tbuckley/cabot-search huggingface dataset:
Hepatic arterial infusion (HAI) in the treatment of breast cancer with liver metastases (BCLM) in patients (pts) who progressed after hormonal and systemic chemotherapy (CTx).
Authors: L. A. Herran, K. L. Jhaveri, A. D. Seidman, D. Patel, A. N. Gewirtz, N. E. Kemeny
Journal: Journal of Clinical Oncology (2011)

e11045 Background: The prognosis of BCLM is poor with a median survival of < 6 months (mths). There is data for improved survival in pts with colorectal liver metastases treated with HAI floxuridine (FUDR)/dexamethasone (Dex) in combination with systemic CTx. Data suggests improved response rates of BCLM can be achieved by regional transcatheter bolus infusion. Methods: We retrospectively reviewed 8 pts with BCLM treated with HAI FUDR/Dex. Pts received FUDR/Dex with or without systemic irinotecan (80 mg/m2 q2wks) or sideport pump Mitomycin C (10 mg/m2 monthly) or both. Partial response (PR), progression free survival (PFS) and overall survival (OS) were used to evaluate efficacy. Results: The median age was 42.5 yrs (range 34 - 53). 7/8 pts had documented stable metastatic sites outside the liver including lung, bone and lymph nodes. All pts had systemic CTx with a median of 8 regimens (range 2-13) prior to HAI. Prior to HAI, pts with positive hormone receptors (8/8) had received hormonal therapy and those with positive Her2/neu (3/8) received trastuzumab. 2/8 pts received treatment with FUDR/Dex alone, 2 received systemic irinotecan as well and 4 pts were treated with all 3 agents. 6/8 had a response; 5 PR and 1 minor response. 5 pts with PR had > 50% reduction in CEA and 4 had > 50% reduction in CA 15-3. The median PFS was 8.9 mths (range 0.8 - 14.8) and median OS from start of HAI was 12.5 mths (range 1 to 116). One patient had progression of extrahepatic metastases to the brain. One patient continues to respond. Toxicity was liver function abnormalities; 4/8 had grade 3/4 elevations in alkaline phosphatase. Conclusions: HAI pump therapy with FUDR/Dex plus sideport Mitomycin C and/or systemic irinotecan is feasible and might be capable of prolonging survival with limited toxicity in a selected group of pts heavily pre-treated for BCLM. Prospective randomized trials are necessary to establish a role of this treatment modality when treating these pts.
Comparison of abiraterone acetate (Abi) versus ketoconazole (Keto) in chemotherapy-naive patients (CN-pts) with metastatic castration resistant prostate cancer (mCRPC).
Authors: Avivit Peer, Avivit Neumann, Avishay Sella, Eli Rosenbaum, Victoria Neiman, Maya Gottfried, Iryna Kuchuk, Svetlana Kovel, David Sarid, Eliahu Gez, Wilmosh Mermershtain, Keren Rouvinov, Michael Anthony Carducci, Mario A. Eisenberger, Victoria J. Sinibaldi, Raanan Berger, Daniel Keizman
Journal: Journal of Clinical Oncology (2016)

260 Background: Abi is a standard treatment (tx) in CN-pts with mCRPC. It is a potent and selective CYP 17 inhibitor. However, in many countries where abi has not been approved yet, keto is used as an alternative CYP 17 inhibitor. Preclinical data suggests that keto is a less specific and potent inhibitor of CYP 17. Clinical data (Peer et al, Prostate 2014) suggests that in docetaxel (D) refractory mCRPC, the outcome of abi tx may be superior to keto. However, there are limited clinical data comparing both agents in CN-pts with mCRPC. We aimed to compare the clinical effectiveness of abi vs keto in CN-pts with mCRPC, who were treated after the year 2004 (approval of D for the tx of mCRPC). Methods: Records from 72 CN-pts with mCRPC treated with abi in 5 Israeli centers were reviewed retrospectively, and matched by pre-tx risk category (favorable, intermediate, poor; Keizman, Oncologist 2012) to pts treated with keto 200 - 400 mg 3x day (international database, n = 156, from 4 centers across the US and Israel). We compared the PSA response (decrease ≥ 50% from baseline), biochemical and radiological progression free survival (PFS), and overall survival (OS) between the groups. PFS and OS were determined by Cox regression. Results: The groups were matched by pre-tx risk category (favorable, intermediate, poor; Keizman, Oncologist 2012), based on pretreatment NLR and PSA doubling time, and the prior response to a gonadotropin-releasing hormone agonist. The