bluuebunny/crossref_metadata_2025 huggingface dataset:
Symptom burden in adult survivors of allogeneic hematopoietic stem cell transplantation.
Authors: Ellithi Moataz , Trinh Jonathan , Nilles Jonathan , Gundabolu Krishna , Haddadin Michael , Maness Lori J. , Wichman Christopher S. , Bhatt Vijaya Raj
Published: June 2024

6557

Background: Progress in allogeneic hematopoietic cell transplantation (HCT) and supportive care has significantly improved transplant outcomes and expanded the number of HCT survivors. A growing responsibility exists to address long-term morbidity and symptom burden. We sought to investigate symptom burden in adult survivors of HCT using a set of validated tools. Methods: We analyzed adults aged 19 years or older with hematologic malignancies who were treated with allogenic HCT at our institution from June 2018 to November 2022. Patients required at least one visit to our survivorship clinic for inclusion. We assessed symptom burden using the National Comprehensive Cancer Network (NCCN) Survivorship Assessment Questionnaire, which is a 25-question survey designed to assesses symptoms related to the following domains: cardiac, mood, cognition, fatigue, lymphedema, hormonal, pain, sexual dysfunction, and sleep. The short physical performance battery (SPPB) and short blessed test were used to assess physical function and conduct cognitive screen, respectively. Finally, we compared scores between patients <60 and ≥60 years old to examine an association between age and post-transplant symptoms. Results: A total of 152 patients have a median age of 61 years (range 21-76); 59.2% were males, and 28.5% had a BMI ≥30. Median Hematopoietic Cell Transplantation-specific Comorbidity Index was 3. The most common indication for transplant was acute myeloid leukemia (48.0%), and the most common donor type was matched unrelated (57.2%). The median time from transplant to the first survivorship clinic visit was 99 days. The most common symptom domains affected, according to the NCCN questionnaire results, were fatigue (50.7%), sleep (45.3%), and cognition (42.0%) whereas the least affected domains were pain (29.5%), cardiac (26.2%), and sexual (19.4%). When we stratified patients by <60 years old and ≥60 years old, we saw similar rates of reported symptoms, particularly regarding sleep disorder (44.3% vs. 45.7%, respectively), mood disturbance (31.4% vs. 34.1%, respectively), and sexual dysfunction (17.9% vs. 20.5%, respectively). Older patients, however, had higher rates of physical impairment according to SPPB scores (50.0% vs. 15.7%, OR = 5.4 [95% CI = 2.2-14.3]). Blessed test showed impaired cognitive screen in 7.2% without a significant difference based on age. Conclusions: Adult survivors of allogeneic HCT at 3-month post-transplant commonly suffer from symptoms across a variety of domains, especially pertaining to fatigue, sleep, and cognition. These symptoms affect both younger and older patients, although older patients are more likely to have physical impairment. The NCCN Survivorship Assessment Questionnaire captures a number of symptoms related to quality of life and can be more widely utilized as a tool to evaluate survivorship symptoms in patients who undergo HCT.
Neoadjuvant chemoimmunotherapy in patients with limited-stage small cell lung cancer: A retrospective study.
Authors: Wang Ting , Huang Kai LI , Pu Dan , Mei Ting , Fan Ming Yu , Tian Long , Li Lu , Zhou Qing Hua
Published: June 2024

e20002

Background: The addition of immune checkpoint inhibitors to chemotherapy significantly improves survival in extensive-stage small cell lung cancer (SCLC) and represents a promising advance in this field. However, the clinical benefit of the implementation of immunotherapy in the first-line setting for limited-stage SCLC (LS-SCLC) remains to be proven. Thus, we conducted a retrospective study to explore the efficacy of neoadjuvant chemoimmunotherapy as a first-line treatment for LS-SCLC. Methods: A retrospective study of patients with LS-SCLC who were treated with neoadjuvant PD-L1/PD-1 inhibitor combined with platinum-based chemotherapy followed by surgery between February 2020 and September 2023 was conducted. Clinical characteristics, R0 resection rate, pathologic complete response (pCR), major pathologic response (MPR), downstaging rate and disease-free survival (DFS) were evaluated. Results: As of September 30, 2023, all 21 patients (stage IIB, n = 4; stage IIIA, n = 9; stage IIIB, n = 8) received 2 to 6 cycles of neoadjuvant chemoimmunotherapy (Table 1). Nine (42.9%) patients achieved pCR and 10 (47.6%) presented an MPR (Table 2). Moreover, the R0 resection rate in total and stage III patients were 95.2% (20/21) and 94.1% (16/17), respectively. After a median follow-up of 11.2 months (range: 2.6-24.2), only two patients relapsed and the median DFS was not reached due to insufficient events. Conclusions: Neoadjuvant immune checkpoint inhibitors combined with chemotherapy demonstrated promising efficacy and feasibility, and are a potential strategy for the management of LS-SCLC. Further prospective clinical trials are necessary to clearly define the benefit of neoadjuvant chemoimmunotherapy and optimize LS-SCLC treatment. [Table: see text][Table: see text]
Sex-based disparities in patients with lung cancer undergoing lobectomy via robotic-assisted thoracoscopic surgery.
Authors: Gadhiya Dhruvkumar , Adla Jala Saisree Reddy , Sakthivel Hemamalini , Dhaliwal Kanwar Bir Singh , Ramphul Kamleshun , Sharma Shivani
Published: June 2024

