bluuebunny/crossref_metadata_2025_split huggingface dataset:
SBRT versus nephrectomy in the treatment of renal cell carcinoma.
Authors: Patel Mausam , Kim Thomas , Li Chenghui , Safar Ahmed , Maraboyina Sanjay 
Published: May 2020

5059 Background: Stereotactic body radiotherapy (SBRT) is being increasingly used for renal cell carcinoma (RCC) treatment in non-surgical candidates. However, no studies have compared survival between nephrectomy and SBRT. The National Cancer Database (NCDB) database was used to assess overall survival in patients undergoing SBRT vs nephrectomy. Methods: All cases of T1-T4, N0, M0 RCC diagnosed between 2004 and 2016 were extracted from the NCDB. Only patients undergoing either nephrectomy or SBRT, but not both, were included in the final analysis. Primary outcome was overall survival, defined as time in months from diagnosis to death due to any cause. Descriptive statistics were calculated for all variables. Univariate survival analysis was performed using the Kaplan Meier method and log rank test. Multivariate Cox proportional hazards regression models were performed to determine the predictive performance of covariates with respect to overall survival, reported as hazard ratio [HR] with 95% CIs. Nephrectomy patients were propensity score matched to SBRT patients for sub-cohort survival analysis. Comparisons were considered statistically significant at P < 0.05. Results: There were 243,754 patients meeting inclusion criteria with 243,488 undergoing nephrectomy and 266 undergoing SBRT. Five year OS rates were 53% and 80% for SBRT and nephrectomy, respectively (P < 0.001). On multivariate Cox regression, SBRT was associated with an increased risk of death as compared to nephrectomy (HR, 2.05; 95% CI, 1.72 – 2.44; P < 0.001). Sex, race, insurance coverage, comorbidity index, tumor grade, lymphovascular invasion status, T-stage, tumor size, and academic status of treatment facility were also independent predictors of survival. After propensity score matching of 266 SBRT patients to 266 nephrectomy patients, there were no significant differences in baseline characteristics between the groups. However, SBRT continued to demonstrate worse survival and an increased risk of death as compared to nephrectomy (HR, 1.85; 95% CI, 1.41 – 2.44; P < 0.001). Conclusions: Among node-negative, non-metastatic RCC patients, SBRT is associated with inferior survival outcomes as compared to nephrectomy, even after correcting for underlying differences in demographics, tumor characteristics, socioeconomic status, and comorbidities. These results indicate that nephrectomy should remain the standard of care for RCC patients, with SBRT reserved for non-surgical candidates.
Baseline and early change of systemic inflammation index (bSII and ΔSII) as prognostic factors in metastatic renal cell carcinoma (mRCC) patients treated with Nivolumab: Final results of the Meet-URO 15 (I-BIO-REC) study.
Authors: Rebuzzi Sara Elena , Atzori Francesco , Di Napoli Marilena , Stellato Marco , Messina Marco , Chiellino Silvia , Vignani Francesca , Cavo Alessia , Soto Parra Hector J. , Roviello Giandomenico , Prati Veronica , Bimbatti Davide , De Giorgi Ugo , Bersanelli Melissa , Paolieri Federico , Zucali Paolo Andrea , Fantinel Emanuela , Procopio Giuseppe , Signori Alessio , Fornarini Giuseppe 
Published: May 2020

5072 Background: Biomarkers to select mRCC patients most likely to benefit to immunotherapy are still needed. The retrospective multicentre Meet-URO-15 study evaluated the prognostic role of peripheral blood cells in mRCC patients treated with Nivolumab. Methods: Complete blood count was collected at the first four cycles of Nivolumab. The primary endpoint was median overall survival (mOS) according to baseline neutrophil-to-lymphocyte ratio. Secondary analyses included bSII defined as platelet x NLR (cutoff = 1375) and ΔSII defined as the difference between SII at 2ndcycle and bSII (median used as cutoff = 383). Results: From October 2015 to October 2019, 470 patients started Nivolumab as 2nd(67%), 3rd(22%) and > 3rd(11%) line. Median age was 66 years, 71% were male and 83% had