tbuckley/cabot-search huggingface dataset:
Results of a phase II randomized trial of cisplatin +/- veliparib in metastatic triple-negative breast cancer (TNBC) and/or germline <i>BRCA</i>-associated breast cancer (SWOG S1416).
Authors: Priyanka Sharma, Eve Rodler, William E. Barlow, Julie Gralow, Shannon Leigh Huggins-Puhalla, Carey K. Anders, Lori J. Goldstein, Ursa Abigail Brown-Glaberman, Thu-Tam Huynh, Christopher Scott Szyarto, Andrew K. Godwin, Harsh B Pathak, Elizabeth M. Swisher, Marc R Radke, Kirsten M Timms, Danika L. Lew, Jieling Miao, Lajos Pusztai, Daniel F. Hayes, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (2020)

1001 Background: PARP inhibitors(i) are effective in BRCA-mutation -associated metastatic breast cancer(MBC). However, there are no studies evaluating PARPi + platin chemotherapy in BRCA wild-type(wt) TNBC. Approximately 1/2 of BRCAwt TNBC demonstrate homologous recombination deficiency (HRD) resulting in a BRCA-like phenotype which might render them sensitive to PARPi. S1416 compared the efficacy of cisplatin plus PARPi veliparib (Vel) or placebo (P) in 3 groups of MBC: gBRCA+; BRCA-like; and non-BRCA-like. Methods: Patients (pts) with metastatic TNBC or g BRCA1/2-associated MBC, who had received &lt; 1 line of prior therapy were treated with cisplatin (75mg/m2) plus Vel or P (300 mg po BID days 1-14), every 3 weeks. All pts underwent central gBRCA testing. A priori established multipronged biomarker panel was used to classify BRCAwt pts into BRCA-like and non-BRCA-like groups, and included myChoice HRD score, somatic BRCA1/2 mutations, BRCA1 methylation and non- BRCA1/2 HR germline mutations. Primary end-point was progression-free survival (PFS) in the three pre-defined groups; secondary end-points included objective response rate (ORR), overall survival (OS), toxicity. Results: 323/335 randomized pts were eligible for efficacy evaluation; 31% had received 1 prior chemotherapy for MBC. 248 pts were classified into the three groups: (1) 37 gBRCA+ (2) 101 BRCA-like; (3) 110 non- BRCA-like. Remaining 75 could not be classified due to missing biomarker information. In the gBRCA+ group (which reached 62% of its projected accrual), numerically better PFS was noted with Vel compared to P (HR=0.64; p=0.26) though this difference was not statistically significant. In BRCA-like group improved PFS was noted with Vel vs P (median PFS 5.7 vs 4.3 months HR=0.58; p=0.023, 1 years PFS 20% vs 7%). Numerically better OS (median OS 13.7 vs 12.1 months, HR=0.66; p=0.14) and ORR (45% vs 35%, p=0.38) were noted with Vel vs P in BRCA-like group. Non-BRCA-like group did not show benefit of veliparib for PFS (HR=0.85; p=0.43) neither did the unclassified group (HR=0.97). Grade 3/4 neutropenia (46% vs 19%) and anemia (23% vs 7%) occurred at higher frequency in Vel arm compared to P. Conclusions: Addition of Vel to cisplatin significantly improved PFS and showed a trend towards improved OS for BRCA-like advanced TNBC. Integral biomarkers used in this study identified a subgroup of BRCAwt TNBC who benefited from addition of PARPi to cisplatin; platinum plus PARPi combination should be explored further in BRCA-like TNBC. Clinical trial information: NCT02595905 .
A randomized, controlled trial of structured palliative care versus standard supportive care for patients enrolled on phase I clinical trials.
Authors: Michelle Elizabeth Treasure, Barbara J. Daly, PingFu Fu, Shufen Cao, Neal J. Meropol, Afshin Dowlati
Journal: Journal of Clinical Oncology (2020)

