Survival and toxicity of radical radiotherapy (with or without brachytherapy) for FIGO stage I and II cervical cancer: a mono-institutional analysis.

PURPOSE OF INVESTIGATION: To add to the existing outcome data regarding radical radiotherapy (RT) for FIGO Stage I and II cervical cancer in a mono-institutional series and to evaluate the cost-benefit ratio of the addition of brachytherapy (BRA) to external-beam radiotherapy (EBRT). MATERIALS AND METHODS: The authors report on 240 patients (pts) with FIGO Stage I and II cervical cancer, consecutively treated with radical RT from 1990 through 2009 at the Istituto del Radio "O. Alberti" (EBRT alone, 32, EBRT and BRA, 189, BRA alone, 19). BRA was delivered with low dose rate (LDR, 133.64%) until 2003 and then with high dose rate (HDR, 75.36%). RT was associated with concomitant chemotherapy (CHT), mainly weekly cisplatin 40 mg/m2, in 87 pts, mostly after 2000. The Chi-square test was used to compare the different variables, the Log-Rank test to compare the actuarial survival values, and the Cox-model for the multivariate analysis. RESULTS: Five-year actuarial overall survival (OS) equalled 65%, disease specific survival (DSS) 77%. Regardless of disease stage, better DSS was evident in pts treated with EBRT and BRA compared with those treated with EBRT alone (82% and 58% respectively, p = 0.005); pts treated with concomitant CHT (dose intensity > or = 50%) and higher RT doses (RT cumulative EQD2 > or = 75 Gy) obtained better DSS. Complete response (CR) rate approached 88.4% (206/233 evaluable pts) and more than half of the subsequent failures (21/36) were in distant sites. Older patients and those given BRA had better OS and DSS, while BRA dose rate did not result related with these outcomes. Chronic G3/G4 toxicity involved more frequently the intestinal/rectal tract than other organs at risk. Rectal and vaginal serious chronic sequelae developed mainly in pts treated with EBRT and BRA and suggest the need for more advanced treatment techniques. CONCLUSIONS: the present mono-institutional analysis confirms the efficacy of radical RT for the treatment of cervical cancer and provides support to the role of BRA to obtain better outcomes. An effort to reduce long-term toxicity of the treatment is needed.

Dosimetry study in patients with autonomous thyroid nodule who are candidates for radioiodine therapy.

UNLABELLED: A dosimetry study was performed on 26 patients with an autonomous thyroid nodule and suppressed serum thyroid-stimulating hormone, to determine the dose to extranodular tissue when the nodule receives 300 Gy for 131I therapy. METHODS: Parameters of radioiodine turnover to be used in the dosimetry formula were separately obtained for the nodule and the contralateral lobe, as a measurable example of the extranodular tissue, using 55 MBq 123I and a computer-assisted gamma camera. The biologic half-life of 123I was then converted into the effective half-life of 131I, and the volumes of the nodule and the lobe were obtained by scintigraphy or sonography. RESULTS: The mean dose to the contralateral lobe from uptake and irradiation by the nodule was calculated to be 32 Gy, and that to the ipsilateral lobe was estimated to be 34 Gy. CONCLUSION: During radioiodine therapy for autonomous thyroid nodules, the extranodular tissue receives a higher dose than is generally assumed, which explains the relatively high rate of post-treatment hypothyroidism reported in the literature.

Effect of trichloromethyl and trichloromethyl peroxyl free radicals on protein sulfhydryl content studies in model and in enzymatic carbon tetrachloride activation systems.

The effect of trichloromethyl and trichloromethyl peroxyl free radicals on protein sulfhydryl content was studied using both, model and enzymatic activation systems. In the model system activation of CCl4 to both free radicals was by UVC light and the target protein was either delipidated or undelipidated albumin. Under air, the CCl3O2. radicals were able to significantly decrease the protein SH in both albumin preparations. A small but signficant effect of UVC alone was observed with defatted albumin. No significant decreases in protein sulfhydryl were observed by .CCl3 attack on the defatted albumin. Reaction of CCl3O2. on cysteine SH led to chloroform formation indicating that a H abstraction reaction is involved in the process. UVC light has an own effect on SH group content. Similar results were obtained when the interaction was with undelipidated albumin rather than with cysteine. Their formation was significantly prevented by Trolox 1 mM in incubation mixture. When the CCl3O2. were generated by liver microsomal activation of CCl4 under air, a significant decrease in microsomal protein SH content was observed. NADPH also exerted an effect of its own. These decreasing effects were fully prevented by either Trolox or EDTA addition to incubation mixtures but not by alpha-tocopherol free or as a succinate ester. Incubation mixtures containing nuclear suspensions and NADPH led to a decrease in protein SH content. This decrease was not enhanced further by the presence of CCl4. No effect on the protein SH content was observed when either mitochondrial or cytosolic fractions were employed to attempt activation of CCl4 to .CCl3/CCl3O2. free radicals. The ability of CCl4 derived free radicals to decrease protein SH in liver microsomes could be involved in loss of activity of key SH enzymes of relevance such as microsomal calcium pump. This pump is known to be damaged during CCl4 poisoning. This effect was blamed to initiate alterations in calcium homeostasis later leading to CCl4 induced liver cell death.

