tbuckley/cabot-search huggingface dataset:
Use of antiresorptive therapy (ART) and skeletal-related events (SREs) in patients with bone metastases of neuroendocrine neoplasms (NEN).
Authors: Leonidas Apostolidis, Dirk Jaeger, Eva Caroline Winkler
Journal: Journal of Clinical Oncology (2017)

4096 Background: Antiresorptive therapy (ART) with bisphosphonates or denosumab is effective in preventing skeletal-related events (SREs) in patients with bone metastases (BM). In neuroendocrine neoplasms (NEN), BM are a negative prognostic factor, however tend to be asymptomatic and SREs are considered a rare event. The role of ART in preventing SREs in NEN has not been investigated so far. Methods: Retrospective analysis of all patients with bone metastases in the NEN database of the National Center for Tumor Diseases who presented at our center between 12/2012 and 01/2017. Overall survival (OS) from diagnosis of BM as well as time to SRE (TTSRE) were calculated. In patients experiencing an SRE within 1 month after diagnosis (i.e. before efficacy of ART could be assessed), TTSRE was defined as the time to a subsequent SRE. Results: In a total of 513 patients in the database, 108 patients with BM could be identified. Median OS was not reached in a median follow-up of 15.2 months. ART was applied to 42.6 % of patients. OS with or without ART did not differ significantly (p = 0.2538). 28.7 % of patients experienced at least 1 SRE, 20.4 % after more than 1 month. Median TTSRE was 63.8 months with ART and 127.0 months without ART (p = 0.1751). TTSRE was shortened in grade 3 vs. grade 1+2 NEN (172 months vs. not reached, HR 4.058, p = 0.0032), as well as in lytic vs. non-lytic metastases (24.5 vs. not reached, HR 7.319, p &lt; 0.0001), however not significantly different in oligometastatic vs. disseminated bone disease (not reached vs. 63,8 months, HR 1.415, p = 0.4287). Application of ART did not significantly change TTSRE in either of these subgroups. Significant toxicity attributable to ART was observed in 15.2 % of ART patients. Conclusions: SREs in NEN patients with BM were not uncommon, especially in patients with grade 3 NEN and osteolytic metastases. Application of ART did not significantly alter median OS or TTSRE, no subgroup with a benefit of ART could be identified. The use of ART in NEN should be questioned and evaluated prospectively.
P04.82 [18F]-FET and [18F]-FAZA PET based radiotherapy of F98 glioblastoma rats
Authors: J Verhoeven, J Bolcaen, S Donche, V de Meulenaere, B Descamps, G Hallaert, K Kersemans, T Boterberg, C Vanhove, F de Vos, I Goethals
Journal: Neuro-Oncology (2018)

Glioblastoma (GB) is the most common primary malignant brain tumor in adults. The standard of care consists of maximal possible surgical resection with concomitant radiation therapy (RT) and temozolomide (TMZ). Currently the target volume delineation for RT is based on CT and MRI. In this study we investigated the feasibility of incorporating PET for guiding RT and the impact on treatment outcome by applying subvolume boosting to a [18F]-FAZA or [18F]-FET defined tumor part. F98 GB cells inoculated in the rat brain were imaged using T2- and contrast-enhanced T1-weighted (CE-T1w) MRI. After tumor growth, a 30 min [18F]-FAZA (2h p.i.) or [18F]-FET (30min p.i.) PET was acquired. Subsequently, a treatment planning CT was obtained on the small animal radiation research platform (SARRP). After manual coregistration of CE-T1w-MRI, CT and PET images, a dose of 20 Gy was delivered to the target volume based on the CE-T1w-MRI (group 1–3). In group 2 and 3 an additional radiation boost of 5 Gy (1x1 mm) was delivered to the region with maximal PET probe uptake. On five consecutive days, TMZ (5 mg i.p.) was administered in groups 1–3. Group 4 was used as a sham group, receiving injections with saline. Tumor volumes on follow-up MRI were determined by drawing volumes of interest around the tumor on CE-T1w-MRI (PMOD). CE-T1w-MRI showed a heterogeneous tumor, enabling to select the MRI target volume. Both [18F]-FAZA and [18F]-FET exhibited an increased tumor uptake. Using three non-coplanar arcs, the dose delivered to the normal surrounding brain tissue was minimized. Significant differences in tumor volumes were found between the therapy and control groups (from day 2 onwards). No significant differences were observed between the different therapy groups (p-value range 0.082 - 1 for [18F]-FET; 0.327–1 for [18F]-FAZA PET). Despite being very labor-intensive, MRI guided irradiation with PET subvolume boosting is feasible. Based on tumor growth, a significant difference was found between therapy and no therapy. Unfortunately, no significant difference could be observed between the treatment groups. Additional information from molecular imaging techniques enables the visualization of metabolically highly active regions. GB are highly heterogeneous solid tumors, hence the concept of biological target volume and multidimensional conformal RT seems promising.
Relapse after cessation of PD-1 based therapy for complete responders in metastatic melanoma.
Authors: Khang Nguyen, Robert Mason, Rahul Ladwa, Lydia Warburton, Michael Millward, Andrew Mark Haydon, Matteo S. Carlino, Jessica Louise Smith, Victoria Atkinson
Journal: Journal of Clinical Oncology (2018)

