tbuckley/cabot-search huggingface dataset:
Germline Genes Specific to Chronic Lymphocytic Leukemia (CLL) and Genes Common to CLL, Lymphoplasmacytic Lymphoma/Waldenström’s Macroglobulinemia, and Other Non-Hodgkin Lymphomas Are Important in Susceptibility
Authors: Ola Landgren, Sigurdur Y Kristinsson, Xueying Sharon Liang, Ingemar Turesson, Magnus Bjorkholm, Neil E. Caporaso, Mary L. McMaster, Stephen Chanock, Lynn R. Goldin
Journal: Blood (2008)
Abstract 11505: Predictive Value of Heart Rate Variability for Appropriate ICD Discharge in Cardiac Resynchronization Therapy Patients
Authors: Judith N ten Sande, Joris R de Groot, Reinoud E Knops, Arthur A Wilde, Pascal F van Dessel
Journal: Circulation (2012)

Heart rate variability (HRV) is used to evaluate autonomic regulation in patients with cardiovascular disease. Decreased HRV is associated with adverse outcomes in patients with congestive heart fa...
Effect of first-line modified schedule of gemcitabine on clinical benefit rate and toxicity in elderly or PS 2 patients with advanced non-small cell lung cancer.
Authors: A. Nacci, E. Maiello, E. Mazzoni, N. Calvani, L. Orlando, F. Sponziello, P. Schiavone, P. Rizzo, P. Fedele, S. Cinieri
Journal: Journal of Clinical Oncology (2010)

e18131 Background: Monochemotherapy with gemcitabine (Gem) is often the treatment of choice in elderly or poor performance status (PS) patients with advanced non-small cell lung cancer (NSCLC). Our study was aimed to assess the efficacy and tolerability of a modified schedule of Gem using a lower dose than standard. Methods: From May through December 2009, twenty-four patients (18 male and 6 female with a median age of 75 years ranging from 64 to 84) with advanced NSCLC (stage IIIB 37,5% and IV 62,5%) were enrolled. Histology was: squamous 38%, adenocarcinoma 25%, large cell 4%, undifferentiated 4%, undetermined 29%. Only four patients (17%) had a WHO PS 0 whereas thirteen (54%) were PS 1 and seven (29%) PS 2. All patients received first-line chemotherapy with 6 cycles of Gem 1,000 mg/sq on days 1 and 8 every 4 weeks. Results: At the time of analysis 17 patients were evaluable for response. Partial response (PR) was achieved in 2 patients (12%), stable disease > 12 weeks (SD) in 8 (47%) whereas 7 had progressive disease (41%). Importantly, the clinical benefit rate (PR + SD) was 59%. Tumour markers (CEA and NSE) were high in 11 patients with a reduction in their values observed in 4 of them (36%). Both pain and PS improved in 2 patients (8%) whereas 12 (50%) had an improvement in pain with no worsening of PS. We observed only grade 2 WHO haematological toxicities including anemia, leucopenia, neutropenia and trombocytopenia. Not-neutropenic fever occurred in 4 patients (17%). Overall, we did not observe any not-haematological treatment-related event. Conclusions: Our data show that a modified schedule of Gem with a lower dose intensity than standard may be beneficial in terms of both disease control and tolerability when employed in elderly or PS 2 patients with advanced NSCLC. No significant financial relationships to disclose.
A phase II trial of high-dose chemotherapy (HDCT) supported by haematopoietic stem cell transplantation (HSCT) in patients (pts) with disseminated germ-cell tumors (GCTs) failing chemotherapy and with adverse prognostic factors: The TAXIF II protocol
Authors: J. Lotz, F. Selle, K. Fizazi, G. Gravis, B. Bui, R. Delva, J. Bay, A. Baron, M. Robain, P. Biron
Journal: Journal of Clinical Oncology (2009)