[Intracavitary brachytherapy in esophageal neoplasms. Experience at the Radiology Institute of Brescia]. / La brachiterapia endocavitaria nelle neoplasie esofagee. L'esperienza dell'istituto del Radio di Brescia.

We investigated the role of brachytherapy in the management of esophageal cancer. From March, 1990, to December 1994, seventy patients, with biopsy-proved esophageal carcinoma, were treated with brachytherapy +/- external beam radiotherapy. According to the TNM staging system, 24 patients were graded as T1, 24 as T2, 10 as T3, 9 as T4, and 3 as Tx. Median Karnofsky score was 80. Dysphagia was the major symptom in 68% of cases. Treatment consisted of low dose rate first, and then high dose rate brachytherapy, with progressive optimization of doses and fractions, up to total doses of 15-30 Gy in low dose rate and 7-21 Gy in high dose rate. When associated, external beam radiotherapy was delivered with conventional schedules. Tolerance to treatment was good with slight acute toxicity. Symptoms were markedly improved, with reduction of dysphagia in 100% of cases. Overall survival was 75%, 47%, 23% and 18% at 6, 12, 24, 36 months; no significant difference was found between low and high dose rate groups. Furthermore, no difference was shown in the overall survival of the group treated with brachytherapy alone and the one with associated external beam radiotherapy. Late toxicity occurred in 10% of patients and was managed by endoscopic procedures in all cases. In our opinion, brachytherapy appears to be an effective palliative treatment; its role as radical treatment remains to be defined.

Carbon tetrachloride-induced free radical mediated protein oxidation in vitro and in vivo.

Trichloromethyl and trichloromethylperoxyl free radicals generated by UVC light activation of carbon tetrachloride promote the formation of protein carbonyls in chicken egg albumin in vitro. Further, UVC light itself exerts a highly significant equivalent effect of its own. The reaction was significantly blocked by Trolox but not by α-tocopherol at a concentration of 1 mM. EDTA (3 mM) partially prevented the oxidative effects of (•)CCl3 or CCl3O2(•) in proteins but not those of UV light. Rat liver microsomes in the presence of NADPH also led to the formation of carbonyl groups in microsomal proteins. That effect was significantly enhanced by the presence of CCl4 in the incubation mixture. Liver microsomes from CCl4 poisoned animals exhibited significantly increased levels of protein carbonyls at 1 and 2 h after administration but not at 3 h. These results suggest that proteins might be targets of CCl4 oxidative effects. Protein carbonyls might arise from either direct attack by (•)CCl3 or CCl3O2(•), or from 4-hydroxynonenal reaction via Michael addition with amino acids at the aldehyde double bond and retaining the carbonyl group attached to the target protein.

High-dose-rate brachytherapy for poor-prognosis, high-grade glioma: (phase II) preliminary results.

AIMS AND BACKGROUND: The purpose of this study was to investigate the palliative effectiveness of an interstitial fractionated high-dose-rate (HDR) brachytherapy regimen in patients with poor-prognosis, high-grade glioma. METHODS: An after-remote-loading microSelectron HDR lr-192 370 GBq unit was used. A unique coaxial after-loading catheter was stereotactically inserted through the center of the target volume. The treatment schedule was: 5 fractions, 5 Gy per fraction, or alternatively 7 fractions, 3.85 Gy per fraction, at the dose specification surface, 2 fractions per day. Twenty-four patients have been treated: in 17 of them (T1 G3-4) the catheter was implanted during stereotactic biopsy procedure; in the other 7 cases (T2 G3-4), subjected to partial resection and reduced to yT1, the catheter was implanted following surgery with a mean delay of 15 days. RESULTS: The treatment was feasible and well tolerated. The complete course takes no more than 7 days. The acute complication rate (2/24) seems to be acceptable. The median survival was 8 months. No less than 45% of the patients had a WHO grade 2 score or better at any time of follow-up. At 4 months of follow-up, functional status, assessed using a verbally administered Barthel index, had improved from the pretreatment level in 29.1% of the 18 surviving patients and remained stable in another 22.2%. A minimal response or stable disease, according to CT scan, was obtained in about half of the assessable survivors at any time of follow-up. CONCLUSIONS: The short course of brachytherapy provides a good palliation in terms of functional improvement in a high proportion of patients, with low and acceptable toxicity.

