bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application value of plasma exosomal long RNA in SCLC diagnosis and prognosis.
Authors: Liu Chang , Wang Jialei , Huang Shenglin , Yu Hui , Zhu Zhengfei , Fan Min 
Published: June 2021

8566 Background: Little research has focused on blood exosomal transcription profile in small cell lung cancer (SCLC). The aim of this study is to identify plasma exosomal specific transcriptional profile in SCLC and explore the application value of plasma exosomal long RNA (exLR) in SCLC diagnosis and prognosis. Methods: This study included 81 healthy people and 40 SCLC patients receiving standard first-line chemotherapy with etoposide and carboplatin/cisplatin. The efficacy was evaluated by progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). 19 Patients who achieved complete response (CR) or partial response (PR) as best response during the first-line therapy and had not progressed within the following 90 days after the end of first-line therapy were defined as chemosensitive. 21 Patients who achieved stable disease (SD) as best response or received progressive disease during the first-line therapy or within the following 90 days after the end of first-line therapy were defined as chemoresistant. Baseline plasma samples were collected from 40 SCLC patients (17 patients’ samples after 2 courses were collected) and 81 healthy people. Plasma exosomes were isolated and purified; exosomal RNA were extracted for high-throughout sequencing analysis. Results: We obtained plasma exLRs profiles from 81 healthy control samples and 57 SCLC samples (baseline samples from 40 patients plus samples collected by 17 patients after 2 courses). Bioinformatics analysis found that exLRs were significantly different between the SCLC and the healthy control group; between the chemosensitive and the chemoresistant group; between the baseline samples and the paired samples after 2 courses. For 40 SCLC patients receiving first-line chemotherapy, ORR was 65.0%, DCR was 90.0% and mPFS was 6.0 months (95% CI, 4.3-7.7 months). Multivariate analysis showed that baseline brain metastases and baseline bone metastases were independent predictors of poor PFS; and 223 genes were independent predictors of PFS. There were 10 genes (AC107954.1, H2AFZP2, CALB2, IFITM9P, GFPT2, PLA1A, CHST10, AC021231.2, SETP20, HILPDA) intersected in differentially expressed genes between the SCLC and the healthy control group, differentially expressed genes between the chemosensitive and the chemoresistant group and independent predictors of PFS. These 10 genes were highly expressed in both the SCLC group and the chemoresistant group, and their high expression was an independent risk factor for poor PFS. Conclusions: This study firstly identified the plasma exLRs profiles in SCLC patients, verified the feasibility and value of identifying biomarkers based on exLRs profiles in SCLC diagnosis and prognosis.
Response to selpercatinib versus prior systemic therapy in patients (pts) with RET fusion+ non-small-cell lung cancer (NSCLC).
Authors: Drilon Alexander E. , Gautschi Oliver , Besse Benjamin , Subbiah Vivek , Tan Daniel Shao-Weng , Park Keunchil , De Braud Filippo G. , Alonso Guzman , Wolf Juergen , Soldatenkova Victoria , French Pearl Plernjit , Lin Aimee K. , Goto Koichi , Solomon Benjamin J. 
Published: June 2021

9032 Background: Selpercatinib, a first-in-class highly selective, potent, CNS-active RET kinase inhibitor, is approved in multiple countries for treatment of RET fusion+ lung or thyroid cancers. Selpercatinib demonstrated durable antitumor activity in previously treated pts with RET fusion+ NSCLC in an ongoing Phase 1/2 trial, LIBRETTO-001 (Besse et al., ASCO 2021). Methods: Pts with RET fusion+ NSCLC enrolled in the global, multicenter, LIBRETTO-001 trial (NCT03157128; 16 countries, 89 sites). Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival, duration of response, and safety. This post-hoc intrapatient analysis was based on a 30 March 2020 data cutoff date. Historical physician-reported best overall response (BOR) from last systemic therapy received prior to enrollment was compared with selpercatinib BOR by independent review committee per RECIST v1.1, with each patient serving as his/her own control. Results: In efficacy-evaluable pts (N = 218) who previously received platinum-based chemotherapy (chemo), median pt age was 61 years, the majority with ECOG of 0/1 (37%/61%), with a median of 2 (range: 1-15) prior systemic therapies. Overall, 57% of patients responded to selpercatinib while 16% responded to the immediate prior therapy. ORR improvements with selpercatinib were observed regardless of prior therapy: chemotherapy + immune checkpoint inhibitor (ICI) (57% vs 14%), single-agent ICI (48% vs 3%), or chemotherapy (58% vs 15%). A total of 108 patients (49%) did not respond to immediate prior therapy but responded to selpercatinib. Fewer patients had progressive disease as their BOR with selpercatinib (2%) compared to the immediate prior therapy (28%). The median duration of therapy for selpercatinib was notably extended compared with that of the immediate prior therapy (11.8 vs. 3.4 months, respectively). Conclusions: In pts with RET fusion+ NSCLC treated on LIBRETTO-001, systemic therapies administered prior to enrollment achieved less meaningful clinical benefit than selpercatinib. Selpercatinib demonstrated consistent efficacy regardless of the type of prior therapy. Clinical trial information: NCT03157128.
