tbuckley/cabot-search huggingface dataset:
Tumor-specific diagnostic values of the diagnostics in lung cancer.
Authors: Lotte Mandigers, Saskia Houterman, Ben Van Den Borne
Journal: Journal of Clinical Oncology (2014)

e18541 Background: Accurate diagnostics is crucial for patients with suspected lung cancer, since delay in the diagnostic process may result in an even poorer prognosis. This study aimed to give an overview of tumor-specific diagnostic values of chest radiograph, CT, PET-CT, bronchoscopy, TBNA, EBUS-TBNA, EUS-FNA and thoracentesis in patients with suspected lung cancer. Methods: In this retrospective descriptive study, data were collected of patients who had a diagnostic procedure for suspected lung cancer at the Catharina Hospital in Eindhoven, the Netherlands, between January 2011 and August 2013. Patients with suspected lung cancer, recurrent disease, pulmonary metastases or pleuritis carcinomatosa were included. The results of the tests were evaluated and diagnostic values were calculated using the standard definitions. Results: 785 patients with suspected lung cancer were included. Sensitivity and negative predictive value of various diagnostics are presented in Table 1. Sensitivity of imaging modalities and bronchoscopy were influenced by size, histology and location of the tumor. Sensitivity of TBNA, EBUS-TBNA, and EUS-FNA were influenced by result of mediastinal staging with PET-CT. Approximately half of the mediastinoscopies could be avoided using endosonographic procedures. Conclusions: For each individual patient with suspected lung cancer the most appropriate diagnostic tests should be chosen. This choice should be based on both test- and tumor characteristics, including size, location, histology and result of mediastinal staging with PET-CT. Sensitivity and negative predictive values of the diagnostics for lung cancer. Diagnostics Sensitivity Negative predictive value Chest radiograph 84.6, (81.2- 87.6) 43.3, (35.0-51.9) CT 95.2, (87.5- 98.4) 89.2, (73.6-96.5) PET-CT 98.0, (96.2- 99.0) 89.9, (81.8-94.8) Brushing 41.7, (36.6- 47.0) 33.4, (28.3-39.0) Washing 41.6, (36.9- 46.6) 34.2, (29.4-39.3) Biopsy 72.4, (64.6- 79.1) 27.1, (16.7-40.5) TBNA 72.9, (62.0- 81.7) 34.3, (19.7-52.3) EBUS-TBNA 95.6, (89.6- 98.4) 93.8, (85.6-97.7) EUS-FNA 92.2, (80.3- 97.5) 89.2, (73.6-96.5) Thoracentesis 78.1, (66.6 – 86.6) 59.0, (42.2-74.0) Data shown as %, (95% CI).
Prior high-dose IL-2 therapy (HDIL2) may improve the outcome of sunitinib (Su) treatment (tx) in patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Eli Rosenbaum, Maya Gottfried, Hans J. Hammers, Mario A. Eisenberger, Michael Anthony Carducci, Victoria J. Sinibaldi, Victoria Neiman, David Sarid, Eliahu Gez, Henry Hayat, Avivit Peer, Avishay Sella, Wilmosh Mermershtain, Keren Rouvinov, Raanan Berger, Daniel Keizman
Journal: Journal of Clinical Oncology (2014)

e15550 Background: Targeted txs are the tx of choice in most mRCC pts. However, HDIL2 which may produce durable responses in a small percentage of cases, is still an option in carefully selected pts. While the effect of prior HDIL2 on the outcome of targeted txs in mRCC pts is poorly defined, a recent single center report (Birkhäuser FD, Cancer J 2013) revealed an improved disease-specific survival in pts treated with prior HDIL2. We aimed to study the effect of prior HDIL2 tx on outcome of mRCC pts treated with sunitinib. Methods: Records from 302 mRCC pts treated with Su from 2004 to 2013 in 9 centers across 2 countries were retrospectively reviewed. We compared the response rate, progression free survival (PFS), and overall survival (OS), between post HDIL2 pts (n=27) and individually matched tx naïve pts (n=27). Progression free survival and overall