tbuckley/cabot-search huggingface dataset:
Impact of advanced clinical and translational research educational programs on oncology specialties and career development.
Authors: Aron Simkins, Michael Lee, Wencesley A. Paez, Cecilia Arana Yi, Heidi E. Kosiorek, Michael Curtis, Timur Mitin
Journal: Journal of Clinical Oncology (2021)

11026 Background: The Clinical and Translational Science Award (CTSA) Program currently supports more than 50 leading medical research institutions in the U.S. with the aims of training, promoting and developing future translational science researchers, with particular emphasis on advanced Clinical and Translational Research (CTR) education. No prior studies have evaluated career development in oncologists who have completed CTR training. The objective of this study is to examine the impact of advanced CTR training on career development, return-on-investment and research productivity in Oncology specialties. Methods: With IRB approval, we conducted a survey study of U.S.-based Hematology/Oncology (H/O), Radiation Oncology (RO), and Surgical Oncology (SO) members of the American Society of Clinical Oncology who completed CTR training. Data was anonymized and collected through Research Electronic Data Capture (REDCap). Outcomes were compared using Chi-square test for frequency data. Results: We received 225 survey responses (62.1% H/O, 23.3% RO, 13.2% SO, 1.4% others). About 28.4% (n = 64) of the respondents had a PhD or Master's degree in CTR (Group A) compared to 71.6% (n = 161) with graduate certificates or non-degree granting courses in CTR (Group B). Specialty ratio was equally distributed between both groups. Overall, 79.7% vs 57.5%; P &lt; 0.001 of respondents worked in academia, of which 55.2% had tenure track positions. Over 49 different CTSA Programs throughout the U.S. were represented. In terms of impact with new research projects, the ability to secure funding and opportunities for multidisciplinary collaboration, satisfaction with CTR training was higher among Group A compared with Group B (P &lt; 0.001; P &lt; 0.01; P &lt; 0.01 respectively). In terms of research output, higher satisfaction was seen in Group A (67.2% vs 47.4%; P &lt; 0.01), however total publications per year were not statistically significant (P = 0.135). Usefulness of a CTR degree on career advancement, a difference of 50.0% vs 19.1%; P &lt; 0.001 was noted. Similarly, usefulness regarding new job opportunities and return-on-investment also favored Group A (P &lt; 0.001). Overall satisfaction with training was significantly higher in Group A (73.4% vs 48.7%; P = 0.004). Conclusions: This study is the first to report satisfaction ratings for CTR training among oncology specialties. Although no significant difference was observed in terms of publication output, those with higher levels of advanced degrees were more satisfied with their CTR training, and viewed it as more impactful to career advancement and research productivity. The evidence presented is useful for informing career development for oncology residents and fellows offered CTR degrees during their training.
The Cytogenetic Aberrations and Their Prognostic Value in 181 Untreated Patients with Lymphoplasmacytic Lymphoma/ Waldenström Macroglobulinemia in China
Authors: Wenjie Xiong, Yuting Yan, Shuhua Yi, Zengjun Li, Zhen Yu, Wei Liu, Rui Lv, Dehui Zou, Yan Xu, An Gang, Lugui Qiu
Journal: Blood (2017)
Abstract NT-118: SEQUENTIAL THERAPEUTIC TARGETING OF OVARIAN CANCER HARBORING DYSFUNCTIONAL BRCA1
Authors: Tahira Baloch, Roy Kessous, David Octeau, Liron Kogan, Ido Laskov, Michael Witcher, Walter H. Gotlieb, Amber Yasmeen