9536 Background: Treatment of metastatic melanoma using programmed death (PD-1) inhibitor has revolutionised systemic therapy, with a proportion able to achieve a durable complete response (CR). Little is known about the longterm relapse rate after cessation of therapy and the outcomes on re-induction. Methods: A retrospective review of patients (pts) who ceased PD-1 therapy after achieving CR was conducted across five institutions. The primary outcome was rate of relapse and response to therapy after relapse. Results: 182 pts that ceased PD-1 therapy following CR were included. Relapse occurred in 19 pts (10.44%), BRAF wildtype (N = 13), BRAF mutant (N = 6). Median follow-up post cessation was 22 (5-34) months. The mean duration on therapy prior to cessation was 16 (3-32) months and the mean interval between cessation of therapy and relapse was 14 (1-33) months. Relapse occurred in a site of new disease (N = 5) and in a site of prior disease (N = 14). On relapse, 12 pts were rechallenged with PD-1 therapy. Currently these pts were in CR (n = 3), partial response (n = 1), stable disease (N = 4) and progressive disease (PD) resulting in death (n = 1) or were waiting restaging (n = 3). Remaining relapses were treated with gamma knife (n = 1, this pt died following PD), gamma knife and PD-1 therapy (n = 1, pt in CR) or surgical resection (n = 3, all in CR). Two pts are waiting restaging following commencement of LAG3 inhibitor (n = 1) or topical imiquimod (n = 1). One pt elected for nil intervention following relapse and is alive with PD. Conclusions: Emerging data is suggesting that cessation of PD-1 based therapy for complete response is possible with durable disease control. This to date is the largest cohort of pts who have been followed up post cessation for complete response to describe patterns of relapse and response to subsequent re-challenge. Further long term follow-up of current trials is needed.
TCT-105 Non-periprocedural Myocardial Infarction After CABG in Patients With Left Main Disease: Analysis From the EXCEL Trial
Authors: Mahesh Madhavan, Akiko Maehara, Joseph Sabik, Bjorn Redfors, David Taggart, John Puskas, Akiko Fujino, Shmuel Chen, William Brown, Ovidiu Dressler, Ori Ben-Yehuda, Patrick Serruys, A. Pieter Kappetein, Gregg Stone
Journal: Journal of the American College of Cardiology (2018)
Nab-paclitaxel plus S-1 as first-line treatment in patients with advanced pancreatic adenocarcinoma.
Authors: Yan Shi, Huan Yan, Quanli Han, Yongkang Nie, Yao Lv, Zhikuan Wang, Guanghai Dai
Journal: Journal of Clinical Oncology (2017)

