tbuckley/cabot-search huggingface dataset:
Combined analysis of single-agent lenalidomide in relapsed/refractory mantle cell lymphoma.
Authors: Thomas E. Witzig, Julie Vose, Pier Luigi Zinzani, Thomas Matthew Habermann, Joseph M. Tuscano, Rajni Sinha, Michael E. Williams, Johannes W. Drach, Rod Ramchandren, Sevgi Kalayoglu Besisik, Lei Zhang, Sherri Cicero, Tommy Fu, Andre Goy
Journal: Journal of Clinical Oncology (2013)

8533 Background: Mantle cell lymphoma (MCL) is an aggressive form of non-Hodgkin lymphoma (NHL) with poor prognosis. The immunomodulatory agent lenalidomide shows consistent activity with tolerable safety in multiple phase II studies of relapsed/refractory aggressive NHL (NHL-002 and NHL-003) and MCL post-bortezomib (MCL-001). This pooled analysis further examined the efficacy and safety of single-agent lenalidomide in patients with relapsed/refractory MCL. Methods: Single-agent lenalidomide was given 25 mg/d PO on days 1-21 of 28-day cycles as tolerated for 52 weeks (NHL-002) or until disease progression (NHL-003 and MCL-001). All MCL patients received ≥1 prior treatment, including bortezomib in MCL-001. Efficacy data were examined by independent central review for MCL-001 and NHL-003 and by investigators for NHL-002. Results: 206 patients with relapsed/refractory MCL were studied. The median age was 67 y (range 33-84; 63% ≥65 y), 91% stage III/IV disease and 51% had received ≥4 prior regimens (76% prior bortezomib). Overall response rate (ORR) with lenalidomide was 32% (10% CR/CRu), with a median time to response of 2.1 months and median duration of response (DOR) of 16.6 months (not yet reached in patients with CR/CRu; Table). Kaplan-Meier estimates for median PFS and OS were 5.4 and 23.9 months, respectively. Mean daily dose of lenalidomide was 21 mg. Grade 3/4 AEs included neutropenia (44%), thrombocytopenia (29%), anemia (11%), and fatigue (7%). Other any-grade AEs included tumor flare reaction (7%), venous thromboembolic events (7%), and invasive second primary malignancies (3%). Conclusions: Lenalidomide produced rapid and durable responses in patients with relapsed/refractory MCL, and exhibited a predictable safety profile among 3 phase II studies of lenalidomide in heavily pretreated patients, including prior treatment with bortezomib. Clinical trial information: MCL-001: NCT00737529; NHL-002: NCT00179660; NHL-003: NCT00413036. [Table: see text]
B-TYPE NATRIURETIC PEPTIDE LEVELS IS A USEFUL PROGNOSTIC MARKER IN THE PATIENTS WITH EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS
Authors: Mina Nakayama, Megumi Yamamuro, Yohei Hanajima, Yuichi Okajima, Naoki Nakayama, Toru Dejima, Masahiko Kanna, Yukiko Morita, Kenichi Tsujita, Kazuo Kimura
Journal: Journal of the American College of Cardiology (2017)
Potential prognostic and predictive factors in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA) in daily clinical practice in Spain.
