tbuckley/cabot-search huggingface dataset:
The impact of BRAF mutation status on clinical outcomes with single-agent PD-1 inhibitor versus combination ipilimumab/nivolumab.
Authors: Vincent The-Luc Ma, Stephanie Daignault, Jessica Waninger, Leslie Anne Fecher, Michael Green, Ajjai Shivaram Alva, Christopher D. Lao
Journal: Journal of Clinical Oncology (2020)

10024 Background: Nearly half of all metastatic melanoma patients possess the BRAF V600 mutation. Several therapies are approved for BRAF mutant metastatic melanoma, but it is unclear if there is a differential outcome to various immunotherapy regimens. Our aim was to better assess if BRAF mutation status has any impact on survival to combination ipilimumab/nivolumab (I/N) versus single-agent PD-1 inhibitor (PD-1i). Methods: We performed a single center, retrospective analysis on a cohort of patients diagnosed with metastatic or unresectable melanoma from 2012 to 2019 at the University of Michigan who were treated with standard I/N or PD-1i (nivolumab or pembrolizumab). A univariate analysis of progression free survival (PFS) and overall survival (OS) was stratified by treatment type and BRAF mutation status. A multivariate Cox regression of survival was used to compare the effects of the treatment groups adjusted by BRAF status, age, gender, pre-treatment LDH level, prior treatment status, and brain metastases status. Results: 323 patients were identified. 132 had BRAF V600 mutation and 191 had BRAF wildtype (WT) status. 138 patients received I/N and 185 patients received PD-1i. In our univariate analysis, there was no difference in PFS [HR: 0.72, 95% CI, 0.46 – 1.13] or OS [HR: 0.78, 0.44 – 1.38] with I/N versus PD-1i in the BRAF mutant cohort, but there was improved PFS [HR: 0.55, 0.35 – 0.88) and OS [HR: 0.52, 0.28 – 0.95] with I/N compared to PD-1i in the BRAF WT group. In the multivariate analysis, the BRAF WT group continued to show PFS benefit with I/N compared to PD-1i [HR: 0.57, 95% CI, 0.35 – 0.95], but the OS benefit no longer achieved statistical significance [HR: 0.54, 0.28 – 1.03]. Conclusions: Our study results were discordant with the observation in the landmark CheckMate 067 trial, which noted improved PFS and OS with I/N compared to nivolumab alone in the BRAF mutant group and no difference in the BRAF WT group. In our real-world retrospective analysis, I/N over PD-1i should be considered as initial immunotherapy for metastatic melanoma patients regardless of BRAF mutation status, but even more favorably in BRAF WT.
Risk factors for emergency room and hospital care for patients with advanced solid tumors on immune checkpoint inhibitor therapy.
Authors: Anish B Parikh, George Mellgard, Qian Qin, Vaibhav G. Patel, Bo Wang, Xiaobo Zhong, Amanda Leiter, Emily J. Gallagher, Matt D. Galsky, William K. Oh, Steven K. Clinton, Amir Mortazavi, Paul Monk, Edmund Folefac, Ming Yin, Yuanquan Yang, Che-Kai Tsao
Journal: Journal of Clinical Oncology (2020)

