Cardiac magnetic resonance imaging findings in 20-year survivors of mediastinal radiotherapy for Hodgkin's disease.

PURPOSE: The recognition of the true prevalence of cardiac toxicity after mediastinal radiotherapy requires very long follow-up and a precise diagnostic procedure. Cardiac magnetic resonance imaging (MRI) permits excellent quantification of cardiac function and identification of localized myocardial defects and has now been applied to a group of 20-year Hodgkin's disease survivors. METHODS AND MATERIALS: Of 143 patients treated with anterior mediastinal radiotherapy (cobalt-60, median prescribed dose 40 Gy) for Hodgkin's disease between 1978 and 1985, all 53 survivors were invited for cardiac MRI. Of those, 36 patients (68%) presented for MRI, and in 31 patients (58%) MRI could be performed 20-28 years (median, 24) after radiotherapy. The following sequences were acquired on a 1.5-T MRI: transversal T1-weighted TSE and T2-weighted half-fourier acquisition single-shot turbo-spin-echo sequences, a steady-state free precession (SSFP) cine sequence in the short heart axis and in the four-chamber view, SSFP perfusion sequences under rest and adenosine stress, and a SSFP inversion recovery sequence for late enhancement. The MRI findings were correlated with previously reconstructed doses to cardiac structures. RESULTS: Clinical characteristics and reconstructed doses were not significantly different between survivors undergoing and not undergoing MRI. Pathologic findings were reduced left ventricular function (ejection fraction <55%) in 7 (23%) patients, hemodynamically relevant valvular dysfunction in 13 (42%), late myocardial enhancement in 9 (29%), and any perfusion deficit in 21 (68%). An association of regional pathologic changes and reconstructed dose to cardiac structures could not be established. CONCLUSIONS: In 20-year survivors of Hodgkin's disease, cardiac MRI detects pathologic findings in approximately 70% of patients. Cardiac MRI has a potential role in cardiac imaging of Hodgkin's disease patients after mediastinal radiotherapy.

Steep dose gradients for simultaneous integrated boost IMRT.

Steep dose gradients between two planning target volumes (PTVs) as may be required for simultaneous integrated boosts (SIB) should be an option provided by IMRT algorithms. The aim was to analyse the geometry of the SIB problem and to implement the results in an algorithm for IMRT segment generation denoted two-step intensity modulated radiotherapy (2-Step IMRT). It was hypothesized that a gap between segments directed to the inner and the outer PTV would steepen the dose gradient. The mathematical relationships were derived from the individual dose levels and the geometry (diameters) of the PTVs. The results generated by means of 2-Step IMRT segments were equivalent or better than the segment generation using a commercial IMRT planning system. The dose to both the inner and the outer PTV was clearly more homogeneous and the composite objective value was the lowest. The segment numbers were lower or equal--with better sparing of the surrounding tissue. In summary, it was demonstrated that 2-Step IMRT was able to achieve steep dose gradients for SIB constellations.

An interlaced IMRT technique for elongated tumor volumes.

Treatment of large target volumes with intensity modulated radiotherapy (IMRT) can be restricted by the maximum field size of the multileaf collimator (MLC). In this work, a straightforward technique for MLC-based IMRT is presented, which is generally applicable and does not depend on the capabilities of the linear accelerator's IMRT delivery system. A dual isocenter technique was developed that maximizes beam overlap. The beams at the first isocenter are arranged such that they interlace with the beams at the second isocenter. All beams contribute to the overlap region, whereas only some contribute to the superior and some to the inferior part of the target. The interlaced technique (9 beams) was compared with an alternative more complex approach (14 beams) for a head-and-neck case with simultaneous integrated boost and 3 different dose levels. The plans were compared in terms of complexity, dosimetry, and the effect of inaccurate translation between the isocenters. The interlaced and the more complex IMRT technique resulted in nearly identical dose distributions without clinically relevant differences. The total number of monitor units (MUs) was comparable with more MUs per segment for the interlaced technique. For the interlaced technique, the number of segments

Comparison of wedge versus segmented techniques in whole breast irradiation: effects on dose exposure outside the treatment volume.

