tbuckley/cabot-search huggingface dataset:
Neuroendocrine gene transcript analysis of blood to define the completeness of surgical resection and identify stable or progressive neuroendocrine tumor disease.
Authors: Mark S. Kidd, Irvin Mark Modlin, Andrea Frilling, Daniele Alaimo, Stephen Callahan, Lisa Bodei, Ignat Drozdov
Journal: Journal of Clinical Oncology (2015)

293 Background: A critical requirement in NET management is a sensitive, specific, reproducible blood biomarker test. Surgery and somatostatin analogs (SSAs) are widely used but efficacy is difficult to determine. Imaging is relatively insensitive for residual/recurrent disease determination and symptoms remains the only way to determine SSA efficacy. We evaluated a PCR-based 51 transcript signature (NETest) comparing it to CgA to determine whether biomarkers were effective in defining surgical resection and SSA efficacy. Methods: GEP-NETs (n=50) [M:F 19:31; median age: 58 years, small intestine: n=35, pancreas n=9, rectum n=3, appendix: n=2, stomach n=1] were evaluated. Groups included surgery (n=15, R0-no disease), and SSA therapy (n=35). qRT-PCR was used for transcript measurement, ELISA (DAKO) for CgA and imaging (RECIST) for clinical status. NETest defined risk of disease activity (low disease activity risk &lt;47%, high risk 47-100%). Results: Resection decreased NETest (pre-surgery: 80±6%; 1 post-surgery: 29±6%, p&lt;0.0001). Thirteen (87%) were high risk before surgery; post-surgery two (13%) remained high risk (despite lowered score), 11 (74%) were low risk and 2 normal. Four (26%) developed recurrence at 6 months. CgA levels were non-informative. In the SSA group, the NETest was lower in clinically stable disease (32±3.7%; n=25) than in progressive disease (82±4.3%, n=10; p&lt;0.0001). All patients in the latter were categorized as high risk disease activity. The accuracy for differentiating stable from active disease was 92% (sensitivity=100%, specificity=88%). Three SSA patients developed clinically progressive disease with concordant increases in NETest. CgA levels were not significant and were non-informative. Conclusions: NET transcript analysis accurately defined surgical cytoreduction and identified biochemical evidence of residual disease. NETest also accurately identified stable and progressive clinical disease activity during SSA treatment. Blood-based multigene analytic measurement will facilitate early detection of residual/recurrent disease and further define therapeutic efficacy for surgery and SSAs.
Early increase in ammonia is a feature of non-alcoholic fatty liver disease and the ammonia lowering drug, ornithine phenylacetate (OCR-002) prevents progression of fibrosis in a rodent model
Authors: F. De Chiara, A. Habtension, N. Davies, F. Andreola, K. Rombouts, N. Arias, K.L. Thomsen, R. Jalan
Journal: Journal of Hepatology (2017)
HIF-1α and EGFR as progonostic factors for therapy response and 1-year locoregional recurrence not for distant metastasis and 2-year OS in unresectable stage IIIA NSCLC treated with combined chemoradiotherapy.
Authors: Y. Yang, J. Yu, L. Xing, X. Sun, M. Hu, D. Mu, A. Han
Journal: Journal of Clinical Oncology (2010)

10640 Background: The purpose is to evaluated the effect of prognosis of HIF-1α and EGFR in unresectable stage IIIA NSCLC treated with chemoradiotherapy. Methods: A retrospective review of 44 patients with unresectable stage IIIA NSCLC treated with chemoradiotherapy (CRT) in 2007 was performed. Stage diagnosis data including PET/CT and CT guided primary tumor biopsy tissue could be obtained. HIF-1α and EGFR expression were inspected by IHC method. Definitive combined CRT schemes were vinorelbine or gemcita plus cisplatin and irradiation with a total dose of 60 to 65 Gy. 36 patients were underwent follow-up (median time 31 ± 2.7 months, range 25-36 months). Results: HIF-1α expression was diffused in cytoplasma and nuclear, EGFR expresssion in cell membrane. Of 44 patients, the cut-off value for HIF-1α positive expression was 72%, 60% for EGFR. HIF-1α and EGFR expression were only correlated with histological type (70% and 33.% for SCC and ADC). HIF-1α, EGFR expression and SUVmax value were significantly correlated. HIF-1α and EGFR were significant predictors for 79.5% effective treatment response (CR+PR) evaluated by RECIST. Of 36 followed-up patients, patients with positive HIF-1α and EGFR expression (cut-off value 78%, 60%) had statistically superior 1-year loco-regional recurrence rate (p = 0.000, 0.004) and shorten mean time to first locoregional recurrence (9.08 ± 1.37 months vs. 10.3 ± 1.37 months) compared with negative expression. However, there is no significance for HIF-1α and EGFR in the 1-year distant-metastasis recurrence (DMR) rate, 2-year overall survival (OS) (p = 0.105, 0.077) by univariate analysis. HIF-1α expression was significant for 1-year loco-regional recurrence (HR 27.11, p = 0.009, 95%CI 2.31-318.73), and both not for 1-year DMR and 2-year OS analysised by COX ratio hazard regression. Conclusions: HIF-1α and EGFR expression were two good prognostic factors for therapy response and HIF-1α for 1-year loco-regional recurrence in stage IIIA NSCLC treated by combined CRT. The results suggest the need for an elaborate examination of HIF-1α protein expression to get its prognostic value. No significant financial relationships to disclose.
A liposomal MUC1 vaccine for treatment of non-small cell lung cancer (NSCLC): Updated survival results from patients with stage IIIB disease
Authors: N. Murray, C. Butts, A. Maksymiuk, E. Marshall, G. Goss, D. Soulieres
Journal: Journal of Clinical Oncology (2005)

