tbuckley/cabot-search huggingface dataset:
NTRK, ALK and RET rearrangements in salivary gland cancer.
Authors: Svetlana Kutukova, Evgeny Imyanitov, Natalia P. Beliak, Julia V. Ivaskova, Alexandra Razumova
Journal: Journal of Clinical Oncology (2021)

e18023 Background: We investigated the prevalence of rare genes rearrangements in salivary gland adenocarcinomas and the impact of these fusions on overall survival (OS) and progression free survival (PFS). Methods: For 51/60 (85.0%) patients with different types salivary gland adenocarcinomas (stage I-IVA), sufficient tumor tissue was available for molecular characterization by polymerase chain reaction (PCR) and has been tested for NTRK, ALK, ROS1, RET and MET deletion. OS and PFS curves were estimated with the Kaplan-Meier method and compared using the log-rank test. Results: Two cases (3.92%) of NTRK translocation were found, both are a classic rearrangement of ETV6ex5; NTRK3ex15. Of the other alterations, 2 cases (3.92%) of unbalanced ALK expression. However, it was not possible to establish the option of rebuilding. In addition, were found 2 cases (3.92%) of highly balanced expression of NTRK2 and ALK, and one case (1.96%) of high expression of ROS1. RET mRNA expression was detected in 13 of 48 cases (27.08%). NTRK, RET, ALK and ROS1 fusions were equally common in both men and women (p = 0.89), not depending on age (0.76). All patients bearing ALK, RET and NTRK fusions had shorter overall survival - 13.2 months, 95% confidence interval [CI] 13.0 to 32.0 months in multivariable model 105.0 moth (95% CI 105.0-105.0) in patient's group without mutations (p = 0.1817); and shorter PFS: 5.0 month (95% CI 5.0-16.0) vs not reached PFC in group (mean of PFS 63.15±5.58; 95% CI 52.20-74.09) without mutations (p = 0.0467). ALK fusion is an independent poor prognosis factor affecting on OS: p = 0.0168, hazard ratio (HR) = 8.65 (95% CI 1.47-50.77); and poor prognosis factor affecting on PFS: p = 0.0170, HR = 7.13 (95% CI 1.42-35.80). Conclusions: ALK, NTRK, ROS1 and RET mutations define a new rare subtype of salivary gland adenocarcinomas with enormously poor prognosis. The presence ALK-mutation is an independent poor prognosis factorб negatively affecting both overall survival and progression-free survival. It’s advisable to consider the possibilities of using ALK, NTRK and RET inhibitors in this cohort of patients.
How to attain gender equality in nursing—an essay
Authors: Thomas Kearns, Paul Mahon
Journal: BMJ (2021)

The covid-19 pandemic shows that where, when, how, and to whom care is delivered has never been more diverse.In today's healthcare, the people delivering care must be similarly diverse, for the benefit of the profession, its practitioners, and patients. 1 -3 Yet around 90% of the world's nurses are women. 4Calls are being made, as they have before, to examine ways to promote the profession among men to tackle this imbalance. 1 5 Nursing is an inherently human experience: it is done for humans, by humans, and as humans, and in human experience no one gender claims primacy.Men have had, and continue to have, a valuable contribution to make to nursing, not simply because they are male but because they are human.Men enter the profession for the same reason as women-to care for people.
PTEN loss as a potential biomarker in patients with castration resistant prostate cancer M0.
