77. Ocena wczesnej toksyczności skojarzonej radio-chemioterapii miejscowo zaawansowanego raka szyjki macicy

CelW związku z wprowadzeniem w ostatnim roku w Swiętokrzyskim Centrum Onkologii skojarzonej radio-chemioterapii w leczeniu miejscowo zaawansowanego raka szyjki macicy, postanowiono ocenić wczesną, toksyczność tej metody leczenia.Materiał i metodyW okresie od 01.05.2000 do 15.11.2000 zakwalifikowano do leczenia skojarzonego w Dziale Radioterapii ŚCO 21 chorych na raka szyjki macicy w II i III stopniu zaawansowania (wg klasyfikacji FIGO). W I etapie leczenia stosowano teleradioterapie skojarzoną z chemioterapią (DDP 40 mg/m2 w dniach 1, 8, 15, 22, 29, 36). W napromienianiu wiązką zewnętrzną zastosowano czteropolową technikę box. Pacjentki otrzymały dawkę. całkowitą, 50.4 Gy we frakcjach po 1.8 Gy, pięćrazy w tygodniu fotonami X 15 MeV. W II etapie chore były leczone dojamową brachyterapią LDR/MDR (Cs-137). Dawkę obliczano w punkcie A podając od 25,31 Gy do 45,08 Gy w 2–3 frakcjach, w odstępach od jednego do dwóch tygodni uzależniając jej wysokość od dawki sumarycznej (teleradioterapia+ brachyterapia) i dawki na narządy krytyczne (pęcherz moczowy i odbytnicę). U wszystkich pacjentek oceniono wczesny odczyn popromienny ze strony skóry, dolnego odcinka przewodu pokarmowego i układu moczowego wg skali EORTC/RTOG. Wczesne powikłania po chemioterapii: leukopenia, trombocytopenia, nudności i wymioty oraz nefrotoksyczność oceniono wg skali WHO.WynikiU żadnej pacjentki nie przerwano teleradioterapii z powodu ostrego odczynu popromiennego i wczesnych powikłań po chemioterapii. 10 pacjentek (48%) otrzymało 6 kursów chemioterapii, 4 pacjentki (19%) 5 kursów, 2 pacjentki (9%) – 4 kursy, 2 pacjentki (9%) – 3 kursy, 1 pacjentka(5%) 2 kursy, i 2 pacjentki (9%) – 1 kurs chemioterapii. Najczęstszą przyczyną odstą-pienia od podania kolejnego cyklu chemioterapii była: leukopenia – 2 i 3 stopień wg WHO u 9 (42%) pac- jentek i trombocytopenia- 3 stopień u 2 (9%) pacjentek. U jednej pacjentki (5%) wystąpiła ostra niewydolność nerek po podaniu 1 kursu chemioterapii i z tego powodu odstąpiono od jej kontynuacji. Dwie pacjentki odmówiły zgody na kolejne cykle chemioterapii w trakcie leczenia. U jednej pacjentki przerwano chemioterapię z powodu anemii w 3 stopniu. Nudności i wymioty obserwowano sporadycznie i nie były one większe niż w stopniu pierwszym. Ostry odczyn popromienny ze strony dolnego odcinka przewodu pokarmowego w stopniu 1 i 2 wystąpił u 11 (51 %) pacjentek, natomiast ze strony pęcherza moczowego o takim nasileniu u 9 (42 %) pacjentek. U 90 % leczonych nie obserwowano odczynu popromiennego ze strony skóry. Nie obserwowano ostrych odczynów popromiennych w stopniu wyższym niż 2.PodsumowanieSkojarzona radio-chemioterapia miejscowo zaawansowanego raka szyjki macicy była dobrze tolerowana przez pacjentki. Powikłania hematologiczne były najczęstszą przyczyną przerw w leczeniu cytostatykiem. Chore dobrze tolerowały radioterapię, u wszystkich leczenie napromienianiem przeprowadzono bez konieczności wprowadzania przerw. Konieczne jest prowadzenie dalszej obserwacji chorych w celu oceny późnej toksyczności i wyników odległych leczenia

Optical second harmonic generation in Yttrium Aluminum Borate single crystals (theoretical simulation and experiment)

