tbuckley/cabot-search huggingface dataset:
Erlotinib for first line treatment in unselected patients (p) with advanced or metastatic non-small cell lung carcinoma (NSCLC)
Authors: U. Jimenez, A. Gurpide, D. Isla, R. Garcia-Campelo, J. Firvida, N. Vinolas, A. Jaen, J. Montalar, P. Regueiro, B. Massuti
Journal: Journal of Clinical Oncology (2007)

7639 Background: Erlotinib is an orally available selective EGFR tyrosine-kinase inhibitor. Erlotinib is approved for the treatment of patients (p) with advanced or metastatic NSCL that have progressed at least to one prior chemotherapy regimen. In certain subgroups erlotinib has demonstrated to be active when administered as first line treatment. We retrospectively analysed efficacy and safety of patients treated with erlotinib as first line included in the Target Study. Methods: The TargeT trial is a multicentric, open-label, non-randomized, phase II study carried out in 101 Spanish institutions. Eligibility criteria included chemonaive p with stage IIIB-IV NSCLC. Subjects were treated with 150 mg/day po until disease progression or unacceptable toxicity. Dose reductions were allowed. Primary end-point was survival. Results: By the time of this interim analysis, data from 437 p treated with erlotinib as first line were available. Median age 72 y (range 26–90). Demographics (%): M/F 59/41; PS0/1/2 19/51/30; pathology adeno 53; current or former smoker 63. In the evaluable population for efficacy best response was: 6 CR, 68 PR, 93 SD, 69 PD (RR 31.35%). Time to progression was 6.6 mo (95% CI 4.8–8.6/ OS 7.1). Overall survival was 7.1 mo (95% CI 5.9–9.1). Most common erlotinib-related adverse events were skin rash (61%) and diarrhea (31.2%) with no unexpected toxicities having been observed. Conclusions: Although at this moment clinical trials are ongoing trying to find the best predicitive factor of response, erlotinib first line was active and well tolerated in this analysis in an unselected population. No significant financial relationships to disclose.
Correlation between the number of positive nodes, number of dissected nodes and survival of patiens with colorectal cancer
Authors: J. C. Marin Marmolejo, C. R. Villegas Mejia, J. P. Cardona Arcila, E. Mulett Vasquez, M. Osorio Chica, G. F. Osorio, L. A. Correa Ramirez, J. A. Chacon Cardona
Journal: Journal of Clinical Oncology (2006)

13585 Background: According to the TNM classification, the prognosis of patients suffering from colon and rectal cancer has been defined taking into account the number of nodes reported positively. Objective: This work is intending to establish a relation between the number of positive nodes and the number of dissected nodes, relating it with the overall survival. Methods: 5500 medical records of patients were reviewed. 771 out of these corresponded to gastrointestinal cancer (14%) from which 351(6.38%) corresponded to colorectal cancer. From this group, 291 patients (82.9%) underwent a surgery. A relation between the number of positive nodes and the number of dissected nodes was established and called proportion of positivity (positive nodes/ dissected nodes × 100) and this was in turn related to a five year overall survival. Two groups were analyzed: proportion of positivity &gt; than 50% and proportion of positivity &lt; than 50%. Results: A report of 209 patients showing nodes was obtained (59.5%), with a means of 10.4 (rank 0–31) of dissected nodes per patient and a means of positive nodes of 2.4 (rank 0–22). Comparing the two groups the statistic significance starts to be obvious from the 18 months and the difference between the two groups continues increasing until the five years. The survival to five years for the group with the proportion &gt; than 50% was 39% (IC 95% :13.4–64.5) compared to the survival for the group with a proportion &lt; than 50% that was 75.7% (IC 95% :67.6–83.7) p&lt;0.05. Conclusions: The proposal shows that not only is the absolute number of positive dissected nodes as only prognostic indicator (TNM) but also that before nodes dissections with low number of them, it is possible to establish a reliable prognostic relationship by calculating the proportion of positivity. The above said does not consider that the nodal dissection can be less than recommended, on the contrary obtaining the biggest number of nodes will mean bigger equivalence of the proposal and a bigger possibility to detect positive nodes. No significant financial relationships to disclose.
Myoepithelioma (myoepithelial carcinoma) of the breast: Case report
Authors: M. S. Fayaz, S. M. Samir, H. G. Amanguno, A. O. Adesina
Journal: Journal of Clinical Oncology (2008)