Authors: Javier Puente, Elena Castro, María Sánchez García, Natalia Vidal, Jesús Moreno, David Hernández, Jose Luis Senovilla, Bernardo Herrera, Alvaro Montesa, Joan Carles, Jacques Planas, Teresa Alonso Gordoa, Sergio Vazquez-Estevez, Sara Álvarez, Francisco Javier Casas, Mateo Paz Cabezas, Ines de Torres, David Olmos
Journal: Journal of Clinical Oncology (2021)

e17043 Background: Until 2018, there were no approved agents for high risk non-metastatic castration-resistant prostate cancer (nmCRPC). Recently, three second-generation anti-androgens (apalutamide, enzalutamide and darolutamide), in combination with ADT, have demonstrated a significant benefit in metastasis-free survival (MFS) and overall survival.According to conventional imaging, nmCRPC state is the opposite to mCRPC. Nevertheless, CRPC is a continuous in which nmCRPC may share similar biology and biomarkers such as PTEN loss, which has proven to be a useful and targetable biomarker in mCRPC. Methods: We performed a prospective and multicenter analysis of 77 patients (pts) with nmCRPC. We collected blood samples as well as prostate cancer diagnostic biopsy whenever they were available. The aim of this study is to find potential biomarkers that could identify pts at a higher risk of metastasis development. Here we report preliminary results according to PTEN status. Results: We have analyzed 32 patients for PTEN loss. We report preliminary results using an IHC assay based on the IPATENTIAL150 PTEN score. Median age was 66 years and 50% of patients had a Gleason score &gt; 8 irrespectively of PTEN status. We identified 24 patients (75%) with PTEN loss with a median PSA at diagnosis of 13,1 ng/ml, and a PSA doubling time (PSA-DT) of 6,3 months vs. 37,35 ng/ml and 3,5 months respectively in the PTEN non-loss pts. In the PTEN loss population, 9 pts (37,5%) did not receive any local treatment vs. 2 pts in the PTEN non-loss (25%). Mediantime from diagnosis to CRPC was 11.5 vs 8.0 yrs in PTEN loss vs. non-loss pts. In the PTEN loss population 2 patients received apalutamide plus ADT and 2 darolutamide plus ADT, these patients were excluded for the MFS analysis. Median MFS was 37 months in the PTEN loss population vs. 23 months in the PTEN non-loss. However, with a median follow-up of 38 months, 54% of PTEN loss pts had developed metastasis and 50% of PTEN non-loss pts. Skeleton was by far the first site of metastasis in PTEN non-loss pts (75%), while PTEN loss pts developed metastasis in lymph nodes (38,5%) nearly as much as in the skeleton (46%). Conclusions: To our knowledge, this is the first data of PTEN loss as a biomarker in nmCRPC. In our study, PTEN loss in primary tumor is more frequent than previously documented for mCRPC. PTEN loss appears to provide a better prognosis and higher lymph node involvement. Further analysis will be performed to corroborate these results and identify other factors involved.
Obituary for Roberto J. Groszmann—The Father of Portal Hypertension
Authors: Vijay H. Shah, Yasuko Iwakiri, James L. Boyer
Journal: Hepatology (2021)

After a year of fellowship in liver disease with Dr. Zimmerman at the Boston VA Hospital (1968-1969) he returned to Washington as a Research Fellow and Instructor in Medicine, Georgetown University, to work with Dr. Cohn (1969-1971). Dr. Cohn was a cardiologist, who was interested in systemic hemodynamics. It is here that Dr. Groszmann recognized that hemodynamic alterations were fundmental to the pathogenesis of cirrhosis. These seminal observations that the splanchnic circulation was hyperdynamic, rather than congestive, gave rise to his paradigm changing publications and set the ground work for subsequenet use of beta-blockers and splanchnic vasoconstrictor therapy leading to his becoming the father of the syndrome of Portal Hypertension (PH).
A 10-hour time-restricted eating intervention to address cancer-related fatigue among cancer survivors.
