tbuckley/cabot-search huggingface dataset:
Correlation of circulating tumor cell phenotypes based on epithelial-mesenchymal transition with prognosis in first-line chemotherapy of HER2-negative metastatic breast cancer.
Authors: Xiuwen Guan, Fei Ma, Chunxiao Li, Shiyang Wu, Shangying Hu, Jiefen Huang, Xiaoying Sun, Jiayu Wang, Yang Luo, Ruigang Cai, Ying Fan, Qiao Li, Shanshan Chen, Pin Zhang, Qing Li, Binghe Xu
Journal: Journal of Clinical Oncology (2018)

e24039 Background: Although evidence indicated that heterogeneity of circulating tumor cells (CTCs) based on epithelial-mesenchymal transition (EMT) phenotype is correlated with disease progression, no standard recommended guidelines have been established for clinical practice. Methods: We enrolled 108 metastatic breast cancer (MBC) patients from the prospective phase III CAMELLIA study (ClinicalTrials.gov,NCT01917279) and applied the CanPatrol CTC enrichment technique to identify CTC phenotypes (including epithelial CTCs, biophenotypic epithelial/mesenchymal CTCs, and mesenchymal CTCs) in peripheral blood samples. ROC curve analyses for 1-year progression free survival (PFS) rate were conducted to determine the optimal cut-off value and Kaplan Meier analysis and Cox proportional hazards regression analysis were performed to investigate the prognostic value of the combined criteria. Results: The ROC curve analyses for 1-year PFS rate were performed in total CTC counts and the proportion of mesenchymal CTCs, of which the optimal cut-off value for total CTC counts was 9.500 (AUC 0.538, 95% CI:0.418–0.657), while 0.107 (AUC 0.581,95% CI:0.463–0.699) for the proportion of mesenchymal CTCs. Taking the cut-off value of both total CTC counts and the proportion of mesenchymal CTCs into consideration, we proposed the combined criteria for reduced PFS in which the total CTC enumeration equaled to or exceeded 10 per 5 ml with a percentage of mesenchymal CTCs surpassing 10.7%. Significantly decreased PFS (median 6.23 vs 9.87 months, p = 0.010) was illustrated in patients who matched the combined criteria, and a nomogram was constructed based on the criteria and significant clinical-pathological characteristics with a C-index of 0.62 (p < 0.001). Conclusions: The assessment criteria combined variation in total CTC enumeration with a switch between epithelial CTCs and mesenchymal CTCs together were demonstrated to be significantly correlated with prognosis for MBC. These findings may provide an uncomplicated and practical approach to therapeutic resistance monitoring and prognosis evaluation in MBC. Clinical trial information: NCT01917279.
P04.89 Investigation of the interaction of simultaneously applied photon irradiation and Tumor Treating Fields using a Geant4 simulation
Authors: M Mayer, G Hürtgen, M Schlenter, A Stahl, M Eble
Journal: Neuro-Oncology (2018)

Tumor Treating Fields (TTFields) are low intensity, alternating electric fields approved for treating glioblastoma. In glioblastoma patients, TTFields are delivered via insulated ceramic transducer arrays applied to the scalp. Preclinical data suggest synergistic effects of simultaneous treatment with radiation and TTFields, which may be applicable clinically. Therefore, we investigated the technical issues involved in simultaneously combining TTFields with radiation using a Geant4 simulation. The Geant4 simulation of a linear accelerator and the ongoing processes in the irradiation with 6 MV photons was extended by implementation of an electric field, which could be switched on within the used phantom. The alternating electric fields were approximated by constant electric fields. Irradiation with 6 MV photons was simulated with and without an electric field in the phantom. The resulting dose distributions in the phantom were compared with each other to identify any influence on the secondary electrons by the electric field. The implementation of the electric field was successfully validated. Electrical field strengths in the range of the TTFields (2 V/cm) in the direction of irradiation and perpendicular to the direction of irradiation did not show any significant changes in the dose distributions. A shift in the position of the maximum of the depth dose curve could only be observed at electric field intensities of 2 MV/cm, which is 106-times the field intensity of TTFields applied in a clinical setting. Regarding the influence of the photon irradiation by TTFields on the secondary electrons, a simultaneous application of both therapies seems feasible. Other aspects of simultaneous therapy remain to be explored. The information obtained by three-dimensional simulation contributes to a better understanding of the simultaneous treatment with TTFields and photon irradiation. In conclusion, simulations suggest that applying TTFields during radiation does not influence the dose distribution and is safe.
