tbuckley/cabot-search huggingface dataset:
Comparison of treatment characteristics between patients diagnosed with immune thrombocytopenia (ITP) and treated with thrombopoietin receptor agonists (TPO-RA).
Authors: Tasneem Lokhandwala, Menaka Bhor, Dana Stafkey-Mailey, Herman Chen, Brian Marc Elliott
Journal: Journal of Clinical Oncology (2017)

e18314 Background: There is limited real-world information on the utilization of TPO-RAs, eltrombopag (ELT) and romiplostim (ROM), for the treatment of ITP. Methods: The study employed a retrospective, longitudinal cohort design using integrated healthcare claims data from July 2008-June 2015. Adults diagnosed with ITP initiating TPO-RA therapy from Jan 2009-July 2014 were included. Patients not continuously enrolled in benefits for 6-months prior and 12-months post the index date (first TPO-RA claim date) were excluded. Index TPO-RA discontinuation rates, concomitant therapy, restarts, subsequent therapy, and treatment free periods were assessed. Results: Of the 1,067 patients included, 26.5% (283) received ELT and 73.4% (784) ROM. Age (58.8 vs 59.3; P= 0.705) and gender (males: 45.9% vs 46.6%; P= 0.858) were similar between cohorts. Among ELT and ROM patients 35.7% and 27.6% continued therapy (no gap of ≥30 days) for ≥1 year ( P= 0.010). The average duration of continuous therapy (up to gap ≥30 days) was 131 and 108 days, respectively ( P= 0.001). During continuous course of index TPO-RA treatment 52.7% ELT and 47.2% ROM patients received concomitant ITP-related treatment ( P= 0.115). Following discontinuation, 42.9% of ELT patients restarted ELT, 22.0% did not initiate any subsequent ITP treatments, and 35.2% started a new ITP treatment. Among patients who discontinued ROM, 38.4% restarted, 26.9% did not receive any subsequent therapy, and 34.7% initiated a new treatment. Treatment free periods (≥30 days with no ITP treatment) were experienced by 52.7% of ELT patients and 61.6% ROM patients ( P= 0.009). Mean duration of treatment free period was 109 and 137 days ( P&lt; 0.001), respectively. Conclusions: ITP patients receiving ELT had a longer duration of treatment and shorter treatment free periods compared to patients receiving ROM. Further research is needed to compare clinical outcomes (e.g., platelet counts, bleeding symptoms and remissions) among ITP patients receiving ELT and ROM, in the real-world setting.
A phase III study of atezolizumab (atezo) vs placebo as adjuvant therapy in renal cell carcinoma (RCC) patients (pts) at high risk of recurrence following resection (IMmotion010).
Authors: Robert Uzzo, Axel Bex, Brian I. Rini, Laurence Albiges, Cristina Suarez, Frank Donaldson, Takashi Asakawa, Christina Schiff, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2017)

TPS4598 Background: Nephrectomy is the SOC in early RCC; however, the 5-y relapse rate is 30-40% in stage II or III pts, with tumor stage and grade correlating with survival and recurrence after surgery. Currently, there is a limited role for adjuvant therapy after nephrectomy in pts who have had complete tumor resection; observation is standard. In a Ph II first-line metastatic RCC study, treatment with single-agent atezo (anti–PD-L1) resulted in an ORR of 25%. Thus, IMmotion010, a Ph III, multicenter, randomized, placebo-controlled, double-blinded trial, will evaluate the efficacy and safety of atezo as adjuvant therapy in RCC pts who are at high risk of recurrence after resection (NCT03024996). Methods: Eligible RCC pts (clear cell or sarcomatoid histologies) will have undergone nephrectomy (radical or partial) and be at high risk of recurrence (T2 Grade 4, T3a Grade 3-4, T3b/c any Grade, T4 any Grade or TxN+ any Grade) or have had complete resection of limited metachronous/synchronous metastasis. Pts must show no residual disease or evidence of metastases by CT scan at enrollment. ECOG PS ≤ 1 and tumor specimens evaluable for PD-L1 will also be required. Pts will be randomized 1:1 to receive atezo 1200 mg IV q3w or placebo IV q3w for 16 cycles or 1 y; stratification will be by disease stage (T2/T3a vs T3b/c/T4/N+ vs metastasectomy), region (North America [excluding Mexico] vs rest of world) and PD-L1 status on tumor-infiltrating immune cells (IC; PD-L1 IC expression &lt; 1% vs ≥ 1%). The primary endpoint is independent review facility (IRF)-assessed disease-free survival (DFS), defined as the time from randomization to the first documented recurrence event (local recurrence, new primary RCC, distant metastasis) or death. Secondary endpoints include OS, investigator-assessed DFS, IRF-assessed and investigator-assessed DFS in pts with ≥ 1% PD-L1 IC, disease-specific survival, distant metastasis-free survival and the 3-y rates of IRF-assessed DFS and investigator-assessed DFS. Safety and biomarkers will be evaluated. The planned analysis will occur when at least ≈ 65% of pts in the 2 populations have died. 664 pts will be enrolled at 150-200 sites worldwide. Clinical trial information: NCT03024996.
Impact of definitive local therapy (LT) in men with primary small cell (or poorly differentiated neuroendocrine) prostate carcinomas (pSCPC).
Authors: Oluchi Oke, Chad Tang, Sherif Shaaban, Lianchun Xiao, Chad A. Reichard, Brian Francis Chapin, Mitchell Steven Anscher, Ana Aparicio
Journal: Journal of Clinical Oncology (2018)