7037 Background: The primary analysis results from a randomized, open label phase IIb trial utilizing L-BLP25 (BLP25 Liposome Vaccine) for the immunotherapy of stage IIIB and IV NSCLC patients with stable or responding disease following any first line chemotherapy were reported in April 2004. Patients were randomized 1:1 to best supportive care (BSC) or BSC + L-BLP25 (TX), with survival as the primary endpoint. Treatment arm patients received a single intravenous dose of 300mg/m2 cyclophosphamide, followed by 8 weekly subcutaneous immunizations with L-BLP25. Maintenance immunizations are then given at 6-week intervals. At primary analysis, the median survival of TX patients in the pre-stratified stage IIIB locoregional (LR) disease subset, had not yet been reached. Methods: Updated survival information was obtained as part of a protocol specified follow-up period at two years after enrollment of the last patient. Survival was calculated from the date of randomization into the trial, to the date of death or last contact. Results: Of 171 patients enrolled, 65 had IIIB LR disease. Of these, 35 were randomized to TX, and 30 to BSC. The IIIB LR subgroup was well balanced in terms of age and ethnicity. More female and ECOG 0 patients were randomized to TX than BSC (51.4 versus 36.7%, and 40.0 versus 26.7%), and more patients in the TX arm received radiotherapy in addition to chemotherapy, for cancer treatment prior to trial enrollment (91.4 versus 76.7%). The current median number of vaccinations received by TX patients is 17, with a maximum of 41. Mild injection site reactions occurred in 54.3% of patients. There were no major toxicities. To date, a survival median for TX patients has not yet been reached (54% alive at >24 months). Conclusion: A clinically meaningful survival advantage appears likely for patients with stage IIIB NSCLC treated with L-BLP25. Further development of the vaccine is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biomira, Roche Aventis, Biomira, Roche
Elective chemotherapy admissions: An opportunity to improve wait times.
Authors: Samantha Meyerholz, Mary E. Dowling
Journal: Journal of Clinical Oncology (2016)

240 Background: Chemotherapy wait times are a well-recognized challenge facing cancer hospitals. Recent publications have stated that not only do wait times affect patients but they increase costs and consume hospital resources. Wait times lead to longer lengths of stay and require additional staff attention. Reducing chemotherapy treatment wait times has long been a priority of Sloan Kettering, with this study focusing on inpatient chemo processes. During October and November of 2014, 6 current state observations were performed in chemo nursing verification, chemo pharmacy and an inpatient chemo unit. Metrics measured included submission of electronic chemo orders, blood work availability, clearing for treatment, PICC line placement, bed availability and drug transport. All system components were analyzed from both a clinical and industrial engineering perspective. Future state analysis was conducted from December 2014 through April of 2015. Process improvement techniques including direct observation, process mapping, waste analysis and time studies were used to assess workflow. Methods: Prior to implementing performance improvement interventions, baseline data was compiled. 12% of electronic chemo orders were submitted 24 hours prior to admission, 36% of the time blood work was not available within 72 hours prior to patient arrival, 46% of treatments experienced pending delays due to ‘Proceed to Treat’ order, 0% of PICC lines were placed prior to admission, 34% of patients were discharged before 2pm and time for drug delivery averaged 1 hour and 47 minutes. The average time from patient admission to first chemotherapy treatment was 9.7 hours. Results: Following the rollout of a newly designed pilot unit in January 2015, data was collected for 192 chemo admissions in February through April of 2015. The use of electronic chemo orders rose to 84%, blood work was available 60% of the time, pending orders reduced to 0%, PICC placement occurred prior to day of admission 98% of the time, 46% of patients discharged before 2pm and drug delivery was reduced to 0 minutes. The time from admission to chemo treatment was reduced to 2.1 hours. Conclusions: The amount of patients treated after day of admission reduced from 17% to 8%, saving 18 patient days.
Phase I trial of gene-mediated cytotoxic immunotherapy combined with resection for pancreatic adenocarcinoma.
Authors: Lawrence Andrew Shirley, Christopher Marsh, Jon Walker, Walter Coyle, Sanaa Tahiri, Andrea G Manzanera, Laura K. Aguilar, Estuardo Aguilar-Cordova, Vincent M. Chung, Mark Bloomston
Journal: Journal of Clinical Oncology (2012)

