tbuckley/cabot-search huggingface dataset:
Abstract IA019: Collagen mineralization and its role in breast cancer bone metastasis
Authors: Claudia Fischbach
Journal: Cancer Research (2021)

Abstract Skeletal metastasis of breast cancer is associated with changes in bone mineral density, therapy resistance, and poor clinical prognosis. Most emphasis to date has been placed on studying the role of bone and marrow cells in this process, but the functional contribution of skeletal extracellular matrix (ECM) remains largely unclear. Better understanding these connections is critical as mineralized collagen, the basic building block of bone, is a key component of the osteogenic niche that tumor cells target during dissemination and that changes as a function of diet, age, and exercise. Using correlative materials science and tissue engineering approaches, we have characterized metastasis-relevant bone matrix characteristics across multiple length scales and recapitulated these properties in vitro to investigate the functional relationship between collagen mineralization and tumor cell phenotype. Breast cancer cells cultured on mineralized substrates exhibited reduced adhesion forces and accordingly reduced collagen fiber alignment relative to cells cultured on control collagen. These changes were attributed to mineral-mediated differences in collagen stress relaxation and altered mechanosignaling with consequences on tumor cell migration and expression of cancer stem cell markers. RNAseq analysis in combination with functional studies confirmed that tumor cells interacting with control vs. mineralized collagen exhibited altered proliferative and therapy-resistant capability. In vivo studies confirmed the relevance of bone matrix mineralization to secondary tumor growth and therapy resistance. These results suggest that changes in collagen mineralization directly impact hallmark features of skeletal metastasis including tumor cell dissemination, growth, and therapy resistance and underline the critical importance of bone mineral in the pathogenesis of breast cancer bone metastasis. Citation Format: Claudia Fischbach. Collagen mineralization and its role in breast cancer bone metastasis [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr IA019.
A longitudinal study for the effect of frailty on the quality of life and lower urinary symptoms following robot-assisted radical prostatectomy.
Authors: Shingo Hatakeyama, Kyo Togashi, Tomoko Hamaya, Yuta Kojima, Hayato Yamamoto, Teppei Okamoto, Takahiro Yoneyama, Yasuhiro Hashimoto, Chikara Ohyama
Journal: Journal of Clinical Oncology (2021)

45 Background: We aimed to evaluate the effect of frailty on health-related quality-of-life (HRQOL) and lower urinary symptoms (LUTS) following robot-assisted radical prostatectomy (RARP) in patients with prostate cancer (PC). Methods: We longitudinally evaluated geriatric 8 (G8), HRQOL, and LUTS for 12 months in 118 patients with RARP from January 2017 to April 2020. Patients were divided into frail (G8 ≤14) and nonfrail (G8 &gt; 14) groups. We compared the effect of frailty on HRQOL and LUTS between the frail and nonfrail groups before and 12 months after RARP. Results: The median age of patients was 68 years. The number of patients in the frail and nonfrail groups were 41 and 77, respectively. No significant difference in patients’ background was observed between the groups, except for the presence of cardiovascular disease (22% vs. 7.8%, p = 0.041). There was no significant difference in HRQOLs and LUTS between the groups at baseline. Similarly, HRQOLs, LUTS, and pad-free continence rates were not significantly different between the groups at 12 months after RARP. In the nonfrail group, LUTS at 12 months following RARP significantly improved compared to those at the baseline, but it did not significantly improve in the frail group. Multivariable logistic regression analysis demonstrated that frailty was not significantly associated with LUTS worsening. Conclusions: Frailty was not significantly associated with the worsening of HRQOL, LUTS, and pad-free continence rates in patients treated with RARP.
<i>CDKN2A</i> alterations as markers of immune checkpoint blockade (ICB) resistance in urothelial carcinoma (UC).
Authors: Amin Nassar, Elio Adib, Elie W. Akl, Sarah Abou Alaiwi, Pier Vitale Nuzzo, Tarek H. Mouhieddine, Guru Sonpavde, Robert I. Haddad, Marios Giannakis, F. Stephen Hodi, Toni K. Choueiri, David J. Kwiatkowski
Journal: Journal of Clinical Oncology (2021)