e17061 Background: Men with pSCPC often suffer progression of their primary tumor resulting in severe morbidity that likely impacts their outcome. We hypothesized that definitive LT to the primary tumor with surgery and/or radiation may decrease the rate of local symptoms and improve time to progression and overall survival (OS). Methods: The MD Anderson Genitourinary Tumor Registry and Natural Language Electronic Medical Record were searched to identify patients with pSCPC treated at MD Anderson between 1991 and 2016. Charts were retrospectively reviewed to determine patient demographics, extent of disease at diagnosis, use of and response to systemic and local therapies, timing of disease progression and death, and the presence of local symptoms (dysuria, hematuria, pelvic pain, perineal pain, rectal obstruction, urinary frequency, incontinence, urgency and retention) at the time of diagnosis, first disease progression (P-1) and any progression (P-any) using CTCAEv5. Results: Of 39 patients identified, 30 (77%) had metastatic (M1) and 9 localized (M0) disease at presentation. 30 (77%) of 39 had Grade ≥ 2 local symptoms at diagnosis. Thirteen (43.3%) of the M1 and 6 (66.7%) of the M0 patients underwent LT to their primary tumor at the time of best response to first-line systemic therapy. In the M1 group, 6 (20%) underwent surgery while 7 (23.3%) received radiation. In the M0 group, 1 (11%) had surgery, 4 (44%) received radiation and 1 received surgery followed by radiation. Grade ≥ 2 local symptoms occurred at P-1 in 5 of 19 (26.3%) men treated with LT vs 7 of 19 (36.8%) without, and at P-any in 5 of 19 (26.3%) men treated with LT vs 10 of 19 (52.6%) without. Median time to P-1 was 8.7 months in men with M1 treated with LT vs 6.3 months without (p = 0.022), and 21.0 months in men with M0 treated with LT vs 3.8 without (p = 0.002). Median OS was 25.8 months in men with M1 treated with LT vs 10.4 without (p = 0.019), and 33.6 months in men with M0 treated with LT vs 13.1 without (p = 0.243). Conclusions: These data support that definitive LT to the primary tumor decreases the rate of local symptoms at progression and improves the outcome of men with pSCPC. Prospective trials are needed to confirm these observations.
Evaluation of the nutritional status in children with acute lymphoblastic leukemia and its effect on the outcome of induction in a developing country.
Authors: Arifa Khalid
Journal: Journal of Clinical Oncology (2017)