12021 Background: Myoepithelial carcinoma of the breast is a rare condition. Here, are 2 cases of malignant myoepithelial documented. Both were 51 year-old Kuwaiti women, presenting with abnormal breast masses. Methods: The first patient underwent mastectomy while the second patient underwent lumpectomy followed by mastectomy for narrow margins. The tumours were clinically, radiologically and macroscopically demarcated. Diagnosis was made based on histological and immunohistochemical studies. Results: Both cases were positive for α-smooth muscle actin, S-100ptn and one case was positive for Vimentin and the other case was positive for Epithelial Membranous Antigen (EMA). From these findings the cases were diagnosed with malignant Myoepithelioma. One case consisted microscopically of tumour cells with clear cytoplasm, possibly making it one of 3 reported cases of clear cell myoepithelial carcinoma. One case locally recurred and metastasized, while the other is still newly diagnosed and under follow-up. Conclusion: Myoepithelial tumours are generally considered benign but do have a spectrum of behaviour with a potential for local recurrence and rarely distant metastases. No significant financial relationships to disclose.
Differences between patient and caregiver ratings of advanced cancer patients' quality of life and correlates of their disagreement.
Authors: Tai Chung Lam, Tracy A. Balboni, Paul K Maciejewski, Holly Gwen Prigerson
Journal: Journal of Clinical Oncology (2014)

9560 Background: Assessment of patient quality of life (QoL) by surrogates, particularly informal caregivers (e.g. spouse), is important to the care of advanced cancer patients. However, accuracy of such surrogate QoL assessments has been questioned. This study sought to assess differences between patients’ QoL self-assessments compared to assessments by their informal caregivers, and to determine characteristics associated with the disagreement. Methods: Data from 570 advanced cancer patient-caregiver dyads participating in the multi-site, Coping with Cancer study were included. Patients assessed their QoL with the McGill QoL questionnaire. Caregivers estimated patients’ QoL using the same questionnaire. Paired t-tests were used to compare the dyadic estimates of QoL scores. Multiple linear regression (MVA) was performed to examine factors potentially associated with the difference in dyadic QoL estimates. Results: Caregivers’ mean age was 53 years, 71% were female, and 51% were spouses. The overall mean patient QoL score, as assessed by caregivers, was lower than the overall mean QoL by patient assessment [6.4 (SD=1.8) vs. 7.1 (SD=1.6), p<.0001]. In MVA assessing factors contributing to patient-caregiver differences in QOL assessment, sociodemographic factors, overall coping, positive religious coping, and interpersonal support were not associated with any significant disagreement. Higher level of caregiver negative religious coping (β=.31, p=.0002) and burden (β=.77, p<.001), lower caregiver self-efficacy (β=-.54, p=.005), higher stressful caregiving adult reactions to experiences of dying scale (SCARED) (β=1.28, p<.0001) and higher patient self-estimated QoL (β=2.92, p<.0001) were significantly associated with greater disagreement between patient and caregiver estimates of patient QoL. Conclusions: Caregiver assessments of patient QoL are underestimated as compared to patient self-assessment. Caregiver factors, including negative religious coping, self-efficacy, burden and SCARED, are associated with patient-caregiver disagreement in estimates of patient QoL, suggesting ways to improve accuracy of caregivers’ evaluation of patient QoL.
Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes
Authors: Swati Naik, Sarah K. Nicholas, Caridad A. Martinez, Ann M. Leen, Patrick J. Hanley, Steven M. Gottschalk, Cliona M. Rooney, I. Celine Hanson, Robert A. Krance, Elizabeth J. Shpall, Conrad R. Cruz, Persis Amrolia, Giovanna Lucchini, Nancy Bunin, Jennifer Heimall, Orly R. Klein, Andrew R. Gennery, Mary A. Slatter, Mark A. Vickers, Jordan S. Orange, Helen E. Heslop, Catherine M. Bollard, Michael D. Keller
Journal: Journal of Allergy and Clinical Immunology (2016)
Genistein synergizes with fludarabine to induce apoptosis in ex-vivo chronic lymphocytic leukemia cells
Authors: A. Mansour, J. S. Harrison, V. T. Chang, S. Srinavas, E. Raveche
Journal: Journal of Clinical Oncology (2004)