Low-toxic myeloablative conditioning regimen in haploidentical hematopietic stem cell transplantation for elderly patients with acute myeloid leukemia.
Authors: Cynthia Aristei, Valentina Lancellotta, Alessandra Carotti, Claudio Zucchetti, Antonio Pierini, Simonetta Saldi, Loredana Ruggeri, Lucia Amico, Martina Iacco, Andrea Velardi, Massimo Fabrizio Martelli
Journal: Journal of Clinical Oncology (2018)

7038 Background: Elderly candidates for hematopoietic stem cell transplantation (HSCT) cannot tolerate myeloablative conditioning regimens because of regimen-related toxicity and mortality rates. To lower them in elderly patients with acute myeloid leukemia (AML) who underwent 1-haplotype mismatched (haploidentical) HSCT, we designed a conditioning regimen with total marrow/total lymphoid irradiation (TMI/TLI) and low chemotherapy doses. The graft contained, as adoptive immunotherapy, a ratio of conventional T cells (Tcons) and T regulatory cells (Tregs) that induce a Graft versus Leukemia effect with a low incidence of Graft versus Host Disease (GvHD). Methods: July 2015-October 2017: 14 AML patients (median age 62 years, 6 in 1th and 7 in 2nd complete remission, 1 in partial remission) underwent haploidentical HSCT. Composite comorbidity/age scores were 1/2 in 7 patients and 3/4 in 8. TMI/TLI target volumes were skeletal bones, major lymph node chains and spleen. TMI/TLI was delivered from day -7 to day -4, in 2 daily fractions of 1.5 Gy (TMI) and 1.3 Gy (TLI) (total doses 13.5Gy and 11.7Gy respectively). Chemotherapy: tiothepa 2.5 mg/kg on days -10 and -9; fludarabine 30 mg/m2 from days -10 to -6; cyclophosphamide 15 mg/kg on days -8 and -7. Haploidentical grafts consisted of 10x106/kg purified CD34+cells, 1x106/kg Tcons, 2 x106/kg freshly isolated Tregs. No post-transplant immunosuppression was given. Results: All patients sustained primary full-donor type engraftment and 11/14 are alive and relapse-free at a median follow-up of 18 months. Grade II-IV acute GvHD developed in 6 patients (43%) and chronic GvHD in none. Transplant-related causes of death were veno-occlusive disease (1), sepsis (1) and acute GvHD (1). Immune reconstitution was good, with peripheral blood T cells rapidly increasing. Conclusions: This innovative TMI/TLI-based conditioning with low dose chemotherapy and adoptive immunotherapy with Tcons and Tregs was efficacious as there have been no relapses to date. It was associated with low regimen-related toxicity and mortality. This exploratory analysis needs to be confirmed in a larger cohort of patients enrolled in a clinical trial.
Phase II study of alisertib, irinotecan, and temozolomide in children with relapsed and refractory neuroblastoma: A report from the New Approaches to Neuroblastoma Therapy (NANT) consortium.
