The influence of the gap in postoperative radiotherapy patients with carcinoma of the larynx

The aim of study was to evaluate the influence of gap in postoperative irradiation on the outcome. For this purpose the retrospective review the cases histories of 311 patients after total laryngectomy and postoperative radiotherapy between 1986 and 1990 was performed. All patients were divided into 3 groups : A- without gap (160 patients), B- with short gap up to 7 days (94 patients) and C- with long gap over 7 days (57 patients). The endpoint in analysis was loco regional rate control. All patients had a minimum follow up 3 years. Based on our data it was calculated that the prolongation of treatment resulted in decrease in loco regional control. The correlation between length the gap and decrease the outcome of treatment was very strong (

56 Efektywność elektronicznego obrazowania napromienianego pola w kontroli jakości radioterapii

Celem pracy jest ocena jakości i efektywności elektronicznego systemu portal imaging (EPID) z możliwością cyfrowego ulepszenia i analizowania otrzymanych obrazów w kontroli jakości radioterapii.Elektroniczne zdjęcia weryfikacyjne wykonano przed rozpoczęciem leczenia u 57% (97/170) napromienianych chorych. Procedura wykonywania djęć weryfikacyjnych przedłuża czas pojedynczej sesji napromieniania o 10% – 20% (1–2 minut). 87% z otrzymanych zdjęć elektronicznych nadawało się do oceny pod względem jakościowym. U 20% (19/97) chorych monitorowanych przy pomocy EPID wprowadzono poprawki przed rozpoczęciem napromieniania na podstawie zdjęć weryfikacyjnych.W monitorowanej grupie tygodniowe zdjęcia weryfikacyjne wykonano 78% napromienianych chorych. Codzienne zdjęcia weryfikacyjne z seriami zdjęć w trakcie napromieniania chorych. Różne błędy zostały zarejestrowane u 33% monitorowanych chorych w trakcie radioterapii. Większość błędów została skorygowana w trakcie leczenia, niektóre zostały zauważone podczas analizy po zakończeniu napromieniania. Zarejestrowano 2132 zdjęć elektronicznych do dalszej analizy. Target View umożliwia weryfikowanie poprawności leczenia u większości leczonych chorych bez zmniejszenia liczby napromienianych pacjentów. Otrzymane zdjęcia elektroniczne są dobrej jakości, co umożliwia zarejestrowanie i korekcję różnych błędów geometrycznych przed rozpoczęciem i w trakcie leczenia.Zarejestrowane zdjęcia elektroniczne mogą być precyzyjnie analizowane poprzez nakładanie na siebie i pomiary zauważonych rozbieżności w celu poprawy jakości radioterapii

10. The comparison between the three – field and four-field techniques of planning of radiotherapy in prostate cancer

Purposeevaluation 3-field(3F) and 4-field(4F) planning techiniques for patients with localized prostate cancer. Materials/methods: Five patients with prostate cancer (T3N0M0) were evaluated. CT images were obtained at 5 mm increments and were transferred to CadPlan_planning_workstation. The planning target volume (PTV) was defined as prostate and seminal vesicles with 15mm margins around clinical target volume (CTV) except prostate-rectum interface where 5 mm margin was applied. CTV was defined as prostate and seminal vesicles. Following organs at risk (OAR) were outlined: rectum, bladder, right femoral head. Following 3F and 4F plans were performed: 3F with angles (0deg-120deg-240deg; 0deg-90deg-270deg) and 4F (Odeg-90deg-180deg-270deg). We also created two versions of treatment plans including of energy; 6 MV and 20 MV for Clinac2300CD. Total dose was 74 Gy. Mean total doses of thirty plans in irradiated organs at risk (rectum, bladder and righ femoral head) were compared. For PTV mean and minimum dose were criteria for comparision of treatment plans. Results: There were no significant dose differenes between evaluated plans of treatment in PTV (0.05). Because mean dose in femoral head in each treatment plan was below tolerance dose, main dose-limiting organ was rectum and bladder. Lowest mean dose 42.7 Gy in rectum was achived by application of 3F technique of 20 MV(0deg-90deg-270deg). Bladder was also spared with the same 3F technique of 20 MV, where mean dose was 45.2 Gy. Conclusions: This study showed that the, T” three-field technique (an anterior and two opposing lateral fields) provided with 20 MV is optimal and assures the lowest rectal dose

The results of salvage surgery combined with reirradiation in nodal recurrence of larynx cancer