clear cell histology. Baseline IMDC group was favorable in 25%, intermediate in 63% and poor in 12%. Lymph-nodes, visceral and bone metastases were present in 54%, 91% and 36%. mOS and progression-free survival (PFS) were 34.8 and 7.5 months. Overall response rate (ORR) and disease control rate (DCR) were 30% and 61%. SII was available in 404 patients: SII < 1375 (82%) correlated with statistically significant improvement of PFS [10.2 vs 4.1 months, HR 2.06 (1.54-2.76), p< 0.001], OS [46.2 vs 9.5 months, HR 3.16 (2.23-4.49), p< 0.001], ORR (35% vs 21%, p= 0.035) and DCR (67% vs 40%, p< 0.001). ΔSII was available in 360 patients: ΔSII < 383 (75%) correlated with statistically significant improvement of PFS [11.3 vs 4.7 months; HR 1.64 (1.23-2.18), p= 0.001] and OS [NR vs 21.1 months; HR 1.76 (1.21-2.56), p= 0.003], ORR (37% vs 24%, p= 0.023) and DCR (68% vs 53%, p= 0.01). Multivariate analyses adjusted for IMDC group, line of therapy and metastatic sites, confirmed the statistically significant correlation of bSII and ΔSII with OS, PFS and DCR. Conclusions: Our study showed the statistically significant correlation of lower bSII and early ΔSII with longer OS, PFS and higher DCR in mRCC patients treated with Nivolumab.
Randomized prospective trial assessing Bifidobacterium-containing probiotic supplementation in metastatic renal cell carcinoma (mRCC) patients receiving vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs).
Authors: Dizman Nazli , Hsu Joann , Bergerot Paulo Gustavo , Gillece John D , Folkerts Megan , Reining Lauren J , Trent Jeffrey M. , Highlander Sarah K , Pal Sumanta K. 
Published: May 2020

5078 Background: Studies suggest a link between the gut microbiome and mRCC outcomes, including evidence that mRCC patients (pts) possess a lower abundance of Bifidobacterium spp compared to healthy adults (Pal et al Clin Cancer Res 2015). The aim of this study was to assess if Bifidobacterium-containing probiotics could modulate the gut microbiome and impact rates of clinical benefit (CB) from VEGF-TKIs. Methods: Pts initiating VEGF-TKI therapy for mRCC were randomized to probiotic supplemented (PSu) or probiotic restricted (PRe) treatment arms. Pts in the PSu arm consumed two 4 oz servings of Activia daily. Stool samples were collected prior to therapy and at wks 2, 3, 4 and 12. Gut microbiota composition was assessed using whole genome shotgun metagenomic sequencing (Zhu et al Microbiome 2018). The primary endpoint was change in Bifidobacterium spp with therapy. Microbiome composition was compared across pts with CB (complete/partial response or stable disease) versus no CB (NCB). Results: In total, 20 pts were enrolled. The most frequent VEGF-TKIs were cabozantinib (45%), sunitinib (25%) and lenvatinib (25%). Median progression-free survival (PFS) was 6.5 months (95%CI 0.3-12.9) and CB rate was 75%. Bifidobacterium animalis, the active ingredient of Activia, reached detectable levels in all pts in the PSu arm, but was only detectable in one pt in the PRe arm. CB rate was not significantly different in PSu vs PRe arms (70% vs 80%, p > 0.05), and there was no difference in PFS. LDA effect size (LEfSe) analysis of MetaPhIAn2 data captured 25 enriched species demonstrating an LDA score > 3 in either CB or NCB. Of those with high LDA scores, Barnesiella intesitinihominis and Akkermansia municiphila were the most significant members (p = 7.4 x 10−6 and p = 5.6 10−3, respectively). While 92% of B. intestinihominis positive pts obtained a CB, only 50% of B. intestinihominis negative pts obtained CB (p = 0.036). Conclusions: This is the first prospective randomized study demonstrating modulation of the gut microbiome with probiotics in mRCC. While microbiome modulation by probiotics did not increase CB rates as intended, consecutive stool specimens allowed us to identify an association between B. intesitinihominis, A. municiphila and CB with VEGF-TKIs. In addition to the previously documented association between A. municiphila and immunotherapy outcome (Routy et al. Science 2018), this species may predict activity with VEGF-TKIs. Clinical trial information: NCT02944617 .