e20005

Background: The 2023 report from the World Health Organization(WHO) ranked lung cancer (LC) as the top cause of cancer-related fatalities worldwide. Recently, minimally invasive procedures such as robotic-assisted thoracoscopic surgery (RATS) have been introduced as part of the treatment of some LC cases. Our study aims to bridge the understanding of potential sex-based disparities among LC patients undergoing lobectomy via RATS. Methods: We analyzed the 2016-2020 National Inpatient Sample (NIS) for adult lung cancer(malignant or carcinoma in situ) patients with a principal procedure code of lobectomy with RATS. Cases with underlying mycoses, mycobacterial infection, and pulmonary abscesses were excluded based on recommendations from prior studies. Multivariate regression models helped evaluate sex-based differences in several complications. Results: An estimated 26385 lung cancer patients underwent lobectomy via RATS, consisting of 56.68% females (14955 cases) and 43.32% males (11430 cases). Age differences were noted as females were younger (mean age 67.80 years vs. 69.14 years, p < 0.01). We also found that females were less likely to report several complications, such as acute kidney injury (AKI) (3% vs. 6.6%, aOR 0.538, p < 0.001), pneumonia (2.8% vs. 4.3%, aOR 0.725, p < 0.001), post-procedural air leak (9.2% vs. 11.2%, aOR 0.797, p < 0.001), post-procedural cardiac arrest (0.6 % vs. 1.6%, aOR 0.349, p < 0.001), pulmonary embolism (0.2% vs. 0.5%, aOR 0.345, p < 0.001), deep vein thrombosis (DVT)(1.5% vs. 2.2%, aOR 0.742, p: 0.003), atrial fibrillation (AF)(13% vs 21.7%, aOR 0.564, p < 0.001), acute myocardial infarction (AMI) (0.2% vs. 0.5%, aOR 0.58, p:0.027), and death (0.3% vs. 0.9%, aOR 0.505, p < 0.001). Notably, females were more likely to have an open procedure conversion (0.2% vs 0.1%, aOR 2.235, p:0.017). However, there is no significant difference between the two sexes regarding post-procedural pneumothorax and respiratory failure, atelectasis, supraventricular tachycardia, and events of acute ischemic stroke. Conclusions: Our most recent analysis confirms that among LC patients undergoing lobectomy via RATS, males were more prone to several complications than females. However, we also found that females were more likely to necessitate an open procedure conversion. We, therefore, advocate for further research to enhance our understanding of such disparities and strategies to address them effectively.
Multiple sclerosis and lung cancer: A single cancer center experience in Philadelphia.
Authors: Palecki Julia , Bernstein Andrew , Melby Garrett , Tucker Matthew , Begun Zoe , Zhan Tingting , Micaily Ida
Published: June 2024

e20027

Background: The association between multiple sclerosis (MS) and lung cancer remains poorly understood. This retrospective, single center study aims to characterize the clinical features and outcomes of lung cancer in patients with MS, shedding light on this unique patient cohort characterized by immune dysregulation and significant immunosuppressive therapy. Methods: This retrospective study analyzed 40 MS patients diagnosed with lung cancer at Sidney Kimmel Cancer Center in Philadelphia, PA between 1/1/2016 and 7/1/2023. Clinical data including patient demographics, MS treatments, cancer diagnosis details (date, stage, histology), molecular and fusion data, PD-L1 status, and patient mortality dates were recorded and analyzed. Results: In our cohort of 40 patients, 28 (70.0%) patients were female, with 28 (70.0%) identifying as White and 7 (17.5%) as Black. NSCLC was seen in 37 patients (26 adenocarcinoma, 5 squamous cell carcinoma), while 3 had SCLC. Among the 33 patients with available MS treatment data, 9 (26.5%) received steroids, and 15 (44.1%) received biologic therapy. The average age at lung cancer diagnosis was 62.8 (±10.9) years, with 18 out of 40 patients (45.0%) diagnosed with stage I disease. Advanced stages were found in 22 patients (55.0%) at diagnosis: 2 (5.0%) with stage II, 1 (2.5%) with stage III, and 19 (47.5%) with stage IV disease. Among 15 patients with molecular testing, BRAF mutation was found in 1 (6.7%), EGFR mutation in 4 (26.7%), and KRAS mutation in 2 (13.3%). One subject demonstrated an ALK fusion (7.1%). PD-L1 testing was recorded in 13 patients: 3 (23.1%) had 0%, 1 (7.7%) had 1%, 5 (38.5%) had 1-49%, and 4 (30.8%) had > 50% PD-L1 expression. The average overall survival was 2.4 years (95% CI: 1.4-8.1 years). Conclusions: In this cohort, MS patients with lung cancer exhibited targetable mutations, such as EGFR mutations and high PD-L1 expression rates. While the use of immunotherapy in lung cancer with concurrent MS has been limited, our data suggests the importance of molecular profiling in all lung cancer patients. We consider that these patients received significant exposure to immunosuppressive therapies for MS, potentially impacting immune surveillance and lung cancer development. Despite this, nearly half of the cohort had Stage 1 lung cancer and showed favorable overall survival rates. Our cohort study suggests a need to investigate the relationship between MS and lung cancer further.
Potential role and prognostic value of Globo-H in lung cancer.
Authors: Kuo Tzer-Min , Lai Jiann-Shiun , Hsu Hui-Ting , Wei Cheng-Yen , Lai Ming-Tain
Published: June 2024

e20037

Background: Globo-H (GH), a globo-series carbohydrate antigen highly expressed on multiple epithelial cancers, is a promising target for cancer immunotherapy. Clinical trials have been conducted to evaluate the efficacy of anti-GH vaccine Adagloxad Simolenin/OBI-821 (in Ph 3) and OBI-833/OBI-821 (in Ph 2) in cancer patients. Epidermal growth factor receptor (EGFR) mutations are well known as a frequent class of driver mutations in lung cancer (LC), which are responsible for tyrosine kinase inhibitors. Besides high expression in cancer cells, GH has been implicated in regulation of EGFR signaling pathway. Knockdown of key enzyme involved in GH biosynthesis β1,3-galactosyltransferase V (β3GalT5) induces apoptosis through disruption of EGFR-related signaling protein complex. In addition, GH is reported to associate the EGFR mutant in LC patients. This study aims to further investigate the potential role of GH in LC. Methods: Clinical study: The level of GH expression was evaluated by immunohistochemistry (IHC) using H-score in clinical samples from 141 patients with lung adenocarcinoma. In vitro study: FACS and Western blotting methods were used to measure the levels of total EGFR, phospho-EGFRs or GH in LC cell lines. Microwestern protein array (MWA) analysis was performed in LC NCI-H1975 cells. Results: Clinical study: Positive GH expression (H score≥1; 18.4%) was significantly associated with poor differentiation grade (p = 0.044) in all samples and disease specific survival in patients with metastasis and stage 4 LC (p = 0.033). In vitro study: Inhibition of EGFR by an EGFR-specific shRNA resulted in a decrease of GH expression in LC cells while overexpression of EGFR resulted in an increase of GH levels. β3GalT5 knockout cells and anti-GH-antibody-treated cells showed a reduction of cell proliferation as well as the total level of EGFR and phosphor-EGFRs expression, which is consistent with the results from previous studies. MWA analysis on LC cells with β3GalT5 knockout, GH ceramide-treated β3GalT5 knockout cells and anti-GH Ab-treated LC cells indicated a positive correlation between the level of GH and EGFR-related signaling proteins including phosphor-JNK, phosphor-c-Jun, phosphor-PP2A, phosphor-PP2A, phosphor-AKT, and Cyclin D1 proteins. In addition, JNK signaling inhibitor partially reduced GH expression in NCI-H1975 cells. These results revealed the mechanistic link between GH regulation and tumor promoting signals in LC. Conclusions: GH expression was associated with the worse survival of LC patients in clinical setting. In addition, the level of GH is positively correlated with levels of EGFR and EGFR-related signaling proteins in vitro. Expression of GH can induce the expression of EGFR and vice versa in LC cells. Furthermore, EGFR downstream JNK signaling pathway might involve in GH regulation by EGFR. Taken together, GH-targeting therapy has a potential application for the treatment of LC patients.
Treating lung cancer in resource limited setting: Retrospective study from Armenia.
Authors: Mailyan Mariam , Zohrabyan Davit , Safaryan Liana , Harutyunyan Lilit , Avagyan Armen , Harutyunyan Martin , Sargsyan Amalya , Karapetyan Nune , Rushanyan Marine , Mkrtchyan Gohar , Avinyan Anna , Sargsyan Mariam , Galoyan Arevik , Kostanyan Julia , Khachatryan Mariam , Baloyan Elen , Bardakhchyan Samvel
Published: June 2024

