tbuckley/cabot-search huggingface dataset:
Are you sure to definitely rule out pleurecomy/decortication plus chemotherapy from treatment of malignant pleural mesothelioma? Our experience with 40 cases
Authors: P. Manente, F. Colaut, L. Toniolo, G. Vicario, L. Sartor, M. Bortolin, P. Visentin, C. Scapinello, C. A. Sartori
Journal: Journal of Clinical Oncology (2004)

7320 Background: MPM prognosis remains dismal.Surgical resection associated with CT + RT,seems to improve overall survival of MPM in well- selected patients.Despite of good patients selection and multimodality approach local disease control remains a no-solved problem. Methods: Since 1985 to 2002 40pts with MPM were submitted pleurectomy/decortication combined to intracavitary chemotherapy.Until 1994 intracavitary chemotherapy consisted of Cisplatinum + Ara C(18 pts treated). Later IFN alfa 2a replaced Ara C (22 pts treated).Treated patients were:28 male and 12 female, age max 78 ys old min 38,mean age 60 ys.Surgery consisted of pleurectomy performed to remove all gross tumor. Histology:22 epithelia subtype,11 mixed,7 sarcomatous. PS: all pts were<or=to 2 according ECOG scale.25 pts received systemic chemotherapy:16 pts Adryamicin and Mytomicin until 1994.4 pts Carboplatin and IFN alfa since 1995 to 1996.Successively 5 pts received Carboplatin and Gemcitabin.15 pts didn't receive systemic chemotherapy owing to comorbidities. Results: Post-operative staging was performed according to TNM by IMIG 1995 .24pts were stage I,7 pts stage II,4 pts stage III,5 pts stage IV. Kaplan-Meier method demonstrated 2ys and 3-ys overall survival was respectively 28% and 17%.After 2ys from intervention only 14% of pts had no PD.Histology has been a significant (p=0.047) prognostic factor for survival but not for PD.After 2ys from intervention 20% of pts with epithelial subtype and 10% of pts with mixed histology had PD, while sarcomatous pts had PD after only 8 mos from intervention.T was not a significant prognostic factor even if 54% of Tla/1b pts (24 pts) had PD after 6 mos from intervention,while 65% of T2/T3/T4 pts (16 pts) had PD before 6 mos yet. Complications:2pts had renal failure.Life quality was satisfactory as well. Conclusions: Results will certainly improve if following requests are satisfied: 1Optimal diagnosis and pre-operative staging(VATS,MR,PET). 2Initial disease(stage Ia and Ib according IMIG). 3Epithelial histology. 4No comorbidities. 5Performance status < or = 2 according ECOG scale. No significant financial relationships to disclose.
2<sup>nd</sup> line chemotherapy for patients with malignant mesothelioma (MPM) pretreated with pemetrexed (PMTX) and platinum (P)
Authors: M. Karthaus, F. Frieler, A. Plahl, N. Wert, K. Tagizadeh, D. Metzner
Journal: Journal of Clinical Oncology (2005)