Journal: Clinical Cancer Research (2019)

Abstract BACKGROUND: Ovarian cancer is the most lethal gynecologic cancer. High grade serous ovarian cancer (HGSC) is the most common and deadly histological subtype. The current standard treatment protocol involves primary debulking surgery followed by platinum-based combination chemotherapy. PARP inhibitors(PARPi) are the first approved personalized treatments used in BRCA1-mutated recurrent ovarian cancer patients and have shown promising clinical results. Previously published data in collaboration with Dr. Witcher's lab, we described a significant reduction in PARP1 protein levels in patients after giving standard carboplatinum-paclitaxel chemotherapy that is effecting the clinical efficacy of PARP inhibitors in clinical trials. PARP inhibitors are currently administered after standard chemotherapy, when PARP levels are the lowest which was clearly shown in the previous published paper. Applying novel strategy and following the sequence of administration, giving PARP inhibitors first followed by standard chemotherapy might improve response rates. This study aims to evaluate this strategy (in vitro) in the pre-clinical models. METHODS: BRCA1 mutated (UWB1.287, SNU-251), epigenetically silenced (OVCAR8), and wild-type BRCA1 (OVCAR3, SKOV3, A2780P &amp; A2780R) cell lines were exposed to clinically relevant doses of PARPi, either followed by standard chemotherapy, or the inverse sequence. Therapeutic efficacy was assessed using colony formation assay. Apoptotic index was evaluated by cell cycle analysis and apoptotic assays using flow cytometry. Western Blotting was used to detect the levels of relevant apoptotic and cell cycle proteins. RESULTS: Exposure to PARPi prior to standard chemotherapy sensitized BRCA1 mutated or epigenetically silenced BRCA1 cell lines to lower doses of Cisplatin (CP) or Paclitaxel (PT). Similarly, pre-treatment with PARPi prior to chemotherapy induced apoptosis more effectively in the same cell lines. Similar results were observed in BRCA1 wild-type cell lines and cell lines in which BRCA1 functionality was restored. CONCLUSION: Pre-treatment of cell lines with PARPi followed by standard chemotherapy is more efficient (in vitro) in inhibiting growth and inducing apoptosis than the present sequence of chemotherapy followed by PARPi. Citation Format: Tahira Baloch, Roy Kessous, David Octeau , Liron Kogan, Ido Laskov, Michael Witcher, Walter H. Gotlieb and Amber Yasmeen. SEQUENTIAL THERAPEUTIC TARGETING OF OVARIAN CANCER HARBORING DYSFUNCTIONAL BRCA1 [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr NT-118.
Evolution in Myeloid Neoplasms Clonal Architecture Post Allogeneic Hematopoietic Cell Transplantation
Authors: Bhumika J. Patel, Sagar S. Patel, Tomas Radivoyevitch, Swapna Thota, Teodora Kuzmanovic, Bartlomiej P. Przychodzen, Cassandra M. Hirsch, Donna M. Abounader, Aziz Nazha, Sudipto Mukherjee, Aaron T. Gerds, Anjali S. Advani, Brian J. Bolwell, Matt Kalaycio, Mikkael A. Sekeres, Ronald Sobecks, Hetty E. Carraway, Navneet S. Majhail, Betty K. Hamilton, Jaroslaw P. Maciejewski
Journal: Blood (2017)
The Israeli national policy for discontinuation of isolation of carbapenem-resistant Enterobacterales carriers by carbapenemase type: a retrospective cohort study
Authors: Yaakov Dickstein, Ester Solter, David Schwartz, Amir Nutman, Inga Harevrich, Liat Wulffhart, Yehuda Carmeli, Mitchell J. Schwaber
Journal: Clinical Microbiology and Infection (2021)
KEYNOTE-629: Health-related quality of life (HRQoL) with pembrolizumab (pembro) in patients (pts) with locally advanced (LA) or recurrent or metastatic (R/M) cutaneous squamous cell carcinoma (cSCC).
