tbuckley/cabot-search huggingface dataset:
Consensus molecular subtypes and CRCassigner classifications in metastatic colorectal cancer (mCRC): Prognostic and predictive impact in the TRIBE2 study.
Authors: Beatrice Borelli, Elisa Fontana, Mirella Giordano, Carlotta Antoniotti, Francesca Bergamo, Sabina Murgioni, Filippo Pietrantonio, Federica Morano, Emiliano Tamburini, Alessandra Boccaccino, Daniele Santini, Veronica Conca, Nicoletta Pella, Evaristo Maiello, Clara Ugolini, Gabriella Fontanini, Alfredo Falcone, Gift Nyamundanda, Anguraj Sadanandam, Chiara Cremolini
Journal: Journal of Clinical Oncology (2020)

4016 Background: The TRIBE2 study (NCT02339116) recently demonstrated the superiority of upfront FOLFOXIRI/bevacizumab (bev) when compared to a pre-planned strategy of doublets/bev in molecularly unselected but mostly (74%) RAS/ BRAF mutant mCRC patients. The Consensus Molecular Subtypes (CMS) and CRCAssigner (CRCA) demonstrated prognostic value in multiple studies, but their predictive role has not been established so far. Given the poor prognosis associated with early stage mesenchymal/stem-like subtypes, we hypothesized that the CMS/CRCA classifiers could predict benefit from the upfront intensified strategy in patients included in the TRIBE2 study. Methods: Untreated formalin-fixed paraffin-embedded samples were classified into CMS/CRCA subtypes using a custom nCounter assay (NanoString Technologies). The impact of subtypes on progression free survival (PFS), progression free survival 2 (PFS2, defined as the time from randomization until the second evidence of disease progression) or overall survival (OS) was evaluated in the profiled population. Results: 426 and 428 (63%) patients enrolled in the TRIBE2 study were profiled according to CMS and CRCA classifications, respectively. The distribution of CMS/CRCA subtypes differed according to primary tumour site (both p &lt; 0.001 for CMS/CRCA) and RAS/ BRAF mutational status (both p &lt; 0.001 for CMS/CRCA). Significant associations of both CMS/CRCA classifiers with PFS, PFS2 and OS were demonstrated (Table). The effect of treatment intensification was independent of CMS subtypes (p for interaction for PFS/PFS2/OS: ns). Significant interaction effect between CRCA subtypes and treatment arm was reported in terms of PFS (p = 0.017), PFS2 (p = 0.010) and OS (p = 0.008). The benefit from the intensification of the upfront chemotherapy seemed more relevant in the stem-like (PFS, HR = 0.60; p = 0.03) and mixed subtypes (HR = 0.44; p = 0.002). Conclusions: CMS subtypes have a prognostic role in mCRC independently of RAS/ BRAF status. CRCA classification may help identifying subgroups of patients who may derive a more substantial benefit from upfront FOLFOXIRI/bev. [Table: see text]
Real-world experience with sipuleucel-T (Sip-T) in Asian men with castrate-resistant prostate cancer (CRPC).
Authors: Jingsong Zhang, Ming Liu, Jiahua Pan, Xiao X. Wei, Matthew Harmon, John Azzolina, Scott Flanders
Journal: Journal of Clinical Oncology (2020)

e17588 Background: Clinical trials of sip-T predominately included white men (over 90%). Previously we explored outcomes with sip-T in white and black patients (pts) (Kantoff PW, NEJM 2010; Sartor AO, ASCO 2019, #5035). In this retrospective analysis of data from electronic medical record and practice management systems, we explored the hypothesis that Asian and white pts who receive sip-T for CRPC exhibit similar overall survival. Methods: Data came from &gt; 100 US community urology practices, predominantly large urology group practice associations. White and Asian pts were matched based on 5 criteria: sip-T treatment year; treatment pattern for oral and sip-T; metastatic site (Bone v. Nodal v. Visceral); prostate-specific antigen (PSA) within 10%; and age at treatment. Parameters retrieved include those listed in the table. Overall survival (OS) was analyzed using Kaplan Meier (KM) methodology with Cox Proportional Hazards Modelling used to generate the hazard ratio (HR) with Asians as the reference. Descriptive summary statistics were generated for other parameters. Results: The analysis identified 102 white and 77 Asian pts; treatment ranged from 2012 to 2019 with 60% receiving sip-T after 2016, impacting the ability to examine long-term outcomes. Characteristics of the 2 groups were broadly similar, although more Asians had Gleason scores ≥8 than whites (Table). In the KM analysis, most pts were censored. While the KM survival curves separate around month 25, favoring Asian pts, the difference is not significant (HR, 0.69 [95% CI: 0.4, 1.4]; P = 0.277). Conclusions: These real-world data do not show a significant difference in OS between Asian and white men. Both groups exhibited relatively low median PSAs near 5 ng/mL, an observation correlated with longer OS in previous studies. [Table: see text]
DREAMM-6: Safety and tolerability of belantamab mafodotin in combination with bortezomib/dexamethasone in relapsed/refractory multiple myeloma (RRMM).
Authors: Ajay K. Nooka, Keith Stockerl-Goldstein, Hang Quach, Adam Forbes, Maria-Victoria Mateos, Amit Khot, Alan Tan, Rafat Abonour, Bikramjit Chopra, Rachel Rogers, Geraldine Ferron-Brady, Jacqueline Davidge, Steve Frey, Anne Yeakey, Mala Talekar, Katarina Luptakova, Ira Gupta, Rakesh Popat
Journal: Journal of Clinical Oncology (2020)