Authors: Amber Kleckner, Jennifer E Reschke, Brian James Altman, Elizabeth Belcher, Richard Francis Dunne, Fergal J. Fleming, Nikesha Gilmore, Marielle Jensen-Battaglia, Ian Kleckner, Po-Ju Lin, Karen Michelle Mustian, Luke Joseph Peppone
Journal: Journal of Clinical Oncology (2021)

12109 Background: Cancer-related fatigue is a common, debilitating condition that can persist for months or years after cancer treatment. Time-restricted eating has been shown to improve circadian rhythm and strengthen rest and activity patterns, and therefore could help reduce persistent fatigue. Herein, we evaluated the feasibility of recruiting cancer survivors to a two-week, single-arm, time-restricted eating intervention with a 10-h eating window, assessed safety of the intervention, monitored adherence, and obtained initial estimates of within-group change in patient-reported fatigue. Methods: We recruited adults 4-60 months post-cancer treatment who had a fatigue level ≥3 on a scale from 0-10 and who did not already consume food within a 10-h window. Participants were asked to consume all food and beverages within a self-selected 10-h eating window for 14 days; water was allowed at all times. Participants completed a daily diary indicating when they began and stopped eating each day. To assess fatigue, participants completed the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the Brief Fatigue Inventory (BFI) at pre- and post-intervention. We report mean±standard deviation and used a t-test to assess differences in pre- vs. post-intervention scores. Results: A total of 21 participants consented (20 breast cancer, 1 prostate cancer; 20 female; age 57.7±11.4 years; 1.6±1.1 years post-primary treatment). The study was feasible: 19/21 (90.5%) completed pre- and post-intervention assessments and daily diaries. It was also safe: there were two mild adverse events—one unlikely (insomnia) and one possibly related to the intervention (acute headache) and no severe adverse events. Most of the participants adhered to the intervention; 14/19 (73.7%) ate all of their food within a 10-h window at least 80% of the days, and 16/19 (84.2%) reported an average eating window ≤10 h. Fatigue scores improved a clinically meaningful degree for FACIT-F total score, FACIT-F fatigue subscale, and the BFI total score from pre- to post-intervention per established cutoffs (Table). Conclusions: Cancer survivors were willing and able to adhere to a two-week time-restricted eating intervention, and the intervention was safe. Also, fatigue was reduced with moderate to large effect sizes after two weeks of time-restricted eating. Based on our results, a follow-up randomized controlled trial to investigate time-restricted eating to alleviate cancer-related fatigue among cancer survivors is indicated. Funding: NIH/NCI UG1CA189961, T32CA102618. Clinical trial information: NCT04243512. [Table: see text]
Local and systemic recurrence following total neoadjuvant therapy (TNT) and resection for borderline resectable and locally advanced pancreatic adenocarcinoma: Long-term follow up from two phase II studies.
Authors: Grace E. Ryan, Janet E. Murphy, Christine A. Ulysse, Beow Y. Yeap, Jennifer Yon-Li Wo, Colin D. Weekes, Jeffrey William Clark, Jill N. Allen, Lawrence Scott Blaszkowsky, Ryan David Nipp, Lorraine C. Drapek, Aparna Raj Parikh, Christine Bolton, Jacob Maruna, Cristina R. Ferrone, Motaz Qadan, Keith D. Lillemoe, David P. Ryan, Carlos Fernandez Del-Castillo, Theodore S. Hong
Journal: Journal of Clinical Oncology (2021)

4133 Background: With the advent of FOLFIRINOX, the management of pancreatic cancer has undergone a profound change. There has been a shift to TNT with FOLFIRINOX followed by radiation and an attempt at surgical resection. Recent trials of TNT have demonstrated an ability to resect locally advanced (LA) and borderline resectable disease. There is a lack of prospective data demonstrating local and systemic recurrence rates after TNT. Methods: Two previously reported prospective clinical trials (Murphy JE, et al, JAMA Oncol 2018, 2019) of total neoadjuvant therapy were conducted between 2012 and 2018 for borderline and LA disease (NCT01591733, NCT01821729). Patients received FOLFIRINOX for 8 cycles. Upon restaging, patients with resolution of vascular involvement received short-course chemoradiotherapy (5 Gy x 5 with protons or 3 Gy x 10 w photons) with capecitabine (N=34). Patients with persistent vascular involvement received long-course chemoradiotherapy with capecitabine (N=56). All patients were considered for resection after TNT except for those patients with metastatic or unresectable disease. Results: 97 eligible patients were enrolled and started treatment on the borderline resectable (n = 48) and locally advanced (n= 49) study. 90 patients completed therapy. 80 patients were taken to the operating room. 61 patients had R0 resection and 5 patients had R1 resection. The table shows the distribution of local recurrences, local recurrences and metastatic disease, and metastatic disease alone. With a median follow-up of 5.2 years (range: 2.4-6.0), of the 61 R0 patients, 22 patients remained alive and free of disease, 7 patients had a local recurrence, 4 patients had locoregional and metastatic recurrence, and 24 patients had a metastatic recurrence. 3 patients who underwent R0 resection died of unrelated causes. Median survival for patients undergoing R0 resection is 43.8 months. Conclusions: Total neoadjuvant therapy for locally advanced and borderline resectable pancreatic cancer is potentially curable and may change the pattern of spread.[Table: see text]
Cost-effectiveness of atezolizumab monotherapy versus pembrolizumab monotherapy for first-line (1L) treatment of metastatic non-small cell lung cancer (mNSCLC).
