bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolated same-basin lymph node recurrence after precision lymph node excision for clinically evident melanoma metastasis.
Authors: Lynch Kevin , Hu Yinin , Farrow Norma , Song Yun , Meneveau Max , Kwak Minyoung , Lowe Michael C. , Bartlett Edmund , Beasley Georgia , Karakousis Giorgos , Slingluff Craig L. 
Published: June 2021

9576 Background: While management of the nodal basin for melanoma has largely moved to observation for microscopic sentinel lymph node (SLN) metastasis, complete lymph node dissection (CLND) remains the current standard of care for melanoma patients with macroscopic, clinically detectable lymph node metastases (cLN). As CLND is associated with high surgical morbidity, we sought to study whether cLN may be safely managed by excision of only clinically abnormal nodes (precision lymph node dissection, PLND). Currently, a small subset of patients with cLN do not undergo CLND because of frailty or patient preference. We hypothesized that in these selected patients, PLND would provide acceptable regional control rates. Methods: Retrospective chart review was conducted at four academic tertiary care hospitals to identify melanoma patients who underwent PLND for cLN. cLN were defined as palpable or radiographically abnormal nodes. Recurrences were categorized as local/in-transit, same-basin lymph node, or distal lymph node/visceral. The primary outcome was isolated same-basin recurrence after PLND. Results: Twenty-one patients underwent PLND for cLN without synchronous distant metastases (characteristics of primary lesions summarized in Table). Reasons for forgoing CLND included patient preference (n=8), imaging indeterminate for distant metastases (n=2), comorbidities (n=4), loss to follow up (n=1), partial response to checkpoint blockade (n=1), or not reported (n=5). The inguinal node basin was the most common site (n=10), followed by the axillary (n=8) and cervical basins (n=3). A median of 2 nodes were resected at PLND, and 68% of resected nodes were positive for melanoma (median: 1, range: 1-3 nodes). Median follow-up was 23 months from PLND, and recurrence was observed in 28.6% of patients overall. Only 1 patient (4.8%) developed an isolated same-basin recurrence. The 3-year cumulative incidence of isolated same-basin recurrence was 5.3%, while risk of isolated local/in-transit recurrence or distant basin/visceral metastasis were 19.8% and 33.3%, respectively. Complications from PLND were reported in 1 patient (4.8%) and were limited to post-operative seroma and lymphedema. Conclusions: These pilot data suggest that PLND may offer acceptable regional disease control for cLN. Post-operative morbidity from PLND was also low, raising the possibility that PLND may provide adequate regional disease control without the morbidity associated with CLND. These data justify additional, prospective evaluation of PLND in selected patients.[Table: see text]
Genome-wide association study to reveal novel germline markers of melanoma survival.
Authors: Chat Vylyny , Ferguson Robert , Morales Leah , Moran Una , Kim Min Jae , Snuderl Matija , Osman Iman , Weber Jeffrey S. , Kirchhoff Tomas 
Published: June 2021

9581 Background: Cutaneous melanoma (CM) is the most invasive form of skin cancer accounting for ̃80% of all skin cancer related deaths. While tumor staging (based on recent AJCC classification) is routinely used in prognostic assessment, a large fraction of the outcomes is not explained by AJCC staging system. This urges for the discovery of a more personalized prognostic surrogates. Growing evidence highlights the role of germline genetics in CM progression; yet, to date no systematic prognostic germline study has been conducted in melanoma. We performed the first genome-wide association analysis (GWAS) to identify germline variants associated with melanoma survival. Methods: A cases/case GWAS was performed using the Infinium global screening array (GSA v3.0) to genotype 1,117 stage 0-III melanoma patients with no history of immunotherapy treatments ascertained at New York University Langone Health (NYULH). We randomly divided the study cohort into a discovery (N=630) and a validation (N=487) sets and tested the association of > 5 million imputed germline variants with melanoma overall survival (OS) by fitting Cox-proportional hazard ratio (HR) regression in an additive genetic model adjusting for sex, age at diagnosis, AJCC 8th staging, tumor anatomic sites, and top 3 principal components. Results: We found 151 independent variants associated with