tbuckley/cabot-search huggingface dataset:
A phase II study of combination of bortezomib, liposomal doxorubin, and dexamethasone (VDD) as first line therapy for multiple myeloma
Authors: A. J. Jakubowiak, J. Friedman, T. Kendall, A. Al-Zoubi, M. S. Kaminski
Journal: Journal of Clinical Oncology (2006)

17504 Background: We have recently reported that a combination of bortezomib (Velcade), liposomal doxorubicin (Doxil), and dexamethasone (VDD) is very active and well tolerated in relapsed/refractory myeloma (MM) producing 83% overall response rate and 33% of complete (CR) or near complete (nCR) response rate. In the current study, we evaluated the activity of VDD as first line therapy in newly diagnosed patients with MM. The primary objective of this study was to determine the efficacy of this regimen. Methods: This is a phase II, single institution trial which opened in July 2005 with target accrual of 30 patients. EBMT criteria were used for evaluation of responses. The regimen was given as follows: Velcade at 1.3 mg/m 2 on days 1, 4, 8, and 11, Doxil at 30 mg/m 2 on day 4, and Dexamethasone for a total of 160 mg per cycle, initially at 40 mg on days 1–4 and then 20 mg on days of Velcade and the day after. VDD was repeated every 3 weeks for a total of 6 cycles. Results: To date, 19 pts have been enrolled, 18 of whom are presently evaluable for response after receiving a mean of 4.7 cycles (range 1–6). The characteristics of the evaluable patients included the following: median age 58 (range 39–83), chromosome 13 deletion in 4 patients, beta2-microglobulin 4.4 (61% &gt; 4.0). CR + nCR have been observed in 2 patients (11%), very good partial response (VGPR) in 5 patients (28%), partial response (PR) in 9 patients (50%) and minor response (MR) in 1 patients (5%) for an overall response (≥ MR) of 94%, ≥ PR of 89% and ≥ VGPR of 39%. All patients who proceeded to stem cell transplant collected without any problems. The regimen was very well tolerated. Most surprisingly, only 1 patient developed peripheral neuropathy grade 1. One patient developed pneumonia and PE and one patient grade 3 diarrhea, which was found to be secondary to cryptosporidium. Grade 3 or 4 neutropenia was observed in 6 patients and grade 3 thrombocytopenia in 1 patient. The most common grade 1 and 2 toxicities were thrombocytopenia and fatigue, both significantly less common than in relapsed patients treated with the same regimen. One patient developed grade 2 DVT and 1 grade 2 PPE. Conclusions: VDD combination shows high overall activity of 94% and ≥ 90% disease reduction of 39%. The regimen is very well tolerated and has a surprisingly low incidence of peripheral neuropathy. [Table: see text]
PET-CT Defined Focal Lesions at Baseline and Day 7 Predict Outcome in GEP 70 Defined High Risk Multiple Myeloma Patients
Authors: Yogesh Jethava, Rachel Hunter-Merrill, Gareth J Morgan, Rashid Z Khan, Aasiya Matin, Christoph Heuck, Maurizio Zangari, Xenofon Papanikolaou, Frits van Rhee, Faith E Davies, Bart Barlogie
Journal: Blood (2014)
Body mass index (BMI) is a predictor for response to neoadjuvant chemotherapy in women with localized breast cancer aged 35 years or younger
Authors: Y. Eralp, T. L. Smith, S.-W. Kau, V. Valero, A. Buzdar, G. N. Hortobagyi, B. Arun
Journal: Journal of Clinical Oncology (2004)

600 Objective: High BMI has been linked to poor outcome in patients with breast cancer. Evidence relating to obesity as a predictor for prognosis in premenopausal patients have been controversial. The aim of this study is to evaluate the impact of BMI on response to treatment and recurrence following neoadjuvant CT in young patients with breast cancer.> Method: In this study, we analyzed the impact of BMI on the outcome of 111 patients who received anthracycline and/or taxane-based neoadjuvant CT for localized breast cancer. Median age at diagnosis was 32 (22–35). Fifty six patients (50.5%) had stage II and 54 had stage III disease. Hormonal receptors were positive in 65 patients (58.6%) and HER-2/neu was overexpressed in 29 patients (26.1%). Pathologic evaluation revealed that 27 patients had (24.3%) had downstaging in axillary LN, while 13 (11.7%) showed complete regression both in the primary tumor and axillary LN following completion of chemotherapy. Patients were grouped in quartiles of BMI calculated prior to initiation of chemotherapy. >Results: After a median follow-up period of 26 months (3–94), 39 patients experienced recurrence (35.1%). Median overall (OS) and progression-free (PFS) survival rates at 5 years were 62.6 %±9.7 and 38.6%±8.1, respectively.Multivariate Cox regression analysis revealed pathologic response (OR:2.3, p=0.04) and recurrence (OR:108.7, p:0.047) as significant independent prognostic factors for PFS and OS, respectively. Lowest BMI quartile was significantly associated with lack of pathologic response to neoadjuvant chemotherapy compared to those with a larger body size (OR: 3.9, p=0.009). Conclusion: Obesity did not correlate with prognosis in young, premenopausal women with early breast cancer. However, patients within the lowest BMI quartile were less likely to respond to neoadjuvant anthracycline or taxane-based chemotherapy. Unresponsiveness to CT may account for the poor outcome in young premenopausal patients compared to older patients. The role of BMI on the outcome of this subset of patients should be validated further by larger prospective studies. No significant financial relationships to disclose.