475 Background: ICB has shown clinical benefit across several metastatic carcinomas; however, predictive biomarkers are still lacking. CDKN2A is one of the most commonly altered genes across human cancers. With prior studies giving conflicting evidence regarding the association between CDKN2A alterations and ICBs, we examined the impact of CDKN2A alterations on clinical outcomes in UC patients treated with ICBs. Methods: Of 809 patients at the Dana Farber Cancer institute (DFCI) treated with ICBs only and with relevant cancer types and targeted exome sequencing data (Oncopanel), 235 (29%) had loss-of-function (LOF) mutations or homozygous deletions in CDKN2A. Overall survival (OS) was compared by Cox logistic regression between CDKN2A altered and CDKN2A wild type (WT) patients. Hazard ratio (HR) was derived using multivariable analysis (MVA), adjusted for prior lines of therapy and tumor mutational burden (TMB). A validation cohort from Memorial Sloan Kettering Cancer Center (MSKCC) (Samstein et al., Nature Genetics, 2019) of 811 cancer patients treated with ICBs was analyzed in a similar manner, adjusted for TMB. As a control, the association between CDKN2A alterations and OS was examined in a cohort of platinum-treated UC patients (N = 56) to determine whether CDKN2A alterations were predictive of response to ICIs. Results: For the DFCI and MSKCC cohorts, median follow-up was 26.9 and 24 months (m), respectively. In the DFCI and MSKCC cohorts, CDKN2A alterations were found in 32/90 (35%) and 22/104 (21.2%) of UC, respectively; 4/55 (7.3%) and 3/131 (2.3%) of renal cell carcinoma, respectively; 73/178 (41%) and 45/194 (23.2%) of melanoma tumors, respectively; 86/370 (23.2%) and 26/260 (10%) of non-small cell lung cancer (NSCLC) tumors, respectively; 18/66 (27.2%) and 4/53 (7.5%) of esophagogastric tumors, respectively; and 22/50 (44%) and 11/69 (15.9%) of head and neck, respectively. CDKN2A alterations were significantly associated with shorter OS and TTF in the DFCI UC and melanoma cohorts by MVA, and showed a trend towards significance in the MSKCC UC cohort (Table). There was no significant association between CDKN2A alterations and OS for the other cancer types in both cohorts; and no association with OS or TTF was seen in the DFCI cisplatin-treated UC cohort. Conclusions: CDKN2A alteration status may serve as a predictive biomarker in patients with UC treated with ICBs. Further studies are needed to examine the mechanism of this clinical effect. [Table: see text]
Response to: “Comment on ‘Long-term effectiveness and safety of treatment with dupilumab in patients with atopic dermatitis: Results of the TREAT NL (TREatment of ATopic eczema, the Netherlands) registry’”
Authors: Angela L. Bosma, Linde E.M. de Wijs, Michel H. Hof, Beau R. van Nieuwenhuizen, Louise A.A. Gerbens, Maritza A. Middelkamp-Hup, DirkJan Hijnen, Phyllis I. Spuls
Journal: Journal of the American Academy of Dermatology (2021)
Effectiveness of early diagnosis for prostate cancer based on PSA and multiparametric MRI: A simulation study.
Authors: Marc-Olivier Timsit, Giulia Baciarello, Christophe Hennequin, Francois Kleinclauss, Marie Laure Bazil, Philippe Bonnard, Segolene Pettre, Blachier Martin, Henri Leleu
Journal: Journal of Clinical Oncology (2021)

224 Background: Multiparametric magnetic resonance imaging (mpMRI) detects ISUP grade≥ 2 prostate cancer (PC) with a sensitivity over 90%. mpMRI can be used for early detection in patients with a risk of clinically significant PC (csPC) either in combination with systematic biopsy (SB) to increase the detection rate of csPC, or to reduce the number of biopsy procedures by performing biopsies only in positive mpMRI patients. Methods: We estimated the numbers of PC diagnosed, PC deaths averted, and biopsy procedures performed with early diagnosis in a simulated population of men beginning at age 50 using a microsimulation model. The model simulates the natural history of PC and the impact of early diagnosis using epidemiological data from a systematic review of literature. Early diagnosis started at age 55 years, with a PSA threshold of 4 ng/mL. The strategies included (S1) SB alone, (S2) SB combined with mpMRI-targeted biopsy (SB/mpMRI-TB), and (S3) SB/mpMRI-TB following selection of patients based on positive mpMRI (PIRAD3-5) or PSA density (PSAd) &lt; 0.15. A sensitivity of 0.92 and specificity of 0.48 for detecting ISUP grade ≥ 2 PC was used for mpMRI. Results: Compared to no early diagnosis, early diagnosis with SB alone (S1) was estimated to avoid 647 PC-related deaths per 100,000 men over their lifetimes. Using mpMRI was estimated to result in an additional 126 and 118 fewer deaths per 100,000 if mpMRI was used in conjunction with SB (S2) or with SB following patient selection for biopsy by mpMRI or PSAd (S3). To avoid a PC-related death was estimated to require screening of 145 men with SB alone, 121 with SB/mpMRI-TB, and 122 with mpMRI or PSAd followed by SB/mpMRI-TB. Adding mpMRI to SB was also found to reduce the predicted number of biopsies performed (21,821 for SB alone versus 16,510 for SB/mpMRI-TB and 15,385 for SB/mpMRI-TB following selection with mpMRI or PSAd). Conclusions: The results indicate that using mpMRI as a detection method will improve the effectiveness of early diagnosis. Compared to SB alone, using mpMRI through the SB/mpMRI-TB approach, with or without prior patient selection based on mpMRI or PSAd assessments, would result in a reduction in PC-related mortality and in the number of biopsies performed. [Table: see text]
Abstract 16119: Dexrazoxane Role in the Prevention of Anthracycline Cardiotoxicity in Sarcoma Patients - A Meta-analysis
Authors: JosÃ© P Sousa, Rogério Teixeira, Carolina Lourenço, Lino Gonçalves
Journal: Circulation (2020)