e20055

Background: Lung cancer (LC) is second most common cancer by incidence in Armenia. Every year approximately 800-900 new cases are diagnosed, from all cases 55.5% are in the 4th stage. Methods: We have collected data from three oncology centers in Armenia: Yeolyan Hematology and Oncology Center, Mikaelyan Institute of Surgery, and Muratsan Hospital Complex of Yerevan State Medical University. In this retrospective hospital-based study the data of patients with LC who were treated at these three centers during the 01 Oct 2009 - 31 Dec 2023 period was collected․ Results: Four hundred and eighty-nine LC patients were involved in the final analysis. Male to female ratio was 6:1. From the all patients 10.6% were diagnosed at age ≤ 50, 79,6% of patients 50-70, and 9.6% ≥ 70 years. In 71.6% of all cases, LC was diagnosed in current or former smokers. Only 3% of patients were diagnosed in stage I, 9.8% in stage II, 44.8% in stage III, 41.1% in stage IV, and for 1.2% of patients' stage was unknown. From all cases 74% of patients had non small cell lung cancer (NSCLC), 22.7% small cell lung cancer (SCLC) and 3.3% had other histological types of lung cancer. Of all patients 63% are dead. The median overall survival (mOS) for all stages was 21 months for the entire cohort. Median OS was not reached for stage I ( > 100 months), was 61 months for stage II, 23 months for stage III, and 13 months for stage IV (p < 0,001). ALK mutation was checked in 22.7%, EGFR in 22%,ROS in 14.1%, KRAS in 11.2%, BRAF in 9.8% and of all patients. From all checked AKL was positive in 1.8%, EGFR in 19.4%, ROS in 2.8%, KRAS in 21.8%, BRAF in 8,3% and of cases. For patients with stage IV lung cancer (41.1%), we found a significant difference in mOS in those who received first line immunotherapy in combination with chemotherapy (19,4%) compared to those who received only chemotherapy (74.1%) (mOS: 24 months vs 11 months accordingly, p = 0.014). For stage I-III LC patients, those who received systematic therapy with cisplatin showed better overall survival than those who received systemic therapy with carboplatin (mOS 31 vs 25 months, p = 0.01), but for stage IV LC patients survival difference was not found (mOS 15 vs 12 months, p = 0.24). Conclusions: In Armenia, lung cancer is mostly diagnosed in the advanced stage where overall survival is approximately one year. In our study population, those who received immunotherapy in combination with chemotherapy showed doubled mOS, compared with only chemotherapy. In the nonmetastatic group, chemotherapy with cisplatin showed a significant increase in mOS compared with carboplatin.
Effect of novel polygenetic variant of HUNT lung cancer model on lung cancer risk assessment over clinical model among light smokers (average <9 pack-years).
Authors: Nguyen Olav Toai Duc , Fotopoulos Yannis , Nøst Therese Haugdahl , Markaki Maria , Lagani Vincenzo , Tsamardinos Ioannis , Røe Oluf Dimitri D.
Published: June 2024

e20066

Background: As lung cancer incidence and mortality increase, methods of early diagnosis are needed to increase survival. The validated HUNT Lung Cancer Model (HUNT LCM) predicts individual 6-year risk of lung cancer in ever smokers with an AUC of 0.87 based on eight clinical variables: sex, age, BMI, pack-years, smoking intensity number of cigarettes per day, quit time, daily cough, and daily indoors smoke exposure. We aimed to explore whether the performance of the HUNT model can be improved by adding genetic information, and in what group of ever smokers these differences in performance emerges. Methods: Based on the eight clinical variables of the HUNT LCM and 22 single nucleotide polymorphisms (SNPs) previously identified in the literature as highly associated with lung cancer risk, the novel lung cancer risk prediction model HUNT Lung-SNP was developed. Clinical and genetical data of ever-smokers from the HUNT2 population study (n = 30746, median follow-up 15.26 years) where 160 individuals were diagnosed with lung cancer within six years were used for the model fitting. External validation was performed in another population-based cohort, the Tromsø Study (n = 2663) where 39 were diagnosed with lung cancer within 6 years. Results: The integrated discrimination improvement index (IDI) between the HUNT Lung-SNP and the HUNT LCM shows that the HUNT Lung-SNP significantly improve the LC risk stratification within six years with an IDI of 0.019 (95% CI 0.015-0.025), p < 0·001 and of 0.013 (95% CI 0.008-0.018), p < 0·001 in the HUNT2 and Tromsø cohorts, respectively. Of the cases, 21/160 (13%) and 10/39 (25%) in the HUNT and Tromsø cohort respectively, were low risk by the HUNT LCM but high risk by the HUNT Lung-SNP model. The main difference in characteristics among cases predicted by the HUNT Lung-SNP model, but missed by the HUNT LCM, was the average number of pack-years: 8.22 vs. 29.8 (p < 0.001) in HUNT2 and 7.7 vs. 33.7 (p < 0.001) in Tromsø cohort. Conclusions: A genetic approach combined with clinical variables of the HUNT LCM can improve the lung cancer risk prediction significantly by increasing the sensitivity among light smokers. Thus, we identified a high-risk population in two independent cohorts that would not be eligible for screening by clinical cutoffs nor with a clinical risk prediction model. This novel HUNT Lung-SNP needs further validation in other populations to evaluate its clinical utility.
Neoadjuvant immuno-chemotherapy in resectable non-small cell lung cancer: A retrospective cohort study.
Authors: Verma Saurav , Vincent Mark David , Black Morgan , Nayak Rahul , Cecchini Matthew , Malthaner Richard , Raphael Jacques , Inculet Richard , Fortin Dalilah , Blanchette Philip , Kuruvilla Sara , Qiabi Mehdi , Younus Jawaid , Breadner Daniel Adam
Published: June 2024