Authors: Chia-Wei Lin, Katherine Rosettie, Pinar Bilir, Hazal Celik, Seye Abogunrin, Sarika Ogale
Journal: Journal of Clinical Oncology (2021)

e18847 Background: Atezolizumab monotherapy is indicated as 1L treatment for mNSCLC patients with high programmed death ligand-1 (PD-L1) expression (≥ 50%) and without epidermal growth factor receptor or anaplastic lymphoma kinase mutations. This analysis assessed the cost-effectiveness of 1L atezolizumab monotherapy vs. pembrolizumab monotherapy for mNSCLC patients with high PD-L1 expression from a US third-party payer perspective. Methods: A Markov model with progression-free, progressive disease (PD), and death states was developed in Microsoft Excel to compare clinical and cost outcomes of atezolizumab monotherapy vs. pembrolizumab monotherapy. Efficacy, safety, and utility data were derived from systematic reviews and indirect comparisons of the IMpower110, Keynote-024, and Keynote-042 trials. Product prescribing information and clinical trials informed dosing and administration. Wholesale acquisition cost (WAC, accessed in January 2021) for drugs were used while other cost inputs were derived from publicly available fee schedules and peer-reviewed literature. The key outcome of interest was the incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained. Deterministic sensitivity analysis with 20% variation and probabilistic sensitivity analyses (PSA) were performed to address uncertainties around input parameters. Results: In the base case, 1L atezolizumab monotherapy was projected to increase life expectancy for patients by 0.60 life-years (4.35 vs. 3.75) and 0.47 QALYs (3.46 vs. 2.98) over pembrolizumab monotherapy at an incremental cost of $27,947 (mean total cost: $396,811 vs. $368,864), resulting in an ICER of $58,841/QALY gained. Results of the deterministic sensitivity analysis were most sensitive to changes in discount rates for costs and care costs in the PD state. The PSA showed that the probability of atezolizumab being cost-effective at willingness-to-pay thresholds of $100,000 and $150,000 was 41% and 49%, respectively. Conclusions: First-line atezolizumab monotherapy had 0.6 life-years and 0.47 QALYs gained compared with pembrolizumab monotherapy and was estimated to be cost-effective (ICER $58,841/QALY). As the ICER falls below the US cost-effectiveness thresholds ( &lt; $100,000-$150,000/QALY), clinicians and payers should consider atezolizumab monotherapy as a cost-effective 1L option for mNSCLC patients with high PD-L1 expression.
Neoadjuvant weekly carboplatin and paclitaxel followed by dose dense adriamycin/cyclophosphamide in locally advanced triple negative breast cancer: A single-center experience in a safety net hospital.