Authors: Pamela Celiz, Alvaro Pinto, Javier Puente, Ray Manneh, Jose Luis Gonzalez Larriba, Enrique Grande, Teresa Alonso, Juan Manuel Sepúlveda, Alfredo Rodriguez, Daniel E. Castellano
Journal: Journal of Clinical Oncology (2014)

e16074 Background: There is a need to find feasible clinical or biochemical markers that may help us to select pts who will get benefit from AA in the pre- and post- CT setting of mCRPC. Methods: We analyzed data from 140 pts at 4 University Hospitals in Madrid. Pts received AA 1.000 mg qd + prednisone 5 mg bid until progressive-disease or unacceptable toxicity. OS and rPFS were analyzed using Kaplan Meier method. Potential prognostic/predictive factors were analyzed using uni- and multivariable logistic regression models. PSA response rate (RR) and radiological assesment were defined according to PCWGII criteria. Results: 119 pts met all criteria. With a median follow-up of 24 mo, 90 pts in post-CT setting were analyzed. Median age:74 y. ECOG 0-1: 86%. Med baseline PSA: 83 ng/ml (81-5122), and 85% had bone mts. Median duration of treatment: 28 wks (range 5 -108); 72% received only 1 prior CT regimen. PSA decline > 50% was observed in 53% (95% CI 27-68%). Median OS was 21 mo (95 % CI 16.7- 24.2). ECOG 0-1 (p 0.006); pre-treatment hemoglobin (Hb) level > 12 g/dl ( p 0.02) and lactate dehydrogenase (LDH) level < 220 U/L (p 0.005) were associated with longer OS. Median rPFS was 8,5 mo (95% CI 6,2- 10,7) . In addition to ECOG 0-1, Hb >12 g/dl, and LDH <220 U/L ;1 prior CT regimen ( p 0.006), baseline PSA < 83 ng/dl ( p 0.025) and PSA response (p 0.04) were significantly associated with a longer rPFS. On multivariate analysis, LDH (HR= 1.43 ,p=0.05) and pts with 1 prior CT regimen (HR= 1.76 ,p=0.02) were associated with longer PFS. In the pre-CT setting29 pts were evaluated. Median rPFS was 14 mo (95% CI 13,2- 15,9) and PSA RR of 75% (CI 95%. 55-87%) There was not significant correlation between baseline characteristics and outcomes. Most common AEs were fatigue and fluid retention. Only 3 pts had G3 AEs, 2 pts with LFT abnormalities and 1 pt with hypokalemia. Conclusions: Our preliminary results confirm the efficacy of AA in mCRPC outside clinical trials. Pts with better ECOG, Hb >12, lower LDH levels, basal PSA <83 and a PSA decline >50% have longer PFS in post-CT setting. If validated, this information might be useful in clinical practice and future clinical trial design.
Comparative effectiveness of second-line targeted therapies for metastatic renal cell carcinoma: Analysis of two practice-based chart reviews.
Authors: James E. Signorovitch, Nicholas J. Vogelzang, Sumanta Kumar Pal, Peggy L. Lin, Daniel J. George, Michael K.K. Wong, Zhimei Liu, Xufang Wang, Kenneth W. Culver, Jeffrey A. Scott, Eric Jonasch
Journal: Journal of Clinical Oncology (2013)

e15504 Background: Second-line targeted therapies for metastatic renal cell carcinoma (mRCC) include mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase inhibitors (TKIs). This study aimed to compare practice-based effectiveness of these therapies in a recent chart review, and to compare findings with a previous chart review (Yang et al., 2012. ASCO). Methods: Community-based medical oncologists/hematologists (N=36) reviewed charts for ≤ 15 patients each. Included patients were aged ≥ 18 years, received a 1st-line TKI and initiated 2nd-line targeted therapy in 2010 or later. The primary outcome was time from 2nd-line initiation to treatment failure (TTF; discontinuation, physician-assessed progression, or death, whichever occurred first). TTF was compared among patients receiving 2nd-line everolimus (EVE), temsirolimus (TEM), or TKI as a class (sunitinib, sorafenib, pazopanib or axitinib), using a multivariable Cox proportional hazards model adjusting for characteristics including type of initial TKI and response, histological subtype, performance status, and sites of metastasis. Hazard ratios (HRs) for TTF were pooled with previously-reported HRs for progression-free survival (PFS) from a previous chart review in a meta-analysis. Results: A total of 138, 64 and 79 patients received 2nd-line therapy with EVE, TEM or a TKI, respectively. Mean age was 63 years, mean duration of mRCC 13.5 months, and median follow-up 6 months. After adjusting for baseline characteristics, EVE was associated with a 28% and 26% reduction in the hazard of TTF compared to TEM and TKI, respectively. Pooling both studies, EVE was associated with significantly reduced hazards of TTF compared to TEM and TKI (Table). TTF differences between TEM and TKI were not significant. Conclusions: In two retrospective chart reviews EVE was associated with consistently reduced hazards of 2nd-line treatment failure in mRCC compared to TEM and TKIs. [Table: see text]
SEX DIFFERENCES IN THORACIC AORTIC ANEURYSM GROWTH: ROLE OF AORTIC STIFFNESS
Authors: Thais Coutinho, Katie Y. Cheung, Munir Boodhwani, Luc Beauchesne, Carole Dennie, Alexander Dick, Sudhir Nagpal, Kwan-Leung Chan
Journal: Journal of the American College of Cardiology (2017)
Analysis of two consecutive series of unresectable high-grade glioma (HGG) patients (pts) treated with or without neoadjuvant chemotherapy before estandar radiochemotherapy (CRT) and adjuvant temozolamide (TMZ).