e15788 Background: Nab-paclitaxel plus gemcitabine and FOLFIRINOX showed survival advantage comparing to gemcitabine monotherapy in metastatic pancreatic cancer (PAC). However, the objective response rates (ORR) were about 30% and still unmet clinical expectation. S-1 is an oral fluoropyrimidine derivative showed comparable and superior clinical benefit in treatment of unresectable and postoperative PAC comparing to gemcitabine. Since nab-paclitaxel and S-1 provided additional clinical benefits in PAC, we conducted a single-arm, phase II trial to investigate the efficacy and safety of nab-paclitaxel plus S-1 as first-line treatment in patients with locally advanced and metastatic PAC. Methods: Nab-paclitaxel was given at 120 mg/m 2 intravenously on day 1 and 8, in combination with S-1 which was orally administered (80-120 mg/d according to the body surface area) on day 1-14 of each 21-day cycle, for 6 cycles. The primary endpoint was ORR, secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Results: Sixty patients including 5 locally advanced and 55 metastatic PAC received a median of 4 cycles (range from 2 to 6). The ORR by either blinded independent review or investigator assessment was 50.0% (Table). Median PFS and OS were 5.7 months (95%CI, 4.9 to 6.6 m) and 9.3 months (95%CI, 8.3 to 10.3 m), respectively. The most common adverse events were neutropenia, sensory neuropathy, and nausea/vomiting. Grade 3 and 4 neutropenia were 22.3% and 11.7%, grade 3 sensory neuropathy was 5%. The patients with grade 3 and 4 neutropenia, and those with biochemical response (50% reduction of CA19-9) achieved better ORR (75% and 76.7%, respectively). Of 52 patients with elevated CA19-9 at baseline, 32 patients (61.5%) had biochemical response showed a better median OS than those without the biochemical response (15.9 m versus 5.7 m, P=0.029). Conclusions: Nab-paclitaxel plus S-1 showed encouraging ORR and being tolerated. Future phase III randomized clinical trial in advanced PAC is warranted. Clinical trial information: NCT02124317. [Table: see text]
Abstract 19408: Impact of Perioperative Liver Dysfunction on In-hospital Mortality and Long-term Survival in Infective Endocarditis Patients
Authors: Mahmoud Diab, Christoph Sponholz, Michael Bauer, Andreas Kortgen, Philipp Scheffel, Thomas Lehmann, Gloria Faerber, Matthias W Pletz, Torsten Doenst
Journal: Circulation (2015)

Background: Infective endocarditis (IE) is a dangerous disease with high mortality (20-40%). A leading cause of death is multi-organ failure (MODS) with liver dysfunction (LD) as major contributor. Data on LD in IE patients are scarce. We assessed the impact of preoperative - and newly occurring LD on in-hospital mortality and long-term survival in IE patients. Methods: We retrospectively reviewed our database for surgery of left-sided endocarditis between 1/07 and 4/13. We used the hepatic Sepsis-related Organ Failure Assessment (hSOFA) score to assess the degree of LD. We performed Chi-Square, Cox regression and multivariate analyses. Results: The 308 patients had a mean age of 62 ±13.9. Preoperative LD (hSOFA &gt; 0, Bilirubin &gt; 32 μmol/L) was present in 1/4 (n=81) of patients and was associated with severely elevated in-hospital mortality (51.9% vs.14.6% without preoperative LD, p&lt;0.001). Newly-occurring postoperative LD developed in another quarter (n=57 of 227 patients without LD) of patients and was associated with elevated in-hospital mortality (24.6% vs. 11.2%, p&lt;0.001). Kaplan-Meyer 5-year survival was significantly better in patients without LD (51% vs. 19.9%, p&lt;0.01). Survival curves were practically identical after the perioperative phase was over (Fig.). Quality of life in survivors was also the same. Cox regression analysis revealed preoperative LD as independent predictor of long-term survival (adjusted hazard ratio 1.695, 95% confidence interval 1.160-2.477, p=0.009) and duration of cardiopulmonary bypass (CPB) and S. aureus infection as independent predictors of newly-occurring postoperative LD. Conclusions: LD in patients with endocarditis is a significant independent risk factor for in-hospital mortality. A considerable fraction of patients develop LD perioperatively, which is associated with cardiopulmonary bypass-duration and S. aureus infection. However, after surviving surgery, prognosis no longer seems to be predicted by LD.
Physician communication and patient understanding of molecular testing of tumors.
Authors: Rebecca D. Pentz, Rachel Hannah Pocock, Ana M Pinheiro, Jeffrey M. Switchenko, Margie D Dixon
Journal: Journal of Clinical Oncology (2017)