e15142 Background: Immune checkpoint inhibitors (ICIs) are increasingly utilized across cancer types. Risk factors for emergency room (ER) and inpatient (IP) care in this patient (pt) population remain poorly defined. Methods: We retrospectively reviewed charts for pts with (w/) advanced solid tumors who received more than 1 ICI dose at Mount Sinai from 1/1/11 – 4/28/17. Demographics, medical history, cancer diagnosis and therapy (tx) details, and outcomes were recorded. Descriptive data detailing ER/IP care during ICI tx (from first dose to 3 months after last dose) were collected. Fisher’s exact test and multivariable regression analyses were used to study differences between pts w/ versus w/out ER/IP care during ICI tx. Significance level was set at 0.05 for all tests. Results: 345 patients met the inclusion criteria for this study. Mean age was 64 years. Common tumor types were non-small cell lung cancer (n = 87), melanoma (n = 78), hepatocellular carcinoma (n = 53), and urothelial carcinoma (n = 38). 83% of patients had metastatic disease. Median duration of ICI tx was 2 months. During ICI tx, 50% received ER care and 43% received IP care, resulting in 369 total episodes of ER and/or IP care. 12% of episodes were attributed to ICI toxicity; 6% required intensive care. Median time to ER/IP care was 111 days. Median IP length of stay was 2 days. Several factors were found to be significant predictors of risk for ER or IP care on multivariable analysis (Table). African-American race and Hispanic ethnicity were each predictive of increased risk for both ER and IP care. Conclusions: ER/IP care is common among pts w/ advanced solid tumors on ICI tx. Understanding demographic and clinical risk factors can help prospectively identify higher-risk pts to inform preventive programs aimed at reducing such care. [Table: see text]
Let’s not forget our female front line
Authors: Nisha Abraham-Thomas, Marcela P Vizcaychipi
Journal: BMJ (2020)

Analysis of covid-19 related deaths among UK healthcare workers implies that it is not only ethnic minority groups that we must worry about12—it is also our majority female NHS front line.3 Age and sex adjusted data indicate that young female NHS workers might have a mortality rate almost twice that of a matched non-NHS employed group. 

Over-representation of women in the NHS, making up 77% of total …
A multidisciplinary immune-related toxicity (IR-Tox) program for immune-related adverse events: A two-year experience.
Authors: Aanika Balaji, Jiajia Zhang, Karthik Suresh, Jenna Mammen, Joanna Melia, Amy K. Kim, Meghan Berkenstock, Inbal Sander, Jose Manuel Monroy-Trujillo, Lyle Wilfred Ostrow, Joanne Riemer, Evan J. Lipson, Patrick M. Forde, William Howard Sharfman, Julie R. Brahmer, Laura Cappelli, Jarushka Naidoo
Journal: Journal of Clinical Oncology (2020)

e15074 Background: Immune checkpoint inhibitors (ICIs) cause immune-related adverse events (irAEs) that may require multidisciplinary input. We developed an IR-Tox program consisting of an electronic irAE referral platform +/- in-person consultation, and a monthly irAE tumor board, run by an IR-Tox team comprising 38 organ-specialists and oncologists. Herein, we present our 2-year experience. Methods: Electronic referrals for patients (pts) treated with ICIs at an academic center were sent to the IR-Tox team between 08/2017-12/2019. Demographic, treatment, and irAE data, including in-person consultations and hospitalizations, were collected in an IRB-approved database. Results: The IR-Tox Team received 270 referrals from 227 discrete pts (outpt: 64% inpt: 36%). Median age was 63 years (range: 3-91), 52% were male, 23% had a prior autoimmune condition, and 28% had a prior irAE. Pts had thoracic (30%), gastrointestinal (18%) or melanoma/skin cancers (17%). The majority of pts received ICI monotherapy (56%) vs. combination (44%). Referrals were for suspected irAE (92%, 209/227) or pre-ICI assessment for known autoimmune disease (8%, 18/227). Referrals for confirmed irAEs (147/209) were mainly for high-grade toxicity (G1 = 8%, 2 = 37%, 3 = 54%), 49% were hospitalized (72/147), and 86% (127/147) improved/resolved. In those who did not have a confirmed irAE (n = 62), an alternative medical condition was the most frequent diagnosis (27%, 17/62). The most common irAEs were pneumonitis (51%), dermatitis (11%), arthritis (7%), hepatitis (6%), and colitis (5%). In the entire cohort, organ-specialists were consulted electronically in 92% of pts (209/227), and 73% were subsequently seen in-person (166/227), with the majority (90/166; 54%) undergoing an invasive diagnostic procedure to confirm the irAE. Of outpatients referred, 64% (94/146) required subsequent in-person consults from organ-specialists and only 12% (18/146) were hospitalized. After all irAE-hospitalizations, continued irAE management was delivered in conjunction with organ-specialists in 51% of cases (32/72). Conclusions: A multidisciplinary IR-Tox program is a utilized service that has assisted in irAE identification and management over 2+ years. Use of an electronic referral platform may impact subsequent need for in-person specialist consultations and/or hospitalizations for irAEs. Ongoing management of complex irAEs is now commonly delivered in a multidisciplinary fashion.
Short-term results of VOLTAGE-A: Nivolumab monotherapy and subsequent radical surgery following preoperative chemoradiotherapy in patients with microsatellite stable and microsatellite instability-high locally advanced rectal cancer.
Authors: Satoshi Yuki, Hideaki Bando, Yuichiro Tsukada, Koji Inamori, Yoshito Komatsu, Shigenori Homma, Mamoru Uemura, Takeshi Kato, Daisuke Kotani, Shota Fukuoka, Naoki Nakamura, Makoto Fukui, Masashi Wakabayashi, Motohiro Kojima, Yosuke Togashi, Akihiro Sato, Hiroyoshi Nishikawa, Masaaki Ito, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2020)