Ipsilateral invasive cancer risk after diagnosis with ductal carcinoma in situ (DCIS): Comparison of patients with and without index surgery.
Authors: Ryser Marc D , Hendrix Laura , Thomas Samantha M. , Lynch Thomas , McCarthy Anne , Mohammed Zahed , Francescatti Amanda B. , Frank Elizabeth S. , Partridge Ann H. , Thompson Alastair Mark , Hyslop Terry , Hwang Eun-Sil Shelley 
Published: May 2020

519 Background: Most women diagnosed with ductal carcinoma in situ (DCIS) undergo surgical resection, potentially leading to overtreatment of patients who would not develop clinically significant breast cancer in the absence of locoregional treatment. We compared the risk of ipsilateral invasive breast cancer (iIBC) between DCIS patients who received breast conserving surgery (BCS) for their index diagnosis of DCIS (BCS group) and patients who did not receive any locoregional treatment within 6 months of diagnosis (surveillance [SV] group). Methods: A treatment-stratified random sample of patients diagnosed with screen-detected and biopsy-confirmed DCIS in 2008-14 was selected from 1,330 Commission on Cancer-accredited facilities (20/site). Excluding patients who received a mastectomy ≤6 months, the final analytic cohort contained 14,245 (88.2%) BCS and 1,914 (11.8%) SV patients. Subsequent breast events were abstracted up to 10 years after diagnosis. Primary outcome was the 8-year absolute difference in iIBC risk between BCS and SV; a subgroup analysis was performed for grade I/II patients. A propensity score (PS) model for treatment was fitted with sampling design (SD) weighting and random effects for patients within facilities. Absolute risk differences were estimated using PS-SD-weighted Kaplan Meier estimators. Results: Overall, median age at diagnosis was 61 years (IQR: 52-69) and median follow-up was 5.8 years (95% CI 5.7-6.1). The majority of patients were Caucasian (81.9%), with estrogen receptor-positive (80.6%), and nuclear grade I/II (54.5%) DCIS. The fraction of patients with a Charlson comorbidity score of ≥2 was higher in SV (14.2%) compared to BCS (6.4%, p < 0.001). The 8-year risk of iIBC was 3.0% (95% CI: 2.4%-3.6%) for BCS and 7.7% (95% CI: 4.9%-10.5%) for SV, with an absolute risk difference of 4.7% (95% CI: 4.5%-4.9%; log-rank p < 0.001). Among patients with grade I/II tumors, the 8-year risk of iIBC was 3.1% (95% CI: 2.3%-4.0%) for BCS and 6.1% (95% CI: 2.5%-9.8%) for SV; difference: 3.0% (95% CI: 2.7%-3.2%; p = 0.005). Conclusions: Despite an increased risk of iIBC in SV patients compared to BCS patients, the 8-year risk did not exceed 10% in either group. The risk of recurrence in BCS patients was comparable to previously reported estimates. These data demonstrate a considerable degree of overtreatment among patients with non-high grade DCIS. Prospective clinical trials will help determine the tradeoffs between universally directed as opposed to selectively applied surgery for low risk DCIS.
Statistical machine learning model to predict Oncotype DX risk category in women over age 50.
