tbuckley/cabot-search huggingface dataset:
A phase II trial of cabozantinib (XL-184) in patients with advanced cholangiocarcinoma.
Authors: Lipika Goyal, Matthew B. Yurgelun, Thomas Adam Abrams, Eunice Lee Kwak, James M. Cleary, Michelle Knowles, Eileen Regan, Amy Gisondi, Susan Sheehan, Hui Zheng, Andrew X. Zhu
Journal: Journal of Clinical Oncology (2015)

800 Background: Cholangiocarcinoma (CCA) carries a poor prognosis in advanced stages, and no standard treatment exists beyond the first line gemcitabine/platinum based combination regimen. Based on preclinical evidence of dysregulation of the VEGF and c-MET pathways in CCA, we performed a single arm phase II study of the dual VEGF receptor and c-MET small molecule inhibitor cabozantinib in patients with advanced CCA. Methods: All eligible pts had histologically confirmed unresectable or metastatic CCA and had progressed after 1 or 2 lines of systemic therapy. Pts were treated with cabozantinib 60mg orally daily continuously for 28 day cycles. Tumor assessments were obtained radiologically every 8 weeks. The primary endpoint was progression free survival (PFS). A Simon two stage design was used, and 9 of 20 pts had to be progression free at 16 weeks in order to proceed to the second stage. Results: Nineteen pts (male 32%; median age 67 years old; intrahepatic vs extrahepatic CCA, 95 vs 5%; 1 vs 2 previous lines of systemic therapy, 53% vs 47%%) were enrolled and all received at least one dose of study drug. After 12 pts failed to be progression free at 16 weeks, the study was terminated as it was determined that the criterion for proceeding to stage 2 could not be met. The median follow-up was 4.07 months (mos). No objective responses were seen. The median PFS was 1.77 mos (95% CI, 1.63-5.37), and the median overall survival was 5.20 mos (95% CI, 2.70-8.17). Eleven (58%) patients required dose reductions. Grade 3 and 4 adverse events occurred in 79% of pts and included neutropenia, epistaxis, hyperbilirubinemia, alkaline phosphatemia, AST/ALT elevation, anemia, lipasemia, and hypertension. One pt had a bowel perforation and another developed an enterocutaneous fistula while on the study drug. VEGF and c-MET pathway-related biomarker analysis is ongoing. Conclusions: Cabozantinib demonstrated limited antitumor activity in an unselected population of pts with advanced CCA. Despite close monitoring, a high rate of &gt; grade 3 toxicities was observed at 60 mg daily dosing. This pt population may be more sensitive to drug doses tolerated by other solid tumor patient populations, and therefore, close monitoring remains critical for these pts in early phase clinical trials. Clinical trial information: NCT01954745.
Objective measures of physical fatigue in women undergoing adjuvant therapy for early-stage breast cancer.
Authors: S. Waliany, C. Dieli-Conwright, A. Hurria, S. Patel, P. H. Frankel, T. H. Luu, J. Chao, J. E. Mortimer
Journal: Journal of Clinical Oncology (2011)

e19680 Background: Cancer-related fatigue (CRF) is prevalent with cancer diagnosis and treatment, and its subjective nature has made it difficult to characterize and treat. To help address this issue, we evaluated objective measures of these parameters and correlated the results with the self-reported measurement of fatigue. Methods: Women with stage I-III breast cancer receiving dose dense doxorubicin and cyclophosphamide (AC) were recruited. Participants were tested at baseline and week 2 after cycle 4 of AC. The assessment included a 6 Minute Walk (6MW), Jamar dynamometer (grip strength), and self-report Brief Fatigue Inventory (BFI). In addition, total daily energy expenditure (TEE) was measured using the Bodybugg (BB) armband for 1 week prior to chemotherapy and week 2 of cycle 4. Results: To date, 20 