melanoma OS (p< 5×10−5) in the discovery cohort. Two of these associations validated in the independent replication set ( Bonferroni threshold for 151 tests: p < 0.003) with enhanced clinical and statistical significance in the pooled meta-analysis: rs4128212 [HR =2.47(1.75-3.48); p=2.2× 10−7], and rs13212644 [HR =2.59 (1.72-3.88); p=4.2× 10−6]. We further tested the combined effect of these two variants and found the presence of at least one risk allele of the variants associated with a substantially increased risk of death, surpassing GWAS level of significance (HR=3.74 (2.43-5.74); p=1.5×10−9). Conclusions: We present the results of first GWAS testing an association of germline variation with melanoma OS. Stemming from a unique patient population with extensive clinical follow-up data, we identified two prognostic germline loci with large HR effect size >2.5 that were independently validated. The observed association is independent of established histopathologic markers. While rs4128212 was mapped to a putative cancer prognostic gene locus (PLPP4: phospholipid phosphatase 4), rs13212644 was an eQTL (expression quantitative trait loci) for GCLC (Glutamate-Cysteine Ligase Catalytic Subunit), a key regulator in glutathione synthesis previously linked with favorable melanoma survival. The significantly enhanced combined effect of these two loci (HR >3.5; p<5×10−9) indicates a great promise for their clinical utility as independent personalized predictive markers of melanoma progression.
Application of RSClin to guide treatment recommendations for premenopausal patients with early-stage hormone-positive breast cancer and intermediate risk oncotype recurrence scores.
Authors: Zimmerman Brittney Shulman , Berwick Shana , Kessler Alaina J , Seidman Danielle , Hovstadius Sara Malin , Moshier Erin , Blanter Julia , Berkalieva Asem , Jaffer Shabnam , Berger Natalie F , Cascetta Krystal Pauline , Tiersten Amy 
Published: June 2021

e12511 Background: The RSClin model, which incorporates the Oncotype Recurrence Score (RS) and clinicopathologic features, was recently developed to further tailor prognosis and prediction of chemotherapy benefit for patients with early-stage hormone positive (HR+) breast cancer (BC) (Sparano et al, 2020). The RSClin calculator is available online to assist treatment planning for situations where chemotherapy benefit is uncertain. Covariates include Oncotype RS, tumor grade, tumor size and patient age. The risk calculator generates a 10-year distant recurrence risk and absolute chemotherapy benefit. This tool may be especially helpful to determine treatment management for premenopausal patients with early-stage HR+ BC with intermediate risk (IR) Oncotype RS (16-25). We retrospectively applied RSClin to this patient population to determine if it would have changed treatment recommendations. Methods: We identified premenopausal women with node-negative early-stage BC with IR RS (16-25) within our large Oncotype database. Using the RSClin model, we selected >5% absolute chemotherapy benefit as a reasonable cutoff to recommend chemotherapy. We compared the treatment recommendation based on RSClin with the treatment previously recommended by breast oncologists at our large academic medical center in New York City. Results: There were 86 patients who met criteria with a median age of 46 years. Of these, 26 patients (30%) were recommended chemotherapy plus endocrine therapy (ET) and 60 (70%) were recommended ET alone. After applying the RSClin model (data available for 83/86 patients), 19 (23%) would have resulted in a change in treatment recommendation and 64 (77%) would have remained unchanged. Overall, 8 (10%) would have withheld chemotherapy when it was previously offered and 11 (13%) would have recommended chemotherapy when it was previously excluded. There were 8 (9%) secondary invasive breast events in this population, with 2 (2%) being ipsilateral, 3 (3%) being contralateral and 3 (3%) metastatic at a median follow up of 46.9 months. Conclusions: The RSClin model would have changed management of premenopausal patients with IR RS in 23% of patients. This model, although not yet prospectively validated, may help individualize therapy for patients with less definitive treatment plans. Using RSClin, we can aim to minimize recurrence rates and avoid unnecessary chemotherapy in selected patients. This model is easy to apply and will have important clinical utility moving forward.
Study on the extract of Huangqi and Ezhu for the crosstalk of exosomes mediating tamoxifen resistance on LCC9 cells.