3634 Background: Phase 1 clinical trials are the first step in developing new cancer therapeutics. Patients enrolled in these studies have typically exhausted standard therapies and are at a point in their disease trajectory where they often are choosing between a phase 1 clinical trial and hospice care. These patients may have significant symptom burden, which can result in early trial discontinuation and confound phase 1 trial outcomes, including toxicity profiles, which may influence further drug development. This study aimed to determine the palliative care needs of patients enrolled on phase 1 clinical trials and their caregivers (CGs), along with differences in study duration, adverse event (AE) and symptom profiles, and quality of life (QOL) between those receiving structured palliative care vs usual supportive care. Methods: 68 patients enrolled on phase 1 clinical trials were randomly assigned to receive structured palliative care or usual supportive care. 39 of their CGs were enrolled and assigned to the same arm as the patient. Quality of life metrics were obtained monthly: the Functional Assessment of Cancer Therapy-General and Memorial Symptom Assessment Scale -Short Form for patients, and The Quality of Life in Life Threatening Illness - Family Carer Version and Caregiver Reaction Assessment for CGs. Palliative care resources utilized were assessed for those in the palliative care arm, and referrals to supportive care services assessed in those in the usual care arm. AEs recorded on the Phase 1 trials were evaluated &amp; compared between arms. Results: Mean duration on phase 1 study was 132 days in the palliative care arm vs 114 days in the usual care arm (p = 0.55). Total weighted AE rate (# of AE [x] AE grade per month) was 26.9 in the palliative care arm vs 34.0 in the usual care arm (p = 0.53). Patients in the palliative care arm experienced better QOL and lower symptom burden, as did their CGs, compared to those in the usual care arm. While the differences in outcomes were not statistically significant, all results favored structured palliative care. Conclusions: Phase 1 patients and their CGs have physical and psychosocial needs which warrant palliative care services. Preliminary results suggest structured palliative care is associated with increased duration on study (by nearly 3 weeks), improved patient and CG QOL, and reduced patient symptom and CG burden. A larger study is warranted to confirm these results and further develop the ideal palliative care intervention in these populations. Clinical trial information: NCT02543541 .
Preliminary studies on effects of methylprednisolone and dexamethasone on Th cytokines in asthmatic children
Authors: Xiang-yu Gag
Journal: BMJ (2008)

Objective This study was carried out to compare chnical efficiency of methylprednisolone (MP) and dexamethasone (Dex) and their effects on Th cytokines in asthmatic children.Methods A total of 39 children with moderate and severe asthma at acute exacerbation were randomly divided into two groups, one (A) with MP 1 -2 mg/kg (n=21) and the other (B) with Dex 0.25 -0.75 mg/kg (n= 18),every 12 -24 h by intravenous drip.Scores of respiratory effort and peak expiratory flow rate prior to and three days after treatment in the asthmatic children aged over five years were evaluated,respectively,as well as the time of wheezing vanishing after treatment.Serum levels of interleukin-2 (IL-2) and IL-4 were determined by radioimmunoassay (RIA) prior to and three days after treatment,respectively.Results There was statistically significant difference in the time of wheezing vanishing between groups A and B (P = 0.042).Three days after treatment,PEER was significantly higher in group A than that in group B (P = 0.025).No statistically significant difference in serum IL-2 and IL-4,as well as ratio of IL-2/IL-4,was found in group B prior to and three days after treatment (P>0.05).Statistically significant difference in serum IL-2 was not observed in group B prior to and three day after treatment (P>0.05),and serum IL-4 decreased significantly (P=0.001) and ratio of serum IL-2/IL-4 (P=0.027) increased significantly three days after treatment than those prior to treatment.No significant correlation between respiratory-effort scores and ratio of serum IL-2/IL-4 prior to treatment was found (P=0.613).Conclusions Up-regulation of IL-2,or inhibition of release of IL-4,probably is not the main anti-inflammatory mechanism of dexamethasone.Methylprednisolone has little effect on serum IL-2,but can effectively reduce serum IL-4, thus increasing the ratio of serum IL-2/IL-4 and counterbalancing function of the Thl/Th2 cells.