241 Background: While surgical resection of pancreatic adenocarcinoma provides the only chance of cure, long-term survival is still poor. Immunotherapy approaches may improve outcomes. Gene Mediated Cytotoxic Immunotherapy (GMCI) generates a systemic anti-tumor vaccine effect through intra-tumoral delivery of an adenoviral vector expressing the HSV-thymidine kinase gene (AdV-tk) followed by anti-herpetic prodrug administration. This is the first application of GMCI in pancreatic cancer. Methods: This study evaluated 4 dose levels of AdV-tk (3x10 10 to 1x10 12 vector particles) injected into pancreatic tumors via EUS 2 weeks before resection. Patients then underwent attempt at resection. If resection was undertaken, AdV-tk was injected into the resection bed. If resection was not possible, AdV-tk was injected into the primary tumor. The prodrug, Valacyclovir, was given for 14 days after each injection. Postoperative therapy was not protocol-driven. Results: The study accrued 14 patients with 12 completing therapy: 3 at each of the 4 planned dose levels. One patient died of an unrelated myocardial infarction 2 days after initial injection and one patient dropped out mid-treatment after metastases were found at surgery. Median age was 67 years (range 40-81). Of 12 patients explored, 4 were not resected due to distant metastases (N=3) or locally advanced disease (N=1). Three patients had Grade 3 possibly-related adverse events: 2 abdominal pain and one dehydration with renal insufficiency. There were no dose limiting toxicities and no grade 4 clinical adverse events. Grade 3-4 laboratory abnormalities were AST/ALT, bilirubin, alkaline phosphatase and lipase, all in patients with obstructive jaundice. Post-operative complications included 2 patients who developed abscesses requiring drainage. Six of 12 patients are alive 5-34 months after start of treatment including 5 resected patients and one unresected. Conclusions: AdV-tk can be safely injected into potentially resectable pancreatic tumors prior to planned resection. Early results are encouraging and justify further evaluation in a Phase 2 study.
Diagnosis and staging of ovarian cancer: Comparative values of PET/CT, Doppler US, CT, and MRI correlated with histopathologic analysis
Authors: E. Nam, Y. Kim, J. Kim, S. Kim, S. Kim, S. Jang, D. Lee, J. Hong, J. Kim
Journal: Journal of Clinical Oncology (2008)

5567 Background: To compare the diagnostic accuracy of positron emission tomography/computed tomography (PET/CT), Doppler ultrasonography (US), Computed tomography (CT), and magnetic resonance imaging (MRI) for detection of ovarian cancer and to assess the role of PET/CT in evaluating dissemination of ovarian cancer. Methods: One hundred thirty three women suspected to have ovarian cancer were enrolled in a prospective study before surgery between March 2005 and August 2007. The accuracy of each modality in detection of malignancy was estimated by computing the relevant areas under the receiver operating characteristics curve. Histopathologic results served as the reference standard. Results: Histopathology showed benign tumors in 25 patients, borderline tumors in 13 patients, and malignant tumors in 95 patients, respectively. In distinguishing malignant from benign and borderline ovarian tumors, the accuracy of PET/CT (0.87) was higher than that of US (0.77) and CT or MRI (0.79). In distinguishing borderline from benign ovarian tumors, the accuracy of PET/CT (0.78) was higher than that of US (0.73) and CT or MRI (0.60). In 95 patients with ovarian cancer, PET/CT revealed 16 (16.8%) unpredicted extra-abdominal lymph node metastasis and 1 (1.0%) intra-hepatic metastasis. Histology verifying the PET/CT findings suspicious metastatic lymph nodes was obtained from 10 patients with supra-clavicular lymph node metastasis. In addition, PET/CT detected new, unexpected co-existing malignant tumors in 7 (5.3%) cases, including thyroid, kidney, breast, pancreas and lung cancer. Conclusions: PET/CT is superior to US, CT, and MRI in diagnosis of malignant ovarian tumors and useful to disclose metastatic ovarian cancer and co-existing malignant tumors. Therefore, we suggest that PET/CT should be included in pre-operative evaluation in patients suspected to have ovarian cancer. No significant financial relationships to disclose.
Peripheral Blood Hematopoietic Progenitor Cell (HPC) Counts At Autologous Stem Cell Collection (ASCC) Are Associated with Prognosis in Multiple Myeloma
Authors: Yoon Ji Choi, Dok Hyun Yoon, Jungmin Jo, Kyoungmin Lee, Eun Hee Kang, Shin Kim, Seongsoo Jang, Chan Jeoung Park, Hyun Sook Chi, Cheolwon Suh
Journal: Blood (2012)
What is needed to implement Institute of Medicine (IOM) 2013 supportive oncology recommendations in community settings?
Authors: Julia Rachel Trosman, Rosa Berardi, Christine B. Weldon
Journal: Journal of Clinical Oncology (2016)