Authors: Cui Shasha , Zhang Dongni , Lu Wenping 
Published: June 2021

e12517 Background: Estrogen receptor (ER)-positive breast cancer is the most frequent subtype accounting for about 70% of all cases. Tamoxifen (TAM) is still the most effective drug for treating ER+/PR+ breast cancer. However, recurrence and metastasis still occur in 30-50% of patients due to TAM resistance. Furthermore, studies have shown that breast cancer stem cells (BCSCs) play an important role in TAM resistance, and exosomes regulate dynamic changes of BCSCs in tumor microenvironment. Additionally, the extract of Huangqi and Ezhu (EHE) has been shown to inhibit multiple TAM-associated resistance signaling pathways. In the current study, we investigated the effect of EHE to reverse TAM-resistance in LCC9 cells via crosstalk of distinct types of exosomes. Methods: Exosomes were extracted from LCC9 cells by ultracentrifugation and characterized by particle size detection, transmission electron microscopy and western blot analysis. Subsequently, isolated LCC9 exosomes were used to treat bone marrow stem cells (BMSCs) with EHE only, TAM only, EHE and TAM (EHETAM), and no treatment (negative control, NC). After treatment, exosomes of BMSCs were isolated and incubated further with LCC9 cells. CCK-8 assay and flow cytometry analysis were performed, and protein expression in treated LCC9 cells was tested by western blot analysis. Results: Data from CCK-8 assay showed that compared with the NC group, proliferation of LCC9 cells was significantly reduced in the presence of exosomes of BMSCs treated with TAM (82.9%, 77.1% , 75.4%), EHE (73.2 %, 69.5% , 68.2 %) and EHETAM (68.9 %, 52.3%，54.1% ) after 24h, 48h, and 72 h, respectively (p < 0.001). EHE and EHETAM groups have more effective inhibition on cell proliferation than TAM only group on the different time separately(p < 0.001).Flow cytometry analysis demonstrated that compared with the NC group(6.1%), increased apoptosis was observed for groups of TAM (8.1%), EHE (12.5%) and EHETAM (12.2%) (p < 0.001). Compared with TAM only group, EHE and EHETAM groups also have significantly higher cell death rate (p < 0.001). Lower CD44 and HER2 expression and higher ERα expression were observed in EHE, TAM, and EHETAM than those of NC group by western blot analysis of treated LCC9 cells. Conclusions: EHE treatment can reverse TAM-resistance by interfering with the crosstalk between BMSCs and breast cancer cells exosomes to induce more active apoptosis and reduce TAM-resistant CD44+ cancer stem cells.
Prediction of long-term prognosis over ten years in ER-positive HER2-negative early-stage breast cancer using 18F-FDG PET/CT before treatment.
Authors: Tsukada Hiroko , Tsukada Jitsuro , Noguchi Eiichiro , Okamoto Takahiro 
Published: June 2021

e12542 Background: Although ER-positive, HER2-negative early-stage breast cancer is considered to have a relatively good prognosis, it is known to occur long-term recurrence for more than 10 years. 18F-FDG PET/CT has been reported to be useful in predicting short-term recurrence of breast cancer (2-5 years), but its correlation with long-term prognosis over ten years in ER-positive HER2-negative breast cancer is not clear. In the present study, we examined whether tumor FDG accumulation of pre-treatment PET/CT can be a predictor of long-term overall survival (OS) in ER-positive, HER2-negative early-stage breast cancer patients. Methods: Of 639 primary breast cancer patients treated at our institution between January 2007 and May 2010, 332 patients with stage 2 or less and ER-positive HER2-negative tumors who were able to confirm whether or not they had recurred at ten years postoperatively were included in the study. The impact of patients' characteristics, tumor background, and tumor FDG accumulation of pretreatment PET/CT image on OS was investigated using Cox regression analysis. P < 0.05 was considered to be a statistically significant difference. Results: There were 33 (9.9%) recurrences and 13 (3.9%) deaths during a median observation period of 121 months. Univariate analysis showed that tumor SUVmax / FDG accumulation in lymph nodes / stage / N category / diameter of invasion / nuclear grade were candidate predictors of OS. Multivariate analysis revealed that SUVmax (Hazzard ratio 1.36 [95% CI 1.13-1.63], P < 0.001) was the only predictor of OS. Conclusions: In patients with ER-positive HER2-negative early-stage breast cancer, tumor SUVmax on pretreatment PET/CT was the only independent predictor of OS.
