tbuckley/cabot-search huggingface dataset:
P05.62 Post-operative cardiovascular complications and time to recurrence in meningioma patients treated with versus without pre-operative embolization: a retrospective cohort study of 741 patients
Authors: H Wirsching
Journal: Neuro-Oncology (2018)

Preoperative embolization of radiographically suspected meningiomas is often performed to facilitate subsequent tumor resection. Its effects on the post-operative course of operated meningiomas have not been studied in detail and randomized trials are lacking. The objective of this study was to explore associations of preoperative meningioma embolization with postoperative outcome. Patients undergoing resection of an intracranial meningioma at a single tertiary center 2000–2013 (N=741) were reviewed for the inclusion of pre-operative embolization in the management strategy. Annotations included demographics, radiographic, surgical, histological and hematological parameters, cardiovascular risk factors, pre- and postoperative neurological function and gene methylation-based classification. Binary regression and Cox proportional hazards models were applied to determine factors associated with outcome. Pre-operative embolization was performed in 337 patients (42%). Cardiovascular events after surgery comprised mostly deep vein thrombosis (N=39) and pulmonary embolisms (N=64). On multivariate analyses of post-operative cardiovascular adverse events controlling for established risk factors, there were associations with embolization (OR 2.38, 95% CI 1.37–4.00), and with female gender (OR 2.18, 95% CI 1.17–4.08). Recurrence-free survival (RFS) of embolized patients was less favorable among patients with WHO grade II or grade III meningiomas (median RFS: 4.3 versus 7.0 years, P=.029) or in patients with intermediate or malignant gene methylation subtype meningiomas (median RFS: 2.0 versus 8.2 years, P=.005), including in a multivariate Cox regression model that controlled for established risk factors. Pre-operative meningioma embolization may cause adverse surgical outcomes. Randomized trials to determine benefit-risk ratios are warranted to clarify the role of pre-operative embolization for meningioma surgery.
First-in-human dose escalation of monalizumab plus durvalumab, with expansion in patients with metastatic microsatellite-stable colorectal cancer.
Authors: Neil Howard Segal, Jarushka Naidoo, Giuseppe Curigliano, Sandip Patel, Solmaz Sahebjam, Kyriakos P. Papadopoulos, Michael S. Gordon, Ding Wang, Ana Gómez Rueda, Xuyang Song, Xia Li, Shannon Marshall, Shaad Essa Abdullah, Jennifer Robinson Diamond
Journal: Journal of Clinical Oncology (2018)

3540 Background: Monalizumab (IPH2201) is a humanized IgG4 antibody targeting CD94/NKG2a to suppress inhibitory signaling by tumors on NK cells. The combination of monalizumab and durvalumab (anti-PD-L1) may promote antitumor immunity via complementary mechanisms targeting both innate and adaptive immune systems. This is a first-in-human, phase 1 dose escalation and expansion study to evaluate monalizumab plus durvalumab in patients with select advanced solid tumors. Methods: Patients received durvalumab 1500 mg every 4 weeks in combination with monalizumab at increasing doses. Escalation was determined using a modified toxicity probability interval. Antitumor activity was based on RECIST v1.1. Following initial efficacy in escalation, an expansion cohort of metastatic microsatellite-stable colorectal cancer (MSS-CRC) was enrolled. Results: We report the experience of 55 patients treated with monalizumab plus durvalumab, including 15 patients in escalation and 40 in MSS-CRC expansion. In escalation, there were no treatment-related adverse events (TRAEs) that led to discontinuations, no grade 3/4 TRAEs, no DLTs, and no deaths; MTD was not reached. Any grade TRAEs were observed in 12 patients (80%); most frequent was diarrhea (n = 4). Safety in expansion was similar to escalation: 19 patients (48%) had any grade TRAEs, 1 patient had a grade 3/4 TRAE (sepsis). PK of both drugs in combination showed no interactions. Monalizumab PK approached linearity at the highest dose level, which was thus chosen for expansion. In MSS-CRC expansion (58% with 3+ lines of prior therapy, n = 37 evaluable for efficacy), there were 3 confirmed PR and 11 SD, including 3 patients with tumor reduction who continued therapy for > 200 days; DCR at 16 weeks was 24%. Updated clinical and biomarker data will be presented. Conclusions: Dose escalation of this first-in-human combination of monalizumab plus durvalumab has been completed, demonstrating a manageable toxicity profile. Preliminary data indicate that the combination has promising activity in patients with MSS-CRC, a population historically nonresponsive to PD-1/PD-L1 blockade. Clinical trial information: 02671435.
KRAS mutational status in metastatic colorectal cancer and thrombotic risk.
Authors: Laurel Anne Menapace, James Bena, Shannon Morrison, Alok A. Khorana
Journal: Journal of Clinical Oncology (2017)