7331 Background: PMTX + P based Ctx is considered standard care for advanced MPM. Although substantial improvement has been achieved with this Ctx doublet, time to progression and overall survival remain short. 2nd line Ctx in pts pretreated on a PMTX based combination has not been evaluated. Methods: We analyzed 67 consecutive pts (54 m/ 13 f) pretreated with PMTX (500 mg/m2) +/-CDDP (75 mg/m2) or carboplatin (AUC 5) regarding 2nd line Ctx for MPM between 12/2002 and 11/2004. All pts were treated at the Ev. Johannes Hospital Bielefeld. Response and survival data of pts receiving 2nd line Ctx were evaluated. Survival was compared with those pts receiving best supportive care (BSC). Results: Out of 67 pts 52 did not receive any 2nd line Ctx. This was due to death from MPM during 1st line Ctx in 32 pts. There was no further need for 2nd line Ctx in 20/52 which were alive and in stable disease (SD) at the end of 11/2004. Three out of these 20 pts were in continuous SD without any further treatment after a median of 6 cycles of 1st line Ctx. 2nd line Ctx was given in 10/67 pts (9 m/1f; mean age 67 ys). This was gemcitabine (1000 mg/m2 d1,8,15 repeated d29) based in 9/10 pts. In one pt PMTX + carboplatin was reintroduced due to progression of MPM 6 months after the end of 1st line Ctx. SD in pts with 2nd line Ctx was observed in 2 pts, while 8 pts progressed on 2nd line Ctx. BSC was given in 5/67 pts (4 m/1 f; mean age 52 ys) following progression after end of 1st line Ctx. Death due to MPM was observed in 6/10 pts receiving 2nd line Ctx and in 3/5 pts with BSC. Median survival in pts receiving BSC was 5 months (range 2 to 15+). Similar survival was observed with 2nd line Ctx (5 months, range 1 to 16+). Final data on TTP and survival in pts receiving 2nd line Ctx for MPM will be presented at the meeting. Conclusions: 2nd line Ctx or BSC was administered in 22,3% of MPM pts failing or relapsing PMTX based 1st line Ctx. Efficacy of 2nd line Ctx was 20% with SD as best response. Our data underline the need for randomized trials evaluating 2nd line Ctx in PMTX pretreated MPM pts. No significant financial relationships to disclose.
Phase III comparative evaluation of PCNU and carmustine combined with radiation therapy for high-grade glioma.
Authors: R P Dinapoli, L D Brown, R M Arusell, J D Earle, J R O'Fallon, J C Buckner, B W Scheithauer, J E Krook, L K Tschetter, J A Maier
Journal: Journal of Clinical Oncology (1993)

PURPOSE We performed a randomized trial to compare survival distributions and toxicity of radiation therapy (RT) and PCNU with those of RT and carmustine (BCNU) in patients with malignant glioma. PATIENTS AND METHODS A total of 346 patients with histologically verified supratentorial grade 3 and grade 4 astrocytoma were studied. After surgery, patients were randomly assigned to receive RT 60 Gy in 30 fractions and either PCNU 100 mg/m2 or BCNU 200 mg/m2 every 7 weeks for 1 year and every 10 weeks for the second year. RT and chemotherapy were started within 72 hours of randomization and usually on the same day. Of 334 assessable patients, 72% had partial or radical resection and 71% had grade 4 tumors. Median age was 59 years, and 85% had performance scores of 0 to 2 (Eastern Cooperative Oncology Group [ECOG]). The follow-up duration of 51 living patients ranged from 10.3 to 63.2 months, with a median of 36.2 months. RESULTS The median survival duration in each group was 47 weeks, and median time to progression was 28 weeks. PCNU produced significantly more leukopenia and thrombocytopenia, whereas BCNU produced significantly more nausea, vomiting, and irritation. CONCLUSION PCNU has no therapeutic advantage at this dose and schedule and does not warrant further study as a single agent for patients with high-grade glioma.
Results of a phase II study of 131 Iodine-labeled anti-tenascin murine monoclonal antibody 81C6 (m81C6) administered to deliver a targeted radiation boost dose of 44 Gy to the surgically created cystic resection cavity perimeter in the treatment of patients with newly diagnosed primary and metastatic brain tumors
Authors: J. J. Vredenburgh, D. Reardon, G. Akabani, A. Friedman, H. Friedman, R. McLendon, J. Quinn, J. Rich, M. Zalutsky, D. Bigner
Journal: Journal of Clinical Oncology (2005)

1510
New entity of an isolated pulmonary non-Langerhans cell histiocytosis
Authors: Michael Kreuter, Claus Peter Heussel, Christian Nagel, Richard P. Baum, Philipp A. Schnabel, Felix J.F. Herth, Dirk Theegarten
Journal: European Respiratory Journal (2013)