3193 Background: Genistein, a soy isoflavone, inhibits tyrosine kinase and exerts anti proliferative effects. B-CLL is characterized by a defective apoptosis mechanism rather than increased cell proliferation. This raised the possibility that CLL cells over express specific anti apoptotic proteins and cytokines which may contribute to decreased sensitivity to chemotherapeutic drugs. The objective of this study is to characterize the effects of fludarabine and genistein on CLL cells as part of a program to develop new therapeutic approaches for CLL Methods: Peripheral blood mononuclear cells (PBMC) or bone marrow (BM) mononuclear cells were obtained from patients with CLL as well as from healthy donors. Cells were treated with Genistein 60μM(G60) or 30μM(G30), fludarabine 3μM(F), or a combination of both for 48–72hrs. Cell cycle distribution was analyzed by flow cytometry using FACS analysis after PI staining. Expression of the anti apopotic genes survivin and bcl-2, the cyclin dependent kinase inhibitor p21, and IL-10 were assessed by PCR. Plasma level of IL-10 was determined by ELISA. Results: There were 11 patients with CLL, 1 pt with prolymphocytic leukemia, one with pre-T cell ALL, and one with Waldenstrom's macroglobulinemia. The median age was 66 years (range 52–81) and of the CLL patients, 9 pts (81%) were stage zero and had not been previously treated. Treatment with G60 alone resulted in decreased expression of Survivin and bcl-2 (P= 0.1 and 0.01 respectively) whereas p21 was up regulated (P<0.01). Both the combination of G60+F and the combination of G30+F resulted in significant induction of apoptosis(P< 0.01and 0.04 respectively), even in cells from a patient with fludarabine resistance. The controls showed little or no apoptosis induction. Conclusions: In ex-vivo CLL cells, genistein showed activity as a cell cycle regulator and apoptosis inducer. Furthermore, it sensitized CLL cells to fludarabine. Studies are warranted to explore the role of genistein in the management of CLL. No significant financial relationships to disclose.
Temozolomide (TMZ) 1 week on/1 week off as initial treatment for progressive low grade oligodendroglial tumors: A phase II AINO study
Authors: R. Soffietti, R. Rudà, E. Trevisan, E. Laguzzi, D. Guarneri, C. Bomprezzi, M. Caroli, B. Leoncini
Journal: Journal of Clinical Oncology (2008)

2019 Background: Protracted low dose TMZ offers potential advantages over standard TMZ, including greater cumulative drug exposure and depletion of MGMT. Few data are available on the efficacy and tolerability of protracted low dose TMZ in patients with low grade gliomas. Methods: In this ongoing phase II study, patients with progressive low grade oligodendroglial tumors after surgery are eligible. TMZ is administered orally at 150 mg/m2/d, days 1–7 and 15–21 every 4 weeks, up to 18 cycles or tumor progression or unacceptable toxicity. Patients undergo clinical and MRI assessment every 4 and 8 weeks respectively, and a monitoring by PET with methionine (every 6 month) is performed in selected centers. The primary endpoint is response (based on FLAIR sequences), and secondary endpoints are progression free-survival (PFS) at 6 mos and 12 mos, median PFS, quality of life and toxicity. The analysis of 1p/19q status by FISH and MGMT promoter methylation by PCR are mandatory. Results: Of the first 31 patients enrolled since 2005, 25 are evaluable for response (median age 41, median KPS 90, and 36% with mild enhancement on MRI). Pathological diagnosis was oligodendroglioma (15) and oligoastrocytoma (10).The response rate was 52% (13/25) with PR 32% and MR 20%, and disease control rate (PR+MR+SD) was 92%. Median time to maximum radiographic response was 6 months; 2 patients had an early response (within the first 2 months), whereas 1 patient had a delayed response up to 6 months after interruption of treatment. Eleven of 17 (65%) patients improved, particularly those with seizures. Twenty of 25 patients are free from progression with a median follow-up of 14 months (range 4–39). Combined 1p/19q or isolated 1p deletion was not associated with response on FLAIR images, but only with response of the enhancing tumor. Grade 3 lymphopenia was observed in 45% of patients, and 15% interrupted the treatment or were changed to standard TMZ. Conclusions: TMZ 1 week on/1 week off, as initial treatment for progressive low grade oligodendroglial tumors, seems more efficacious than standard dose TMZ, and is relatively safe. Updated results, correlation between MGMT promoter methylation, 1p/19q loss and response, and monitoring with PET will be presented. No significant financial relationships to disclose.
Immunotherapy with intraperitoneal catumaxomab in patients with advanced ovarian cancer after a complete response to chemotherapy: A phase II study.
Authors: R. W. Holloway, M. Roche, L. DeMars, J. A. Williams, A. Enke, A. Klein, R. G. Linke, C. N. Krasner
Journal: Journal of Clinical Oncology (2010)