Allogeneic Stem Cell Transplantation in First Chronic Phase CML during the Last Decade: Retrospective Analysis of the National SFGM-TC Registry
Authors: Franck-Emmanuel Nicolini, Valerie Coiteux, Gerard Socie, Didier Blaise, Eric Deconinck, Patrice Chevallier, Pierre Simon Rohrlich, Stephanie Nguyen, Thierry Lamy, Jean-Henri Bourhis, Marie-Thérèse Rubio, Felipe Suarez, Jerome Cornillon, Gandhi Damaj, Natacha Maillard, Noel Milpied, Patrice Ceballos, Mohamad Mohty, Claude-Eric Bulabois, Bruno Lioure, Gerard Michel, Norbert Ifrah, Yves Beguin, Anne Huynh, Nathalie Contentin, Jacques-Olivier Bay, Yves Bertrand, Yves Perel, Jean-Hugues Dalle, Gaelle Guillerm, jean-Valere Malfuson, Aude Marie-Cardine, Mauricette Michallet, Nicole Raus, Marie Balsat, Helene Labussiere, Regis Peffault De Latour, Ibrahim Yakoub-Agha
Journal: Blood (2016)
Prognostic power of molecular subtypes in inflammatory breast cancer: A multicentric study.
Authors: Zineb Benbrahim El Mekkeoui, Ahmed El Saied El Bastawisy, Soumaya Labidi, Adil Najdi, Chakib Nejjari, Hammouda Boussen, Nawfel Mellas
Journal: Journal of Clinical Oncology (2014)

e11546 Background: Inflammatory breast cancer (IBC) represents up to 15% of all breast cancer in North Africa. However, this form is poorly characterized and its subtypes defined by hormonal receptor (HR) and HER2 status have not been well studied yet.In this study, we compared pathological complete response (pCR) rates, progression free survival (PFS) and overall survival (OS) by HR/HER2 subtype in IBC North African population. Methods: We retrospectively reviewed data of sixty six non metastatic IBC patients from Morocco, Egypt and Tunisia. All patients had received neoadjuvant sequential chemotherapy: 3 cycles of anthracyclines based regimen then 3 cycles of taxanes based regimen. Trastuzumab was associated to taxanes in erb2 overexpressed cases. Patients included had available information on estrogen receptor, progesterone receptor, HER2 status and Mib1 score. Kaplan-Meier method was used to estimate median PFS and OS durations from the time of first cycle of chemotherapy. The Cox proportional hazards regression model was used to determine the effect of molecular subtypes on PFS and OS. Results: The mean patient age was 46.5 ± 10.5 years. Premenopausal status at diagnosis was frequently noted (60% of cases). The histological grade distributions were 55.9 % for grade II tumors, 40.7 % for grade III. The immune-histochemical study showed that 1.6 % of the tumors were classified as luminal A, 69 % as luminal B, 9.5 % as HER2 overexpressing and 19% as triple negative. The overall pCR rate was 4.5%, with the HR-positive/HER2-positive subtype showing the highest rate (16.66%). The median PFS was 651 days (95% CI: 314 – 987) and median OS was 780 days (95% CI: 346 – 1213). In the multivariate analysis, there was no significant statistic difference between all the molecular subtype groups. Conclusions: Molecular subtypes had limited predictive and prognostic power in our IBC population. All molecular subtypes of IBC had a poor prognosis. To improve outcome, further specific therapeutic strategies have to be developed in the neoadjuvant setting. PFS and OS according to molecular subtypes in IBC North African population. PFS (days) p OS (days) p Triple negative 180 0.22 487 0.5 HER2 + 331 527 Luminal B HER2- 436 600 Luminal B HER2 + 853 1260
Chemotherapy and brain function in long-term survivors of childhood acute lymphoblastic leukemia (ALL).