e15140 Background: There is limited clinical evidence suggesting a possible association between KRAS mutational status and thrombotic risk in metastatic colorectal cancer (mCRC). We attempted to confirm previously published findings in a single institution study of mCRC patients initiating treatment at Cleveland Clinic. Methods: We evaluated the association of observed venous thromboembolic (VTE) events in relation to KRAS mutational status in a retrospective cohort of mCRC patients receiving treatment at Taussig Cancer Institute between 2009 and 2013.KRAS mutational status obtained from pathologic tissue specimens,specifically wild-type (WT) or mutant status, was recorded for each patient. Both inpatient and outpatient radiologic reports were reviewed for presence of pulmonary embolism (PE), deep venous thrombosis (DVT), and visceral vein thrombosis (VVT). All observed VTE events were analyzed, including asymptomatic or incidentally discovered VTE. Results: A total of 184 patients with newly diagnosed metastatic colorectal cancer were included in the analysis. There were a total of 47 combined VTE events observed in 42 patients. 5 subjects had more than one thrombotic event during the investigative period. 55.4% (n = 102) of mCRC patients were identified as WT whereas the remainder harbored a KRAS mutation (44.6%, n = 82). Both groups had similar rates of bevacizumab exposure. There were slightly more VTE events in the KRAS mutant cohort, with a total of 26 observed VTE events in 24 patients (29.3%) versus a total of 21 thrombotic events in 18 mCRC WT patients (17.6%). There were 16 DVTs, 6 PEs and 4 VVTs in the KRAS mutant group as compared to 10 DVTs, 9 PEs, and 2 VVTs in the WT cohort. There was no statistically significant difference in combined VTE (Odds Ratio 1.90 [0.96 - 3.91], p = 0.062), DVT (OR 0.82 [0.28 - 2.39], p = 0.06), PE (OR 2.23 [0.95 - 5.22], p = 0.71) and VVT (OR 2.60 [0.46 -14.4], p = 0.41) between groups. There was no difference in survival measured in days between KRAS mutant and WT mCRC patients. Conclusions: Based on these results, there is limited evidence that mCRC patients harboring KRAS mutations may be at greater risk for VTE. Further study of KRAS mutational status as a biomarker of thrombotic risk in cancer is indicated.
Role of ATDC gene as a biomarker of doxorubicin response in triple-negative breast cancer
Authors: R. Cervera Vidal, C. Lozano Asencio, R. Tébar Martinez, F. Martinez Martinez, J. Forés Martos, J. Climent Bataller
Journal: Annals of Oncology (2018)

Background: Breast cancer is a complex and heterogeneous disease where the patients present the same symptoms and suffer the same disease, but due to different genetic reasons. Breast cancer recurrence is one of the biggest morbidity causes in patients that suffer the disease, and 15-20% of them will develop triple-negative breast cancer tumors (TN). The mortality of patients harbouring TN tumors is higher comparing with other tumor subtypes, in part, due to the difficulty of getting personalized treatments, where chemotherapy is the standard treatment. These data show the need to look for new drug strategy, where clinical, genetics and molecular data could be integred and compared, in order to predict more accurate treatment responses. Here we study the role of the gene ATDC, previously related with radioresistance, in TN breast cancer cell lines treated with Doxorubicin. Methods: To perform the experiments, knock-down of ATDC gene was performed in order to downregulate their expression. Modifyed and control cell lines treatment with Doxorubicin was done at different concentrations and at different times, measuring the number of viable cells by MTS assay and by flow cytometry, trying to observe possible changes when ATDC is not present. Finally, a possible relationship between ATDC and the phosphorylation levels of γ-H2AX was studied. Knocked-down and control cell lines were treated with Doxorubicin and the phosphorylation rate was analyzed by Western Blot. Results: Modifying the expression of ATDC in TN breast cancer cell lines who overexpress the gene, allowed us to observe differences in cell viability and apoptosis levels after Doxorubicin treatment. Those cells with lower levels of ATDC showed lower levels of viable cells and higher apoptosis, obtaining significant statistically differences between both groups. Furthermore, ATDC knock-down cell lines treated showed lower pohsporylation levels of γ-H2AX, comparing it with treated control cell lines. Legal entity responsible for the study: Health Research Institute. INCLIVA. Conclusions: ATDC expression is related with the sensitivity of a treatment based in Doxorubicin, due to their function in DNA damage protection. Is furhtermore related with γ-H2AX phosphorilation levels and their consecuent activation, allowing the activation of DNA repair system mechanisms. Funding: Carlos III Health Institute. Spanish Government. Disclosure: All authors have declared no conflicts of interest.
A Retrospective Review of the Multidisciplinary Management of Medullary Thyroid Cancer.
Authors: Georgia Samantha Geller, Janessa J. Laskin, Winson Y. Cheung, Cheryl Ho
Journal: Journal of Clinical Oncology (2016)