of the planned 25 participants have been enrolled in the clinical trial and 15 have completed pre and post chemotherapy assessments. The mean change in BFI score was +1.8 (increased fatigue). While all measures of physical function decreased (mean): TEE (-4.4%), dominant hand grip strength (-2.7%), 6MW (-3.7%), correlations with BFI were weak (|r|<0.1) for all measures other than TEE (r=-0.321) and 6MW (r=-0.312). Conclusions: The self-report of fatigue may be associated with objective tests of total daily energy expenditure and 6 minute walk, and continued accrual is warranted. Change in study measures in patient sample (post assessment – pre assessment). Pt BFI TEE (%) Hand grip strength (%) 6MWORK* (%) Dominant Nondominant 1 + 4.0 + 5.7 + 5.9 - 30.9 - 21.5 2 - 1.1 - 16.3 - 39.4 - 7.1 - 5.6 3 + 0.0 + 3.5 + 0.0 + 0.0 + 9.1 4 + 2.2 - 4.2 - 12.8 - 8.6 - 19.9 5 + 5.9 - 14.6 - 5.6 + 32.0 + 3.7 6 - 1.2 + 26.7 + 0.0 + 9.1 + 1.0 7 + 0.0 - 9.1 + 0.0 + 0.0 - 9.7 8 - 0.9 + 14.3 + 19.0 - 16.7 - 1.4 9 + 4.7 - 8.4 + 0.0 - 8.0 + 3.2 10 + 4.3 - 15.3 + 5.9 - 5.9 - 8.7 11 - 1.2 - 28.8 + 5.0 + 11.1 + 1.2 12 + 5.9 - 12.6 - 15.0 - 5.0 - 15.4 13 - 1.1 + 4.0 + 3.0 + 16.0 + 3.1 14 + 5.0 - 9.2 + 0.0 + 0.0 + 1.0 15 - 0.1 - 2.2 - 6.7 + 3.1 + 4.6 Mean + 1.8 - 4.4 - 2.7 - 0.7 - 3.7 * 6MWORK (kg-m) = patient’s weight (kg) × distance traveled (m).
Patterns and trends in management of locoregional prostatic adenocarcinoma with PSA ≥20 ngm/ML.
Authors: Jerry J Trulson, Danny Huynh, Majdee Islam, Abishek Rao, Naveen Pokala
Journal: Journal of Clinical Oncology (2014)

172 Background: Extremely high prostate specific antigen (PSA) at diagnosis has traditionally precluded a surgical approach for prostate cancer. This database study evaluates the national trends in management of patients with high PSA at prostate cancer diagnosis. Methods: Men age 75 or less with a diagnosis of prostatic adenocarcinoma and a PSA of 20ngm/ml and over were identified from the SEER 18 Database (2004 to 2009). Exclusion criteria included patients with metastatic disease at diagnosis, more than one primary cancer, unknown stage, unknown Gleason score, unknown treatment, or diagnosis at autopsy. Patients were analyzed for demographics, stage at presentation, treatment patterns, and survival using appropriate statistics. Results: A total of 15,485 patients with PSA between 20 and 98.8ngm/ml were identified. Mean age at diagnosis was 64±7.3 years. A total of 4,510 (29.1%) patients did not receive any definitive treatment (NDT group), 6,503 (52%) received Radiation, and 4,472 (28.9%) underwent surgery. A total of 531 patients underwent adjuvant radiation after surgery. The mean PSA of patients who underwent surgery (47.3ngm.ml) or RT (44.3 ngm/ml) was lower than the patients who did not have any definitive treatment (50.9 ngm/ml). Increasing age and increasing T and N stage were associated with a trend towards a surgical approach while Gleason score and PSA levels were not associated a trend towards surgery. Increasing age and Gleason score were associated with an increasing trend towards radiation while increasing PSA, T stage, and N stage were associated with a decreasing trend towards radiation. Increasing age and PSA was associated with an increasing trend towards NDT, while an increasing stage was associated with a reduced trend towards NDT. The N stage and Gleason score did not predict a trend for the NDT. Conclusions: The PSA level, even when very high, is not the sole factor that determines whether or not patients with prostate cancer receive surgery. Nationwide trends suggest that while radiation is the most common treatment modality undertaken by patients with PSA over 20 ngm/ml, patients younger than age 50 are more likely to undergo surgery irrespective of the PSA level.