Authors: Yin Ting Cheung, Slim Fellah, Wei Liu, Robert J. Ogg, Deokumar Srivastava, Cara I. Kimberg, Tara M. Brinkman, Ching-Hon Pui, Leslie L. Robison, Melissa M. Hudson, Kevin R. Krull
Journal: Journal of Clinical Oncology (2015)

10001 Background: Limited data are available on associations among chemotherapy treatment and brain function in long-term survivors of childhood ALL. This study evaluated associations between treatment exposure, neurocognitive testing, and functional magnetic resonance imaging (fMRI) in children treated on an institutional protocol, which featured chemotherapy without cranial irradiation. Methods: Long-term survivors of ALL (n = 213; 51.2% male; mean[SD] age 14.8[4.8]; 7.7[1.7] years post-diagnosis), completed neurocognitive testing and brain fMRI during an executive function/attention task. During chemotherapy, serum concentrations of high-dose intravenous methotrexate (HD-MTX), plasma homocysteine (HYC) following HD-MTX, and dexamethasone (DEX) were quantified as area under the curve (AUC). Serum cortisol level was also measured following oral DEX. These variables, along with number of triple intrathecal therapy doses, were analyzed with general linear modeling as predictors of neurocognitive and fMRI outcomes. fMRI analysis was performed using SPM8. Results: Survivors performed below normative data on two standard measures of executive function: cognitive flexibility (mean[SD] Z-score = -0.55[1.2]) and fluency (-0.38[0.9]), both p’s < 0.0001. After adjustment for demographic factors, poorer cognitive flexibility was associated with higher MTX AUC (Est. -0.024; p = 0.015) and higher HYC AUC (Est. -0.011; p = 0.049). Poorer fluency was also associated with higher MTX AUC (Est. -0.023; p = 0.007). Survivors diagnosed at younger ages performed poorly on fluency at any level of MTX AUC, while those diagnosed at older ages performed poorly only if exposed to high MTX AUC (p = 0.063). Brain activation was positively correlated with MTX AUC in bilateral frontal and caudate nuclei, and left putamen and anterior cingulate cortex. Of note, these brain regions are associated with cognitive flexibility and fluency, as well as other executive functions. Conclusions: Higher serum concentrations of MTX and plasma HYC following HD-MTX for childhood ALL may predict those at greatest risk for neurocognitive problems, particularly executive dysfunction, and altered brain activity during long-term survivorship.
A first-in-human phase I imaging study using hyperpolarized <sup>1</sup>c-13 pyruvate (h-Py) in patients (pts) with localized prostate cancer (l-PCa).
