tbuckley/cabot-search huggingface dataset:
Accuracy of gravity based automatic infusion system applied to chemoport for intravenous infusion.
Authors: Jonggwon Choi
Journal: Journal of Clinical Oncology (2024)

191 Background: When a vesicant drug is administered to the peripheral vein, a gravity drip method rather than an peristaltic infusion pump is recommended. In addition, it is reported that the gravity based pump has less particle generation than the peristaltic pump that injects fluid through constant peristaltic movement. However, it is pointed out that the disadvantage of gravity based pump is that the rate of administration can easily change according to the change in the location of the injection site. We evaluate the accuracy of new gravity based pump (pressure-sensitive speed control fluid injection device, Accudrip made by Hanvit MD ) at various injection rates and hanging heights common to hospital settings. Methods: The accuracy and safety of the intravenous (IV) flow controller were evaluated for patients receiving IV chemotherapy in the oncology department. It was verified whether the accurate injection rate could be maintained even in various fluid heights, fluid amounts, and types of anticancer drugs that could affect the injection rate. Various anticancer drugs, including immune checkpoint inhibitor, were mixed with 250 ml/500 ml of normal saline and administered for 30 min/60 min, and glucose 500 ml/1000 ml was administered for 60 min/120 min to measure accuracy, each progressed 25 times. Medical staff were surveyed on the ease and limitations of medical practice for each peristaltic infusion pump and new gravity based pump. In addition, side effects occurring in patients during fluid administration were recorded. Results: The mean degree of error in the estimated end time of gravity based automatic infusion system was 3.09% (2.09 ~ 4.10). The error of the gravity based automatic infusion system was statistically significant depending on the patient age (p=.001) and the infusion time (p=.016), but the degree of error according to the type of fluids (p=.302) and fluid concentration (p=.844) was not statistically significant. Among the subjects of the study, nurses' satisfaction with the application of gravity based pump was 4.10 (±0.62) out of 5, and among the general characteristics of nurses, age ( p&lt;.078), and working department (p&lt;.91) did not show a statistically significant difference, but work experience ( p &lt;.021) showed a statistically significant difference. Conclusions: The accuracy of Gravity based automatic infusion system was determined because the degree of error in the expected end time of infusion was not significant according to the infusion variable. In a survey of nurses who have used gravity based pump directly, it was found that the ease of use and satisfaction were similar to those of the conventional peristaltic pump. These findings will contribute greatly to the precise drug administration (over or under-administration) and minimization of adverse events in real-world hospital settings.
Intracranial outcomes of 1L selpercatinib in advanced <i>RET</i> fusion-positive NSCLC: LIBRETTO-431 study.
Authors: Minji Uh, Maurice Perol, Koichi Goto, Benjamin J. Solomon, Keunchil Park, Ernest Nadal, Emilio Bria, Claudio Martin, Jair Bar, Justin Williams, Tarun Puri, Jian Li, Boris K. Lin, Caicun Zhou
Journal: Journal of Clinical Oncology (2024)