Renal nephrometry score and predictors of pathologic upstaging in patients undergoing partial and radical nephrectomies.
Authors: Deepak Kumar Pruthi, Ruchi Chhibba, Darrel E Drachenberg, Thomas McGregor
Journal: Journal of Clinical Oncology (2015)

412 Background: To examine the predictive capability of pre-operative anatomic imagining characterization of the R.E.N.A.L. Nephrometry Score (RNS) in assessing pathologic upstaging of clinical T1 (cT1) lesions to pathologic T3 (pT3) in partial and radical nephrectomy specimens. Methods: We conducted a retrospective review of all patients undergoing radical and partial nephrectomies between January 1, 2011 and May 31, 2014 for cT1 renal masses. All pre-operative imaging scans were reviewed and the R.E.N.AL. Nephrometry score (radius for tumor size as maximal diameter, exophytic/endophytic tumor properties, nearness of deepest portion of tumor to collecting system or sinus, anterior/posterior descriptor and location relative to polar line) was applied to each scan. Chi-square, Fisher exact test, and Student t test were utilized to examine associations. Results: Of the 229 patients who underwent partial or radical nephrectomy for cT1, 124 (54%) underwent partial nephrectomy. On pathologic evaluation 195 (85%) patients had malignancy. Of all tumors 26 (13%) were pathologically upstaged to pT3 with the majority attributable to renal sinus/fat (35%) or perinephric fat (31%) involvement. High RNS (&gt;10) was significant in predicting pathologic T3 upstaging (p=0.039) but did not predict high grade (Furhman grade 3-4) disease (p=0.803). While a high nephrometry score trended toward predicting malignancy vs benign disease (p=0.086), a higher mean nephrometry score (7.81 vs. 6.84) significantly predicted malignancy (p=0.015). When controlled for cT1a lesions, tumor location relative to polar lines (L=3 vs. L1+2) was predictive of pT3 upstaging (24 vs. 6%, p=0.03). Age &gt;65 was significantly associated with upstaging (26 vs. 7%, p=0.0001). Conclusions: Surveillance of small renal masses is common but high RNS and age &gt;65 significantly predicted pathologic upstaging. Mean nephrometry score was also useful in predicting malignancy. Nephrometry score may aid in deciding on early surgical intervention.
Therapeutic impact and timing of gastrointestinal malignancy genomic profiling: A single-institution experience.
Authors: Kristin Lynn Koenig, Jarred Burkart, Sameh Mikhail, Christina Sing-Ying Wu, Anne M. Noonan, Richard M. Goldberg, Tanios S. Bekaii-Saab, Kristen Keon Ciombor
Journal: Journal of Clinical Oncology (2016)

4100 Background: Tumor genomic profiling has become critical in the identification of targeted therapeutic options for patients (pts) with advanced malignancies. Mutational frequencies and their therapeutic importance vary among tumor types. This analysis was undertaken to characterize the landscape of genomic alterations in gastrointestinal (GI) malignancies found in a large academic institutional practice, and to determine the frequency of alteration-specific targeted therapy selection based on genomic profiling. Methods: Adult pts with GI malignancies presenting to the Ohio State University Comprehensive Cancer Center oncology clinics were offered next generation sequencing through FoundationOne testing as part of routine clinical care. Institutional review board approval was obtained to retrospectively analyze results from FoundationOne testing performed between 2012 and 2015. Results: 271 pts with GI malignancies underwent successful genomic profiling. A total of 1203 genomic alterations were found, with an average of 4.5 per tumor (range 0-20); 365 (30%) of these were potentially actionable and most often found in colorectal or gastroesophageal tumors. 14 pts (5.3%) had actionable alterations in MET, CDKN2A/B, FGFR2, KRAS, BRAF, or NF2 that led to enrollment in genotype-directed clinical trials or off label use of targeted therapies beyond standard of care. Pt performance status at the time of genomic alteration identification was a significant factor in precluding genotype-directed therapy. One variant of unknown significance involving FGFR2 identified at initial testing subsequently became actionable and led to pt enrollment on a clinical trial. One pt with rectal cancer was found to have a KRAS wild-type and BRAF mutant primary but KRAS mutant and BRAF wild-type liver metastasis. Conclusions: Genomic profiling of GI malignancies through FoundationOne testing is feasible and can lead to genotype-directed therapy selection; however, it should be considered early in the pt’s course to optimize use of targeted therapies through clinical trials. Consideration should be given to serial tumor testing to identify emerging genomic alterations for optimal therapy selection.