groups were balanced regarding age (72 abi vs 70 keto), time from primary tx to disease relapse, gleason score, pre-tx disease extent (limited-axial skeleton and/or nodal vs extensive- appendicular skeleton and/or visceral), and ECOG PS. In the groups of abi vs keto, PSA response was 75% vs 47% (OR 3.8, p = 0.04), median biochemical PFS 12 vs 6 months (HR 0.62, p = 0.03), median radiological PFS 16 vs 8 months (HR 0.54, p = 0.01), median OS not reached after a median follow-up time of 18 months vs 26 months, and tx interruption d/t adverse events 10% vs 22% (0R 0.65, p = 0.05). Conclusions: In CN-pts with mCRPC, the outcome of pts treated with abi may be superior to keto.
A multicenter phase II study of pemetrexed as second-line chemotherapy for the treatment of hormone refractory prostate cancer (HRPC); Hoosier Oncology Group GU-0367
Authors: N. M. Hahn, R. T. Zon, T. Jones, F. Ademuyiwa, W. M. Dugan, C. Whalen, M. Yu, R. Shanmugam, T. Skaar, C. J. Sweeney
Journal: Journal of Clinical Oncology (2008)

16019 Background: Chemotherapy options after docetaxel based regimens for HRPC are needed. The multi-targeted anti-folate, pemetrexed (P), is a broadly active cytotoxic that may benefit this group of patients. Methods: HRPC patients with progressive disease after docetaxel with a Karnofsky performance status (KPS) of at least 70 were treated with P 500 mg/m2 iv d1 with vitamin support on a q21d cycle. The primary endpoint was PSA response per consensus criteria. A two-stage simon design was employed. A pharmacogenetic analysis of reduced folate carrier-1 gene (RFC1) was performed. Results: 49patients were enrolled with a median age of 68 (53–83) and a median KPS of 90 (70–100). A median of 3 cycles (1–20) were administered. 9 patients (19.4%) experienced grade 3/4 hematologic toxicity (neutropenic fever - 2 pts) and 17 patients (34.7%) experienced grade 3 non-hematologic toxicity (fatigue - 6 pts, infection - 4 pts, bone pain/arthralgia/dyspnea/liver function abnormalities - 3 pts each). Best PSA response was: confirmed > 50% decline in 4 patients (8.2%, 95% CI 0.5–15.8%), stable disease lasting at least 12 weeks in 10 patients (20.4%, 95% CI 9.1–31.7%), and progressive disease in 32 patients (65.3%, 95% CI 52.0–78.6%). Among 26 patients with measurable disease by RECIST, 2 patients (7.7%) demonstrated a partial response and 10 patients (38.5%) has confirmed stable disease at 12 weeks. The median time to PSA progression, objective progression, and overall survival were 2.0, 4.4, and 14.0 months respectively. 12 patients (24.5%) had improvement from their baseline pain scores. Pharmacogenetic analyses of the RFC1 G80A wild-type (G/G), heterozygous (G/A), and mutated (A/A) genotype frequencies did not show a relationship between genotypes and time to PSA progression, objective progression and overall survival. Conclusions: Pemetrexed treatment for HRPC patients with progression after docetaxel therapy was associated with 25% of patients having disease control at 12 weeks. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly Eli Lilly
Clinical Implications of Genetic Mutations in Myelodysplastic Syndrome
Authors: James A. Kennedy, Benjamin L. Ebert
Journal: Journal of Clinical Oncology (2017)

Myelodysplastic syndrome (MDS) is clonal disorder characterized by ineffective hematopoiesis and a tendency to evolve into acute myeloid leukemia (AML). Genetic studies have enabled the identification of a set of recurrently mutated genes central to the pathogenesis of MDS, which can be organized into a limited number of cellular processes, including RNA splicing, epigenetic and traditional transcriptional regulation, and signal transduction. The sequential accumulation of mutations drives disease evolution from asymptomatic clonal hematopoiesis to frank MDS, and, ultimately, to secondary AML. This detailed understanding of the molecular landscape of MDS, coupled with the emergence of cost- and time-effective methodologies for DNA sequencing has led to the introduction of genetic studies into the clinical realm. Here, we review recent advances in our genetic understanding of MDS, with a particular focus on the emerging role for mutational data in clinical management as a potential tool to assist in diagnosis, risk stratification, and therapeutic decision-making.
