tbuckley/cabot-search huggingface dataset:
A phase 2 clinical trial of pemetrexed (P) plus gemcitabine (G) as front-line chemotherapy for patients with peritoneal mesothelioma (PM)
Authors: G. R. Simon, P. A. Janne, C. J. Langer, C. F. Verschraegen, A. Dowlati, S. M. Gadgeel, K. Kelly, L. Taylor, C. K. Obasaju, H. L. Kindler
Journal: Journal of Clinical Oncology (2005)

7235 Background: P in combination with cisplatin is approved for the treatment of malignant pleural mesothelioma. In an Expanded Access Program, P ± cisplatin was shown to have activity in peritoneal mesothelioma. P plus G are synergistic in preclinical models, but the activity of this combination in peritoneal mesothelioma is unknown. The median overall survival for all peritoneal mesotheliomas is below one year. This study was conducted to determine overall survival of pts with PM. Methods: Nineteen pts were accrued with malignant peritoneal mesothelioma. Treatment consisted of G 1250 mg/m2 given over 30 minutes on D 1 and 8, with P 500mg/m2 given over 10 minutes on D 8, immediately before G. Treatment was repeated every 21 days for a total of 6 cycles or until progressive disease. All pts received folic acid, vitamin B12 and steroid prophylaxis. There is no staging system for PM to quantify anatomic response. Patients were followed for survival only. Results: Data are available on fifteen pts. Median age was 68 years (range: 46 - 79). Pathologic diagnosis epithelial:other = 10:5, M:F = 11:4, and ECOG PS 0:1:2 = 7:4:3. Grade 3/4 events included neutropenia (46.7%), febrile neutropenia (13.3%) (including one toxic death), fatigue (13.3%), abdominal pain (6.7%), and dyspnea (6.7%). A total of 67 cycles within the first 6 cycles of treatment were administered. For P plus G, median number of doses was 5 and 11 and median dose intensity was 96.1% and 86.2%, respectively. Median TTP was 10.4 months (95% CI = 4.4, –), and at 12 months, 63% of patients had disease progression. Conclusions: Though these data are preliminary and reflect a small sample size, P plus G was well tolerated and median TTP was promising in peritoneal mesothelioma. Survival data will be presented at the 2005 ASCO meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly Eli Lilly Eli Lilly
Molecular Detection of CMV in Biological Fluids Other Than Plasma. Clinical Relevance After Allogeneic Hematopoietic Cell Transplantation.
Authors: Apostolia Papalexandri, Tasoula Touloumenidou, Ioannis Zorbas, Maria Gounari, Panagiota Zerva, Christos Smias, Chryssa Apostolou, Ioannis Batsis, Panayotis Kaloyannidis, Ioanna Sakellari, Achilles Anagnostopoulos
Journal: Blood (2009)
Response evaluation in GIST treated with imatinib - misdiagnosis of disease progression on CT due to cystic change in liver metastases
Authors: K. M. Linton, M. B. Taylor, J. A. Radford
Journal: Journal of Clinical Oncology (2005)

9047 Background: Treatment with imatinib mesylate remains the only successful therapy for metastatic or unresectable GIST. In this paper we show that computed tomography (CT) assessment of treatment response to imatinib in GIST may lead to the erroneous diagnosis of progressive disease (PD). Methods: We report two cases of metastatic, unresectable GIST treated with imatinib 400mg daily, and evaluated using contrast enhanced CT. Results: In patients 1 and 2, response evaluation CT after 8–12 weeks of treatment showed the appearance of new, low density liver metastases consistent with PD, although other sites of disease had become smaller. Patient 1 experienced a considerable symptomatic improvement and so treatment was continued despite the CT findings. All sites of disease remained stable on CT for a further two years, at the same dose of imatinib. Patient 2 developed new symptoms after commencing imatinib, and treatment was stopped. It was later considered that the development of new low density liver lesions on the early response evaluation CT may have been due to cystic response within previously occult metastases. Imatinib 400 mg daily was therefore restarted two years later (at a time of rapid PD), and within 8 weeks a significant response was seen on CT. All sites of disease have continued to respond after 6 months of ongoing imatinib treatment. Conclusions: Cystic degeneration of pre-existing solid liver metastases is known to occur during effective imatinib therapy in GIST. We report how solid GIST metastases may not be visible on pre-treatment contrast enhanced CT, because the density of these lesions may be similar to that of the surrounding normal liver. Following successful imatinib treatment a fall in lesion density due to cystic change can result in an increased conspicuity of liver metastases, which may lead to the appearance of apparently new lesions at a previously uninvolved site. This should not be confused with the development of new liver lesions due to disease progression and imatinib failure. In the assessment of response to imatinib this possibility should be considered and correlation made with other sites of disease and symptoms. GIST treatment guidelines should be amended. No significant financial relationships to disclose.
Imaging-guided core needle biopsies (CNB) compared to surgical biopsies (SB) for soft tissue tumors: A cost-effectiveness analysis.
Authors: S. Taieb, Y. Robin, M. Morel, F. Watelle, L. Vanseymortier, N. Penel
Journal: Journal of Clinical Oncology (2010)