e22004 Background: Acute Lymphoblastic Leukemia (ALL) is the most frequently occurring cancer among the children and adolescents. Cure rate is improved up to 90% with early diagnosis and better supportive care. Under nutrition among pediatric acute leukemia patients is more in developing countries 60% as compared to 10% in developed countries. The poor nutritional status is found to be associated with poor outcome. Therefore, optimum nutritional support can play a vital role in the outcome of induction. Methods: The population of research was newly diagnosed patients of ALL, reported from June 2016 to January 2017, in the Pediatric Hematology &amp; Oncology Department of Children’s Hospital, Lahore. A sample of 151 patients of Acute Lymphoblastic Leukemia was analyzed prospectively. The study subjects were stratified into undernourished &amp; well nourished based on the Z-score for weight for age.The data was collected irrespective of any discrimination based on demographic factors. and the following characters were recorded in both the groups: Mid treatment &amp; end of treatment bone marrow response, culture proved infection, duration of hospital stay &amp; outcome. Results: Among the 151 patients of ALL 80.1 % (n = 121) were Pre-B and 19.8% (n = 30) were Pre-T .Male to female ratio was 1.5:1. Malnutrition was established in 98 (64.9%) patients on the bases of Z-score. The undernourished group had significantly increased rate of culture proven sepsis (11% vs. 2%) respectively and required longer duration of hospital stay (p &lt; 0.001).Rapid early response was observed in 21.8% malnourished and 32.8% well-nourished patients. End of treatment complete response was recorded in 63% vs. 69.1% respectively with significant p value. Expiry was observed in 9.1% malnourished patients. Conclusions: On the basis of this study it is concluded that the nutritional status at the initial presentation had a significant impact on the induction outcome. The undernourished patients of ALL are more prone to infections, requiring longer duration of hospital stay. Therefore, optimum nutritional support to such patients can help to decrease the chances of infections &amp; ultimately improve the outcome.
Mediastinal gray zone lymphoma-morphollogically heterogenous group of lymphomas.
Authors: Evgeniya Vladimirovna Kharchenko, Tatiana Semiglazova
Journal: Journal of Clinical Oncology (2017)

e19050 Background: Mediastinal Gray zone lymphoma (MGZL) could be refer to group of large B-cell lymphomas of mediastinum, where Hodgkin’s lymphoma and Diffuse large B-cell lymphoma also included. These kinds of lymphomas have common pathogenic mechanisms, but different epidemiological,clinical , morphological, IHC features, different therapy and prognosis. Methods: We analyzedhistological and IHC features of 11 patients with MGZL. Middle age of patients were 35 years old (25-42), Man(7 )and woman (4) ratio was 1,75:1. Results: We distinguished 5 types of MGZL: 1) Hodgkin’s lymphoma-like variant (ring-shaped fibrosis, expressed cellular polymorphism, large cells seems like Hodgkin’s and Reed-Shteinberg cells,mixed-cell background infiltrate; high expression of CD 20 and another B-lines antigens. 2) type, seems like primary mediastinum large B-cell lymphoma (PMBL-like) (about monotonous composition of the cells, diffuse alveolar stroma’sfibrosis, scarce background infiltrate, high diffuse expression of CD 30 and/or lack of LCA and CD 20 expression 3) mixed variant (mixture of cells PMBL and Hodgkin's lymphoma, irregularly expressed fibrosis, lack of zonality, transientimmunophenotype. 4) dual-component variant (well-defined zonality, Hodgkin's like areas and structuresspecific for PMBL with appropriate or changed immunophenotype 5) Metachronous variant (during progression or relapse we observedmodification of morphological and IHC features). Conclusions: MGZL is heterogenous group of neoplasms with different morphological and IHC features causes difficulties in differential diagnostics in large B-cell lymphomas of mediastinum group.Diagnostic algorithm should be used for high efficacy and accuracy. Clinical features and prognostic factors in these subtypes of MGZL is still unclear and need further investigations.
Integrative therapy use amongst patients and providers at an NCI-Designated Cancer Center.
Authors: Masey Marie Ross, Sarah E. Braun, Tara A. Albrecht
Journal: Journal of Clinical Oncology (2017)