PURPOSE: To compare two irradiation techniques for whole breast irradiation: tangential wedged beams (WT) versus "open" fields (without wedges) with forward planned segments (ST). PATIENTS AND METHODS: For 20 patients two comparative 3-D plans were defined using Pinnacle P3D and analyzed with respect to dose, dose homogeneity in the target volume, and scattered dose to organs at risk. The plans of six patients were reproduced in an Alderson phantom. Measurements were performed in the planning target volume (PTV), contralateral breast, lungs, heart, thyroid gland and in mid-pelvis. RESULTS: Dose distribution in the PTV was nearly identical for WT and ST with the exception of D(1). Scattered doses were significantly smaller for ST. In the contralateral breast the doses per 2-Gy fraction were 7.3 cGy +/- 2.1 cGy (WT), and 4.7 cGy +/- 1.9 cGy (ST; p < 0.01). Similar doses were measured for lung and heart. In mid pelvis the largest difference was observed (WT: 1.0 cGy +/- 0.2 cGy, ST: 0.2 cGy +/- 0.1 cGy; p < 0.01). CONCLUSION: Partial volume segments can replace wedges for improved dose coverage and homogeneity in the PTV. The ST causes significantly less scattered dose to extra-target organs. This may have implications for long-term risks after exposure to low radiation doses.

Effects of HIF-1 inhibition by chetomin on hypoxia-related transcription and radiosensitivity in HT 1080 human fibrosarcoma cells.

BACKGROUND: Hypoxia-inducible factor-1 (HIF-1) overexpression has been linked to tumor progression and poor prognosis. We investigated whether targeting of HIF-1 using chetomin, a disrupter of the interaction of HIF-1 with the transcriptional coactivator p300, influences the radiosensitivity of hypoxic HT 1080 human fibrosarcoma cells. METHODS: Optimal dose of chetomin was determined by EGFP-HRE gene reporter assay in stably transfected HT 1080 cells. Cells were assayed for expression of the hypoxia-inducible genes carbonic anhydrase 9 (CA9) and vascular endothelial growth factor (VEGF) by RT-PCR and for clonogenic survival after irradiation with 2, 5 or 10 Gy, under normoxic or hypoxic (0.1% O2, 12 h) conditions in the presence or absence of chetomin (150 nM, 12 h, pre-treatment of 4 h). RESULTS: Chetomin treatment significantly reduced CA9 and VEGF mRNA expression in hypoxic cells to 44.4 +/- 7.2% and 39.6 +/- 16.0%, respectively, of untreated hypoxic controls. Chetomin clearly reduced the modified oxygen enhancement ratio (OER') compared to untreated cells, from 2.02 to 1.27, from 1.86 to 1.22 and from 1.49 to 1.06 at the 50%, 37% and 10% clonogenic survival levels, respectively. CONCLUSION: HIF-1 inhibition by chetomin effectively reduces hypoxia-dependent transcription and radiosensitizes hypoxic HT 1080 human fibrosarcoma cells in vitro.

A comparison between 2-Step IMRT and conventional IMRT planning.

BACKGROUND AND PURPOSE: 2-Step intensity modulated radiation therapy (2-Step IMRT) is an IMRT segmentation procedure based on analytical approximations [Bratengeier K. 2-Step IMAT and 2-Step IMRT: a geometrical approach. Med Phys 2005;32:777-785; Bratengeier K. 2-Step IMAT and 2-Step IMRT in three dimensions. Med Phys 2005;32:3849-3861]. The aim was to benchmark it with other IMRT algorithms and to establish it as planning tool for fast IMRT application with a reduced number of segments. MATERIALS AND METHODS: 2-Step IMRT plans were compared with IMRT-solutions obtained with methods from a commercial planning system (Pinnacletrade mark TPS). The four clinical cases chosen were: paraspinal tumour, carcinoma of the prostate, head and neck carcinoma and breast carcinoma. In addition the "Quasimodo" phantom study was used to compare the quality of the 2-Step IMRT method with respect to other planning procedures in the ESTRO study. RESULTS: The number of segments (and - to a minor degree - the monitor units per dose) of the majority of 2-Step IMRT plans was lower than for the commercial algorithms. The quality of the 2-Step IMRT-plan was comparable. In the Quasimodo comparison 2-Step IMRT plans with nine beams would place in the mid-range of all participants, whereas the 15-beam arrangements could compete with the best results. CONCLUSIONS: 2-Step IMRT is a valuable IMRT segmentation method, especially if the number of segments is to be limited (e.g. for reasons of precision, speed and leakage radiation).

3-D reconstruction of anterior mantle-field techniques in Hodgkin's disease survivors: doses to cardiac structures.

