tbuckley/cabot-search huggingface dataset:
“We Understand the Prognosis, but We Live with Our Heads in the Clouds”: Understanding Patient and Family Outcome Expectations and Their Influence on Shared Decision Making
Authors: Laura C. Feemster, J. Randall Curtis
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

should be noted that a dose of only 50 mg losartan was used in this study, which is not likely high enough to completely antagonize angiotensin.Third, the effect of treating sleep apnea with CPAP continues to have a relatively small effect on BP when all patients are considered, as has been reported previously (3, 6).The difference in BP between the CPAP-treated patients and those receiving no additional therapy was 4.4, 1.9, and 2.5 mm Hg for 24-hour systolic, diastolic, and mean arterial pressure.However, these effects were somewhat larger for the group of patients who used CPAP for more than 4 hours per night (6.5, 3.8, and 4.6 mm Hg for systolic, diastolic, and mean arterial BP).These later values represent a more substantial and clinically important reduction in BP.Thus, the question arises as to whether treating obstructive sleep apnea is an effective method of reducing BP in a hypertensive patient with OSA who is otherwise asymptomatic.I believe this study would suggest that the answer to this question remains "maybe."Only 13% of the patients with OSA achieved optimal BP control on losartan alone, recognizing, however, that only a starting dose of the medication was used.This optimal BP control went up to 25% of patients when CPAP was added, and 38.5% when CPAP was used "adequately" (more than 4 h per night).Thus, most of the patients with OSA in this study would require a higher dose of losartan or the addition of a second antihypertensive drug, even while using CPAP.As we all know, getting patients to use CPAP is a difficult task ( 7), particularly if we are talking about regular CPAP use for the rest of the patient's life, which would be the case if the treatment of hypertension is the goal.However, adherence with long-term pharmacologic management of hypertension is not easy as well.A recent study reported that 12.7% of hypertensive patients were taking none of their antihypertensive medication, and 34.9% were not complying with the entire regimen (8).That is not greatly worse than CPAP adherence.One needs to consider also that in most patients with OSA, hypertension is not the only consequence of the sleepdisordered breathing.Thus, CPAP could contribute to BP control while also improving quality of life and possibly reducing the risk for cardiovascular disease.That combination of outcomes would seem to make CPAP use a worthy goal in the treatment of high BP.
Phase I dose-finding study of trabectedin (T) in combination with cisplatin (C) in patients (pts) with advanced solid tumors.
Authors: C. Sessa, E. Gallerani, G. Del Conte, A. Christinat, A. Perotti, P. Lardelli, C. M. Kahatt, A. Florez, C. Fernandez, M. Miani, L. Gianni
Journal: Journal of Clinical Oncology (2011)

2517 Background: T is a synthetic compound originally derived from the marine organism Ecteinascidia turbinata with a mechanism of action based on DNA binding and involving the transcription-dependent nucleotide excision repair system. In vitro and in vivo preclinical data have shown a synergistic effect of the combination -T+C-. Methods: Primary Objectives: to identify the recommended dose (RD) of T given as 3-hour infusion in combination with standard dose of C every 3 weeks. Secondary: safety, antitumor activity and pharmacokinetics (PK). Pts with advanced solid tumors for whom treatment with T or platinum compounds was indicated were recruited. A maximum of 1 prior chemotherapy line and platinum sensitivity was required. T was given at escalating doses in subsequent cohorts of pts from 0.75 mg/m2 with a fixed dose of 75 mg/m2 C. The maximum tolerated dose was the dose level (DL) at which 1/3 or 2/6 pts had dose limiting toxicities (DLTs); the RD was set at 1 DL immediately below that. Results: At a T dose of 0.75 mg/m2 (DL1), 2 of 4 pts had DLTs: grade (G) 4 neutropenia >7 days and uncontrolled G 3 vomiting. T dose was reduced to 0.60 mg/m2 (DL-1) and 6 pts were recruited: 2 with ovarian carcinoma (OC) and 4 with soft tissue sarcoma (STS). No DLTs were reported. The most common adverse events were fatigue nausea, vomiting; the most common lab abnormalities were ALT elevations, G 3-4 neutropenia and G 3-4 thrombocytopenia. Out of 10 evaluable pts, 1 partial response (OC) and 5 stable disease (1 OC, 1 breast and 3 STS; 4 of them lasting ≥4 cycles) were reported. PK studies in 6 pts at 0.6 mg/m2 shown that the plasma exposure (AUC) to T and to C was about double and 60% higher, respectively, in the combination as compared to single agents in separate series. Conclusions: The RD of T given as 3-hour infusion in combination with 75mg/m2 of C is 0.6 mg/m2, 50 % lower than the RD as single agent. At these dose level and schedule the safety profile of both drugs is comparable to that of either single agent and is associated with antitumor activity. PK interaction leading to increased plasma exposure to both drugs may explain the clinical findings. Additional pts with platinum sensitive OC will be accrued at the RD to better define the PK profile.
