bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional changes in brain metabolism during the progression of mild cognitive impairment: a longitudinal study based on radiomics
Authors: Mu Xuxu , Cui Caozhe , Liao Jue , Wu Zhifang , Hu Lingzhi 
Published: July 2024

Abstract
Background
This study aimed to establish radiomics models based on positron emission tomography (PET) images to longitudinally predict transition from mild cognitive impairment (MCI) to Alzheimer's disease (AD).

Methods
In our study, 278 MCI patients from the ADNI database were analyzed, where 60 transitioned to AD (pMCI) and 218 remained stable (sMCI) over 48 months. Patients were divided into a training set (n = 222) and a validation set (n = 56). We first employed voxel-based analysis of 18F-FDG PET images to identify brain regions that present significant SUV difference between pMCI and sMCI groups. Radiomic features were extracted from these regions, key features were selected, and predictive models were developed for individual and combined brain regions. The models' effectiveness was evaluated using metrics like AUC to determine the most accurate predictive model for MCI progression.

Results
Voxel-based analysis revealed four brain regions implicated in the progression from MCI to AD. These include ROI1 within the Temporal lobe, ROI2 and ROI3 in the Thalamus, and ROI4 in the Limbic system. Among the predictive models developed for these individual regions, the model utilizing ROI4 demonstrated superior predictive accuracy. In the training set, the AUC for the ROI4 model was 0.803 (95% CI 0.736, 0.865), and in the validation set, it achieved an AUC of 0.733 (95% CI 0.559, 0.893). Conversely, the model based on ROI3 showed the lowest performance, with an AUC of 0.75 (95% CI 0.685, 0.809). Notably, the comprehensive model encompassing all identified regions (ROI total) outperformed the single-region models, achieving an AUC of 0.884 (95% CI 0.845, 0.921) in the training set and 0.816 (95% CI 0.705, 0.909) in the validation set, indicating significantly enhanced predictive capability for MCI progression to AD.

Conclusion
Our findings underscore the Limbic system as the brain region most closely associated with the progression from MCI to AD. Importantly, our study demonstrates that a PET brain radiomics model encompassing multiple brain regions (ROI total) significantly outperforms models based on single brain regions. This comprehensive approach more accurately identifies MCI patients at high risk of progressing to AD, offering valuable insights for non-invasive diagnostics and facilitating early and timely interventions in clinical settings.
Cytokines in new-onset refractory status epilepticus: ready for clinical use?
Authors: Jin Zhenghan , Zhan Yixin , Chen Shijia , Zheng Yang 
Published: July 2024

AbstractNew-onset refractory status epilepticus (NORSE) is a rare and challenging condition characterized by refractory status epilepticus in an otherwise healthy patient without obvious causes. Increasing evidence suggests a change in cytokine profiles in NORSE. However, the clinical utility of cytokine testing remains uncertain, primarily because of the lack of robust study designs and limited sample sizes. A recent study published in Annals of Neurology investigated the cytokine profiles in both serum and cerebrospinal fluid samples of NORSE patients. The study found elevated levels of CXCL8, CCL2, and MIP-1α in the serum and elevated levels of IL-1ß in the cerebrospinal fluid of NORSE patients compared to those with other forms of refractory status epilepticus (RSE). Furthermore, patients with cryptogenic NORSE had even higher levels of CXCL8, CCL2, and MIP-1α in the serum. Patients with NORSE who exhibited elevated levels of innate immunity cytokines in the serum had worse outcomes at discharge and several months after the NORSE ended. In summary, these findings highlight the association between inflammation-related cytokines and NORSE, providing new insights into clinical diagnosis and treatment approaches.
Irinotecan plus anlotinib or further in combination with penpulimab as second-line treatment of metastatic colorectal cancer (ZL-IRIAN).
Authors: Wang Chenchen , Li Wenhua , Zhu Xiaodong , Geng Qirong , Zhao Xiaoying , Guo Weijian 
Published: June 2024