Authors: Åse Bratland, Eva Muñoz-Couselo, Laurent Mortier, Osama Roshdy, Rene Gonzalez, Jacob Schachter, Ana Maria Arance, Florent Grange, Nicolas Meyer, Abhishek Jagdish Joshi, Salem Billan, Brett Gordon Maxwell Hughes, Jean-Jacques Grob, Karthik Ramakrishnan, Eric (Pingye) Zhang, Burak Gumuscu, Ramona F. Swaby, Ralf Gutzmer
Journal: Journal of Clinical Oncology (2021)

9546 Background: KEYNOTE-629 is a single-arm phase 2 study of pembro for cSCC. At second interim analysis (IA), pembro had robust and durable antitumor activity and manageable safety in LA and R/M cohorts. At first IA, pembro maintained HRQoL in the R/M cohort; LA was not analyzed because of ongoing accrual. HRQoL of pts with LA or R/M cSCC at second IA (database cutoff July 29, 2020; additional 15-mo follow-up since IA1 for the R/M cohort) is shown. Methods: Pts with LA or R/M cSCC received pembro 200 mg IV Q3W for ≤35 cycles. HRQoL was a prespecified exploratory end point assessed using EORTC QLQ-30 and EuroQol EQ-5D-5L instruments administered at baseline, wk 3, and wk 6; then Q6W through y 1; then Q9W until treatment end/discontinuation; and at the 30-day safety follow-up. HRQoL was analyzed in pts who received ≥1 pembro dose and completed baseline and ≥1 postbaseline HRQoL assessments. Mean change from baseline in EORTC QLQ-C30 global health status (GHS)/quality of life (QoL), physical functioning (PF), and EQ-5D-5L visual analog scale (VAS) scores were evaluated at wk 12 to ensure adequate completion rate and through last pt visit at wk 75 for EORTC QLQ-C30 GHS/QoL and PF scores. HRQoL was categorized as improved or deteriorated based on ≥10-point change in EORTC QLQ-C30 scores (considered clinically meaningful). Results: The HRQoL analysis population for LA had 47 pts for EORTC QLQ-C30 and EQ-5D-5L; the R/M cohort had 99 pts for EORTC QLQ-C30 and 100 for EQ-5D-5L. At wk 12, compliance rates were &gt;75% for LA and &gt;80% for R/M cohorts for EORTC QLQ-C30 and EQ-5D-5L. Mean change from baseline to wk 12 was minimal for EORTC QLQ-C30 GHS/QoL, PF, and EQ-5D-5L VAS scores for both cohorts (Table). Mean change from baseline in EORTC QLQ-C30 GHS/QoL and PF scores remained stable over 48 wk in the LA cohort (75-wk data unavailable) and over 75 wk in the R/M cohort. Most pts had improved or stable EORTC QLQ-C30 GHS/QoL and PF scores relative to baseline during follow-up. Conclusions: HRQoL was generally maintained with pembro in LA and R/M cSCC cohorts and was not negatively impacted by tumor progression or AEs. Clinical trial information: NCT03284424. [Table: see text]
Off-label targeted therapy (TT) use in recurrent/metastatic NSCLC.
Authors: Victoria Wang, Chenming Cui, Lei Yang, Gerald Li, Alexa Betzig Schrock, Meijuan Li, Jeffrey Michael Venstrom, Khaled A. Tolba
Journal: Journal of Clinical Oncology (2021)

e18688 Background: Comprehensive genomic profiling (CGP) is an established diagnostic approach to select patients for TT. As CGP gains wide adoption, an increasing number of patients are found to harbor driver mutations for which no approved TT is available. This is often addressed through use of matched TKI and mAb approved for other mutations or anatomic sites. In this work, we examined the clinical efficacy of off-label TT in R/M NSCLC. Methods: Using a de-identified NSCLC clinico-genomic database (CGDB), we identified 6590 NSCLC patients who underwent Foundation Medicine CGP, of whom 17.8% harbored an actionable genomic alteration (GA) for which an FDA-approved TT was available and 2% (133) whose GA (MET ex-14, uncommon EGFRm, EGFR ex20ins, HER2 amp/mut, RET fusion, BRAF class 2/3) lacked an FDA-approved TT (62 in 1L and 71 in ≥2L ) who received matched off-label TT. ESMO Scale for Clinical Actionability (ESCAT) was used to grade levels of evidence. For patients who progressed on initial chemotherapy (range 2 – 9 lines, median 3), we calculated clinical efficacy using the ratio of real world PFS on targeted therapy (rw-PFS2) to rw-PFS on the last prior line of therapy (rw-PFS1) and used a cut-off of PFS2/PFS1 &gt; 1.3 to determine off-label drug efficacy. Results: Of the 133 patients reviewed, 72 were classified as ESCAT level IB (uncommon EGFRm, MET-ex14), 45 IIB (HER2m/amp, EGFR ex-20ins), 7 IC (RET fusions). PFS varied significantly by mutation and line of therapy (table 1) with uncommon EGFRm+ and MET-ex14 exhibiting best response while EGFR ex20 ins, BRAF class 2/3 and HER2 amp fared significantly worse. 