Radiation Oncology - Latest articles

Radiation-induced skin injury in the animal model of scleroderma: implications for post-radiotherapy fibrosis.

2008-11-24

Background: Radiation therapy is generally contraindicated for cancer patients with collagen vascular diseases (CVD) such as scleroderma due to an increased risk of fibrosis. The tight skin (TSK) mouse has skin which, in some respects, mimics that of patients with scleroderma. The skin radiation response of TSK mice has not been previously reported. If TSK mice are shown to have radiation sensitive skin, they may prove to be a useful model to examine the mechanisms underlying skin radiation injury, protection, mitigation and treatment. Methods: The hind limbs of TSK and parental control C57BL/6 mice received a radiation exposure sufficient to cause approximately the same level of acute injury. Endpoints included skin damage scored using a non-linear, semi-quantitative scale and tissue fibrosis assessed by measuring passive leg extension. In addition, TGF-beta1 cytokine levels were measured monthly in skin tissue. Results: Contrary to our expectations, TSK mice were more resistant (i.e. 20%) to radiation than parental control mice. Although acute skin reactions were similar in both mouse strains, radiation injury in TSK mice continued to decrease with time such that several months after radiation there was significantly less skin damage and leg contraction compared to C57BL/6 mice (p<0.05). Consistent with the expected association of transforming growth factor beta-1(TGF-beta1) with late tissue injury, levels of the cytokine were significantly higher in the skin of the C57BL/6 mouse compared to TSK mouse at all time points (p<0.05). Conclusion: TSK mice are not recommended as a model of scleroderma involving radiation injury. The genetic and molecular basis for reduced radiation injury observed in TSK mice warrants further investigation particularly to identify mechanisms capable of reducing tissue fibrosis after radiation injury.

Dose volume histogram analysis of normal structures associated with accelerated intracavitary partial breast irradiation delivered by high dose rate brachytherapy and comparison with whole breast external beam radiotherapy fields

2008-11-19

Purpose To assess the radiation dose delivered to the heart and ipsilateral lung during accelerated partial breast brachytherapy using a MammoSiteTM applicator and compare to those produced by whole breast external beam radiotherapy (WBRT). Method and Materials Dosimetric analysis was conducted on patients receiving MammoSite breast brachytherapy following conservative surgery for invasive ductal carcinoma. Cardiac dose was evaluated for patients with left breast tumors with a CT scan encompassing the entire heart. Lung dose was evaluated for patients in whom the entire lung was scanned. The prescription dose of 3400cGy was 1cm from the balloon surface. MammoSite dosimetry was compared to simulated WBRT fields with and without radiobiological correction for the effects of dose and fractionation. Dose parameters such as the volume of the structure receiving 10Gy or more (V10) and the dose received by 20cc of the structure (D20), were calculated as well as the maximum and mean doses received. Results: Fifteen patients were studied, five had complete lung data and six had left-sided tumors with complete cardiac data. Ipsilateral lung volumes ranged from 925-1380 cc. Cardiac volumes ranged from 337-551 cc. MammoSite resulted in a significantly lower percentage lung V30 and lung and cardiac V20 than the WBRT fields, with and without radiobiological correction. Conclusion: This study gives low values for incidental radiation received by the heart and ipsilateral lung using the MammoSite applicator. The volume of heart and lung irradiated to clinically significant levels was significantly lower with the MammoSite applicator than using simulated WBRT fields of the same CT data sets. Trial Registration Dana Farber Trial Registry number 03-179

Pre-segmented 2-Step IMRT with subsequent direct machine parameter optimisation - a planning study

Klaus Bratengeier, Jurgen Meyer and Michael Flentje — 2008-11-06

Background: Modern intensity modulated radiotherapy (IMRT) mostly uses iterative optimisation methods. The integration of machine parameters into the optimisation process of step and shoot leaf positions has been shown to be successful. For IMRT segmentation algorithms based on the analysis of the geometrical structure of the planning target volumes (PTV) and the organs at risk (OAR), the potential of such procedures has not yet been fully explored. In this work, 2-Step IMRT was combined with subsequent direct machine parameter optimisation (DMPO -Raysearch Laboratories, Sweden) to investigate this potential. Methods: In a planning study DMPO on a commercial planning system was compared with manual primary 2-Step IMRT segment generation followed by DMPO optimisation. 15 clinical cases and the ESTRO Quasimodo phantom were employed. Both the same number of optimisation steps and the same set of objective values were used. The plans were compared with a clinical DMPO reference plan and a traditional IMRT plan based on fluence optimisation and consequent segmentation. The composite objective value (the weighted sum of quadratic deviations of the objective values and the related points in the dose volume histogram) was used as a measure for the plan quality. Additionally, a more extended set of parameters was used for the breast cases to compare the plans. Results: The plans with segments pre-defined with 2-Step IMRT were slightly superior to DMPO alone in the majority of cases. The composite objective value tended to be even lower for a smaller number of segments. The total number of monitor units was slightly higher than for the DMPO-plans. Traditional IMRT fluence optimisation with subsequent segmentation could not compete. Conclusions: 2-Step IMRT segmentation is suitable as starting point for further DMPO optimisation and, in general, results in less complex plans which are equal or superior to plans generated by DMPO alone.