Key words: 
Methylpredniselone; Dexamethasone; Interleukin
Pretreatment of dialyzer with high-dose vitamin C reduces oxidative stress of patients withhemodialysis
Authors: Yi-nan Li, Yan-lin Zhang, Ling-hui Zhou, Qiu-yue Chen, Jun Zhang, Heng-yuan, Wei-ping Hu
Journal: BMJ (2012)

Sixty patients who had hemodialysis over half year were randomly divided into 3 groups with 20 cases in each group:group A received conventional hemodialysis,group B received hemodialysis with oral administration of compound danshen (salvia miltiorrhiza bunge) tablets and vitamin E,group C had the same treatment as group B but the dialyzer was pretreated with solution containing 5 g vitamin C ; 20 healthy adults served as normal controls. Serum levels of advanced oxidation protein products (AOPP) and superoxide dismutase (SOD) were measured in all groups.The levels of AOPP in groups A,B,C were higher and SOD levels were lower than those of normal controls ( all P ＜ 0.01 ).The levels of AOPP in groups B,C were lower and SOD were higher than those in group A at the same time points (P ＜0.01 ).The levels of AOPP in group C were lower and SOD were higher than those in group B at the same time points (P ＜0.0l ).The results suggest that pretreatment of the dialyzer with high dose vitamin C plus vitamin E and compound danshen tablets can alleviate oxidative stress in patients with maintaining hemodialysis.

Key words: 
Renal dialysis; Oxidative stress
Obstructive sleep apnea syndrome and cerebral-cardio vascular diseases
Authors: Si Tang
Journal: BMJ (2016)

阻塞性睡眠呼吸暂停低通气综合征(OSAS)已被认为是心脑血管疾病的独立危险因素，而针对OSAS的治疗应当成为防治心脑血管疾病的新方向。本文就OSAS与几种常见心脑血管疾病相关性以及通过治疗OSAS能否改善心脑血管疾病进行讨论。
眼眶嗜酸细胞肉芽肿一例
Authors: 姜鹏飞, 孙英, 唐东润, 刘静
Journal: BMJ (2010)

患者男,12岁,因左眼眶外上方被手指戳伤后持续肿胀2个月余于2008年5月20日以左眶占位性病变入青岛大学医学院附属烟台毓璜顶医院.2个月前外伤后在当地医院以眶部炎症予抗生素联合激素抗炎治疗,肿胀稍减轻.体检:心、肺、肝、脾、肾均未见异常,无家族遗传疾病史.眼科检查:国际标准视力表测定双眼裸眼视力:1.0,眼前节及眼底检查均正常.左眶外上方肿胀,未触及明显肿物.眼球运动不受限.眼球突出度:双眼眼球突出度均为12 mm。
Factors associated with referral for perioperative geriatric comanagement (GERI-CO) program in 12,398 older adults with cancer.
Authors: Armin Shahrokni, Koshy Alexander, Soo Jung Kim, Sincere McMillan, Robert J. Downey, Beatriz Korc-Grodzicki
Journal: Journal of Clinical Oncology (2020)

12034 Background: At ASCO 2019, we showed that the Memorial Sloan Kettering (MSK) Geriatric Co-management (GERI-CO) program was associated with improvement in 90-day postoperative mortality rate. Now, we present factors associated with the use of such program. Methods: At MSK, patients aged 75+ can be referred for perioperative GERI-CO. We retrospectively reviewed the available data of patients aged 75+ who underwent surgery within two months of their initial visit with the surgeon (2011 to 2019). Patients that were referred for GERI-CO were compared with those who were not: sociodemographic, frailty, comorbid conditions, and surgery characteristics. Frailty level was determined using the MSK Frailty Index (score ranges from 0-11, higher scores suggest more frailty). Multivariable regression analysis was used to assess factors associated with the use of the GERI-CO Program. Results: In total 12,398 patients (4422, 35.7% GERI-CO) were included. Average time from surgical consult to geriatric visit was 9 days. Patients in the GERI-CO program were older (80.7 vs. 79.6), less likely to be non-Hispanic White (87% vs. 91%), have English as primary language (84% vs. 89%), and be fit (12% vs. 17% with MSK-FI 0). They were more likely to have stroke history (5% vs. 4%), have diabetes (DM) (25% vs.20%), hypertension (78% vs. 71%), and peripheral vascular disease (14% vs. 12%), but less likely to have cardiac disease (22% vs. 26%), myocardial infarction (MI) (7% vs. 10%), pulmonary disease (13% vs. 16%). Patients referred for GERI-CO were more likely to undergo 3+ hours surgeries (25% vs. 8%), with 100+ cc intraoperative blood loss (41% vs. 22%), and hospital length of stay (LOS) of 3+ days (42% vs. 19%). In multivariable analysis, being frail (OR = 1.3 and 1.6 for MSK-FI 1-2 and 3+), longer surgery (OR = 2.6 and 3.6 for operation time 1.5-3 and 3+ hours), longer LOS (OR = 1.3 and 1.5 for LOS 1-2 and 3+ days), older age (OR = 1.06), having DM (OR = 1.15) were associated with higher likelihood of GERI-CO while having history of cardiac disease (OR = 0.55), MI (OR = 0.84), pulmonary disease (OR = 0.69) were associated with less likelihood of referral for GERI-CO. Conclusions: Our result shows the unique characteristics of patients managed in the GERI-CO program. This has implications for both implementation of GERI-CO program in other institutions and assessing outcomes of these patients.
Receipt of chemotherapy among Medicaid-enrolled patients diagnosed with regional colon cancer
Authors: K. L. Foley, J. A. Tooze, E. Y. Song, H. D. Klepin, A. M. Geiger
Journal: Journal of Clinical Oncology (2009)