Impact of timing of biochemical failure on the eventual development of clinical failure after definitive treatment with brachytherapy or external beam radiotherapy for prostate cancer.
Authors: Jay P. Ciezki, Chandana A. Reddy, Eric A. Klein, James Ulchaker, Kenneth Angermeier, Rahul D. Tendulkar, Kevin L. Stephans, Steven C. Campbell, Andrew J. Stephenson
Journal: Journal of Clinical Oncology (2015)

53 Background: Late treatment failure is often considered to be a rare event. We will assess the influence of the timing of biochemical failure (bF) after definitive brachytherapy (BT) or external beam radiotherapy (EBRT) for prostate cancer on its frequency and association with clinical failure (cF). Methods: Patients with prostate cancer treated between 1996 and 2009 with at least 5 years of follow-up (N= 2,293; 1,060 EBRT, 1,233 BT) were studied in the context of an IRB-approved inception cohort study. Those with a bF were reviewed to determine the timing of bF [&lt; 5 years after treatment (bF&lt;5) vs. &gt; 5 years after treatment (bF&gt;5)] and occurrence of cF post-bF. The bF definition used was the nadir + 2.0 ng/mL version. Results: Of the total patient population, 477 (21%) were noted to have bF- 244 (11%) bF&lt;5 vs. 233 (10%) bF&gt;5. The median follow-up after bF for the bF&lt; 5 group is 41 months while in the bF&gt; 5 group it is 22 months. In the BT group, 94 (8%) failed &lt; 5 years and 87 (7%) failed &gt; 5 years. In the EBRT group, 150 (14%) failed &lt; 5 years and 146 (14%) failed &gt; 5 years. The median PSA value (ng/mL) at the time of bF for all patients, EBRT, and BT in the bF&lt;5 group was 3.70, 3.65, and 3.80, respectively (p=not significant). The median PSA value (ng/mL) at the time of bF for all patients, EBRT, and BT in the bF&gt;5 group was 3.01, 3.01, and 3.04, respectively (p=not significant). Overall, 53.3% of patients in the bF&lt;5 group developed cF while 27% of patients in the bF&gt;5 group developed a cF. The actuarial five year rate of cF for the bF &lt;5 group was 50% vs. 38% for the bF&gt;5 group (p= 0.028). The detection of bF and cF was closely linked to PSA testing frequency ( p &lt; 0.0001). Conclusions: The risk of bF does not appear to decrease &gt;5 years post treatment. Late bF (i.e. &gt;5 years after treatment) may still result in eventual cF. While cF is less common after bF &gt; 5 years post definitive therapy, it still affects 27% of those with bF and is strongly associated with PSA testing frequency. The lower rate of cF after 5 years may relate to the shorter follow-up time for this group.