survival were determined by Cox regression. Results: All pts had prior nephrectomy and clear cell histology. The groups were matched by age (median 61), gender (male 74%), Heng risk (favorable 37%, intermediate 59%, poor 4%), sunitinib induced hypertension (67%), sunitinib dose reduction/treatment interruption (41%), smoking status (active 7%), use of angiotensin system inhibitors (41%), the presence of more than one metastases site (96%), and pre-tx neutrophil to lymphocyte ratio (> 3 in 22%). Furthermore, they were balanced regarding the presence of lung (68%), liver (31%), and bone (43%) metastases, and the use of bisphosphonates (32%). In prior HDIL2 versus tx naïve pts, objective response was partial response/stable disease 89% (n=24) versus 74% (n=20), and progressive disease at first imaging evaluation within the first 3 months (mos) 11% (n=3) versus 26% (n=7) (p=0.29, OR 2.4). Median progression free survival was 21 versus 12 mos (HR 2.3, p=0.005), and median overall survival 25 versus 20 mos (HR 2.2, p=0.013). Conclusions: In metastatic renal cell carcinoma patients treated with sunitinib, prior high dose IL-2 therapy may improve the outcome.
Abstract 20618: Phosphorylation of Acetyl-coa Carboxylase by Ampk In Platelets Controls Thromboxane Generation, Dense Granules Secretion and Thrombus Formation
Authors: Sophie Lepropre, Shakeel Kautbally, Luc Bertrand, Gregory Steinberg, Bruce E Kemp, Alexandre Hego, Odile Wera, Sanne Brouns, Frauke Swieringa, Bruno Guigas, Johan W Heemskerk, Cecile Oury, Sandrine Horman, Christophe Beauloye
Journal: Circulation (2017)

Introduction: AMPKα1 is activated in thrombin- or collagen-stimulated platelets. Acetyl-CoA carboxylase (ACC), the bona-fide substrate of AMPK, is phosphorylated/inhibited upon platelet stimulation but its role in platelets has never been investigated. ACC is a central regulator of lipid metabolism. Hypothesis: Given the roles of lipids in platelets, namely structural, energy storage and signaling, we hypothesized that ACC phosphorylation could affect platelet functions and thrombus formation. Methods: Platelets were isolated from a knock-in mouse model (KI) expressing a genetically modified ACC that can no longer be phosphorylated/inhibited by AMPK. In vitro, platelet adhesion and thrombus formation were measured using a flow chamber-based assay. Hemostasis was assessed via the measurement of bleeding time. Thrombosis was studied upon ferric chloride-induced carotid artery injury Results: Platelets express the ACC1 isoform. Thrombin or collagen stimulation led to a rapid increase in ACC phosphorylation i...
Molecular Predictors and Current Management of Minimal Residual Disease (MRD) Following Induction Chemotherapy for Acute Myeloid Leukemia (AML)
Authors: Aaron D Goldberg, Christopher Famulare, Sean M Devlin, Noushin Farnoud, Kamal Menghrajani, Minal Patel, Sheng Cai, Andrew Dunbar, Zachary D. Epstein-Peterson, Erin McGovern, Jessica Schulman, Jacob L Glass, Justin Taylor, Aaron D Viny, Bartlomiej Getta, Maria E Arcila, Ross L. Levine, Brian C. Shaffer, Boglarka Gyurkocza, Esperanza B. Papadopoulos, Miguel-Angel Perales, Elli Papaemmanuil, Sergio Giralt, Yanming Zhang, Mikhail Roshal, Martin S. Tallman
Journal: Blood (2018)
Impact of Donor Chimerism-Guided Immunomodulation after Allogeneic Stem Cell Transplant on the Outcome of Patients with AML and MDS
Authors: Juliane Steinmann, Sarah Lindner, Zuzana Jedlickova, Salem Ajib, Saskia C. Gueller, Tobias Berg, Julia Riemann, Fabian Lang, Rosa Toenges, Hans Martin, Michael Kramer, Johannes Schetelig, Hubert Serve, Christian Thiede, Gesine Bug
Journal: Blood (2018)
Partial cytoreductive nephrectomy versus cytoreductive nephrectomy in metastatic renal cell carcinoma.