e17551 Background: Medullary thyroid carcinoma (MTC) accounts for 4-10% of all thyroid cancers. Our aim was to review the treatment of MTC and the effect of newer therapies on patient outcomes. Methods: The British Columbia Cancer Agency (BCCA) provides cancer care to a population of 4.3 million people. A retrospective chart review was conducted of all patients with MTC referred to the BCCA from 1998 to 2014. Clinical characteristics, pathology and outcome data were collected. DFS and OS were determined for patients based on staging and treatment. Results: Of the 98 patients referred to the BCCA during the study period, the median age of diagnosis was 54 years (range 10-95). Inherited mutations were found in 6% and 60% did not receive genetic testing. Based on clinical SEER staging, there were 50% localized, 38% regional, and 12% distant cases. Among the 77% of patients who had complete surgical resection, 25% received adjuvant radiation therapy. Median DFS for clinical SEER stage: localized 18.97 years and regional 6.52 years (p = 0.028). Initial treatment of 23 patients with unresectable/metastatic disease consisted of: 2 surgery only, 4 radiation only, 11 surgery and radiation, 3 radiation and chemotherapy, 1 trimodality and 2 best supportive care. In the 9 patients who received one or more course of chemotherapy, there were variations in the initial regimen: 2 cisplatin/etoposide, 2 sunitinib, 3 sorafenib, 1 vandetanib, 1 adriamycin. Median overall survival based on clinical SEER stage: localized 19.93 years, regional 16.09 years, and distant 0.93 years (p < 0.001). Median OS for all patients was 16.10 yrs. Conclusions: MTC has a good prognosis with a long median OS. Treatment patterns reflect multidisciplinary management based on patients disease characteristics. Only 10% of patients required systemic therapy at some point during their disease trajectory.
Unexplained Cardiac Arrest in an Apparently Healthy Young Woman
Authors: Fabian Noti, Babken Asatryan, Jens Seiler, Samuel H. Baldinger, Helge Servatius, Stefano F. de Marchi, Michele Vittorio Martinelli, Lukas Christoph Hunziker Munsch, Anna Lam, Juerg Fuhrer, Hildegard Tanner, Laurent Roten, Argelia Medeiros-Domingo
Journal: Circulation (2018)

ECG CHALLENGEAn 18-year-old woman with a history of anorexia nervosa and multiple episodes of dizziness and syncope of unknown cause was transferred to the emergency department by ambulance 1 hour after starting to feel palpitations, dizziness, tightness in the chest, and presyncope at school.At the time of presentation, she was hemodynamically stable, but the symptoms persisted.The ECG recorded at admission is shown in Figure 1A.A supraventricular tachycardia with aberrancy was suspected.Conversion attempts first with vagal maneuvers (carotid sinus massage and Valsalva maneuver) followed by adenosine (6 mg IV) were unsuccessful, but the ventricular rate and the QRS duration normalized gradually within 12 hours.The full cardiovascular and laboratory workup showed unremarkable findings, and the patient was discharged with prescription of metoprolol 25 mg/d.One week after discharge, the patient was rehospitalized after experiencing syncope at school with rapid deterioration of consciousness.A transthoracic echocardiogram reveled severely compromised cardiac function, and extracorporeal membrane oxygenation was rapidly initiated.The ECG recorded at admission is shown in Figure 1B.On the basis of ECG findings, what is the most likely cause of this patient's arrhythmias and cardiac arrest?Please turn the page to read the diagnosis.
Neo-adjuvant chemotherapy and distress in breast cancer patients: The moderating role of generalized self-efficacy.
Authors: Stefano Magno, Stefania Carnevale, Francesco Dentale, Daniela Belella, Marinella Linardos, Riccardo Masetti
Journal: Journal of Clinical Oncology (2017)