55.8% of the patients (39 of 71) reached a PFS2/PFS1 ratio &gt; 1.3 (two-sided 95% CI, 45.3 % – 68.7 %), ranging from 93% in uncommon EGFRm+ down to 20% in HER2 amp and 44% in ex20ins. Conclusions: We provide real-world evidence to assess off-label TT in NSCLC. Clinical benefit derived from off-label TT is unevenly distributed across various mutations with most survival advantage accruing to specific mutations (MET-ex14 and uncommon EGFRm) at the expense of others (HER2 amp). Survival advantage was highly influenced by two factors: A) the timing of CGP with the earlier recipients of genomic profiling achieving better outcome, B) the identity of the driver mutation, highlighting the role of clinical actionability tier system to define level of evidence supporting such intervention.[Table: see text]
Health-related quality-of-life (HRQoL) analysis from the phase 3 CLEAR trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) or everolimus (EVE) versus sunitinib (SUN) for patients (pts) with advanced renal cell carcinoma (aRCC).
Authors: Robert J. Motzer, Camillo Porta, Boris Alekseev, Sun Young Rha, Toni K. Choueiri, Maria Jose Mendez-Vidal, Sung-Hoo Hong, Anil Kapoor, Jeffrey C. Goh, Masatoshi Eto, Jinyi Wang, Janice Pan, Alemseged Ayele Asfaw, Cixin Steven He, Kalgi Mody, David Cella
Journal: Journal of Clinical Oncology (2021)

4502 Background: LEN + PEMBRO improved PFS, OS and ORR vs SUN in the first-line treatment of pts with aRCC; LEN + EVE improved PFS and ORR vs SUN (Motzer R et al. NEJM. 2021). We report results of a secondary objective of the CLEAR trial comparing the impact of LEN + PEMBRO or EVE vs SUN, on HRQoL. Methods: Pts (N=1069) were randomized (1:1:1) to receive LEN 20 mg PO QD + PEMBRO 200 mg IV Q3W; LEN 18 mg + EVE 5 mg PO QD; or SUN 50 mg PO QD (4 wks on/2 wks off). HRQoL was assessed per FKSI-DRS, EORTC QLQ-C30, and EuroQoL EQ-5D-3L, at baseline, on day 1 of subsequent 3 wk cycles starting with cycle 2, and at the off-treatment visit. HRQoL analyses (unless otherwise noted) were based on data from randomized pts with any HRQoL data who received ≥1 dose of study treatment. No adjustments for multiple testing or estimation were used; P-values and CIs are nominal and descriptive. Results: For comparisons of LEN + PEMBRO vs SUN, overall changes from baseline at mean follow-up (wk 46) favored LEN + PEMBRO with significant differences between treatments for physical functioning (least squares mean difference [LS MD] [95% CI]: 3.0 [0.5, 5.5]) and fatigue (−2.8 [−5.5, −0.1]), dyspnea (−2.8 [−5.3, −0.3]), and constipation (−2.2 [−4.2, −0.2]). LS MD of the FKSI-DRS total score was 0.2 (−0.4, 0.7). For comparisons of LEN + EVE vs SUN, overall changes from baseline at wk 46 favored SUN with significant differences in overall HRQoL (−2.8 [−5.1, −0.5] assessed by the EORTC QLQ-C30 GHS/QoL scale) and pain (2.8 [0.1, 5.5]), appetite loss (4.2 [1.3, 7.1]), and diarrhea (5.3 [2.6, 7.9]). LS MD of the FKSI-DRS total score was −0.4 (−1.0, 0.2). 14 of 18 scales for both LEN + PEMBRO and LEN + EVE vs SUN had no significant differences in LS MD comparisons. The LEN + PEMBRO arm is favored over SUN for the median time to first deterioration (TTD) for physical functioning, dyspnea, appetite loss and EQ-5D VAS (Table). 15 of 19 scales for both LEN + PEMBRO and LEN + EVE vs SUN had no significant differences in TTD comparisons. Conclusions: Compared with SUN, pts in LEN + PEMBRO group had similar or better symptoms and HRQoL. Clinical trial information: NCT02811861. [Table: see text]
