Four US National Clinical Trials Network components (Southwest Oncology Group, Cancer and Leukemia Group B/Alliance, Eastern Cooperative Oncology Group, and the AIDS Malignancy Consortium) conducted ...a phase II Intergroup clinical trial that used early interim fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to determine the utility of response-adapted therapy for stage III to IV classic Hodgkin lymphoma.
The Southwest Oncology Group S0816 (Fludeoxyglucose F 18-PET/CT Imaging and Combination Chemotherapy With or Without Additional Chemotherapy and G-CSF in Treating Patients With Stage III or Stage IV Hodgkin Lymphoma) trial enrolled 358 HIV-negative patients between July 1, 2009, and December 2, 2012. A PET scan was performed after two initial cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and was labeled PET2. PET2-negative patients (Deauville score 1 to 3) received an additional four cycles of ABVD, whereas PET2-positive patients (Deauville score 4 to 5) were switched to escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) for six cycles. Among 336 eligible and evaluable patients, the median age was 32 years (range, 18 to 60 years), with 52% stage III, 48% stage IV, 49% International Prognostic Score 0 to 2, and 51% score 3 to 7.
Three hundred thirty-six of the enrolled patients were evaluable. Central review of the interim PET2 scan was performed in 331 evaluable patients, with 271 (82%) PET2-negative and 60 (18%) PET2-positive. Of 60 eligible PET2-positive patients, 49 switched to eBEACOPP as planned and 11 declined. With a median follow-up of 39.7 months, the Kaplan-Meier estimate for 2-year overall survival was 98% (95% CI, 95% to 99%), and the 2-year estimate for progression-free survival (PFS) was 79% (95% CI, 74% to 83%). The 2-year estimate for PFS in the subset of patients who were PET2-positive after two cycles of ABVD was 64% (95% CI, 50% to 75%). Both nonhematologic and hematologic toxicities were greater in the eBEACOPP arm than in the continued ABVD arm.
Response-adapted therapy based on interim PET imaging after two cycles of ABVD seems promising with a 2-year PFS of 64% for PET2-positive patients, which is much higher than the expected 2-year PFS of 15% to 30%.
There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human ...samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n = 151) and plasma-derived (n = 120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer. Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.
Display omitted
•Proteomic profiles of extracellular vesicles and particles (EVPs) from 426 human samples•Identification of pan-EVP markers•Characterization of tumor-derived EVP markers in human tissues and plasma•EVP proteins can be useful for cancer detection and determining cancer type
A comprehensive proteomic analysis of extracellular vesicles and particles (EVPs) from 426 human samples identifies pan-EVP markers, biomarkers for EVP isolation, for cancer detection and determining cancer type.
Research shows that displaying face time—being observed by others at work—leads to many positive outcomes for employees. Drawing on this prior work, we argue that face time helps employees to receive ...better work and leads to career advancement because it is a strong signal of their commitment to their job, their team, and their organization. But when employees are geographically distributed from managers who control the assignment of work, they are often unable to display face time. To compensate, employees must engage in other behaviors that signal commitment. Our study of two large, globally distributed, product-development companies demonstrates that employees who engage in certain behaviors can effectively signal their commitment to the organization and, as a consequence, will receive better work assignments. But because they operate in a competitive signaling environment, they have to continually engage in the behaviors that produce desired signals to the point where they often feel that they are sacrificing their personal lives for their job. We induct a model from our data that explains why simple behaviors that signal commitment eventually turn into feelings of sacrifice and why employees at headquarters who have the power to assign better work fail to notice the sacrifice behind the signals. We discuss the implications of this model and the signal misalignment it explains for theories of distributed work and signaling in organizations.
The online appendix is available at
https://doi.org/10.1287/orsc.2018.1265
.