199 Background: Selpercatinib is a highly selective and potent CNS active RET inhibitor approved for treatment of advanced RET fusion-positive ( RET+) NSCLC. Treatment or prevention of CNS disease is critical in RET+ NSCLC patients (pts), who have nearly a 50% lifetime prevalence of brain metastases (mets) (Drilon et al. JTO 2018). LIBRETTO-431 is the first study to compare intracranial (IC) efficacy of a targeted therapy to chemo/IO in pts with oncogene driven NSCLC. Methods: LIBRETTO-431 (NCT04194944) is a randomized, open-label, phase 3 trial comparing 1L selpercatinib vs chemotherapy (cisplatin/carboplatin + pemetrexed) +/- pembrolizumab. As previously reported, the study met its primary endpoint of PFS by blinded independent central review (BICR) at the pre-planned interim analysis. IC analyses included CNS and non-CNS PD, IC PFS and IC responses by BICR per RECIST 1.1 in all pts who had a baseline and one or more post-baseline CNS scans (CNS-evaluable) and were designated to receive pembrolizumab if randomized to the control arm (CNS-pembro population). Adverse events were evaluated in the CNS safety population. Results: A total of 192 of 261 pts enrolled were CNS-evaluable (selpercatinib: 120, control: 72). Baseline characteristics were generally balanced with the selpercatinib arm having a slightly lower proportion of pts with BICR-assessed baseline brain mets (21% vs 25%) and prior CNS radiotherapy (RT; 6% vs 10%) compared to the control arm. Selpercatinib delayed CNS PD as evidenced by a lower 12 mo cumulative incidence rate (CIR) for CNS PD, as well as delaying non-CNS PD compared to control in pts with and without brain mets (Table). In pts with measurable brain mets at baseline (n=29), median time to IC response per RECIST 1.1 was similar between selpercatinib and control (1.4 mo [range: 1.2-2.9] vs 1.6 mo [range: 1.2-2.9]); however, as previously reported the IC response rates were higher (82% vs 58%) and more durable (12 mo DOR rate 76% vs 63%) with selpercatinib vs control (Zhou et al. NEJM 2023). IC responses to selpercatinib were more common in pts without prior CNS RT (14/15, 93%) than with prior CNS RT (3/6, 50%). Conclusions: Selpercatinib delayed IC progression in advanced RET+ NSCLC pts with or without baseline brain mets and achieved higher IC response rates compared to chemotherapy + pembrolizumab. LIBRETTO-431 is the first study to demonstrate IC efficacy improvement of a targeted therapy vs chemo/IO in a biomarker selected NSCLC population. These data further support selpercatinib as the preferred 1L regimen in pts with advanced RET+ NSCLC. Clinical trial information: NCT04194944 . [Table: see text]
Effectiveness of using risk communication to help smokers with cancer quit smoking: A randomized controlled trial.
Authors: William Ho Cheung Li, David Chi Leung Lam, Kit Man Sin, Eliza Lai Yi Wong, Carlos K H Wong, Herbert H. Loong, Kai Yeung Cheung, Wei Xia, Peige Song, Joyce Oi Kwan Chung
Journal: Journal of Clinical Oncology (2024)

158 Background: Despite evidence that patients living with cancer who continue to smoke after diagnosis are at a higher risk for all-cause mortality and reduced treatment efficacy, many cancer patients continue to smoke. This study aimed to examine the effectiveness of using a brief risk communication approach to help smokers with cancer quit smoking. Methods: A randomized controlled trial was conducted on 528 patients who continued to smoke and were follow-up at five out-patient clinics in Hong Kong. A total of 268 subjects were randomly assigned to the intervention group that received health warnings on smoking, and 260 subjects were randomly assigned to the control group that received usual care. All subjects had follow-up telephone calls at 1week, 1 month, 3 months, 6 months and 12 months to assess smoking status. Results: The biochemically validated quit rate at the 6-month follow-up was higher in the intervention group than in the control group (5.2% vs 3.8%; OR 1.38, 95% CI 0.60–3.16). The rate of at least 50% self-reported reduction of smoking at 6 months, was higher in the intervention group than in the control group (16.8% vs 12.3%; OR 1.43, 95% CI 0.88–2.35).The results showed that many smokers diagnosed with cancer believed that it was too late to quit smoking. Many participants claimed that overcoming cigarette cravings was extremely difficult, and therefore felt that the barriers to quitting outweighed the perceived benefits. Conclusions: It is crucial to proactively implement novel and effective smoking cessation interventions for smokers with cancer. Importantly, it will help to improve the physical well-being and health-related quality of life of smokers with cancer and protect the public, especially vulnerable groups such as women and children, from exposure to second-hand smoke. This will ultimately save more lives, protect the environment, and boost sustainable development. Clinical trial information: NCT01685723 .
Resolving disparities in access to cancer care in LMIC-positive learning using a 10-year-old model.
Authors: Dinesh Pendharkar, Chandramauli Tripathi, Ashok Kumar Nagar
Journal: Journal of Clinical Oncology (2024)