4100 Background: Chemoradiotherapy (CRT) followed by radical surgery (S) is standard therapy for patients (pts) with locally advanced rectal cancer (LARC). Sequential use of an anti-PD-1 antibody after radiation demonstrates synergistic effects in in vivo models, and an anti-PD-1 antibody is effective in pts with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). We studied nivolumab (nivo) and radical S following CRT (50.4 Gy with capecitabine 1,650 mg/m 2 ) in T 3–4 N any M 0 LARC. Methods: After the quality-assured CRT, 240 mg q2 weeks x 5 cycles of nivo and radical S were investigated. In cohort A-1, for pts with microsatellite stable (MSS) LARC, the primary endpoint was a centrally confirmed pathological complete response (pCR) rate using AJCC tumor regression grading. The estimated required sample size assuming null and alternative hypotheses pCR = 10% and 30% was 37 pts, with a 1-sided alpha of 5% and power of 90%. In Cohort A-2, 5 pts with MSI-H LARC were included in an exploratory manner. Results: From Jan/2017 to Oct/2019, a targeted number of pts was included and assessed. In cohort A-1, 30% (11/37; 90% CI 18-44%) of pCR (AJCC grade (gr) 0) rate and 38% (14/37) of major pathological response (MPR) (AJCC gr 0+1) rate were observed. Clinical CR was observed in one additional pt (3%) refusing S after nivo. In cohort A-2, 60% (3/5) of pCR rate and 60% (3/5) of MPR rate were observed. As of Jan/2020, only 2 pts (1 local and 1 metastatic) in cohort A-1 and none in cohort A-2 recurred. Immune-related severe adverse events were observed in 3 pts (gr 3 myasthenia, gr 3 interstitial nephritis, and gr 2 peripheral motor neuropathy); all fully recovered and received radical S. During the follow-up period, one additional pt with gr 2 colitis was observed. No treatment-related deaths were observed. Conclusions: Promising pCR rates of 30% and 60%, with mild toxicities, were shown in MSS and MSI-H LARC pts treated with nivo plus radical S after CRT, suggesting the candidate therapy for the future non-surgical approach. Clinical trial information: NCT02948348 .
Examination of necrosis in tumors treated with AVM0703 compared to chemotherapy.
Authors: Theresa Deisher
Journal: Journal of Clinical Oncology (2020)