10073 Background: Core-needle biopsies are rarely used outside referral centers for diagnosis of soft tissue tumours, as many surgeons prefer to perform surgical biopsies. Methods: We had conducted a decision model analysis of the cost and the effectiveness of either strategies, i.e CNB first followed by SB if CNB provides technically poor non-representative tissue versus SB first followed by CNB if necessary. The main outcome was adequate surgery for soft tissue tumor. Utility was graded as follow: 1.0 if patients with sarcoma underwent planned surgery for sarcoma or if patients with benign tumor underwent adequate treatment, 0.5 if patients with benign tumor underwent large surgery as recommended for a sarcoma and 0 if a patient with sarcoma underwent a treatment as for benign tumor. Inputs were extracted from literature data (8 reports issued between 1996 and 2005). This analysis was conducted in societal perspective with one-month time-horizon (until time of curative- intent surgery). Model and variable uncertainties were explored by Monte-Carlo probabilistic sensitivity analysis. Results: According to literature data, SB provided representative tissue in 93% of cases, Se of 84% and Sp of 100%. CNB provided representative tissue in 89% of cases, Se of 96% and Sp of 95%. Mean cost of the strategy “SB first” was 3433 Euros (± 1148) and mean effectiveness was 93.5% (±3.7). Mean cost of the strategy CNB first was 2,052 Euros (± 449) and mean effectiveness was 96.5% (± 1.1). In the base-case analysis, the strategy CNB first was less expensive and beneficial. Results were confirmed by sensitivity analysis. Conclusions: The strategy “CNB first” provided a cost-saving of 1381 Euros (1,900 US$) per patient. In France (65 millions of inhabitant/4,000 sarcoma expected each year) this strategy may provide a total cost saving of about 2,700,000 Euros per year. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer
Development and implementation of clinical pathways in lung cancer at an academic comprehensive cancer center.
Authors: Sally Tan, Julie M. Porter, Constance Barysauskas, Stacy L. Mach, Ed Rodgers, Aymen Elfiky, Joseph O. Jacobson, David Michael Jackman
Journal: Journal of Clinical Oncology (2014)

98 Background: Clinical pathways (CP) is an emerging tool aiming to reduce unwarranted variation and maximize value in cancer care. We describe the preliminary experiences and challenges of developing, implementing and testing pathways at a comprehensive cancer center. Methods: Dana-Farber Cancer Institute (DFCI) partnered with Via Oncology to develop and pilot institution-derived CP in lung cancer. The Via platform tracks usage rate, adherence to the DFCI-designed CP (on-pathway rate), and reasons why off-pathway treatments were chosen. An online satisfaction survey was conducted among providers participating in the pilot. Results: Between 1/27/14 and 5/30/14, 277 chemotherapy treatments were initiated, with 124 new patients. CP was used to generate 98% of new chemotherapy orders; 63% were on-pathway. The most common off-pathway reasons were 1) poor patient performance status and 2) treatment beyond 3rd line. 22 of 41 specialists who participated in the CP pilot at DFCI’s main campus responded to the survey (54% response rate). Respondents ranked the Institute as the stakeholder who most benefits from CP, followed by payers, DFCI network community physicians, DFCI main campus physicians, and patients. Respondents recognized CP reflects appropriate care but are concerned about workflow (Table). Conclusions: Implementation of an institution-derived CP is feasible at a comprehensive cancer center. Physician input into pathway design is essential to build buy-in. Academic specialists perceived more benefit of CP for their community peers and raised concerns about workflow. On-pathway rates were lower than those reported in community settings, due to many potential factors (to be explored with updated data for final presentation). [Table: see text]
The role of HER-3 expression in the prediction of clinical outcome for advanced colorectal cancer patients receiving irinotecan/cetuximab.
Authors: M. Scartozzi, A. Mandolesi, R. Giampieri, A. Zaniboni, E. Galizia, L. Giustini, R. R. Silva, R. Berardi, I. Bearzi, S. Cascinu
Journal: Journal of Clinical Oncology (2011)

