tbuckley/cabot-search huggingface dataset:
Evaluation of quality of life from a phase II study of anamorelin HCl in NSCLC patients.
Authors: Jennifer S. Temel, Shailesh Arjun Bondarde, Minish Mahendra Jain, Ying Yan, Elizabeth Manning Duus, Suzan Allen, William Mann
Journal: Journal of Clinical Oncology (2013)

42 Background: Anamorelin HCl (ANA) is an oral ghrelin receptor agonist in development for non-small cell lung cancer (NSCLC)-associated anorexia/cachexia. Cancer cachexia is a multifactorial syndrome, characterized by decreased body weight and muscle, and worsened survival and quality of life (QoL). Here we present Phase II data, including an evaluation of QoL using the MD Anderson Symptom Inventory (MDASI) to assess severity of core symptoms in cancer patients and their impact on daily life. Methods: An international, randomized, double-blind, placebo-controlled, 12-week Phase II trial (NCT00622193) enrolled 226 Stage IIIB/IV NSCLC patients (N=76 for 50 mg ANA; N=73 for 100 mg ANA; N=77 for placebo [PL]). Co-primary endpoints were body weight and handgrip strength (HGS); safety was also assessed. QoL by MDASI was a secondary endpoint; a negative change in MDASI score represents improvement. Assessments were performed at baseline and approximately every 3 weeks over the 12-week treatment period. Results: MDASI total and domain scores improved with 100 mg ANA vs PL, although these changes were not statistically significant (mean±SE change from baseline at Week 12 for 100 mg ANA vs PL was -8.6±4.58 vs -1.5±3.29 for total score; -6.7±2.98 vs -2.9±2.24 for symptom domain score; and -1.9±1.99 vs 1.5±1.39 for interference domain score). Seven individual MDASI symptom/interference items most improved in the 100 mg ANA vs PL group were fatigue, nausea, work around the house, disturbed sleep, distressed, general activity, and mood. Over 12 weeks, ANA also significantly increased body weight vs PL (mean change from baseline was 0.14 kg, -0.3 kg, and -1.32 kg for 100 mg ANA, 50 mg ANA, and PL, respectively [p=0.0005]), and directional (non-significant) changes in HGS were also noted for both active arms vs PL. ANA was safe and well-tolerated, with less adverse events of fatigue, anorexia, and nausea reported in ANA vs PL patients. Conclusions: In this study, ANA significantly increased body weight, improved HGS and QoL, and had an overall favorable safety/tolerability profile. MDASI individual item changes demonstrated improvements in key cancer-related symptoms including fatigue, and were consistent with the adverse event profile. Clinical trial information: NCT00622193.
Association of translocation t(11;14) with survival in patients with light chain (AL) amyloidosis
Authors: A. H. Bryce, R. Ketterling, M. A. Gertz, R. A. Kyle, S. Zeldenrust, M. Q. Lacy, S. Hayman, F. Buadi, R. Fonseca, R. Knudson, A. Dispenzieri
Journal: Journal of Clinical Oncology (2008)

8549 Background: Light chain amyloidosis (AL) is related to other plasma cell dyscrasias like multiple myeloma (MM) and MGUS. Interphase fluorescence in situ hybridization (FISH) coupled to cytoplasmic staining of specific Ig (cIg-FISH) on bone marrow plasma cells is well established in the evaluation of MM. Abnormalities of particular significance are t(4;14), t(11;14), t(14;16), -13/del13q, -17p, and hyperdiploidy. The t(11;14) carries a neutral to improved prognosis, while t(4;14), t(14;16), -17p all portend shortened survival. Methods: We reviewed 56 patients with AL who had cIg-FISH performed as part of their routine clinical testing using the screening panel used in MM at our institution. We excluded patients who had clear MM at any point in their clinical course. Results: Seventy percent of patients had abnormal cIg-FISH. The most common abnormalities were IgH translocations 47%, t(11;14) [39%], and del13/del13q [30%]. No deletions of 17p (p53) were observed. There was a trend towards a significantly worse survival for patients with any cIg-FISH abnormality, and a hazard ratio of death of 3.0 (CI 1.1–8.7) for patients harboring the t(11;14) translocation. The median survival with t(11;14) was 16.2 months compared to 61.6 months in all others (p=0.027). The influence of t(11;14) on overall survival was independent of bone marrow plasmacytosis (BMP%) and plasma cell proliferation on Cox modeling, though patients with cIg-FISH abnormalities were more likely to have a BMP% at or above the median (8%) (p=0.0005) or higher PCLI (p=0.0029). Patients with t(11;14) had lower levels of circulating immunoglobulin free light chain than patients with other abnormalities. Conclusion: We are the first to report decreased survival in AL based on a FISH abnormality. The decreased survival with t(11;14) is distinct from what is seen in MM. The question remains the determination of the mechanistic contribution of the abnormalities to pathogenesis. It appears that there is a distinct genetic profile differentiating MM from amyloidosis, and that the differentiation is not merely a matter of the structural qualities of the immunoglobulin light chain. Our results suggest that cIg-FISH testing should be adopted for amyloidosis as these results may be important in risk stratification. No significant financial relationships to disclose.
Retrospective evaluation of patients with colorectal cancer (CRC) and type II non-insulin-dependent diabetes (NIDDM).
Authors: H. Hassabo, M. Hassan, B. George, S. Wen, V. Baladandayuthapani, S. Kopetz, D. R. Fogelman, B. K. Kee, C. Eng, C. R. Garrett
Journal: Journal of Clinical Oncology (2011)