Authors: Pawloski Kate R. , Gonen Mithat , Wen Hannah Yong , Tadros Audree B. , Abbate Kelly , Thompson Donna , Morrow Monica , El-Tamer Mahmoud 
Published: May 2020

524 Background: The 21-gene Oncotype DX Breast Recurrence Score multigene assay (RS) identifies women with ER positive, HER negative, axillary node-negative breast cancer (BC) for whom chemotherapy provides no invasive disease-free survival benefit compared to endocrine therapy alone. International adoption of RS testing is limited by cost and resource availability. We created a supervised statistical machine learning model using standard clinicopathologic data to predict RS risk category in women > 50 years old. Methods: From 2012 to 2018, women with ER positive, HER2 negative, pathologically node-negative BC of all ages were retrospectively identified from a prospective institutional database. Standard clinicopathologic data and RS were collected. Per institutional protocol, RS are ordered for all early-stage, ER positive tumors > 5 mm. Data were randomly split into training (n=3755) and validation sets (n=1609). A random forest model with 500 trees was developed on the training set, then evaluated on the validation set. Model predictors included age, tumor size, histologic subtype, hormone receptor status, lymphovascular invasion, and overall grade. The model was used to predict RS category (low risk: RS ≤ 25, high risk: RS > 25) in women > 50 years old. Results: 5364 unique tumors in 5189 women were identified. 3731 (70%) of tumors were identified in women > 50 years; median age was 63 years (IQR 57-69). In women > 50, median tumor size was 12 mm (IQR 9-17). Most tumors were invasive ductal (79%), low or intermediate grade (79%), and LVI was absent in 82% of tumors. Median ER staining by IHC was 95%; 28% of tumors had negative or weakly positive PR staining (1-20%). The model correctly classified 96.8% of patients as low risk (95% CI: 95.7-97.7). Negative predictive value for identifying low risk category was also high (92.3%, 90.7-93.6). Sensitivity for identifying high-risk women was 44.7% (37.4-52.1) and positive predictive value was 67.2% (58.2-75.3). A classification table on the validation set includes tumors with complete data available, including predictors and RS. Conclusions: Our model was highly specific (96.8%) for identifying women > 50 with RS ≤ 25 who do not benefit from adjuvant chemotherapy. This model may be utilized in lieu of RS testing if cost and availability are prohibitive. True RS > 25 was not as well predicted. The model will be refined following pathologic review of discordant cases to reduce false negatives. [Table: see text]
The predictive potential of the spatial signature of lymphocytes in breast cancer patients.
Authors: Balint-Lahat Nora , Mayer Chen , Ben-Baruch Noa , Yosepovich Ady , Sacks Kira , Ish-Shalom Shahar , Molchanov Yossef , Dadiani Maya , Morzaev-Sulzbach Dana , Gal-Yam Einav Nili , Achtenberg Albert , Gabay Yuval , Gluskin Roman , Griosman Alon , Shachaf Yuval , Luchtenstein Amir , Zelichov Ori , Alexander Kathrina , Lazar Alexander J. , Barshack Iris 
Published: May 2020

530 Background: Tumor-infiltrating lymphocytes in breast cancer have emerged as both a prognostic and a potentially predictive immunotherapy biomarker. Advancements in artificial intelligence can extract pathology-based spatial immune fingerprints for use as treatment decision support tools. Methods: We examined 908 primary breast cancer patients with whole slide images (WSI) available from TCGA database. Digital structuring of WSIs included automated detection of lymphocytes, tumor and tumor adjacent stroma, using deep learning-based semantic segmentation. Prognosis was defined as progression free interval (PFI). A Cox Survival analysis was used to detect prognostic spatial features. We used principal component analysis (PCA) to reduce and decorrelate significant features. The resulting PCA features were used to fit the final model. The model was then validated on an independent database of WSI of breast lumpectomies, from two tertiary hospitals in Israel. Results: The analysis included 908 WSI. The average age was 58.4 years old, with a majority of early stage breast cancer (76.7%, stage I and II). The detection performance for tumor area and lymphocytes reached F1 scores of 99% and 97% respectively, in comparison to human annotation. In the Kaplan Meier (KM) analysis of 414 early stage luminal breast cancers, a high number of lymphocyte clusters (LC) and a high ratio between stromal lymphocyte density and tumor lymphocyte density (LD-S/LD-T) were significantly associated with longer PFI (p = 0.005 and p = 0.038, respectively). Based on these features, two continuous PCA features were added to the multivariate model, and remained significantly associated with PFI after adjusting for age (HR = 1.19, 95% CI 1.05-1.35; HR = 1.26 95% CI 1.03-1.55). The validation set was underpowered (n = 79) and data is still being collected. In a preliminary KM analysis of 37 early stage luminal breast cancer cases from the validation set, LD-S/LD-T was significantly associated with longer PFI (p = 0.046). Conclusions: In our study, LC and LD-S/LD-T, presumably surrogate measures of peritumoral lymphocytes, were found significantly associated with longer PFI.