Background: Histiocytic disorders are rare, heterogeneous diseases with abnormal tissue infiltration by histiocytes. So far, pulmonary manifestation in Non-Langerhans cell histiocytoses (NLCH) occurred only as a part of a systemic disease.  Case: A 37 year old male stonesculptor suffered from progressive dyspnea and thoracic tightness. He was admitted under suspicion of pulmonary capillary hemangiomatosis (PCH). Asthma was diagnosed 6 years ago and he had a former smoking history of 5 pack years. Pulmonary function testing demonstrated obstructive lung disease (FEV1 48%) with negative bronchospasmolysis and compromised diffusion capacity (DLCO 50%, KCO 54%). Cardiopulmonary exercise testing showed a maximum work load of 150 W with VO2peak 20 ml/min/kg (56%). Surgical lung biopsies excluded PCH and revealed interstitial histiocytic infiltrates. These showed immunohistochemical positivity for CD68 and negativity for CD1a and Langerin, therefore NLCH was diagnosed. CT and metabolic imaging with F-18 FDG PET/CT scanning -as used diagnosing manifestation in Erdheim-Chester disease- demonstrated bipulmonary, FDG-avid nodular infiltrates and excluded extrapulmonary manifestations. After multidisciplinary discussion a watch and wait strategy was chosen. The patient is currently stable since 18 months with regards to clinical, functional and radiological parameters.  Conclusion: Here we describe a new entity of an isolated pulmonary NLCH. Clinical, patho- & radiological features are not consistent with any other NLCH reported so far. The association with asthma might be coincidental. The etiopathogenesis is unclear and might however be occupational or smoking-related in this case. Long term prognosis seems to be dubious.
The efficacy of systemic lymphadenectomy for overall survival in epithelial ovarian cancer: A systematic review and meta-analysis by KOGYMAG
Authors: H. Kim, W. Ju, B. Jee, J. Kim, Y. Song, H. Lee
Journal: Journal of Clinical Oncology (2009)

e16509 Background: The role of systemic lymphadenectomy remains unclear for improving overall survival in epithelial ovarian cancer (EOC) till now. To evaluate the efficacy of systemic lymphadenectomy for survival in EOC, Korean Gynecologic Meta-analysis Group (KOGYMAG) performed a meta-analysis of all studies which compared systemic lymphadenectomy versus non-systemic lymphadenectomy (not performed or lymph node sampling). Methods: Studies were retrieved by searching PubMed, Embase, and Cochrane Controlled Trials Register (CENTRAL) electronic database. The literature search was conducted between 1995 and 2008. The meta-analysis was carried out on 11 studies (2 randomized controlled and 9 retrospective studies) and a total of 30,534 patients with EOC who underwent staging laparotomy including systemic lymphadenectomy or nonsystemic lymphadenectomy. The study endpoint was overall survival, and we extracted adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival from all studies and obtained pooled estimates using an inverse-variance model. Results: In all studies, systemic lymphadenectomy was a favorable factor for overall survival as compared to non-systemic lymphadenectomy (HR, 0.76, 95% CI, 0.65 to 0.88; random-effects model). When we performed sub-analysis according to disease status, patients treated with systemic lymphadenectomy showed improved overall survival compared to those with non-systemic lymphadenectomy in 3 studies where only patients with early-stage EOC (FIGO stage I-II) were included (HR, 0.70; 95% CI, 0.63 to 0.77; fixed-effects model). Furthermore, systemic lymphadenectomy was also a significant factor for improved overall survival in 5 studies where only patients with advanced-stage EOC (FIGO stage III-IV) were enrolled (HR, 0.91; 95% CI, 0.85–0.96; fixed-effects model). Conclusions: These results support that systemic lymphadnectomy may improve overall survival in patients with EOC. However, there are some limitaions including few randomized controlled studies and the deviation of weight in this meta-analysis. Thus, large-scale randomized controlled trials are required to evaluate the efficacy of systemic lymphadenectomy in EOC. No significant financial relationships to disclose.
Randomized phase III trial of sorafenib in advanced renal cell carcinoma (RCC): Impact of crossover on survival
Authors: T. Eisen, R. M. Bukowski, M. Staehler, C. Szczylik, S. Oudard, W. M. Stadler, B. Schwartz, R. Simantov, M. Shan, B. Escudier
Journal: Journal of Clinical Oncology (2006)