Multidisciplinary, biopsychosocial factors contributing to return to running and running related stress urinary incontinence in postpartum women
Authors: Isabel S Moore, Megan L James, Emma Brockwell, Joanna Perkins, Alex L Jones, Gráinne M Donnelly
Journal: British Journal of Sports Medicine (2021)

Objectives To examine contributory factors behind postpartum return-to-running and return to pre-pregnancy running level, in addition to risk factors for postpartum running-related stress urinary incontinence (SUI). Methods 881 postpartum women completed an online questionnaire. Clinically and empirically derived questions were created relating to running experiences and multidisciplinary, biopsychosocial contributory factors. Logistic regression was used to determine predictors for return-to-running, returning to pre-pregnancy level of running and running-related SUI. Results Median time to first postpartum run was 12 weeks. Running during pregnancy (OR: 2.81 (1.90 to 4.15)), a high weekly running volume (OR: 1.79 (1.22 to 2.63)), lower fear of movement (OR: 0.53 (0.43 to 0.64)) and not suffering vaginal heaviness (OR: 0.52 (0.35–0.76)) increased the odds of return-to-running. Factors that increased the odds of returning to pre-pregnancy running level were a low weekly running volume (OR: 0.38 (0.26 to 0.56)), having more than one child (OR: 2.09 (1.43 to 3.05)), lower fear of movement (OR: 0.78 (0.65 to 0.94)), being younger (OR: 0.79 (0.65 to 0.96)) and shorter time to running after childbirth (OR: 0.74 (0.60 to 0.90)). Risk factors for running-related SUI were having returned to running (OR: 2.70 (1.51 to 4.76)) and suffering running-related SUI pre-pregnancy (OR: 4.01 (2.05 to 7.82)) and during pregnancy (OR: 4.49 (2.86 to 7.06)); having a caesarean delivery decreased the odds (OR: 0.39 (0.23 to 0.65)). Conclusion Running during pregnancy may assist women safely return-to-running postpartum. Fear of movement, the sensation of vaginal heaviness and running-related SUI before or during pregnancy should be addressed early by healthcare providers.
Community-based lung cancer screening adherence to Lung-RADS recommendations.
Authors: Roger Kim, Katharine A. Rendle, Christine Neslund-Dudas, Robert T. Greenlee, Andrea N. Burnett-Hartman, Stacey A. Honda, Michael J. Simoff, Jennifer M. Croswell, Debra P. Ritzwoller, Anil Vachani
Journal: Journal of Clinical Oncology (2021)

10540 Background: In the NLST and NELSON trials, most low-dose CT (LDCT) screen-detected lung cancers were not diagnosed during the first round of screening, suggesting that longitudinal adherence to lung cancer screening (LCS) recommendations is key. Adherence was as high as 95% in clinical trials, but limited data exist regarding LCS adherence in clinical practice. We aimed to determine adherence to Lung-RADS recommendations among community-based patients undergoing LCS. Methods: We performed a multicenter retrospective cohort study of patients screened for lung cancer at healthcare systems within the Lung Population-based Research to Optimize the Screening Process (PROSPR) Consortium. We included 55-80 year-old current or former smokers who received a baseline (T0) LDCT with a Lung-RADS score between January 1, 2015 and September 30, 2017 and excluded patients who were diagnosed with lung cancer prior to the T0 scan. Over a 24-month period, we calculated the proportion of patients adherent to Lung-RADS recommendations and evaluated associations with patient-level (age, sex, race, ethnicity, smoking status, body mass index, Elixhauser comorbidities, year of T0 scan, and Lung-RADS score) and census tract (median family income, level of education) data, using multivariable logistic regression with mixed effects to