e20077

Background: Neoadjuvant (NA) nivolumab-chemotherapy (nivo-chemo) has shown an improved survival and pathological complete response (pCR) rate, vs chemo alone, in early-stage, resectable non-small cell lung cancer (NSCLC). Nevertheless, there is a paucity of real-world data. Methods: We performed a real-world, retrospective analysis of outcomes and toxicities in patients with resectable NSCLC (stage IB-IIIA; EGFR/ALK alterations excluded) treated with three cycles of NA nivo-chemo followed by surgery at a single, tertiary-level Canadian cancer centre from September 2022 to September 2023. Results: Fifteen patients were treated with NA nivo-chemo. The median age was 70 years (range, 58 to 78) and 66% were males. 20% (n-3) and 40% (n-6) had N1 and N2 nodes, respectively. All patients completed three cycles of NA nivo-chemo. Objective response rate was 73% (n-11); including 1 complete response. Progression was noted in two patients (the CT predated initiation of treatment by more than 8 weeks in these patients). The median time to surgery was 10.6 weeks (range, 6-17.5). 80% patients (n-12) had a surgery (1 pneumonectomy, 11 lobectomies); and of these, 83% (n-10) are on surveillance while two patients had an event (death or progression). All (n-11) had R0 resection except one. 33% patients (n-5) had a pCR, including two with stage IIIA disease (PDL1 TPS < 1% in three patients, PDL1 TPS ≥ 50% in two patients). 60% patients were started at a reduced chemo dose in cycle 1. 25% patients required further dose reduction. Grade 3 or 4 toxicities were seen in 25% patients (n-4) (neutropenia (n-2), febrile neutropenia (n-1) and pneumonitis (n-1)). Surgical complications were seen in 33% patients (n-5), including death in one patient due to postoperative intrathoracic bleed. Conclusions: NA nivo-chemo in resectable NSCLC is safe and associated with improved pCR rate. A few patients may progress on NA treatment or have a grade 3-5 toxicity precluding curative surgery. Hence, individualized informed decisions should be made. There is an unmet need of biomarkers/models that can predict pCR/toxicity for better patient selection. [Table: see text]
Factors associated with early-stage lung cancer diagnosis (ESLCD) in Brazil, 2013-2019: A multivariable analysis.
Authors: Emmerick Isabel M , Rodrigues Campos Mônica , Castanheira Debora , Sequeira Valerio Tayná , Vinhal Faria Lara , Muzy Jéssica , Marques Aline , Arueira Luisa , Sobreira da Silva Mario Jorge
Published: June 2024

e20091

Background: Lung cancer has the highest mortality rate among the leading deadly cancers worldwide. Despite improvements in tobacco cessation and treatment over the years, disparities in access to care, timely diagnosis, and proper treatment remain prevalent. This study aims to identify the factors associated (FA) with Early-Stage Lung Cancer Diagnosis (ESLCD) in Brazil. Methods: This retrospective cohort study includes individuals diagnosed with lung cancer from January 2013 to December 2019, registered in the Brazilian hospital-based Cancer Registry (HBCR). Descriptive and bivariate analysis was performed, and T-tests and Chi-square were used to compare early vs late-stage groups. Multivariable backward stepwise logistic regression identified FA with ESLCD at a 95% confidence interval (CI). Results: The study was conducted with data on 86,558 individuals registered in the HBCR; 56.6% were men, 64 years old on average, and 54.8% were white. We found a high percentage of patients without education information (23.9%), and 70% had completed high school. As for behavioral characteristics, only 20% of the patients had never smoked; the others were current smokers (40%) or former smokers (40%). Almost half of the patients were from the Southeast region of Brazil (44.6%), 27% from the South, 19.9% from the Northeast, 3.9% from the North and 3.9% from the Midwest. The vast majority of the individuals were diagnosed at a late stage (85.6%), while 14.4% were ESLCD. In the bivariate analysis, being less than 65 years old, being female, white, never smoking, having a college degree, and living in the south or southeast regions were associated with ESLCD. In the final multivariable model the Factors Associated with ESLCD were having less than 65 years (OR=1.28 [95% CI: 1.22-1.34]), of the female gender (OR=1.26 [95% CI: 1.22-1.32]), having education greater than a college degree (OR=1.49 [95% CI: 1.38-1.61]), and living on the southeast (OR=1.22 [95% CI: 1.15-1.30]); and in the south region (OR=1.21 [95% CI: 1.18-1.32]); which are the wealthiest regions in the country. Conclusions: The education level was the most decisive factor associated with ESLCD. Geographic location played an important role in ESLCD, indicating issues related to wealth and access to health services. Improving access to lung cancer diagnosis, especially for vulnerable populations, can reduce disparities in the rates of early-stage diagnosis and improve overall survival. [Table: see text]
Exploring the role of pembrolizumab in mesothelioma: A single-arm analysis of available data.
Authors: Naqvi Syed Mujtaba Ali , Shafique Nouman , Muhibullah - , Kaur Navneet , Ahmed Jawad , Zain Sarmad , Kunwar Digbijay , Ur Rehman Atta , Nawaz Hassan , Haider Ali , Qadeer Abdul , Bajwa Shammas , Javeed Zainab , Ghaffar Ali , Tariq Sheraz Ahmad , Ahmed Muhammad Ihsan , Ehsan Amna , Shafiq Iqra , Iqbal Abdul Ghani , Safi Adnan
Published: June 2024