Introduction: Cardiotoxic side effects limit anthracycline use. Dexrazoxane has been proved cardioprotective in the setting of low-dose exposure, but its value in young sarcoma patients, who are treated with higher doses, remains elusive. Purpose: To perform a meta-analysis in order to appraise the efficacy and safety of dexrazoxane in sarcoma patients managed with anthracyclines. Methods: We systematically searched Embase, MEDLINE, Web of Science, Cochrane CENTRAL and Google Scholar databases, using the terms “sarcoma”, “anthracycline” and “dexrazoxane”, from inception to June 1, 2020. Studies targeting cardiotoxicity, primary cancer outcome (suboptimal response to treatment, disease progression and oncologic death), secondary malignancy and mortality were selected. The primary endpoint was a composite of heart failure, ventricular arrhythmias and left ventricular systolic deterioration. Therapeutic arms were those of dexrazoxane and no drug or placebo. A random-effects model with Mantel-Haenszel method was used to calculate pooled odds ratios (OR) or mean differences (MD) and their 95% confidence interval (CI). Results: We encompassed 11 studies, of which 5 were prospective. 9 studies were conducted in children and doxorubicin was the most represented anthracycline. 1574 patients were included, of whom 679 were under dexrazoxane. There were 73 primary endpoint events, 21 secondary malignant neoplasms and 29 deaths. Cumulative doxorubicin dose was higher in the dexrazoxane arm (MD 70.66mg/m2, 95% CI 46.43-94.89, i 2 24%). Nevertheless, this agent reduced the odds of the primary endpoint (OR 0.37, 95% CI 0.20-0.71, i 2 11%), as well as numerically decreased acute heart failure events (OR 0.15, 95% CI 0.02-1.09, i 2 0%) and significantly halted left ventricular ejection fraction deterioration (MD 5.25%, 95% CI 1.98-8.53, i 2 26%). On the other hand, primary cancer outcome and risk of secondary malignancy did not differ between the two arms (OR 1, 95% CI 0.47-2.15, i 2 0% and OR 0.98, 95% CI 0.39-2.47, i 2 0%, respectively). Likewise, all-cause mortality was similar (OR 1.65, 95% CI 0.68-4.00, i 2 0%). Conclusion: Dexrazoxane seems to maintain its efficacy and safety in young sarcoma patients managed with high-dose anthracyclines.
Management of localized prostate cancer during the Covid-19 pandemic at a multidisciplinary cancer center in New York City, New York.
Authors: Andrew Wood, Benjamin Shpeen, Jeffrey Lee, Rose Snyder, Yiqing Xu, Srinath Kotamarti, Ervin Teper, Marc Lubin, David Silver, Kevin Douglas Becker, Trishala Meghal, Ariel Schulman
Journal: Journal of Clinical Oncology (2021)

