Definition of stereotactic body radiotherapy: principles and practice for the treatment of stage I non-small cell lung cancer.

This report from the Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (Deutschen Gesellschaft für Radioonkologie, DEGRO) provides a definition of stereotactic body radiotherapy (SBRT) that agrees with that of other international societies. SBRT is defined as a method of external beam radiotherapy (EBRT) that accurately delivers a high irradiation dose to an extracranial target in one or few treatment fractions. Detailed recommendations concerning the principles and practice of SBRT for early stage non-small cell lung cancer (NSCLC) are given. These cover the entire treatment process; from patient selection, staging, treatment planning and delivery to follow-up. SBRT was identified as the method of choice when compared to best supportive care (BSC), conventionally fractionated radiotherapy and radiofrequency ablation. Based on current evidence, SBRT appears to be on a par with sublobar resection and is an effective treatment option in operable patients who refuse lobectomy.

Radiation treatment planning in brain tumours: potential impact of 3-O-methyl-6-[(18)F]fluoro-L-DOPA and PET.

AIM: Amino acid PET has become an important diagnostic tool for brain tumour imaging. In this data analysis, the potential impact of amino acid PET with 3-O-methyl-6-[(18)F]fluoro-L-DOPA ([(18)F]OMFD) on radiation treatment planning is addressed by the following questions: 1. Was tumour tissue identified with OMFD-PET which was not covered by the conventionally derived planning target volume (PTV)? 2. Would the PTV have been changed incorporating OMFD-PET? PATIENTS, METHODS: OMFD-PET of 25 patients after subtotal resection of malignant glioma was evaluated. The region of elevated tracer uptake of PET and of contrast enhancing masses on MRI were outlined as separate gross tumour volumes (GTV(MRI) and GTV(OMFD)) and reconstructed in the planning CT for comparison with the conventionally drawn GTV(conv). A PTV(new) based on GTV(conv+MRI) was calculated. Pairwise differential volumes were calculated to estimate overlap and differential volumes delineation by each image modality and the PTV(conv) and PTV(new) respectively. RESULTS: Differential volume analysis showed > 10 cm(3) of GTV(OMFD) outside GTV(conv) and GTV(MRI) in 5/25 patients respectively. From GTV(MRI) > 10 cm(3) were found outside GTV(OMFD) in 8/25 patients. Although all tumour areas indicated by [(18)F]OMFD were covered by the conventionally derived PTV, based on a GTV(OMFD+MRI), the PTV(new) would have been enlarged >20% in seven patients. In seven patients the PTV(new) would have been reduced. CONCLUSION: OMFD-PET indicated tumour tissue outside the tumour region identified with MRI, adding valuable information for the delineation of the GTV in radiation treatment planning. OMFD-PET contains the potential to tailor the high dose radiation to the appropriate tumour volume, especially if dose escalation is desired.

Sustained elevation of NF-kappaB DNA binding activity in radiation-induced lung damage in rats.

PURPOSE: To characterize the cellular distribution and DNA binding activity of the nuclear factor kappaB (NF-KappaB) in a model of radiation-induced lung damage in the rat. MATERIAL AND METHODS: The right lung of Fischer rats was irradiated with a single dose of 20 Gy. The cellular distributions of NF-KappaB proteins and mRNA were detected with immunohistochemistry and in-situ hybridization respectively. The DNA binding activity of NF-KappaB, nuclear and cytoplasmic levels of NF-KappaB proteins, and kinase activity towards IkappaBalpha (IKappaBAlpha) were determined using electrophoretic mobility shift assays (EMSA), Western blots and kinase assays, respectively. The mRNA level of interleukin 6 (IL-6) was determined using quantitative room temperature polymerase chain reaction. RESULTS: There was a continuous elevation of NF-KappaB DNA binding activity in the rat lung after ionizing irradiation over 6 months. The irradiated lung tissue exhibited an increased kinase activity towards IKappaBAlpha and a selective loss of nuclear IKappaBAlpha. The NF-KappaB-DNA binding complex switched from p50-p65 heterodimers in normal lung tissue to p50 homodimers in irradiated lung tissue. The increased level of IL-6 mRNA suggests transcriptional activation of NF-KappaB-dependent genes in the irradiated rat lung. CONCLUSIONS: The DNA binding activity of NF-KappaB is continuously activated after irradiation of the rat lung by loss of nuclear IKappaBAlpha. This might play a role in sustaining chronic inflammation and hyperproliferation of mesenchymal cells after irradiation.

3-O-methyl-6-[18F]fluoro-L-DOPA and its evaluation in brain tumour imaging.