Assessment of the treatment results in patients with breast cancer coexisting with pregnancy: A single-center observational study.
Authors: Skrzypczyk-Ostaszewicz Anna , Jagiello-Gruszfeld Agnieszka I. , Giermek Jerzy , Nowecki Zbigniew 
Published: June 2021

e12566 Background: This study discusses the analysis of the prospectively collected material on pregnant patients treated for breast cancer at the Department of Breast Cancer and Reconstructive Surgery of the Maria Skłodowska-Curie National Oncology Institute - National Research Institute (until 2020: Oncology Center - Institute) in Warsaw, in the years 1995 - 2020. 84 patients were included into the final analysis and 72 children were assessed simultaneously. Methods: The paper summarizes information on the diagnosis and treatment of breast cancer during pregnancy, the course of pregnancy and childbirth and the birth parameters of children i.e. weight, length and Apgar score, as well as the dependencies between them, mainly the impact of some breast cancer, diagnosis and treatment process features on the newborns. The patietnt’s survavial - DFS ( disease free survival) and OS ( overall survival) - was also analyzed. The course of breast cancer diagnosis and treatment data were obtained from the patients’ medical documentation (medical records) and from information provided by the mothers during follow-up visits and read in the children's health books. In order to answer the research questions, statistical analyzes were conducted using the IBM SPSS Statistics 26 package. Results: In the analyzed period, the disease recurrence was recognized in 34 (40.5%) patients, and 24 (28.6%) patients died. The median disease-free survival (DFS) was 12.3 years (147.5 months), and the median overall survival (OS) was not reached during the follow-up period. The estimated 5-year survival rates for DFS and OS were 57.9% and 74.5% respectively, and for 10-year survival - 51.4% and 64.5%. The study showed a statistically significant relationship between the baseline clinical advancement and DFS. It has been also analyzed how the diagnosis, treatment and method of pregnancy termination changed in two time periods (1995-2012 and 2013-2020). There were no statistically significant differences in survival - both DFS and OS - between the group of patients treated before and after 2012. In the assessment of the impact of some factors on the birth children parameters (weight and length), statistically significant results were obtained for: pregnancy advancement at diagnosis, breast cancer stage at diagnosis, pregnancy advancement at the start of chemotherapy, the chemotherapy regimen (classic or dose-dense), the number of cycles of chemotherapy given during pregnancy, and the number of drugs used in supportive treatment. Conclusions: The entire analysis has become not only an insightful characteristic of the studied group, but also these results may be important in everyday clinical practice and may help to optimize the management of an extremely complex and difficult situation, which is the coexistence of pregnancy with a malignant disease that threatens the mother’s life.
A nomogram to predict the value of mammary adipose index (MAI) for prediction of response to neoadjuvant chemotherapy in breast cancer patients.