3570 Background: The irinotecan based chemotherapy in combination with bevacizumab had become the standard second-line treatment for metastatic colorectal cancer (mCRC), but the efficacy was limited. Anlotinib, an oral anti-angiogenic tyrosine kinase inhibitor, had initially shown promising clinical effects when combined with chemotherapy in the first-line treatment of mCRC. Whether anlotinib could bring clinical benefit in the second line treatment warrants further exploration. The PD-1 antibody might have partial effects when combined with anti-angiogenic agents with or without chemotherapy in first- and third-line treatment for proficient mismatch repair (pMMR)/ microsatellite stable (MSS) mCRC. Our study was to explore the rationality of anlotinib plus chemotherapy or further combined with a novel anti-PD-1 IgG1 antibody—penpulimab in the second line treatment of mCRC. Methods: This study was an open label, non-randomized, multi-cohorts, phase II prospective clinical trial that included pts with pMMR/MSS mCRC who were eligible for the second-line systemic treatment. Two cohorts were established as follows: Cohort A consisted of anlotinib(10mg daily, d1-10, q2w) + irinotecan (180mg/m2 d6, q2w) (n=23); Cohort B consisted of anlotinib (8mg daily, d1-10, q2w)+irinotecan (180mg/m2 d6, q2w) + penpulimab (200mg, d6, q2w) (n=23). Pts were initially enrolled in Cohort A. If the ORR in Cohort A was ≥15% (at least four patients in Cohort A reached CR/PR), the enrollment of Cohort B started. The primary endpoint was ORR. Secondary endpoints included progress free survival (PFS), overall survival (OS), duration of response (DoR), disease control rate (DCR) and safety. Results: A total of 23 Pts were enrolled in A cohort from March 9 2022 to December 3 2023. With an ORR of 39.1% (9/23) and DCR of 87.0% (20/22), the median PFS was 9.57 months (95% CI 5.24-13.90 months), and the 6-month and 12-month PFS rates were 70.9% and 38.2%, respectively. Pts in B cohort were enrolled from October 25 2022 to November 22 2023, a total of 23 pts were enrolled, 2 pts withdrew their informed consent before treatment and 21 pts received at least one dose of treatment. ORR of 21 pts was 42.9% (9/21), and the DCR was 90.5% (19/21). The median PFS had not reached, with the 6-month and 12-month PFS rates as 70.7% and 55%, respectively. Safety profile indicated that 65.2% (15/23) and 57.1% (12/21) experienced grade≥3 adverse events in A cohort and B cohort, respectively. Conclusions: The combination of anlotinib with irinotecan +/- PD-1 blockade in second-line treatment for mCRC had shown promising efficacy and good safety. Whether PD-1 blockade could bring extra survival benefits required longer follow-up. Clinical trial information: NCT05229003 .
Identification of prognostic genomic biomarkers in metastatic clear cell renal cell carcinoma (mccRCC): An analysis of the large retrospective real world clinico-genomic data from Flatiron Health (FH)-Foundation Medicine, Inc. (FMI) clinico-genomic database (CGDB).
Authors: Rizzo Mimma , Pezzicoli Gaetano , Porta Camilla , Povero Massimiliano , Pradelli Lorenzo , Sicari Emilia , Barbiero Valentina Sara , Porta Camillo 
Published: June 2024