49 Background: The IOM 2013 report recommends supportive oncology services from diagnosis through survivorship and end of life. We examined what community institutions need to implement IOM recommendations. Methods: Survey of 35 institutions in a urban area (13 cancer centers; 14 cancer support centers, 8 hospices). Institutions ranked the top 5 supportive oncology project ideas, that their organization was most interested in participating in, from a list of 27. Results: Survey response rate was 100%. Respondents agreed on 8 of top 10 priorities across the three organization types (Table). Local inter-institutional collaboration leveraging respective resources and facilitating care consistency across sites was the most frequently need. It was followed by the need for stratified care processes based on patient need and improved supportive oncology reimbursement. Priorities differed between Cancer Centers and other institution types on Consolidated screening tools* (p = .05, .09) and Care process for family / caregiver** (p = .006, .04). Conclusions: Supportive oncology care processes and tools are needed to implement IOM recommendations in the community. Our findings inform a roadmap for practical collaborative implementation of the IOM recommendations. Differing priorities across cancer institution types should be further explored and addressed within the roadmap. [Table: see text]
Impact of integrated palliative care model on end-of-life (EOL) quality metrics for patients with kidney cancer (RCC) and melanoma (M).
Authors: Jessica A. Lynch, Susan DeSanto-Madeya, Jessica A. Zerillo, Matt Gregas, David F. McDermott, Kenneth J. Mukamal, Mary K. Buss
Journal: Journal of Clinical Oncology (2015)

137 Background: Early palliative care (PC) improves quality of life (QOL) and enhances end-of-life (EOL) care, but the optimal timing and most effective model for integrating PC into oncologic care is uncertain. To understand the impact of an integrated model with PC providers embedded with oncologists vs. usual care (UC) with referral at the discretion of the same oncologists, we examined the timing and delivery of PC and Quality Oncology Practice Initiative (QPOI) EOL metrics among patients with RCC and M in a single clinic. We hypothesized that integrated PC would result in more referrals, earlier contact with PC and better QOPI EOL metrics compared with UC. Methods: In a retrospective cohort study of patients with RCC and M in the Beth Israel Deaconess Biologics Clinic who expired between 10/1/12 and 12/31/14, we compared patients seen 2 days/week, when referral to PC was discretionary, with a third day when PC providers shared the clinic for real-time consultations. Patients were identified as meeting PC eligibility if they had recurrent, metastatic disease and were on active treatment or had a symptom severity of 7+ on Edmonton Symptom Assessment Scale (ESAS). Two oncologists saw all patients, regardless of day. Results: Seventy-six patients expired, 19 in the Integrated PC model and 57 with UC. Patients were similar with respect to diagnosis and demographics except for smoking. The integrated model substantially improved timing and location of PC. In the integrated PC model, 85% were seen by PC compared with 45% in UC (P = 0.002). All patients in the integrated model began PC as an outpatient compared with 36% in UC (P &lt; 0.001). The mean number of days from first PC contact to death was 28 (SD = 54) for UC and 118 (SD = 120) with integrated PC (P &lt; 0.001). The location of death did not differ significantly between models, occurring outside the hospital with hospice among 71% of patients in the integrated model and 53% in UC (P = 0.25). Results were similar in relative risk models adjusted for smoking. Conclusions: A practice model that integrated PC with oncologic care was associated with more PC referrals, earlier contact, and a nonsignificant trend toward fewer deaths in hospital and ICU.
Association of hematological toxicity (tox) and outcome to doxorubicin (DOX) in advanced soft tissue sarcoma (STS): A retrospective analysis of the EORTC-Soft Tissue and Bone Sarcoma Group database.
Authors: Stefan Sleijfer, Elisa Rizzo, Saskia Litière, Ron H.J. Mathijssen, Ian Robert Judson, Hans Gelderblom, Antoine Italiano, Winette T.A. Van Der Graaf, Alessandro Gronchi
Journal: Journal of Clinical Oncology (2015)