404 Background: Preclinical data suggested that in presence of HER3 altered activation colorectal cancer cells may escape anti-EGFR mediated cell death. HER3 overexpression may then represent a key factor for resistance to anti-EGFR antibodies in colorectal cancer. The aim of our analysis was to investigate a possible correlation between HER3 expression and clinical outcome in KRAS wild-type advanced colorectal cancer receiving cetuximab and irinotecan. Methods: We retrospectively analyzed immunoreactivity for HER3 in KRAS wild-type advanced colorectal cancer patients receiving irinotecan-cetuximab. Results: Eighty-four advanced KRAS wild- type colorectal cancer patients were available for HER3 analysis. Forty patients (48%) showed HER3 negative colorectal tumor, whereas the remaining 44 cases (52%) were deemed HER3 positive. In HER3 negative and HER3 positive tumors we observed a partial response in 17 (42%) and 8 (18%) patients respectively (p = 0.04). Progressive disease was obtained in 11 (35%) and 26 (53%) patients with respectively HER3 negative and positive tumor (p = 0.007). No differences were observed for stable disease. Median PFS was 6.3 months in patients showing HER3 negative tumors and 2.8 months for those who had HER3 overexpressing tumors (p &lt; 0.0001). Median overall survival was 13.6 months in patients showing HER3 negative tumors and 10.5 months for those who had HER3-expressing tumors (p = 0.01). Conclusions: HER3 proved to be a predictive factor for clinical outcome in KRAS wild-type colorectal cancer patients treated with cetuximab. Combined HER3 and KRAS analysis may represent an effective strategy for a better selection of responding colorectal tumors. Furthermore besides identifying colorectal cancer patients refractory to EGFR directed treatment, HER3 overexpression may also represent a potential biological indicator for the development of a new class of antineoplastic agents in this setting. No significant financial relationships to disclose.
The role of ZNF395 in renal cell carcinoma proliferation, migration, and invasion.
Authors: Chen Zhao, Christopher G. Wood, Jose A. Karam, Tapati Maity, Lei Wang
Journal: Journal of Clinical Oncology (2016)

592 Background: Zinc finger protein 395 (ZNF395) is frequently altered in several tumor types. However, the role of ZNF395 remains poorly studied in patients with clear cell renal cell carcinoma (RCC). In this study, we investigated the in vitro and in vivo role of ZNF395 in ccRCC. Methods: cBioPortal For Cancer Genomics was used to correlate the expression of ZNF395 with RCC patient clinical, pathological and molecular profiles. ZNF395 protein and mRNA levels were studied in several RCC cell lines in vitro. Subsequently, ZNF395 knockdown was performed in 786-O and UMRC3 RCC cells and overexpression was done in Caki-1 and 769-P RCC cells. We then evaluated ZNF395 modulation in these cell lines by in vitro MTT, migration and invasion assays. Finally, we studied the effect of ZNF395 knockout and overexpression in vivo using SCID xenograft models. Results: Patients with higher expression of ZNF395 experienced longer disease-free survival and overall survival. Using in vitro models, we confirmed that knockdown of ZNF395 decreased ZNF395 expression, and increased proliferation, migration and invasiveness of 786-O and UMRC3, while overexpression of ZNF395 increased ZNF395 expression, and reduced proliferation, migration and invasiveness of Caki-1 and 769-P. Using in vivo mouse models, knockdown of ZNF395 expression in 786-O promoted tumor growth while its overexpression in Caki-1 resulted in tumor growth inhibition. We are currently performing experiments to understand the process by which ZNF395 regulates ccRCC pathogenesis. Conclusions: Our data support the role of ZNF395 as an important tumor suppressor gene in the pathogenesis of RCC.
Incidence of cytogenetic (CG) abnormalities in multiple myeloma (MM) in a minority population.
Authors: G. S. Sidhu, R. Khillan, C. A. Axiotis, A. S. Braverman
Journal: Journal of Clinical Oncology (2011)