4553 Background: Despite a number of therapeutic improvements, mccRCC still has a poor prognosis, with limited prognostic predictors for clinical practice. The aim of this study was to evaluate the prognostic value of three clusters of co-occurring genes in mccRCC. Methods: We conducted a retrospective analysis of adult patients with mccRCC who were profiled by performing FMI genomic tests using tissue biopsies or blood samples. Data were from the nationwide (US-based) de-identified FH-FMI CGDB, originating from approximately 280 US cancer clinics (~800 sites of care). Patients diagnosed from January 01, 2011 to June 30, 2022 were followed until death or the last available observation (within December 31, 2022). Overall Survival (OS) was estimated using the Kaplan-Meier methods, while Cox proportional hazard model with risk set adjustment was used to assess the prognostic role of three pre-specified clusters of co-occurring genes; cluster 1 (C1) included VHL, SETD2, PBRM1, KDM5C, MTOR, and NFE2L2, cluster 2 (C2) included TP53, TSC1, and TERT, while cluster 3 (C3) included CDKN2A, CDKN2B, BAP1, NF2, MTAP, and ARID1A. Patients were considered cluster-positive (+) if they exhibited mutations in at least one gene within the cluster, and none in the other clusters. Results: 789 mccRCC patients were included [median age: 61 years, male: 71.1%, white race: 71.2%]. Among the 720 (91.3%) treated patients, 516 (71.7%) and 59 (8.2%) were classified per IMDC score as poor/intermediate and favorable risk, respectively (145 missing). Overall, almost half (45.5%; 359) were profiled after the diagnosis of metastasis (median gap time of 7.9 months) and 29 (3.7%) underwent multiple profile assessments, resulting in a total of 818 specimens analyzed. 332 (42.1%), 27 (3.4%), and 32 (4.1%) patients were C1+, C2+, and C3+, respectively. Median OS was 37 months (95% CI: 34-42). C1+ patients had higher OS compared to C1- (median OS: 50 vs. 30 months; HR: 0.57, p<0.001), while C3+ was associated with worse OS (median OS: 38 vs. 20 months; HR: 1.94, p=0.004). No association was found between C2 and OS (HR: 1.27; p=0.4). C1+ patients were more frequently classified as favorable risk compared to C1- (10.2% C1+ vs. 6.8% C1-, p=0.046) and they had longer duration of first-line (L1) treatment (median DoT: 9 vs. 7 months, p = 0.02). No significant differences between C2+ and C2-, C3+ and C3- patients were observed in L1 duration and IMDC distribution. Conclusions: This large-scale study identified two independent prognostic gene clusters in mccRCC. Further analyses will focus on the validation of the predictive role of these biomarkers with the ultimate aim of helping us develop tailored treatment strategies.
Association of immune-related adverse events, inflammatory biomarkers, and clinical outcomes in patients treated with ICIs for advanced renal cell carcinoma.
Authors: Yildirim Ahmet , Wei Mengting , Liu Yuan , Goswamy Rohit Vivek , Choi Yujin , Brown Jacqueline T , Nazha Bassel , Martini Dylan J. , Hartman Caitlin , McClintock Greta Russler , Zhuang Tony , Kissick Haydn , Harris Wayne B. , Carthon Bradley Curtis , Kucuk Omer , Master Viraj A. , Bilen Mehmet Asim 
Published: June 2024