e20097

Background: Malignant Mesothelioma (MMe) is a neoplasm of mesothelium and has a very poor survival rate. Over half the patients of MMe express programmed death-ligand 1 (PD-L1) which binds to the PD-1 receptor on T-cells which in turn suppresses their ability to kill tumors. Pembrolizumab is a PD-1 inhibitor antibody and it has shown efficacy in combating MMe. Our analysis aims to summarize data related to objective response rates (ORR) and adverse effects of Pembrolizumab therapy in MMe patients. Methods: We conducted an online search through PubMed, Cochrane, and Clinicaltrials.gov databases from their inception till January 25, 2024, to identify studies that reported the use of Pembrolizumab in patients with MMe. Data were extracted and analyzed and proportions with their 95% confidence interval have been reported. Onlinemeta v1.0 was used for all analyses. Results: A total of six studies with 549 patients reported the use of Pembrolizumab in patients with MMe. ORR was observed in 36.2% (32.3% - 40.4%; p < 0.01) of patients receiving Pembrolizumab while 20.4% (17.2%- 24.0%; p < 0.01) of patients experienced adverse effects of the therapy. Median survival ranged from 9.5 to 17.3 months whereas progression-free survival ranged from 2.5 to 7.1 months in patients. Conclusions: Pembrolizumab has an ORR and safety profile comparable to other immunotherapies. Further studies are needed to extensively study the drug and its effects in detail in patients with MMe. [Table: see text]
A randomized phase II trial of adjuvant pembrolizumab versus observation following curative resection for stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm: Big Ten Cancer Research Consortium BTCRC-LUN18-153.
Authors: Durm Greg Andrew , Furqan Muhammad , Hall Richard Delmar , Chiappori Alberto , Ma Patrick C. , Feldman Lawrence Eric , Kulkarni Amit , Haigentz Missak , Ganti Apar Kishor , Owen Dwight Hall , Sanborn Rachel E. , Hanna Nasser H.
Published: June 2024

TPS8118

Background: Each year, approximately 35,000 patients are diagnosed with stage I lung cancer in the United States. Despite early detection, the 5-year overall survival for this population remains disappointing, ranging between 73-86% with recurrence rates from 18-38%. The current standard of care for stage I NSCLC is surgery alone followed by observation as prior trials of adjuvant chemotherapy in this subgroup have failed to show benefit. More modern therapies such as programmed death-1 (PD-1) inhibitors have not been evaluated in the stage I setting but have demonstrated significant improvements in pathologic complete response, event free survival, and overall survival when added to chemotherapy for patients with fully resected stage II and III disease. The use of PD-(L)1 inhibition has also demonstrated clinically and statistically significant improvements in OS in both unresectable stage III NSCLC following chemoradiation and in the metastatic setting. Given the activity of PD-(L)1 inhibition in nearly every other subset of NSCLC patients, we aimed to evaluate this therapy following resection in stage I NSCLC patients. Methods: This study is a randomized phase II multicenter trial of adjuvant Pembrolizumab versus observation alone following complete resection of stage I NSCLC with tumors between 1-4cm. The trial randomizes patients 1:1 to either Pembrolizumab 400mg IV every 6 weeks for up to 9 cycles or observation alone. Patients are stratified by PD-L1 score (PD-L1 ≥50% vs. < 50%) and tumor size (1-2cm vs. > 2-4cm), and they undergo repeat CT imaging every 12 weeks. The study is being conducted through the Big Ten Cancer Research Consortium, and there are currently 11 sites open to accrual with one additional site pending activation. The primary endpoint is disease free survival with secondary endpoints including OS, DFS at multiple timepoints (1-, 2-, and 3-years), and safety. The trial initially opened to accrual at the lead site, Indiana University, in May 2020, and enrollment is currently at 95 patients with a planned enrollment of 244. (NCT04317534) Clinical trial information: NCT04317534 .
Neoadjuvant immunotherapy in sarcomatoid mesothelioma (Alliance A082101).
Authors: Mansfield Aaron Scott , Wang Xiaofei F. , Wigle Dennis A. , Watt Colleen , Kelley Kathryn , Masters Gregory A. , Berg Stephanie A. , Kozono David E. , Stinchcombe Tom
Published: June 2024

TPS8125

Background: Sarcomatoid mesothelioma is the most aggressive form of pleural mesothelioma and is associated with the worst prognosis of the histologic variants of this disease. In the Checkmate 743 clinical trial the patients with sarcomatoid mesothelioma who received ipilimumab and nivolumab had survival outcomes that were similar to those of patients with epithelioid mesothelioma. In comparison, the patients with sarcomatoid mesothelioma who received chemotherapy had the worst outcomes in this trial, highlighting the known limited efficacy of chemotherapy against this histologic variant. Checkmate 743 demonstrated that ipilimumab and nivolumab is a new standard of care for non-epithelioid mesothelioma. Surgery typically has not been offered to this group of patients given their historically poor outcomes. With the significant survival gains seen patients with sarcomatoid mesothelioma treated with immunotherapy, we hypothesized that surgery may extend the benefits seen with immunotherapy. Methods: Alliance for Clinical Trials in Oncology A082101 is a prospective, phase 2 nonrandomized clinical trial for patients with sarcomatoid mesothelioma. The co-primary objectives are to determine the percentage of patients with potentially resectable sarcomatoid mesothelioma able to proceed with surgery after neoadjuvant ipilimumab and nivolumab, and the progression-free survival (PFS) at 12 months (12-month PFS) after the initiation of ipilimumab and nivolumab. For sample size determination, we assumed that if the true rate of surgery is 75% or greater, it would indicate that neoadjuvant immunotherapy is feasible to be given prior to surgery. On the other hand, if the true rate of surgery is 50% or less it would indicate that neoadjuvant immunotherapy is not worthy of further investigation. Twenty-six (26) eligible patients will be needed to receive neoadjuvant immunotherapy. If 16 or fewer of the 26 eligible patients proceed to surgery, it will be concluded that the experimental therapy is not worthy of further investigation. Otherwise, it will be concluded that the experimental therapy is worthy of further investigation. Safety monitoring will be done through a 6-week run-in for the first 10 patients to assess for pre-operative and post-operative toxicities and complications. Sequential boundaries will be used to monitor severe toxicity and complication rates. Accrual will be halted if excessive numbers of severe toxicity and complications in pre-operative and post-operative phases are seen. The accrual and safety data will be summarized in reports for semiannual reviews by Alliance Data and Safety Monitoring Board. Tumor and blood-based biomarkers will be included as exploratory biomarkers. Support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . Clinical trial information: NCT05647265 .
DAREON-8: A phase I, open-label, dose escalation/expansion trial of the DLL3-targeting T-cell engager, BI 764532, combined with first-line (1L) standard of care (platinum, etoposide, and anti-PD-L1 antibody) in patients (pts) with extensive-stage small cell lung carcinoma (ES-SCLC).
Authors: Peters Solange , Champiat Stephane , Yoshida Tatsuya , Dorleacq Nicolas , Ma Yiyuan , Geng Lijiang , Leal Ticiana
Published: June 2024