156 Background: Despite significant advances in cancer diagnosis and treatment, there are wide disparities in access to cancer care, more so in low- and middle-income countries. The problem is multifactorial, such as patient-related, health system-related, socio-cultural-related to language and literacy, and socio-cultural-related to beliefs and stigma. These disparities extend across the cancer continuum, from diagnosis to end-of-life care. It is imperative to address these disparities. Here we report 10-year experience from an innovative access delivery model in one go, comprehensively addressing many of these challenges. Methods: Learning from the WHO framework of health system strengthening, a model that affects the major contributors to health system strengthening was developed. These include government-owned health departments, district hospitals, and physicians. Various regulations strengthened each of these components. The regulations were issued to create systems in district hospitals, train an alternative oncology workforce, and make oncology drugs available in the periphery. This measure allowed cancer-care-related services to be feasible in the existing peripheral health system. Results: In 2014, one of the states in India decided to initiate cancer care services in government-run district hospitals. One physician and two nurses from every district hospital were trained to offer cancer-related services locally from diagnosis to end-of-life, including cancer chemotherapy, under the 24 x7 mentorship of a senior oncologist. To date, more than 250 physicians and 500 nurses have been trained in this field. The program has been extended to eight states and 198 districts, covering an area of over a million square kilometers and a population of over 380 million. Data from only one district alone showed that nearly 7000 new patients availed of services (average 700 per year) with more than 17000 sessions of chemotherapy (Table). Conclusions: The majority of the world, including LMICs, is dependent on the services provided by government-run health institutions. The empowerment of government health systems appears to be the single most important factor in improving access to cancer care. This model of cancer cere delivery has consistently proven its robustness, replicability, and scalability. This finding deserves consideration for further research and expansion to other countries. [Table: see text]
In-hospital outcome of patients hospitalized for leukemia with comorbid acute decompensated heart failure: An analysis of National Inpatient Sample (NIS).
Authors: Thanathip Suenghataiphorn, Phuuwadith Wattanachayakul, Narathorn Kulthamrongsri, Thitiphan Srikulmontri, Panat Yanpiset, Sakditad Saowapa
Journal: Journal of Clinical Oncology (2024)

173 Background: Recent evidence found increase incidence of heart failure in leukemia patients, influenced by various factors such as the underlying disease and medication usage. Nevertheless, there remains a scarcity of data regarding the in-hospital outcome for individuals admitted for leukemia with comorbid acute decompensated heart failure. Thus, we aim to examine the impact of heart failure on clinical outcomes in leukemia patients. Methods: We utilized the 2020 U.S. National Inpatient Sample (NIS) to investigate patients admitted for leukemia with concurrent diagnosis of heart failure, identified through ICD-10 CM codes. Adjusted odds ratios (aORs) for predefined outcomes were determined using multivariable logistic and linear regression model, adjusting for comorbidities. The primary outcome assessed was inpatient mortality, while secondary outcomes included complications related to various body systems. Results: We identified 43,955 patients with a primary discharge diagnosis of leukemia. The mean age was 54.5 years; 49.7% were female. Caucasians accounted for 66%, followed by African Americans (13%). Of these, 11.86% (5,220/43,955) had a concurrent diagnosis of heart failure. In a survey multivariable logistic and linear regression model adjusting for patient and hospital factors, comorbid acute decompensated heart failure was associated with higher in-hospital mortality (aOR 1.57, 95% CI: 1.2, 1.94, p &lt; 0.001), higher mean length of stay (Beta-coefficient 1.93; 95% CI: 0.65, 3.21, p = 0.003), mean total hospital cost (Beta-coefficient 9,472, 95% CI: 2,339, 16,604, p = 0.004), shock (aOR 2.41, 95% CI: 1.84, 3.15, p &lt; 0.001), sepsis (aOR 1.71, 95%CI: 1.38, 2.12, p &lt; 0.001), acute respiratory failure (aOR 2.37, 95% CI: 1.96, 2.87, p &lt; 0.001), and acute kidney injury (aOR 1.57, 95% CI: 1.32, 1.85, p &lt; 0.001). Conclusions: Our study revealed that hospitalized leukemia patients with concurrent heart failure experience higher risk of in-hospital mortality and various adverse in-hospital outcomes. Close monitoring of this factor during hospitalization is essential, and additional longitudinal research is warranted to fully understand this association.
Analysis of prognostic factors in uterine cervical malignancy treated with concurrent chemoradiation therapy: A retrospective study in two centers in Korea.
Authors: Seung-Mi Lee, Juhun Lee, Hyun Jung Lee, Seungho Song, Yujin Heo, Jieon Lee, Hee Jung Kim
Journal: Journal of Clinical Oncology (2024)