4556 Background: Immune Checkpoint Inhibitors (ICIs) have been the mainstay treatment for advanced renal cell carcinoma (aRCC). However, irAEs are still a challenge in clinical practice. We tested irAEs with inflammatory biomarkers and their association with clinical outcomes. Methods: A retrospective analysis was conducted on adult patients with aRCC treated with ICIs at Emory Winship Cancer Institute between 2018 and 2023. irAEs determined by the primary oncologist and reported by CTCAE v5.0. Univariate and multivariate analyses were conducted to determine the association between race, gender, OS, PFS, clinical benefit (CB, stable disease, partial response, complete response), modified Glasgow Prognostic Score (mGPS), neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), neutrophil to eosinophil ratio (NER), and any grade irAE. MVA was built by controlling gender, race, smoking status, and prior treatment. Results: We analyzed 401 patients; 191 (47.6%) patients experienced any grade irAEs, with 41 (21.5%) of those classified as grade 3 or higher. Of 401 patients, 139 (34.6%) were treated with PD-1 inhibitor (PD-1i) monotherapy, 131 (32.6%) with PD-1i and CTLA-4 inhibitor combination, 108 (26.9%) with PD-1i and tyrosine kinase inhibitor combination. The median follow-up time was 43.0 months (36.5-51.3). On univariate analysis, the incidence of irAEs was higher in females than males (Odds ratio (OR),1.66 (1.08-2.57), p=0.021), White patients had a higher incidence of irAEs compared to African American patients (OR 2.20 (1.32-3.66), p=0.009). On multivariate analysis, low mGPS was correlated with a higher risk of irAEs (OR for mGPS of 0-1-2 was 6.03 (2.07-17.62), 3.75 (1.31-10.70), and reference respectively; p=0.004). irAEs were correlated with greater CB (OR 2.56 (1.53-4.29); p <.001), longer OS (HR 0.55 (0.37-0.82); p=0.003), and longer PFS (HR 0.51 (0.37-0.71); p <.001). Conclusions: Female patients, White patients, and patients with low inflammatory biomarkers may have a higher likelihood of experiencing irAEs. Patients who experienced irAEs may have better outcomes. Future prospective trials are needed for further evidence. [Table: see text]
Disparities in trends in bladder cancer mortality between urban and rural patients: A 2000-2020 analysis.
Authors: Al Armashi Abdul Rahman , Thierheimer Marisa , Bukavina Laura , Calaway Adam C. , Vince Randy , Mendiratta Prateek , Garcia Jorge A. , Brown Jason R 
Published: June 2024

4583 Background: Patients in rural areas in the US often have worse healthcare outcomes due to socioeconomic deprivation, higher rates of smoking, and limited access to medical care. Despite a general decline in bladder cancer mortality over the past two decades, comprehensive studies comparing these trends between urban and rural mortality are scarce. Methods: Utilizing the CDC WONDER database, we extracted mortality data for bladder cancer from 2000 to 2020. Age-adjusted mortality rates per 100,000 persons were standardized to the Year 2000 US standard population. Data segmentation by urbanity utilized the 2013 National Center for Health Statistics Urban-Rural Classification Scheme. The National Cancer Institute's Joinpoint Regression Program was employed to calculate average annual percent changes (AAPCs) and annual percent changes (APCs). Results: In our analysis, we identified a total of 306,750 bladder cancer death cases from 2000 to 2020. Significant improvements in bladder cancer mortality were observed in urban areas, with large central metros experiencing the most pronounced decrease (AAPC -1.0%, p<0.001). This decline was moderate between 2000 and 2016 (APC -0.3, p< 0.001) but accelerated between 2016 and 2020 (APC -3.8%, p<0.001). Large fringe and medium metros also saw comparatively smaller but significant declines (AAPC -0.6%, P<0.05) and also accelerated between 2016-2020. In contrast, small metro and rural areas (micropolitan and noncore) showed no significant improvement, with mortality rates remaining stable between 2000 and 2020 (AAPC 0.2%, P=0.099). Conclusions: This analysis, the largest to date comparing urban and rural mortality trends in bladder cancer, highlights significant disparities in outcomes between large urban and rural areas. The marked improvement in urban areas, especially noted around the time novel agents such as immunotherapy were introduced, underscores the potential impact of advanced treatments. However, the stable mortality rates in rural areas suggest that access to advanced care, environmental influences, socioeconomic status, and slower adaptation of new guidelines in rural settings may play critical roles. These findings underline the urgent need for strategies to close the urban-rural gap. [Table: see text]
Prognostic factors of relapse in surgically resected small cell neuroendocrine carcinomas of the urothelial tract (SCNEC-URO).
Authors: Moussa Mohammad Jad , Wilson Nathaniel R. , Xiao Lianchun , Tabet Georges C. , Gao Jianjun , Shah Amishi Yogesh , Corn Paul Gettys , Goswami Sangeeta , Msaouel Pavlos , Tannir Nizar M. , Lee Byron H. , Kamat Ashish M. , Adibi Mehrad , Dinney Colin P.N. , Hansel Donna E. , Guo Charles C. , Siefker-Radtke Arlene O. , Campbell Matthew T , Alhalabi Omar 
Published: June 2024