TPS8127

Background: Platinum/etoposide chemotherapy in combination with anti-PD-L1 antibodies is the 1L standard of care (SoC) for pts with ES-SCLC. However, most pts relapse and subsequent treatment (Tx) options are limited. Hence, outcomes are poor with a 5-year survival rate of < 7%. Delta-like ligand 3 (DLL3) is a Notch receptor ligand expressed on tumor cells but not on normal cells. BI 764532 is an IgG-like T-cell engager (TcE) that binds simultaneously to CD3 on T-cells and DLL3 on tumor cells, resulting in selective, T-cell mediated tumor cell lysis. An ongoing Phase I trial of BI 764532 (NCT04429087) in pts with pretreated DLL3-positive tumors demonstrated an overall response rate of 28%, a disease control rate of 54%, and a manageable safety profile. Here, we describe DAREON-8 (NCT06077500), a Phase I open-label dose escalation/expansion trial of BI 764532 plus SoC as a 1L Tx for pts with ES-SCLC. Methods: Pts will be recruited from ~20 sites into this two-part trial. In Part A (dose escalation), ~30 pts will receive escalating doses of intravenous BI 764532 (target dose after step-in dosing) plus carboplatin/etoposide + atezolizumab. Dose escalation will be guided by a Bayesian logistic regression model with overdose control. Tx with BI 764532 will continue for 36 months, withdrawal or progressive disease (PD). The primary objective is to determine the maximum tolerated dose (MTD) of BI 764532 and/or the recommended dose for expansion (RDE)/recommended Phase II dose (RP2D) for BI 764532 plus SoC. Safety, efficacy and/or PK assessments will guide the RDE/RP2D. The primary endpoint focuses on the occurrence of dose-limiting toxicities (DLTs) in the MTD evaluation period. In Part B (dose expansion), ~30 pts will receive BI 764532 at the RDE/RP2D determined in Part A for 36 months, withdrawal or PD and platinum/etoposide + either atezolizumab or durvalumab. The primary objective of Part B is to confirm the safety and tolerability of BI 764532 at the RDE/RP2D plus SoC Tx as measured by the occurrence of DLTs during the on-Tx period. Key inclusion criteria include confirmed ES-SCLC; no prior systemic treatment for ES-SCLC; and eligibility to receive platinum/etoposide chemotherapy + anti-PD-L1 antibodies. Key exclusion criteria include previous Tx with DLL3-targeting TcEs; persistent, unresolved toxicity from previous Txs; immunodeficiency, or systemic steroid or other immunosuppressive therapy ≤7 days prior to first dose of BI 764532; and significant cardio/cerebrovascular disease. Clinical trial information: NCT06077500 .
Epicardial Adipose Tissue Is Associated With Geometry Alteration and Diastolic Dysfunction in Prediabetic Cardiomyopathy
Authors: Hsu Jung-Chi , Huang Kuan-Chih , Lin Ting-Tse , Lee Jen-Kuang , Su Mao-Yuan M , Juang Jyh-Ming Jimmy , Wu Cho-Kai , Lin Lian-Yu
Published: June 2024

Background

Diastolic dysfunction and alterations in cardiac geometry are early indicators of diabetic cardiomyopathy. However, the association between cardiac changes across the glucose continuum and the contribution of epicardial adipose tissue (EAT) to these changes has not yet been investigated.

Purpose

In this study, we aimed to investigate the EAT on cardiac diastolic function and structural alterations along the diabetic continuum using cardiac magnetic resonance imaging (CMRI).

Methods

We enrolled individuals who were categorized into groups based on glucose tolerance status. Left ventricular structure and diastolic function were assessed using echocardiography and CMRI to determine the EAT, intramyocardial fat, and associated parameters. Multivariable logistic regression models were also used.

Results

In a study of 370 patients (209 normal glucose tolerance, 82 prediabetes, 79 diabetes), those with prediabetes and diabetes showed increased heart dimensions and diastolic dysfunction, including the ratio of early mitral inflow velocity to mitral annular early diastolic velocity (7.9 ± 0.51 vs 8.5 ± 0.64 vs 10.0 ± 0.93, P = .010), left atrial volume index (28.21 ± 14.7 vs 33.2 ± 12.8 vs 37.4 ± 8.2 mL/m2, P < .001), and left ventricular peak filling rate (4.46 ± 1.75 vs 3.61 ± 1.55 vs 3.20 ± 1.30 mL/s, P < .001). EAT significantly increased in prediabetes and diabetes (26.3 ± 1.16 vs 31.3 ± 1.83 vs 33.9 ± 1.9 gm, P = .001), while intramyocardial fat did not differ significantly. Prediabetes altered heart geometry but not diastolic function (odds ratio [OR] 1.22 [1.02-1.83], P = .012; and 1.70 [0.79-3.68], P = .135). Diabetes significantly affected both heart structure and diastolic function (OR 1.42 [1.11-1.97], P = .032; and 2.56 [1.03-5.40], P = .034) after adjusting for covariates.