5028 Background: HDCT using the etoposide-carboplatin ± ifosfamide regimen is able to circumvent resistance in GCT pts, even when used as third-line or later therapy (Lotz, Ann Onco.l 2005 / Einhorn, N Eng J Med. 2007). Pts whose relapses occur more than 4 w after CDDP-based CT are probably the best candidates for HDCT. Epirubicine (E) and paclitaxel (P) possess interesting activity in GCTs. Thiotepa (TTP) and P can be safely combined at HD with good efficacy. The ICE regimen is a well-known worldwide used regimen. Methods: Non-resistant/refractory GCTs pts failing CT and with adverse prognostic factors were planned to receive 2 cycles combining (mg/m 2 ) E (100) and P (250), given on day 1 and 14 supported by filgrastim (F), followed by 3 consecutive HDCTs [1 course combining a 3-d combination of P (360) + TTP (720), followed by 2 ICE regimens (IFM, 12 g/m 2 , CBDCA, AUC 20, VP16, 1,500 mg/m 2 ), given on 5 days with HSCT and F]. Inclusion criterias were mainly: radiologically and/or biologically mesurable disease, seminomatous GCT in relapse after 2 lines of CT (BEP/VeIP), non-seminomatous GCT in relapse after 1 or 2 lines of CT or in PR after 1 line of CT, primary mediastinal GCT in first relapse. Resistant / refractory pts were excluded. PBSC were collected after the first ± the second courses of EP (aim: 9x10E6 CD34+/kg BW). We report herein on the preliminary results of this multicentric study. Results: From 09/04 to 12/07, 45 pre-treated (BEP ± VeIP) pts with gonadal (89%) or extra-gonadal T (11%) were treated in second-line (27%), 3rd-line (44 %) or more (29 %). Thirty-five pts received 1 HDCT, 29 two HDCTs and 21 pts could receive the whole protocol. At the time of analysis (12/08), the final overall response rate was 47%, 10 pts were in continuous CR (median time, 8 m; range, 1–18), and 37 pts (82%) were alive at a median F/U of 9 m (range, 1–26). The 1-y survival rate was 90%. The 1-y PFS rate was 62%. One pt died of multi-organ failure and 7 died of disease progression. Conclusions: This HDCT program preceded by 2 semi-intensive cycles of E-P is highly effective in non-resistant/refractory pts with disseminated GCTS failing CT and with adverse prognostic factors. No significant financial relationships to disclose.
Tolerability of a weekly schedule of docetaxel-cisplatin as first-line treatment in patients with stage IIIB/IV non-small cell lung cancer (NSCLC)
Authors: D. Binder, M. Hackenthal, L. Graseck, H. Schweisfurth, C. Schäper, B. Temmesfeld-Wollbrück, N. Suttorp, T. Beinert, K. Hellriegel
Journal: Journal of Clinical Oncology (2006)

17112 Background: Recent trials have shown that the combination docetaxel-cisplatin is an effective first-line treatment in locally advanced or metastatic NSCLC. However, the regimen can be associated with a marked rate of neutropenia. The present study tests the efficacy and tolerability of a weekly schedule of docetaxel and cisplatin. Methods: Patients (pts) with histologically confirmed NSCLC stages UICC IIIB (malignant effusion) or IV were treated with docetaxel (35 mg/m 2 , 30 min. infusion) and cisplatin (25 mg/m 2 , 30 min. infusion) on days 1, 8 and 15 repeated every 4 weeks for 4 to 6 cycles. This phase II study is scheduled to include 50 pts and primary endpoint is tumour response rate. Pts received 8 mg of ondansetron and 8 mg of dexamethasone i.v. preceding every day of therapy and oral dexamethasone 2 × 4 mg from the day before until the day after chemotherapy. NK1-antagonists were given at discretion of the investigator. In total, 2750 ml of volume were infused on each day of therapy. Most of the pts were treated in an outpatient department. Safety was assessed via common terminology criteria for adverse events v3.0 (CTCAE 3.0). Interim tolerability data is presented. Results: Currently, 28 pts were evaluable for this interim tolerability analysis. Pts received a median of 3 full cycles. There were no treatment-related deaths. Dose reductions of docetaxel and cisplatin due to poor tolerability were necessary in 3 pts (11%). No pts suffered from neutropenic fever while grade 3 neutropenia occurred in only 2 pts (7%). There was no grade 2/3/4 thrombocytopenia. 5 pts (18%) had grade 2 anemia, and 2 pts (7%) had an elevation of the plasma creatinine (both grade 1). Other toxicities were non-neutropenic infections (5/1/1 pts with grade 2, 3, 4, respectively), diarrhea (3 pts [11%] with grade 3), constipation (5 pts [18%] with grade 2) and mucositis (4 pts [14%] with grade 2/3). There was no grade 3/4 nausea or vomiting; 3 pts [11%] had grade 2 nausea/vomiting. Conclusions: In the present study, the combination of docetaxel and cisplatin appears well tolerated. It was associated with a very low frequency of severe hematologic toxicity or neutropenic fever. With relatively low hydration volumes it can be safely administered in an outpatient setting. [Table: see text]
Capecitabine (X) in the first-line treatment of metastatic breast cancer (MBC).
Authors: N. Harbeck, M. Kaufmann, F. Siedentopf, P. Dalivoust, M. Debled, N. J. Robert, J. O'Shaughnessy
Journal: Journal of Clinical Oncology (2011)