4524 Background: Sorafenib was approved for advanced RCC in the USA December 2005. A Phase III randomized double-blind, placebo-controlled trial demonstrated an estimated 39% improvement in survival for patients receiving sorafenib versus placebo (HR= 0.72, p = 0.018) (ECCO 2005). These data supported independently reviewed doubling of PFS to 24 weeks in RCC patients receiving sorafenib compared with placebo (12 weeks) (p &lt; 0.000001) (ASCO 2005). Based on the statistical significance and magnitude of PFS benefit, patients were unblinded and placebo patients allowed to crossover to sorafenib in April 2005. A prospectively planned interim OS analysis reflecting impact of crossover of placebo patients is presented. Methods: OS data up to November 30, 2005, were analyzed in this interim analysis using a stratified log-rank test comparing the two treatment groups. In order to examine the effect of crossover on OS, a secondary analysis was performed censoring data from patients randomized to placebo at June 30, 2005. Results: A total of 903 patients were randomized (451 to sorafenib, 452 to placebo) and &gt;200 placebo patients crossed over to sorafenib. Baseline characteristics were similar between treatment arms. There were 367 deaths. The median OS was 19.3 months for sorafenib versus 15.9 months for placebo (HR = 0.77; 95% CI 0.63, 0.95; p = 0.015); although this did not attain the level of significance specified for the interim analysis (α = 0.009), a continued favorable trend in survival benefit was observed. With censoring of crossover data, the median OS was 19.3 months for sorafenib versus 14.3 months for placebo (HR = 0.74, 95% CI 0.58, 0.93; p = 0.010). Conclusion: Sorafenib is the first novel, oral approved treatment for advanced RCC in more than a decade. Previous information on the effect of crossover on OS in randomized oncology studies is limited. The lower HR observed after censoring placebo patients crossed over to sorafenib suggests a continued beneficial effect of sorafenib. Final results await more mature data. [Table: see text]
Low dose docetaxel, estramustine and thalidomide followed by maintenance thalidomide for the treatment of hormone refractory prostate cancer (HRPC): A phase II community based trial
Authors: R. C. Frank, A. Coscia, L. Versea, N. Cohen, R. Zelkowitz, A. Ruskin, A. Skeris, P. Dodds, K. Nair
Journal: Journal of Clinical Oncology (2004)

4681 Background: Elderly men in the community often have co-morbidities that limit their ability to tolerate standard doses of chemotherapy. This trial was designed to minimize exposure to chemotherapy by exploiting its potential synergy with anti-angiogenesis agents and to evaluate the role of maintenance anti-angiogenic therapy. Methods: Eligible patients had progressive HRPC after hormone therapy and antiandrogen withdrawal, adequate performance status (0–2) and no prior treatment with chemotherapy or angiogenesis inhibitors. All patients received the TET regimen: Docetaxel (Taxotere) 25 mg/m2 weekly for 3 weeks per month, Estramustine 140 mg po tid x 3 days per week beginning the day before Taxotere, and daily Thalidomide (Thal) 100 or 200 mg as tolerated. TET was given for six months followed by six months of Thal alone as maintenance therapy. Coumadin 2 mg per day was given for prophylaxis. Results: 12 patients have been enrolled thus far. The median age is 76 (55–85), median PS 1 (0–2), and median PSA 83 (24–377). Metastases were present in bone in 10/12 (83%) and in lymph nodes in 7/12 (58%). 9 patients (pt) are evaluable for response after a minimum 3 cycles of treatment. PSA was reduced ≥50% in 6/9 (67%), ≥75% in 4/9 (44%), and normalized in 2/9 (22%). Of the 5 pts with measurable disease, 2 had PR (40%) and 2 SD. Two patients entered the maintenance phase: one completed 6 months and experienced an additional 9 months of stable disease, the other relapsed after 4 months on Thal. Grade 3 toxicities included asthenia (2 pt) and constipation (1 pt.), all other toxicities were grade 1–2. There was one DVT and one patient died of hepatic toxicity complicated by prior alcoholism. Conclusions: The TET regimen is safe and appears effective for HRPC; the ability of thalidomide to maintain remissions awaits further study results. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Pharmaceuticals; Celgene Corp.
Longitudinal Study of Adaptation to the Stress of Bone Marrow Transplantation
Authors: Betsy L. Fife, Gertrude A. Huster, Kenneth G. Cornetta, Victoria N. Kennedy, Luke P. Akard, E. Randolph Broun
Journal: Journal of Clinical Oncology (2000)