Authors: Nan Chen, Shaun Bulsara, Susan G. Hilsenbeck, Mothaffar F. Rimawi, Julie R. Nangia
Journal: Journal of Clinical Oncology (2021)

e12629 Background: Locally advanced triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer comprising 10-15% of new diagnoses each year. Optimization of neoadjuvant therapy is necessary to decrease risk of relapse. Carboplatin has been explored as an addition to standard chemotherapy to increase rates of pathologic complete response (pathCR) and improve disease free (DFS) and overall survival. Studies have shown varying degrees of benefit, and the ideal usage of carboplatin remains unclear. Methods: A retrospective chart review was conducted in the Harris County Health System to examine outcomes of patients receiving carboplatin. 71 patients with TNBC were identified as treated with weekly carboplatin at an AUC of 2 and paclitaxel followed by dose dense adriamycin/cyclophosphamide (ddAC) between 2015 and 2020. Results: The average age at diagnosis was 50 (range 31 – 73). 44 (62%) patients were Hispanic, 19 (27%) were African American. 11 (15%) were BRCA carriers. 30 (42%) patients had clinical Stage II disease, 41 (58%) patients had clinical stage III disease. 53 (75%) patients had T3 or T4 disease. 48 (68%) patients had nodal disease at diagnosis. The pathCR rate for the overall population was 43%, of the patients who did not achieve a pathCR, 6 (15%) had residual cancer burden (RCB) I, 21 (51%) had RCB II, and 14 (34%) had RCB III at the time of surgery. 5 year disease free survival (DFS) after surgery for all patients was 70% (95% CI 56-86%). 5 yr DFS was 63% (95% CI 45-88%) for patients without pathCR compared to 79% (95% CI 62-100%) for patients with pathCR (p = 0.3, logrank test). 61% of patients had between 3 – 5 adverse events. 30 (42%) patients required a treatment delay. 12 (17%) patients required treatment discontinuation. The most common serious adverse event was neutropenia affecting 9 (12%) patients. Conclusions: Our single center data in a safety net clinical setting demonstrates that a neoadjuvant regimen of weekly carboplatin/taxol followed by ddAC was safe and efficacious in a high-risk group of primarily minority patients. Despite having more advanced disease compared to patients in randomized trials receiving weekly carboplatin such as GeparSixto, our patients still had similar response rates. Additionally, our data supports the continued use of pathCR as a valid indicator of disease free and overall survival.
The correlation between tumor microenvironment and the clonality of the T-cell repertoire in lung cancer and colorectal cancer.
Authors: Hua Cao, Jingxian Duan, Shunda Jiang, Tianhao Mu, Ruilian Xu
Journal: Journal of Clinical Oncology (2021)

e14524 Background: The tumor microenvironment has been shown to affect the responsiveness of immunotherapy. Effective anti-tumor immune response requires the activation and expansion of specific antigen-reactive T cell clones. It was reported that increased T cell clonality was associated with improved response to immunotherapy. However, what type of tumor microenvironment facilitates T cell clonal expansion remained controversial. The study aims to investigate the correlation between tumor microenvironment and the clonality of the T cell repertoire in lung cancer and colorectal cancer. Methods: 4 lung cancer patients and 4 colorectal cancer patients were enrolled in this study. Tumor tissues and peripheral blood samples were collected for RNA sequencing and T cell receptor CDR3 sequencing. The infiltration levels of 28 immune cells were estimated based on the mRNA expression of the genetic markers. The T cell clonality was defined as 1-Peilou’s evenness. Data were presented as mean± S.E.M. Results: The mean T cell clone counts in the blood samples of the 8 patients were 25676±4782 (ranging from 10259 to 45016), and the mean clonality of the TCR repertoires was 0.20±0.02 (ranging from 0.11 to 0.27). The clonality of T cells in colorectal cancer patients was similar to that of the lung cancer patients (0.22±0.02 versus 0.18±0.03, p = 0.31), showing comparable potentials of antigenic responses. The tumor infiltration of regulatory T cells, type 17 T helper cells, CD56 bright natural killer cells, and natural killer cells varied greatly among patients, the coefficient of variation of those cells were 54.61%, 54.61%, 54.43%, and 55.62% respectively. In contrast, the coefficient of variation of monocytes was 23.34%, displaying a relatively even distribution among patients. The Pearson’s correlation coefficient was calculated to show the correlation between T cell clonality and the infiltration level of all 28 types of immune cells. Notably, only the infiltration of type 17 T helper cells significantly associated with T cell clonality, the positive correlation gave an R square value of 0.68 (r = 0.82, 95% confidence interval of 0.04-0.98, p = 0.04). The infiltration levels of CD4+ T cells, CD8+ T cells, regulatory T cells, type 1 and type 2 T cells, and gamma delta T cells were not affected by T cell clonal expansion. The expression of B cells, dendritic cells, macrophages, natural killer cells, and monocytes did not correlate with T cell clonal expansion. However, the abundance of neutrophils appears to positively correlate with T cell clonality (p = 0.09). Conclusions: The clonal expansion was significantly associated with the infiltration of type 17 T helper cells but not other subtypes of T cells, showing that the type 17 T helper cells are crucial to the antigenic responses in lung cancer and colorectal cancer. A neutrophil enriched tumor microenvironment may facilitate T cell clonal expansion.