1080 Background: The utility of anthracyclines/taxanes in MBC is decreasing as their use in EBC increases. Alternative agents are needed for treatment-resistant/-refractory pts presenting in the first-line MBC setting. We evaluate evidence for X as a first-line therapy. Methods: We reviewed data from phase II/III randomized trials and observational cohorts. Results: Significantly prolonged OS (p=0.02) was seen with first-line X 1,000mg/m2 bid vs CMF (tTable); in the X arm 40% of pts received therapy for >6 months and 18% for >1 year vs 21% and 5% of pts in the CMF arm. First-line X 1,250mg/m2 bid showed comparable efficacy (p=ns) to pegylated liposomal doxorubicin (PLD). In the SO14999 study (O’Shaughnessy JCO 2002), X 1,250mg/m2 bid + docetaxel (T) gave an ORR of 42% vs 31% for T in 169 pts receiving first-line therapy; ORR + SD rates were 82% and 72%. In combination with biologics, first-line X 1,000mg/m2 bid + bevacizumab (X-A; HR for PFS 0.69; p=0.0002) or sorafenib (X-S) (PFS, p=0.002) showed superior efficacy to X + placebo (X-pl). Results in the control arm of these studies were consistent with other studies of X monotherapy. First-line X 1,000mg/m2 bid was also effective in the single-arm, phase II MONICA study. Across the phase II/III trials, X was associated with minimal myelosuppression and alopecia, with hand-foot syndrome and diarrhea the most frequently reported grade 3/4 AEs. Results from observational studies in MBC pts receiving first-line X in routine clinical practice in Germany and France (n=479) confirmed the data reported in the interventional studies (Dalivoust SABCS 2010, Siedentopf Onkologie 2009). Conclusions: First-line X, often given at a dose of 1,000mg/m2 bid, is a well supported therapy in anthracycline-/taxane-pretreated MBC or in pts unsuited to taxanes, with proven efficacy and manageable safety in the first-line setting. Study Pts, n Median OS, months Median TTP/PFS, months ORR, % ANZBCTG0001 Stockler ASCO 2007 X vs CMF 214 vs 109 22.0 vs 18.0 6.0 vs 7.0 21.0 vs 18.0 PELICAN Jager ASCO 2010 X vs PLD 105 vs 105 29.4 vs 22.4 7.1 vs 6.2 24.4 vs 22.9 RIBBON-1 Robert ASCO 2009 X-A vs X-pl 409 vs 206 29.0 vs 21.2 8.6 vs 5.7 35.4 vs 23.6 SOLTI-0701 Baselga SABCS 2009 X-S vs X-pl 50 vs 62* – 7.6 vs 4.1 – MONICA Kaufmann EJC 2010 X 165 17.1 7.3 26.1 * First line only.
Low dialysate [K+] decreases efficiency of hemodialysis and increases urea rebound.
Authors: G M Dolson, H J Adrogué
Journal: Journal of the American Society of Nephrology (1998)