Authors: Steven G. DuBois, Araz Marachelian, Elizabeth Fox, Rachel A. Kudgus, Joel M. Reid, Susan G. Groshen, Jemily Malvar, Rochelle Bagatell, Lars M. Wagner, John M. Maris, Randall Hawkins, Jesse Courtier, Hollie Lai, Fariba Goodarzian, Hiroyuki Shimada, Najee Boucher, Scarlett Czarnecki, Denice D Tsao-Wei, Katherine K. Matthay, Yael P. Mosse
Journal: Journal of Clinical Oncology (2016)

10556 Background: In phase I testing in 22 patients with neuroblastoma, the maximum tolerated dose of alisertib tablets with irinotecan/temozolomide was 60 mg/m2/dose. This combination showed significant activity [31.8% response rate; 52.4% 2-year PFS]. This study sought to: confirm the activity of this regimen; evaluate an alisertib oral solution (OS); and identify predictors of response and toxicity. Methods: We conducted a two-stage phase II trial of alisertib tablets (60 mg/m2/dose x 7 days), irinotecan (50 mg/m2/dose IV x 5 days), and temozolomide (100 mg/m2/dose orally x 5 days) in patients 1-30 years of age with relapsed/refractory neuroblastoma. The primary endpoint was best response. Secondary endpoints were toxicity, PFS, and pharmacokinetics. A cohort was treated with alisertib OS at 45 mg/m2, a dose anticipated to be bioequivalent to 60 mg/m2 tablets. Exploratory analyses evaluated predictors of response and toxicity using data from phase I, II, and OS cohorts. Results: Twenty and 12 patients were treated in phase II and OS cohorts, respectively. Hematologic toxicities were the most common adverse events. In phase II, 4 responses (20%) were observed as well as 4 patients with minor responses. The 1-year PFS was 64.5%. In the OS cohort, 3 patients (25%) had first course dose-limiting toxicity (DLT). Two of 12 patients had objective responses (16.6%) and 1 had a minor response. The alisertib OS at 45 mg/m2 had higher median Cmax (8.7 vs. 3.9 mM) and exposure (58 vs. 45 mM·hr) compared to tablets at 60 mg/m2. Across 54 patients in all cohorts, there were trends to suggest that MYCN amplification and prior irinotecan treatment were associated with lower response rates. Alisertib exposure and trough concentrations were associated with higher rates of first course DLT. Conclusions: Alisertib with irinotecan/temozolomide is an active combination. Alisertib oral solution at 45 mg/m2 is tolerable in this context. Additional studies of biomarkers of response and toxicity are ongoing. Clinical trial information: NCT01601535.
Induction gemcitabine cisplatin followed by chemoradiation in locally advanced nasopharyngeal cancer.
Authors: Sadaf Usman, Sara Rasheed, Ali Raza, Raza Hussain, Arif Jamshed
Journal: Journal of Clinical Oncology (2017)

6027 Background: The current standard of treatment in locally advanced nasopharyngeal cancer is concurrent chemoradiation, however recent addition of induction chemotherapy in the already established regimen has presented an attractive alternative approach. We report on survival with induction Gemcitabine and Cisplatin (GC) followed by chemoradiation (CRT) in the treatment of advanced nasopharyngeal carcinoma. Methods: Between 2005 and 2015, 300 patients (M 70%: F 30%) with histologically confirmed nasopharyngeal carcinoma. Histological subtypes WHO I 4% (13) and WHO III 96% (287). AJCC (7 th edition) stage was Stage III 28% (85) and Stage IV 72% (215) patients. IC included a 2 drug combination; intravenous gemcitabine 1000 mg/m 2 on day 1 and 8 and cisplatin 75 mg/m 2 on day 1 only. Radiotherapy was given as a phase treatment to a total dose of 70 Gy in 35 fractions. Concurrent three weekly cisplatin (75 mg/m 2 ) was administered to all patients. Results: Median follow up time was 30 months. The 5-year overall survival (OS), loco regional control (LRC) and relapse free survival (RFS) rates were 70% (95% CI 6.43 – 7.52), 69% (95% CI 6.52 – 7.64) and 52% (95% CI 5.25 – 6.34) respectively. One hundred and seven patients failed treatment; local or loco-regional 39% (42), regional 16% (17) and distant 45% (48). Conclusions: We conclude that induction gemcitabine and cisplatin followed by chemo-radiation is an effective regimen in management of nasopharyngeal carcinoma, meriting further investigation in randomized clinical trials.