Increased risk of immune-related hepatitis among adolescent and young adults (AYAs) with melanoma during immunotherapy with checkpoint inhibitors (ICIs).
Authors: Darwin Alicia , Reed Damon R. , Tanvetyanon Tawee 
Published: June 2021

9584 Background: Melanoma is the second most common malignancy affecting AYA patients after lymphoma. Nevertheless, AYA melanoma does constitute a minority of all melanoma cases. Additionally, the AYA population is not well represented in prospective clinical trials, including immunotherapy trials. While previous research has demonstrated the efficacy of ICIs across age groups, it remains unclear if toxicity profiles will be similar. In the general population, age-related changes in the immune milieu result in differential incidences of autoimmune diseases by age. This study aims to compare the toxicity profile between a cohort of AYA melanoma versus elderly melanoma patients receiving ICI therapy. Methods: In this single NCCN institutional study, electronic medical records of melanoma patients treated with ICIs between 01/2007-01/2019 were reviewed. Subjects receiving concurrent investigational agents or chemotherapy were excluded. The AYA cohort included those aged 15-40 years. The elderly cohort included those aged ≥65 years. Adverse events were coded according to CTC-AE version 5.0. Multivariable logistic regression analyses were performed. Results: Analyses included 184 treatment courses. In the AYA cohort (N = 57), median age at ICI initiation was 28.8 years (range: 17.9-39.3). In the Elderly cohort (N = 127), median age at ICI initiation was 72.3 years. More AYA patients (28.1% AYA vs. 7.9% Elderly) received ICI combination regimens. The most common adverse events amongst both cohorts were transaminitis (23.4%), rashes (49.5%), and diarrhea/colitis (20%). Incidences of pneumonitis, colitis, hypothyroidism, and hypophysitis did not differ significantly between cohorts. However, the AYA cohort experienced a higher incidence of transaminitis (38.6% AYA vs. 16.5% Elderly, p =0.001 ) and increased occurrence of treatment related hospitalization (26.3% AYA vs. 7.1% Elderly, p <0.001 ). Moreover, a higher proportion of severe grade ≥3 transaminitis occurred in the AYA group (27.3% AYA vs. 9.5% Elderly, p =0.004). While occurrence of transaminitis was significantly associated with combination ICIs, the association between AYA status and transaminitis remained significant after adjusting for ICI regimen (OR 2.75, 95% CI: 1.3-5.8). There was a trend toward shorter time to transaminitis onset among the AYA than Elderly cohort (median 53.0 vs. 74.5 days [non-parametric p= 0.28]). To date, median survival has not been reached in both groups ( p= 0.09). Conclusions: In this large cohort of AYA melanoma patients treated with ICI, we found a significantly higher incidence of immune-related transaminitis than in the Elderly cohort. Other immune-related AEs were comparable between cohorts. This finding was independent of ICI regimen. Further investigation will be needed to understand these differences between the AYA and Elderly cohorts.
Can Intratumoral neutrophil lymphocyte ratio (NLR) be a prognostic biomarker in breast cancer patients?