Recent advances in magnetic resonance imaging (MRI) technology now allow the tracing of developmental changes in the brains of children. We applied computer-matching algorithms and new techniques for ...measuring cortical thickness (in millimeters) to the structural MRI images of 45 children scanned twice (2 yr apart) between the ages 5 and 11. Changes in brain size were also assessed, showing local brain growth progressing at a rate of approximately 0.4-1.5 mm per year, most prominently in frontal and occipital regions. Estimated cortical thickness ranged from 1.5 mm in occipital regions to 5.5 mm in dorsomedial frontal cortex. Gray matter thinning coupled with cortical expansion was highly significant in right frontal and bilateral parieto-occipital regions. Significant thickening was restricted to left inferior frontal (Broca's area) and bilateral posterior perisylvian (Wernicke's area on the left) regions. In the left hemisphere, gray matter thickness was correlated with changing cognitive abilities. For the first time, developmental changes in gray matter thickness, brain size, and structure-function relationships have been traced within the same individuals studied longitudinally during a time of rapid cognitive development.
The prevalence of dyads in social life Peperkoorn, Leonard S; Becker, D Vaughn; Balliet, Daniel ...
PloS one,
12/2020, Letnik:
15, Številka:
12
Journal Article
Recenzirano
Odprti dostop
A salient objective feature of the social environment in which people find themselves is group size. Knowledge of group size is highly relevant to behavioural scientists given that humans spend ...considerable time in social settings and the number of others influences much of human behaviour. What size of group do people actually look for and encounter in everyday life? Here we report four survey studies and one experience-sampling study (total N = 4,398) which provide evidence for the predominance of the dyad in daily life. Relative to larger group sizes, dyads are most common across a wide range of activities (e.g., conversations, projects, holidays, movies, sports, bars) obtained from three time moments (past activities, present, and future activities), sampling both mixed-sex and same-sex groups, with three different methodological approaches (retrospective reports, real-time data capture, and preference measures) in the United States and the Netherlands. We offer four mechanisms that may help explain this finding: reciprocity, coordination, social exclusion, and reproduction. The present findings advance our understanding of how individuals organize themselves in everyday life.
Patients with advanced-stage Hodgkin lymphoma (HL) demonstrated excellent 2-year progression-free survival (PFS) after receiving positron emission tomography (PET)–adapted therapy on SWOG S0816. ...Patients received 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Patients achieving complete response (CR) on PET scan following cycle 2 of ABVD (PET2) continued 4 additional cycles of ABVD. Patients not achieving CR on PET2 were switched to escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) for 6 cycles. After a median follow-up of 5.9 years, a subset of 331 eligible patients with central review of PET2 was analyzed. PET2 was negative in 82% and positive in 18%. For all patients, the estimated 5-year PFS and OS was 74% (95% confidence interval CI, 69%-79%) and 94% (95% CI, 91%-96%), respectively. For PET2− and PET2+ patients, the 5-year PFS was 76% (95% CI, 70%-81%) and 66% (95% CI, 52%-76%), respectively. Seven (14%) and 6 (2%) patients reported second cancers after treatment with eBEACOPP and ABVD, respectively (P = .001). Long-term OS of HL patients treated on S0816 remains high. Nearly 25% of PET2− patients experienced relapse events, demonstrating limitations ABVD therapy and of the negative predictive value of PET2. In PET2+ patients who received eBEACOPP, PFS was favorable, but was associated with a high rate of second malignancies compared with historical controls. Our results emphasize the importance of long-term follow-up, and the need for more efficacious and less toxic therapeutic approaches for advanced-stage HL patients. This trial was registered at www.clinicaltrials.gov as #NCT00822120.
•Nearly 25% of PET2− patients relapsed, demonstrating limitations of frontline ABVD and low negative predictive value of PET2.•In patients with a positive PET2 who received eBEACOPP, PFS was favorable, but was associated with a high rate of second cancers.
Display omitted
Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and ...brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.