A matched analysis comparing the epidemiology of intraductal papillary mucinous neoplasms to standard pancreatic adenocarcinoma and healthy controls.
Authors: E. Ludwig, S. H. Olson, R. C. Kurtz, J. Simon, M. F. Brennan, W. R. Jarnagin, P. J. Allen
Journal: Journal of Clinical Oncology (2011)

173 Background: The epidemiology of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas is poorly defined. Methods: An epidemiologic questionnaire was administered to patients (pts) with IPMN (n=79), pancreatic adenocarcinoma (PC) (n=689) and healthy controls (n=307). Results were adjusted for age, gender and BMI. IPMN was defined either by surgical pathology (n=62) or characteristic endoscopic ultrasound appearance and cyst fluid CEA&gt;200 ng/ml (n=17). Results: In unadjusted analysis IPMN pts were more likely to be ≥ 70 years of age (OR 5.40 [2.88, 10.46]) when compared with PC pts (OR 2.82) and controls. After adjustment for age, gender and BMI, current tobacco smoking was associated with PC (OR 3.06 [1.78, 5.23]) but not IPMN. Pts with IPMN more often had diabetes mellitus for &gt;3 years compared with controls (OR 3.25 [1.45, 7.00], while pts with PC (OR 1.52 (0.86, 2.67]) did not. IPMN pts were more likely to have a history of hypercholesterolemia compared with controls (OR 1.77 [1.05-2.98]); this was not seen for PC pts (OR 1.16 [0.87-1.55]). A first degree relative with PC was not associated with increased risk for IPMN (OR 0.84 [0.27, 2.62]) or PC (OR 1.48 [0.82, 2.67]). Compared to PC, pts with IPMN were more likely to have a history of an unrelated cancer (OR 1.84 [1.08, 3.14]). Conclusions: Risk factors for IPMN and PC may differ. Compared to PC and control pts, IPMN patients were older; more often had diabetes mellitus and hypercholesterolemia; and did not currently smoke. IPMN was more often associated with a prior history of cancer than PC. No significant financial relationships to disclose.
Immunosupressive properties of human placenta-derived mesenchymal stem cells on control of acute graft-versus-host disease in mice.
Authors: M. J. Jang, S. Y. Oh, H. Kim, H. Shin, G. J. Kim, S. Y. Chong, D. Oh, H. Chung
Journal: Journal of Clinical Oncology (2011)

6547 Background: Graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) is still associated with significant morbidity and mortality. High-dose corticosteroids are standard in initial treatment of patients with acute GVHD achieving response rates of 30-70%. However, no standard therapy exists once a patient has developed acute GVHD refractory to corticosteroids. In this respect, the immunomodulatory properties of mesenchymal stem cells (MSC) have been applied to reduce the incidence the GVHD after allogeneic HSCT. Among the various sauces of MSC which have immunomodulatory effect in vitro, only human placenta MSC (hP-MSC) has not elucidated in the GVHD in vivo model. In this study, we characterize the phenotype of hP-MSC, investigate their immunomodualotory properties in vitro and evaluate the clinical possibilities of hP-MSC for the control of GVHD in MHC mismatch mice model. Methods: A GVHD mouse model was established by transplanting C57BL/6 donor bone marrow (BM) cells and spleen cells into lethally irradiated BALB/c recipient mice. To control the GVHD, hP-MSC was transplanted to recipient mice (5 x 105 or 1 x 106). Results: We purified and expanded the hP-MSC characterized by flow cytometry (positive for CD105, CD73, CD44, CD56 and HLA-ABC but negative for CD3, CD14, CD31, CD45, CD11a, CD34 and CD117). These cells also exhibited mesenchymal differentiation potential, as assessed by culturing in adipogenic, osteogenic, or chondrogenic medium. In vitro experiment, the hP-MSC suppressed mitogen-stimulated T cell proliferation in a dose-dependent manner. Moreover, hP-MSC inhibited cytokine secretion (IL-12, TNF-α, and INF-γ) of T-cells in response to mitogen. In vivo experiment, survival rate in hP-MSC (1x106) group was higher than in the control group, and histological scores were low in hP-MSC (1x106) group. Conclusions: We conclude that hP-MSC can efficiently control the GVHD associated with allogeneic HSCT in mice model.