Authors: Iuriy Vitruk, Oleksandr Stakhovskyi, Oleg Voylenko, Volodymyr Kotov, Maxim Pikul, Eduard Stakhovsky
Journal: Journal of Clinical Oncology (2014)

e15591 Background: Role of partial cytoreductive nephrectomy (PCN) for patients with metastatic renal cell carcinoma (mRCC) is still questionable nowadays. But in era of TKI’s such patients live longer and renal isufficiency that may be triggered by cytoreductive nephrectomy (CN), which is currently standard of care, may impact survival. Our objective was to present the update on outcomes of patients with mRCC treated with PCN and to compare survival with patients who underwent standard CN. Methods: We retrospectively identified data of 116 patients with mRCC who underwent treatment in our institution from 2008 to 2013. Mean age was 55.9±6.4. PCN was performed in 44(37.9%) cases and CN in 72(62.1%) patients. Clinical data was analyzed and survival curves were calculated for both groups. Results: Mean follow up for the whole group was 19.3±12 (ranging from 3 to 65) months. PCN and CN groups comparison revealed no significant difference between the groups in terms of age, ECOG status, follow-up, use of targeted therapy, intraoperative blood loss, preoperative creatinine levels, postoperative hospital stay. The only difference was seen in tumor size: 59.3mm ± 27.3 vs. 80.4mm± 36.5 (g< 0.001). Kaplan-Meier survival curves showed significant difference in survival favouring the group of PCN (p=0.007). Median overall survival for PCN was 35 months versus 16 months for group of CN. Conclusions: PCN show very promising primary results for selected group of patients with resectable primary lesions in mRCC and it should be evaluated in larger cohort of patients or prospective randomized trial. Preserving additional functional renal parenchyma may effect into increased survival while maintaining the main advantages of cytoreduction.
Effects of temozolomide and bevacizumab in patients with pretreated relapsed uterine leiomyosarcoma.
Authors: Naoki Sasaki, Hiroko Kouta, Masashi Takano, Tomoko Goto, Ryoko Kikuchi, Yuji Ikeda, Kazuya Kudoh, Sayaka Ikeda, Tsunekazu Kita, Kenichi Furuya, Yoshihiro Kikuchi
Journal: Journal of Clinical Oncology (2014)

5603 Background: Treatments for patients with uterine leiomyosarcoma (ULM) include anthracyclin-based chemotherapy and Docetaxel/Gemcitabine, but these regimens are not satisfactory. Temozolomide (T) has been reported to show a moderate response rate in advanced or recurrent ULM. In addition, ULM has a plenty of vascularity, unlike leiomyoma. Thus, we evaluated the effects of T combined with bevacizumab (B) in patients with pretreated/relapsed ULM. Methods: Simon's two-stage design was used. In the first stage, 7 patients were accrued. If there were no responder in these patients, the study would be stopped. Otherwise, seven additional patients will be accrued for a total of 14. If three or more responder were observed in 14 patients, this design yields a type I error rate of 0.03 and power of 0.81 when the true response rate were 30%. Enrolled patients with pretreated/relapsed ULM were treated with weekly B (2mg/kg; days 1, 8, and 15, q4w) and T (80mg/day, daily), and treatment continued until disease progression. Results: Among 7 patients in the first stage, two responses were observed, and a total of 14 patients were analyzed in this study. Among 14 cases, two (14%) had a complete response (CR) and three (21%) had a partial response (PR). Additionally, six patients (43%) had a stable disease (SD) for at least three months. The response rate (CR+PR) and clinical benefit rate (CR+PR+SD>3mo) were 35% and 78%, respectively. The median progression-free survival was 10.5 months (range from 3 to 44 months). There were no treatment-related deaths or CTCAE grade 4 toxicities, and no dose reduction due to toxicity was observed. Conclusions: T combined with B was effective in patients with relapsed ULM with tolerable toxicity profile. Remarkably, two cases achieved a complete remission more than 6 months. The regimen could be a candidate for the patients with ULM in further prospective studies.