Abstract 14997: Zn2+ and mPTP Mediate ERS Inhibition-induced Cardioprotection Against Ischemia/Reperfusion Injury
Authors: Jinkun Xi, Yonggui He, Shuo Fei, Huan Zheng, Zhelong Xu
Journal: Circulation (2014)

While the role of endoplasmic reticulum stress (ERS) in myocardial ischemia/reperfusion (I/R) injury has been extensively investigated, the precise mechanism by which inhibition of ERS induces cardioprotection remains unclear. We aimed to explore the mechanism of ERS inhibition-induced cardioprotection against I/R injury, focusing on the role of Zn 2+ and the mitochondrial permeability transition pore (mPTP). Exposure of H9c2 cells to 800 μM H 2 O 2 for 20 min increased GRP78 and GRP94 expressions (296.2 ± 41.0 and 150.6 ± 13.5 %, respectively), suggesting that H 2 O 2 can induce ERS. Cells treated with H 2 O 2 showed a significant decrease (40.6 ± 7.4 %) in TMRE fluorescence compared to the normal group (92.6 ± 0.1 %), indicating that H 2 O 2 can induce the mPTP opening. In contrast, ERS inhibitor TUDCA (30 μM) prevented the loss of TMRE fluorescence (77.8 ± 6.8 %), implying that inhibition of ERS can prevent the mPTP opening. This effect of TUDCA was blocked by zinc chelator TPEN (37.7 ± 13.0 %), indicating a role of Zn 2+ in the action of TUDCA on the mPTP opening. In support, TUDCA increased intracellular free zinc, as indicated by a marked increase in Newport Green DCF fluorescence intensity. In isolated rat hearts, GRP78 expression was not increased during ischemia but was increased upon reperfusion (1.3, 1.5, 1.9, and 1.6-fold increases at 10, 30, 60, and 120 min of reperfusion). Hearts treated with TUDCA showed a significant reduction of GRP78 expression 30 and 60 min after the onset of reperfusion, an effect that was reversed by TPEN. The immunofluorescence study also showed that the effect of TUDCA on GRP78 expression was reversed by TPEN. TUDCA reduced infarct size, and this was reversed by the mPTP opener atractyloside, indicating that ERS inhibition may protect the heart by modulating the mPTP opening. Experiments with transmission electron microscopy and hematoxylin-eosin staining revealed that TUDCA prevented endoplasmic reticulum and mitochondrial damages at reperfusion, which was blocked by TPEN. In conclusion, reperfusion but not ischemia initiates ERS and inhibition of ERS protects the heart from reperfusion injury through prevention of the mPTP opening. Increased intracellular free Zn 2+ accounts for the cardioprotective effect of ERS inhibition.