The recurrence in the regional lymph nodes of patients after total laryngectomy and postoperative radiotherapy is a still serious therapeutic problem. The conditions that are altered following the combined primary treatment make it difficult to achieve satisfactory results of the second surgical treatment.The aim of our study was to evaluate the outcome of a salvage operation (lymphadenectomy) and reirradiation in 50 patients with recurrence in regional lymph nodes (rN). Beetwen 1991 and 1996, 650 patients with larynx carcinoma were treated in our institiutions. All patients during the primary irradiation received a total dose of about 60 Gy. In the case of regional recurrence (rN) patients had selective lymphadenectomy and reirradiation (total dose 40 Gy) when capsulae were found to be infiltrated. The survival rates were for 1, 2 and 3 years : 34 (68%), 22 (44%), only 9 (18%) respectivly. This strategy of a second combined treatment had a good tolerance level, without any unacceptable side effects (complications)

79. The effectivness of pain treatment with Strontium 89 in patient with osseous metastases

Aimof this study was to assessment of 89 Sr therapy as pain treatment modality in the group of patients with multiple bone metastases.Material and methodsFrom January 2000 to October 2000 in our center were treated 41 patients; 17 – prostate cancer and 24 – breast cancer patients. All patients had applied only one dose of 150 MBq of 89 Sr. Before and follow-up each patient has been evaluated; performance status according to the Karnofsky Scale and paro intensity according the VAS scale. We did not observe any clinical important haematological side effects. The ionisation dosemetric monitoring of the sources and the radioactive refuse were recorded. The radioactive refuse was storage in special container when the activity decreased to the background.ResultsWe noted relief of paro as follow:-“complete” 18 of 41 patients (8-prostate cancer, 10 – breast cancer),-“partial” 12 of 41 patients (3- prostate cancer, 9- breast cancer),-“no effect” 11 of 41 patients (6-prostate cancer, 5- breast cancer).ConclusionsWe suggest that therapy of painful multiple bone metastases with application of 89 Sr is effective nd safe

Randomized, Double-Blind, Placebo-Controlled Phase III Study of Tasquinimod in Men With Metastatic Castration-Resistant Prostate Cancer

PURPOSE: Tasquinimod, a novel oral therapy targeting the tumor microenvironment, significantly improved progression-free survival (PFS) in a randomized, placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). This phase III study was conducted to confirm the phase II results and to detect an overall survival (OS) benefit. PATIENTS AND METHODS: Men with chemotherapy-naïve mCRPC and evidence of bone metastases were assigned (2:1) to receive tasquinimod once per day or placebo until progression or toxicity. The primary end point was radiographic PFS (rPFS; time from random assignment to radiologic progression or death) per Prostate Cancer Working Group 2 criteria and RECIST 1.1. The study had 99.9% power to detect an rPFS hazard ratio (HR) of 0.6 with a two-sided alpha error of .05 and 80% power to detect a target HR of 0.8 for OS, the key secondary end point. RESULTS: In all, 1,245 patients were randomly assigned to either tasquinimod (n = 832) or placebo (n = 413) between March 2011 and December 2012 at 241 sites in 37 countries. Baseline characteristics were balanced between groups: median age, 71 years; Karnofsky performance status ≥ 90%, 77.3%; and visceral metastases, 21.1%. Estimated median rPFS by central review was 7.0 months (95% CI, 5.8 to 8.2 months) with tasquinimod and 4.4 months (95% CI, 3.5 to 5.5 months) with placebo (HR, 0.64; 95% CI, 0.54 to 0.75; P < .001). Median OS was 21.3 months (95% CI, 19.5 to 23.0 months) with tasquinimod and 24.0 months (95% CI, 21.4 to 26.9 months) with placebo (HR, 1.10; 95% CI, 0.94 to 1.28; P = .25). Grade ≥ 3 adverse events were more frequent with tasquinimod (42.8% v 33.6%), the most common being anemia, fatigue, and cancer pain. CONCLUSION: In chemotherapy-naïve men with mCRPC, tasquinimod significantly improved rPFS compared with placebo. However, no OS benefit was observed

Asymmetry of 13C labeled 3-pyruvate affords improved site specific labeling of RNA for NMR spectroscopy