BACKGROUND: The long-term dose-effect relationship for specific cardiac structures in mediastinal radiotherapy has rarely been investigated. As part of an interdisciplinary project, the 3-D dose distribution within the heart was reconstructed in all long-term Hodgkin's disease survivors (n = 55) treated with mediastinal radiotherapy between 1978 and 1985. For dose reconstruction, original techniques were transferred to the CT data sets of appropriate test patients, in whom left (LV) and right ventricle (RV), left (LA) and right atrium (RA) as well as right (RCA), left anterior descending (LAD) and left circumflex (LCX) coronary arteries were contoured. Dose-volume histograms (DVHs) were generated for these heart structures and results compared between techniques. RESULTS: Predominant technique was an anterior mantle field (cobalt-60). 26 patients (47%) were treated with anterior mantle field alone (MF), 18 (33%) with anterior mantle field and monoaxial, bisegmental rotation boost (MF+ROT), 7 (13%) with anterior mantle field and dorsal boost (MF+DORS) and 4 (7%) with other techniques. Mean +/- SD total mediastinal doses for MF+ROT (41.7 +/- 3.5 Gy) and for MF+DORS (42.7 +/- 7.4) were significantly higher than for MF (36.7 +/- 5.2 Gy). DVH analysis documented relative overdosage to right heart structures with MF (median maximal dose to RV 129%, to RCA 127%) which was significantly reduced to 117% and 112%, respectively, in MF+ROT. Absolute doses in right heart structures, however, did not differ between techniques. Absolute LA doses were significantly higher in MF+ROT patients than in MF patients where large parts of LA were blocked. Median maximal doses for all techniques ranged between 48 and 52 Gy (RV), 44 and 46 Gy (LV), 47 and 49 Gy (RA), 38 and 45 Gy (LA), 46 and 50 Gy (RCA), 39 and 44 Gy (LAD) and 34 and 42 Gy (LCX). CONCLUSION: In patients irradiated with anterior mantle-field techniques, high doses to anterior heart portions were partly compensated by boost treatment from non-anterior angles. As the threshold doses for coronary artery disease, cardiomyopathy, pericarditis and valvular changes are assumed to be 30 to 40 Gy, cardiac toxicity must be anticipated in these patients. Thus, dose distributions in individual subjects should be correlated to the corresponding cardiovascular findings in these long-term survivors, e. g. by cardiovascular magnetic resonance imaging.

Radiotherapy of prostate cancer with multileaf collimators (MLCs) optimization of the undulating dose distribution at the MLC edge.

BACKGROUND AND PURPOSE: A technical modification for radiotherapy of prostate cancer is presented to smooth the scalloped dose pattern that occurs at treatment field edge, when a multileaf collimator (MLC) has been used. MATERIAL AND METHODS: Ten patients with prostate cancer receiving postoperative, adjuvant irradiation were studied prospectively. By a three-dimensional planning system (TMS, Helax 6.1B) the irradiation was planned for an 18-MV linear accelerator (Primus 1, Siemens). The volumes of interest (VOI) were the planning target volume (PTV; the region of the prostate including the seminal vesicles), the volume of rectum (V(rectum)) and urinary bladder (V(bladder)). Two four-field techniques (0 degrees , 90 degrees , 180 degrees , 270 degrees ) were planned using "beam's eye view" for setting the leaf position of the MLC. For technique A the MLC was adapted to the PTV using a 0 degrees collimator angle for the lateral fields. For technique B the collimator angle of the lateral fields was optimized to compensate the cascade field shape. Dose-volume histograms of PTV, V(rectum) and V(bladder) were analyzed. The dose was prescribed for the reference point according to ICRU 50. Film dosimetry was used to show the dose pattern at the field edge produced by the two techniques. RESULTS: Dose to PTV did not differ between technique A and B. Median dose to V(rectum) was 82.6% for technique A and 77.3% for technique B (p < 0.001). Technique A irradiates a larger V(rectum) than technique B being significant for all isodose levels tested. Median dose to V(bladder) did not differ for technique A and B (p > 0.05). CONCLUSION: The presented technical modification is an effective method to blur the staggered dose distribution that results, when the MLC is conventionally stepped to adapt to the dorsal, irregular PTV border in irradiation of prostate. Especially for irradiation to escalated dose levels, this modification may reduce the dose to the rectum and thus the rectal side effects in comparison to the conventional MLC fields.