507 Background: Patients with NIDDM have an increased risk of colorectal adenomas and CRC possibly mediated through the insulin growth factor receptor pathway. Metformin is associated with anticancer efficacy in preclinical models and a lower risk of cancer mortality in patients with NIDDM. We undertook to evaluate the difference in outcome in NIDDM patients with CRC based upon their medications taken for glycemic control. Methods: We conducted an IRB-approved (DR09-0719) retrospective analysis of 4,758 patients seen at a single institution (University of Texas M. D. Anderson) with CRC between the years of 2005-2008, to determine the prevalence of NIDDM in this patient population, in addition to determining whether patient survival differs based upon their diabetic therapy. Results: 425 out of 4,758 CRC patients (8.9%) were identified as having NIDDM. Gender, male:female 283:142 (67%, 33%), age, mean 62 years (range 31-91), stage I/II/III/IV 37:55:175:158 (8.7%, 12.9%, 41.2%, 37.2%). Overall survival (OS) for the 397 patients with follow-up data available, by univariable Kaplan Meier analysis, was 63.7 months (95% confidence interval (CI), 52.3-75.5). Patients with NIDDM and CRC treated with metformin as one of their diabetic medications had a survival of 76.9 months (95% CI, 61.4-102.4) as compared to 56.9 months in those patients not treated with metformin (95% CI, 44.8- 68.8), p = 0.048. By using a Cox regression model adjusted for age, sex, race, body mass index, and initial stage of disease we demonstrated that NIDDM patients treated with metformin had a 30% improvement in OS when compared to NIDDM patients treated with other diabetic agents. There was a non-statistically significant trend toward higher complete and minor pathologic response rate (≤ 10% residual tumor) in NIDDM patients with rectal cancer receiving chemoradiation who were treated with metformin when compared to those who were not (14/19, 74% vs. 9/19, 47%, p = 0.09). Conclusions: In this analysis the use of metformin in NIDDM patients with CRC was associated with an improved overall survival. While these results are consistent with the findings in other solid tumors they will need to be validated in other colorectal cancer data sets. No significant financial relationships to disclose.
Sustained Graft-Versus-Lymphoma Effect among Patients (pts) with Mantle Cell Lymphoma (MCL) Given Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation (HCT).
Authors: Mohamed L. Sorror, Barry Storer, Brenda M. Sandmaier, Michael Maris, Thomas Chauncey, Richard T. Maziarz, Michael Pulsipher, Judith Shizuru, Dietger Niederwieser, Edward Agura, James C. Wade, Amelia A Langston, Rainer F. Storb, David G. Maloney
Journal: Blood (2008)
Downregulation of RUNX3 by protein mislocation and gene inactivation in human epithelial ovarian cancer cells
Authors: Y. Kawakami, K. Miyamoto, K. Takehara, M. Kumagai, O. Samura, M. Hanaoka, M. Egawa, T. Mizunoe, K. Taniyama, F. Saji
Journal: Journal of Clinical Oncology (2008)