Selective isotopic labeling provides an unparalleled window within which to study the structure and dynamics of RNAs by high resolution NMR spectroscopy. Unlike commonly used carbon sources, the asymmetry of 13C-labeled pyruvate provides selective labeling in both the ribose and base moieties of nucleotides using E. coli variants, that until now were not feasible. Here we show that an E. coli mutant strain that lacks succinate and malate dehydrogenases (DL323) and grown on [3-13C]-pyruvate affords ribonucleotides with site specific labeling at C5′ (~95%) and C1′ (~42%) and minimal enrichment elsewhere in the ribose ring. Enrichment is also achieved at purine C2 and C8 (~95%) and pyrimidine C5 (~100%) positions with minimal labeling at pyrimidine C6 and purine C5 positions. These labeling patterns contrast with those obtained with DL323 E. coli grown on [1, 3-13C]-glycerol for which the ribose ring is labeled in all but the C4′ carbon position, leading to multiplet splitting of the C1′, C2′ and C3′ carbon atoms. The usefulness of these labeling patterns is demonstrated with a 27-nt RNA fragment derived from the 30S ribosomal subunit. Removal of the strong magnetic coupling within the ribose and base leads to increased sensitivity, substantial simplification of NMR spectra, and more precise and accurate dynamic parameters derived from NMR relaxation measurements. Thus these new labels offer valuable probes for characterizing the structure and dynamics of RNA that were previously limited by the constraint of uniformly labeled nucleotides

Site-specific labeling of nucleotides for making RNA for high resolution NMR studies using an E. coli strain disabled in the oxidative pentose phosphate pathway

Escherichia coli (E. coli) is a versatile organism for making nucleotides labeled with stable isotopes (13C, 15N, and/or 2H) for structural and molecular dynamics characterizations. Growth of a mutant E. coli strain deficient in the pentose phosphate pathway enzyme glucose-6-phosphate dehydrogenase (K10-1516) on 2-13C-glycerol and 15N-ammonium sulfate in Studier minimal medium enables labeling at sites useful for NMR spectroscopy. However, 13C-sodium formate combined with 13C-2-glycerol in the growth media adds labels to new positions. In the absence of labeled formate, both C5 and C6 positions of the pyrimidine rings are labeled with minimal multiplet splitting due to 1JC5C6 scalar coupling. However, the C2/C8 sites within purine rings and the C1′/C3′/C5′ positions within the ribose rings have reduced labeling. Addition of 13C-labeled formate leads to increased labeling at the base C2/C8 and the ribose C1′/C3′/C5′ positions; these new specific labels result in two- to three-fold increase in the number of resolved resonances. This use of formate and 15N-ammonium sulfate promises to extend further the utility of these alternate site specific labels to make labeled RNA for downstream biophysical applications such as structural, dynamics and functional studies of interesting biologically relevant RNAs

Applications of click chemistry in modification of nucleosides and oligonucleotides

Since the year 2001 new ideology of clean and simple synthesis in organic chemistry has been established. The outstanding scientists Meldal and Sharpless presented their concepts of Click Chemistry. Among the reactions chosen for this concept the reaction of Copper(I) Catalyzed Alkyne-Azide Cycloaddition (CuAAC) became the most popular one. It is the basis of syntheses employed for building blocks synthesis in medicinal chemistry and material science. Libraries of potentially pharmacologically active anticancer and antivirus compounds possessing neutral triazol linkage could be easily obtained. Remarkable efficiency of CuAAC reaction influenced on DNA- and RNAbased synthesis of novel oligonucleotides derivatives. Many of nucleic acid molecular modifications found applications in enzymatic transformation, nucleic acid hybridization, molecular tagging and gene silencing. The CuAAC reaction allows for introducing modifications into practically every region of nucleoside/nucleotide/ oligonucleotide. This includes versatile modifications of the base moiety both aiming at the base pairing ability or specific labeling of the nucleoside unit. Different conjugates (bio-, fluorescent-, affinity- or spin labels) are being attached to the base part of the nucleic acid taking advantage of the presence of azide or alkyne substituents, which can be installed without great difficulty. Labeling at the sugar part of the nucleoside can be realized at the position 2’, 3’ or 5’, the latter two giving rise to the end-labeled oligonucleotides and the 2’ position serving as the attachment point for labeling inside the oligonucleotide chain. These kind of nucleic acid modifications are very promising. Versatility of CuAAC reactions is demonstrated by numerous examples of introducing modifications into practically every reactive site of the nucleotide/oligonucleotide molecule. The review systematically presents application of the “click” technique for modification of nitrogenous base, sugar or pseudosugar moiety or phosphorus center. Possibility of creating new kind of chain linkage, devoid of negative charge and nuclease resistant is also shown. This allows to design a new class of nucleic acid analogues, similar in its DNA-mimicking properties to PNA’s