66. Late effects of CNS prophylactic irradiation in childhood due to LLA using Magnetic Resonance Spectro-skopy. (preliminary report)

PurposeThe aim of this study was to evaluate changes in magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) of the brain in survivars with Acute Lymphoblastic Leukemia to assess neurotixicity follow profilactic brain irradiation.MethodsTen from 100 patients with LLA treated in Department of Pediatric Hematology from 1990 to 1995 and irradiated in Centre of Oncology were icluded in MRI and MRS studies. The study group included 6 male and 4 female. All patients had been irradiated for brain using fraction dose of 1,8 Gy up to total dose of 18 Gy and had recived MTX based chemotherapy in doses depending on level of risk. Two of them were included in low risk and eight in intermediate risk.ResultsMRI of brain was abnormal in 5 cases. There were mild white matter changes.The changes were Been in H- MRS metabolite ratios. In one of these cases we observed a impair of verbal functions.ConclusionsThe MRS could be valuable method to access brain tissue metabolism after radiotherapy. That noninvasive method may be recomended for children with LLA to observe neurotoxicity of profilactic irradiation

5/Zastosowanie techniki ćwierćwiązek z użyciem jednego izocentrum w radioterapii chorych na raka piersi

Cel pracyCelem pracy jest przedstawienie nowej techniki radioterapii zastosowanej u chorych na raka piersi, po zabiegach operacyjnych.MetodaNapromienianie wszystkich pól przeprowadza się bez zmiany ułożenia chorej, z wykorzystaniem jednego izocentrum, które jest zlokalizowane na granicy pól tangencjalnych i nadobojczykowo-pachowych. Stosuje się pola asymetryczne. Pola tangencjalne napromienia się ćwierćwiązką, a pola nadobojczykowe - półwiązką.Wnioski1. Prezentowana technika radioterapii pozwala na lepszą odtwarzalność leczenia w porównaniu do stosowanych standardowych technik radioterapii. 2. Opisana technika, pomimo większego nakładu pracy przy planowaniu leczenia jest mniej pracochłonna i zajmuje mniej czasu przy codziennym napromienianiu. 3. Poprawie ulega jednorodność rozkładu dawki na granicy obszarów

Frequency and Diversity of Nitrate Reductase Genes among Nitrate-Dissimilating Pseudomonas in the Rhizosphere of Perennial Grasses Grown in Field Conditions

A total of 1246 Pseudomonas strains were isolated from the rhizosphere of two perennial grasses (Lolium perenne and Molinia coerulea) with different nitrogen requirements. The plants were grown in their native soil under ambient and elevated atmospheric CO2 content (pCO2) at the Swiss FACE (Free Air CO2 Enrichment) facility. Root-, rhizosphere-, and non-rhizospheric soil-associated strains were characterized in terms of their ability to reduce nitrate during an in vitro assay and with respect to the genes encoding the membrane-bound (named NAR) and periplasmic (NAP) nitrate reductases so far described in the genus Pseudomonas. The diversity of corresponding genes was assessed by PCR-RFLP on narG and napA genes, which encode the catalytic subunit of nitrate reductases. The frequency of nitrate-dissimilating strains decreased with root proximity for both plants and was enhanced under elevated pCO2 in the rhizosphere of L. perenne. NAR (54% of strains) as well as NAP (49%) forms were present in nitrate-reducing strains, 15.5% of the 439 strains tested harbouring both genes. The relative proportions of narG and napA detected in Pseudomonas strains were different according to root proximity and for both pCO2 treatments: the NAR form was more abundant close to the root surface and for plants grown under elevated pCO2. Putative denitrifiers harbored mainly the membrane-bound (NAR) form of nitrate reductase. Finally, both narG and napA sequences displayed a high level of diversity. Anyway, this diversity was correlated neither with the root proximity nor with the pCO2 treatmen

Verwey transition in Fe3_{3}O4_{4} at high pressure: quantum critical behavior at the onset of metallization