8502 Background: Belantamab mafodotin, a B-cell maturation antigen targeting immunoconjugate, demonstrated clinically meaningful, single-agent activity in patients with heavily pre-treated RRMM refractory to an immunomodulatory agent, a proteasome inhibitor, and refractory and/or intolerant to an anti-CD38 monoclonal antibody (DREAMM-2, NCT03525678, Lancet Oncol.2020). The multimodal mechanism of action and manageable safety profile make belantamab mafodotin a promising candidate for use in different RRMM combination regimens. Methods: DREAMM-6 (NCT03544281) is an ongoing, two-part, two-arm, study evaluating the safety, tolerability, and clinical activity of belantamab mafodotin in combination with bortezomib/dexamethasone (BorDex) and lenalidomide/dexamethasone in patients previously treated with ≥1 prior therapy line. Here, we present data for belantamab mafodotin in combination with BorDex. Part 1 (dose escalation) and Part 2 (dose expansion) evaluated belantamab mafodotin (2.5 and 3.4 mg/kg) administered as SINGLE (Day 1) or SPLIT dose (divided equally on Days 1 and 8) in combination with BorDex. Results: As of February 6, 2020, 52 patients were enrolled: 6 patients were enrolled at 2.5 mg/kg single dose and 7 at 3.4 mg/kg single dosing in Part 1, and 45 patients in Part 2. No dose-limiting toxicities were observed. Corneal events (including keratopathy, blurred vision, and dry eye) and thrombocytopenia were the most frequently reported AEs and were clinically manageable. Conclusions: In DREAMM-6, preliminary data demonstrate that the combination of belantamab mafodotin and BorDex has an acceptable safety profile, with no new safety signals identified. Funding: GlaxoSmithKline (207497). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT03544281 .
Patient-reported out-of-pocket costs and financial toxicity during early-phase oncology clinical trials.
Authors: Ryan Huey, Goldy George, Penny Phillips, Revenda White, Siqing Fu, Filip Janku, Daniel D. Karp, Aung Naing, Sarina Anne Piha-Paul, Vivek Subbiah, Apostolia Maria Tsimberidou, Shubham Pant, Timothy A Yap, Jordi Rodon Ahnert, Funda Meric-Bernstam, Ya-Chen T. Shih, David S. Hong
Journal: Journal of Clinical Oncology (2020)