In a previous study, it was reported that hemodialysis with dialysate [K+] (KD) of 1.0 or 2.0 mmol/L caused an increase in BP shortly after completion of treatment due to arteriolar constriction. With this background, it was hypothesized that a low KD might decrease dialysis efficiency by a similar mechanism. To evaluate this hypothesis, paired observations of two consecutive 3-h treatments, with KD of 1.0 or 3.0 mmol/L, were performed in 14 stable end-stage renal disease patients. A KD of 1.0 mmol/L resulted in lower values for both urea reduction ratio and Kt/V evaluated at completion of dialysis and 1 h thereafter. Values at equilibrium were urea reduction ratio 42+/-1% versus 47+/-2% (P < 0.02), Kt/V 0.65+/-0.03 versus 0.73+/-0.03 (P < 0.02) for KD 1.0 or 3.0 mmol/L, respectively. The mechanisms responsible for the observed differences in dialysis efficiency were examined using a urea kinetics model that predicts urea sequestration caused by impaired blood flow to urea-rich tissues. For this purpose, urea rebound and its effect on Kt/V (by means of deltaKt/V, calculated as equilibrated minus single pool value) with KD 1.0 and 3.0 mmol/L were assessed. Greater urea rebound, 12.8+/-1.6% versus 8.6+/-1.4% (P < 0.001), and larger deltaKt/V, 0.12+/-0.01 versus 0.10+/-0.02 (P < 0.02), were observed with KD 1.0 mmol/L compared with 3.0 mmol/L. The theoretical model accurately predicted the deltaKt/V observed with KD 1.0 mmol/L. It is concluded that a low KD decreases dialysis efficiency. This effect is likely caused by reduced blood perfusion to nonvisceral organs, largely skeletal muscle. Conversely, hemodialysis with KD 3.0 mmol/L facilitates tissue perfusion, minimizes urea trapping in poorly perfused areas, and improves the efficiency of this treatment modality.
A phase II study of aflibercept (VEGF trap) in recurrent or metastatic gynecologic soft-tissue sarcomas: A study of the Princess Margaret Hospital Phase II Consortium
Authors: C. Townsley, H. Hirte, P. Hoskins, R. Buckanovich, H. Mackay, S. Welch, L. Wang, R. Polintan, A. Chen, A. M. Oza
Journal: Journal of Clinical Oncology (2009)

5591 Background: Targeting angiogenesis and vascular endothelial growth factor (VEGF) represents a promising approach to treat highly vascular tumors, like gynecologic sarcomas. Aflibercept, a long-acting inhibitor of VEGF signaling, potently binds and inactivates VEGF, thus blocking tumor angiogenesis and growth. Methods: This is a single-arm, open-label, two-stage phase II clinical trial designed to evaluate the efficacy and toxicity of aflibercept as treatment for patients (pts) with recurrent, or metastatic gynecologic soft tissue sarcoma. Aflibercept was administered at 4 mg/kg IV every 2 weeks and pts had radiologic imaging performed every 8 weeks. The primary endpoints were response rate and prolonged stable disease. Results: Twenty-five pts with leiomyosarcoma of the uterus and 13 pts with carcinosarcoma of the uterus were enrolled in 2 cohorts. In the leiomyosarcoma group, 24/25 pts had an ECOG of &lt;1, most pts (22/25) had &lt;1 previous lines of treatment and 7/25 pts had prior radiotherapy. A total of 149 cycles were administered for this group, with a median of 4 (range 2–28). In the carcinosarcoma group, 10/13 pts had an ECOG of &lt;1, most pts (12/13) had &lt;1 previous lines of treatment and 5/13 pts had prior radiotherapy. A total of 31 cycles were administered with a median of 3 (range 1–4). The most frequent adverse events experienced by all pts, of any grade, were fatigue 71% pts, constipation 53% and hypertension 39% . The most frequent grade 3 or higher, adverse events were hypertension 18%, fatigue 13% and lymphopenia 8%. Eight pts with leiomyosarcoma had stable disease (4pts &gt; 6 mo). No reponses were seen in either cohort and no stable disease was seen in the carcinosarcoma group. Median overall survival was 15.1 mo (95% CI: 8.5 - not reached) for the leiomyosarcoma cohort and 3.1 mo for the carcinosarcoma cohort (95% CI: 1.9 - not reached). The requirements to proceed to stage 2, in leiomyosarcoma, were met after more than 2/21 patients had &gt; 6 mo PFS. Carcinosarcoma cohort has not finished stage 1 and both cohorts continue accrual. Conclusions: VEGF-trap was well tolerated in this pt population with acceptable side effects. Initial efficacy data suggests modest activity, particularly in patients with leiomyosarcoma. [Table: see text]
Management of Asthma during Pregnancy
Authors: Paul A. Greenberger, Roy Patterson
Journal: New England Journal of Medicine (1985)

