Radiation therapy combined with intracerebral administration of carboplatin for the treatment of brain tumors

Background: In this study we determined if treatment combining radiation therapy (RT) with intracerebral (i.c.) administration of carboplatin to F98 glioma bearing rats could improve survival over that previously reported by us with a 15 Gy dose (5 Gy × 3) of 6 MV photons.Methods: First, in order to reduce tumor interstitial pressure, a biodistribution study was carried out to determine if pretreatment with dexamethasone alone or in combination with mannitol and furosemide (DMF) would increase carboplatin uptake following convection enhanced delivery (CED). Next, therapy studies were carried out in rats that had received carboplatin either by CED over 30 min (20 μg) or by Alzet pumps over 7 d (84 μg), followed by RT using a LINAC to deliver either 20 Gy (5 Gy × 4) or 15 Gy (7.5 Gy × 2) dose at 6 or 24 hrs after drug administration. Finally, a study was carried out to determine if efficacy could be improved by decreasing the time interval between drug administration and RT.Results: Tumor carboplatin values for D and DMF-treated rats were 9.4 ±4.4 and 12.4 ±3.2 μg/g, respectively, which were not significantly different (P = 0.14). The best survival data were obtained by combining pump delivery with 5 Gy × 4 of X-irradiation with a mean survival time (MST) of 107.7 d and a 43% cure rate vs. 83.6 d with CED vs. 30-35 d for RT alone and 24.6 d for untreated controls. Treatment-related mortality was observed when RT was initiated 6 h after CED of carboplatin and RT was started 7 d after tumor implantation. Dividing carboplatin into two 10 μg doses and RT into two 7.5 Gy fractions, administered 24 hrs later, yielded survival data (MST 82.1 d with a 25% cure rate) equivalent to that previously reported with 5 Gy × 3 and 20 μg of carboplatin.Conclusions: Although the best survival data were obtained by pump delivery, CED was highly effective in combination with 20 Gy, or as previously reported, 15 Gy, and the latter would be preferable since it would produce less late tissue effects.peer-reviewe

Geology of the historical Bodrogköz

Abstract The Bodrogköz is predominantly a flat area surrounded by the rivers Tisza, Bodrog and Latorica. The Hungarian-Slovakian border cuts it into two parts; consequently, the geologic data in the two countries are different in terms of scale and in approach. The authors harmonized the different data on the two sides and created a unified geologic database for the entire area. The Bodrogköz is part of the depression at the northeastern part of the Great Hungarian Plain. It is covered mostly by Quaternary formations but in the Slovakian part there are smaller outcrops of Permian formations and Miocene volcanics

Patients with femoral or distal forearm fracture in Germany: a prospective observational study on health care situation and outcome

BACKGROUND: Distal radius and proximal femoral fractures are typical injuries in later life, predominantly due to simple falls, but modulated by other relevant factors such as osteoporosis. Fracture incidence rates rise with age. Because of the growing proportion of elderly people in Western industrialized societies, the number of these fractures can be expected to increase further in the coming years, and with it the burden on healthcare resources. Our study therefore assessed the effects of these injuries on the health status of older people over time. The purpose of this paper is to describe the study method, clinical parameters of fracture patients during hospitalization, mortality up to one and a half years after discharge in relation to various factors such as type of fracture, and to describe changes in mobility and living situation. METHODS: Data were collected from all consecutive patients (no age limit) admitted to 423 hospitals throughout Germany with distal radius or femoral fractures (57% acute-care, femoral and forearm fractures; 43% rehabilitation, femoral fractures only) between January 2002 and September 2003. Polytrauma and coma patients were excluded. Demographic characteristics, exact fracture location, mobility and living situation, clinical and laboratory parameters were examined. Current health status was assessed in telephone interviews conducted on average 6–7 months after discharge. Where telephone contact could not be established, at least survival status (living/deceased/date of death) was determined. RESULTS: The study population consisted of 12,520 femoral fracture patients (86.8% hip fractures), average age 77.5 years, 76.5% female, and 2,031 forearm fracture patients, average age 67.6 years, 81.6% female. Women's average age was 6.6 (femoral fracture) to 10 years (forearm fracture) older than men's (p < 0.0001). Only 4.6% of femoral fracture patients experienced changes in their living situation post-discharge (53% because of the fracture event), although less than half of subjects who were able to walk without assistive devices prior to the fracture event (76.7%) could still do so at time of interview (34.9%). At time of interview, 1.5% of subjects were bed-ridden (0.2% before fracture). Forearm fracture patients reported no change in living situation at all. Of the femoral fracture patients 119 (0.95%), and of the forearm fracture patients 3 (0.15%) died during hospital stay. Post-discharge (follow-up one and a half years) 1,463 femoral fracture patients died (19.2% acute-care patients, 8.5% rehabilitation patients), but only 60 forearm fracture patients (3.0%). Ninety percent of femoral fracture deaths happened within the first year, approximately 66% within the first 6 months. More acute-care patients with a pertrochanteric fracture died within one year post-discharge (20.6%) than patients with a cervical fracture (16.1%). CONCLUSION: Mortality after proximal femoral fracture is still alarmingly high and highest after pertrochanteric fracture. Although at time of interview more than half of femoral fracture patients reported reduced mobility, most patients (96%) attempt to live at home. Since forearm fracture patients were on average 10 years younger than femoral fracture patients, forearm fractures may be a means of diagnosing an increased risk of later hip fractures

