Response evaluation in third- and fourth-line treatment of GIST: the role of PET

Background: Response evaluation in gastrointestinal stromal tumors is difficult. Computed tomography and size-based assessments have been found inadequate to draw prognostic conclusions in patients treated with tyrosine kinase inhibitors (TKI). Density criteria (CHOI) have recently been shown to better define prognostic subsets of patients evaluated with CT. Still, positron emission tomography (PET) might be better at identifying responders with good outcome early, as shown for first and recently second-line treatment in GIST (Prior et al.; J Clin Oncol 2009). We wanted to evaluate the role of PET in third- and fourth-line TKI treatment of GIST. Methods: We retrospectively reviewed patients with GIST who had received third- or fourth-line treatment with TKI and had undergone PET for response evaluation. Patient needed to have a baseline and at least one subsequent PET. Results of the first "early" PET after treatment start have been used throughout this analysis and EORTC PET Study Group criteria applied. Results: Twelve treatment courses were evaluable, seven with Nilotinib in third- and five with Sorafenib in fourth-line treatment, in 8 patients, median age 60 y (range 36−78 y), who had all failed prior Imatinib and Sunitinib treatment due to disease progession. Baseline and follow-up PET were performed within a median of 34 days (range 9−84 days). Median progression-free survival (PFS) was 262 days in patients responding to PET versus 76 days in patients with stable or progressing disease (p = 0.15). Conclusions: This small series suggests that PET retains its value for outcome prediction in third- and fourth-line TKI treatment of GIST. This could be of particular clinical value in these vulnerable patients with large tumour masses. Early PET may help in stopping ineffective, but toxic therapy and help switching to a more effective therapy. PET should be evaluated further in this patient population.

The heart challenge: The effect of regular aerobic exercise on body fat distribution in third and fourth grade school children: A randomized clinical trial

The pattern of body fat distribution known as "centralized", and characterized by a predominance of subcutaneous fat on the trunk and a "pot belly", has been associated with an increased risk of chronic disease. These patterns of fat distribution, as well as the lifestyle habit variables associated with adult fatness and chronic morbidity clearly begin to develop during childhood, indicating the need for intervention and primary prevention of obesity, particularly the centralized form, during childhood or adolescence. The purpose of this study was to determine whether regular aerobic exercise could beneficially alter the distribution of body fat in 8 and 9 year old children. One hundred and eighty-eight participants were randomized into either a regular aerobic exercise treatment group or a standard physical education program control group. A variety of aerobic activities was used for intervention 5 days per week during physical education class for a period of 12 weeks. Fat distribution was measured by a number of the most commonly used indices, including ratios of body circumferences and skinfolds and indices derived from a principal components analysis. Change over time in average pulse rate was used to determine if intervention actually occurred. Approximately 10% of the students were remeasured, allowing the calculation of intra- and interexaminer measurement reliability estimates for all indices.^ This study group was comparable to the U.S. population, though the study children were slightly larger for certain measures. No effect of the exercise intervention was found. The most likely explanation for this was inadequacy of the intervention, as indicated by the lack of any change in average pulse rate with treatment. The results of the measurement reliability analysis are reported and indicate that body circumference ratios are more precise than skinfold ratios, particularly when multiple observers are used. Reliability estimates for the principal component indices were also high.^ It remains unclear whether the distribution of body fat can be altered with exercise. It is likely that this issue will remain undecided until one highly reliable, valid, and sensitive measure of fat distribution can be found. ^

Tannhäuser, minnesinger and knight templar, a metrical romance of the third and fourth crusades;

Mode of access: Internet.

The philosophy of Spinoza as contained in the first, second, and fifth parts of the "Ethics" and in extracts from the third and fourth /

Includes bibliographical references and index.

The effects of cross -age peer tutoring on writing and reading comprehension skills and attitudes and self -perceptions as writers of third and fourth grade students

The purpose of this study was to investigate the effects of cross-age peer writing response groups on the writing and reading achievement of third and fourth grade students. Students' attitudes about writing and their perceptions of themselves as writers were also measured at the end of the study. ^ One hundred and twenty-two third and fourth grade students enrolled in a public school in a middle-class, multi-cultural neighborhood participated in the study. Four existing classes of students were randomly assigned to either the experimental condition (EC) or the control condition (CC). Both groups were pretested and posttested for writing and reading achievement. The intervention, cross-age peer writing groups, met for eleven weeks. ^ Three hypotheses were examined in this study: (a) writing improvement score, (b) reading comprehension improvement score, and (c) students' attitudes toward writing and their perception of themselves as writers based on the five scales measured on the Writer Self-Perception Scale. ^ ANOVAs were done on the pretests and posttests for writing and the Stanford Achievement Test reading comprehension subtest scores for the year of the study and the previous year. ANOVAs were also done for the five areas of the Writer Self-Perception Scale. Cross-tabulations were also used to compare improvement level verses treatment group, and grade level. ^ Analysis of the data revealed that there was no evidence that the tutoring (EC) groups made more progress than the non-tutoring (CC) groups in writing and reading. There was evidence of growth in writing, especially by the fourth graders. Most importantly, the fourth grade tutors, the experimental group, had the most positive feelings about writing and themselves as writers. ^