e18217 Background: Molecular testing is being used with increasing prevalence to diagnose and treat cancer. Novel technical terminology is required to describe this testing to patients; however, it is unknown what language is being used and whether this language is understood, This study aimed to determine how oncologists describe this testing to patients and whether patients understand the technical terms and conceptual topics used by physicians. Methods: Patients and oncologists were consented for this study at one academic and two community hospitals. Conversations including a discussion of molecular testing were recorded; patients were then interviewed to assess their understanding of the terminology and topics described by their physicians. Recordings were transcribed and qualitatively analyzed; descriptive statistics were calculated from the coded data to identify the most frequently used technical terms and conceptual topics, assess overall patient understanding, and calculate an understanding score for each patient. Results: Sixty conversations about molecular testing were observed and recorded between 60 patients and 19 physicians. Thirty-four different technical terms were used by oncologists to describe 5 technical themes (mutation, molecular testing, targeted therapy, driver mutation, and biomarker). Patients understood 45% of undefined technical terms and 43% of defined technical terms. Physicians explained why the molecular testing was ordered in 67% of conversations, with 71% of patients demonstrating understanding, and how the testing would determine the patient’s treatment in 93% of conversations, with 80% of patients demonstrating understanding. Conclusions: Oncologists use variable language to describe molecular testing to patients. Patients do not understand most of the terms being used and defining technical terms does not improve patient understanding. Despite this, oncologists are effectively communicating the purpose of molecular testing and the effect of such testing on patient treatment. Future studies are warranted to determine which language and methods are most effective for describing molecular testing to patients. Guidelines and training for oncologists may be beneficial.
Circulating miRNA and extracellular vesicle containing miRNA as response biomarkers of anti PD-1/PD-L1 therapy in non-small-cell lung cancer.
Authors: Takehito Shukuya, Joseph Amann, Vikas Ghai, Kai Wang, David Paul Carbone
Journal: Journal of Clinical Oncology (2018)

3058 Background: Anti PD-1/PD-L1 antibody is a standard first or second-line treatment for advanced non-small cell lung cancer (NSCLC), and PD-L1 immunohistochemisty is used as a predictive biomarker for therapeutic response. However, because patients with lower PD-L1 expression also show durable response in NSCLC, and the usefulness of PD-L1 immunohistochemisty results has not been shown in the other malignancies, more accurate and non-invasive predictive biomarkers are needed. Circulating miRNA and that packaged in extracellular vesicles (EVs) are considered to play a role in intercellular communication among immune cells and between immune cells and tumor cells. Methods: Pretreatment plasma of advanced NSCLC patients treated with single agent anti PD-1 or PD-L1 antibody was used in this study. Circulating miRNA was extracted from plasma by miRNAeasy kit (QIAGEN). EVs were isolated using size-exclusion chromatography column (Izon), and miRNA was extracted by miRNAeasy kit. Modified small-RNA library construction was used to make small RNA sequencing libraries, and sequenced on a NextSeq 500 sequencer (Illumina). The sequencing results were analyzed with sRNAnalyzer (http://srnanalyzer.systemsbiology.net/). Results: Samples from 14 responders (patients who showed PR or SD ≥ 6 months) and 15 non-responders (patients who showed PD in RECIST) were analyzed. Extraction of EVs was confirmed by electron microscopy. Quality and quantity of circulating miRNA and EV encapsulated miRNA were assessed by Bioanalyzer. In total, 26 circulating miRNAs (p = 0.0030 – 0.049) and 4 EV associated miRNAs (p = 0.019 – 0.043) showed significant concentration differences between responders and non-responders. Of these, 2 miRNAs were in common. Conclusions: Circulating miRNA and EV containing miRNA have potential as predictive biomarkers for anti PD-1/PD-L1 treatment response. We are in the process of identifying and validating circulating miRNA and EV miRNA signatures associated with response to anti PD-1/PD-L1 therapy.
Efficacy of haloperidol versus olanzapine for control of chemotherapy induced nausea and vomiting.
Authors: Soniya Dulal, Bishnu D. Paudel, Aarati Shah
Journal: Journal of Clinical Oncology (2018)