7082 Background: Clinical trials are an important therapeutic option for cancer patients (pts). Although financial burden in cancer treatment is well-documented, the financial burden associated with clinical trials is not well understood, especially for pts with lower income. Methods: We conducted a survey regarding economic burden and financial toxicity in cancer pts who had been on Phase I clinical trials for ≥1 month. Financial Toxicity Score (FTS) was assessed using the validated COmprehensive Score for Financial Toxicity (COST) survey (scale 0-44, lower scores indicate worse toxicity). Pts also reported monthly out-of-pocket (OOP) medical and non-medical expenses. We applied multivariable logistic regression to analyze risk of financial toxicity, and unanticipated expenses. Results: Early-phase clinical trial pts (N = 213, median age = 59y; 59% female; 74% White, 45% w/ annual income ≤$60K; 50% lived &gt; 300 miles from the clinic; 40% required air travel; 37% had Medicare, 54% had employer sponsored insurance) had a median FTS of 20, with interquartile range of 12. Median monthly OOP costs for non-medical expenses was $1075, and for medical expenses was $475. Median total monthly OOP costs was $1750. 55% and 64% of pts reported that actual medical and non-medical expenses were higher than expected, respectively. Worse financial toxicity (≤ median FTS) in pts was associated with yearly household income &lt; $60K (OR: 2.7, P = 0.008), having medical costs higher than expected (OR: 3.2, P = 0.024), participation on ≥1 Phase I clinical trial prior to their current trial (OR: 2.2, P = 0.028), and living &gt; 100 miles away from the clinical trials hospital (OR: 2.3, P = 0.043). However, 34% of pts who lived &gt; 100 miles away received partial/full reimbursement of clinical trial-related travel costs from study sponsor/other/insurance. Racial/ethnic minority (OR: 2.6, P = 0.008) and pts who were unemployed or not working outside the home (OR: 2.4, P = 0.023) were more likely to report that actual medical costs were much higher than expected. 53% of pts used savings and 18% retirement accounts to pay for treatment. Conclusions: Among cancer pts participating on clinical trials, economic burden is high, and most of pts’ OOP costs were on non-medical expenses. Financial toxicity is disproportionally higher in pts with lower income. OOP costs can be substantial and are often unexpected for pts. Furthermore, prior participation in ≥1 Phase I clinical trial and living far away from the clinical trials hospital seem to increase risk of financial toxicity.
Inflammatory breast cancer (IBC) in native Hawaiians and Pacific Islanders: Frequency of IBC and impact of socioeconomic status on survival outcomes.
Authors: Kyle S.Y. Miyazaki, Jared David Acoba, Takeo Fujii
Journal: Journal of Clinical Oncology (2020)

e19083 Background: IBC is one of the most aggressive types of breast cancer, accounting for only 1-4% of all breast cancer cases while causing 8-10% of breast cancer related deaths. Previous studies have demonstrated that IBC has distinct epidemiological characteristics, but the prevalence of IBC particularly in Native Hawaiian (NH) and Pacific Islander (PI) populations, and the socioeconomic disparities related to survival outcomes, are not fully understood. Our primary objective was to determine the frequency at which NH and PI breast cancer patients are diagnosed with IBC, and the association between socioeconomic status and overall survival (OS). Methods: Patients with newly-diagnosed primary invasive breast cancer were identified from January 1, 2000 through December 31, 2018 using Queen’s Medical Center Tumor Registry. Clinical T4d was used to differentiate IBC and non-IBC. OS was defined as the time from diagnosis to death or last follow-up. Patients who were alive at the date of last follow-up were censored. Univariate and multivariate cox proportional hazard models were used to assess the effects of variables of interest on OS. Results: A total of 3,715 patients were included in analysis. There were 98 (2.6%) patients with IBC and 3,617 (97.4%) with non-IBC. Proportion of IBC relative to non-IBC was significantly higher in PI (9.0%) than in White (W) (2.7%) (P &lt; 0.001). Proportion of IBC was higher in NH (4.7%) than W but the difference was not statistically significant (P = 0.08). In multivariate analysis among the non-IBC group, OS was significantly shorter for both PI and NH than W (HR 1.72, [95%CI, 1.13-2.6]; P = 0.01, HR 1.48 [95% CI, 1.14-1.93]; P = 0.003, respectively). There were no significant racial differences seen in OS among IBC patients. Being under or uninsured was also significantly associated with short OS outcomes among patients with non-IBC but not those with IBC. Conclusions: PI have a significantly high proportion of IBC relative to non-IBC. Race and insurance status were not associated with OS in IBC although they were significantly associated with short OS in non-IBC. This result suggests that in IBC, the potential effect of racial disparity on OS is negated by the aggressive and insidious nature of the cancer. The effect of a relatively small sample size cannot be excluded, and further study in a larger population is warranted.
冷静看待新药
Authors: 曾昭耆
Journal: BMJ (2005)

随着科学技术的发展,大量高科技成果被引进临床医学领域,促成了近几十年来在诊断治疗方面的快速发展.虽然如此,当前医学的水平与人们的愿望之间,仍存在着巨大差距.因此,无论是医务人员或广大公众,都向往在维护健康、战胜疾病方面,能有更多更新的武器.药物是医生治病最常用的手段,研制开发新药成了药学家和药品生产厂家的经常性任务,这也符合公众的希望.为了提高现有治疗水平,医生们也随时关注着新药上市。
Different prognosis in patients of peritoneal dialysis with high peritoneal solute transport
Authors: Xiao-ling Zhou, Qing-feng Han, Yue Wang, Ling-hua Sun, Jian-dong Nie
Journal: BMJ (2011)