Efficacy of imatinib mesylate plus hydroxyurea regimen in the treatment of recurrent malignant glioma: Phase II study results
Authors: H. S. Friedman, J. Quinn, J. Rich, J. Vredenburgh, A. Desjardins, S. Sathornsumetee, A. Salvado, Z. Nikolova, D. Bigner, D. Reardon
Journal: Journal of Clinical Oncology (2005)

1515 In this phase 2 study we evaluated the activity of imatinib mesylate (Gleevec), an inhibitor of the PDGF receptor tyrosine kinase with anti-angiogenic activity and the ability to decrease tumor interstitial pressure, combined with hydroxyurea in the treatment of patients with recurrent malignant glioma. Eligibility criteria include: recurrent malignant glioma; age > 18 years; KPS 60% or greater; less than grade 2 intratumoral hemorrhage; adequate hepatic, renal, and bone marrow function. Hydroxyurea is administered at 500 mg BID while Gleevec is administered at 500 mg BID for patients on enzyme-inducing anticonvulsants (EIAC; phenytoin, carbamazepine and phenobarbitol) and at 400 mg QD for those not on EIAC. A treatment cycle lasted 28 days and evaluations for response were performed after every other cycle. Enrollment includes 64 patients: 32 with recurrent GBM and 32 with recurrent AA/AO. The median age is 46 (range 21 to 68); 55% are male and 45% are on EIAC. All patients had prior XRT and the median number of prior chemotherapy agents was 3 (range, 1–5) while the median number of prior progressions was 2 (range, 1–7). Toxicity has included grade 3 or 4 hematologic events in 20% and 5% respectively, grade 3 edema in 8% and grade 3 LFT abnormalities in 3%. Nine percent of GBM patients achieved a radiographic response while 35% achieved stable disease. Median progression free survival (PFS) for patients with recurrent AA/AO and GBM are 10.9 and 14.4 weeks respectively. At 6 months, 26.3% of GBM patients are progression free. Among heavily pretreated patients with recurrent GBM enrolled on this study, the rate of radiographic response, median PFS and 6-mth PFS rate compare favorably to results achieved with temozolomide in first relapse indicating that a randomized trial of imatinib mesylate plus hydroxyurea versus temozolomide is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
Identification of prognostic groups in patients with hormone-sensitive metastatic prostate cancer at the present time: An analysis of the GETUG 15 phase III trial.