Prognostic role of lymphocyte to monocyte ratio in patients treated with CAR-T for aggressive lymphoma.
Authors: Henan Zhang, Radhika Bansal, Kodi Peterson Martinez, Matthew Hathcock, Zuoyi Shao, Gabriele McCoy, Anatilde Gonzalez-Guerrico, N. Nora Bennani, Jonas Paludo, Yucai Wang, Patrick Johnston, Stephen M. Ansell, Saad Kenderian, Luis F. Porrata, Jose Caetano Villasboas, Yi Lin
Journal: Journal of Clinical Oncology (2021)

7558 Background: A low absolute lymphocyte to monocyte ratio (ALC/AMC) has been found to predict decreased survival in lymphoma patients receiving chemotherapy and stem cell transplant. We report its clinical significance and additional cellular phenotype changes in patients receiving chimeric antigen receptor T-cell (CART) therapy. Methods: Records were reviewed for patients (pts) who received axicabtagene ciloleucel between 6/2016 and 12/2020. Receiver operator curve was generated using nominal logistic regression to predict CR as best response. Survivals were calculated using Kaplan- Meier method. Blood immune phenotype were assayed by multiparametric flow. Principle component analysis (PCA) was performed using ClusterVis. Results: Low ALC/AMC (≤0.8) prior to lymphodepletion (LD) chemotherapy on day -5 was associated with lower CR rate (AUC=0.68, Table). Our cohort of 81 pts had similar baseline characteristics except that noted in Table. Low ALC/AMC ratio is associated with shorter EFS and OS (EFS: 2.6 vs. 6.4 months, P&lt;0.0001; OS: 5.3 months vs. not reached, P=0.0006), respectively. Prognostic association remained significant in multivariate analysis including ASCT, bridging therapy and CRP. Interestingly, compared to the high ALC/AMC group, the low ALC/AMC group had decreased CD8 Tem, increased CD16+CCR2+ monocytes and increased monocytes’ producing IL12, IL-10, and IL-1β (n=26). Unsupervised PCA identified 3 clusters: 1. Low ALC/AMC, all non-CR; 2. High ALC/AMC, some non-CR; 3. High ALC/AMC, all CR. Compared to cluster 1 and 2, cluster 3 had increased CD4 Tnaive, CD8 Tcm and IL-17 producing CD4 T and NK cells. Conclusions: ALC/AMC is a clinically accessible test that is strongly associated with CAR-T response and survival. Immune characterization revealed that the biologic effect is not just associated with cell ratio. Increased inflammation has been found to negatively impact CAR-T response, with some cytokines known to be from the myeloid lineage. We show that CRP is elevated in the low ALC/AMC group with increased cytokine production by monocytes. In addition, presence of T cell subset and IL-17 producing cells, before LD, are associated with clinical response. Further investigation on optimizing host immunity may help improve clinical outcome with CAR-T.[Table: see text]