125 Background: Cervical cancer is prevalent in most developing countries, and immune checkpoint inhibitors are very expensive to be standard treatment in limited-resource conditions. In these circumstances, concurrent chemoradiation therapy (CCRT) remains a preferred treatment. This study aims to evaluate prognosis and identify prognostic markers in cervical cancer patients treated with CCRT in Korea. Methods: This retrospective study utilized data from two centers (KNUH and KNUCH) January 2012 to September 2023. Disease stage was determined based on the FIGO 2018 system, including patients between stages IIB to IIIC-2. PET/CT assessed lymph node status. All patients received CCRT as the first-line treatment with cisplatin (40 to 60 mg/m 2 ) chemotherapy and EBRT with or without ICR, guided by gynecologic radiation oncologist. Pelvic MRI or CT within 5 months after CCRT was used to evaluate radiosensitivity, including the size of the residual primary cervical tumor. The primary endpoint was 5-year disease-free survival (DFS), determined via systemic imaging studies like concurrent chest and abdomen CT or PET/CT. Median DFS was evaluated using Kaplan-Meier survival analysis. Prognostic factors were stratified and analyzed using Cox’s proportional hazard ratio regression. Multivariate analysis was conducted using only significant factors identified in the univariate analysis. Receiver operating characteristic curve and Youden’s index were used to determine the cutoff value. Results: Ninety-seven patients were enrolled. The median DFS within 5 years was not reached; mean DFS was 41.5 months (95% CI=36.2–46.8). Multivariate Cox’s proportional hazard regression identified two significant clinical factors for 5-year DFS; residual primary tumor size after CCRT and initial serum CA-125 level (p=0.001, p=0.007, respectively). The cutoff values were 1.85 cm for residual primary tumor size and 24.650 U/mL for CA-125 to predict the 5-year DFS rate (CR or NED vs. PR, SD, PD or recurrence). Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for residual tumor size (36.4%, 98.4%, 92.3%, 73.4%, respectively) and CA-125 (67.9%, 60.7%, 46.3%, and 79.1%, respectively). Conclusions: The size of the residual primary tumor or initial serum CA-125 level can be useful in predicting 5-year DFS rate after CCRT. [Table: see text]
Outcome analysis of autologous stem cell transplantation in refractory and relapsed Hodgkin lymphoma: Insights from a North African single-institution study.
Authors: Marouane Maaroufi, Soukaina Douma, Mohamed Rachid, Ilias Aajafir
Journal: Journal of Clinical Oncology (2024)

172 Background: The standard therapy for primary refractory or relapsed Hodgkin lymphoma (HL) involves the administration of high-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT). Nevertheless, several risk factors may influence survival outcomes. We assessed outcomes of patients in this setting who underwent HDC/ASCT by performing survival analysis and studying prognostic factors affecting survival. Methods: We conducted a single-institution retrospective analysis of patients with relapsed/refractory HL who received HDC/ASCT between January 2018 and December 2022. Patients’ status evaluation before ASCT was performed by Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) Scan and Computed Tomography (CT) Scan. The used conditioning regimen was BEAM (Carmustine, Etoposide, Cytarabine, and Melphalan). The primary endpoints were progression-free survival (PFS) and overall survival (OS). Survival analysis was performed using the Kaplan-Meier method, and survival differences between groups were assessed using the Log-Rank test. Results: Thirty-five patients diagnosed with relapsed/refractory HL were included in the study. Among them, 26 patients (74%) had refractory disease, while 9 patients (26%) relapsed following completion of first-line chemotherapy. All patients were treated with HDC/ASCT. Prior to ASCT, 30 patients underwent assessment using FDG-PET Scan, while CT Scan was employed for evaluation in 5 patients. Twenty-three patients (66%) were in complete remission, 8 patients (23%) were in partial remission, and 4 patients (11%) had progressive disease. With a median follow-up of 24.36 months after transplantation, 28 patients (80%) were in remission, 6 patients (17%) had disease progression, and one patients died of septic shock. The 2-year PFS and OS rates for the total population were 85.4% and 97.1%, respectively. Response to first-line chemotherapy did not have a substantial impact on prognosis, as evidenced by a 2-year PFS rate of 76.2% vs. 88.9% (p=0.88) and a 2-year OS rate of 100% vs. 96.2% (p=0.56) for patients with relapsed and refractory disease, respectively. The 2-year PFS and OS rates for patients receiving autograft during complete remission, partial response, and tumor progression were 93.8% vs. 87.5% vs. 50% (p=0.005), respectively; and 95.7% vs. 100% vs. 100%, respectively (p=0.77). Patients who had negative pre-transplant PET-Scans demonstrated a 2-year PFS rate of 92.9% vs. 64.8% for those with positive PET-scans (p=0.004). Conclusions: The findings of our study affirm the established practice of HDC/ASCT for individuals facing relapsed/refractory HL. The disease status at transplant and the pre-transplant PET-Scan status prove to be crucial factors in predicting patients’ outcomes, while response to first-line chemotherapy did not influence prognosis.
Unsupervised clustering of brain tumor leukocytes to reveal atypical lymphoid cell subsets.
Authors: Ismaïl Hermelo, Tuomo Virtanen, Iida Salonen, Reetta Nätkin, Sofia Keitaanniemi, Aliisa Tiihonen, Suvi Lehtipuro, Laura Kummola, Kristiina Nordfors, Hannu Haapasalo, Minna Rauhala, Juha Kesseli, Matti Nykter, Joonas Haapasalo, Kirsi Rautajoki
Journal: Journal of Clinical Oncology (2024)

