79). Interestingly, when evaluating the MC TNBC cohort according to receipt of chemotherapy, intratumoral CD56 was associated with improved outcome only in patients who received chemotherapy (p 0.02 vs. 0.07). In both cohorts, higher expressions of intratumoral PD-L1, HLA-DR, and CD8 were associated with improved outcome. Conclusions: Using an in-depth analysis with spatially defined context, we identify that intratumoral CD56-positive NK cells are associated with improved outcome in TNBC. Our study highlights the potential role of NK cells in TNBC and future implications for biomarkers and therapeutic targets.Support: W81XWH-15-1-0292, P50CA116201-9, P50CA015083. Clinical trial information: NCT00114816 .
HIV-related outcome disparities between transgender women living with HIV and cisgender people living with HIV served by the Health Resources and Services Administration’s Ryan White HIV/AIDS Program: A retrospective study
Authors: Pamela W. Klein, Demetrios Psihopaidas, Jessica Xavier, Stacy M. Cohen
Journal: PLoS Medicine (2020)

In the United States, approximately one-fifth of transgender women are living with HIV-nearly one-half of Black/African American (Black) transgender women are living with HIV. Limited data are available on HIV-related clinical indicators among transgender women. This is because of a lack of robust transgender data collection and research, especially within demographic subgroups. The objective of this study was to examine retention in care and viral suppression among transgender women accessing the Health Resources and Services Administration's (HRSA) Ryan White HIV/AIDS Program (RWHAP)-supported HIV care, compared with cisgender women and cisgender men.We assessed the association between gender (cisgender or transgender) and (1) retention in care and (2) viral suppression using 2016 client-level RWHAP Services Report data. Multivariable modified Poisson regression models adjusting for confounding by age, race, health care coverage, housing, and poverty level, overall and stratified by race/ethnicity, were used to calculate adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs). In 2016, the RWHAP served 6,534 transgender women (79.8% retained in care, 79.0% virally suppressed), 143,173 cisgender women (83.7% retained in care, 84.0% virally suppressed), and 382,591 cisgender men (81.0% retained in care, 85.9% virally suppressed). Black transgender women were less likely to be retained in care than Black cisgender women (aPR: 0.95, 95% CI: 0.92-0.97, p < 0.001). Black transgender women were also less likely to reach viral suppression than Black cisgender women (aPR: 0.55, 95%I CI: 0.41-0.73, p < 0.001) and Black cisgender men (aPR: 0.55, 95% CI: 0.42-0.73, p < 0.001). A limitation of the study is that RWHAP data are collected for administrative, not research, purposes, and clinical outcome measures, including retention and viral suppression, are only reported to the RWHAP for the approximately 60% of RWHAP clients engaged in RWHAP-supported outpatient medical care.In this study, we observed disparities in HIV clinical outcomes among Black transgender women. These results fill an important gap in national HIV data about transgender people with HIV. Reducing barriers to HIV medical care for transgender women is critical to decrease disparities among this population.
Results of a completed first-in-human phase Ib dose-escalation study of oral CBL0137 in patients with advanced solid tumors.
Authors: Mikhail Fedyanin, Alexey Tryakin, Alla Sergeevna Lisyanskaya, Ekaterina Solovyeva, Natalia Fadeeva, Oleg Gladkov, Vladimir Moiseyenko, Sergey V. Cheporov, Polina Shpigotskaya, Andrei Purmal, Langdon L. Miller, Andrey Leonov, Kristina Zakurdaeva, Katerina Gurova, Andrei Gudkov, Sergei Tjulandin
Journal: Journal of Clinical Oncology (2020)

3607 Background: Curaxin CBL0137 is a novel compound with broad anticancer activity in animal models. The drug is a non-genotoxic DNA intercalator that interferes with histone/DNA binding causing decondensation of chromatin in tumor cells, functional inactivation of histone chaperone FACT, activation of p53 and IFN responses, and inhibition of pro-cancer transcriptional factors, MYC, NF-kB, HSF1, and HIF1a. Methods: The study enrolled adults with advanced chemorefractory solid tumors, ECOG PS ≤2, and adequate organ function. The primary objective was to find the maximum tolerated dose (MTD) and recommended dosing regimen (RDR). Secondary objectives were to evaluate CBL0137 safety, pharmacokinetics, and efficacy. CBL1037 was given orally once daily (QD) for the first 14 days of repeated 28-day cycles. A 3+3 dose escalation determined the MTD, defined as the highest dose at which ≤1 of 6 pts had Cycle 1 dose-limiting toxicity (DLT). Pharmacokinetics were assessed on Days 1 and 13. Efficacy was evaluated every 8 weeks. Results: 60 pts were enrolled (females/males [n]: 42/18; median [range] age 56 [25-76] years; ECOG PS [n] 0/1/2: 8/49/3); cancer types [n]: ovarian cancer [15], colorectal cancer [14], breast cancer [11], others [20]) over 16 dose levels ranging from 4 mg to 200 mg QD. Durations of therapy ranged from 6 to 342 days. Three DLTs were observed: prolongation of QTc Gr 3 (88 mg QD), neutropenia/thrombocytopenia Gr 4 (200 mg QD), and LV dysfunction Gr 3 (200 mg QD). Dose-dependent nausea/vomiting was observed and was Gr 2-4 at 200 mg QD. Gr 1/2 photosensitization occurred in 11 subjects across doses from 48 to 200 mg QD but was successfully managed with sun protection and resulted in no dose modifications or discontinuations. On Day 1, mean (range) plasma CBL0137 T max values were 5.1 (1-10) hrs. Generally linear increases in AUC occurred with increasing CBL0137 dose. Mean (range) t 1/2 values were 25.6 (0.3-166) hrs, with minor dose dependency. Mean (range) Day 13/Day 1 C trough ratios showed 3.6 (1.7-7.2)-fold accumulations. Disease control was registered in 11 pts who had stable disease (SD). Target lesion regressions up to 21% were documented in 4 patients with breast cancer (2), sarcoma (1), and ovarian cancer (1). Pts with breast cancer (1) and sarcoma (1) had SD for &gt; 36 weeks. Conclusions: The Phase 2 RDR for oral CBL0137 was established as 180 mg QD x 14 days in 28-day cycles based on bone marrow and gastrointestinal DLTs at 200 mg QD. CBL0137 showed a manageable safety profile with efficacy signals. Further study as a component of combinations is planned. Clinical trial information: 847 .