Abstract 19427: Epidemiology and Outcomes of Out-of-hospital Cardiac Arrest in Qatar
Authors: Furqan B Irfan, Zain A Bhutta, Tooba Tariq, Loua A Shaikh, Pregalathan Govender, Robert C Owen, Jassim A Suwaidi, Rajvir Singh, Therese Djarv, Stephen Thomas, Karen Smith, Maaret Castren, Peter Cameron
Journal: Circulation (2015)

Aim: There is a scarcity of population based studies on out-of-hospital cardiac arrest (OHCA) in the Middle East and the wider Asian region. This study describes the Epidemiology and outcomes of OHCA in Qatar, a Middle Eastern country. Methods: Data was extracted retrospectively from a national registry on all adult cardiac origin OHCA patients attended by Emergency Medical Services (EMS) in Qatar, from June 2012 - May 2013. Results: The annual crude incidence rate of cardiac origin OHCA attended by EMS was 23.5 per 100,000. The age-sex standardized incidence rate was 87.83 per 100,000 population. The annual sex-standardized incidence rate for males and females was 91.5 and 84.25 per 100,000 population respectively. Of 447 adult, cardiac origin OHCA patients included in the final analysis, most were male (n=360, 80.5%) with median age of 51 years (IQR = 39-66). Frequently observed nationalities of OHCA cases were Qatari (n=89, 19.9%), Indian (n=74, 16.6%) and Nepalese (n=52, 11.6%). Common initial cardiac arrest rhythms were asystole (n=301, 67.3%), ventricular fibrillation (n=82, 18.3%) and pulseless electrical activity (n=49, 11%). OHCA was unwitnessed (n=220, 49%) in nearly half of the cases while bystanders witnessed it in 170 (38%) patients. Bystander CPR was carried out in 92 (20.6%) of the cases. Of 187 (41.8%) patients who were given shocks, bystander defibrillation was delivered to 12 (2.7%) patients. Prehospital outcomes; 332 (74.3%) patients did not achieve return of spontaneous circulation (ROSC), 40 (8.9%) patients achieved unsustainable ROSC, 58 (13%) achieved ROSC till Emergency department (ED) handover and 5 patients achieved ROSC but rearrested again before reaching ED. Survival to hospital discharge occurred in 38 (8.5%) patients. Neurological outcomes were assessed utilizing Cerebral Performance Category [CPC] scores with a favorable CPC score of 1-2 at discharge in 27 (6%) patients, while 11 (2.5%) patients had a poor CPC score of 3-4. Of those with CPC score 1-2 at hospital discharge, 59% and 26% had CPC score 1-2, at 1 and 3 years follow-up respectively. Overall survival was 9.7%. Conclusion: Standardized rates are comparable to western countries, there are significant opportunities to improve outcomes, including better bystander CPR.
Pilot study of NY-ESO-1<sup>c259</sup> T cells in advanced myxoid/round cell liposarcoma.