e18568 Background: Genomic aberrations are associated with MM survival and disease evolution. The combination of cytogenetics and Fluorescence in situ hybridization (FISH) reveals more anomalies than CG alone. The incidence of CG abnormalities in African American MM patients (AA) is not known. Methods: Records of patients with MM seen at Kings County Hospital and Downstate Medical Center from 2004 through 2010 were reviewed. Results: Of the 185 records reviewed, 181 (98%) patients had MM; 3 had plasma cell leukemia. Their age ranged from 36-89 years (median 66). There were 84 men (46%) and 97 women. CG analysis was done in 86 patients, 41 (48%) female and 45 (52%) male; of whom 82 were AA. CG was abnormal in 14 male and 6 female patients. Aneuploidy was present in 15 of 20 (75%); 11 of the 15 (73%) were hyperdiploid and 4 (26%) hypodiploid. Hyperdiploid chromosome number ranged from 49 to 67 (median 53). The most frequently aberrant chromosomes were 1, 4, 5 and 15. FISH was done in 42 patients for abnormal chromosomes 13, 14 and 17. One of 37 chromosomes 13 (2.6%), 3 of 28 (11%) chromosomes 14, and 1 of 14 (7.1%) chromosomes 17 displayed molecular abnormalities. In no case was more than one abnormality found. FISH on 28 patients with normal CG yielded only 1 (3.6%) abnormality. Conclusions: Abnormal CG was not more frequent in this AA population than in MM patients from other ethnic groups, but was in male AA patients. Fewer molecular abnormalities were found in this population.
Long-term response in metastatic renal cell carcinoma patients receiving first-line therapy with VEGF TKIs.
Authors: Srinivas Kiran Tantravahi, Shiven B. Patel, Sowmya Ravulapati, Julia A. Batten, Joseph Merriman, David D. Stenehjem, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2015)

436 Background: A subset of metatstatic renal cell carcincoma (mRCC) patients (pts) on first-line (1st) vascular endothelial growth factor inhibitors (VEGF TKIs) will have a long-term response (LTR) defined as a progression free survival (PFS) of &gt;18 months (mos) on continuous therapy, and may be candidates for intermittent VEGF TKI therapy. Methods: From our institutional dataset of mRCC pts, we identified pts receiving 1 st VEGF TKIs and who achieved a LTR. Data on clinical characteristics and survival outcomes were compared between those with LTRs and rest of the patients (control). Continuous and categorical variables were assessed by Wilcoxon rank sum and chi-square, respectively; and survival outcomes were compared by log-rank tests. Results: Of 89 pts, 24 (33%) had LTRs, of whom 5 pts have discontinued treatment (range 1-5 years) without subsequent disease progression, and 4 pts took treatment breaks for 3-9 mos. Baseline pts or disease characteristics were not predictive of LTRs (Table). Conclusions: A subset of mRCC pts receiving 1 st VEGF TKIs achieve a LTR, and are not currently identifiable by baseline clinical characteristics including prognostic risk categorization. Identification of biomarkers predictive of LTR may allow intermittent or even deferred therapy with VEGF TKIs minimizing toxicity and cost. [Table: see text]
Pegylated liposomal doxorubicin and carboplatin in malignant mixed epithelial mesenchymal and mesenchymal gynecologic tumors: A phase II trial of the AGO study group.
Authors: P. Harter, U. Canzler, H. Lueck, A. Reuss, W. Meier, T. N. Fehm, A. Staehle, A. Burges, C. Kurzeder, J. Sehouli, K. H. Baumann, L. C. Hanker, P. Wimberger, W. Schroeder, M. Gropp, S. Mahner, A. Du Bois
Journal: Journal of Clinical Oncology (2011)