Authors: Laia Capdevila, Sara Cros, Nuria Pardo, Jose Luis Cuadra, Olatz Etxaniz, Salvador Villà, Carmen Balana
Journal: Journal of Clinical Oncology (2012)

e12504 Background: Standard treatment of HGG is based in CRT with TMZ. Neoadjuvant treatment before radiotherapy has been studied in small series. Methods: We retrospectively analyzed 2 consecutive series of non-resectable HGG pts treated with neoadjuvant chemotherapy (TMZ &amp; cisplatin) before the 2005 with those treated with TMZ and concurrent and adjuvant TMZ &amp; radiotherapy (after 2005). Results: 46pts diagnosed between August 2003 and October 2010 were selected. 23 received neoadjuvant therapy with TMZ (200mg/m2/d x 5d) and cisplatin (75mg/m2) followed by radiotherapy -60Gy 6w- (NA group), and the remaining 23pts received standard treatment with concomitant TMZ and radiotherapy -60Gy 6w- and adjuvant TMZ (CRT group). In the NA group, 87% of pts were ≥50 years, 43.5% were men, 65.2% had performance status (PS) &lt;2, 38.4% Barthel index &lt;70. Histology: 78.3% were glioblastoma (GB). 30.4% of pts had multifocal lesions and 43.5% had seizures at the diagnosis. 95.7% of pts required dexamethasone. In the CRT group, 91.3% of pts were ≥50 years, 78.3% were men, PS was &lt;2 in 60.9% and Barthel index &lt;70 in 21.7% of cases. Histology: 69.6% were GB, 26.1% pts had multifocal lesions and 26.1% had seizures at diagnosis. 87% of pts required dexamethasone. All factors were uniformly distributed in the two groups. 82.6% of pts completed scheduled radiotherapy in NA group in front 91.3% in the CRT group (P= 0.66). PFS was 2.9 months (m) (CI 95%: 0.5 – 5.5) in NA group versus 5.1m (CI 95%: 3.1 – 7.1) in the CRT group (p=0.62), OS was 8.5m (CI 95%: 4.0 – 12.9) vs 8.2m (CI 95%: 1.2 – 15.2) respectively (p=0.45). Conclusions: No differences were found in either PFS or OS between the two treatment groups. The administration of neoadjuvant therapy does no have a negative impact on the ability to receive radiotherapy. These results provide a basis to justify clinical trials in this setting with promising drugs before radiotherapy treatment.
CONTEMPORARY NATIONWIDE TRENDS IN INFERIOR VENA CAVA FILTER IMPLANTATION RATES IN THE UNITED STATES AND THE EFFECT OF FOOD AND DRUG ADMINISTRATION ADVISORY
Authors: Satyajit Reddy, Vladimir Lakhter, Chad Zack, Saurav Chatterjee, Vikas Aggarwal, Riyaz Bashir
Journal: Journal of the American College of Cardiology (2017)
Alemtuzumab Used with Fludarabine and Cyclophosphamide (FCC) for Stem Cell Transplantation in Acquired Aplastic Anemia Is Associated with a Low Risk of Graft Versus Host Disease and Viral Infections and with Sustained Engraftment.