4605 Background: SCNEC-URO are rare aggressive cancers with limited treatments. Although they frequently co-exist (60-70%) with urothelial carcinoma (UC) at diagnosis, most metastatic biopsies of relapsing patients (pts) show pure small cell (SC) morphology. There are major unmet needs to predict relapse after definitive surgery. Methods: Data was extracted from a historical cohort of n=216 pts with surgery for surgically resectable disease (cT1-T4, N0 or N+, M0) at MD Anderson between November 1985 and June 2021. Morphology at resection was defined as: ‘pCR’ (pathological complete response, including no residual carcinoma or carcinoma in situ), ‘Any SCNEC’ (persistence of SC with UC in sample) or ‘Non-SCNEC’ (UC only). Relapse events after surgery were analyzed as time-to-event (TTE) outcome with competing risk non-parametric method. Univariable and multivariable analyses identified prognostic factors of relapse. Results: In TTE analysis, cohort events (n=216) included: n=70 censored (alive and relapse-free), n=92 failure events (with relapse), and n=54 competing events (death without known relapse). n=154 (71.3%) received neoadjuvant chemotherapy, including SCNEC regimens in 125/154 (81.2%) and UC regimens in 16/154 (10.4%). The 5-year cumulative incidence function (CIF) of relapse for all pts was 41.92% [95% CI: 35.2% - 48.5%]. CIF rates were significantly different per morphology at resection (Gray’s test, p<.0001). Pts with pCR had the lowest 5-year CIF rate for relapse (18.5%) [11.1% - 27.4%], while pts with ‘Any SCNEC’ had the highest CIF (69.6%) [58.6% - 78.9%]. Pts with Non-SCNEC had an intermediate CIF risk (31.6%) [17.6% - 46.7%]. Staging at resection also showed different CIF rates (Gray’s test, p<.0001). Pts with pT0N0 had the lowest CIF rate (12.8%) [5.6% - 23.2%], with CIF rates increasing with higher staging: pTisN0 (25%) [11.6% - 41%]; pT1N0 (25%) [5.4% - 51.7%]; pT2 or greater, but N0 (52.4%) [41% - 62.7%]. Pts staged node-positive (pN+) did not have an estimated 5-year CIF as most died within 5 years. In multivariable analysis, clinical staging at diagnosis, pathological staging and cellular morphology at resection were associated with relapse (Table). Conclusions: Besides staging at diagnosis and surgery, morphology at resection is a key predictor of relapse. Persistence of the SC component predicts a higher chance of relapse than its eradication and persistence of the UC component. While adjuvant therapy in UC has made significant progress recently, a tailored adjuvant approach addressing the residual SC component at definitive surgery is needed to improve outcomes and decrease relapse. [Table: see text]
Survival outcomes and subgroup analyses derived from a phase III randomized trial comparing afatinib to chemotherapy in treatment-naïve non-small cell lung cancer with a sensitizing uncommon epidermal growth factor receptor mutation (ACHILLES/TORG1834).
Authors: Sato Yuki , Miura Satoru , Misumi Toshihiro , Yoshioka Hiroshige , Tokito Takaaki , Fukuhara Tatsuro , Yamaguchi Ou , Yokoyama Toshihide , Kuyama Shoichi , Kurata Takayasu , Kato Terufumi , Horinouchi Hidehito , Takiguchi Yuichi , Goto Yasuhiro , Tanaka Kentaro , Mori Masahide , Ikeda Satoshi , Ichihara Eiki , Tanaka Hiroshi , Okamoto Hiroaki 
Published: June 2024