Authors: Andrea Lynne Harzstark, Vivian K. Weinberg, Krystyna Grycz, Ralph E. Hurd, Jan Henrik Ardenkjaer-Larsen, Jonathan Murray, Albert Chen, Marcus Ferrone, Ilwoo Park, Galen Reed, Pamela N. Munster, Eric Jay Small, Lucas E. Carvajal, Mark E. VanCriekinge, Peder E. Larson, Jose Chang, Robert A. Bok, Sarah J. Nelson, Daniel B. Vigneron, John V. Kurhanewicz
Journal: Journal of Clinical Oncology (2012)

4660 Background: Preclinical studies demonstrated that the conversion of h-Py to hyperpolarized 13 C lactate (h-lac) is detectable on MRI-spectroscopy and is a useful marker of differentiation in PCa. H-Py MRI provides more than 10,000-fold enhancement in signal to noise ratio (SNR), allowing for rapid detection of metabolic alterations in vivo. Hyperpolarized compounds have not been previously studied in man. Methods: Pts with biopsy-proven untreated l-PCa were enrolled in a phase I study of h-Py MRI. Following a modified 3+3 design, 6 pts were enrolled at each dose level (0.14, 0.28 and 0.43 mL/Kg): 3 to monitor kinetics of h-Py, and 3 to evaluate the spatial distribution of metabolism in PCa and normal prostate (nl-P). An expansion cohort of 15 pts explored the biological variability of metabolism. A dynamic nuclear polarization (DNP) system, the first human system anywhere, generated and delivered 230 mM sterile h-Py. IV injection of h-Py was followed by imaging with a 3T MR scanner with custom transmit and receive coils. Monitoring included EKG, vital signs, and laboratory testing. Results: 31 pts were imaged. 23 pts had Gleason (G) 6, 6 pts G7, and 2 pts G8 PCa. Median age was 63 years (range 45-75); median PSA was 5.9 ng/mL (1.88-20.2). No dose limiting toxicities or &gt;grade (gr) 2 toxicity was observed. Toxicity included: gr 1dysgeusia (6 pts), gr 1 hypokalemia, gr 1 hypocalcemia, gr 1 dizziness, and gr 2 diarrhea (1 pt each). Median time from dissolution of the agent to delivery into patients was 66 seconds (43-88). Signals from h-Py and h-Lac were seen in PCa and nl-P at all doses; 0.43 mL/Kg showed the best SNR and discrimination between PCa and nl-P and was therefore established as the phase II dose. There appeared to be an association between h-Lac levels and PCa grade. Conclusions: H-py metabolic imaging has minimal toxicity and provides the ability to discriminate Ca from nl-P based on increased levels of h-lac. The correlation with grade and changes with therapy require further study.
Down-Regulation of Glucocorticoid-Induced TNF Receptor (GITR) Ligand on Human Tumors by Proteolytic Shedding Increases Anti-Tumor Reactivity of NK Cells.
Authors: Katrin M. Baltz, Matthias Krusch, Tina Baessler, Mercedes Kloss, Ingrid Kumbier, Andrea Peterfi, Lothar Kanz, Helmut R. Salih
Journal: Blood (2006)
IMPACT OF ARRHYTHMIA DURATION AND INDEX LEFT VENTRICULAR EJECTION FRACTION ON RECOVERY OF LEFT VENTRICULAR FUNCTION IN PATIENTS WITH ARRHYTHMIA-INDUCED CARDIOMYOPATHY
Authors: Rahul Dhawan, Christopher R. Angus, Robert A. Pearce, Abbas Bitar, Brian Guinn, Dhanunjaya Lakkireddy, Brian Olshansky, Rakesh Gopinathannair
Journal: Journal of the American College of Cardiology (2017)
Pre-Emptive Treatment with Cidofovir for Cytomegalovirus Antigenemia in Autologous Bone Marrow Recipient and CLL Patients on Therapy with Alemtuzumab.
Authors: Emilio Iannitto, Viviana Minardi, Antonino Mulè, Renato Scalone, Giuseppina Calvaruso, Alessandra Crescimanno, Concetta Lo Biundo, Eliana Liardo, Vincenzo Abbadessa, Maurizio Musso, Serenella Arista
Journal: Blood (2006)
AT9283, a Small Molecule Multi-Targeted Kinase Inhibitor Induces Antimyeloma Activity Via Potent Aurora Kinase and STAT3 Inhibition.