Intrafraction motion of the prostate during an IMRT session: a fiducial-based 3D measurement with Cone-beam CT

2008-11-05

Background: Image-guidance systems allow accurate interfractional repositioning of IMRT treatments, however, these may require up to 15 minutes. Therefore intrafraction motion might have an impact on treatment precision. 3D geometric data regarding intrafraction prostate motion are rare; we therefore assessed its magnitude with pre- and post-treatment fiducial-based imaging with cone-beam-CT (CBCT). Methods: 39 IMRT fractions in 5 prostate cancer patients after 125I-seed implantation were evaluated. Patient position was corrected based on the 125I-seeds after pre-treatment CBCT. Immediately after treatment delivery, a second CBCT was performed. Differences in bone- and fiducial position were measured by seed-based grey-value matching. Results: Fraction time was 13.6 ± 1.6 minutes. Median overall displacement vector length of 125I-seeds was 3 mm (M = 3 mm, Σ = 0.9 mm, σ = 1.7 mm; M: group systematic error, Σ: SD of systematic error, σ: SD of random error). Median displacement vector of bony structures was 1.84 mm (M = 2.9 mm, Σ = 1 mm, σ = 3.2 mm). Median displacement vector length of the prostate relative to bony structures was 1.9 mm (M = 3 mm, Σ = 1.3 mm, σ = 2.6 mm). Conclusion: a) Overall displacement vector length during an IMRT session is < 3 mm.b) Positioning devices reducing intrafraction bony displacements can further reduce overall intrafraction motion.c) Intrafraction prostate motion relative to bony structures is < 2 mm and may be further reduced by institutional protocols and reduction of IMRT duration.

Normal tissue toxicity after small field hypofractionated stereotactic body radiation

Michael T Milano, Louis S Constine and Paul Okunieff — 2008-10-31

Stereotactic body radiation (SBRT) is an emerging tool in radiation oncology in which the targeting accuracy is improved via the detection and processing of a three-dimensional coordinate system that is aligned to the target. With improved targeting accuracy, SBRT allows for the minimization of normal tissue volume exposed to high radiation dose as well as the escalation of fractional dose delivery. The goal of SBRT is to minimize toxicity while maximizing tumor control. This review will discuss the basic principles of SBRT, the radiobiology of hypofractionated radiation and the outcome from published clinical trials of SBRT, with a focus on late toxicity after SBRT. While clinical data has shown SBRT to be safe in most circumstances, more data is needed to refine the ideal dose-volume metrics.

Acute and late toxicity in prostate cancer patients treated by dose escalated intensity modulated radiation therapy and organ tracking

2008-10-20

Background: To report acute and late toxicity in prostate cancer patients treated by dose escalated intensity-modulated radiation therapy (IMRT) and organ tracking. Methods: From 06/2004 to 12/2005 39 men were treated by 80Gy IMRT along with organ tracking. Median age was 69 years, risk of recurrence was low 18 %, intermediate 21 % and high in 61 % patients. Hormone therapy (HT) was received by 74 % of patients. Toxicity was scored according to the CTC scale version 3.0. Median follow-up (FU) was 29 months. Results: Acute and maximal late grade 2 gastrointestinal (GI) toxicity was 3 % and 8 %, late grade 2 GI toxicity dropped to 0 % at the end of FU. No acute or late grade 3 GI toxicity was observed. Grade 2 and 3 pre-treatment genitourinary (GU) morbidity (PGUM) were 20 % and 5 %. Acute and maximal late grade 2 GU toxicity was 56 % and 28 % and late grade 2 GU toxicity decreased to 15 % of patients at the end of FU. Acute and maximal late grade 3 GU toxicity was 8 % and 3 %, respectively. Decreased late greater than or equal to grade 2 GU toxicity free survival was associated with higher age (P=.025), absence of HT (P=.016) and higher PGUM (P<.001). DiscussionGI toxicity rates after IMRT and organ tracking are excellent, GU toxicity rates are strongly related to PGUM.