account for site variability. Results: Of the 6,723 patients in our cohort (median age 65 years [IQR 60-69]; 45.1% female; 73.0% white; 59.0% current smokers), 5,583 (83.0%) had Lung-RADS 1 or 2 T0 scans, 733 (10.9%) Lung-RADS 3, 274 (4.1%) Lung-RADS 4A, and 133 (2.0%) Lung-RADS 4B or 4X. Overall, 55.2% (3,709/6,723) of patients were adherent (Table). In the final multivariable model, Black patients had reduced adherence compared to white patients (adjusted odds ratio [aOR] 0.79, 95% CI 0.66-0.94), while greater adherence was observed in former smokers compared to current smokers (aOR 1.33, 95% 1.19-1.49). Compared to individuals with a negative T0 scan (Lung-RADS 1 or 2), those with Lung-RADS 3 (aOR 1.56, 95% CI 1.31-1.86), 4A (aOR 1.63, 95% CI 1.24-2.15), or 4B/4X (aOR 3.59, 95% CI 2.30-5.60) T0 scans had greater odds of adherence. Conclusions: In the largest study of real-world patients receiving LCS to date, adherence to Lung-RADS recommendations is lower than previously observed in clinical trials. Our results highlight the need for further study of system-level mechanisms to improve longitudinal LCS adherence rates.[Table: see text]
Low expression of microRNA-195 is a poor prognostic marker for ER-positive breast cancer patients.
Authors: Yoshihisa Tokumaru, Masanori Oshi, Eriko Katsuta, Vijayashree Murthy, Nobuhisa Matsuhashi, Manabu Futamura, Kazuhiro Yoshida, Kazuaki Takabe
Journal: Journal of Clinical Oncology (2021)

e12576 Background: MicroRNA-195 (miR-195) is a tumor suppressive microRNA in breast cancer; however, its clinical relevance remains debatable because most data is either in vitro or from small cohort studies. In this study, we hypothesized that miR-195 low expressing tumors associate with high proliferative characteristics and poor survival. Methods: We obtained the clinical data and survival information of breast cancer patients from two large publicly available databases and one small cohort; The Cancer Genome Atlas (TCGA),The Molecular Taxonomy of Breast Cancer International Consortium (METARBRIC), and GSE45666. Total of 755, 1287, and 116 patients’ data were obtained from TCGA, METABRIC, and GSE45666 respectively. Survival analysis, Overall survival (OS) and Disease-free survival (DFS) was performed by comparing the high and low expression groups. CYT score, xCell, and other immunological factors were used to evaluate intratumoral immune cell composition. Also, gene set enrichment analysis (GSEA) was performed between miR-195 high and low expression groups. Results: The patients were divided into miR-195 high and low groups by utilizing median cutoff. At first, we confirmed that miR-195 expression was significantly lower in tumors compared to normal breast tissue in TCGA as well as GSE45666. Advanced grades were significantly associated with lower expression of miR-195 in ER positive/HER2 negative (ER+/HER2) subtype with both TCGA and METABRIC cohorts ( p&lt; 0.001 and p&lt; 0.001, respectively). On the contrary this was not consistent with other subtypes, HER2+ and triple negative (TN). Also, Low miR-195 expressing tumors demonstrated higher MKI67 expressions in ER+/HER2- subtype with TCGA ( p&lt; 0.001). This was validated with METABRIC cohort ( p&lt; 0.001). Furthermore, GSEA demonstrated that low miR-195 expressing tumors enriched the gene sets related with cell cycle or cell proliferation, such as MYC signaling, mTOR signaling, E2F signaling, G2M Checkpoint signaling and PI3K_Akt_mTOR signaling, compared with high miR-195 expressing tumors in ER+/HER2-. Conclusions: Low expression of miR-195 was associated with improved OS in ER positive breast cancer patients. Also, low miR-195 expressing tumors were found to associate with advanced grades as well as enriching the genes relating to cell proliferation and cell cycle, which may explain the poor survival of low miR-195 expressing patients in ER positive breast cancer.