PURPOSE: This prospective longitudinal study of adaptation to bone marrow transplantation (BMT) addressed three questions: (1) When during BMT do individuals experience the greatest distress? (2) What factors are associated with this distress? (3) Are there variables that could be potential clinical indicators of persons in greatest need of preventive intervention? PATIENTS AND METHODS: One hundred one participants undergoing either an autologous or allogeneic BMT completed questionnaires before hospitalization, before bone marrow infusion, 7 days and 14 days after transplantation, and then 1 month, 3 months, and 12 months after hospitalization. Adaptation was indicated by the degree of emotional distress. Independent variables were personal control, social support from specific sources, cognitive response, self-perception, and coping strategies, controlling for symptomatology. RESULTS: The greatest emotional distress occurred after admission to the hospital and before the bone marrow infusion. Anxiety and depression decreased 1 week after the transplant, although symptomatology increased during this time. The periods of least emotional distress were 3 months and 1 year after transplantation. Factors that accounted for the greatest variance in emotional distress/adaptation were the degree of emotional distress at baseline, personal control, cognitive response, and symptomatology. CONCLUSION: According to this longitudinal study, which includes pretransplant data, data from in-hospital transplantation, and posttransplant data, (1) psychosocial vulnerability of these BMT recipients was greatest during hospitalization before the transplant, (2) perceived personal control may be a potential indicator of vulnerability to secondary psychosocial morbidity, and (3) the demonstrated significance of psychosocial well-being before BMT indicates the importance of obtaining prospective data for both research and clinical purposes.
Abstract 15245: COUP-TFII Determines the Atrial Identity Through Regulation of Multiple Pathways
Authors: San-Pin Wu, Chiang-Min Cheng, Chung-Yang Kao, Rainer B Lanz, Xander H Wehrens, Ming-Jer Tsai, Sophia Y Tsai
Journal: Circulation (2013)

Emerging evidence reveals the presence of plasticity in cardiomyocytes that allows them to be reprogrammed into atrial, ventricular or nodal fates. We show that Chicken Ovalbumin Upstream Promoter ...
Use of tumor size decrease at 6 weeks (w) to predict response (OR), time to progression (TTP), and survival (OS) in chemorefractory metastatic colorectal cancer (cmCRC) treated with cetuximab (CTX) (BOND trial)
Authors: H. Piessevaux, W. De Roock, E. Van Cutsem, S. Tejpar
Journal: Journal of Clinical Oncology (2008)