To investigate association between prognosis of patients of peritoneal dialysis with their initial high peritoneal solute transport and complications. Two hundred and two patients with end-stage renal disease who began peritoneal dialysis during September 1,2006 to September 1, 2008 at Peking University Third Hospital, Beijing were recruited in the study. They were undergone peritoneal equilibration test within six weeks after initiating peritoneal dialysis, and their types of peritoneal solute transport, complications,nutrition status and outcomes were all recorded until August 31,2010. Their survival rate was estimated by Kaplan-Meier method. Compare to those with other types of solute transport, patients with high peritoneal solute transport showed higher proportion of complications ( P < 0. 05 ) during dialysis, but less ultrafiltration function ( P < 0. 05 ), worse nutrition status ( P < 0. 05 ) and lower cumulative survival rate ( P < 0. 01 ).Among patients with high peritoneal solute transport, cumulative survival rate in those with complication was lower than those without it ( P = 0. 031 ). Prognosis of patients with high peritoneal solute transport possibly varies with their complications in dialysis.

Key words: 
Peritoneal dialysis; Kaplan-Meiers estimate
The benefits of an open art studio for patients with cancer: A mixed methods study.
Authors: Sam Brondfield, Cynthia Perlis
Journal: Journal of Clinical Oncology (2020)

e24152 Background: Art therapy can improve quality of life (QOL) and symptoms in patients with cancer. However, prior studies have focused on time-limited interventions. At the University of California, San Francisco, the Art for Recovery Open Art Studio (OAS) allows patients with cancer to create art and discuss experiences as a group with an art therapist (C.P.) each week. Most patients participate weekly. Our research question was: What is the value of the OAS that keeps patients coming back? Methods: In April 2019, C.P. identified all 23 patients who had attended the OAS over the past three months. We excluded one due to cognitive impairment. We designed a one-time email survey with closed- and open-ended questions. We chose a survey rather than interviews to minimize burden to patients, minimize social desirability bias, and maximize time for reflection before responding. We drew upon S.B.’s formal training in survey design and C.P.’s decades of experience with the OAS for content validity. We conducted cognitive interviews with two patients for response process validity which did not result in changes. We reported closed-ended responses using descriptive statistics. We used a paired t-test to compare, retrospectively, mean QOL before attending the OAS to mean present QOL, on a five-point scale (poor to excellent). We felt a longer QOL survey could burden symptomatic patients. S.B. and C.P. independently coded open-ended responses and aligned codes through discussion. Results: Eighteen of 22 patients (82%) responded. Mean age was 54 (range 37-76). Mean duration of attendance was four years (range 10 months to 11 years), and median frequency was three times per month. All respondents found the OAS “very helpful,” and 17 of 18 (94%) felt the friendships from the OAS were “very valuable” (top of four-point scale). Mean QOL improved from 2.7 to 4.2 (p &lt; 0.001). Coding revealed themes of self-reflection, emotional experience, artistic engagement, togetherness, and familiar surroundings as OAS benefits. Conclusions: Our study focuses on OAS elements that keep patients with cancer coming back for years. While our results align with prior studies showing improved QOL, our study additionally reveals the multifaceted benefits of experiencing the OAS longitudinally. Study limitations include small sample size, incomplete validity evidence for the survey, and social desirability bias in survey responses. Our study supports further exploration of longitudinal OAS experiences, which may provide benefits such as friendship and community that briefer art therapy interventions may lack.
Temporal Trends in Prevalence and Prognostic Implications of Comorbidities Among Patients With Acute Decompensated Heart Failure
Authors: Ambarish Pandey, Muthiah Vaduganathan, Sameer Arora, Arman Qamar, Robert J. Mentz, Sanjiv J. Shah, Patricia P. Chang, Stuart D. Russell, Wayne D. Rosamond, Melissa C. Caughey
Journal: Circulation (2020)