5093
Development and implementation of competency-based orientation program for advanced practice providers at an academic cancer center.
Authors: David W. Dougherty, Julie Ann Berkhof, Cheryl Hokula, Julie Kozlowski, Jennifer Galdys, Nicole Zimmer
Journal: Journal of Clinical Oncology (2016)

119 Background: Increased utilization of Advanced Practice Providers (APPs) has been identified as a means to increase oncology visit capacity and improve productivity. Many APPs have little experience in oncology or are new to the APP role. As a result, there is a need for a comprehensive, competency-based orientation and mentorship program to aid in this transition and ensure effective integration of APPs into the complex oncology environment. Methods: We developed and implemented a comprehensive, competency-based orientation and mentorship program for APPs hired into the Wilmot Cancer Institute. In addition to basic institutional orientation, APPs are assigned primary &amp; secondary preceptors and complete a 12-week oncology-specific orientation that includes specific clinical activities relevant to their role. Oncology educational articles and lectures are provided and APPs meet weekly with preceptors to identify goals, accomplishments and improvement needs. Faculty mentors are assigned for additional oncology-specific and professional development, as well as oversight of chemotherapy ordering. If deficiencies are identified, APPs are provided an Individual Development Plan with milestones necessary for progression. Results: From January 2013 to July 2015, 16 APPs were hired and enrolled into the orientation program. 11 APPs had no prior oncology experience and 10 had no prior experience as an APP. 14 of 16 APPs (87.5%) successfully completed the orientation program. 2 APPs were placed on Individual Development Plans and subsequently did not complete the program. All 14 APPs successfully completing orientation have been retained in their position, leading to 100% retention rate for those completing the program since its inception. Conclusions: This framework for a comprehensive, competency-based orientation and mentorship program for APPs at an academic cancer center has improved our ability to successfully integrate APPs into the cancer care environment. In addition, APPs having difficulty transitioning or who are unable to complete the orientation were efficiently identified, leading to individualized improvement plans required for ongoing employment.
Pretreatment skeletal muscle depletion as an adverse prognostic factor in metastatic gastric cancer.
Authors: Hiroko Hasegawa, Kazumasa Fujitani, Yusuke Yamaoka, Motohiro Hirao, Shoichi Nakazuru, Mistugu Sekimoto, Eiji Mita
Journal: Journal of Clinical Oncology (2014)

161 Background: Body composition has emerged as an important prognostic factor in cancer patients. Especially, skeletal mass depletion has been associated with poor performance status, toxicity of chemotherapy and shortened survival in cancer patients. However, the impact of pre-treatment skeletal muscle index on survival or toxicity in metastatic gastric cancer patients remains uncertain. Methods: In this retrospective study, we reviewed 98 metastatic gastric cancer (mGC) patients who received S-1 based combination chemotherapy as first-line treatment from April 2006 to March 2013. Pre-treatment skeletal muscle mass was quantified by CT cross sectional area at the third lumbar vertebrae and evaluated as lumbar skeletal muscle index (SMI) (cm 2 /m 2 ) after normalization for stature (m 2 ). Patients were categorized into 2 groups depending on initial SMI: 35 patients with SMI ≤ 40 and 63 patients with SMI &gt; 40. Results: Median overall survival was significantly shorter in the SMI ≤ 40 group than in the SMI &gt;40 group (439 days versus 565 days; p= 0.03). Progression free survival was also better in the SMI&gt; 40 group without statistical significance (175 days versus 151 days; p= 0.17). Toxicity (grade 3 or 4) was more common in the SMI ≤ 40 group than in the SMI &gt;40 group. (41.1% versus 11.1%; p=0.001). In multivariate analysis, performance status of 2 (HR 4.711, 95%CI 1.065 to 20.832, p=0.04), presence of primary tumor (HR 2.322, 95%CI 1.007 to 5.357, p=0.04) and pre-treatment SMI (HR 2.525, 95%CI 1.145 to 5.568, p=0.02) were independent prognostic factors for OS. Conclusions: The present study suggests that skeletal muscle depletion at the initiation of first-line chemotherapy might be an independent prognostic factor for mGC patients.