10053 Background: Prevention of chemotherapy induced nausea and vomiting (CINV) is an essential part of cancer care. In resource scarce countries like Nepal, determining anti-emetic combinations of highest value is of utmost importance. The purpose of the study was to compare the efficacy and toxicity of Olanzapine (OLN) (a higher cost drug) and Haloperidol (HAL) (a lower cost drug) in the prevention of CINV in patients (pts) receiving highly emetogenic chemotherapy (HEC) in a developing country. Methods: An IRB approved randomized phase II trial was performed in chemotherapy-naive pts receiving cisplatin ≥70 mg/m2 or cyclophosphamide ≥ 500 mg/m2 and doxorubicin ≥ 50 mg/m2. Pts were randomized to receive OLN 10 mg orally on day 1 to 4 or HAL 1 mg orally on day 1 and 0.5 mg BID on days 2 to 4. Both groups received ondansetron (OND) 16 mg and dexamethasone (DEX) 12 mg intravenously on day 1. Use of additional antiemetics for CINV refractory to assigned treatment arm was permitted. From day 1 to day 5, pts recorded their nausea using the Edmonton Symptom Assessment Scale (ESAS). They also recorded their daily episodes of vomiting (number and when) and the use of additional antiemetics. The primary endpoint was complete nausea prevention (CNP) (ESAS - 0). The secondary endpoint was complete emesis prevention (CEP) without the use of additional antiemetics. Results: Sixty pts consented and were randomized, 30 in each arm. There was no difference in CNP during the overall period (day 1-5 post chemotherapy) between OLN and HAL (66.6% vs 70%; p = 0.78). In both the acute period (24 hours post chemotherapy) and delayed period (day 2-5 post chemotherapy) CNP was similar between OLN and HAL (acute - 83.3% vs. 80.0%; delayed - 66.6% vs. 73.3%). No difference was identified in the rate of CEP during the overall period (80% OLN vs. 76.6% HAL; p = 0.75) nor in the acute period ( 93.3% OLN vs. 90% HAL) or delayed period (83.3% OLN vs. 83.3% HAL). No difference in toxicities was noted between treatment arm. Conclusions: In this study, HAL was comparable to OLN in the control of CINV with no statistically significant difference in the primary and secondary endpoints suggesting it is the higher value option in pts receiving HEC in a resource scarce country.
Global survey of physicians’ attitudes toward biologic and biosimilar therapies.
Authors: Anna L Molinari, Harry L Gewanter, Arturo Loaiza-Bonilla, Michael Reilly, Brian Kennedy, David Charles
Journal: Journal of Clinical Oncology (2016)

e18025 Background: Biologics and biosimilars, including interferons, monoclonal antibodies, and botulinum toxins, are novel therapies that are being increasingly utilized in various medical specialties. Despite their similarities, biologics and biosimilars are structurally distinct, and even small structural differences can yield significantly different results and effects in patients. It is important that physicians understand the differences between biologics and biosimilars and that physicians are notified of substitutions based on biosimilarity. Methods: Physicians from various practice settings in the U.S., Latin America (Colombia, Mexico, Brazil, and Argentina), and Europe (Italy, France, Germany, UK, and Spain) completed an online survey regarding their attitudes toward and understanding of biologics and biosimilars. Respondents were recruited from the following specialties: Oncology, Rheumatology, Neurology, Dermatology, Nephrology, and Endocrinology. Results: The survey was completed by 376 physicians in the U.S., 399 in Latin America, and 470 in Europe. U.S. physicians were 20% and 3% more likely to be familiar or very familiar with biologics than Latin American and European physicians, respectively. Eighty percent of U.S., 87% of Latin American, and 77% of European physicians believed that receiving notification when a biosimilar is substituted for the prescribed innovator biologic is critically or very important. Physicians in the U.S. were 45% and 64% more likely than Latin American and European physicians, respectively, to believe that patients can switch biologics mid-treatment and expect the same results. Conclusions: The majority of physicians in the U.S., Latin America, and Europe are familiar with biologics and biosimilars and want to be notified of substitutions. However, physicians, particularly those in the U.S., lack technical knowledge and understanding about the effects of biologics and biosimilars sharing the same non-proprietary name. Future educational initiatives should aim to dispel the misconception that biologics and biosimilars are structurally and therapeutically identical, and to promote a better understanding of their differences in order to improve patient care.