e21570 Background: Neo-Adjuvant Chemotherapy (NAC) is commonly recommended as a preoperative treatment for patients with locally advanced breast cancers (BC). However, several studies have shown that NAC can increase patients’ distress. A first aim of this study was to evaluate if BC patients treated with NAC show higher levels of distress as compared to patients undergoing primary surgery (PS). A secondary aim was to evaluate if distress could be significantly correlated with patients’ depression and anxiety, and if generalized self-efficacy (GSE) may moderate these relationships. Methods: one hundred and twenty-four BC patients (61 waiting for PS and 63 undergoing NAC), with a mean age of 51.64 (SD = 9.67), were instructed to complete a series of questionnaires evaluating socio-demographic data, anxiety, depression, distress and GSE. Results: An analysis of covariance was conducted, including treatment condition (NAC vs PS) as an independent variable, patients’ distress as a dependent variable, and age as a covariate. A significant mean difference emerged between groups [F(1, 121) = 5.66, p &lt; .05)]. In particular, NAC patients showed a higher distress (Mean = 6.79) than PS ones (Mean = 5.72). Moreover, patients’ distress appeared moderately correlated with both anxiety (r = .34, p &lt; .05) and depression (r = .36 &lt; .05). Finally, results revealed a significant interaction effect of distress and GSE on depression (β = -.19, p &lt; .05), confirming the moderating role of GSE. In particular, for low levels of GSE (-1 SD), the correlation between distress and depression was large and significant (r = .53, p &lt; .001), while for high level of GSE (+1 SD) this relationship was definitively lower (r = .14, p = .03). No significant moderating effects of GSE were found for stress-anxiety relationship. Conclusions: Results of this study seems to confirm that NAC may induce distress in BC patients. Moreover, distress, significantly related to anxiety and depression, may play a detrimental role for patients’ psychological well-being. Finally, GSE emerged as a moderator of distress-depression relationship, suggesting that negative consequences of stress could be reduced during NAC using GSE-based psychological intervention.
Pathophysiology and therapeutic strategies for peritoneal recurrence after gastric cancer surgery.
Authors: Satoshi Murata, Katsushi Takebayashi, Hiroshi Yamamoto, Tsuyoshi Yamaguchi, Sachiko Kaida, Hirokazu Kodama, Reiko Ohtake, Tomoharu Shimizu, Tsuyoshi Mori, Yuki Kawai, Naomi Kitamura, Toru Miyake, Hiroya Akabori, Hiroya Iida, Tomoyuki Ueki, Hiromichi Sonoda, Haruki Mori, Nobuhito Nitta, Shigeyuki Naka, Masaji Tani
Journal: Journal of Clinical Oncology (2017)

4050 Background: We recently showed that cancer cells, with proliferative and tumorigenic potential, can spill into the peritoneal cavity during curative (R0) gastric cancer (GC) surgery, which is associated with peritoneal recurrence (PM). To elucidate the pathophysiology of PM, the relationship between spilled cancer cells and cancer stem cells was evaluated. Furthermore, to identify a therapeutic strategy for PM, the prognostic impact of hyperthermic intraperitoneal chemotherapy (HIPEC) following GC surgery with spillage of cancer cells was evaluated. Methods: Patients with advanced GC (≥pT2 [MP]) who underwent R0 gastrectomy between 2010 and 2015 were enrolled. Ninety-four consecutive patients with negative results in peritoneal cytology and cancer cell culture (CCC [-]) following peritoneal washing (PW) before GC surgery were included. Spilled cancer cells in PW after GC surgery (PW-Post) were examined to identify any CD44-positive cancer stem-like cells associated with cancer metastasis. Based on the PW-Post CCC results, associations between HIPEC and recurrence-free survival (RFS), or overall survival (OS) were evaluated. HIPEC was performed following GC surgery using CDDP, MMC, and 5-FU in 5 L saline maintained at 42 ˚ C for 30 min. Results: Spilled cancer cells included CD44 + cancer stem-like cells. In 48 patients with PW-Post positive CCC (CCC [+]), the number of patients with pStage I, II, and III were 4, 7, and 15, respectively, in those who received HIPEC (n = 26), and 3, 9, and 10, respectively, in those who did not (n = 22). Among patients with CCC (+), the 5-year peritoneal RFS, hepatic RFS, and lymph node RFS rates were 93.3%, 100%, and 68.5%, respectively, in patients who received HIPEC, and 56.7%, 35.6%, and 66.7%, respectively, in those who did not ( P = 0.008, P = 0.008, and P= 0.24, respectively). Among patients with PW-Post CCC (-), none developed recurrence, regardless of whether they received HIPEC (n = 28) or not (n = 18). Conclusions: The results show that PW-Post CCC is a promising predictive biomarker for recurrence after R0 GC surgery. Adjuvant HIPEC performed with R0 GC surgery showed preventive effects on peritoneal and hepatic recurrence and survival benefits for patients with PW-Post CCC (+).
A trial-based EuroQol EQ-5D health utility analysis in patients with classical Hodgkin lymphoma.
Authors: Elise Wu, Jane Liao, Arun Balakumaran
Journal: Journal of Clinical Oncology (2017)