CETUFTIRI, a new combination of UFT with leucovorin (LV), irinotecan, and cetuximab as first-line treatment for patients (pts) with unresectable metastatic colorectal cancer (mCRC): Preliminary results from a multicenter phase II trial
Authors: J. Bennouna, R. Faroux, E. François, C. Ligeza, C. El Hannani, H. Perrier, J. Jacob, F. Desseigne, G. Perrocheau, J. Y. Douillard
Journal: Journal of Clinical Oncology (2007)

4087 Background: A phase II study (ASCO 2004) established that the combination of UFT (tegafur-uracil) with LV and irinotecan (TEGAFIRI) could be safely administered to pts with unresectable mCRC, with an objective response rate (ORR) of 34% and a median time to progression (TTP) of 5.7 months. We initiated CETUFTIRI, a phase II study, to evaluate the efficacy and tolerability of cetuximab added to TEGAFIRI in chemonaïve pts with unresectable mCRC. Methods: Patients in this single-stage study were aged =18 years, with histologically or cytologically confirmed, bidimensionally measurable mCRC, ECOG performance status 0 or 1, and adequate bone marrow, renal, and hepatic function. EGFR expression was not an inclusion criterion. Treatment consisted of UFT 250 mg/m 2 /day d1–14, LV 90 mg/day d1–14, and irinotecan 250 mg/m 2 d1 every 3 weeks, plus cetuximab 400 mg/m 2 week 1 then 250 mg/m 2 weekly thereafter. The primary endpoint was ORR and the planned sample size was 61 pts. The study is now closed to accrual. Results: To date, 48 patients are evaluable for safety and 31 are evaluable for efficacy. Patient characteristics (n=48): median age 65 years (range 45–84 years); ECOG PS 0/1: 73/27%; male 65%; tumor sites: colon 69%; rectum 17%; junction 14%; liver metastasis 83%; lung metastasis 46%; other 27%. Adverse events per patient (n=48) after a total of 230 cycles were: grade G3 mucositis 10%; G3/4 neutropenia 10%; G3 nausea/vomiting 8%; G3 asthenia 6%; febrile neutropenia 6%; G3 hypokalemia 6%; G3/4 anemia 4%; G3 diarrhea 2%; acne-like rash G1/2 50% (G3 4%); infusion- related reaction to cetuximab 6%. Two of 31 evaluable pts had a complete response and 11 had a partial response, for an ORR of 42%; 5 pts had stable disease (16%) and 11 pts had progressive disease (35.5%). An independent radiologist review is planned for all 61 pts included up to December 2006. Conclusions: The CETUFTIRI combination seems to have an acceptable toxicity profile with an attractive objective response rate in the first-line treatment of pts with mCRC. No significant financial relationships to disclose.
<sup>68</sup>Gallium-DOTATATE PET in meningioma: A reliable predictor of tumor growth rate?
Authors: Michael Sommerauer, Jan-Karl Burkhardt, Karl Frontzek, Elisabeth Rushing, Alfred Buck, Niklaus Krayenbuehl, Michael Weller, Niklaus Schaefer, Felix P. Kuhn
Journal: Neuro-Oncology (2016)

DOTATATE-based radionuclides have added new options in the diagnosis and treatment of meningiomas; however, a reliable predictor of tumor growth has still not been established. We analyzed 64 meningiomas imaged with 68Ga-DOTATATE PET. Tumor growth rates were calculated by volumetric analysis of sequential MRI scans. Maximums of standardized uptake values (SUVmax) were correlated with tumor growth and covariates. World Health Organization (WHO) grades I and II meningiomas showed a correlation of SUVmax and tumor growth rate (meningiomas limited to the intracranial compartment: r = 0.757, P < .001, and transosseous growing meningiomas: r = 0.819, P = .024). SUVmax was significantly higher and the slope of the linear regression significantly steeper in transosseous compared with intracranial meningiomas (both P < .001). The association remained significant in multivariate analysis, and the prediction of tumor growth rate was independent of WHO grade. Anaplastic meningiomas showed no significant correlation of SUVmax and tumor growth. 68Ga-DOTATATE PET is a reliable predictor of tumor growth in WHO grades I and II meningiomas and provides additional information to conventional cross-sectional imaging modalities. Hence, 68Ga-DOTATATE PET can assist in selecting the time point for treatment initiation. Furthermore, meningiomas with fast tumor growth and transosseous expansion elicit the highest DOTATATE binding; therefore, they might be especially suited for DOTATATE-based therapy.