Dosimetry of 169 Yb seed model X1267.

Unlike previous brachytherapy sources a number of published studies have been addressed to the dosimetry of 169 Yb seeds, manufactured in several prototypes, before widespread clinical use has been made. Discrepancies seen in the dosimetry obtained for ytterbium seed prototypes appear to be related to inconsistency and non-reproducibility in the vendor's calibration procedure to determine contained activity. Av. The comparison of 169 Yb seed dosimetries demonstrates a need for more accurate implementation of calibration procedures to determine the air kerma rate for the definitive 169 Yb seed design. This paper reports an experimental procedure to determine the reference air kerma rate, Kr (mu Gy h-1), defined as the kerma rate at 1 m along the source transverse axis in free space for the new 169 Yb seed, model X1267. A mean value of the ratio Kr/Av = 1.53 mu Gy h-1 mCi-1 was obtained from determining the Kr value of eleven seeds. Since this ratio is only 3% less than the air kerma rate constant for the 169 Yb point source, (gamma delta)k = 1.58 mu Gy h-1 m2 mCi-1, this means that the Av is closer to an apparent activity than a contained activity, Ac. A Monte Carlo simulation to determine the ratio between reference air kerma rate and the contained activity gave Kr/Ac = 1.33 mu Gy h-1 mCi-1. For the dose rate constant in water we obtained DKr (1, pi/2) = 1.20 +/- 0.05 cGy h-1 (mu Gy h-1)-1, using calibrated thermoluminescent dosimeters (TLDs) and DKr (1, pi/2) = 1.21 +/- 0.03 cGy h-1 (mu Gy h-1)-1 by Monte Carlo simulation. TLDs were used both to determine the radial dose distribution along the seed transverse axis and to calibrate GAFChromic films to obtain the two-dimensional dose distribution around the seed.

Mechanistic understanding of enamel mineralization under fluoride regime.

In order to learn more about how the microenvironment for enamel mineralization is modified by fluoride at low concentrations (0 through 1 ppm) and how excess fluoride retards the degradation and removal of amelogenins, we studied precipitation reactions in an in vitro model utilizing a dialysis chamber. The results showed that, with the limited supply of Ca ions through the ultrafiltration membrane, the solution composition surrounding the seed crystals showed a proximity to the steady-state condition after 12-24 h equilibration. Major findings were that (a) fluoride overcame partially the inhibition of precipitation and growth reactions by enamel proteins and (b), with this accelerating effect of fluoride, the steady-state Ca concentrations in the media surrounding the seed crystals decreased substantially as a function of fluoride concentration. The overall results support the concept that the presence of fluoride in the mineralizing milieu can modify markedly the steady-state concentrations of mineral lattice ions, particularly decreasing free Ca2+ concentrations, which in turn may modulate protease activities in situ.

High-dose interstitial brachytherapy for glioblastoma multiforme.

AIMS AND BACKGROUND: The long-term prognosis for survival of patients with inoperable glioblastoma multiforme (GBL) is very poor. Conventional external radiotherapy gives only transitory result. This severe prognosis led us to elaborate a high-dose rate (HDR), after-remote-loading brachytherapy treatment protocol: our aim was both therapeutic and psychologic. METHODS: Five patients with GBL (T1 G4 UICC) were treated with stereotactic biopsy followed by HDR brachytherapy. A unique coaxial after-loading catheter was stereotactically inserted through the center of the target volume. The treatment schedule considered 5 fractions, 5 Gy/fraction at the dose specification surface, 2 fractions per day. RESULTS: The treatment was well tolerated. Tumor progression started again at the 8th to the 16th week from the end of the treatment. ECOG performance status at the 8th week was better than before the therapy in 2 of 5 patients and was stable in 2 of 5 patients. Order neuroperformance status was stable in 2 patients at 8 weeks. At the 16th week there was neurologic deterioration. The average survival was 21 weeks. CONCLUSIONS: Our approach seems to be of some interest for the palliation of GBL, and it offers some advantages, in particular regarding the short treatment period. Our procedure can be improved: a multi-catheter implant and a more fractionated schedule could be taken into account.