e15016 Background: Although overall improvements in colon cancer mortality have been observed, persistent disparities marked by socioeconomic inequality remain. Inadequate treatment received by the poor leads to disparities in overall and disease-free survival. This paper evaluates the patient, health services, and community characteristics associated with receipt of chemotherapy among poor Medicaid beneficiaries diagnosed with SEER-staged regional colon cancer. Methods: A dataset was constructed from Medicaid-enrolled patients diagnosed with colon cancer from 1999 to 2002 (n=692). Using claims data, North Carolina Central Cancer Registry data, and U.S. Census data, multivariable models were constructed to evaluate the association between patient, health services, and community characteristics and adjuvant chemotherapy. Results: Characteristics of the study population include: 66% female; 25% ages 65–74 and 46% ages 75+; and 42% African American. 1 in 4 of individuals with regional stage colon cancer had a Medicaid or Medicare claim for chemotherapy within 12 months of diagnosis. Individuals under age 65 (OR 6.4, CI 3.6–11.1) and ages 65- 74 (OR 4.4, CI 2.6–7.7) were significantly more likely to receive chemotherapy than individuals 75 and older in the multivariable model. Although non-cancer related comorbidity, class of case, and poverty were significantly associated with received chemotherapy in unadjusted models, their effects were no longer significant after controlling for age. Conclusions: A substantial percentage of Medicaid enrollees do not receive recommended adjuvant chemotherapy. The poor elderly may be especially at risk for under treatment. No significant financial relationships to disclose.
Preliminary results of sintilimab plus different dose of IBI305 (anti-VEGF monoclonal antibody) in patients with advanced hepatocellular carcinoma: A phase Ib study.
Authors: Wen Zhang, Xinyu Bi, Yongkun Sun, Yue Yu, Jian-guo Zhou, Huiying Zeng, Fan Wu, Yang Luo, Yong Yang, Mingxia Chen, Yan Wang, Hui Zhou, Jianqiang Cai, Hong Zhao, Aiping Zhou
Journal: Journal of Clinical Oncology (2020)

3079 Background: The study aimed to evaluate the safety and efficacy of sintilimab, a PD-1 blockade, plus IBI305, a biosimilar candidate of bevacizumab, in patients (pts) with advanced hepatocellular carcinoma (HCC). Methods: Adults with histocytologically confirmed advanced or metastatic HCC were enrolled in this two-part study. Part 1 was dose escalation trial, with initial dose of sintilimab 200 mg plus IBI305 7.5 mg/kg, q3w (low-dose group). If tolerable, IBI305 was escalated to 15 mg/kg (high-dose group). In part 2 for extension, at least 20 pts were enrolled to each tolerable dose group. Results: As data cutoff (Jan. 7, 2020), 50 pts were enrolled, 29 in low-dose group and 21 in high-dose group. 41 patients were systemic treatment naïve. The median treatment cycle was 4 (range: 1-19) in low-dose group and 11 (range: 1-16) in high-dose group. Most TRAEs were G1-2 with the most common being hypertension (28.0%) and pyrexia (26.0%). Totally, the grade 3 or more TRAEs were occurred in 6 (12.0%) pts, including hypertension occurred in 2 (4%) pts. The objective response rate (ORR) per RECIST v1.1 was 24.1% (95%CI: 10.3 - 43.5) in low-dose group, and 33.3% (95% CI:13.3 - 59.0) in high-dose group. As with the cutoff date, the median PFS has not been reached and the 6-month PFS rates were 60.5% (95%CI 36.1, 78.0) and 75.8% (95% CI: 47.3, 90.2), respectively. Conclusions: The combination of sintilimab and IBI305 showed promising efficacy and favourable safety profile in advanced HCC in both low-dose and high-dose groups. The preliminary result of this study warrant further exploration of dose selection for anti-VEGF/VEGFR agent when combined with PD-1/PD-L1 antibody. Clinical trial information: NCT04072679 . [Table: see text]
Prevalence of <i>BRCA1/2</i> pathogenic variants in triple negative breast cancer patients stratified according to age at diagnosis.
Authors: Ana Blatnik, Marta Banjac, Ksenija Strojnik, Simona Hotujec, Vida Stegel, Petra Škerl, Vita Šetrajčič Dragoš, Gašper Klančar, Srdjan Novakovic, Simona Borstnar, Nikola Besic, Janez Žgajnar, Andraž Perhavec, Mateja Krajc
Journal: Journal of Clinical Oncology (2020)