Conclusion

Elevated EAT was observed in patients with prediabetes and is associated with adverse alterations in cardiac structure and diastolic function, potentially serving as an underlying mechanism for the early onset of diabetic cardiomyopathy.
Does Baseline Facet Arthropathy Influence Early Clinical and Radiographic Outcomes After Cervical Disc Replacement?
Authors: Anwar Fatima N. , Nie James W. , Federico Vincent P. , Roca Andrea M. , Medakkar Srinath S. , Loya Alexandra C. , Lopez Gregory D. , Sayari Arash J. , Singh Kern
Published: June 2024

BACKGROUND AND OBJECTIVES:

Severe facet arthropathy is generally a contraindication to undergoing cervical disc replacement (CDR) due to associated instability and potentially limited improvement in neck pain caused by arthropathy. This study evaluates the influence of facet arthropathy on radiographic/early clinical outcomes after CDR.

METHODS:

One/two-level CDR patients from a single surgeon's prospectively maintained database created 2 cohorts based on facet arthropathy: grade 0-1 or 2-3 (milder/moderate arthropathy). Patient-reported outcome measures for neck disability, neck/arm pain, depressive burden, mental/physical health/function were obtained preoperatively and through final follow-up (average follow-up: 8.5 ± 6.5 months). Preoperative/postoperative radiographs measured segmental lordosis and C2-C7/segmental range of motion (ROM) and determined facet grade for each operative level. Demographic differences, perioperative variables, baseline patient-reported outcomes, and intercohort differences/changes for postoperative patient-reported/radiographic outcomes were determined.

RESULTS:

Of 161 patients, 100 were in the milder arthropathy group. There were no differences in baseline patient-reported outcomes. Patients with moderate arthropathy reported superior 6-week 12-Item Veterans Rand Mental/Physical Composite Scores (P ≤ .047, all). By final follow-up, moderate patients reported better 12-Item Veterans Rand Mental/Physical Composite Scores/Patient-Reported Outcome Measurement Information System-Physical Function/Patient-Health Questionnaire-9 (P ≤ .049, all). Cohorts reported similar improvements in all patient-reported outcomes by 6 weeks/final follow-up. Those with more severe facet arthropathy had significantly shorter preoperative disc heights (P < .001). Accounting for baseline disc height differences, by final follow-up, moderate patients had lower segmental ROM (P = .036). There were no significant differences in radiographic measurement changes (P ≥ .264, all).

CONCLUSION:

Postoperatively, patients with moderate facet arthropathy reported lower depressive burden, better mental health/physical function, and lower segmental ROM. However, this did not translate to inferior short-term clinical outcomes. Further study should be conducted on the relationship between clinical/radiographic outcomes in CDR patients with facet arthropathy.
Extent and Boundaries of Lymph Node Stations During Minimally Invasive Esophagectomy: A Survey Among Dutch Esophageal Surgeons
Authors: Ketel M. H. M. , van der Aa D. C. , Henckens S. P. G. , Rosman C. , van Berge Henegouwen M. I. , Klarenbeek B. R. , Gisbertz S. S. ,   DES Collaboration Group
Published: June 2024

Background

The optimal extent of lymph node dissection (LND) and the anatomic boundaries per lymph node station (LNS) during minimally invasive esophagectomy (MIE) for esophageal cancer remain a topic of debate. This study investigated the opinion of Dutch esophageal cancer surgeons on their routine LND extent and anatomic boundaries per LNS during MIE.

Methods

In April 2023, an English web-based cross-sectional survey was conducted. In each of the 15 Dutch hospitals performing MIE, two MIE surgeons were asked to participate. The routine LND extent (quantity, specific LNS) for distal esophageal adenocarcinoma, (dis)agreement with the TIGER definition, and anatomic boundaries for each LNS in six directions were queried.

Results

The survey was completed by 24 Dutch MIE surgeons (80% response rate). Consensus on the routine LND extent ( ≥ 85% of the participating surgeons) included the left and right paracardial, left gastric artery, celiac trunk, proximal splenic artery, common hepatic artery, subcarinal middle mediastinal paraoesophageal, lower mediastinal paraoesophageal, pulmonary ligament, and upper mediastinal paraoesophageal LNSs. Other LNSs were not widely considered routine. Although, certain anatomic boundaries were consistent among the surgeons, the majority varied, even when they agreed on the TIGER definition.

Conclusion

Significant variations in surgical practice among Dutch esophageal surgeons regarding their routine extent of LND and anatomic boundaries of LNSs during MIE were demonstrated. Variation may have an impact on clinical outcomes, hampering uniform treatment strategies and hindering comparison of performance assessments. This study highlighted the need for an international follow-up study toward one uniform defined LND during MIE for esophageal cancer.
Συγκριτική μελέτη των φρασεολογικών μονάδων που εμπεριέχουν τα ρήματα κίνησης πηγαίνω και έρχομαι στην ισπανική και την ελληνική γλώσσα
Authors: Παπαϊωάννου Μιχαλία
Published: June 2024