Decreased incorporation of 14C-leucine in different liver nuclear protein fractions at early stages of carbon tetrachloride poisoning in the rat.

Administration of CCl4 to 12-14 h starved Sprague Dawley male rats (220-240 g) at a dose of 5 ml of a 20% (v/v) olive oil solution/kg i.p. decreased the incorporation of 14C-leucine into microsomal and nuclear proteins at 1 or 2 h after the hepatotoxin. Decreased amino acid incorporation capacity in nuclear but not in microsomal proteins returned to control values at 4 h after poisoning. Cycloheximide given i.p. at a dose of 1 mg/kg in saline either alone or before CCl4 also decreased to a similar or greater extent the incorporation of 14C-leucine into both, microsomal and nuclear proteins at 1 h. The CCl4-induced decrease in amino acid incorporation was observable and significant even 1 h after CCl4 and involved histone and different non-histone nuclear protein fractions. Results suggest that decreased protein synthesis at the endoplasmic reticulum occurring in the very early stages of CCl4 poisoning might provoke temporary deficiencies in protein supplies to nuclei with as yet unknown consequences. However, some of the proteins involved have major regulatory properties in DNA expression.

A comparison of accuracy of computer treatment planning systems in brachytherapy.

An intercomparison was made between dose-rate point calculations with five commercial computer treatment planning systems used in brachytherapy. Sixteen Italian radiotherapy medical physics institutions performed a twofold test, respectively for point and linear sources, reproducing actual clinical implants and the results were compared to references values. The test was designed in order to determine the errors introduced separately by computation and by implant reconstruction via orthogonal films. The results show that for point sources a better accuracy can be achieved than for linear sources. It is also shown that a large variation of results exists between computation systems and the variability is larger for linear sources. The digitizing procedure adds a large amount of error. In the whole set of calculation points, the overall percent difference between computed and reference dose-rate values is larger than +/- 5% in 18% cases for point and in 52% cases for linear sources, with data input by digitizer. It seems that relevant errors do occur when computing actual dose rates, resulting in clinically relevant inaccuracies in the calculated absorbed dose and in its relative effectiveness.

Resampling algorithms for diagnostic radiology.

The use of digital image resampling can be highly suitable for diagnostic radiology. It can be applied not only to obtain zoom effects but also to solve various problems related to the comparison of images of different origin (NMR, CT, NM). The mathematical approach to this kind of algorithm, based on rational assumptions, can be very wide and diversified. In this work the principles of the stochastic and of the analytical methods have been analyzed. In particular, a complete mathematical treatment of the integral analytical methods, which are both the most theoretically interesting and analytically complex, has been performed. The practice of these techniques has to be determined each time from the analysis of the specific problem to which they are to be applied in the routine, and after a retrospective analysis of the results obtained.

Adsorption/desorption of human serum albumin on hydroxyapatite: a critical analysis of the Langmuir model.

We studied the adsorption of human albumin onto synthetic hydroxyapatite, using a radiotracer technique and a special flow cell. Adsorption was studied under various conditions corresponding to different thermodynamic paths. It appears that (i) as is the usual case, the isotherms obtained within a short time range (a few hours) do not correspond to a true equilibrium situation; (ii) when the adsorption process is followed for longer times, which is necessary at low bulk concentrations, one always reaches the plateau surface adsorption; (iii) this plateau value is independent of the "history" of the adsorption process and corresponds well to the jamming limit predicted by the random sequential adsorption model; and (iv) surface denaturation, leading to enhanced surface binding and thus decreasing desorption constants, is the important phenomenon that can partly and qualitatively explain our observations. Its time dependence, however, remains to be clarified.

[Simulation of an instrumental head for 6 MeV electron beam therapy]. / Simulazione di una testata di terapia per fasci di elettroni di 6 MeV.

Simulation of a therapy head for 6 MeV electron beams. We present the results of a simulation, performed using a Monte Carlo method, of depth dose curves in water for electron beams of initial kinetic energy of 6.4 MeV, generated by a radiotherapy microtron MM22 Scanditronix. The Fortran code in EGS4: comparison is made between simulated curves, obtained using various approximation criteria, and the experimental one.