We provide evidence for the existence of a {\em quantum critical point} at the metallization of magnetite Fe$_{3}$O$_{4}$ at an applied pressure of $p_{c} \approx 8$ GPa. We show that the present ac magnetic susceptibility data support earlier resistivity data. The Verwey temperature scales with pressure $T_{V}\sim (1-p/p_{c})^{\nu}$, with $\nu\sim 1/3$. The resistivity data shows a temperature dependence $\rho(T)=\rho_{0}+AT^{n}$, with $n\simeq 3$ above and 2.5 at the critical pressure, respectively. This difference in $n$ with pressure is a sign of critical behavior at $p_{c}$. The magnetic susceptibility is smooth near the critical pressure, both at the Verwey transition and near the ferroelectric anomaly. A comparison with the critical behavior observed in the Mott-Hubbard and related systems is made.Comment: 5 pages, 5 figure

66. Late effects of CNS prophylactic irradiation in childhood due to LLA using Magnetic Resonance Spectro-skopy. (preliminary report)

PurposeThe aim of this study was to evaluate changes in magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) of the brain in survivars with Acute Lymphoblastic Leukemia to assess neurotixicity follow profilactic brain irradiation.MethodsTen from 100 patients with LLA treated in Department of Pediatric Hematology from 1990 to 1995 and irradiated in Centre of Oncology were icluded in MRI and MRS studies. The study group included 6 male and 4 female. All patients had been irradiated for brain using fraction dose of 1,8 Gy up to total dose of 18 Gy and had recived MTX based chemotherapy in doses depending on level of risk. Two of them were included in low risk and eight in intermediate risk.ResultsMRI of brain was abnormal in 5 cases. There were mild white matter changes.The changes were Been in H- MRS metabolite ratios. In one of these cases we observed a impair of verbal functions.ConclusionsThe MRS could be valuable method to access brain tissue metabolism after radiotherapy. That noninvasive method may be recomended for children with LLA to observe neurotoxicity of profilactic irradiation

Evaluation of the Algorithms and Parameterizations for Ground Thawing and Freezing Simulation in Permafrost Regions

Ground thawing and freezing depths (GTFDs) strongly influence the hydrology and energy balances of permafrost regions. Current methods to simulate GTFD differ in algorithm type, soil parameterization, representation of latent heat, and unfrozen water content. In this study, five algorithms (one semiempirical, two analytical, and two numerical), three soil thermal conductivity parameterizations, and three unfrozen water parameterizations were evaluated against detailed field measurements at four field sites in Canada’s discontinuous permafrost region. Key findings include: (1) de Vries’ parameterization is recommended to determine the thermal conductivity in permafrost soils; (2) the three unfrozen water parameterization methods exhibited little difference in terms of GTFD simulations, yet the segmented linear function is the simplest to be implemented; (3) the semiempirical algorithm reasonably simulates thawing at permafrost sites and freezing at seasonal frost sites with site-specific calibration. However, large interannual and intersite variations in calibration coefficients limit its applicability for dynamic analysis; (4) when driven by surface forcing, analytical algorithms performed marginally better than the semiempirical algorithm. The inclusion of bottom forcing improved analytical algorithm performance, yet their results were still poor compared with those achieved by numerical algorithms; (5) when supplied with the optimal inputs, soil parameterizations, and model configurations, the numerical algorithm with latent heat treated as an apparent heat capacity achieved the best GTFD simulations among all algorithms at all sites. Replacing the observed bottom temperature with a zero heat flux boundary condition did not significantly reduce simulation accuracy, while assuming a saturated profile caused large errors at several sites

Two cilengitide regimens in combination with standard treatment for patients with newly diagnosed glioblastoma and unmethylated MGMT gene promoter: results of the open-label, controlled, randomized phase II CORE study