Authors: Sandra P. D'Angelo, Mihaela Druta, David A. Liebner, Scott Schuetze, Neeta Somaiah, Brian Andrew Van Tine, William D. Tap, Tim Pulham, Karen Chagin, Elliot Norry, Rafael G. Amado
Journal: Journal of Clinical Oncology (2018)

3005 Background: Metastatic myxoid/round cell liposarcoma (MRCLS) has a poor prognosis. NY-ESO-1 is expressed in 80-90% of MRCLS tumors. This study evaluates affinity enhanced autologous NY-ESO-1c259T cells recognizing an NY-ESO-1 derived peptide complexed with HLA-A*02 (SPEAR T-cells) in MRCLS (NCT02992743). Methods: This open label phase I/II single arm pilot study evaluates efficacy, safety and translational research endpoints. Eligible pts are ≥ 18 yr; HLA-A*02:01+, *02:05+ or *02:06+; have advanced MRCLS expressing NY-ESO-1 at 2+/3+ intensity in ≥30% of tumor cells by IHC; measurable disease; received anthracycline therapy; ECOG status 0 or 1; and adequate organ function. Following apheresis, T cells are isolated, expanded, transduced with a lentiviral vector containing the NY-ESO-1c259TCR, and 1– 8 × 109 transduced T-cells are infused on day 1 after lymphodepletion with Flu 30 mg/m2/d and Cy 600 mg/m2/d on d -7 to -5. Response is assessed at 4, 8, 12, and 24 wk and then every 3 mo until disease progression. Results: 37 patients were screened; 19 had the requisite HLAs. NY-ESO-1 was present at required levels in 13/14 tumors tested. 2 patients received the TCR therapy (as of 30Jan18). The tumors of treated pt expressed NY-ESO-1 at 3+ in 100% and 2 or 3+ in 60% of tumor cells. The 1st patient received 5.00 × 109 transduced T-cells and achieved an unconfirmed partial response; the target lesions showed 32% reduction from baseline at wk 12. AEs include grade (G) 4 lymphopenia, neutropenia, leukopenia, G3 thrombocytopenia and G2 anemia; all were considered related to lymphodepletion and resolved. G1 CRS with fever, G1 AST elevation, and G2 ALT elevation were also reported. The CRS resolved and was considered related to TCR therapy. Transduced cells were detected in peripheral blood 12 wk post infusion. The 2nd patient received 1.04 × 109 transduced T-cells and achieved an unconfirmed partial response; target lesions showed 37% reduction from baseline at wk 4. AEs include G4 lymphopenia, G3 anemia, G2 thrombocytopenia, G2 CRS with fever and rash. Confirmatory scans are pending. Conclusions: The data indicate that treatment with NY-ESO-1c259T cells in MRCLS is feasible with potential for anti-tumor effects. We will report updated results. Clinical trial information: NCT02992743.
LC-hrms metabolomics profiling in breast cancer: Searching for biomarkers in human plasma samples.
Authors: Pedro Sánchez Rovira, Ana Laura Ortega Granados, Mónica Fernández Navarro, María Ruiz Sanjuan, Capilla de la Torre Cabrera, Francisco José García Verdejo, Natalia Luque Caro, David Fernández Garay, Cesar Ramirez Tortosa, Ricardo Collado Martín, Reinald Pamplona Gras, Mariona Jové Font, JA Olid, V Rivas, Olga Genilloud, Caridad Díaz Navarro, Francisca Vicente Pérez, Maria Lomas Garrido, Ana Jaén Morago, Jose Pérez del Palacio
Journal: Journal of Clinical Oncology (2017)

e23053 Background: Breast cancer (BC) is most common cancer in women and development of new technologies for understanding molecular changes involved in BC progression is essential. Metabolic changes precede phenotypic changes, due to cellular regulation affects use of small-molecule substrates for cell division, growth or environmental changes, such as hypoxia. Metabolomics (profiling of metabolites in biofluid, cell and tissue) is routinely applied as a tool for biomarker discovery. Liquid chromatography−mass spectrometry(LC−MS)is the dominating platform. Methods: With the aim to find metabolomic profiles for diagnostic and prognostic of newly diagnosticated breast cancer (BC) we have investigated plasma samples in neoadjuvant setting (134 BC patients with median age of 51 years, stages T1-4,N1-2,M0 and 135 healthy controls) using high resolution mass spectrometry couple to liquid chromatography in reverse phase and HILIC modes which provided resolved chromatography of highly polar as well as hydrophobic analytes, enabling the analysis of a wide range of chemicals, necessary for untargeted metabolomics. Chromatograms were processed with software (Markerview) to generate a table listing retention times with associated ion masses and intensities. To identify potential biomarkers, we used in combination 2 independent variable selection techniques: principal component analysis and Student t-test. Results: We observed a significant difference in metabolic profile between the 2 groups. 15 molecular features [oleamide, KDNalpha2-3Galbeta1-4Glcbeta-Cer(d18:1/22:0)] were found significantly down/up regulated in BC patients compared with healthy subjects, and they were selected as diagnostic biomarkers. Additionally, ROC curve analysis was used to assess their clinical usefulness, obtaining an AUC of 0.963 (95% CI 0.919-0.989) when using a multivariate model of 3 features. As an outcome, we showed that selected biomarkers are useful as diagnostic biomarkers. Conclusions: The present study demonstrates potential of metabolomics in identifying novel biomarkers for BC. Further studies may reveal the potential of metabolites as diagnostics biomarkers for BC and their role in pathogenesis.