4068 Background: We previously reported that patients (pts) with cmCRC treated with CTX + irinotecan (IRI) showing tumor shrinkage >9.66% at 6 w had a significantly better progression-free survival and OS (De Roock 2007). There was a strong correlation between early size decrease and KRAS status of the tumor. Aim: To evaluate in an independent series the performance of this criterion as a predictor for TTP and OS in crmCRC treated with CTX. A secondary aim was to study the robustness of the quantitative tumor size evaluation. Methods: Data was extracted from the anonymized BOND trial database (Cunningham 2004). Of the 329 ITT pts, 292 had a measurement both at w 0 and at w 6 (192 CTX + IRI and 100 CTX). Tumor shrinkage was expressed as a relative decrease of the sum of the longest diameters of the target lesions to baseline (RECIST). The agreement between the measurements of 2 central reviewers (rev) was assessed by the intraclass correlation coefficient (ICC). The agreement between early tumor shrinkage statuses was evaluated using a kappa statistic. Kaplan-Meier plots were constructed for TTP and OS and compared with the Log rank test. Results: W 6 tumor shrinkage and OR, as assessed by the investigators, were significantly correlated (χ²; P<0.0001). In OR pts, 34/62 (55%) had a time to response beyond 6 w. The median TTP was 6.3 (95%CI 5.1–7.5) and 1.5 months (95%CI 1.4–1.6) in patients with or without w 6 tumor shrinkage (HR: 4.5 (95%CI 3.3–6.2). Similarly, the median OS was 13.7 (CI NA) and 6.8 months (95%CI 6.1–7.6) (HR: 5.0 (95%CI 3.3–7.4)), respectively. The PPV and NPV for OS above median were 82.2% and 62.3%. The measurements were highly concordant between both rev (ICC: 0.980 (95%CI 0.975–0.985) both at w 0 and w 6). There was a good agreement between central rev and the investigators measurements (ICC: 0.629 (95%CI 0.552–0.696)) and classification (kappa=0.661 (SD=0.048)). There was no difference between pts treated with CTX alone or in combination with IRI in any of the analyses. Conclusions: Tumor shrinkage > 9.66% at w 6 is a reliable tool to predict TTP and OS in cmCRC pts treated with CTX±IRI. This finding may be exploited in early discontinuation/crossover trials. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck Merck, Merck Serono
Expression of tumor-associated antigen C-terminal binding protein-2 in epithelial ovarian tumors and effect on response to HDAC inhibitors in vitro.
Authors: L. M. Barroilhet, J. Yang, K. Hasselblatt, W. Welch, R. S. Berkowitz, S. Ng
Journal: Journal of Clinical Oncology (2010)

5079 Background: Tumor-associated antigens may have mechanistic function in cancer development. Antibodies to CtBP-2, a component of Wnt signaling pathway that interacts with histone deacetylases (HDACs), were identified in patient serum using an innovative reverse capture array method. Methods: CtBP-2 expression was studied in 105 ovarian tumors by immunohistochemistry (IHC). Functional assays were performed with human ovarian cancer cell lines SKOV3 and MCAS that integrated a CtBP2-targeting short-hairpin RNA (shRNA) construct. Protein expression was examined by western blotting. Cell proliferation was evaluated by cell counting. Adhesion to extracellular matrix was evaluated using a CytoMatrix Screen kit from Millipore. Cell migration assays were performed with a Boyden chamber-based assay. ß-catenin activity was measured using a TOPFLASH luciferase reporter assay. Cellular sensitivity to HDAC inhibitors was measured using MTT assay. Results: 83% of ovarian epithelial tumors stained positive with a mean score of 4.77 (borderline tumors) and 5.49 (invasive tumors) and showed a significant difference (p- value < 0.001) when compared with normal and benign ovarian tissues that had a mean score of 0.33 and 1.15, respectively. A panel of 17 ovarian cancer cell lines showed elevated levels of CtBP2 protein by Western analysis. Cancer cell lines harboring CtBP-2 shRNA constructs showed reduced expression of CtBP-2 by > 75% and showed reduced proliferation rates. The knock-down cell lines also showed 40%-80% reduction in adhesion to extracellular matrix proteins collagen I and collagen IV, 50%-70% reduction in cell migration capacity, suppressed ß-catenin activity, and enhanced sensitivity to the HDAC inhibitors trichostatin A, M344, and splitomycin. Conclusions: CtBP-2 is overexpressed in ovarian tumors and cancer cell lines. Ovarian cancer cell lines with CtBP-2 knockdown show a reduction in proliferation rate and cell migration, which may be related to suppressed ß-catenin activity. Knockdown cell lines are also more sensitive to specific HDAC inhibitors, suggesting that CtBP-2 might modulate cellular response to HDAC inhibitors. No significant financial relationships to disclose.