10544 Background: DOX pharmacokinetics vary substantially between patients leading to large differences in systemic drug levels. Given potential dose-effect relations, patients with the greatest tox may also have the best outcome. We assessed whether severity of hematological tox during treatment is associated with outcome in advanced STS patients treated with first-line DOX (monotherapy; 75 mg/m2 q 3 weeks). Methods: Worst tox (anaemia, leukopenia, neutropenia and thrombocytopenia) scored during treatment according to CTCAE v4.0 was included in this analysis. Differences in overall survival (OS), progression free survival (PFS) and response rate (RR) between patients with or without high haematological tox (grade 0-2 vs 3-4) were assessed using conventional statistical tests in landmarked subsets, to avoid bias from patients stopping treatment early. Potential confounders were collected including relative dose intensity (RDI), patients’ and tumor characteristics. Results: In 557 patients eligible for this analysis, 32% were between 50-60 years, 51% female, 72% had a grade II/III tumor. Leiomyosarcoma (28%) and liposarcoma (15%) were the most common subtypes. 47.2% of the patients received at least 6 cycles of treatment; 45% stopped treatment early due to progression, 3% because of tox. RDI was constant over the cycles. During treatment, grades 3/4 anemia, leukopenia, neutropenia and thrombocytopenia were observed in 6.1%, 35.9%, 51.9%, and 1.6%, respectively. After cycle 1, grade 3 tox occurrence was constant over the diverse cycles, grade 4 tended to decrease after cycle 1 (21.0% at cycle 2, 12% at cycle 3). OS and PFS did not differ between patients experiencing high versus low tox at the end of cycles 1, 2 and 3. Also for RR, no association was seen with severity of haematological tox. Conclusions: In this large series, there was no association between outcome and haematological tox during DOX. This information may be useful to reassure advanced STS patients that failure to experience haematological tox during treatment does not equate to under-treatment.
Triplet chemotherapy combination with gemcitabine, cisplatin, and docetaxel in patients with chemotherapy-naive advanced non-small cell lung cancer.
Authors: F. Tas, F. Sen, N. Guney, I. Yildiz, H. Camlica, S. Keskin, L. Kilic
Journal: Journal of Clinical Oncology (2011)

e18064 Background: The synergistics effects of new generation chemotherapeutics when combined with cisplatin have encouraged the development of new triplet combination in treatment of advanced non-small cell lung cancer (NSCLC). We conducted the feasibility of triplet chemotherapy using weekly cisplatin-docetaxel-gemcitabine for patients with chemotherapy naive NSCLC. Methods: Twenty seven patients with stage IIIB/IV disease and performance status of 0 to 2 were included. Combination of gemcitabine 750 mg/m2, cisplatin 25 mg/m2 and docetaxel 25 mg/m2 was administered on days 1, 8 and 15, with cycles repeated every 3 weeks. Results: Leucopenia and/or neutropenia and to a lesser extent thrombocytopenia were the main dose-limiting toxicities. Grade 3-4 neutropenia and thrombocytopenia occurred in 26% and 7% of the patients, respectively. Only one patient developed febrile neutropenia. Dose reductions were required in 26% of patients, delays in 44% patients and early treatment discontinuation in 15% of patients. The overall response rate was 52%, and all of them were partial response. Median progression free and overall survival survivals were 6 months and 13 months, respectively. One-year survival rate was 46%. Conclusions: Weekly administration of cisplatin-gemcitabine-docetaxel combination is an active first line therapy with acceptable toxicity in advanced NSCLC patients.
Relevance of the Daily Dose of Imatinib Mesylate (IM) Rather Than Its Trough Plasma Concentration for Achieving Deep Molecular Response in Patients with Chronic Myeloid Leukemia.
Authors: Chikashi Yoshida, Takuya Komeno, Mitsuo Hori, Tomofumi Kimura, Masami Fujii, Yasushi Okoshi, Kazumi Suzukawa, Shigeru Chiba, Yuichi Hasegawa, Harumi Yamamoto Mukai, Takayoshi Ito, Seiichi Shimizu, Masaharu Kamoshita, Daisuke Kudo, Atsushi Shinagawa, Norio Chikatsu, Yuriko Monma, Norimichi Watanabe, Hiroshi Kojima
Journal: Blood (2009)