3-O-Methyl-6-[(18)F]fluoro-L-DOPA (OMFD) is a major metabolite of 6-[(18)F]fluoro-L-DOPA. Although synthesis of OFMD was primarily established to study the dopaminergic system, as it is an amino acid analogue, uptake in experimental tumours has been found. The aim of this study was to evaluate the applicability of OMFD for brain tumour imaging and to obtain initial estimates of whole-body biodistribution and radiation dosimetry in humans. Nineteen patients with suspected or confirmed brain tumours were investigated with OMFD and dynamic brain PET, complemented by whole-body PET in seven patients. Tracer kinetics were compared for normal brain and intracerebral lesions. Tissue accumulation was quantified with standardised uptake values (SUVs). Whole-body distribution in combination with tracer kinetics from animal experiments was used for the calculation of radiation dosimetry data. On the basis of OMFD PET, viable brain tumour was suspected in 16 patients with SUVs of 3.0+/-0.8 and a tumour to non-tumour ratio of 1.9+/-0.5. Highest tumour and normal brain uptake occurred between 15 and 30 min, with a subsequent slow decrease. Late whole-body tracer distribution was uniform without specific organ accumulation. Elimination occurred via urine. The mean radiation dose to the whole body was estimated at 0.016 mSv/MBq, with the kidneys as dose-critical organ (0.033 mGy/MBq). In conclusion, OMFD enables the visualisation of brain tumours with SUVs similar to other fluorinated amino acids. The whole-body radiation exposure from OMFD is comparable to that from FDG imaging.

Patient position reproducibility in fractionated stereotactically guided conformal radiotherapy using the BrainLab mask system.

PURPOSE: Dedicated mask systems nowadays allow the use of stereotactic radiotherapy in fractionated regimes, therefore combining the advantages of high precision radiotherapy with the biological benefit of fractionation. Therefore the knowledge of institution specific isocenter accuracy is essential for decision-making about margins to be allowed to form the planning target volume. PATIENTS AND METHOD: Measurements of isocenter deviations during fractionated treatments were performed in 33 patients using the simulator Simulix-xy (Oldelft) in connection with the BrainLab angiographic localizer-box as well as port-films. In both cases repeated images were overlaid by use of anatomical landmarks with a methodical accuracy in the order of 0.5 mm. RESULTS: Both methods yield random isocenter deviations of less then 2 mm (standard deviation) in all three directions and no significant systematic deviations. These values are in the order of the accuracy of the method, obtained by comparison of two independent investigators, as well as they are comparable with the literature. CONCLUSIONS: The accuracy of less than 2 mm indicates safety margins of 3-4 mm as sufficient for clinical routine to cover the target in 95.5% of all set-ups (2 SD).

Response of pig lung to irradiation with accelerated 12C-ions.

The response of pig lungs to irradiation with 12C-ions was assessed in two experiments to validate the procedures for heavy ion therapy planning at the Gesellschaft für Schwerionenforschung (GSI) and to explore their range of applicability. In both experiments, the target volume (spread-out Bragg peak, SOBP) was planned to be a 4 cm long cylinder with a diameter of 4 cm. Doses in the SOBP were prescribed to be equivalent to 5x4 Gy, 5x5.5 Gy and 5x7 Gy of x-rays in the first experiment, and to 5 fractions of 7 Gy and 9 Gy in the second experiment. The lung response in the first experiment was less than expected on the basis of earlier experiments with photons. Pneumonitis reaction and chronic fibrotic changes were observed outside the prescribed high-dose region. In the second experiment, the effects were more pronounced than had been expected on the basis of the first experiment. Changes were most intense in the high-dose region, but were also seen throughout the lung along the beam channel. Moreover, significant skin reactions were observed at the beam entrance site in all animals and - less pronounced - at the beam exit site in 3 of the 6 animals. In conclusion, the complex irradiation geometry of the pig lung, the changes of body weight between the two experiments, and insufficient accounting for a change in the relative biological effectiveness (RBE) computation led to substantial deviations of the observed reactions from expectations, the reasons for which could be identified in a subsequent analysis. The less pronounced lung reaction in the first experiment was due to an overestimation of RBE in a preliminary version of the algorithm for its determination. The extension of the fibrotic reaction resulted from the smear-out of the high-dose region due to density variations in tissue structures, respiratory movement, and limited positioning accuracy. The skin reactions at the entrance port reflect the different treatment geometry in the two experiments. The one unexplained observation is the mild skin reaction that was observed in the second experiment at the beam exit site.

Stereotactically guided conformal radiotherapy for meningiomas.