非血縁ドナー移植における移植片対宿主疾患予防のためのペントスタチン,タクロリムス,およびミニメトトレキサートの併用: 第1/2相アダプティブな対照無作為化試験
Authors: Parmar Simrit, S Andersson Borje, Couriel Daniel, F Munsell Mark, Fernandez-Vina Marcelo, B Jones Roy, J Shpall Elizabeth, Popat Uday, Anderlini Paolo, Giralt Sergio, Alousi Amin, Cano Pedro, Bosque Doyle, Hosing Chitra, DE Padua Silva Leandro, Westmoreland Michael, Wathen J. Kyle, Berry Donald, E Champlin Richard, J De Lima Marcos
Journal: Journal of Clinical Oncology (2011)
Measuring quality of life in chronic hematologic malignancy: The QUALMS-1.
Authors: Yolanda Martins, Robert Klaassen, Fabio Efficace, Rena Buckstein, Sara Tinsley, Corey D. Watts, Joseph G. Jurcic, Gregory Alan Abel
Journal: Journal of Clinical Oncology (2014)

263 Background: Disease-specific measures of quality of life (QoL) allow for assessment of disease-specific symptoms and psycho-social factors, an especially important endeavor for patients with chronic hematologic malignancies. We aimed to determine if disease-specific QoL could be measured for patients with myelodysplastic syndromes, and what underlying constructs would inform such a measure. Methods: We previously reported on the development of the QUALMS-1, a 33-item QoL tool for MDS patients. 124 MDS patients completed the QUALMS-1 and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Chart review was conducted to collect disease characteristics, lab tests, treatments, transfusions, and use of growth factors. Participants were recruited from MDS centers across the USA, Canada and Italy. QUALMS-1 items were scored on a scale ranging from 1 “Never” to 5 “Always”, with 4 reverse-scored items. Items were averaged to create a preliminary total scale score, with higher scores indicating poorer MDS-specific QoL. Results: Mean total scores on the QUALMS-1 ranged from 1.0 - 3.9. The measure had excellent internal consistency reliability (α=.92) and was moderately correlated with the QLQ-C30’s global health, physical functioning, role functioning, emotional health, cognitive functioning, social functioning, fatigue, nausea and pain measures (r range from 0.34 – 0.65, all p &lt;.01). Patients with Hg &lt;= 10 showed a small but consistent higher QUALMS-1 score (M = 2.5; SD =.59) than those with Hg &gt;10 (M = 2.1; SD =.54; p =.03). Preliminary analyses suggested that four latent factors underlie the QUALMS-1, corresponding to the following subscales: physical burden, disease information and uncertainty, emotional burden, and disease-related positives. Conclusions: Our data suggest that the QUALMS-1 is internally consistent and has construct validity in patients with MDS. The measure provides a unique assessment of disease information and uncertainty, as well as disease-related positives. These are psychosocial constructs that may be particular to chronic hematologic malignancies such as MDS and are not well-assessed by generic or cancer-related measures.
Wilms' Tumor 1 (WT1) Gene Mutations in Pediatric T-Acute Lymphoblastic Leukemia.
Authors: Aline Renneville, Sophie Kaltenbach, Emmanuelle Clappier, Sandra Collette, Jean-Baptiste Micol, Brigitte Nelken, Pascale Lepelley, Nicole Dastugue, Yves Benoit, Yves Bertrand, Claude Preudhomme, Hélène Cavé
Journal: Blood (2009)
MicroRNA oncogenes and tumor suppressors controlling malignant melanoma cell growth, apoptosis, migration, and invasion.