e20029 Background: AVM0703 should be the first choice for no-option cancer patients. AVM0703 is a fast-acting formulation that lympho-ablates while sparing HSCs, MSCs, platelets, and RBCs. Its transient and manageable side effects reduce the need for additional maintenance treatments while improving quality of life. AVM0703 induces a novel NKT that induces tumor-killing activity without causing GvHD or CRS. AVM0703 is a versatile formulation that can be safely redosed or given in combination with known chemotherapeutics. It is predicted to be safe for previously neglected patient populations. Methods: Mice were monitored over the course of 13 weeks or endpoint criteria. Body weights and tumor measurements were taken 3x per week. Both group and individual growth was tracked. Tumors were dissected from the right flank on takedown and fixed for 24 hours in 4% paraformaldehyde, then stored in 70% ethanol. For analysis, tumors were sent to HistoTox Labs, embedded in paraffin blocks, then sliced and stained for H&amp;E. In a separate study, mice with subcutaneous A20 were treated with increasing concentrations of AVM0703 and allowed to go to endpoint. Tumors were dissected and stained for H&amp;E, CD3, NKp46, and AC3. Finally, tumor bearing mice were treated with high doses of AVM0703 48 hours before takedown. Tumors were dissected and sent to HistoTox for embedding, slicing and staining for H&amp;E, NKp46, CD3, CD49b, AC3, CD31, B220, Ly6G, Sca-1, and PSR. Results: Mice treated with repeat doses of AVM0703 did not display significant loss of body weight or worsening of condition, which was observed in mice treated with chemotherapy. All combination mice displayed significantly higher tumor necrosis and resorption compared to all other treatment groups. Significant necrosis was observed in tumors in as little as 48 hours post dosing. At endpoint, apoptosis was slightly increased at all doses compared to placebo. CD3 and CD49b were decreased in doses above 18 mg/kg, indicating activation of NKT cells in comparison to placebo and low dose AVM0703. There was also an increase in NKp46 staining along the border of large necrotic regions within the tumor. While necrosis was prevalent within the tumor, there was only a slight increase in apoptosis staining. Conclusions: AVM0703 can be repeatedly dosed without significant signs of toxicity. A single dose after 48 hours displays large regions of necrosis within the tumor, indicating that AVM0703 is a fast-acting formulation. AVM0703 is able to replace a dose of Cy/Flu in mice with similar efficacy and increased tumor killing in comparison to Cy/Flu alone with less toxicity.
中药醋调散外敷治疗带状疱疹临床研究
Authors: 朱运喜, 王海涛, 丁丽君
Journal: BMJ (2008)

带状疱疹是由水痘-带状疱疹病毒引起的常见皮肤病,伴有剧烈的神经痛.在临床应用中药醋调散取得较好疗效的基础上,为系统进行观察,我们于1995年10月至2005年12月分别用中药研面外敷疱疹患处和口服阿昔洛韦片治疗带状疱疹患者各80例,临床疗效满意,现报道如下。
Serum resistin and neuron-specific enolase in patients with cerbral infarction or multi-infarct dementia
Authors: Yong-qin Zhou, You-min Huang, Guo-qing Zhang, Hou-yi Zhang
Journal: BMJ (2008)

Serum concentrations of resistin and neuron-specific enolage(NSE)were determined in 72 patients with cerebral infarction(CI),60 patients with multi-infarct dementia(MID),and 60 healthy controls by means of ELISA.Our data showed that serum resistin and NSE in the CI acute phase group were significantly higher than those in the normal control group(P＜0.01).No significant difference was found in serum resistin and NSE between the CI recovery phase group and normal controls group.Moreover,no significant difference was found in serum resistin between the MID group and CI recovery phase and normal control groups(P＞0.05);but NSE Was relatively lower(P＜0.05).This study suggest that serum resistin and NSE might be of great significance to patient's condition and prognosis.

Key words: 
Brain infarction; Dementia,multi-infarct
Characterization of sociodemographic and clinicopathological features and associated outcomes of patients (Pts) with anal squamous cell cancer (ASCC): Analysis of 44,084 pts in the National Cancer Database (NCDB).
Authors: Joanna Alyse Young, Sally Jeanne Trufan, William Mills Worrilow, Laura W. Musselwhite, Reza Nazemzadeh, Kunal C. Kadakia, Seungjean Chai, John Stuart Salmon, Jimmy J. Hwang, Edward S. Kim, Derek Raghavan, Mohamed E. Salem
Journal: Journal of Clinical Oncology (2020)