16545 Background: Runt-related transcription factor 3 (RUNX3) is mapped to 1p36, which is frequently deleted and has been recognized as a tumor suppressor gene in human gastric cancer and breast cancer, and its expression is frequently lost or down-regulated due to epigenetic gene silencing. Recent research also has revealed that RUNX3 is mislocalized to the cytoplasm and plays a more prominent role in gastric carcinogenesis than previously estimated. Methods: In this study, the expression and localization of RUNX3 protein in 63 primary epithelial ovarian cancer specimens were evaluated by immunohistochemistry using anti-RUNX3 monoclonal antibodies and correlation between these results and clinicopathological features was examined. Results: RUNX3 protein was expressed in cell nuclei in 21 of 63 (33.3%) ovarian cancer samples. RUNX3 was not detectable in 20.6% (13/63) of ovarian cancers and a further 46.0% (29/63) exhibited exclusive cytoplasmic localization, suggesting that RUNX3 is functionally inactive in 66.7% of epithelial ovarian cancers. The rate of inactivation was 51.7% (15/29) in serous cystadenocarcinoma, 100.0% (4/4) in endometrioid adenocarcinoma, 68.8% (11/16) in mucinous cystadenocarcinoma, 77.8% (7/9) in clear cell carcinoma and 60.0% (3/5) in the other subtypes. Inactivation of RUNX3 was not associated with the other clinicopathological features of breast cancer such as age, stage or survival. Conclusions: In conclusion, RUNX3 was found to be inactive in 66.7% of primary human ovarian cancers, primarily due either to protein mis-localization to the cytoplasm or gene inactivation. Our results suggest that RUNX3 may play a role in human epithelial ovarian cancer development and progression. No significant financial relationships to disclose.
Neutrophil-lymphocyte ratio in small renal masses.
Authors: Wassim Bazzi, Sheila Dejbakhsh, Melanie Bernstein, Paul Russo
Journal: Journal of Clinical Oncology (2014)

522 Background: Neutrophil-lymphocyte ratio has been shown to be a prognostic serum marker in some malignancies. We evaluated the association between preoperative neutrophil-lymphocyte ratio and baseline characteristics in patients with small renal masses. Methods: The charts of patients with renal masses ≤ 4 cm who underwent nephrectomy at Memorial Sloan-Kettering Cancer Center from January 2007 to July 2012 were reviewed retrospectively. Bivariable and multivariable analyses were used to examine the association between preoperative neutrophil-lymphocyte ratio (absolute neutrophil count/absolute lymphocyte count) and demographic and clinicopathologic variables. Results: Our cohort consisted of 1001 patients. Bivariable analysis showed significantly higher mean preoperative neutrophil-lymphocyte ratios in men (3.0 vs. 2.6 in women, p &lt; 0.001) and Caucasians (2.9 vs. 1.9 in African-Americans, p &lt; 0 .001), but no significant differences between patients with high (III−IV) or low (I−II) co-morbidity scores (2.9 vs. 2.8, p = 0.085) or between benign or malignant pathology (2.9 vs. 2.8, p = 0.972). Linear regression analysis showed a positive correlation between age and preoperative neutrophil-lymphocyte ratio (Pearson correlation coefficient (r) = 0.1268; p &lt; 0.001), and a negative correlation between preoperative estimated glomerular filtration rate and preoperative neutrophil-lymphocyte ratio (r = -0.1246; p &lt; 0.001). Multivariable analysis showed older age, male gender, and lower preoperative estimated glomerular filtration rate were associated with higher preoperative neutrophil-lymphocyte ratio. Conclusions: In patients with small renal masses, there is no evidence of an association between preoperative neutrophil-lymphocyte ratio and tumor pathology, but there is evidence it is affected by age, gender, and renal function.
Life satisfaction regarding the ability to have children among female cancer survivors.
Authors: Penelope P Howards, Amy Fothergill, Jessica B Spencer, Ann Mertens
Journal: Journal of Clinical Oncology (2016)