Authors: Loredana Santo, Teru Hideshima, Erik A. Nelson, Diana Cirstea, Madhavi Bandi, Hiroshi Ikeda, Gullu Gorgun, Sonia Vallet, Samantha Pozzi, Giulia Perrone, Kishan Patel, Yiguo Hu, Matthew S Squires, Murray Yule, Elisabetta Calabrese, Dharminder Chauhan, Nikhil C. Munshi, Kenneth C. Anderson, Noopur Raje
Journal: Blood (2009)
Immunotherapy for <i>HER2</i>-positive medulloblastoma: Regression of experimental tumors by transfer of <i>HER2</i>-redirected T cells in vivo
Authors: N. M. Ahmed, M. K. Ratnayake, B. Savoldo, L. Perlaky, G. P. Dotti, W. Wels, M. Bhattacharjee, D. H. Shine, C. M. Rooney, H. E. Heslop, S. Gottschalk
Journal: Journal of Clinical Oncology (2006)

9008 Background: The long-term objective of this project is to develop an innovative HER2-targeted immunotherapeutic approach for medulloblastoma, the most common malignant brain tumor of childhood. HER2 is expressed in 40% of medulloblastomas and at present less than one third of patients with HER2-positive tumors are cured by conventional therapies. The aim of this study was to determine if T cells grafted with a HER2-specific chimeric antigen receptor (CAR) recognize and kill HER2-positive medulloblastomas. Methods: Mitogen-activated T cells from healthy donors and medulloblastoma patients were transduced with a retroviral vector encoding a HER2-specific CAR with a ζ-signaling domain (HER2T-cells). We analyzed the ability of HER2T-cells to 1) proliferate, 2) produce immunostimulatory cytokines (IFN-γ and IL-2), and 3) kill HER2-positive targets in cytoxicity assays upon exposure to HER2-positive primary medulloblastoma cells and cell lines. The in vivo function was tested in an orthotopic murine xenograft model of human medulloblastoma, which allows for serial imaging by bioluminescence. Results: HER2T-cells killed both HER2-positive primary medulloblastoma cells and cell lines in cytotoxicity assays, whereas HER2-negative tumor cells were not killed. Stimulation of HER2T-cells resulted in T-cell proliferation and secretion of IFN-γ and IL-2 in a HER2-dependent manner. No functional difference was observed between cells generated from medulloblastoma patients receiving dexamethasone and healthy donors. In vivo, the adoptive transfer of HER2T-cells resulted in sustained regression of established medulloblastomas in an orthotopic murine xenograft model as judged by bioluminescence imaging. In contrast, delivery of non-transduced T cells did not change tumor growth in comparison to untreated tumors. Conclusions: This study shows for the first time that HER2 is a target antigen for the immunotherapy of medulloblastoma. HER2-redirected T-cells not only recognized and killed HER2-positive medulloblastomas ex vivo, but also induced regression of experimental medulloblastoma in vivo. Hence, adoptive transfer of HER2-redirected T-cells may represent a promising immunotherapeutic approach for medulloblastoma. No significant financial relationships to disclose.
Polymorphisms of IL-10, IL-17A, IL-17F and IL-18 Affect the Clinical Features of Multiple Myeloma in Japanese Patients
Authors: Atsushi Iwasaki, Takayuki Saitoh, Chiaki Ushie, Norihiko Moriyama, Tomonori Takani, Hikaru Hattori, Hiroshi Handa, Morio Matsumoto, Jun Isoda, Morio Sawamura, Hatsue Ogawara, Hirokazu Murakami
Journal: Blood (2012)
ARRHYTHMIA BURDEN &amp; OUTCOMES IN EISENMENGER SYNDROME
Authors: Shankar Baskar, Philippa Horne, Samantha Fitzsimmons, Philip Khoury, Joseph Vettukattill, Koichiro Niwa, Teiji Agaki, Mark Spence, Gruschen Veldtman
Journal: Journal of the American College of Cardiology (2017)
Correlation between the DCIS score and traditional clinicopathologic features in the prospectively designed E5194 clinical validation study.