Cost-effectiveness analysis (CEA) of current immunotherapy: World comparison results.
Authors: Fernanda Oliveira, Frederico Leal, Joao PsDN Lima
Journal: Journal of Clinical Oncology (2018)

e18930 Background: CEA must address a technology in a very specific medical indication in a given contry. We aimed to survey and compare CEAs of recent breakthrough immunotherapies for cancer care. Methods: We performed a systematic review in PubMed, Google scholar, Dare, Central, and Lilacs database for published CEA of current immunotherapaies (IO) (Jan 2012 to Jan 2018). We extracted the drug name, indication, incremental cost effectiveness ratio (ICER), source of study, and the willingness to pay (WTP) threshold. We compared those features across countries, indications and diseases. ICERs were show in USD. Results: 248 CEA studies were found, with 25 CEA dealing with IO in melanoma (10), lung (10), kidney (2), and head & neck (3) cancers in Europe, US, Canada and Australia. 66% of CEAs had ICERs above the local WTPs, with an average premiun of 31% above the local WTP(95% confidence interval +12% to +50%). The premium was higher in academic CEAs (+34%) than in pharma-sponsored ones (13%), however with no statistical significance (P = 0.23). Disease-wise, CEAs in renal cancer had the highest premiums (+86%), followed by lung (+32%), head&neck (+25%), and melanoma (19%). Different CEAs of the same comparison varied little, showing the robustness of current health-economic methods. Ipilimumab-nivolumab versus ipilimumab for melanoma in US had the highest ICER ($245600; +146%) whereas nivolumab versus ipilimumab in Australia had the lowest ($23770; -32%). Conclusions: The current immunotherapies have ICERs far above the WTP in nearly all scenarios, with considerable variation across regions. These premiums must be properly discussed with payers and most importantly with patients in order to circumvent the present limitations for the universal access to those practice-changing drugs.
Impact of gender difference on adjuvant chemotherapy after radical resection in patients with non-small cell lung cancer.
Authors: Lu Yang, Xiaoyu Zhai, Qiwen Zheng, Ziping Wang
Journal: Journal of Clinical Oncology (2016)

e20064 Background: Gender was an important prognostic factor in patients with advanced non-small cell lung cancer(NSCLC). However, there are few studies reporting the impact of gender difference on the efficacy of adjuvant chemotherapy(ACT) in NSCLC patients. Methods: 900 patients (584 men and 316 women) who received post-operative ACT in the Cancer Hospital of the Chinese Academy of Medical Sciences between 2001 and 2013 with complete records in the database of the hospital were analyzed in this study for analysis. The primary end point was disease-free survival (DFS) in terms of gender. Survival analysis was performed using Kaplan–Meier estimates, log-rank tests and Cox’s proportional hazards regression analysis. Propensity score matching (PSM) was used, and survival analysis of the match data was carried out. Results: There was no significant difference in DFS between the two groups in terms of gender before propensity score was matched (23.23months [95%CI 19.16, 27.31] vs.21.9 months [95%CI 19.09, 24.71], P = 0.524). Furthermore, no significant impact of gender on DFS was observed between the PS-matched groups (22.73months [95%CI 17.03, 28.43] vs. 22.53months [95%CI 16.43, 28.63], P = 0.570). Conclusions: The results suggest that gender was not a prognostic factor on ACT after radical resected NSCLC. However, these conclusions are limited by the nature of this retrospective study, and therefore prospective trials are required for further verification.