Disparities in receipt of and time to adjuvant therapy after lumpectomy.
Authors: Dankwa-Mullan Irene , Roebuck M. Christopher , Tkacz Joseph , Fayanju Oluwadamilola Motunrayo , Ren Yi , Jackson Gretchen Purcell , Arriaga Yull Edwin 
Published: May 2020

534 Background: Adjuvant treatment after breast conserving surgery (BCS) has been shown to improve outcomes, but the degree of uptake varies considerably. We sought to examine factors associated with post-BCS receipt of and time to treatment (TTT) for adjuvant radiation therapy (ART), cytotoxic chemotherapy (ACT) and endocrine therapy (AET) among women with breast cancer. Methods: IBM MarketScan claims data were used to select women diagnosed with non-metastatic invasive breast cancer from 01/01/2012 to 03/31/2018, who received primary BCS without any neoadjuvant therapy, and who had continuous insurance eligibility 60 days post-BCS. Logistic and quantile regressions were used to identify factors associated with receipt of adjuvant therapy (ART, ACT, AET) and median TTT in days for ART (rTTT), ACT (cTTT), and AET (eTTT), respectively, after adjustment for covariates including age, year, region, insurance plan type, comorbidities, and a vector of ZIP3-level measures (e.g., community race/ethnicity-density, education level) from the 2019 Area Health Resource Files. Results: 36,270 patients were identified: 11,996 (33%) received ART only, 4,837 (13%) received ACT only, 3,458 (10 %) received AET only, 5,752 (16%) received both ART and AET, and 9,909 (27%) received no adjuvant therapy within 6 months of BCS. (318) 1% of patients received combinations of either ART, AET or ACT. Relative to having no adjuvant therapy, patients > 80 years were significantly less likely to receive ART only (relative risk ratio [RRR] 0.65), ACT only (RRR 0.05), or combination ART/AET (RRR 0.66) but more likely to receive AET alone (RRR 3.61) (all p < .001). Patients from communities with high proportions of Black (RRR 0.14), Asian (RRR 0.13), or Hispanic (RRR 0.45) residents were significantly less likely to receive combination ART and AET (all p < .001). Having HIV/AIDS (+11 days; p = .01) and residing in highly concentrated Black (+8.5 days; p = .01) and Asian (+12.2 days; p = .04) communities were associated with longer rTTT. Longer cTTT was associated with having comorbidities of cerebrovascular disease (+6.0 days; p < .001), moderate to severe liver disease (+12.3 days; p < .001) and residing in high-density Asian communities (+18.0 days; p < .001). Shorter eTTT (-11.4 days; p = .06) and cTTT (-14.8 days; p < .001) was observed in patients with comorbidities of dementia. Conclusions: Results from this cohort of privately insured patients demonstrate disparities in receipt of post-BCS adjuvant radiation and systemic therapy along multiple demographic dimensions and expose opportunities to promote timely receipt of care.
Association of intraoperative opioids with improved recurrence-free survival in triple-negative breast cancer.