e19011 Background: Pembrolizumab has shown a high response in patients classic Hodgkin lymphoma (cHL) patients who have experienced disease progression after brentuximab vedotin in KEYNOTE (KN)-087 and the results have been presented. This study aimed to evaluate the health-related quality of life (HRQoL) of the trial patients in KN087. Methods: KN-087 is an ongoing single-arm multi-center, non-randomized Phase II trial evaluating pembrolizumab 200mg Q3W IV in patients with relapsed or refractory cHL. In KN-087, HRQoL data were collected at baseline and every drug administration over the 18 months of follow-up. HRQoL was assessed using both the EQ-5D and EORTC QLQ-C30 instruments. The generic health statuses assessed from both instrument were converted to population-based utility values using published algorithms. More specifically, US-based scoring was applied to US patients, UK-based scoring for UK patients and EU-based scoring for all other patients. HRQoL was reported by status of respond and disease progression. Response was defined based upon IWG criteria. Furthermore, stratified analyses were conducted to examine the health disabilities of the patients who experienced grade 3+ adverse events (AEs), and by ECOG performance and the number of prior therapies. Results: Among 210 trial patients, HRQoL data were collected for 205 patients at baseline and the mean health utility score was 0.759 (95% CI 0.730-0.788). Mean health utility score among responders and non-responders was 0.826 (95% CI 0.811-0.842) and 0.760 (95% CI 0.718-0.801), respectively. The difference is considered clinically significant. Mean utility decreased from 0.820 (95% CI 0.807-0.833) for time spent prior to progression to 0.806 (95% CI 0.780-0.832) post disease progression. Progression-free patients who experienced grade 3+ AEs (N=17) had a mean health utility of 0.736 (95% CI 0.662-0.811), compared with 0.825 (95% CI 0.811-0.838) among those did not. Conclusions: The results showed a substantial HRQoL impact of R/R cHL. Treatment response was associated with significant clinically meaningful improvement in HRQoL. The utility estimates from the study are important for economic evaluations of treatments in R/R cHL patients. Clinical trial information: NCT02453594.
Long-term outcomes in laparoscopic D2 gastrectomy for gastric cancer: A large comprehensive study proposing novel hypotheses.
Authors: Tuanjie Li, LEI Huang, Guoxin Li
Journal: Journal of Clinical Oncology (2018)

e16025 Background: The long-term outcomes of LG versus open gastrectomy (OG) for GC remain obscure, especially for advanced cancer and disease affecting the upper stomach and in older patients. This study aimed to comprehensively assess the long-term efficacy of laparoscopic gastrectomy (LG) for gastric cancer (GC) using a large prospective database. Methods: Totally 1,877 consecutive patients (1,186 receiving LG and 691 OG) operated in 2004-2016 were analyzed, with a median follow-up of 63 months. Association of LG versus OG with cancer-specific survival (CSS) and disease-free survival (DFS) overall and in various subgroups and survival-associated clinicopathologic factors were investigated using multivariable Cox regression. Propensity-score matching (PSM) was performed for sensitivity analysis. LG-specific prognostic nomograms were further developed incorporating factors remaining after backward selection. Results: Before PSM, overall there was no significant association of LG versus OG with survival after multivariable adjustment; however, in subgroup analyses, LG was associated with superior CSS in patients aged ≥70 years, those with upper GC, and those with metastatic disease. No significant associations regarding DFS were observed overall or in stratifications. PSM analyses revealed similar results or trends. Median CSS and DFS were 75 and 42 months, and 5-year CSS and DFS rates were 52% and 38% in total patients undergoing LG. Multivariable analysis showed that age, hepatitis B, performance status, tumor histology, stage, and vascular invasion were significantly associated with post-LG survival. LG-specific nomograms were then constructed with concordance indexes of 0.814 (CSS) and 0.809 (DFS) and excellent calibration. Conclusions: In this large institutional analysis, while LG for GC was associated with CSS and DFS similar to those for OG overall, non-inferior/better LG-associated survival especially CSS was observed in some subgroups rarely investigated in prospective or randomized settings. These findings suggest the non-inferiority of LG versus OG in various subgroups, offering novel hypotheses for further validation.