e13677 Background: Triple negative breast cancer (TNBC) is strongly associated with germline BRCA1 pathogenic/likely pathogenic variants (PV/LPVs), with up to 28% TNBC patients being BRCA1 PV/LPV carriers. More recently, PALB2 variants have also been shown to be associated with TNBC. Genetic testing in Slovenian hereditary breast and ovarian cancer (HBOC) patients yields consistently high BRCA1/2 detection rates. Four BRCA1 PVs are particularly common, suggesting possible founder effects. Our aim was to analyze the results of panel based genetic testing in Slovenian TNBC patients, with an emphasis on BRCA1/BRCA2 mutational spectrum and detection rates depending on age at diagnosis. Methods: We evaluated the results of genetic testing, performed using a multi-gene panel in 1000 consecutive breast cancer cases. Only 210 patients with TNBC were included in further analysis. We analyzed the mutational spectrum and BRCA1/2 detection rates in TNBC patients stratified according to age at diagnosis. Results: In 80/210 (38.1%) TNBC patients PV/LPVs in BRCA1/2 were identified. Of these, the majority (74/80) were BRCA1-positive. The following variants: c.181T &gt; G, c.5266dupC, c.1687C &gt; T, and c.844_850dupTCATTAC were identified in 64.4% of BRCA1 carriers. BRCA1/2 detection rate decreased with age at diagnosis but was still 18.2% after age 60 (for BRCA1/2 detection rates stratified according to age at diagnosis see table). In 12/210 (5.7%) TNBC patients PV/LPVs in three other genes were identified (3.3% PALB2, 1.4% CHEK2, and 1% ATM). Conclusions: Prevalence of PVs in BRCA1 appears very high in Slovenian TNBC patients and warrants further population-based allele frequency studies with implications for future population screening. High rates of BRCA1/BRCA2 PVs in patients older than 60 years at diagnosis justify testing all TNBC patients, especially in view of treatment options which now include PARP inhibitors. PALB2 was the second most commonly mutated gene in our patients. [Table: see text]
Randomized phase III study of first-line pembrolizumab plus pemetrexed/platinum followed by pembrolizumab and maintenance olaparib versus pemetrexed in patients with metastatic nonsquamous non-small cell lung cancer (NSCLC): KEYLYNK-006.
Authors: Jhanelle Elaine Gray, Taofeek Kunle Owonikoko, Terufumi Kato, Andres Felipe Cardona Zorrilla, Joanne Wagman, Xinqun Chen, Bin Zhao, Christian Schulz
Journal: Journal of Clinical Oncology (2020)