8588 Background: The ACHILLES/TORG1834 trial is the first randomized phase 3 study, demonstrating the superiority of afatinib to chemotherapy in terms of progression-free survival (PFS) as a primary endpoint in sensitizing uncommon epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) (the hazard ratio [HR] of PFS was 0.422, p=0.0007). This trial was early terminated due to efficacy according to the recommendation by the data and safety monitoring committee. Here we report the overall survival (OS) result, subgroup analysis of PFS, and the response data according to detailed mutation status at the primary analysis. Methods: In this open-label phase III study, treatment-naïve patients (n=109) with sensitizing uncommon EGFR mutant NSCLC were randomized 2:1 to oral afatinib (30 mg or 40 mg daily) or the combination of platinum (cisplatin 75 mg/m2 or carboplatin AUC 5 or 6) and pemetrexed (500 mg/m2), followed by pemetrexed maintenance therapy every 3 weeks. The primary endpoint was PFS per RECIST 1.1. The secondary endpoints included objective response rate (ORR), time to treatment failure (TTF), and OS. Results: Median follow-up time was 12.5 (range, 0 to 43.5) months. The OS HR of afatinib compared to chemotherapy was 0.989 (95% confidence interval [CI], 0.457 to 2.141; p=0.9772; 29/109 events, 26.6% maturity). Median OS was not reached in either population. All subgroups of PFS did better in the afatinib arm. In the subgroup regarding the starting dose of afatinib, the PFS HR in the 40mg afatinib arm (HR 0.128, 95%CI, 0.050 to 0.327) were favorable compared to that in the 30mg afatinib arm (HR 0.704, 95%CI, 0.352 to 1.406). In this subgroup, there were several differences in the baseline characteristics regarding age and gender. The detail of ORR and PFS according to mutations status was shown in the table. The safety profiles in both arms were consistent compared to previous reports. Conclusions: A consistent PFS benefit of afatinib over platinum-doublet chemotherapy was shown regardless the mutation status in patients with uncommon or compound EGFR mutations. The OS data were immature, and further follow-up will be warranted. Clinical trial information: 031180175. [Table: see text]
Survival differences in advanced non-small cell lung cancer after developments in regimens with immune check point inhibitors: Population based retrospective study from United States SEER database.
Authors: Kshetree Binay , Bhandari Supradepti 
Published: June 2024

e20516 Background: Metastatic non-small cell lung cancers (NSCLC) are being treated with immune checkpoint inhibitors (ICI). Nivolumab was approved in 2015, pembrolizumab (pz) /atezolizumab (az) in 2016, pz-chemotherapy (Ch) (pemetrexed + carboplatin) in 2017; durvalumab, pz-Ch (paclitaxel) and az-Ch (bevacizumab, carboplatin, paclitaxel) in 2018. We aim to study population based overall survival (OS) differences before and after these approval. Methods: We used Surveillance, Epidemiology and End Results (SEER) research plus database (Nov 2022 submission,17 registries). Patients aged ≥ 20 years with NSCLC as “distant” (combined summary stage) from 2013-2018 were included. Time was stratified as Pre-ICI from 2013-2014, initial single agent ICI from 2015-2016 (ICI) and new ICI/ICI-Ch from 2017-2018 (n/ICICh). OS in these time periods was calculated using Kaplan Meier (KM) method and were compared with log rank tests. Multivariate analysis was done using cox proportional hazard ratios. p < 0.05 was considered for statistical significance. IBM SPSS was used for analysis. Results: Total of 6375 patients had advanced NSCLC from 2013-2018. 4 and 5-year survival from 2017-2018 was not available due to data up to 2020. The survival difference among three timelines was statistically significant (log rank test, χ2 = 20.795, p < 0.001). On multivariate analysis, ICI and n/ICICh had significantly lower risk of dying as in table compared to Pre-ICI. Male, age ≥50 years, Black/Asian/Pacific Islanders were at higher risk and who received radiotherapy/chemotherapy had a lower risk of dying. There was no significant difference among Hispanic versus non-Hispanic and among marital status. Conclusions: ICI shows clear survival benefits in advanced NSCLC in this population-based study which supports clinical trials. Racial, gender and older age disparities shown in this study will further help in guiding appropriate measures. Future analysis with new ICI/Ch therapy with new timelines will help show population-based survival benefits after updated database. [Table: see text]