Authors: Sunil S. Badve, Robert James Gray, Frederick L. Baehner, Lawrence J. Solin, Steven M Butler, Carl Yoshizawa, Steven Shak, Lorie L. Hughes, David L Page, George W. Sledge, Nancy E. Davidson, Edith A. Perez, James N. Ingle, William C. Wood, Joseph A. Sparano
Journal: Journal of Clinical Oncology (2012)

1005 Background: We previously reported that in the E5194 clinical trial patients with ductal carcinoma in situ (DCIS) treated with wide local excision (WLE) without radiation (RT), the DCIS Score was significantly associated with 10 year risk of an ipsilateral breast event (IBE - recurrence of in situ or invasive carcinoma), whether evaluated as a continuous or categorical variable (P=0.02 for both). Here we evaluate correlation between DCIS Score and clinicopathologic (CP) features and if DCIS Score provides independent recurrence risk information. Methods: The study population included 327 women with DCIS prospectively selected for treatment with WLE without RT, including low-intermediate grade tumors ≤2.5 cm or high-grade ≤1 cm. CP variables included age, menopausal status, tamoxifen treatment (used in 29%) and expert centrally determined tumor size, grade, comedo necrosis, tumor type, and margin status. The association between DCIS Score and CP variables was examined by spearman rank correlation, and proportional hazards regression models were used to determine variables significantly associated with IBE. Results: Lesion size (p=0.009) and menopausal status (p=0.03) were significantly associated with IBE, while grade (p=0.69) and comedo necrosis (p=0.47) were not. DCIS Score was significantly associated with IBE after adjustment for CP features and tamoxifen use (p=0.02). DCIS Score was moderately correlated with grade (r s =0.46; 95% CI 0.37,0.54), percentage comedo necrosis (r s =0.49; CI 0.41,0.57), and lesion size (r s =0.18; CI 0.08,0.29) but not other features. Exploratory analyses in all CP subgroups, including the multicomponent Van Nuys Prognostic Index, showed a wide range of DCIS Scores in each subgroup. Concordance of the grades among readers was low: local vs parent central, 68%; local vs central nuclear grade, 45%; parent central vs central nuclear grade, 37%. Conclusions: DCIS Score is moderately correlated with grade, comedo necrosis, and tumor size. DCIS Score provides recurrence risk information independent of these features and identifies subjects with DCIS who are at high risk for local invasive and in-situ local recurrence after WLE alone.
A phase II study of tivantinib (ARQ-197) for metastatic triple-negative breast cancer.
Authors: Sara M. Tolaney, Hao Guo, William Thomas Barry, Katherine Larrabee, Jane E. Brock, Nikhil Wagle, Eliezer Mendel Van Allen, Cloud Paweletz, Elena Ivanova, Pasi A. Janne, Beth Overmoyer, John Joseph Wright, Geoffrey Shapiro, Eric P. Winer, Ian E. Krop
Journal: Journal of Clinical Oncology (2014)

1106 Background: Data suggests that MET expression and activation is important for initiation and progression of triple-negative breast cancer. Tivantinib (ARQ 197) is an orally administered agent that was originally presumed to target MET, though recent preclinical data suggests it may inhibit microtubule polymerization. Methods: We conducted a two-stage, single arm study of tivantinib in patients (pts) with metastatic triple-negative breast cancer. Pts could receive 1 to 3 prior lines of chemotherapy in the metastatic setting and were required to have measurable disease. Treatment consisted of twice daily oral dosing of tivantinib (360 mg po bid), on a 21 day cycle. Pts underwent restaging scans at 6 weeks, and then every 9 weeks. Response was evaluated using RECIST 1.1, and the primary endpoint was progression-free interval of 6 months (PFS≥6). The target samples size was 26 pts, and if ≥5 pts had PFS≥6 the null rate (10%) would be rejected in favor of a 31% rate of activity. Tumor biomarkers that may predict response to tivantinib were explored. Results: The study closed for futility after 22 pts were enrolled; pts had received a median of 2 prior lines of chemotherapy for metastatic disease. Only 1 pt had PFS≥6 (4.5%, 95% CI 0.2%-24.7%). One pt achieved a partial response (PR) for a 4.5% overall response rate, and 6 pts (27%) had stable disease as the best response. The median PFS was 1.2 month (95% CI 1.0-1.4). There were few grade 3+ adverse events (1 grade 3 anemia, 1 grade 3 fatigue, and 3 pts with grade 3/4 neutropenia). Whole exome sequencing of archival tumor tissue and tissue from time of progression in the pt who experienced a PR was also performed. Somatic alterations identified in the post-progression biopsy include mutations in known breast cancer genes MAP2K4 and TP53, as well as a mutation of unknown significance in the kinase domain of JAK2. Biomarker studies of MET expression and amplification in archival tumor tissue are ongoing. Conclusions: This represents the first study of tivantinib for the treatment of metastatic triple-negative breast cancer. These results suggest that tivantinib is well tolerated, but is largely inactive when used as monotherapy to treat metastatic triple-negative breast cancer. Clinical trial information: NCT01542996.