TPS9632 Background: First-line treatment with pembrolizumab + pemetrexed/platinum improved clinical outcomes in patients with advanced nonsquamous NSCLC in KEYNOTE-021 and KEYNOTE-189. Poly(ADP-ribose) polymerase inhibitors (PARPi), including olaparib, have been shown to upregulate PD-L1 expression in preclinical studies, and preliminary evidence suggests potential therapeutic benefit and acceptable safety with PARPi plus anti–PD-(L)1 therapy. KEYLYNK-006 (NCT03976323) evaluates first-line pembrolizumab + pemetrexed/platinum followed by pembrolizumab + olaparib vs pembrolizumab + pemetrexed in patients with metastatic nonsquamous NSCLC. Methods: This phase III, randomized, open-label trial enrolls patients aged ≥18 years with histologically/cytologically confirmed treatment-naive, metastatic, nonsquamous NSCLC. Patients (target n = 792) receive induction pembrolizumab 200 mg + pemetrexed 500 mg/m 2 + carboplatin AUC 5 mg/mL/min or cisplatin 75 mg/m 2 Q3W for 4 cycles. Patients with PR/CR or SD are randomized (target n = 618) 1:1 to pembrolizumab 200 mg Q3W (31 cycles) + maintenance olaparib 300 mg twice daily or pembrolizumab + pemetrexed 500 mg/m 2 Q3W stratified by ECOG PS (0 vs 1), PD-L1 tumor proportion score (&lt;50% vs ≥50%), and response (CR/PR vs SD). Tumor imaging per RECIST version 1.1 (≤5 per organ; maximum 10 total lesions) by central review (BICR) is performed at baseline and Q6W until 60 weeks after randomization, then Q9W until disease progression, start of new cancer therapy, study withdrawal, or death. Primary endpoints are PFS (RECIST 1.1 by BICR) and OS estimated by the Kaplan-Meier method, stratified log-rank test, and Cox proportional hazard model with Efron’s method of tie handling. Secondary endpoints are safety and quality of life; ORR and duration of response are exploratory endpoints. AEs are monitored throughout the study until 30 days after the last dose of treatment (90 days for serious AEs) and graded using NCI CTCAE, version 4.0. The study began enrolling in June 2019. Clinical trial information: NCT03976323 .
MSK-ACCESS for the detection of fibroblast growth factor receptor-3 (FGFR3) mutations in plasma cell-free (cf)DNA of metastatic urothelial carcinoma (mUC) patients (pts) pre- and on erdafitinib (erda) therapy.
Authors: Michal Sarfaty, Min Yuen Teo, Samuel Aaron Funt, Chung-Han Lee, David Henry Aggen, Neha Ratna, Ashley Marie Regazzi, Hikmat Al-Ahmadie, Angela Rose Brannon, Michael F. Berger, David B. Solit, Jonathan E. Rosenberg, Dean F. Bajorin, Gopa Iyer
Journal: Journal of Clinical Oncology (2020)

e17034 Background: The pan-FGFR inhibitor erda was recently FDA-approved for pretreated mUC pts harboring FGFR2/3 alterations. We explored concordance of FGFR3 mutation profiles between the primary tumor and cfDNA using the MSK-ACCESS platform. We also correlated changes in FGFR3 cfDNA mutant allele fraction (MAF) with response to drug. Methods: Plasma samples were collected from mUC pts started on erda at baseline, on treatment (tx), and at progression. Demographic and clinical characteristics were obtained. Baseline tumors were sequenced with MSK-IMPACT (ref) and plasma samples were sequenced using MSK-ACCESS, a cfDNA platform that sequences 129 genes using unique molecular indexes to generate &gt; 15,000x coverage and detection of somatic mutations down to 0.1% MAF. Results: Between 08/2019-1/2020, 11 pts received erda 8mg daily. Of these, 3 pts increased dose to 9mg daily based on phosphorus level, 4 required dose reductions and 6 dose interruptions. In 5 pts, erda was discontinued for disease progression. FGFR3 S249C was the most frequent alteration detected (64%) followed by Y373C (18%), R248C and S371C (both 9%). Pre-treatment plasma FGFR3 profiles were concordant with tissue in 91% (10/11) of pts and additional FGFR3 mutations were detected in 3 cases (27%, Table), including 1 pt with an FGFR3-TACC3 fusion and hotspot mutations only in cfDNA. In 2 responding pts, the mutant allele was undetectable on erda. Conclusions: A high degree of concordance between primary tumor and cfDNA FGFR3 mutation detection was observed. FGFR3 mutations exclusive to cfDNA were found in a subset of pts. Further pt accrual and follow-up are ongoing to assess for correlations between erda response and tx-related changes in cfDNA MAF, and to assess whether cfDNA can identify resistance mechanisms. [Table: see text]