Authors: Tokumaru Yoshihisa , Oshi Masanori , Murthy Vijayashree , Katsuta Eriko , Matsuhashi Nobuhisa , Futamura Manabu , Yoshida Kazuhiro , Takabe Kazuaki 
Published: June 2021

e12573 Background: In breast cancer patients, it is well known that the elevation of neutrophil lymphocyte ratio (NLR) in the blood are reported to associate with poor prognosis based on the notion that neutrophils represent pro-cancer, and lymphocytes represent anti-cancer immune cells. Tumor immune microenvironment has been demonstrated to play critical roles in the outcome of breast cancer patients. However, there is scarce evidence on the clinical relevance of intratumoral NLR in breast cancer patients. In the current study, we hypothesized that intratumoral NLR high tumors are associated with worse survival particularly in TNBC that is known to have high immune cell infiltration. Methods: A total of 1904 breast cancer patients’ data from METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) and analyzed. NLR was calculated by the gene expressions of CD66b (CEACAM8) and CD8 (CD8A). NLR high and low were divided by the median. Overall Survival (OS) and Disease-Free Survival were calculated utilizing Kaplan Meier method between intratumoral NLR high and low groups. xCell algorithm was used to analyze the infiltrated immune cells within the tumor immune microenvironment as we have previously published. Results: Intratumoral NLR high group was associated with worse OS in whole, ER-positive/HER2-negative, and triple negative (TN) subtypes, in agreement with the previous studies. TN subtype alone demonstrated worse DFS of NLR high group. Surprisingly, gene set enrichment analysis (GSEA) demonstrated no gene set enrichment to NLR high group, which implicates that there is no distinctive mechanism that associate with worse survival. Whereas, immune response-related gene sets significantly enriched to NLR low group in TN subtype. This enrichment was consistent in ER-positive/HER2-negative. Compared with ER-positive/HER2-negative subtype, anti-cancer immune cells such as CD4+ T cells, CD8+ T cells, M1 macrophage, and helper T helper type 1 cells were significantly infiltrated in TN patients (p < 0.001 for all genes), where M2 macrophages and neutrophils were less and regulatory T cells and T helper type 2 cells were more infiltrated in TN subtype. Furthermore, intratumoral NLR was significantly lower in TN compared with ER-positive/HER2-negative subtype (p < 0.001). These results suggest that intratumoral NLR low group is associated with better survival due to favorable tumor immune microenvironment in TN subtype rather than NLR high group has worse survival. Conclusions: Intratumoral NLR low tumor demonstrated more favorable OS and more favorable DFS in TN patients. Intratumoral NLR low breast cancer was associated with enhanced immune response and higher infiltration of anti-cancer immune cells were observed in TN subtype compared to ER-positive/HER2-negative which may contribute to the favorable outcome of in TN breast cancer.
Breast cancer surgical delays in a racially and ethnically diverse California cancer registry cohort.
Authors: Navarro Stephanie , Yang Yifei , Ochoa Carol , Kim Sue , Liu Lihua , Lerman Caryn , Farias Albert 
Published: June 2021

e12589 Background: Surgical delays for invasive breast cancer have been increasing over time and are associated with an increased risk of mortality. Black and Hispanic breast cancer patients are more likely to experience surgical delays than white patients; however, surgical delays among Asian ethnic subgroups remain unstudied. Methods: We used data from the population-based California Cancer Registry to identify all females diagnosed with stage I-III invasive breast cancer from 2012-2017. Our main independent variable was patient race/ethnicity, including five Asian ethnic subgroups. Covariates captured tumor, treatment-related, and patient sociodemographic characteristics. We conducted multivariable logistic regression to determine the odds of receiving surgery within 30 and 90 days of diagnosis and multivariable Cox proportional hazards regression to determine the risk of shorter time to surgical treatment. Results: Of 106,441 breast cancer patients, 57.5% were