Authors: Judith C W Marsh, Vikas Gupta, ZiYi Lim, David Marks, Edward C. Gordon-Smith, Ghulam J Mufti
Journal: Blood (2009)
Phase II study of R-CHOP with GM-CSF cytokine support for elderly patients with untreated diffuse large B-cell lymphoma (DLBCL): A Wisconsin Oncology Network study
Authors: B. S. Kahl, R. S. Go, G. Rodrigues, F. A. Sanchez, T. J. Saphner, J. E. Werndli, H. M. Kirkpatrick, W. L. Longo
Journal: Journal of Clinical Oncology (2006)

7566 Background: According to mature data from the GELA study, approximately 55% of elderly patients with DLBCL will be cured with R-CHOP. We hypothesized that sargramostim (GM-CSF), added to R-CHOP may potentiate the efficacy of rituximab by upregulating tumor cell CD20 expression and by augmenting antibody dependent cellular cytotoxicity (ADCC). Methods: Patients &gt; 60 years old with untreated stage I-IV DLBCL were eligible if they had PS ≤ 2, measurable disease, adequate organ function, and provided informed consent. R-CHOP for 6–8 cycles was given every 21 days with GM-CSF given subcutaneously at a dose of 250 mg/m 2 days 3–10 of each cycle. The primary endpoint was to estimate the CR/CRu rate. Secondary endpoints included estimates of the ORR, EFS, and OS. Results: Thirty-eight/forty patients have been enrolled to date and data are available for 36. One patient is too early and another was deemed ineligible after centralized pathology review. Baseline characteristics include median age 72 (range 61–86), 25% PS 0, 44% PS 1, 31% PS 2, 80% stage III/IV, 56% elevated LDH, 8% IPI 0–1, 25% IPI 2, 36% IPI 3, 31% IPI 4–5. Thirteen/thirty-six (36%) patients did not complete 6 cycles of protocol therapy, 8 due to intolerance of R-CHOP and 5 due to intolerance of GM-CSF. By intent-to-treat analysis, 17/36 patients achieved CR/CRu (47%) and 9/36 achieved PR (25%) for an ORR of 72%. No patients progressed while on study and all non-responders were deemed so secondary to inability to complete protocol therapy. The median follow-up time for surviving patients is 19 months. Considering inability to complete protocol therapy as an event, the 2-year EFS is 38%, the 2-year PFS is 56%, and the 2-year OS is 74%. Conclusions: Any benefit that may be conferred by GM-CSF is likely to be offset by toxicity and intolerance, with 14% of patients in this series unable to complete GM-CSF therapy. Additionally, R-CHOP is more toxic in elderly patients than is commonly appreciated with, 22% of patients unable to complete 6 cycles. Despite recent advances, DLBCL in the elderly remains a difficult problem and new approaches to therapy must be developed. [Table: see text]
Effectiveness of peptide receptor radionuclide therapy for neuroendocrine neoplasms: A multi-institutional registry study with prospective follow-up.