Asthma has been reported to occur in 0.4 to 1.3 per cent of pregnant women,1 , 2 making it the most common obstructive pulmonary disease during pregnancy.3 Uncontrolled episodes of wheezing have been associated with maternal and perinatal mortality,4 although the pregnancy outcome for women with corticosteroid-dependent asthma is almost as favorable as that for the general population when asthma is controlled satisfactorily.5 , 6 The goals of therapy in managing asthma in a pregnant woman are similar to those in a nonpregnant woman with asthma; in order of decreasing importance, they are to prevent death, respiratory failure, status asthmaticus, emergency room visits, and . . .
Serum prostate-specific antigen screening for prostate cancer: Analysis of the costs and benefits
Authors: W. Mermershtain, D. Bone, T. Shteiman, S. Ariad
Journal: Journal of Clinical Oncology (2007)

15602 Background: PSA (prostate specific antigen) blood test used as a diagnosing aid for prostate cancer. Physicians disagree on the test performance policy and its necessity, and as a result the referring practices vary from physician to another. We examine whether the use of PSA test in General Health Services, was performed rationally, and cost effectively. Methods: Phase 1: Collection of data on all the prostate cancer patients registered at the Soroka University Medical Center until 2004 and people insured by the Clalit Health Services, that underwent PSA tests in 2002–2004. Phase 2: Cross examination of the patients’ data with data on patients undergoing the test. Phase 3: Determining the number of excessive tests (over 4 tests per person a year). Phase 4: A random study of 90 medical files of patients that underwent a PSA test. The number of references made not according to the instructions (in the files) was multiplied by the number of conducted tests (except those in phase 3), thus reaching the number of irrational tests. Phase 5: Multiplying the number of tests in phases 3–4 by the public rates of the Health Ministry for PSA tests (62 NIS). In addition, a questionnaire was distributed among primary care physicians to learn about their attitudes regarding defensive medicine. Results: In years 2002–2004, 19,418 patients underwent 25,674 PSA tests. 88.6% of the tests turned out as irrational - accumulating to a cost of 1,410,438 NIS. In the course of the recent years there is a trend of increase in the number of tests provided not according to the custom instructions, and this state of affairs suggests lack of awareness to such a high rate of irrational tests, or alternatively, awareness and failure to assign appropriate importance to the problem. Likewise, it was found that there are doctors referring patients to PSA tests as a result of defensive medicine. Conclusions: High percentage of the referrals to PSA test was provided not according to the customary instructions, and some of these referrals stems from defensive medicine. We suggest, guiding rules must be set for referring patients to PSA tests. It is necessary to update primary care doctors on the use and miss use of the tests. No significant financial relationships to disclose.
Lack of consensus on post-operative radiotherapy (PORT) fields used in non-small cell lung cancer (NSCLC)
Authors: S. Senan, C. Le Péchoux, F. O. Spoelstra, S. Ishikura, F. Casas, D. Ball, A. Price, D. DeRuysscher, J. R. van Sörnsen de Koste
Journal: Journal of Clinical Oncology (2007)