non-Hispanic white (NHW), 20.7% were Hispanic, 5.9% were non-Hispanic black (NHB), and 12.6% were Asian (consisting of 33.7% Filipino, 24.6% Chinese, 8.1% Asian Indian or Pakistani (AIP), 7.7% Japanese, 6.7% Korean, and 19.2% other Asian (OA) patients). Compared to NHWs, Hispanics and NHBs were less likely to receive surgical treatment within 30 and 90 days of diagnosis (Hispanic, 30-day: OR = 0.94, 95% CI = 0.89-0.98; Hispanic, 90-day: 0.89, 0.85-0.92; NHB, 30-day: 0.91, 0.85-0.98; NHB, 90-day: 0.86, 0.80-0.92). However, Chinese and AIP patients were more likely than NHWs to receive surgery within 30 and 90 days of diagnosis (Chinese, 30 day: OR = 1.30, 95% CI = 1.19-1.41; Chinese 90-day: 1.26, 1.08-1.47; AIP 30-day: 1.29, 1.11-1.50; AIP 90-day: 1.34, 1.17-1.53). In addition, Koreans were more likely than NHWs to receive surgery within 90 days of diagnosis (OR = 1.26, 95% CI = 1.08-1.47). Hispanics, NHBs, and OAs were less likely to receive timely treatment compared to NHWs (Hispanic: HR = 0.95, 95% CI = 0.94-0.97; NHB: 0.91, 0.89-0.94; OA: 0.95, 0.92-0.99), while Chinese, AIP, and Korean patients were more likely to receive timely treatment compared to NHWs (Chinese: HR = 1.15, 95% CI = 1.11-1.20; AIP: 1.10, 1.04-1.17; Korean: 1.10, 1.03-1.17). Lastly, patients diagnosed in 2017 were 14% less likely to receive timely treatment than those diagnosed in 2012 (HR: 0.86, 95% CI = 0.84-0.88). Conclusions: In this population-based cohort of female breast cancer patients in California, Hispanics and NHBs continue to experience surgical treatment delays and Asian American minority subgroups experience similar delays compared to NHWs. In addition, increasing delays over time could potentially exacerbate racial/ethnic disparities in breast cancer mortality. Continued work investigating the causes of breast cancer treatment delays among Asian ethnic subgroups is necessary to fully elucidate and target racial/ethnic treatment disparities.
Targeted axillary lymph node dissection in breast cancer patients using I-125 microseeds for prostate cancer brachytherapy.
Authors: Emelyanov Alexander , Petr Krivorotko , Pesotskiy Roman , Bessonov Alexander , Gorelov Viktor , Semiglazov Vladimir 
Published: June 2021

e12601 Background: To date, targeted axillary lymph node dissection is one of the possible methods of de-escalation of surgical aggression on the areas of regional lymph flow in breast cancer patients with confirmed metastases in the axillary lymph nodes prior to the neoadjuvant chemotherapy. There are no specialized microseeds for targeted axillary dissection. The purpose of our study was to determine the possibility of using I-125 microseed for prostate cancer brachytherapy for targeted axillary dissection. Methods: A prospective study of patients with biopsy-confirmed nodal axillary metastases with a I-125 microseed placed in the node was performed. I-125 microseed for prostate cancer brachytherapy was used to mark the axillary lymph node. After neoadjuvant therapy, patients underwent targeted axillary lymph node dissection in combination with SLNB with pathomorphological examination of marked lymph node and total axillary lymph node dissection with pathomorphological examination of over lymph nodes for FNR evaluation. Results: 45 breast cancer patients stage cT1-3N1M0 were enrolled in the study. The frequency of reaching ypN0 was 58%. Residual disease identified in 19 patients. The clipped node revealed metastases in 18 patients, resulting in an FNR of 5.26% (95% CI, to 20.6) for the clipped node. CIs for FNR were calculated using exact (Clopper-Pearson) confidence limits for the binomial proportion. Conclusions: Marking the biopsy-confirmed lymph node using a I-125 microseed prior neoadjuvant chemotherapy and performing targeted axillary lymph node dissection in combination with SLNB is a safe method for diagnosing axillary lymph nodes and allows you to abandon routine ALD for ypN0 patients. Advantages of I-125 microseed for prostate cancer brachytherapy: fixation in the lymph node without migration, the ability to use a standard gamma-probe to locate the microseed during the operation, these microseeds are registered for the treatment of cancer patients.
SGK1 regulated apoptosis in invasive breast carcinoma.