Clonal B cells in Waldenström’s macroglobulinemia exhibit functional features of chronic active B-cell receptor signaling
Authors: K V Argyropoulos, R Vogel, C Ziegler, G Altan-Bonnet, E Velardi, M Calafiore, A Dogan, M Arcila, M Patel, K Knapp, C Mallek, Z R Hunter, S P Treon, M R M van den Brink, M L Palomba
Journal: Leukemia (2016)

Waldenström's macroglobulinemia (WM) is a B-cell non-Hodgkin's lymphoma (B-NHL) characterized by immunoglobulin M (IgM) monoclonal gammopathy and the medullary expansion of clonal lymphoplasmacytic cells. Neoplastic transformation has been partially attributed to hyperactive MYD88 signaling, secondary to the MYD88 L265P mutation, occurring in the majority of WM patients. Nevertheless, the presence of chronic active B-cell receptor (BCR) signaling, a feature of multiple IgM+ B-NHL, remains a subject of speculation in WM. Here, we interrogated the BCR signaling capacity of primary WM cells by utilizing multiparametric phosphoflow cytometry and found heightened basal phosphorylation of BCR-related signaling proteins, and augmented phosphoresponses on surface IgM (sIgM) crosslinking, compared with normal B cells. In support of those findings we observed high sIgM expression and loss of phosphatase activity in WM cells, which could both lead to signaling potentiation in clonal cells. Finally, led by the high-signaling heterogeneity among WM samples, we generated patient-specific phosphosignatures, which subclassified patients into a 'high' and a 'healthy-like' signaling group, with the second corresponding to patients with a more indolent clinical phenotype. These findings support the presence of chronic active BCR signaling in WM while providing a link between differential BCR signaling utilization and distinct clinical WM subgroups.
Ten-year follow-up of a randomized controlled trial of adjuvant clodronate treatment in node-positive breast cancer patients
Authors: T. Saarto, L. Vehmanen, C. Blomqvist, I. Elomaa
Journal: Journal of Clinical Oncology (2004)

527 Background: There are three studies available of the effect of adjuvant bisphosphonate treatment on survival in primary operable breast cancer with conflicting results. We here present the extended 10 year follow-up result of the Finnish adjuvant clodronate study. Methods: Between 1990 and 1993, 299 women with primary node positive breast cancer were randomized to oral clodronate 1600 mg daily (149) or control groups (150) for three years. All patients received adjuvant chemo- or endocrine therapy. The final population was 282 patients. Intent-to-treat analyses were also performed. Pretreatment characteristics were well balanced between the groups except PgR receptor status. In the clodronate group there were more PgR negative patients (p = 0.03). Results: Within ten years bone metastases were detected at the same frequency in the clodronate and control groups: 44 (32 %) vs. 42 (29 %), respectively, (p = 0.35). The frequency of nonskeletal recurrences (visceral and local) was significantly higher in the clodronate group 69 (50 %) as compared to the controls 51 (36 %) (p = 0.005). Ten-year disease-free survival (DFS) remained significantly lower in the clodronate group (45 % vs. 58%, p = 0.01, respectively). In ER positive patients ten-year DFS was 55 % in the clodronate group, and 59 % in the controls with no difference between the groups (p = 0.47); while in ER negative patients the DFS difference was highly significant in favor of the controls: 25 % vs. 58 %(p = 0.004), respectively. In multivariate analyses of DFS nodal status, tumor size, PgR status and study treatment group remained statistically significant. No significant overall survival difference was found between the groups.Conclusions: As previously reported three-year adjuvant clodronate treatment did not prevent the development of bone metastases in node-positive breast cancer patients. A negative effect of clodronate on DFS by increasing the development of visceral metastases was still seen at 10 years especially in ER negative patients, but this did not significantly compromise overall survival. No significant financial relationships to disclose.