e21565 Background: Historically, use of integrative health (IH) therapies among patients with cancer is high. Less is known about provider use and provider perceptions. The study aim was to evaluate the use of IH approaches among patients and providers and to gauge provider knowledge, familiarity, and referrals. Methods: We conducted a single-institution patient and provider survey in the outpatient hematology/oncology clinics at a NCI designated cancer center. Results: In 145 patients surveyed (mean age 58±13, 64% female, 56% white), 66% reported use of at least one IH approach. Of these, the highest reported were vitamins/herbs/special diets (66%), physical activity (54%), and mindfulness/meditation/prayer (44%). In 53% of patients who used IH, the therapy was recommended by someone; of these, 58% of the recommendations came from their oncologist or PCP. In all, 37% of patients wished their provider would supply more information regarding IH approaches. In 87 providers surveyed (46% MD/DO, 30% RN, mean age 46±12, 61% male, 79% white), 89% reported prior personal use of an IH therapy. Seventy-four percent reported that they received IH inquiries from patients “sometimes” or more, with 9% receiving inquiries frequently. Thirty-six percent rated their knowledge of IH low, with 24% not feeling comfortable discussing IH approaches with patients. Provider comfort level with IH therapies was positively correlated with frequency of reported patient inquiries ( r= .391, p= .01). Overall, 85% of providers thought IH therapies had the potential to be beneficial and 77% had recommended their use. The highest reported barrier to referral was lack of knowledge (18%) followed by lack of resources (14%). Conclusions: Use of IH therapies among cancer patients and providers is high and most providers have recommended IH approaches to their patients. Patients would like more provider-directed education on IH, yet more than 1/3 of providers rate their knowledge of IH low with a correlation between provider comfort level and frequency of reported patient inquiries. These data suggest that efforts should be aimed at improving educational resources and programs for providers to increase their awareness and comfort level with IH approaches.
Ramucirumab (R) plus pembrolizumab (P) in treatment naive and previously treated advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: A multi-disease phase I study.
Authors: Ian Chau, Johanna C. Bendell, Emiliano Calvo, Rafael Santana-Davila, Hendrik-Tobias Arkenau, Gu Mi, Jin Jin, Jessicca Rege, David Ferry, Roy S. Herbst, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2017)

4046 Background: Angiogenesis and immunosuppression are hallmarks of tumor growth. This is the first study to combine R (anti-VEGFR2) with P (anti-PD-1) to simultaneously target both processes in the tumor microenvironment. Methods: Ongoing, multi-cohort, phase 1a/b trial enrolled pts with G/GEJ adenocarcinoma, measurable disease, ECOG PS 0-1, previously treated (Cohorts A and B) or untreated (Cohort A2) for advanced disease. PD-L1 was positive (tumor proportion score [TPS] ≥1%) or negative (TPS &lt; 1%) using the DAKO PD-L1 22C3 IHC pharmDx assay. R was administered at 8 mg/kg on Days 1&amp;8 (Cohorts A and A2) or 10 mg/kg on Day 1 (Cohort B) with P 200 mg on Day 1 q3W. Primary objective- assess safety and tolerability of R+P; preliminary efficacy will be examined. Results: As of 21-Nov-2016, 41 previously treated G/GEJ pts were enrolled. Median age was 58 y, 76% male, 66% had ECOG PS of 1, 46% were PD-L1+, and 59% received study treatment as third or subsequent line. Median duration on therapy was 2.8 mo and 4.1 mo for A and B, respectively. Overall, 33 (80%) pts experienced a treatment-related AE (TRAE) and similar between cohorts A and B. Ten (24%) pts experienced grade 3-4 TRAEs, most commonly colitis (7%) and hypertension (7%). One treatment-related death occurred (pneumonitis and pulmonary sepsis). Responses occurred in 3 (7%) pts with 46% disease control rate (DCR). Progression-free and overall survival rates at 6 mo were 22.4 % (95% CI, 9.8-38.0) and 51.2% (95% CI, 33.9-66.1) respectively. Nine (22%) pts remain on treatment. Eighteen of 25 planned treatment naïve G/GEJ pts were enrolled. Median age was 70 yr, 83% male, 56% had ECOG PS of 0, and PD-L1 status is pending. Median duration on therapy was 2.1 mo. Twelve (67%) pts experienced a TRAE. Grade 3 TRAEs occurred in 5 (28%) pts (hypertension [n = 3], diarrhea, and acute kidney injury). No grade 4-5 events occurred. Preliminary efficacy data showed 3 (17%) pts responded with 50% DCR. Median PFS is immature and 89% of pts remain on treatment. Conclusions: R+P generated no new safety signals and demonstrated encouraging antitumor activity in treatment naïve and previously treatedadvanced G/GEJ adenocarcinoma. Clinical trial information: NCT02443324.
Granulocyte–macrophage colony‐stimulating factor ( <scp>GM</scp> ‐ <scp>CSF</scp> ) as a therapeutic target in psoriasis: randomized, controlled investigation using namilumab, a specific human anti‐ <scp>GM</scp> ‐ <scp>CSF</scp> monoclonal antibody
Authors: K.A. Papp, M. Gooderham, R. Jenkins, R. Vender, J.C. Szepietowski, T. Wagner, B. Hunt, B. Souberbielle
Journal: British Journal of Dermatology (2018)