Authors: Song Yuxin , Li Lei , Fei YinJiao , Chen Wenquan , Wo Guan qun , Tang Jinhai 
Published: June 2021

e13061 Background: Worldwide, breast cancer is the most common type of cancers and the presentation of drug resistance is often associated with poor prognosis. Previous studies have shown the mechanism of drug resistance was affected by apoptosis at different levels in the signaling cascades. This article is aimed to explore the relationship between the serum and glucocorticoid-regulated kinase 1 (SGK1) and apoptosis in invasive breast cancer (IBC). Methods: We evaluated the expression of SGK1 in IBC using publicly available data from The Cancer Genome Atlas (TCGA) and Curtis Breast program. TaqMan probe-based qRT-PCR assay and Western Blot analysis were performed to quantitatively detect the expression of SGK1 at RNA and protein levels in the IBC specimens. Clinicopathologic characteristics associated with overall survival were tested by Cox regression. Gene Set Enrichment Analysis (GSEA) was performed to mine the biological pathways involved in IBC pathogenesis related SGK1 regulatory network using MSigDB database. Immunohistochemistry staining (IHC) was used to detect apoptotic markers Fas, Bcl2 and SGK1 in the IBC specimens. Results: Totally 1109 IBC samples with SGK1 expression data were downloaded from TCGA databases for analyzed. SGK1 expression was elevated in normal breast tissues compared with both invasive ductal carcinoma and invasive lobular carcinoma (p < 0.0001). Among them, SKG expression in 112 tumor tissues was significantly lower than that in paracancerous tissues, especially in advanced patients with TNM stage IV. Western Blot and qRT-PCR assay confirmed that SGK1 expression in IBC was distinctly lower than normal. The Kaplan-Meier survival analysis showed that decreased expression of SGK1 was significantly correlated with the clinical stage (p = 0.036). In Curtis Breast program, we further verified SGK1 gene expression was reduced in stage IV than stage I. The univariate analysis demonstrated that clinicopathologic variables associated with poor survival include age, advanced stage, lymph nodes, distant metastasis and deep myometrial invasion. GSEA revealed that apoptosis was differentially enriched when SGK1 was highly expressed. Similarly, TCGA data indicated that the positive rate of SGK1 was higher in Fas positive IBCs, and the same result was also obtained by IHC in the IBC specimens. Conclusions: Expression of SGK1 regulated apoptosis in invasive breast carcinoma, which might be a potential therapeutic target to overcome refractory and drug-resistant breast cancer.
Treatment patterns of older adults with metastatic breast cancer in community practices.
Authors: McShane Melissa , Dotan Efrat , Obeid Elias , Handorf Elizabeth A. 
Published: June 2021

e13063 Background: The median age at diagnosis of breast cancer is 62 with 45% of patients over the age of 65. At diagnosis, up to 5% of patients will have metastatic breast cancer (MBC) and up to 30% of patients with early-stage disease will develop MBC. There are no clear guidelines on how to treat older adults with MBC (OA-MBC) due to their poor representation in clinical trials. This lack of recommendations can often lead to under treatment of OA-MBC. This study evaluated the self-reported treatment patterns of practitioners in community practices for OA-MBC and evaluated the actual treatment their OA-MBC patients received. Methods: This is a secondary analysis of a multi-phase trial which initially evaluated the gaps in practice patterns that exist in the assessment and management of OA-MBC and did a prospective comparison between the older patient’s geriatric assessment and provider’s clinical assessment. In this analysis we focused on the practice patterns in the community. Physicians completed questionnaires detailing their front-line treatment choices for each subcategory of MBC in women over the age of 65. Data was then collected on patients in these physicians’ practices including their current line of treatment, treatment regimen, comorbidities, performance status and demographics. The appropriateness of treatment choice was then evaluated based on MBC subcategory and line of treatment using the NCCN guidelines for breast cancer. Patient and physician characteristics and treatment choices were summarized using descriptive statistics. Results: 44 providers from 9 community practices located in PA, DE, NJ, MT, and WA participated. Majority of providers were Caucasian (57%) and had been in practice for >11 years (53%). 100 patients were evaluated from these practices between December 2016 – April 2019. Median age 73 (65-90). In response to front-line therapy choices, 27/44 (61%) providers selected endocrine only therapy for HR+ but in practice, 29/37 (78%) of HR+ patients were treated with combination endocrine & CDK 4/6 inhibitors. For HER2+, 20/44 (45%) providers selected trastuzumab + chemotherapy for front-line therapy and in practice 8/8 (100%) of patients received this combination. For TNBC, 37/44 (84%) providers agreed with sequential single agent chemotherapy over combination and in practice 6/7 (86%) patients received this. Including all lines of therapy, 84/100 patients were treated in accordance with NCCN guidelines. Conclusions: Despite the lack of older adult guidelines, our community-based practitioners are treating the majority of their OA-MBC patients appropriately and in accordance with NCCN guidelines. In our cohort of OA-MBC there was no evidence of under treatment, however, due to the lack of sufficient data in this patient population it is not clear that this approach is beneficial. Additional research is needed to refine the treatment approach of this unique patient population.