Background Survival outcomes for patients with glioblastoma remain poor, particularly for patients with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) gene promoter. This phase II, randomized, open-label, multicenter trial investigated the efficacy and safety of 2 dose regimens of the selective integrin inhibitor cilengitide combined with standard chemoradiotherapy in patients with newly diagnosed glioblastoma and an unmethylated MGMT promoter. Methods Overall, 265 patients were randomized (1:1:1) to standard cilengitide (2000 mg 2×/wk; n = 88), intensive cilengitide (2000 mg 5×/wk during wk 1−6, thereafter 2×/wk; n = 88), or a control arm (chemoradiotherapy alone; n = 89). Cilengitide was administered intravenously in combination with daily temozolomide (TMZ) and concomitant radiotherapy (RT; wk 1−6), followed by TMZ maintenance therapy (TMZ/RT→TMZ). The primary endpoint was overall survival; secondary endpoints included progression-free survival, pharmacokinetics, and safety and tolerability. Results Median overall survival was 16.3 months in the standard cilengitide arm (hazard ratio [HR], 0.686; 95% CI: 0.484, 0.972; P = .032) and 14.5 months in the intensive cilengitide arm (HR, 0.858; 95% CI: 0.612, 1.204; P = .3771) versus 13.4 months in the control arm. Median progression-free survival assessed per independent review committee was 5.6 months (HR, 0.822; 95% CI: 0.595, 1.134) and 5.9 months (HR, 0.794; 95% CI: 0.575, 1.096) in the standard and intensive cilengitide arms, respectively, versus 4.1 months in the control arm. Cilengitide was well tolerated. Conclusions Standard and intensive cilengitide dose regimens were well tolerated in combination with TMZ/RT→TMZ. Inconsistent overall survival and progression-free survival outcomes and a limited sample size did not allow firm conclusions regarding clinical efficacy in this exploratory phase II stud

Phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer: ENGOT-en9/LEAP-001

BACKGROUND: Pembrolizumab plus lenvatinib is a novel combination with promising efficacy in patients with advanced and recurrent endometrial cancer. This combination demonstrated high objective response rates in a single-arm phase 1b/2 trial of lenvatinib plus pembrolizumab in patients with advanced endometrial cancer (KEYNOTE-146/Study 111) after ≤2 previous lines of therapy. In a randomized phase 3 trial of lenvatinib in combination with pembrolizumab versus treatment of physician's choice in patients with advanced endometrial cancer (KEYNOTE-775/Study 309), after 1‒2 previous lines of therapy (including neoadjuvant/adjuvant), this combination improved objective response rates, progression-free survival, and overall survival compared with chemotherapy. PRIMARY OBJECTIVE: To compare the efficacy and safety of first-line pembrolizumab plus lenvatinib versus paclitaxel plus carboplatin in patients with newly diagnosed stage III/IV or recurrent endometrial cancer, with measurable or radiographically apparent disease. STUDY HYPOTHESIS: Pembrolizumab plus lenvatinib is superior to chemotherapy with respect to progression-free survival and overall survival in patients with mismatch repair-proficient tumors and all patients (all-comers). TRIAL DESIGN: Phase 3, randomized (1:1), open-label, active-controlled trial. Patients will receive pembrolizumab intravenously every 3 weeks plus lenvatinib orally daily or paclitaxel plus carboplatin intravenously every 3 weeks, stratified by mismatch repair status (proficient vs deficient). Patients with mismatch repair-proficient tumors will be further stratified by Eastern Cooperative Oncology Group performance status (0/1), measurable disease (yes/no), and prior chemotherapy and/or chemoradiation (yes/no). MAJOR INCLUSION/EXCLUSION CRITERIA: Adults with stage III/IV/recurrent histologically confirmed endometrial cancer that is measurable or radiographically apparent per blinded independent central review. Patients may have received previous chemotherapy only as neoadjuvant/adjuvant therapy and/or concurrently with radiation. Patients with carcinosarcoma (malignant mixed Müllerian tumor), endometrial leiomyosarcoma, or other high grade sarcomas, or endometrial stromal sarcomas were excluded. PRIMARY ENDPOINTS: Progression-free and overall survival (dual primary endpoints). SAMPLE SIZE: About 875 patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Enrollment is expected to take approximately 24 months, with presentation of results in 2022. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03884101