25 Background: The brain tumor immune microenvironment (TiME) is characterised by suppression of tumor-infiltrating leukocytes. The lymphocyte niche activity is particularly downregulated within this TiME milieu. Methods: Here, using data-driven approaches in flow cytometry and RNA sequencing analysis, we aimed at dissecting leukocyte cell types infiltrating human brain tumor TiME. Results: Unsupervised clustering provided T lymphocyte subsets including double-negative (CD3 + CD4 - CD8 - ) T cells (DNT). Our DNT phenotype was validated with an independent dataset, suggesting DNT to be compatible with γδ T cell phenotype. In our cohort, myeloid immune cell frequencies were associated with malignancy type as previously reported, while a gliosarcoma notably presented unexpectedly high lymphocyte frequencies. Consistently, double-positive (CD4 + CD8 + ) T cells (DPT) had higher frequency in the gliosarcoma than other tumors. The flow cytometry results were supported by transcriptome patterns and the activity of immune-related genes in these tumors. Conclusions: Our findings feature the benefit of data-driven approaches for brain TiME lymphocyte analysis, and show that primary brain tumors can entail atypical lymphocyte subsets like DNTs and DPT cells. Unbiased lymphocyte characterisation can potentially outline novel targets for immune checkpoint blockade therapy.
Effect of iPSC-derived NK cells with site-specific integration of CAR19 and IL24 at the rDNA locus on anti-tumor activity and proliferation.
Authors: Desheng Liang, Yuxuan Zhang, Qingxin Shi, Qian Hu, Lingqian Wu
Journal: Journal of Clinical Oncology (2024)

175 Background: The generation of CAR-NK cells using induced pluripotent stem cells (iPSCs) has emerged as a paradigm for manufacturing off-the-shelf cell products for universal immunotherapy. However, enhancing the potency, safety and multi-actions of CAR-NK cells is still full of challenges. Methods: Interleukin 24 (IL24) and CD19-specific chimeric antigen receptor (CAR19) were site-specifically integrated at the ribosomal DNA (rDNA) locus in human iPSCs by using TALENickases. The engineered iPSCs were differentiated into NK (CAR-iNK) cells by adopting a 38-day differentiation protocol followed by expansion using magnetic beads in vitro. Results: Compared with the CAR-iNK cells, IL24 armored CAR-iNK (CAR19-IL24-iNK) cells showed higher cytotoxic capacity and amplification ability in vitro. Meanwhile, CAR19-IL24-iNK cells inhibited tumor progression more effectively and exhibited better survival without significant side effects in the B-ALL (Nalm-6(Luc1))-bearing mouse model. Interestingly, RNA-sequencing analysis suggested that IL24 may enhance iNK cell function by attracting neutrophils and upregulating FAS and TNFSF10-related genes while exerting a direct effect on tumor cells. Conclusions: This study encourages the exploration of IL24 and other molecules to enhance antitumor properties of CAR-NK cells, suggesting a novel strategy to modulate tumor microenvironment while attacking tumor cells with the potential of promising off-the-shelf immunotherapy.
Dioxins vs. PFAS: Science and Policy Challenges
Authors: Alex J. George, Linda S. Birnbaum
Journal: Environmental Health Perspectives (2024)

Dioxin-like chemicals are a group of ubiquitous environmental toxicants that received intense attention in the last two decades of the 20th century. Through extensive mechanistic research and validation, the global community has agreed upon a regulatory strategy for these chemicals that centers on their common additive activation of a single receptor. Applying these regulations has led to decreased exposure in most populations studied. As dioxin-like chemicals moved out of the limelight, research and media attention has turned to other concerning contaminants, including per- and polyfluoroalkyl substances (PFAS). During the 20th century, PFAS were also being quietly emitted into the environment, but only in the last 20 years have we realized the serious threat they pose to health. There is active debate about how to appropriately classify and regulate the thousands of known PFAS and finding a solution for these "forever chemicals" is of the utmost urgency.