Molecular profiling of serous ovarian carcinoma to identify extreme response phenotypes and diagnostic discrepancies.
Authors: Douglas A. Levine, Sheri Sanders, Dennis Chi
Journal: Journal of Clinical Oncology (2014)

5532 Background: Patients with serous ovarian cancer (SOC) generally require multiple lines of chemotherapy for the long-term management of disease. Clinical trials and standard care are increasingly stratified by histologic subtypes. Molecular profiling may help to select chemotherapy regimens and identify diagnostic discrepancies that influence treatment decisions and clinical trial stratification. We aimed to identify extreme resistance phenotypes and diagnostic discrepancies through commercial molecular profiling. Methods: Patients with a clinical diagnosis of SOC who underwent molecular profiling in a CLIA-certified laboratory were identified through database searches. Results from immunohistochemistry and target capture next-generation sequencing were reviewed. Extreme phenotypes were identified through a combination of putative resistance markers. Diagnostic discrepancies were identified when mutation profiles were inconsistent with reference frequencies defined by The Cancer Genome Atlas (TCGA) ovarian cancer project. Two-sided statistical tests were used, as appropriate, with significance at P < 0.05. Results: An extreme drug resistance phenotype was identified in 20 (3.4%) of 597 patients through a combination of ABCB1 overexpression and either high expression of TUBB3 or low expression of TOP2A, suggesting resistance to taxanes and anthracyclines, respectively. PTEN loss was identified in 60 (16.6%) of 361 patients with pathogenic TP53 mutations, suggesting potential therapeutic utility for AKT/mTOR pathway inhibitors. KRAS, NRAS or BRAF mutations were identified in 41 (7.1%) of 578 patients sequenced. Most (82.9%) of these mutations were in patients without TP53 mutations, suggesting a diagnostic discrepancy as SOCs typically have universal somatic TP53 mutations and no RAS/RAF mutations. Conclusions: Molecular profiling can identify putative extreme resistance phenotypes and diagnostic discrepancies. As gynecologic oncology moves toward stratified treatments for SOC, accurate histologic subtyping is increasingly important. Future studies are needed to demonstrate the predictive accuracy of putative resistance phenotypes.
Characteristics of Patients (pts) Who Relapse and Die of Multiple Myeloma (MM) within One Year Post Frontline Autologous Stem Cell Transplant (ASCT) in the Novel Agent Era: An Ultra-High Risk Population
Authors: Hatem Alahwal, Heather J. Sutherland, Shruthi Ganeshappa Kodad, Stephen H. Nantel, Yasser Abou Mourad, Michael J. Barnett, Donna L. Forrest, Alina S. Gerrie, Donna E. Hogge, Sujaatha Narayanan, Thomas J. Nevill, Maryse Power, David Sanford, Cynthia L. Toze, Jennifer White, Raewyn Broady, Kevin Song
Journal: Blood (2018)
Non-clear cell renal cell carcinoma (nccRCC): A Brazilian experience.