Diagnosis in oncology. Hand-foot syndrome.
Authors: A Jucgla, G Sais
Journal: Journal of Clinical Oncology (1997)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1997.15.9.3164 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9312563 Diagnosis in oncology. Hand-foot syndrome. A JucglaxA JucglaSearch for articles by this author , G SaisxG SaisSearch for articles by this author Show More Hospital Princeps d'Espanyo Ciutat Sanitària, Barcelona, Spain. https://doi.org/10.1200/JCO.1997.15.9.3164 PDF "Diagnosis in oncology. Hand-foot syndrome.." Journal of Clinical Oncology, 15(9), p. 3164© 1997 by American Society of Clinical Oncology
Phase I trial of motexafin gadolinium (MGd) and docetaxel (D) chemotherapy in the treatment of advanced solid tumors
Authors: D. P. Petro, M. J. Egorin, R. K. Ramanathan, S. Ramalingham, D. Friedland, S.-C. Phan, L. Brown, C. L. Naret, C. P. Belani, G. Chatta
Journal: Journal of Clinical Oncology (2005)

3164 Background: The anti-cancer agent motexafin gadolinium (MGd, Xcytrin) is one of a class of engineered porphyrin-like molecules called texaphyrins. In preclinical models, MGd selectively disrupts metabolic and repair mechanisms in tumor cells and renders them more vulnerable to ionizing radiation and chemotherapy. D is a cytotoxic agent with documented activity in a broad range of solid tumors. Because, MGd-mediated production of reactive oxygen species may render tumor cells more susceptible to D by lowering the threshold for D-induced apoptosis, we performed a Phase I and pharmacokinetic (PK) study of MGd and D. Methods: To evaluate the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), recommended phase II dose (RP2D), and characteristics of D and MGd, escalating intravenous doses of MGd and D, were given weekly to cohorts of 3–6 patients (pts), using a modified Fibonacci schema. Each cycle consisted of weekly treatment for 3 out of 4 weeks, with patients receiving MGd (2.5mg/kg/week) + D (30mg/m2/week) in cohort 1; and MGd (5mg/kg/week) + D (30mg/m2/week) in cohort 2. MGd was infused IV 30 minutes before D. Evaluation for DLTs was done during cycle 1. Treatment responses were evaluated every 2 cycles. PK studies are planned after reaching the RP2D dose. Results: Ten patients with advanced solid tumors and acceptable organ function were enrolled (cohort 1, 3 pts; cohort 2, 7 pts). Pt characteristics: Male: 6; Age 58–78 (median 70.5); ECOG performance status 0 (n=6), 1(n=4). The tumor types were lung (n=5), GI (n=4) and GU (n=1). There were no DLTs in either cohort. However, both cohorts were associated with several Grade I/II toxicities: GI, hematologic, hyperbilirubinemia, metabolic, musculoskeletal, neuropathy, and respiratory. 1 pt experienced Gr 3 neutropenia. Non-infectious diarrhea occurred in 50% of the patients. Pts completed a mean of three cycles of the regimen. No objective responses have been seen to date, but 4 pts continue on treatment with stable disease. Conclusions: This novel regimen of MGd and D is well-tolerated and continues to accrue patients. (Supported by Pharmacyclics, Inc and NIH/NCCR/GCRC#5M01RR00056 to the University of Pittsburgh) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pharmacyclics Aventis Pharmacyclics Aventis Aventis, Pharmacyclics
A Phase I Study of the Mek1/2 Inhibitor Selumetinib in Combination with First-Line Chemotherapy Regimens for Nsclc
Authors: E. Dean, N. Steele, H. Arkenau, F. Blackhall, N.M. Haris, C. Lindsay, M. Saggese, R. Califano, A. Greystoke, M. Voskoboynik, D. Ghiorghiu, A. Dymond, I. Smith, R. Plummer