Experimental measurements of the second order susceptibilities for the second harmonic generation are reported for YAl3(BO3)4 (YAB) single crystals for the two principal tensor components xyz and yyy. First principles calculation of the linear and nonlinear optical susceptibilities for Yttrium Aluminum Borate YAl3(BO3)4 (YAB) crystal have been carried out within a framework of the full-potential linear augmented plane wave (FP-LAPW) method. Our calculations show a large anisotropy of the linear and nonlinear optical susceptibilities. The observed dependences of the second order susceptibilities for the static frequency limit and for the frequency may be a consequence of different contribution of electron-phonon interactions. The imaginary parts of the second order SHG susceptibility chi_{123}^{(2)}(omega), chi_{112}^{(2)}(omega), chi_{222}^{(2)}(omega), and chi_{213}^{(2)}(omega) are evaluated. We find that the 2(omega) inter-band and intra-band contributions to the real and imaginary parts of chi_{ijk}^{(2)}\l(omega) show opposite signs. The calculated second order susceptibilities are in reasonably good agreement with the experimental measurements.Comment: 16 pages, 11 figure

Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade 653 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design

Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE).

BACKGROUND: Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. PATIENTS AND METHODS: In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8\u2009mg/kg loading dose, then 6\u2009mg/kg every 3\u2009weeks (q3w)] and pertuzumab (840\u2009mg loading dose, then 420\u2009mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). RESULTS: Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54\u2009years; 29% had received prior trastuzumab. Median treatment duration was 16\u2009months for pertuzumab and trastuzumab and 4\u2009months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1\u2009months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%). CONCLUSIONS: Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile. CLINICALTRIALS.GOV: NCT01572038

Band structure and optical properties of LiKB4O7 single crystal

The band structure (BS), electronic charge density distribution and linear optical properties of the LiKB4O7 (LKB4) single crystal are calculated using a self-consistent norm-conserving pseudo-potential method within the framework of the local density approximation theory. Dispersion of the imaginary,part of dielectric susceptibility. as well as of density of states is found. Comparison of the theoretically calculated and the experimentally measured optical and X-ray photoelectron spectra shows a good agreement. The specific of the charge density distribution, band structure dispersion and of the optical spectra originate from two anionic groups, (B3O8)(7-) and (B5O10)(5-) groups, forming infinite spiral chains parallel to the [100] crystallographic direction, which are interconnected by sharing oxygen atoms with (B5O10)(5-) groups. The observed behaviour of band structure is principally different from the tihium pentaborate (LBBOH) and beta-BaB2O4 (BBO) single crystals. In the LBBOH single crystals, the anisotropy of the optical and the charge density distribution is caused by different projection of the orbitals originating from particular borate clusters on the particular crystallographic axes. In the case of the BBO, the anisotropy is caused prevailingly by a different local site symmetry of oxygen within the borate planes. (C) 2003 Elsevier Science B.V. All rights reserved

Changes in survival of colorectal cancer patients in Swietokrzyskie Province (Southern Poland) from the second half of the 1990s to the early 21st century - a population-based study

Introduction and objectives. For years, the increase in cancer incidence and deaths has constituted a significant health and social problem. Variation in the burden in cancers in different regions of the world requires constant monitoring of the epidemiological situation in this regard. Assessing survival in cancer patients is a valuable source of information for patients and physicians alike, as well as for politicians who have a direct impact on the shaping of health policy and health systems. The aim of the present study was to assess the changes in the 5-year relative survival of colorectal cancer patients during 1995–2014. Materials and method. The data of 8,970 patients with colorectal cancer in the years 1995–2014, 5,033 males and 3,937 females aged 67.5 ± 11.7 from Świętokrzyskie Cancer Registry were used. Cases were classified according to the topographical codes ICD-O-3: C18.0-C18.9, C19.9, C20.9, C21.0-C21.2, C21.8. The end of follow-up was fixed at 31 December 2014. Four five-year calendar periods were defined. In each calendar period, relative survival rates using the Ederer II method were estimated separately for males and females. Results. In 2010–2014 (against 1995–1999), the absolute increase in the 5-year relative survival in males and females with colon cancer was the highest and reached 9.8 percentage point (p.p.) and 9.6 p.p., respectively. Patterns of survival for both colon and rectal cancer patients according to gender and age were very similar. Conclusions. In 1995–2014, an increase in the value of relative survival rates of males and females with colorectal cancer was observed. Systematic increase in funding in health care was a chance for reducing the burden of colorectal cancer by more widespread and equal access of effective early detection and cancer treatment