PURPOSE: Stereotactically guided conformal radiotherapy, (SCRT) is a high precision technique of conformal radiotherapy (RT) which reduces the volume of normal tissue irradiated compared to conventional RT and may lead to a reduction in long-term toxicity We describe the technique and the preliminary results in patients with inoperable, residual or recurrent meningiomas. MATERIAL AND METHODS: From July 1993 to November 1997, 24 patients (median age: 56 years, range: 28-72) with base of skull (n = 21). falx or upper skull (n = 3) meningiomas were treated with SCRT. The technique employed immobilization in a Gill-Thomas-Cosman (GTC) frame and CT localization with a Brown-Roberts-Wells (BRW) fiducial system for stereotactic space definition. The planning target volume (PTV) was defined as gross tumour volume (GTV) and a 0.5-1 cm margin. Treatment was delivered with three (12 patients) or four non-coplanar conformal fixed fields (12 patients) Conformal blocking was achieved either with lead alloy blocks (n = 11) or with a multi-leaf collimator (MLC) (n = 13). Patients were treated on a 6 MV linear accelerator to doses of 50-55 Gy, in 30-33 daily fractions. The treatments were carried out as part of a routine work of a busy radiotherapy department. RESULTS: Median GTV for 24 meningiomas was 21.7 cm3 (range: 4.4-183 cm3). SCRT was well tolerated with minimal toxicity Three months after the end of radiotherapy, seven of 15 patients with neurological deficit had an improvement and eight remained unchanged. Two patients experienced early side effects (one VII nerve palsy, one Addisonian state). At a median follow-up of 13-months (range: 3-43) the 1 year progression free survival and overall survival are 100%. which is within the range expected for conventional fractionated radiotherapy for meningiomas. CONCLUSIONS: SCRT is a feasible technique of high precision conformal RT for patients with meningiomas. Potential advantages in tumour control, survival and toxicity over conventional RT, require evaluation in long-term prospective studies.

Patient position reproducibility in fractionated stereotactic radiotherapy: an update after changing dental impression material.

The reproducibility of patient positioning within the Gill-Thomas-Cosman relocatable stereotactic frame was re-evaluated following the substitution of a new, softer, dental impression material for the original hard acrylic compound. The average total displacement for a series of 10 patients was 1.1 mm (+/- 0.6 mm). Rotational discrepancies were small. This technique cannot deliver accurate repositioning in the absence of patient co-operation.

Fractionation effect on radiation-induced growth retardation of tibia in rabbits and rats.

A study of the sensitivity to fractionation of the growing tibia of rabbits and rats was conducted by comparing the growth of the treated right bone to that of the untreated left side in each individual animal using radiographic measurements. The experimental endpoint was the percentage of normal growth 24 weeks after irradiation in rabbits and 14 weeks after treatment in rats. The results show clear dose-response relationships in all experimental arms. A clear-cut fractionation effect was demonstrated in both species. The alpha/beta-ratios determined by maximum likelihood analysis according to the LQ-model with graded responses were 3.2 Gy (95% C.I. 1.1; 5.6) in rabbits and 6.9 Gy (5.3; 8.7) in rats, when all data were included in the calculations. When single-dose data were excluded the alpha/beta-values were -0.6 Gy (-3.1; 2.3) in rabbits and 5.0 Gy (3.5; 7.0) in rats. Our data provide further evidence that low doses per fraction should be used when irradiation of the epiphysis cannot be avoided in pediatric patients.

[Gynecologic brachytherapy--from low-dose-rate to high-tech]. / Gynäkologische Brachytherapie--von Low-dose-rate zu High-tech.

The transition from low-dose-rate (LDR) brachytherapy to high-dose-rate (HDR) afterloading treatment is in progress in most centres of radiation therapy. First reports of studies comparing HDR and LDR treatment in cervix cancer demonstrate nearly equal local control. In our own investigations on 319 patients with primary irradiated carcinoma of the cervix (125 HDR/194 LDR) we found the following control rates: Stage FIGO I 95.4%/82.9% (HDR versus LDR), stage FIGO II 71.4%/73.7%, stage FIGO III 57.9%/38.5%. The results are not significant. The side effects--scored after EORT/RTOG criteria--showed no significant differences between both therapies for serious radiogenic late effects on intestine, bladder and vagina. The study and findings from the literature confirm the advantage of the HDR-procedure for patient and radiooncologist and for radiation protection showing at least the same results as in the LDR-area. As for radiobiological point of view it is important to consider that the use of fractionation in the HDR-treatment is essential for the sparing of normal tissues and therefore a greater number of small fractionation doses in the brachytherapy should be desirable too. On the other hand the rules, which are true for fractionated percutaneous irradiation therapy (overall treatment time as short as possible to avoid repopulation of tumor cells) should be taken into consideration in combined brachy-teletherapy regime in gynecologic tumors. The first step in this direction may be accelerated regime with a daily application of both treatment procedures. The central blocking of the brachytherapy region from the whole percutaneous treatment target volume should be critically reflected, especially in the case of advanced tumors.

[Afterloading contact therapy in childhood tumors]. / Afterloading-(AL)-Kontakttherapie bei kindlichen Tumoren.

Two examples are presented to apply high dose rate afterloading therapy in treatment of tumors in childhood. The AL-therapy can be indicated in tumors in natural or artificial openings of the body that are limited locoregionally or were operated in sano. Applying brachytherapy radiogenic late-effects can be prevented in normal tissue like gonads and skeleton predominantly. On the other hand a tumor dimension greater than the target volume attainable by contact therapy has to be excluded certainly to avoid local recurrences.