Authors: Rosely Yamamura, Jose A. Rinck, Victor Hugo Fonseca Jesus, Monique Celeste Tavares, Ana Luisa de Castro Larciprete, Pietro Schettini Iennaco, Helano C. Freitas, Isabela Werneck Cunha, Marcello Ferretti Fanelli
Journal: Journal of Clinical Oncology (2014)

e15608 Background: nccRCC is a rare and heterogeneous group of tumors, accounting for 25% of all renal cell carcinomas (RCC). There are limited data about its natural history, prognosis and management. We looked at the clinical features, prognostic factors and treatment outcomes of this group at our institution. Methods: The records of 125 patients (pts) diagnosed with nccRCC and followed between 2007 and 2013 were retrospectively studied. Overall survival (OS), relapse-free survival (RFS) and progression-free survival (SLP) were estimated by Kaplan-Meier method. Univariate analysis using Cox regression model was performed to determine possible prognostic factors associated with the risk of relapse. Results: Median age at diagnosis was 55 years. 68% were male. 44.8% pts had hypertension, 21.6% other primary malignancies and 4% a family history of kidney cancer. Histologic distribution: papillary (36%); chromophobe (22.4%); oncocytoma (20.8%); collecting duct (4%); medullary (7.2%); other (5.6%). 2 different histologies were seen in 10.4% pts. 64% pts presented with stage I disease; 4% had stage IV nccRCC. 71.2% of the cases were incidentally discovered. Median follow-up was 20.3 months. In the subgroup of pts with localized disease, RFS and OS at 1, 3 and 5 years were 90% and 99%, 86% and 92%, and 55% and 87%, respectively. Factors associated with risk of relapse were type of surgery, histology, pathological T (pT), necrosis and incidental diagnosis. Considering those with metastatic disease (at diagnosis and during follow-up), 16 of 20 pts received systemic therapy in first-line: 8 received VEGF inhibitors, 3 Temsirolimus, 1 immunotherapy and 4 chemotherapy. Median PFS with first-line therapy was 6.01 months. 7 pts received second-line therapy and 5 pts third-line. OS at 1, 2 and 3 years were 74%, 64% and 50% respectively. The most common metastatic sites were bone (55%), lymph nodes (55%), lung (50%) and liver (35%). Conclusions: In our study, median age at diagnosis was lower than that known for RCC. High frequency of association with other primary cancers was found. Type of surgery, incidental diagnosis, pT, necrosis and histology were predictors of relapse.
Impact of age and frailty on survival in older adults with squamous cell carcinoma of the anus.
Authors: Daniel Yokom, Shabbir M.H. Alibhai, Martine Puts, James D. Brierley, John Kim, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2018)

786 Background: Patients with anal cancer (AC) can achieve long-term disease control with chemoradiation (CRT), however, the treatment has serious adverse effects. Most patients with AC are ≥65 but little is known about cancer outcomes in this population. Frailty measures have been proposed to determine the risk of treating older adults. The purpose of this study was to evaluate the impact of age and frailty on outcomes in patients with AC. Methods: A retrospective review was performed of patients age ≥65 with non-metastatic AC treated from 2007-2016 at Princess Margaret Cancer Centre. A 44-item Cumulative Deficit Score was constructed to quantify frailty as per the Rockwood model. The impact of age and frailty on treatment toxicity and overall survival (OS) was analyzed using multivariable logistic regression and survival models, respectively, adjusting for ECOG performance status (PS), stage and treatment modality. Results: Among 92 patients, median age was 72 and 42.4% were age ≥75. Seventy (76.1%) patients were treated with CRT and 17 with radical radiotherapy (RT). After a median follow-up of 34.9 mo (range 0.5-103.9) 34 patients died – 16 from metastatic AC, 16 from other or unknown causes, and 2 treatment-related deaths. For patients treated with CRT or RT (N = 87), 53 (60.9%) required treatment modification due to toxicity. Twenty patients (22.9%) had an emergency room visit or hospitalization. Frailty did not significantly increase the risk of toxicity in multivariable analysis (OR 1.9, 95% CI 0.35-10.8). Treatment with CRT increased the risk of toxicity compared to RT alone (OR 9.5, 95% CI 1.7-53.8). Patients ≥75 had shorter OS on univariable analysis (HR 1.9, 95% CI 1.0-3.8) but not on multivariable modeling (HR 1.5, 95% CI 0.72-3.4). Factors associated with shorter OS were increased frailty (HR 3.8 CI 1.4-10.2) and ECOG ≥2 (HR 3.9, 95% CI 1.7-9.1). There was good discrimination of the model with a C-statistic of 0.77. Conclusions: Older adults with AC experience a high rate of treatment toxicity especially with CRT relative to RT alone. OS was significantly associated with frailty as well as PS but not age. Frailty assessment may improve treatment planning and understanding survival for older patients with AC.