Background: Patients with heart failure (HF) have multiple coexisting comorbidities. The temporal trends in the burden of comorbidities and associated risk of mortality among patients with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) are not well established. Methods: HF-related hospitalizations were sampled by stratified design from 4 US areas in 2005 to 2014 by the community surveillance component of the ARIC study (Atherosclerosis Risk in Communities). Acute decompensated HF was classified by standardized physician review and a previously validated algorithm. An ejection fraction &lt;50% was considered HFrEF. A total of 15 comorbidities were abstracted from the medical record. Mortality outcomes were ascertained for up to 1-year postadmission by linking hospital records with death files. Results: A total of 5460 hospitalizations (24 937 weighted hospitalizations) classified as acute decompensated HF had available ejection fraction data (53% female, 68% white, 53% HFrEF, 47% HFpEF). The average number of comorbidities was higher for patients with HFpEF versus HFrEF, both for women (5.53 versus 4.94; P &lt;0.0001) and men (5.20 versus 4.82; P &lt;0.0001). There was a significant temporal increase in the overall burden of comorbidities, both for patients with HFpEF (women: 5.17 in 2005–2009 to 5.87 in 2010–2013; men: 4.94 in 2005–2009 and 5.45 in 2010–2013) and HFrEF (women: 4.78 in 2005–2009 to 5.14 in 2010–2013; men: 4.62 in 2005–2009 and 5.06 in 2010–2013; P -trend&lt;0.0001 for all). Higher comorbidity burden was significantly associated with higher adjusted risk of 1-year mortality, with a stronger association noted for HFpEF (hazard ratio [HR] per 1 higher comorbidity, 1.19 [95% CI, 1.14–1.25] versus HFrEF (HR, 1.10 [95% CI, 1.05–1.14]; P for interaction by HF type=0.02). The associated mortality risk per 1 higher comorbidity also increased significantly over time for patients with HFpEF and HFrEF, as well ( P for interaction with time=0.002 and 0.02, respectively) Conclusions: The burden of comorbidities among hospitalized patients with acute decompensated HFpEF and HFrEF has increased over time, as has its associated mortality risk. Higher burden of comorbidities is associated with higher risk of mortality, with a stronger association noted among patients with HFpEF versus HFrEF.
Incidence of PI3K pathway alteration and response to neoadjuvant therapy (NAT) in triple negative breast cancer (TNBC) subtypes.
Authors: Reva K Basho, Clinton Yam, Jason B White, Li Zhao, Lei Huo, Elizabeth A. Mittendorf, Alastair Mark Thompson, Jennifer Keating Litton, Banu Arun, Bora Lim, Vicente Valero, Debu Tripathy, Jianhua Zhang, Beatriz E Adrada, Lumarie Santiago, Elizabeth Ravenberg, Stacy L. Moulder, Senthil Damodaran
Journal: Journal of Clinical Oncology (2020)

561 Background: Limited cell line and human data suggest that TNBCs characterized as mesenchymal and luminal androgen receptor (LAR) commonly have alterations in the PI3K pathway. More data is needed to better characterize the role of the PI3K pathway across TNBC subtypes. Methods: Pre-treatment tumor biopsies were collected from operable TNBC patients (pts) enrolled on a clinical trial of genomically tailored NAT (ARTEMIS; NCT02276443). Tumors were categorized into 5 groups using the Pietenpol criteria: basal-like (BL) comprised of BL-1 and BL-2, mesenchymal and mesenchymal stem-like (M), immunomodulatory (IM), LAR, or unspecified (UNS). Using whole exome sequencing data, variants (single nucleotide polymorphisms and insertions/deletions) and copy number variations (CNVs) were identified in 32 genes known to activate the PI3K pathway. Results: Tumor subtyping and pathologic response to NAT was available in 127 pts (clinical stage I: 9; II: 84; III: 34). PI3K pathway alteration defined as a variant in one of the evaluated genes and/or deletion of PTEN was seen in 76 (60%) tumors. The most frequent alterations were: PTEN deletion (21%), PIK3CA variant (11%), and PIK3R1 variant (8%). PI3K alteration and residual cancer burden (RCB) rates across TNBC subtypes are shown in the table. There was a significant difference in pathologic complete response (pCR)/RCB 0 rate after NAT across TNBC subtypes (chi 2 test; P = 0.02). There was a significant difference in the incidence of PI3K pathway alteration across TNBC subtypes (chi 2 test; P &lt; 0.01). Overall, the presence of PI3K alteration was not associated with pCR (Fisher exact test; P = 0.85). Pts with M tumors had a higher rate of substantial residual disease (RCB II-III) after NAT. Presence of PI3K pathway alteration was common in the M subtype and associated with RCB II-III (82% in PI3K-altered vs 33% in wild-type tumors; Fisher exact test; P = 0.02). Presence of PI3K pathway alteration was common but not associated with response in the LAR subtype. Conclusions: The incidence of PI3K pathway alteration varied by TNBC subtype but was not associated with pathologic response to NAT with the exception of increased substantial residual disease (RCB II-III) in the M subtype. [Table: see text]