Authors: R. W. Georgantas, K. Streicher, W. Zhu, R. Carrasco, Z. Xiao, Z. Liu, P. Brohawn, C. Morehouse, D. Tice, B. W. Higgs, L. Richman, P. Kiener, B. Jallal, Y. Yao
Journal: Journal of Clinical Oncology (2011)

8549 Background: Melanoma incidence is increasing faster (3%-7% per annum) than any other cancer. Data from the SEER Study showed a melanoma incidence rate of 19.5/100,000 for males and 14.4/100,000 for females in the USA, resulting in roughly 14,000 cases/year in the USA alone. Emalignant melanomas are generally easily treated by resection; but treatment ability changes dramatically once the tumor becomes metastatic. Such patients have a five year survival rate less than 5%, with median survival of only six to twelve. Dacarbazine (DTIC) is the only approved treatment for malignant melanoma, yet patient responses are infrequent (~10-20% of patients). Even in responders, DTIC extends lifespan for only 3-6 months. Methods: We examined the function, of miRs found to be differentially expressed in thirty-six melanoma skin biopsies compared to sixteen normal donor skin biopsies, on cell growth rate, caspase 3/7 activation, migration, invasion, and susceptibility to DTIC in five different melanoma cell lines, one normal melanocyte line, and normal primary melanocytes. Results: Of the ninety-eight differentially expressed miRs, informatics predicted twelve putative tumor suppressor and five putative oncogene microRNAs, as well as one putative oncogenic microRNA cluster (miR-506-514 cluster; presented in a separate abstract by Streicher et al). Subsets of these miRs showed potent statistically significant effects in at least three malignant melanoma cell lines compared to normal melanocytes. Transfection of miR-126, -193b, -203 miR mimics or miR-146a or -21 miR inhibitors significantly increased caspase 3/7 activation in melanoma cell lines. MiR-126, -193b, or -206 miR mimics or miR-21 or -146a miR inhibitors significantly decreased tumor growth rate. Mir-193b, -206, -let7c miR mimics or miR-146a, -21, of -31 miR inhibitors decreased melanoma cell migration and invasion. None of the tested miRs showed an effect on susceptibility to dacarbazine. Conclusions: In summary, we functionally annotated eight differentially expressed miRs as functional oncogenes or tumor suppressors in malignant melanoma cell lines that represent potential targets for melanoma therapy and biomarkers.
Effect of bridging therapy for hepatocellular carcinoma prior to orthotopic liver transplantation on disease control and response.
Authors: J. W. Chuy, M. Kinkhabwala, J. Reinus, K. Tanaka, A. Kaubisch
Journal: Journal of Clinical Oncology (2011)

343 Background: Orthotopic liver transplantation (OLT) is curative for both hepatocellular carcinoma (HCC) and underlying cirrhosis, but this option is limited by lengthy waiting times and donor organ shortages. Various bridging therapies have been employed to slow tumor progression, with reported results radiographically confirming local control with variable rates of tumor necrosis on pathologic examination of explants. Methods: We retrospectively studied 11 patients who underwent a total of 26 locoregional therapies prior to OLT for HCC. One patient was also maintained on sorafenib. The effectiveness of bridging therapies was assessed by radiologic response and histopathological examination of the explanted livers. Results: Sixteen tumor nodules identified in liver explants were evaluated. Pretransplant treatments included: TACE alone (5), TACE + sorafenib (2), RFA alone (1), TACE + RFA (6), or TACE + alcohol ablation (2) prior to OLT. Two nodules (13%) achieved complete tumor necrosis on explant analysis; these had been treated with TACE + RFA. Among 11 patients who underwent bridging therapies, 5 patients (45%) had no radiologic evidence of viable tumor prior to OLT. Among these patients, explant examination showed 2 patients with partial necrosis, 2 patients with at least 90% necrosis, and one patient with no evidence of viable tumor. Three patients with enhancing lesions on imaging prior to OLT had 100% concordance rate on pathological examination of the liver explant with respect to number of nodules identified. Conclusions: Although bridging therapy prior to OLT is effective in achieving disease control, most patients have viable tumor present upon assessment of explanted livers. Absence of viable tumor by radiologic evaluation following bridging therapy does not correspond to complete tumor necrosis. [Table: see text] No significant financial relationships to disclose.
The effectiveness of the shared medical visit among patients with a gynecologic malignancy undergoing chemotherapy along the Texas-Mexico border.