The relevance of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the management of psoriasis has not been studied previously. GM-CSF is important in the initiation and maintenance of chronic inflammatory processes.To investigate the clinical use of GM-CSF neutralization by evaluating the efficacy and safety of namilumab (AMG203), a monoclonal antibody GM-CSF inhibitor, in patients with moderate-to-severe plaque psoriasis.A phase II, multicentre, randomized, double-blind, placebo-controlled, parallel-group, dose-finding, proof-of-concept study (NEPTUNE) was conducted. Four doses of namilumab (20, 50, 80 and 150 mg, via subcutaneous injection) were compared with placebo. Assessment of the primary end point - the proportion of patients achieving ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75 treatment response) - was performed at week 12. Exploratory investigation at the tissue level was conducted in a subset of the overall study population. The trial was registered with the number NCT02129777.In total, 122 patients were enrolled and 106 (86·9%) completed the double-blind treatment; 16 (13·1%) prematurely discontinued study medication. Serum concentration-time profiles were as expected for subcutaneous delivery of an IgG1 monoclonal antibody, and exposure increased proportionally with dose elevation. The number of patients showing PASI 75 treatment response at week 12 was low in all groups; no significant difference was recorded in this end point between placebo and any namilumab group. Similar outcomes were recorded for other clinical study end points. Moreover, no significant treatment-related changes from baseline were observed in laboratory investigations of cell types or subpopulations, or cytokines relevant to inflammatory pathways in psoriasis.GM-CSF blockade is not critical for suppression of key inflammatory pathways underlying psoriasis.
Nonconforming Gender Expression and Associated Mental Distress and Substance Use Among High School Students
Authors: Richard Lowry, Michelle M. Johns, Allegra R. Gordon, S. Bryn Austin, Leah E. Robin, Laura K. Kann
Journal: JAMA Pediatrics (2018)

The cultural roles and expectations attributed to individuals based on their sex often shape health behaviors and outcomes. Gender nonconformity (GNC) (ie, gender expression that differs from societal expectations for feminine or masculine appearance and behavior) is an underresearched area of adolescent health that is often linked to negative health outcomes.To examine the associations of GNC with mental distress and substance use among high school students.Cross-sectional study based on data from the Youth Risk Behavior Survey (YRBS) conducted in 2015. The setting was 3 large urban US school districts (2 in California and 1 in Florida). Participants were a racially/ethnically diverse population-based sample of 6082 high school students representative of all public school students in grades 9 through 12 attending these 3 school districts.Sex-stratified adjusted prevalence ratios (APRs) (adjusted for race/ethnicity, grade, and sexual identity) for high gender-nonconforming students (very/mostly/somewhat feminine male students or very/mostly/somewhat masculine female students) and moderate gender-nonconforming students (equally feminine and masculine students) relative to a referent group of low gender-nonconforming students (very/mostly/somewhat masculine male students or very/mostly/somewhat feminine female students).Among 6082 high school students, 881 (15.9%) were white, 891 (19.1%) black, 3163 (55.1%) Hispanic, and 1008 (9.9%) other race/ethnicity. Among female students (2919 [50.0% of the study population]), moderate GNC was significantly associated with feeling sad and hopeless (APR, 1.22; 95% CI, 1.05-1.41), seriously considering attempting suicide (APR, 1.41; 95% CI, 1.14-1.74), and making a suicide plan (APR, 1.52; 95% CI, 1.22-1.89); however, substance use was not associated with GNC. Among male students (3139 [50.0% of the study population]), moderate GNC was associated with feeling sad and hopeless (APR, 1.55; 95% CI, 1.25-1.92); high GNC was associated with seriously considering attempting suicide (APR, 1.72; 95% CI, 1.16-2.56), making a suicide plan (APR, 1.79; 95% CI, 1.17-2.73), and attempting suicide (APR, 2.78; 95% CI, 1.75-4.40), as well as nonmedical use of prescription drugs (APR, 1.81; 95% CI, 1.23-2.67), cocaine use (APR, 2.84; 95% CI, 1.80-4.47), methamphetamine use (APR, 4.52; 95% CI, 2.68-7.61), heroin use (APR, 4.59; 95% CI, 2.48-8.47), and injection drug use (APR, 8.05; 95% CI, 4.41-14.70).This study suggests mental distress is associated with GNC among female and male students. Substance use also appeared to be strongly associated with GNC among male students. These findings underscore and suggest the importance of implementing school-based programs to prevent substance use and promote student mental health that are inclusive of gender diversity in students.