248 Background: Some cancer treatments can cause sub-fertility in female cancer survivors, which has led to recommendations that all reproductive-aged cancer patients receive fertility counseling at the time of cancer diagnosis. However, little is known about how reproductive-aged cancer survivors feel about their quality of life with respect to their ability to have children. Methods: The FUCHSIA Women’s Study recruited reproductive-aged (22-45 years) female cancer survivors diagnosed with cancer between the ages of 20-35 years, who were at least 2 years post-diagnosis (median 7). All reportable malignant cancers and in situ breast cancer diagnosed from 1990 to 2009 in Georgia were eligible. Participants (n = 1,282) completed a detailed interview about their reproductive history including questions about their feelings about their ability to get pregnant and to have more children as well as their comfort with assisted reproductive technology (ART). Women were classified as premenopausal or menopausal, which included surgical and non-surgical menopause. Results: At the time of the interview, 31% of the study participants did not have a child. Overall, childless women were less likely to feel that having a biologic child was important (46%) than women who had a child (89%). However, 61% of childless, premenopausal women wanted to have a biologic child in the future, and 89% of menopausal women without children reported that they would have liked to have a child if they could. Menopausal women without children were more likely to report being comfortable with the idea of using ART to become pregnant (67% vs. 38% of menopausal women with children). A quarter of premenopausal women without children indicated that they would be dissatisfied with life if they were unable to have a child, and 10% of menopausal women without children indicated they were dissatisfied with life because they could not have children. Conclusions: In general, women without children were more likely to report a poorer quality of life with respect to their reproductive potential. However, our results suggest there is a complex relation between women’s reproductive desires and their feelings about their actual situation.
Cardenolide-related UNBS1450 compound target the Src kinase in the Na+/K+-ATPase signalosome and exert potent in vitro and in vivo anti-tumor activities in experimental human glioblastomas
Authors: Tatjana Mijatovic, Florence Lefranc, Isabelle Camby, Janique Dewelle, Eric Van Quaquebeke, Francis Darro, Robert Kiss
Journal: Cancer Research (2005)

2571   Malignant gliomas are among the most challenging of all cancers to treat successfully, since they are characterized not only by aggressive proliferation and expansion but also by their inexorable invasion of distant brain tissue. Classical cardenolides (including ouabain and digitoxin) are known to exert significant anti-tumor activities, both  in vitro  and  in vivo , for example for patients with breast cancer. For the first time, we show that a novel cardenolide (UNBS1450) hemisynthesized from 2“-oxovoruscharin (UNBS1244, a novel cardenolide that we identified in  Calotropis procera ) exhibits marked (equivalent to vincristine and far more potent than temodal, tamoxifen, carmustine, lomustine and procarbazine)  in vitro  anti-tumor activities on U373 and T98G human glioblastoma cell lines.  In vivo  data show that UNBS1450 exerts dramatic anti-tumor effects in clinically relevant orthotopic xenograft model of human chemoresistant U373 glioma cells. Cardenolides exert their effects by interacting with Na + , K + -ATPase (the so-called sodium pump) which is preassembled with its partners in caveolae. The cardenolide binding to the pump results in assembly of multiple protein complexes, or signalosome, which transmit signals to different intracellular compartments. The signaling pathways that are rapidly elicited by the interaction of cardenolides with Na + ,K + -ATPase (independently of changes in intracellular Na +  and K +  concentrations) include the activation of Src kinase, the transactivation of the epidermal growth factor receptor by Src, and the activation of Ras and p42/p44 mitogen-activated protein kinases. A proteomic approach based on PowerBlot® analysis demonstrates that UNBS1450 treatment affect the expression and phosphorylation status of several components (caveolin, PLC-gamma-1, ERK1/2) of the signalosome. The use of the siRNA approach is to target Src expression aimed to demonstrate the central role of Src in UNBS1450-mediated signaling in U373 cell line. The use of western blotting approach, phospho-ELISA assays and activity assays enabled us to suggest that potent UNBS1450-mediated anti-tumor effects on human glioma U373 cells resulted from signaling pathways elicited by Src and EGFR and achieved by induction of vacuolization-related nonapoptotic cell death and progressive detachment of U373 cells from the substrate.
Is there a withdrawal syndrome with abiraterone acetate (AA)?
Authors: Laurence Albiges, Edouard Auclin, Benoit Rousseau, Elouen Boughalem, Antonin Levy, Yohann Loriot, Mario Di Palma, Christophe Massard, Karim Fizazi
Journal: Journal of Clinical Oncology (2013)