213 Background: In March 2020, the coronavirus disease (COVID-19) spread across New York City. All non-emergent medical care was delayed, and healthcare resources were redirected to COVID-19 patients. Physicians managing prostate cancer faced unprecedented decisions to balance risks of the pandemic against risks of cancer progression. Here we review management of localized prostate cancer at an Urban Cancer Center in New York City during the height of the pandemic. Methods: We examined men with newly diagnosed, localized prostate cancer seen in initial consultation by Urology or Radiation Oncology between January 1 and June 30, 2020 (COVID-19 cohort). We reviewed cancer management, as well as the impact of the pandemic on treatment choice and patterns of care. Chi square and t-test analyses were performed to compare the COVID-19 cohort to a similar cohort managed before the pandemic from July 1, 2019 to December 31, 2019 (pre-COVID-19 cohort). Results: We identified 75 men in the COVID-19 cohort. NCCN risk profile: 20% low risk, 53.4% intermediate, and 26.7% high. During the height of the pandemic, there was 7 week pause in both new radiation therapy (RT) and radical prostatectomy. 11 patients continued previous RT, 1 of which developed a symptomatic covid infection and required a 2 week pause in treatment. During the operating room restart, 11 patients underwent radical prostatectomy including 8 with unfavorable-intermediate or high-risk disease. No surgical patients acquired COVID-19. Compared to the pre-COVID-19 cohort, the COVID-19 cohort had longer time from initial visit to treatment (92.1 days vs 71.0 days, p = 0.045) and a larger percentage of patients who were seen but did not return for management (25.3% vs 14%, p = 0.044). Conclusions: Our cancer center had a coordinated, 7-week cessation in primary RT and surgery for prostate cancer during the height of the COVID-19 pandemic. There were no severe COVID-19 infections among patients finishing RT, or the first cohort of men having surgery during the restart of treatments, suggesting that localized prostate cancer treatments can be safely delivered in the event of a second wave. We identified a substantial number of men who were seen, but did not return for management, highlighting a cohort who need to be reintegrated into the healthcare system. [Table: see text]
Association of circulating tumor cells (CTC) with survival outcomes in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) in a real-world cohort.
Authors: Umang Swami, Taylor Ryan McFarland, Benjamin Haaland, Adam Kessel, Roberto Nussenzveig, Nicolas Sayegh, Andrew Warren Hahn, Nityam Rathi, Deepika Sirohi, John Esther, Haoran Li, Manish Kohli, Benjamin Louis Maughan, Amir Goldkorn, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2021)

59 Background: In mCSPC, baseline CTC counts have been shown to correlate with PSA responses and progression free survival (PFS) in small studies in the context of androgen deprivation therapy (ADT) without modern intensification with docetaxel or novel hormonal therapy. Similar correlation of CTC count with PSA responses and PFS was recently reported from an ongoing phase 3 trial in mCSPC setting (SWOG1216) without reporting the association in the context of ADT intensification. Furthermore, none of these studies correlated CTCs with overall survival (OS). Herein we evaluated whether CTCs were associated with outcomes including OS in a real world mCPSC population treated with intensified as well as non-intensified ADT. Methods: Eligibility criteria: new mCSPC receiving ADT with or without intensification and enumeration of baseline CTCs by FDA cleared Cell Search CTC assay. The relationship between CTC counts (categorized as: 0, 1-4, and ≥5/7.5 ml) and both PFS and OS was assessed in the context of Cox proportional hazards models, both unadjusted and adjusted for age, Gleason, PSA at ADT initiation, de novo vs. non-de novo status, and ADT intensification vs. non-intensification therapy. Results: Overall 99 pts were identified. Baseline characteristics are summarized in Table. In unadjusted analyses, CTC counts of ≥5 as compared to 0 were strongly associated with inferior PFS (hazard ratio [HR] 3.38, 95% CI 1.85-6.18; p &lt; 0.001) and OS (HR 4.44 95% CI 1.63-12.10; p = 0.004). In multivariate analyses, CTC counts of ≥5 as compared to 0 continued to be associated with inferior PFS (HR 5.49, 95% CI 2.64-11.43; p &lt; 0.001) and OS (HR 4.00, 95% CI 1.31-12.23; p = 0.015). Within the ADT intensification subgroup also, high CTC counts were associated with poor PFS and OS. For PFS, the univariate HR for CTC ≥5 vs. 0 was 4.87 (95% CI 1.66-14.30; p = 0.004) and multivariate HR for CTC ≥5 vs. 0 was 7.43 (95% CI 1.92-28.82; p = 0.004). For OS, the univariate HR for CTC ≥5 vs. 0 was 15.88 (95% CI 1.93-130.58; p = 0.010) and multivariate HR for CTC ≥5 vs. 0 was 24.86 (95% CI 2.03-304.45; p = 0.012). Conclusions: To best of our knowledge this is the first study to show that high baseline CTC counts are strongly associated with inferior PFS as well as OS in pts with newly diagnosed mCSPC, even in those who received intensified ADT therapy. Identifying these pts at highest risk of progression and death can help with counselling and prognostication in clinics as well as design and enrollment in future clinical trials. [Table: see text]
Do females have worse surgical outcomes after radical cystectomy? Impact of gender on 30-day complications in a national cohort.
Authors: Srinath Kotamarti, Michael Silver, Andrew Wood, Ervin Teper, David Silver, Ariel Schulman
Journal: Journal of Clinical Oncology (2021)