It sounds rather odd to say that digital artifacts -- like software -- have material properties because people generally think of materials or materiality as physical substances such as wood, steel, ...and stone. Yet scholars increasingly talk about the "materiality" of digital artifacts. What do they mean? In this paper, I explore two definitions of the adjective "material" -- practical instantiation and significance -- in addition to its normal connotation as matter. I argue that treating materiality as the practical instantiation of theoretical ideas (like policies that allow women to vote help make material the idea that sexes are equal) or as what is significant in the explanation of a given context (like material evidence in a courtroom trial) provides a more useful framework for understanding how digital artifacts affect the process of organizing. I contend that moving away from linking materiality to notions of physical substance or matter may help scholars of technology integrate their work more centrally with studies of discourse, routine, institutions and other phenomena that lie at the core of organization theory, specifically, and social theory more broadly.
Diffuse large B-cell lymphoma (DLBCL) presents as a limited-stage disease in 25% to 30% of patients, with better overall survival (OS) than that for advanced-stage disease but with continuous relapse ...regardless of treatment approach. The preferred treatment is abbreviated rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and radiation therapy. On the basis of promising results of positron emission tomography (PET)-directed treatment approaches, we designed a National Clinical Trials Network (NCTN) study to improve outcomes and decrease toxicity.
Patients with nonbulky (< 10 cm) stage I/II untreated DLBCL received 3 cycles of standard R-CHOP therapy and underwent a centrally reviewed interim PET/computed tomography scan (iPET). Those with a negative iPET proceeded with 1 additional cycle of R-CHOP, whereas those with a positive iPET received involved field radiation therapy followed by ibritumomab tiuxetan radioimmunotherapy.
Of 158 patients enrolled, 132 were eligible and 128 underwent iPET, which was positive in 14 (11%) of the patients. With a median follow-up of 4.92 years (range, 1.1-7.7 years), only 6 patients progressed and 3 died as a result of lymphoma. Eleven patients died as a result of nonlymphoma causes at a median age of 80 years. The 5-year progression-free survival estimate was 87% (95% CI, 79% to 92%) and the OS estimate was 89% (95% CI, 82% to 94%), with iPET-positive and iPET-negative patients having similar outcomes.
To our knowledge, S1001 is the largest prospective study in the United States of limited-stage DLBCL in the rituximab era, with the best NCTN results in this disease subset. With PET-directed therapy, 89% of the patients with a negative iPET received R-CHOP × 4, and only 11% had a positive iPET and required radiation, with both groups having excellent outcomes. The trial establishes R-CHOP × 4 alone as the new standard approach to limited-stage disease for the absolute majority of patients.
Despite unprecedented clinical activity in mantle cell lymphoma (MCL), primary and acquired resistance to ibrutinib is common. The outcomes and ideal management of patients who experience ibrutinib ...failure are unclear. We performed a retrospective cohort study of all patients with MCL who experienced disease progression while receiving ibrutinib across 15 international sites. Medical records were evaluated for clinical characteristics, pathological and radiological data, and therapies used pre- and postibrutinib. A total of 114 subjects met eligibility criteria. The median number of prior therapies was 3 (range, 0-10). The Mantle Cell Lymphoma International Prognostic Index (MIPI) scores at the start of ibrutinib were low, intermediate, and high in 46%, 31%, and 23% of patients, respectively. Of patients with available data prior to ibrutinib and postibrutinib, 34 of 47 and 11 of 12 had a Ki67 >30%. The median time on ibrutinib was 4.7 months (range 0.7-43.6). The median overall survival (OS) following cessation of ibrutinib was 2.9 months (95% confidence interval CI, 1.6-4.9). Of the 104 patients with data available, 73 underwent subsequent treatment an average of 0.3 months after stopping ibrutinib with a median OS of 5.8 months (95% CI, 3.7-10.4). Multivariate Cox regression analysis of MIPI before postibrutinib treatment, and subsequent treatment with bendamustine, cytarabine, or lenalidomide failed to reveal any association with OS. Poor clinical outcomes were noted in the majority of patients with primary or secondary ibrutinib resistance. We could not identify treatments that clearly improved outcomes. Future trials should focus on understanding the mechanisms of ibrutinib resistance and on treatment after ibrutinib.
•Patients with mantle cell lymphoma who progressed during treatment with ibrutinib have a poor outcome.•There are no therapies that appear to be uniquely successful in the postibrutinib setting. The postibrutinib setting is an unmet need.
PDF