Authors: Xu Wenxiu , Tang Jinhai 
Published: June 2021

e12607 Background: Breast cancer (BCa) is the most common malignancy in females on a global scale. Neoadjuvant chemotherapy (NACT) is a promising therapeutic approach for the treatment of locally advanced BCa, which result in primary tumor regression and optimal surgical planning. Cumulative evidence has identified a deleterious crosstalk between cancer cells and the surrounding mammary adipose tissue during tumor progression. Mammary adipose index (MAI) is a novel indicator defined by us, which represents the percentage of adipose tissue in breast. Therefore, this study aims to investigate the correlation between MAI and NACT efficacy of BCa by establishing an intuitive nomogram. Methods: Clinical data of 221 BCa patients who received NACT at the First Affiliated Hospital of Nanjing Medical University from January 1, 2018 to May 31, 2020 were retrospectively collected. Besides, patients were divided into major histological response and non-major histological response group in line with Miller-Payne pathology grading. The level of MAI was collected from magnetic resonance imaging of breast, and was divided into two groups according to the cut-off value. The level of MAI and clinicopathological characteristics were collected to assess the predictive roles of NACT response. Univariate analysis was performed by Chi-square test or Fisher’s exact test. Indicators with P < 0.05 were included in multivariate binary logistic regression analysis. The nomogram was constructed based on results of multivariate logistic analysis. The predictive accuracy and discriminative ability were evaluated by C-index and the calibration curve. Results: Among the 221 patients enrolled, 77 cases (34.84%) were represented by major responses of pathologic histology. In univariate analysis, the level of MAI, tumor size, node status, ER status, PR status HER-2 status and Ki-67 status were correlated with NACT. Multivariate Logistic regression analysis showed that tumor size, HER-2 status and the level of MAI were independent influencing factors for the response to NACT in BCa patients. The patients with a high level of MAI (≥0.6916) were more likely to have a worse NACT response. MAI was an independent predictor for NACT efficacy, and area under the curve of ROC, specificity and sensitivity of the predictive model were 0.805, 0.632 and 0.774 respectively. The nomogram established based on these factors showed its discriminatory ability, and the C-index for prediction was 0.881. The calibration curve indicated that the predictive ability of the nomogram was a good fit to actual observation. The difference was statistically significant (P < 0.05). Conclusions: The nomogram constructed in the present study indicated that the level of MAI could predict the efficacy of NACT in BCa patients, which might provide clinical guidance for the selection of appropriate treatment decisions.
Intra- and inter-observer variability in tumor infiltrating lymphocyte scoring in breast cancer core needle biopsy.
Authors: Geršak Klara , Gazic Barbara , Klevisar Ivancic Andreja , Ruzic Gorenjec Nina , Grasic Kuhar Cvetka 
Published: June 2021

e12626 Background: Morphological evaluation of tumor lymphocyte infiltration (TIL) in breast cancer (BC) is gaining importance in the clinical setting, as it provides good prognostic information. Most institutions adhere to TIL working group guidelines for evaluating TIL, while having to settle on an acceptable error margin due to its subjective nature, which leads to intra and inter-observer scoring discordance. We aimed to analyze both at our institution, using experienced and inexperienced examiners, with a continuous variable scoring system. Methods: 209 BC core needle biopsy (CNB) samples were stained using hematoxylin-eosin. The percentage of stromal TIL was scored using a numerical variable ranging from 1 to 100. The examination group consisted of two experienced pathologists (pathologist A and B) and one inexperienced examiner - a medical oncology resident with a learning process containing study of the TIL working group analysis criteria and about 100 samples analysed together with an experienced pathologist Pathologist A and the resident analyzed the study samples twice, pathologist B once. Intraclass correlation coefficient (ICC) was used to measure overall intra and inter-observer agreement. Statistical analysis was performed using Google Sheets and Python. Results: 203 CNB samples were analysed (6 were excluded due to inadequate quality or an inconclusive diagnosis). Patients were aged 26 to 79 years (median 49). Sample size ranged from 1 to 16 mm (median 8). The proportion of BC subtypes was: luminal A-like 18%, luminal B-like 39%, HER2+ 10%, luminal B-like HER2+ 12%, TNBC 18%, not defined 2%. The highest proportion of high stromal TIL (≥50%) was seen in HER2+ (30%) and TNBC (22%) subtypes, as observed by pathologist A. We found good intra and inter-observer ICC (Table). Conclusions: Acceptable intra and inter-observer variability was observed in experienced pathologists, suggesting that the proposed methodology could reliably be used in clinical practice, research and trials. Interestingly, variability analysis of scores from a trained non-pathologist has also produced good results. However, it is important to note that inexperienced scoring could be prone to errors, for example counting non-lymphocyte cells as such, not recognizing regions of necrosis or sample damage, or not distinguishing between the tumor and peripheral stroma. Intraclass correlation: two-way random, single score (ICC2); pathologist A and resident (R) first and second analysis (A1, A2, R1, R2); pathologist B analysis (B1). Interpretation of ICC: <0.50 poor; 0.50-0.75 moderate; 0.75-0.90 good (0.75 = minimal acceptable value for a reliable clinical measurement); >0.90 excellent. Clinical trial information: 2018-000547-11. [Table: see text]