Authors: Montagna Giacomo , Hannum Margaret L , Tan Kay See , Plitas George , McCormick Patrick J. , Fischer Gregory W , Morrow Monica , Mincer Joshua S 
Published: May 2020

542 Background: Opioid-induced immunomodulation may be of particular importance in triple negative breast cancer (TNBC) where an immune response is associated with improved outcome and response to immunotherapy. We evaluated the association between intraoperative opioids and outcomes in a large TNBC cohort. Methods: Consecutive patients with stage I-III primary TNBC treated between 03/2010 and 12/2016 were identified from our prospectively maintained database. Total intraoperative opioid dose was extracted from anesthetic records and converted to oral morphine milligram equivalents (MME) (10 MME = 50 mcg fentanyl IV). Univariable and multivariable (MVA) Cox proportional hazards analysis (adjusting for relevant clinicopathological features, (neo)adjuvant therapy, anesthesia technique and morbidity score), were performed to quantify the association between opioid exposure and recurrence-free survival (RFS) and overall survival (OS). Results: 1143 patients were included. Median age was 54 years (IQR 45, 64). 911 (80%) had ductal histology, 359 (31%) had nodal metastases, and 1070 (94%) were poorly differentiated. 781 (68%) received adjuvant chemotherapy and 313 (27%) received neoadjuvant chemotherapy. 525 (46%) received total intravenous anesthesia and 618 (54%) had general anesthesia. Median intraoperative opioid dose was 30 MME (IQR 20, 60). 5-year RFS was 81% (95% CI 79%-84%), 5-year OS was 86% (95% CI 84%-88%). In MVA, higher opioid administration was associated with favorable RFS but did not significantly affect OS (Table). Conclusions: Our study is the first to directly evaluate intraoperative opioid administration in TNBC and suggests a protective effect on RFS. Future work will focus on elucidating the underlying mechanism for this effect, including possible modulation of endogenous opioid signaling pathways and immunologic correlates. [Table: see text]
A novel biosignature to assess residual risk in ductal carcinoma in situ (DCIS) patients after standard treatment.
Authors: Bremer Troy , Shah Chirag , Patel Rakesh , Wadsten Charlotta , Kesslering Christy , Shivers Steven , Whitworth Pat W. , Warnberg Fredrik , Vicini Frank 
Published: May 2020

548 Background: There is an unmet need to identify women diagnosed with DCIS with elevated risk after standard treatment for whom enhanced treatment strategies should be considered. A response type (RSt) signature has been assessed in women treated with breast conserving surgery (BCS) with or without radiotherapy (RT), or with mastectomy. Methods: Women diagnosed with pure DCIS and treated with BCS or, BCS with whole breast RT were consecutively collected in Sweden, 1986-2004 and the USA, 1999-2008. A third cohort treated with mastectomy was collected in Sweden from 1986-2004. Patients with FFPE tissue were included unless they had prior or simultaneous invasive breast cancer (IBC). The RSt and DCISionRT biosignatures were calculated using biomarkers (p16/INK4A, Ki-67, COX-2, PgR, HER2, FOXA1, SIAH2), scored by board certified pathologists. Pathology and clinical data were collected from medical records. Only women at elevated risk by DCISionRT (DS > 3) and negative margins were included in analysis. Total breast event risk included either ipsilateral DCIS or IBC. Multivariate Cox proportional hazards and survival analysis were used to assess cumulative incidence risk differences, hazard ratios, and 10-year risks adjusted for year of diagnosis. Results: Women with a poor RSt were all HER2 positive and remained at particularly elevated risk after BCS and RT (23% 10-yr risk, p < 0.0001, Table), with a risk profile similar to women treated with BCS without RT (RSt not evaluated). The distribution of age and size were not statistically different for good versus poor RSt, but poor RSt were more commonly Grade 3. In a small cohort of women treated with mastectomy, those women with a poor RSt were still at elevated risk after surgery, comparered to women with a good RSt (HR = 5.4, p = 0.014). The 10-year risk profile for women with a good RSt treated with BCS plus RT or mastectomy, was low (table). Conclusions: A novel biosignature identified women with a good and poor RSt, where the good RSt identified women with an apparent substantial benefit from RT, as well as women with a poor RSt who remained at particularly elevated risk after RT, and for whom enhanced treatment strategies should be considered. Additional validation studies are ongoing. [Table: see text]