4052 Background: ASCC incidence is rising. There are limited data on the relationships between sociodemographic &amp; clinicopathological features and outcomes of ASCC pts. Methods: Pts diagnosed with ASCC between 2004 and 2016 were retrospectively reviewed. Data obtained from the NCDB were used to examine the impact of sociodemographic status on clinicopathological features and outcomes. Pts were categorized based on low (median &lt; $38,000) or high (≥$68,000) income and low ( &gt; 21% with no high school diploma) or high ( &lt; 7% with no high school diploma) education areas based on zip code at time of diagnosis. Logistic regression and chi-square were used to examine differences between groups. Results: In total, 44,084 pts with ASCC were identified: median age, 59 yrs, 86% white; 11% black; 64% female. Most pts (84%) resided in metro areas; 29.7% vs 19.8% lived in high vs low income areas; 22.9% vs 17.8% lived in high vs low education areas. Seven percent were uninsured, 50% had government (Gov), and 43% had private insurance. Male gender (HR 1.62, CI 1.41-1.85, p &lt; 0.001), low income area (HR 1.28, CI 1.19-1.37, p = 0.014), and insurance status (Gov, HR 1.55, CI 1.32-1.82, p &lt; 0.001 and uninsured, HR 1.37, CI 1.37-1.85, p = 0.039) were associated with a higher risk of death. After adjusting for age, sex, race, stage, grade, insurance status, and comorbidity, pts from low income/education (n = 6695) vs high income/education (n = 4316) areas had a 33 % increased risk of death (HR: 1.33, p &lt; 0.001). Pts with stage IV ASCC in the low income/education (n = 227) vs high income/education (n = 295) groups had worse overall survival (mOS, 1.4 vs 1.9 yrs, p &lt; 0.020). Of the 44,084 pts, 5461 (12.4%) had confirmed HPV status. Of these, 2658 (48.7%) were HPV+ (high risk subtypes) and 2803 (51.3%) were HPV-. Compared to the HPV- pts, HPV+ pts were more likely to be women (71.8% vs 67.8%, p = 0.001), have stage 3 (38.1% vs 33.6%) or 4 (7.9% vs 5.9%, p &lt; 0.001) cancer, and have poorly differentiated (29.5% vs 25.6%, p &lt; 0.001) tumors. There were no significant differences in race, education, income, metro area, insurance status, or comorbidity between the HPV+ and HPV- pts. Moreover, HPV status did not impact OS (HR 0.92, CI 0.81-1.04, p = 0.195). Conclusions: HPV status was not correlated to income, education or insurance status, and did not impact OS in ASCC pts. Male gender and insurance status were associated with increased risk of death. Pts living in low income and low education areas were associated with worse survival.
Chronic abdominal pain in primary care: a new horizon
Authors: Dong Wu
Journal: BMJ (2019)

慢性腹痛是基层医疗机构的常见病，病因复杂，诊断和治疗均有一定的难度。应通过审慎、合理、全面的临床评估区分器质性腹痛和功能性腹痛，并避免过度检查。多数慢性腹痛系功能性疾病所致，其中以中枢介导的腹痛综合征为代表。不明原因的严重、持续性腹痛是本病的突出表现，病史和体格检查对诊断有提示意义。良好的医患沟通对于诊治慢性腹痛十分重要。由器质性疾病导致的慢性腹痛以治疗原发病为主。药物治疗、认知行为治疗及心理干预对功能性腹痛有效。
PFS by blinded independent central review (BICR) in the VELIA trial of veliparib (V) plus carboplatin/paclitaxel (CP) and as monotherapy in newly diagnosed patients (pts) with high-grade serous ovarian cancer (HGSC).
Authors: Carol Aghajanian, Michael A. Bookman, Gini F. Fleming, Mark F. Brady, Elizabeth M. Swisher, Karina Dahl Steffensen, Michael Friedlander, Aikou Okamoto, Kathleen N. Moore, Danielle Marie Sullivan, Mathias Fallstrom, Minh Dinh, Christine Ratajczak, Robert L. Coleman
Journal: Journal of Clinical Oncology (2020)