402 Background:: Men have higher rates of bladder cancer and are more likely to undergo cystectomy than women, yet women seem to have worse oncologic outcomes. This is attributed to biologic factors including adverse histologic variants and social factors including delay in diagnosis. There is early evidence that women also have worse surgical outcomes. We further examined the role of gender in 30-day perioperative outcomes following radical cystectomies in a national cohort. Methods: We examined the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) from 2012 to 2016. The database was searched for CPT codes reflecting radical cystectomy and a diagnosis of “cancer of the bladder.” Frailty was estimated by the modified frailty index (functional status, diabetes, chronic obstructive pulmonary disorder, history of chronic heart failure, and hypertension requiring medication.) To compare demographic and perioperative characteristics between genders, Chi-Square analyses were performed for categorical variables, student’s t test to compare averages, and the Wilcoxon rank sum test for operative time and length of stay (LOS). Results: 4,681 radical cystectomies were identified including 842 (18.0%) females. Of the female cohort, average age was 68.6 (+/-11.2 years), 77.3% was Caucasian and 278 (33%) had a BMI of at least 30. There were no differences appreciated between genders with regards to age, average ASA score, frailty, or minimally-invasive approach (all p=NS). Compared to males, female gender was associated with longer operative time (350 vs. 336 min, p&lt;0.009), length of stay (LOS) (8 vs 7, p&lt;0.001) and lower rates of discharge to home (79.9% vs 87.0%, p&lt;0.0001). Reoperation (4.8% vs. 6.0%), readmission (22.2% vs 20.6%), and death within 30 days (1.9% vs. 2.0%) were similar. Clavien 3 or greater was also similar among gender (Table). Conclusions: Female patients comprise a minority of radical cystectomies with slightly longer LOS and less home discharge than men, yet 30-day major complications, reoperation and mortality appear similar. [Table: see text]
Abstract 20327: Variability in Pricing of Generic Drugs for Heart Failure: Caveat Emptor
Authors: Zackary D Goff, Andrija Vidic, John T Chibnall, Barry Bleske, Paul J Hauptman
Journal: Circulation (2016)

Introduction: The advent of generic medications for CHF lessened the financial burden on uninsured and underinsured patients; however, recent controversies about pricing have raised concern about i...
Abstract IA-03: Unsupervised resolution of intra- and inter-tumoral heterogeneity using deep learning
Authors: Phedias Diamandis
Journal: Clinical Cancer Research (2021)

Abstract Applications of deep learning to histopathology has demonstrated expert-level performance, but approaches have been largely concentrated on supervised classification tasks requiring context-specific training and deployment. We demonstrate that deep neural networks, previously trained to recognize diverse histomorphologies in one environment can effectively extrapolate their learned representations to resolve clinically relevant intra- and inter-patient tissue pattern differences in other cancer types without explicit instruction or additional optimization. Moreover, this unsupervised approach highlighted numerous human misclassifications, suggesting that repositioning of existing histology-educated networks could provide scalable approaches for quality assurance and discovery of unappreciated subgroups of disease. Citation Format: Phedias Diamandis. Unsupervised resolution of intra- and inter-tumoral heterogeneity using deep learning [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr IA-03.
Interactions of host‐associated multispecies bacterial communities
Authors: Heidi Goodrich‐Blair
Journal: Periodontology 2000 (2021)

Abstract The oral microbiome comprises microbial communities colonizing biotic (epithelia, mucosa) and abiotic (enamel) surfaces. Different communities are associated with health (eg, immune development, pathogen resistance) and disease (eg, tooth loss and periodontal disease). Like any other host‐associated microbiome, colonization and persistence of both beneficial and dysbiotic oral microbiomes are dictated by successful utilization of available nutrients and defense against host and competitor assaults. This chapter will explore these general features of microbe‐host interactions through the lens of symbiotic (mutualistic and antagonistic/pathogenic) associations with nonmammalian animals. Investigations in such systems across a broad taxonomic range have revealed conserved mechanisms and processes that underlie the complex associations among microbes and between microbes and hosts.