BNCT: Status and Dosimetry Requirements

BNCT is a binary cancer treatment modality, consisting of the delivery of a suitable boron compound to tumour cells followed by irradiation of the tumour by thermal neutrons. Originally proposed by Locher in 1936, the first clinical trials at Brookhaven and at MIT in the 1950s were unsuccessful because of the non-selectivity of the boron compound used. New classes of boron carriers have since been developed and neutron sources have been optimised. Since 1968 more than 100 patients have been treated in Japan. Clinical studies have again started in the USA (1994 at MIT and BNL) and are expected soon to begin in Europe. Basic principles of this treatment modality and general requirements for boron compounds and reactor or accelerator based neutron sources are reviewed. Complexities involved in macro- and microdosimetry and thus the biological evaluation of boron compounds are discussed

Tumor Volume Delineation in Head and Neck Cancer With Imaging Modalities: CT, PET, MRI, Compared With Pathological Tumor Volume

Accurate delineation of the gross tumor volume is crucial in radiation treatment planning. It has been reported that the gross tumor volume determined by CT (GTVCT) or MRI (GTVMRI) is larger than that by PET (GTVPET). The tumor volume determined by a standardized uptake value (SUV) has been reported not to correlate well with tumor volume as judged by the surgically resected pathological specimen (GTVPA). In order to more accurately guide radiation therapy, correlation between the pathological tumor volumes and various imaging-based tumor volume delineations is essential to validate the efficacy of these imaging methodologies

SU-E-T-352: Why Is the Survival Rate Low in Oropharyngeal Squamous Cell Carcinoma?

Purpose: Tumors are composed of a large number of clonogens that have the capability of indefinite reproduction. Even when there is complete clinical or radiographic regression of the gross tumor mass after treatment, tumor recurrence can occur if the clonogens are not completely eradicated by radiotherapy. This study was to investigate the colonogen number and its association with the tumor control probability (TCP) in oropharyngeal squamous cell carcinoma (OSCCA). Methods: A literature search was conducted to collect clinical information of patients with OSCCA, including the prescription dose, tumor volume and survival rate. The linear-quadratic (LQ) model was incorporated into TCP model for clinical data analysis. The total dose ranged from 60 to 70 Gy and tumor volume ranged from 10 to 50 cc. The TCP was calculated for each group according to tumor size and dose. The least χ^2 method was used to fit the TCP calculation to clinical data while other LQ model parameters (α, β) were adopted from the literature, due to the limited patient data. Results: A total of 190 patients with T2–T4 OSCCA were included. The association with HPV was not available for all the patients. The 3-year survival rate was about 82% for T2 squamous cell carcinoma and 40% for advanced tumors. Fitting the TCP model to the survival data, the average clonogen number was 1.56×10^(12). For the prescription dose of 70 Gy, the calculated TCP ranged from 40% to 90% when the tumor volume varied from 10 to 50 cc. Conclusion: Our data suggests variation between the clonogen number and TCP in OSCCA. Tumors with larger colonogen number tend to have lower TCP and therefore dose escalation above 70 Gy may be indicated in order to improve the TCP and survival rate. Our result will require future confirmation with a large number of patients

BNCT: a promising area of research?

The renewed interest in boron neutron capture therapy (BNCT) is driven mainly by the disappointing progress in the treatment of brain tumors by other modalities over the last decades. Even though molecular biology newer drugs and strategies may promise better results in the future, BNCT is an attractive approach. Brain tumors kill by local growth and not be metastases. Boron can be delivered to the tumor while normal brain is protected by the blood brain barrier, which can be disrupted to the degree desired. Tumor selectivity can be obtained not only by improved drug barrier, which can be disrupted to the degree desired. Tumor selectivity can be obtained not only by improved drug delivery but also by restricting the capture reaction to the region of interest by targeted radiation. Both boron drug and thermal neutrons alone are to some extent innocuous to tumor and normal tissues in this binary form of therapy. The pattern of treatment failure from uncontrolled primary tumor, the blood brain barrier protection of normal surrounding tissue and the limited range of epithermal neutrons explain why brain tumors are the main focus of BNCT research