Authors: Dieter Hörsch
Journal: Journal of Clinical Oncology (2013)

4033 Background: Peptide receptor radionuclide therapy targets somatostatin receptors expressed on well differentiated neuroendocrine neoplasms. Retrospective monocentric studies indicate that peptide receptor radionuclide therapy is an effective treatment for patients with neuroendocrine neoplasms. Methods: We initiated a multi-institutional, prospective and board reviewed registry study for patients treated with peptide receptor radionuclide therapy. 450 patients were included and followed for a mean of 24.4 months. Patients were treated with Lutetium-177 (54%), Yttrium-90 (17%) or both radionuclides (29%). Primary neuroendocrine neoplasms were derived of pancreas (38%), small bowel 30%), unknown primary (19%), lung (4%) and colorectum (3,5%). Most neuroendocrine neoplasms were well differentiated with a proliferation rate below 20% in 54% and were pretreated by 1 or more therapies in 73%. Results: Overall survival of all patients from the beginning of therapy was 59 months in median. Median survival depended on radionuclides used (Yttrium-90: 38 months; Lutetium-177: not reached; both: 58 months), proliferation rate (G1: median not reached; G2: 58 months; G3: 33 months; unknown: 55 months) and origin of primary tumors (pancreas: 53 months; small bowel: not reached; unknown primary: 47 months; lung: 38 months) but not upon number of previous therapies. Median progression-free survival measured from last cycle of therapy accounted to 41 months for all patients. Progression-free survival of pancreatic neuroendocrine neoplasms was 39 months in median. Similar results were obtained for neuroendocrine neoplasms of unknown primary with a median of 38 months whereas neuroendocrine neoplasm of small bowel were progression-free for a median of 51 months. Side effects like G3-G4 nephrotoxicity or hematological function were observed in 0.2% and 2% of patients. Conclusions: Peptide receptor radionuclide therapy is effective for patients with G1-G2 neuroendocrine tumors irrespective of previous therapies with a survival advantage of several years compared to other therapies and only minor side effects.
Different prediction of distant recurrence risk in primary breast cancer patients stratified by ER and ERBB2 status
Authors: P. Urban, V. Vuaroqueaux, M. Labuhn, M. Delorenzi, P. Wirapati, H. Dieterich, S. Ehret, G. Fürstenberger, R. Morant, U. Eppenberger, S. Eppenberger-Castori
Journal: Journal of Clinical Oncology (2006)

20120 Background: Molecular profiling recently defined biological characteristics of several long-recognized breast cancer subtypes including ER-positive (luminal subtype), ER-negative/ERBB2-positive (ERBB2 subtype) and ER-negative/ErBB2-negative (basal-like subtype). Each of these particular subtypes has different impact on patient outcome and should be therefore taken in consideration for individual scoring calculations. Methods: The quantitative RNA expression levels of 70 relevant genes were simultaneously determined in fresh frozen samples of 317 primary breast cancer (BC) patients comprehending ER-positive (70%), ER-negative/ERBB2-positive (15%) and ERBB2-negative/ER-negative (15%) and with known follow-up data. Five years distant recurrence scoring systems were calculated by means of Cox-hazard regression models. Results: Two main prognostic scoring systems were developed: one based on genes relative to proliferation representing tumor growth and its velocity, the other based on proteases. A low proliferation score identified 30% of patients at very good prognosis (probability of distant recurrence 12%, CI: 1.5–22%) all belonging to the ER-positive subcategory as compared to cases with higher proliferation (probability of distant recurrence 31%, 32–38%). The probability to develop distant recurrence within 5 years for 30% of ERBB2-positive patients was of only 12% (CI 0–25%) when accompanied by low levels of proteases as compared to the remaining ERBB2-positive patients with a probability of recurrence of 40% (CI 22–54%). Conclusions: ER, ERBB2 and the expression levels of the few identified genes involved in tumor proliferation and invasion can be easily and precisely detected by means of QRT-PCR. This robust method allows fine tuned prognosis and gives predictive information for the treatment of individual breast cancer. [Table: see text]