Motion compensation with a scanned ion beam: a technical feasibility study

2008-10-14

Background: Intrafractional motion results in local over- and under-dosage in particle therapy with a scanned beam. Scanned beam delivery offers the possibility to compensate target motion by tracking with the treatment beam. Methods: Lateral motion components were compensated directly with the beam scanning system by adapting nominal beam positions according to the target motion. Longitudinal motion compensation to mitigate motion induced range changes was performed with a dedicated wedge system that adjusts effective particle energies at isocenter. Results: Lateral compensation performance was better than 1% for a homogeneous dose distribution when comparing irradiations of a stationary radiographic film and a moving film using motion compensation. The accuracy of longitudinal range compensation was well below 1 mm. Conclusion: Motion compensation with scanned particle beams is technically feasible with high precision.

SCLC extensive disease – treatment guidance by extent or/and biology of response?

Franziska Eckert and Arndt-Christian Müller — 2008-10-02

In extensive disease of small cell lung cancer a doubling of the one-year-survival rate was reported in August 2007 by prophylactic cranial irradiation applied to patients who experienced any response to initial chemotherapy. We discuss the treatment concept of extensive disease in the face of the latest results and older studies with additional thoracic irradiation in this subgroup. A randomized trial with prophylactic cranial irradiation published in 1999 demonstrated an improvement of 5-year-overall-survival for complete responders (at least at distant levels) receiving additional thoracic radiochemotherapy compared to chemotherapy alone (9.1% vs. 3.7%). But, these results were almost neglected and thoracic radiotherapy was not further investigated for good responders of extensive disease. However, in the light of current advances by prophylactic cranial irradiation these findings are noteworthy on all accounts. Considering both, a possible interpretation of these data could be a survival benefit of local control by simultaneous thoracic radiochemotherapy in the case of improved distant control due to chemotherapy and prophylactic cranial irradiation. Furthermore the question arises whether the tumor biology indicated by the response to chemotherapy should be integrated in the present classification.

The prognostic value of nestin expression in newly diagnosed glioblastoma: Report from the Radiation Therapy Oncology Group

2008-09-25

Background: Nestin is an intermediate filament protein that has been implicated in early stages of neuronal lineage commitment. Based on the heterogeneous expression of nestin in GBM and its potential to serve as a marker for a dedifferentiated, and perhaps more aggressive phenotype, the Radiation Therapy Oncology Group (RTOG) sought to determine the prognostic value of nestin expression in newly diagnosed GBM patients treated on prior prospective RTOG clinical trials. Methods: Tissue microarrays were prepared from 156 patients enrolled in these trials. These specimens were stained using a mouse monoclonal antibody specific for nestin and expression was measured by computerized quantitative image analysis using the Ariol SL-50 system. The parameters measured included both staining intensity and the relative area of expression within a specimen. This resulted into 3 categories: low, intermediate, and high nestin expression, which was then correlated with clinical outcome. Results: A total of 153 of the 156 samples were evaluable for this study. There were no statistically significant differences between pretreatment patient characteristics and nestin expression. There was no statistically significant difference in either overall survival or progression-free survival (PFS) demonstrated, although a trend in decreased PFS was observed with high nestin expression (p = 0.06). Conclusion: Although the correlation of nestin expression and histologic grade in glioma is of considerable interest, the presented data does not support its prognostic value in newly diagnosed GBM. Further studies evaluating nestin expression may be more informative when studied in lower grade glioma, in the context of markers more specific to tumor stem cells, and using more recent specimens from patients treated with temozolomide in conjunction with radiation.

Impact of different leaf velocities and dose rates on the number of monitor units and the dose-volume-histograms using intensity modulated radiotherapy with sliding-window technique

Hilke Vorwerk, Daniela Wagner and Clemens F Hess — 2008-09-23

Background: Intensity modulated radiotherapy (IMRT) using sliding window technique utilises a leaf sequencing algorithm, which takes some control system limitations like dose rates (DR) and velocity of the leafs (LV) into account. The effect of altering these limitations on the number of monitor units and radiation dose to the organs at risk (OAR) were analysed. Methods: IMRT plans for different LVs from 1.0 cm/sec to 10.0 cm/sec and different DRs from 100 MU/min to 600 MU/min for two patients with prostate cancer and two patients with squamous cell cancer of the scalp (SCCscalp) were calculated using the same "optimal fluence map". For each field the number of monitor units, the dose volume histograms and the differences in the "actual fluence maps" of the fields were analysed. Results: With increase of the DR and decrease of the LV the number of monitor units increased and consequentially the radiation dose given to the OAR. In particular the serial OARs of patients with SCCscalp, which are located outside the end position of the leafs and inside the open field, received an additional dose of a higher DR and lower LV is used. Conclusion: For best protection of organs at risk, a low DR and high LV should be applied. But the consequence of a low DR is both a long treatment time and also that a LV of higher than 3.0 cm/sec is mechanically not applicable. Our recommendation for an optimisation of the discussed parameters is a leaf velocity of 2.5 cm/sec and a dose rate of 300–400 MU/min (prostate cancer) and 100–200 MU/min (SCCscalp) for best protection of organs at risk, short treatment time and number of monitor units.