Authors: Gwenaelle Gravis, Karim Fizazi, Florence Joly, Stephane Oudard, Frank Priou, Igor Latorzeff, Remy Delva, Ivan Krakowski, Brigitte Laguerre, Frederic Rolland, Christine Theodore, Gael Deplanque, Jean-Marc Ferrero, Damien Pouessel, Loic Mourey, Philippe Beuzeboc, Sylvie Zanetta, Benjamin Esterni, Muriel Habibian, Michel Soulie
Journal: Journal of Clinical Oncology (2013)

26 Background: Patients with upfront metastases at the time of prostate cancer (PC) diagnosis are less frequent than in the past in Western countries, but still represent 5-10% of all patients and almost one half of PC patients will eventually die of the disease. Prognostic factors (lymph node metastases/appendicular vs axial bone disease, performance status &gt; 1, Gleason score &gt; 8 and PSA &gt; 65 ng/ml) have been proposed (Glass et al., 2003), leading to the definition of three subgroups with good, intermediate and poor prognosis. However, the current natural history of metastatic prostate cancer has not been well described. Methods: Patients with hormone sensitive metastatic PC were randomized to receive continuous androgen deprivation therapy (ADT) plus docetaxel (75 mg/m²/21d up to 9 cycles) and prednisone or ADT alone. Glass risk groups were used as stratification factors. Results: From October 2004 to December 2008, 385 pts were included. They were distributed into good (50%), intermediate (29%), and poor (21%) prognosis groups. The median follow up was 50 months [95% CI: 49 - 54]. The primary endpoint analysis showed no difference in overall survival (OS) (HR: 1.01 [95%CI: 0.75-1.36]) between the 2 arms but a significant PFS improvement was observed in the docetaxel group (HR: 0.75 [0.59-0.94] p=0.0147) (Gravis, ESMO 2012). The median OS in the ADT alone arm was 54 months [42-NR]. It was 69 [95% CI: 60.9-NR], 47 [95% CI: 37.7-NR, HR = 1.6] and 37 [95% CI: 28.5-58.9, HR = 2.12] months respectively in the good, intermediate, and poor prognosis groups (p=0.001) in the whole cohort. No interaction between prognosis groups and treatment was found. A detailed analysis using the Cox model will be presented. Conclusions: At the present time, median life expectancy of patients with metastatic PC seems to exceed 4 years. Subgroups with favorable or unfavorable outcome can be identified. Clinical trial information: NCT00055731.
High-Dose Therapy (HDT) with Autologous Hematopoietic Stem Cell Transplantation (HSCT) in Patients with Poor Prognosis Ewing Family Tumors (EFT).
Authors: Ellen Bolotin, Marianna Shakhnovits, Laurence Cooper, Dajun Qian, Debbie Hitt, Robert Sweetman, Judith Sato, James Miser, Stephen Forman, Joseph Rosenthal
Journal: Blood (2005)
Phase II study of bevacizumab plus erlotinib for recurrent malignant gliomas
Authors: S. Sathornsumetee, A. Desjardins, J. J. Vredenburgh, J. N. Rich, S. Gururangan, A. H. Friedman, H. S. Friedman, D. A. Reardon
Journal: Journal of Clinical Oncology (2009)

2045 Background: Bevacizumab (B), a neutralizing VEGF monoclonal antibody, has anti-glioma activity as single agent and in combination with cytotoxic therapy. Erlotinib (E), an EGFR tyrosine kinase inhibitor, may exhibit anti-tumor activity in some malignant glioma (MG) patients. B plus E was associated with clinical benefit in several solid tumors. We performed a single-arm, phase II study to evaluate the efficacy of B and E in patients with recurrent MG. Methods: The primary endpoint was 6-month progression-free survival (PFS-6). Radiographic response, pharmacokinetics and correlative biomarkers were secondary endpoints. E was orally administered daily at 200 mg/day for patients not on enzyme-inducing anticonvulsants (EIAC) and 500 mg/day for patients on EIAC. All patients received 10 mg/kg of B intravenously every two weeks. Key eligibility criteria included: age ≥ 18 years; KPS ≥ 60; &gt; 4 weeks from prior surgery, XRT or chemotherapy. Patients with either &gt; 3 prior progressions, requirement for therapeutic anti-coagulation or acute hemorrhage on pre-treatment imaging were excluded. Results: Fifty-six patients with recurrent MG (n = 24 for glioblastoma multiforme [GBM] and n = 32 for anaplastic gliomas [AGs]) were assessable for outcome. The PFS-6 rates were 25% for GBM and 50% for AGs. There was no survival difference between EIAC and non-EIAC groups. Rash (54% grade 1–2 and 38% grade 3) was the most common side effect. Nausea, diarrhea, and fatigue were common but mostly grade 1–2. Serious side effects were rare and included two patients with pulmonary embolism, single patients with either intestinal perforation, ischemic stroke, gastric bleeding, or nasal septal perforation. Pharmacokinetic and tissue biomarker profiles are in preparation. Conclusions: Among heavily pretreated recurrent MG patients, bevacizumab plus erlotinib is tolerated and associated with encouraging anti-tumor benefit. No significant financial relationships to disclose.