89 Background: The withdrawal syndrome phenomenon in prostate cancer is defined as a subset of patients (pts) who experience decreasing prostate-specific antigen (PSA) values with or without clinical improvement from the withdrawal of androgen receptor (AR) inhibitors or steroids used as endocrine therapies in castration-resistant prostate cancer (CRPC). In view of its steroidal backbone and structural similarity to progesterone, abiraterone acetate (AA) might act as an AR agonist in certain subsets of CRPC. So far, this phenomenon has not been reported with AA. The aim of this study was to assess the incidence and clinical meaning of such a PSA decrease in pts after AA discontinuation Methods: A retrospective review of 218 consecutive pts treated with AA for metastatic CRPC received after docetaxel between 01/2009 and 08/2012 was conducted in two French centers. PSA values were evaluated before, during and at the end of AA treatment. We retrospectively collected PSA values performed after AA discontinuation (at 4 weeks) and until further treatment or death. Pts were typically kept on prednisone at AA discontinuation. Results: Amongst 218 consecutive patients, 66 pts (30%) were assessed for PSA follow-up after AA discontinuation; reasons for no assessment were mostly: immediate chemotherapy (13%), death (21%); ongoing AA (23%), non evaluated (14%). Amongst the 66 pts, AA therapy was associated with a PSA decrease in 65% pts. Median AA treatment duration was 5.1 months[1.5-39.9]. Twenty-one out of 66 pts (32%) had a PSA decrease when measured at AA disruption and 4 weeks afterwards. The median PSA decrease was 19% [3-68%]. A PSA decrease of greater than 50% was observed in 4 pts (19%). The median duration before progression was 5.5 weeks [1.7-54]. Two of the 4 pts with a PSA decrease&gt;50% exhibited clinical benefit. PSA decrease duration in the 4 pts was7.1 wks [1.1-11.5]. Conclusions: A serum PSA decrease occurred in 32% of pts after AA discontinuation. PSA decrease greater than 50% was observed in 6% of pts with a potential clinical benefit. This event was usually of minor magnitude and short-term. Physiopathological explanations for this observation remain unclear and may be related to the direct activity of AA on the AR.
Blood transfusions at end of life for stem cell transplant patients.
Authors: Winnie S Wang, Joseph D. Ma, Sandahl H Nelson, Carolyn Revta, Gary T Buckholz, Carolyn M. Mulroney, Eric Roeland
Journal: Journal of Clinical Oncology (2016)

115 Background: Transfusions are an essential palliative tool in the stem cell transplant (SCT) population. Limited data exist regarding transfusion practices at end-of-life for SCT patients and whether these practices may limit enrollment in hospice. Methods: A retrospective chart review was conducted of deceased patients with hematologic malignancies who underwent SCT at an academic medical center from 2011 to 2015. The primary objective was to determine the difference between the dates of last transfusion and death in patients enrolled and not enrolled in hospice. A secondary objective was evaluation of the number of transfusions between groups. Data were compiled from a single electronic medical record. Descriptive analyses were performed. Days to last transfusion were analyzed using the Wilcoxon-Mann-Whitney test. Number of packed red blood cell (PRBC) transfusions and platelets transfusions on the last day were analyzed using Fisher and chi-squared tests, respectively. Results: A total of 633 SCT were performed from 2011 to 2015 including 39% (n = 245) allogeneic and 61% (n = 388) autologous transplants (n = 29 patients had 2 transplants). Mean ± SD age of SCT patients was 55 ± 13 years. As of January 2016, 20% (n = 119) of these SCT patients have died. Of those that died, 15% (n = 18) were enrolled in hospice. For SCT patients enrolled in hospice, the mean ± SD time of last blood transfusion from death was 42.3 ± 63.4 days, with mean ± SD 0.67 ± 0.77 units of PRBC’s and 0.72 ± 0.75 units of platelets administered. For SCT patients not enrolled in hospice, the mean ± SD time of last blood transfusion from death was 14.2 ± 47.9 days, with mean±SD total 0.69 ± 1.03 units of PRBC’s and 1.14 ± 1 units of platelets administered. Hospice patients had a statistically significant longer number of days until last blood transfusion compared to non-hospice patients (p &lt; 0.001). There was no difference between SCT patients enrolled in hospice and not enrolled in PRBC transfusions (p = 0.069), but there was a significantly higher amount of platelet transfusions in patients not enrolled in hospice (p &lt; 0.005). Conclusions: This data suggests that time to last transfusion may be a significant obstacle for SCT patients when enrolling in hospice, but requires further validation.
Kinetics of Molecular Response with Different Tyrosine Kinase Inhibitors (TKI) Used As Frontline Therapy in Chronic Myeloid Leukemia-Chronic Phase (CML CP),
Authors: Kiran Naqvi, Hagop M Kantarjian, Rajyalakshmi Luthra, Elias Jabbour, Susan O'Brien, Elizabeth M Burton, Srdan Verstovsek, Farhad Ravandi, William G. Wierda, Gautam Borthakur, Alfonso Quintas-Cardama, Jorge E. Cortes
Journal: Blood (2011)