Στον τομέα της φρασεολογίας ο όρος φρασεολογική μονάδα συμπεριλαμβάνει τόσο τις φράσεις και λεξιλογικές συνάψεις όσο και τις παροιμίες. Η παρούσα εργασία επικεντρώνεται στη μελέτη των παροιμιών και πιο συγκεκριμένα των παροιμιολογικών μονάδων, όπως επιλέξαμε να τις ονομάσουμε κατ’αντιστοιχία του όρου φρασεολογική μονάδα. Αντικείμενο της παρούσας εργασίας αποτελεί η αντιπαραβολική μελέτη και ανάλυση των παροιμιολογικών μονάδων που περιέχουν τα ρήματα κίνησης ir και venir της ισπανικής γλώσσας και πηγαίνω και έρχομαι της ελληνικής αντίστοιχα. Σκοπός της παρούσας μελέτης είναι ο εντοπισμός παροιμιολογικών αντιστοιχιών ανάμεσα στις δύο γλώσσες, καθώς και η πρόταση παροιμιολογικών αντιστοιχιών, όπου δεν κατέστη δυνατή η εύρεσή τους κατά την αποδελτίωση. Η παρούσα εργασία διαρθρώνεται σε δυο κύρια μέρη: ένα θεωρητικό, στο οποίο παρουσιάζονται η φρασεολογία και η παροιμιολογία ως επιστημονικοί κλάδοι και ένα πρακτικό, το οποίο περιλαμβάνει τη συλλογή δεδομένων και τη μεθοδολογία που ακολουθήσαμε, την παρουσίαση και ανάλυση των παροιμιολογικών μονάδων, καθώς επίσης και τα συμπεράσματα. Η συλλογή των δεδομένων μας στηρίχτηκε κατά βάση στην αποδελτίωση 18 μονόγλωσσων και δίγλωσσων λεξικών της ισπανικής και ελληνικής γλώσσας από την οποία προέκυψε ένα σώμα 405 παροιμιολογικών μονάδων. Κατά την αποδελτίωση εντοπίσαμε τις παροιμιολογικές μονάδες σε καθένα από αυτά τα λεξικά για κάθε γλώσσα ξεχωριστά, αναζητώντας τις μονάδες αυτές στα λήμματα ir-venir και πηγαίνω-έρχομαι αντίστοιχα. Για την καταγραφή τους λάβαμε υπόψη τα πεδία (λεξιλογικές παραλλαγές, θέμα, είδος, σημασία, συγκείμενο, συνώνυμες, κυριολεκτική και εννοιολογική αντιστοιχία, χρήση) του παροιμιολογικού δελτίου που είχαμε δημιουργήσει βάσει του οποίου στη συνέχεια πραγματοποιήσαμε την ανάλυση των μονάδων. Ανάμεσα στα βασικά συμπεράσματα της έρευνάς μας συγκαταλέγεται το γεγονός ότι και στις δύο γλώσσες εντοπίσαμε πλήθος παροιμιολογικών μονάδων που να περιέχουν τα εν λόγω ρήματα κίνησης με τις περισσότερες να αφορούν την ισπανική γλώσσα. Τέλος, αναφορικά με τις παροιμιολογικές αντιστοιχίες προκύπτει πως το ποσοστό κυριολεκτικής αντιστοιχίας που εμφανίζουν οι μονάδες αυτές ήταν αρκετά μικρό σε σχέση με εκείνο της εννοιολογικής τους αντιστοιχίας.
Σχεδιασμός, Ανάπτυξη και Αξιολόγηση Διαδραστικής Ψηφιακής Ιστορίας σχετικά με την Αποφυγή Σπατάλης Τροφίμων στο Νηπιαγωγείο
Authors: Χατζηνικόλα Χαριστούλα , Κρητικός Γεώργιος , Παπαβασιλείου Βασίλειος
Published: June 2024

Στο ελληνικό νηπιαγωγείο, η υγιεινή διατροφή προωθείται μέσα από το αναλυτικό πρόγραμμα, στο πλαίσιο της βιωματικής μάθησης και της διαθεματικότητας, ενώ την ευθύνη της διατροφής των νηπίων έχει η οικογένεια. Σκοπός της παρούσας έρευνας είναι να διαπιστωθεί η βελτίωση του εγγραμματισμού των τροφίμων των νηπίων και ειδικότερα η κατανόηση της έννοιας της σπατάλης τροφίμων, μέσα από την εφαρμογή μίας διαδραστικής ψηφιακής ιστορίας. Τα παιδιά χωρίστηκαν σε δύο ομάδες, μία ελέγχου και μία πειραματική. Η ομάδα ελέγχου συμμετείχε σε μία παραδοσιακή διδασκαλία σχετικά με την υγιεινή διατροφή και τη σπατάλη τροφίμων. Η πειραματική ομάδα συμμετείχε στην εξέλιξη μίας διαδραστικής ψηφιακής ιστορίας, στην οποία ένα παιδί –ο κεντρικός ήρωας– επιλέγει υγιεινά μικρογεύματα και γεύματα, ενώ η κάθε επιλογή επιδρά διαφορετικά στο περιβάλλον και στην υγεία του. Στο τέλος, τα παιδιά και από τις δύο ομάδες κλήθηκαν να εμπλακούν σε δραστηριότητες αξιολόγησης σχετικά με τον εγγραμματισμό των τροφίμων και τη σπατάλη τροφίμων.
Οι Φυσικές Επιστήμες στην Πρακτική Άσκηση: μελλοντικοί/μελλοντικές νηπιαγωγοί επιλέγουν, σχεδιάζουν και αποτιμούν τους εκπαιδευτικούς τους σχεδιασμούς
Authors: Σιδηροπούλου Χρηστίνα , Πλιόγκου Βασιλική , Ζουπίδης Αναστάσιος
Published: June 2024

Τα σύγχρονα αναλυτικά προγράμματα των Φυσικών Επιστημών (ΦΕ) υποστηρίζουν την αξιοποίηση διερευνητικών περιβαλλόντων διδασκαλίας και μάθησης, στα οποία οι διερευνητικές πρακτικές αποτελούν, ταυτόχρονα, μέσο και μαθησιακό στόχο. Ένας βασικός παράγοντας για την επίτευξη αυτής της πρότασης θεωρείται η βασισμένη στην έρευνα εκπαίδευση των μελλοντικών εκπαιδευτικών. Μέσα από τη μελέτη 45 διδακτικών σεναρίων από 30 ημερολόγια Πρακτικής Άσκησης εξετάσαμε πώς προσεγγίζουν οι μελλοντικοί/μελλοντικές νηπιαγωγοί τις θεματικές, που επιλέγουν από τον χώρο των ΦΕ και πώς αποτιμούν την προσπάθειά τους. Η έρευνα βασίστηκε στην ποιοτική ανάλυση περιεχομένου. Τα αποτελέσματα έδειξαν ότι τα διδακτικά σενάρια αφορούν συχνά στην ευρύτερη περιοχή των ΦΕ και διαφοροποιούνται ως προς τη γνώση του περιεχομένου και τη διδακτική των ΦΕ. Εντοπίζεται, κυρίως, ένα μικτό μοντέλο δασκαλοκεντρικών πρακτικών με μερική εφαρμογή στοιχείων εποικοδομητισμού και αποσπασματική αξιοποίηση επιστημονικών πρακτικών. Στα περισσότερα, παρατηρείται σύνθεση από μεμονωμένα στοιχεία διαφορετικών μοντέλων διδασκαλίας ΦΕ και όχι η εφαρμογή ενός συγκεκριμένου μοντέλου με εσωτερική συνοχή.