Third Floor, Fourth Floor, Hollis Hall, 1874

Floor plan of renovations for the third and fourth floors of Hollis Hall, as drawn by William Rotch Ware in 1874. Includes dimensions for Pi Eta Society rooms, student chambers, hallways, and coal furnaces.

Third Floor, Fourth Floor, Stoughton, 1874

Floor plan of renovations for the third and fourth floors of Stoughton Hall, as drawn by William Rotch Ware in 1874. Includes dimensions for student chambers, H.P. Club Rooms, hallways, and coal furnaces.

Sorafenib as third- or fourth-line treatment of advanced gastrointestinal stromal tumour and pretreatment including both imatinib and sunitinib, and nilotinib: A retrospective analysis.

BACKGROUND: Tyrosine kinase inhibitors (TKI) improve the outcome of patients with advanced gastrointestinal stromal tumour (GIST), but treatment failure is frequent, and prognosis then bleak. Smaller trials in this setting suggested activity for sorafenib, a multikinase inhibitor of receptor tyrosine kinases and RAF serine/threonine kinases. PATIENTS AND METHODS: We retrospectively evaluated the efficacy of sorafenib, starting dose 400mg twice daily, in a large community-based cohort of 124 patients treated in 12 European and one United States (U.S.) cancer centre. All but one patient had a WHO performance score 0-2. All had failed both imatinib and sunitinib, 68 patients nilotinib and 26 had failed investigational therapy, too. RESULTS: Twelve (10%) patients responded to sorafenib and 70 (57%) patients achieved disease stabilisation. Sorafenib was moderately tolerated, and toxicity reported in 56% of the patients. Rash, hand-foot-syndrome and diarrhea occurred frequently. Sorafenib dosage was reduced in a third of patients, but this did not have an impact on progression-free survival (PFS) (p=0.15). Median PFS was 6.4months (95% confidence interval [CI], 4.6-8.0months) and median overall survival (OS) 13.5months (95% CI, 10.0-21.0months). Patients with a good performance status and those who responded to sorafenib had a significant better PFS. CONCLUSION: We conclude that sorafenib is active in GIST resistant to imatinib, sunitinib and nilotinib. These results warrant further investigation of sorafenib or similar molecules in GIST.

Different effects on rat arterial pressure and heart rate when losartan is injected into the third or fourth ventricle

Cardiovascular responses to central losartan (LOS), a non-peptide angiotensin II (ANG II) receptor antagonist, were investigated by comparing the effects of LOS injection into the 3rd and 4th cerebral ventricles (3rdV, 4thV) on mean arterial pressure (MAP) and heart rate (HR). Adult male Holtzman rats were used (N=6 animals per group). Average basal MAP and HR were 114±3 mmHg and 343±9 bpm (N=23), respectively. LOS (50, 100 or 200 nmol/2 μl) injected into the 3rdV induced pressor (peak of 25±3 mmHg) and tachycardic (peak of 60±25 bpm) responses. LOS injected into the 4thV had no effect on MAP, but it induced bradycardia (peak of -35±15 bpm). KCl (200 nmol/2 μl) injected into the 3rdV or into the 4thV had no effect on either MAP or HR compared to 0.9% saline injection. The results indicate that LOS injected into the third ventricle acts on forebrain structures to induce its pressor and tachycardic effects and that bradycardia, likely dependent on hindbrain structures, is obtained when LOS is injected into the fourth ventricle.

Catalogue of maps, prints, drawings, etc. : forming the geographical and topographical collection attached to the library of His late Majesty King George the Third, and presented by His Majesty King George the Fourth to the British Museum.

Also issued the same year in a 2 vol. octavo edition.

Catalogue of maps, prints, drawings, etc. forming the geographical and topographical collection attached to the library of His late Majesty King George the Third, and presented by His Majesty King George the Fourth to the British museum.

Mode of access: Internet.

Multinational corporations and United States foreign policy : hearings before the Subcommittee on Multinational Corporations of the Committee on Foreign Relations, United States Senate, Ninety-third - [Ninety-fourth] Congress.

Hearings held March 1973-Sept. 1976.