6077 Background: The phase III VELIA trial (NCT02470585) demonstrated statistically significant improvement in PFS per investigator (INV) for V added to CP and continued as maintenance (CPV-V) vs. CP alone in pts with newly diagnosed HGSC in the BRCA mutated ( BRCAm), homologous recombination deficient (HRD), and whole populations. Here we present pre-specified analyses of PFS per BICR. Methods: Pts with Stage III-IV HGSC received V or Placebo (PL) with CP (6 cycles) and as maintenance (30 additional cycles). Primary analysis of PFS by INV compared CPV-V to CP alone in the BRCAm, HRD, and whole populations. Exploratory analyses of PFS in BRCA wildtype (wt) and non-HRD HGSC were performed. Radiologic tumor assessments were also prospectively submitted to an independent central reviewer for blinded assessment per RECIST v 1.1. PFS per BICR and rates of concordance between INV and BICR for determination of disease progression were analyzed. Safety data from the primary analysis were previously reported. Results: 1140 total pts were enrolled (CPV-V 382; CP 375). In the whole population, 26% of HGSCs were BRCAm and 55% were HRD. Concordance rates between INV and BICR were 68-85% by arm for each population. Analyses of PFS per BICR and per INV were consistent (Table). PFS was prolonged in the CPV-V vs. CP arm in all primary and exploratory populations assessed. Conclusions: Analyses of PFS per BICR supported the primary analysis of PFS per INV in the BRCAm, HRD, and whole populations, as well as exploratory BRCAwt and non-HRD populations. Median PFS per BICR was longer compared to PFS per INV assessments in all populations and in both arms. These findings support the reliability of PFS by INV in ovarian cancer trials. Alternate strategies like audits may be appropriate to support PFS by INV with less time and expense than full BICR. Clinical trial information: NCT02470585. [Table: see text]
Real-world sustained minimal residual disease (MRD) negativity using NGS in multiple myeloma.
Authors: Audrey Demaree, Anthony Hewitt, Lik Wee Lee, Benjamin Eckert
Journal: Journal of Clinical Oncology (2020)

e19280 Background: MRD assessment has been increasingly incorporated into guidelines and routine care for patients (pts) with multiple myeloma (MM). It has been widely shown that pts who achieve deep MRD negativity (MRD-) have longer PFS/OS. Clinical guidelines now include sustained MRD- (two consecutive MRD- results; (10 −5 , 12 mo. apart) as a response criterion. . NGS MRD (clonoSEQ; Adaptive Biotechnologies; Seattle, WA) is the only FDA authorized method for bone-marrow MRD assessment in MM. A large longitudinal database of quantitative NGS MRD values from routine patient care now enables real-world analysis. We used our data to provide insight into testing patterns and sustained MRD-. Methods: The population included internal data of NGS MRD clinical samples from Jan 2018 to Jan 2020. We examined MRD- achievement overall and sustained MRD- as defined by guidelines. For pts who achieved sustained MRD- and had subsequent MRD testing, we examined if they remained in an MRD- state. Results: We identified 1,675 pts with MM who had ≥1 MRD tests after baseline Clonality (ID) assessment. The age/sex distribution (med. age = 65; 58% male) was consistent with epidemiologic data. 837 (49.9%) and 541 (32.2%) achieved MRD- at 10 −5 or 10 −6 thresholds, respectively. Of the 190 pts with ≥2 MRD tests at least 12 mos. apart, 82 (43.2%) and 45 (23.7%) had sustained MRD- at 10 −5 and 10 −6 thresholds, respectively. Of 82 pts who achieved 12 mo. sustained MRD- at 10 −5 , 15 had a subsequent MRD test, of which all remained MRD-. Of 45 pts who achieved 12 mo. sustained negativity at 10 −6 , 4 had a subsequent MRD test, of which all remained MRD-. Conclusions: We believe this represents one of the earliest real-world study examining NGS MRD attainment of sustained MRD- defined by guidelines. It is notable that many pts reached deep MRD negativity, with a significant percentage having sustained MRD negativity meet guideline-defined criteria. Long-term follow-up and incorporation of clinical parameters &amp; outcomes data will enable further insights from this real-world dataset. [Table: see text]