5015 Background: While most patients with advanced ovarian cancer respond to standard chemotherapy following surgery, relapses are common. In previous studies in patients with malignant ascites the trifunctional antibody catumaxomab demonstrated the ability to destroy EpCAM-positive tumor cells in the peritoneal cavity. This study was conducted primarily to evaluate the safety and tolerability of intraperitoneal (IP) catumaxomab in the consolidation setting for patients with minimal residual disease. Methods: 47 patients with advanced ovarian cancer (FIGO stage IIb-IV) with a complete response to standard chemotherapy were included in this single-arm study. For each patient a four-dose series of IP catumaxomab infusions was attempted, consisting of 10, 20, 50, and 150 μ g, respectively, by constant-rate 3-hour infusion. The primary objective was to assess the safety and tolerability of administering the planned catumaxomab therapy within a 21-day period. Patients were followed for safety for 90 days after treatment and then for 24 months post-study. Results: 32 patients (68.1%) received all 4 infusions, and 29 (61.7%) completed the four-dose series of catumaxomab infusions within 21 days. Among the 37 patients (78.7%) who received more than one infusion, 32 (86.5%) received all of the planned infusions. At sites where more than 2 patients were treated, 30 of 40 patients (75%) received all infusions within 21 days. All patients experienced at least 1 treatment-emergent adverse event (AE) assessed as related to study drug (731 total events). Most common AEs were nausea, pyrexia, vomiting and abdominal pain. AEs decreased with subsequent infusions; only 1 patient had a grade ≥ 3 AE after the fourth infusion. Kaplan-Meier estimates of PFS and OS at 24 months post treatment were 26.3% and 80.3%, respectively. Conclusions: IP catumaxomab appears tolerable as a consolidation regimen, with results reflecting data from other studies of this drug in early and late-stage ovarian cancer. While AEs were more frequent in this study, they were similar in nature to those in previous studies of this drug. Tolerability of the four-dose regimen was higher at sites where more patients were treated. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Fresenius Biotech, Fresenius Biotech GmbH AstraZeneca, Lilly Fresenius Biotech
Initial therapeutic strategy in follicular lymphoma (FL): An analysis from the National LymphoCare Study (NLCS)
Authors: J. W. Friedberg, J. Huang, H. Dillon, C. Farber, S. Feliciano, J. Hainsworth, B. Link, R. Steis, J. Vose, A. Zelenetz
Journal: Journal of Clinical Oncology (2006)

7527 Background: Initial treatment strategies in FL include observation (obs), rituximab (R), chemotherapy ± R, and XRT. A recent study suggests initial therapy may impact FL survival (JCO 23:8447). NLCS is the first prospective observational study in the US designed to assess FL presentation, prognosis, treatment, and clinical outcomes. We describe initial therapeutic strategy in NLCS FL pts. Methods: FL pts diagnosed within 6 months with no prior lymphomas were recruited in this ongoing study. Data collected includes histology, stage, therapy, response, relapse and death. There is no specified treatment regimen. Results: From 3/04 to 11/05 1493 pts enrolled at 237 sites in the United States. Demographics have been initially reported at ASH 2005 (Blood 106:293a) and are comparable to SEER. Initial therapeutic strategy was: obs, 19%; R-monotherapy, 13%; chemo+R, 51%; XRT, 5%; chemo only, 4%. Chemo+R regimens were: R-CHOP, 59%; R-CVP, 19%; R-fludarabine based,11%; other, 11%. Choice to initiate therapy was associated with FLIPI, stage, and grade (p &lt; 0.0001). Significant regional differences (p &lt; 0.0001) were noted: obs was used in 13% of pts in Southeast and 31% in Northeast (NE); fludarabine-based R-chemo was used in 18% of pts in Southwest and only 3% in NE. Academic sites were more likely than community sites to treat pts on clinical trials (12% vs 4%). In pts treated with R or chemo+R, a higher FLIPI was not associated with decision to utilize chemotherapy. 26% of initially observed pts have switched to active therapy after a median of 2.8 months on obs since diagnosis; this was associated with baseline grade (III&gt;II&gt;I), but not stage or FLIPI. Conclusions: Diverse regimens are used for initial management of FL in the United States. Few pts are treated on clinical trials. Significant differences among regions and between center types suggest physician preference may drive initial therapy. Studies such as NLCS are needed to better understand the impact of initial therapy on short- and long-term outcomes. [Table: see text]
Molecular analysis of tamoxifen-resistant pathways in breast cancer cell-lines and breast cancer tissues
Authors: C. Yeoh, C. Chelala
Journal: Journal of Clinical Oncology (2009)