7658 Background: Survival in patients with a completely resected stage III-N2 NSCLC may be improved by PORT. LungART is a phase III trial for patients with resected N2 disease who will be randomized to between PORT and no PORT, irrespective of the use of chemotherapy. LungArt target volumes are based upon the post-surgical findings in each patient, and on the surgical literature. A ‘dummy run’ was performed to study PORT volumes used internationally and to evaluate the LungART protocol. Methods: A CD-rom based contouring program containing the planning CT scans of 2 patients (post-lobectomy and pneumonectomy, respectively) were mailed to 17 thoracic radiation oncologists from 4 continents. Relevant clinical, radiological and pathological reports were provided in order to allow clinicans to contour their ‘routine’ clinical target volumes (CTV). Contours were saved onto a CD-rom and mailed to the study center. The LungART protocol was then provided and ‘protocol’ CTVs were generated. Contours of each case were transferred to a template CT dataset of that patient, and nodal CTVs were jointly generated by two clinicians using published definitions. An optimised treatment plan was generated for all CTV's. Results: For each case, a total of 10 routine CTVs were received. Both routine and protocol CTVs were provided for each case by 6 clinicians. The routine CTVs varied up to 3-fold between clinicians and this was significantly decreased by use of the protocol (F test, p=0.00003 and p=0.00002 for cases 1 and 2, respectively). Coverage of nodal stations 2R and 4R improved when CTVs were defined using the protocol. Risks of lung toxicity, as defined by the lung volumes treated to 20 Gy and 5 Gy, varied between the smallest and second largest routine CTVs. For the post-lobectomy case, the V 20 (range) was 11.8–19.3% and a V 5 of 33.8–57.9%. The corresponding V 20 and V 5 values were 1.5–2.1% and 31.6–39.7% for the post-pneumonectomy case. Both cardiac volumes receiving 45 Gy and spinal doses were similar for both CTVs. Conclusions: The variations in PORT volumes generated by experts led to important differences in the risk of radiation-induced lung toxicity. Standardized target definitions are needed in order to optimize the survival benefits from PORT, and the LungArt protocol may serve this purpose. No significant financial relationships to disclose.
Prognostic value of the absolute lymphocyte count reduction in patients with diffuse large B-cell lymphoma treated with R-CHOP.
Authors: S. Kim, B. Kang, Y. Chae, J. Kim, Y. Kim, S. Sohn
Journal: Journal of Clinical Oncology (2010)

8101 Background: The International Prognostic Index (IPI) or absolute lymphocyte count (ALC) was known as a prognostic factor in diffuse large B-cell lymphoma (DLBCL). But in the rituximab era, new predictive marker relating to rituximab may be needed. We evaluated prognostic factors for survival in patients with early staged-DLBCL after R-CHOP treatment. Methods: From Aug 2003, 78 patients with early staged DLBCL, who finished R-CHOP as scheduled, were retrospectively reviewed. Survival analyses were performed according to clinical parameters (age, performance status, LDH, extra-nodal involvement, stage, ALC, and the reduction rate of WBC or ALC). Results: Among 78 patients with early staged DLBCL, 26 patients (33.3%) were classified as stage I. Seventy three patients (93.6%) presented with a good performance status, while LDH was elevated in 20 patients (25.6%). According to IPI, 67 (85.9%) patients were classified to the low-risk group, 8 (10.3%) to the low-intermediate group, and 3 (3.8%) to the high-intermediate risk group. The overall response rate was 100% including 94.8% complete response. Survival analysis demonstrated that the reduction rate of ALC after the first R-CHOP treatment was the only factor associated with time-to-progression (p = 0.037), whereas age was the single most important prognostic factor for overall survival (p = 0.006). Conclusions: In the present study, the reduction rate of ALC on addition to age was found to be a significant prognostic factor in patient, with early stage DLBCL treated with R-CHOP regimen. No significant financial relationships to disclose.