Journal: Annals of Oncology (2014)
A Prospective Observational Study for Monitoring Egfr T790M Using Plasma Dna in Lung Cancer Patients
Authors: Kentaro Iwanaga, Naoko Aragane, Nobuyuki Katakami, Miyako Satouchi, Soichiro Yokota, Keisuke Aoe, Kojiro Otsuka, Shinya Kimura, Shunichi Negoro
Journal: Annals of Oncology (2014)
Hypofractionated stereotactic radiosurgery with concurrent chemotherapy for recurrent head and neck squamous cell carcinoma (RH&amp;NSCC)
Authors: K. Lassi, J. F. Deeken, J. J. Hwang, A. K. Esnakula, B. Davidson, K. Newkirk, E. Bischoff, K. W. Harter
Journal: Journal of Clinical Oncology (2008)

17041 Background: The prognosis of patients with RH&NSCC remains dismal, with a median survival of 4 months without treatment and 6 months with palliative chemotherapy. Surgery remains the best treatment option, but only a minority of patients are suitable candidates. Using conventional radiation in a previously irradiated neck may be beneficial in treating RH&NSCC, but toxicities to surrounding normal tissues can be severe. Cyberknife Stereotactic Radiosurgery (CSR) delivers hypofractionated radiation more precisely than conventional radiotherapy. Chemotherapy agents can sensitize SCC to the effects of radiation. Methods: We conducted a single institution retrospective analysis of 22 consecutive patients treated with CSR and concurrent chemotherapy for RH&NSCC between May 2002 and December 2007. All patients had received prior radiation as part of their initial primary or adjuvant treatment. Sixteen of 22 patients received CSR with concurrent chemotherapy for their first disease recurrence, four received treatment for their second recurrence, and two patients received it for both their first and second recurrences. Results: Median patient age was 62 years (38 to 82). The median duration of follow-up was 14 months (2.4 to 50.7), and among the seven surviving patients the median follow-up was 22.3 months. Patients received CSR typically over 5 fractions at a daily dose of 500 to 600cGy and the average total dose was 2,800cGy. Chemotherapy agents used concurrently with CSR included: cetuximab (n=10), cisplatin/carboplatin single agent or doublets (n=10), capecitabine (n=1) or gemcitabine/docetaxel (n=2). Kaplan-Meier methods were used to estimate median and one-year survival times. The median survival was 7.6 mos. The percentage of patients alive at one year was 43.0% (SD 10.8%). Treatment was well tolerated. Acute toxicities were grade 1 or 2 and included rash (23%), mucositis (14%), dysphagia/odynophagia (14%), fatigue (14%), neutropenia (5%), and tinnitus (5%). No grade 3 or 4 toxicities were observed. Conclusion: CSR combined with chemotherapy is feasible and well tolerated. Given the observed survival of patients in this series, and the poor prognosis of patients with RH&NSCC, further clinical study is warranted. No significant financial relationships to disclose.
Clarification of automatic optical diagnosis of small colorectal lesions by laser-induced autofluorescence
Authors: Michael Oliver
Journal: Endoscopy (2015)

The article published in the January 2015 edition of Endoscopy entitled “Automatic optical diagnosis of small colorectal lesions by laser-induced autofluorescence” [1] utilized data gathered in 2011 from the WavSTAT3 system. The third-generation product was discontinued in 2012 and is no longer available. We believe the results generated in this evaluation do not accurately reflect the performance of the current WavSTAT4 Optical Biopsy System (SpectraScience, Inc., San Diego, California, USA).