e22094 Background: Oestrogen receptor positive (ER+) breast cancer (BC) is heterogeneous with regard to their clinical behaviour and response. The ER and Progesterone receptors (PgR) are currently the best predictors of response to the anti-oestrogen agent tamoxifen, yet up to 30–40% of ER+ breast cancers will relapse despite tamoxifen treatment. New prognostic biomarkers and further biological understanding of tamoxifen resistance is required. There has been an explosion of greater understanding since the arrival of new cutting-edge genomic profiling technology. Methods: RNA from the BC cell lines and frozen tissue was extracted and qualified using Qiagen Mini Kit and BioAgilent respectivelly. Probe preparation and scanning of the chips were carried out according to Affymetrix protocol. The normalisation and analysis of data (Limma) was performed using Bioconductor software. RT- PCR probes were purchased from Applied Biosystem and performed on ABI7500 instrument. The IHC-P was done using Ventana. TMA prepared with TMABooster, Alphelys (Plaisir, France). Results: Gene expression changes were studied in the TR breast cell lines MCF7 (tenovus), T47D and ZR by using the Affymetrix Hu133 plus 2.0 platform. Common genes of significant expression from the 3 TR cell lines were validated by real-time PCR (RT-PCR) and immuno-histochemistry (IHC-P) staining. 7 (MAGEA2, AKR1C3, VGLL1, THRAP5, GREB1, PDZK1, MYBL1, HnRNPA2B1, PGR) out of the 9 chosen genes were successfully validated. Proliferation studies on MageA2 overexpressing clones were performed. Stable overexpression of MageA2 in T47D and MCF-7 confers a proliferation advantage in tamoxifen-containing media as shown in proliferation and cell cycle analysis. MageA2 has been shown to alter the p53 pathway. The expression of KAP1, which interacts with p53 and inactivates it, was enhanced by MageA2 overexpression. In addition, overexpression of MageA2 is seen to increases histone deacetylase (HDAC3), and p53 expression as seen by immunoblotting. Validation of MageA2 on TMA of 100 patients is underway. Conclusions: MageA2 is a possible selective molecular target for the reversal of tamoxifen resistance. No significant financial relationships to disclose.
Exercise related desaturation in patients with COPD - Another step towards phenotyping the disease
Authors: Roman Kalinov, Vladimir Hodzhev, Blagoi Marinov, Stefan Kostianev
Journal: European Respiratory Journal (2013)

Desaturation during 6MWT is considered as an important predictor of mortality in COPD patients.  Aim: To investigate relationship among exercise related desaturation (6MWT), symptoms, spirometric indices and number of exacerbations within last year (risk assessment).  Patients and methods: Fifty patients (age 64.5 ± 9.2; BMI 24.6±4.5; smoking pack/years. 39.0 ± 23.3) had lung function assessment and exercise test (6MWT). Desaturation was considered when SpO2 dropped ≥4% for at least 3 min.  Results: All patients had marked airway obstruction (FEV1% = 40.8 ± 13.8; KCO% = 76.0 ± 27.9; PO2 = 64.4 ± 9.7mm Hg), moderately decreased functional capacity (6MWT 492 ± 91m.) and high symptom scores (MRC = 2.3±1.0 ; CAT = 21.4 ± 7.5). They were divided in two groups according to their exercise SpO2 – without desaturation (A; n=24) and with desaturation (B; n=26). The two groups differed significantly with regard to FEV1% 47.9±12.4 vs 34.2±11.8; p = 0.001; KCO% 90.8±22.4 vs 63.4±26.1 p  Conclusion: Desaturation in patients with COPD is associated with deterioration in lung function but not with symptom severity and number of exacerbations in the last year. Presumably, the patients with exercise (6MWT) related desaturation represent separate phenotype of COPD.
Delaying cord clamping is linked to improvements in fine motor skills
Authors: J. Wise
Journal: BMJ (2015)

Delaying clamping the umbilical cord for around three minutes is associated with better fine motor function and social skills in children at the age of 4 years, a randomised controlled trial has found.1

Delaying umbilical cord clamping by two to three minutes after delivery allows fetal blood remaining in the placental circulation to be transfused back into the newborn baby. It has previously been shown to produce higher haemoglobin concentrations after birth and increased iron stores until 6 months of age. However, there has been little evidence …