Multicenter study of radiosensitizing gemcitabine combined with fractionated radioimmunotherapy for repeated treatment cycles in advanced pancreatic cancer
Authors: K. Pennington, M. J. Guarino, A. N. Serafini, C. Rocha-Lima, K. Suppiah, C. J. Schneider, D. V. Gold, R. M. Sharkey, W. A. Wegener, D. M. Goldenberg
Journal: Journal of Clinical Oncology (2009)

4620 Background: In a phase I study, a single dose of 90 Y-labeled anti-mucin humanized antibody, hPAM4 ( 90 Y-hPAM4), led to several transient reductions or stabilization of lesions in advanced pancreatic cancer, with bone marrow toxicity limiting the maximum tolerated dose to 20 mCi/m 2 . Preclinical studies showed gemcitabine enhanced radioimmunotherapy, so a phase Ib study was undertaken to evaluate repeated treatment cycles of 90 Y-hPAM4 plus gemcitabine. Methods: Patients (pts) with previously untreated, locally advanced or metastatic, pancreatic cancer were treated in 4-week cycles (200 mg/m 2 gemcitabine once-weekly; 111 In-hPAM4 the 1 st wk for imaging, biodistribution, and dosimetry; 90 Y-hPAM4 once-weekly the last 3 wks), which could be repeated in the absence of progression or unacceptable toxicity. The 90 Y-dose was escalated by patient cohort following a 3+3 design, with tumor responses assessed by CT and FDG/PET imaging, and by CA19.9 serum levels. Results: Eight pts (3F/5M, 56–72 years old, 7 with metastatic disease) have now been treated at the first 2 dose levels (6.5 and 9.0 mCi/m 2 90 Y-hPAM4 x 3) with hematologic toxicity all transient Grade 1–2 (NCI CTC v3). 111 In-hPAM4 imaging showed normal biodistribution, evidence of tumor targeting and acceptable dosimetry estimates to normal organs per treatment cycle. Two pts had tumor responses to initial treatment with significant decreases in FDG metabolic activity on PET imaging, regression of lesion sizes on CT, and CA19.9 decreases. Both pts continue in excellent performance status now at 9 and 11 months after study entry, after receiving a total of 3 and 4 treatment cycles, respectively, without additional toxicity. A 3 rd pt with a stable response by PET and CT 4 weeks after initial treatment and decreases in CA19.9 levels is now undergoing a 2 nd treatment cycle. Four other pts had early progression of disease by or before post-treatment week-4 evaluation, and the remaining pt is still being evaluated. Conclusions: Dose escalation is continuing after fractionated radioimmunotherapy with 90 Y-hPAM4 plus low-dose gemcitabine demonstrated therapeutic activity at the first two 90 Y dose levels, with minimal hematologic toxicity, even after 4 treatment cycles. [Table: see text]
EFFECT OF LEFT ATRIAL REMODELING ON PREDICTION OF INCIDENT ATRIAL FIBRILLATION WITH CHARGE-AF SCORE: DATA FROM THE FRAMINGHAM OFFSPRING STUDY
Authors: Mayank Sardana, Steven Lubitz, Nisha Parikh, Connie Tsao, Emelia Benjamin, Nelson Schiller, Vasan Ramachandran, David McManus
Journal: Journal of the American College of Cardiology (2017)
Erratum: Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer
Authors: Akihiro Fujimoto, Mayuko Furuta, Yasushi Totoki, Tatsuhiko Tsunoda, Mamoru Kato, Yuichi Shiraishi, Hiroko Tanaka, Hiroaki Taniguchi, Yoshiiku Kawakami, Masaki Ueno, Kunihito Gotoh, Shun-ichi Ariizumi, Christopher P Wardell, Shinya Hayami, Toru Nakamura, Hiroshi Aikata, Koji Arihiro, Keith A Boroevich, Tetsuo Abe, Kaoru Nakano, Kazuhiro Maejima, Aya Sasaki-Oku, Ayako Ohsawa, Tetsuo Shibuya, Hiromi Nakamura, Natsuko Hama, Fumie Hosoda, Yasuhito Arai, Shoko Ohashi, Tomoko Urushidate, Genta Nagae, Shogo Yamamoto, Hiroki Ueda, Kenji Tatsuno, Hidenori Ojima, Nobuyoshi Hiraoka, Takuji Okusaka, Michiaki Kubo, Shigeru Marubashi, Terumasa Yamada, Satoshi Hirano, Masakazu Yamamoto, Hideki Ohdan, Kazuaki Shimada, Osamu Ishikawa, Hiroki Yamaue, Kazuki Chayama, Satoru Miyano, Hiroyuki Aburatani, Tatsuhiro Shibata, Hidewaki Nakagawa
Journal: Nature Genetics (2016)