Early Detection and Molecular Characterization of Therapy-Related Leukemia in Children Reveals Patterns of Disease Transformation and Guides Future Surveillance Protocols
Authors: Barbara Spitzer, Gunes Gundem, Noushin Farnoud, Nathan Millard, Erin McGovern, Minal Patel, Max Levine, Juan Medina, Yangyu Zhou, Juan E. Arango Ossa, Michael Francis Walsh, Ross L. Levine, Irene Y. Cheung, Scott A. Armstrong, Nai-Kong V. Cheung, Elli Papaemmanuil
Journal: Blood (2018)
A Breath-Taking Diagnosis
Authors: Ersilia M. DeFilippis, Anju Nohria, Harold J. Burstein, Leona A. Doyle, Amy L. Miller, Joseph Loscalzo
Journal: New England Journal of Medicine (2019)

A 71-year-old woman with a history of locoregional recurrent breast cancer and a remote and recent history of radiation therapy presented with new, progressive dyspnea on exertion that had developed during the previous week.
Bisphosphonate treatment of primary breast cancer patients with disseminated tumor cells in the bone marrow.
Authors: Andreas D. Hartkopf, Markus Wallwiener, Markus Hahn, Diana Stefanescu, Sven Becker, Erich Solomayer, Tanja Fehm, Sara Brucker, Diethelm Wallwiener, Florin-Andrei Taran
Journal: Journal of Clinical Oncology (2014)

11044 Background: The role of the addition of bisphosphonates (BPs) to adjuvant breast cancer treatment is unclear. Recent trials have reported different results in terms of survival. In a large meta-analysis, menopausal status was found to predict efficacy of BPs. As BPs primarily target the skeletal system to modify disease progression, we aimed to investigate whether primary breast cancer (PBC) patients that harbor disseminated tumor cells (DTCs) in their bone marrow (BM) might benefit from adjuvant BPs. Methods: BM aspirates were collected from patients that underwent surgery for PBC at Tuebingen University Hospital, Germany between 01/2001 and 01/2013. DTCs were identified by immunocytochemistry (pancytokeratin antibody A45/B3) and cytomorphology. Patients with a DTC-positive BM were included into this retrospective analysis. The influence of BP therapy on disease free (DFS) and overall survival (OS) was analyzed in an univariate (log-rank test) and multivariate analysis (cox regression). Results: 794 patients were available for this retrospective analysis. In 329 (41%) of these patients, BPs were added to conventional adjuvant therapy. Univariate analysis revealed that there was a significant risk reduction in terms of DFS (hazard ratio (HR)=0.42 [95% confidence interval (CI): 0.25-0.69], p<0.001) and OS (HR=0.49 [95% CI: 0.30-0.82], p=0.006) in patients treated with BPs. In a subgroup analysis, BPs significantly enhanced DFS (p=0.018) but not OS (p= 0.235) in premenopausal patients; in postmenopausal patients BPs improved DFS (p=0.014) and OS (p=0.009). In a multivariate analysis, independent predictors of reduced DFS were BP treatment and nodal status and independent predictors of reduced OS were BP treatment, nodal status and PR status. Conclusions: Adjuvant BP therapy can improve survival in primary breast cancer patients that harbor DTCs in the BM. Whether the DTC status is predictive for BP treatment efficacy must be evaluated in prospective trials.