Authors: Kayla E. Castañeda, Loretta L. Hernandez, Zuber Mulla, Harvey Greenberg, J. Salvador Saldivar
Journal: Journal of Clinical Oncology (2014)

63 Background: The goal of this program was developed in response to The Institute of Medicine’s (IOM) “Crossing the Quality Chasm: A New Health System for the 21st Century” (2001) to provide patient-centered care that would result in improved patient satisfaction and decreased stress through the use of a shared medical visit (SMV) for patients with a gynecologic malignancy undergoing chemotherapy in place of an individual visit. Methods: The study design was a prospective cohort at a university health sciences center located on the Texas-Mexico border. A total of 20 patients will be enrolled in the SMV and 20 in the individualized visit. Participants attended group sessions with the provider that combined assessment, education, and social support. Patient-centered care was achieved by assisting them to obtain their own vital signs and by using a facilitative learning approach during the educational and social support component. Patients in the comparison group were patients who continued in the individual visits. The average differences between the pre- and post-session scores for perceived stress and patient satisfaction were calculated for both groups. Differences between both patient groups were tested for statistical significance using the Student’s independent two sample t-test. Results: The first twelve patients completed pre- and post-session questionnaires on perceived stress and patient satisfaction. For perceived stress, a lower score indicated lower stress. The average change in score for the individual group (n=6) was 0.67, and the average change in score for the SMV group (n=6) was -2.83 (p=0.28). For patient satisfaction, a higher score indicated higher satisfaction. The average change in score for the individual group (n=6) was -5.5; the average change in score for the SMV group (n=6) was -7.5 (p=0.80). Conclusions: Overall, patients felt they benefited from the shared medical visit. While the results of our interim analyses were not statistically significant, it appears that patient stress with the shared medical visit model may decrease over time. Based on our preliminary results we will continue to enroll patients and evaluate this unique program.
Fluorescence in situ hybridization (FISH) and array-comparative genomic hybridization (a-CGH) from percutaneous needle biopsy compared to renal mass histology.
Authors: Massimiliano Spaliviero, Kelly Lynn Stratton, Timothy F. Donahue, Banumathy Gowrishankar, Charles Ma, Jeremy C. Durack, Stephen Barnett Solomon, Jane Houldsworth, Jonathan A. Coleman
Journal: Journal of Clinical Oncology (2013)

471 Background: Image-guided percutaneous needle biopsies are increasingly utilized for the diagnosis of renal tumors. Histologic diagnosis of renal mass subtypes, including malignant clear cell (ccRCC), papillary (pRCC), chromophobe (chrRCC) renal cell carcinoma, and benign oncocytomas (OC) can be challenging due to the low cellularity and damaged architecture of needle biopsy specimens. However, each subtype exhibits unique genetic aberrations that can assist in histologic classification and potentially assist in guiding management decisions. We report our initial experience correlating renal mass histology to subtype-associated genomic alterations detected by FISH and a-CGH of percutaneous needle biopsy specimens. Methods: In an ongoing IRB-approved blinded study, 17 samples obtained from 15 patients with known renal masses were submitted to FISH (FReCaD) and targeted a-CGH (UroGenRA-Kidney). Specimens were classified using a subtype classification decision tree algorithm based on the presence/absence of genomic abnormalities. The results were compared to biopsy histology or surgical specimen when available. Results: Histology revealed ccRCC in 6 patients, pRCC in 4, OC in 2, Angiomyolipoma in 1, and unclassified type RCC in 2. In 6 of 9 cases FISH achieved a diagnosis, which correlated with histology in 4. FISH incorrectly classified as ccRCC two cases with pRCC on histology. A-CGH was diagnostic in 14 of 15 cases and correlated with histology in 13. In one case, a-CGH showed a genomic profile not consistent with ccRCC, pRCC, chrRCC, or OC according to the algorithm. Conclusions: The addition of genetic tumor tissue studies to complement histology from biopsy tissues may supplement or improve the accuracy of classification and biological characterization of renal tumor biopsies and influence treatment planning. In our initial experience, a-CGH showed better correlation with histology in subtype classification of malignant and benign renal masses than FISH. Prospective testing will be required to validate these results.