Cornelis P.J. Raaijmakers

An improved breast irradiation technique using three-dimensional geometrical information and intensity modulation

BACKGROUND AND PURPOSE In spite of the complex geometry of the breast, treatment planning for tangential breast irradiation is conventionally performed using two-dimensional patient anatomy information. The purpose of this work was to develop a new technique which takes the three-dimensional (3D) patient geometry into account. MATERIALS AND METHODS An intensity-modulated radiotherapy (IMRT) technique was developed based on the division of the tangential fields in four multi-leaf collimator (MLC) shaped segments. The shape of these segments was obtained from an equivalent path length map of the irradiated volume. Approximately 88% of the dose was delivered by two open fields covering the whole treated volume. Dose calculations for the IMRT technique and the conventional technique were performed for five patients, using computer tomography (CT) data and a 3D calculation algorithm. A planning target volume (PTV) and ipsilateral lung volume were delineated in these CT data. RESULTS All patients showed similar equivalent path length patterns. Analysis of the dose distribution showed an improved dose distribution using the IMRT technique. The dose inhomogeneity in the PTV was 9.0% (range 6.4-11.4%) for the conventional and 7.6% (range 6.5-10.3%) for the IMRT technique. The mean lung dose was reduced for the IMRT technique by approximately 10% compared with the conventional technique. CONCLUSION A new breast irradiation technique has been developed which improves the dose homogeneity within the planning target volume and reduces the dose to the lung. Furthermore, the IMRT technique creates the possibility to improve the field matching in case of multiple field irradiations of the breast and lymph nodes.

Parotid Gland Function after Radiotherapy: The Combined Michigan and Utrecht Experience

PURPOSE To analyze the combined and updated results from the University of Michigan and University Medical Center Utrecht on normal tissue complication probability (NTCP) of the parotid gland 1 year after radiotherapy (RT) for head-and-neck (HN) cancer. PATIENTS AND METHODS A total of 222 prospectively analyzed patients with various HN malignancies were treated with conventional and intensity-modulated RT. Stimulated individual parotid gland flow rates were measured before RT and 1 year after RT using Lashley cups at both centers. A flow ratio <25% of pretreatment was defined as a complication. The data were fitted to the Lyman-Kutcher-Burman model. RESULTS A total of 384 parotid glands (Michigan: 157; Utrecht: 227 glands) was available for analysis 1 year after RT. Combined NTCP analysis based on mean dose resulted in a TD(50) (uniform dose leading to 50% complication probability) of 39.9 Gy and m (steepness of the curve) of 0.40. The resulting NTCP curve had good qualitative agreement with the combined clinical data. Mean doses of 25-30 Gy were associated with 17-26% NTCP. CONCLUSIONS A definite NTCP curve for parotid gland function 1 year after RT is presented, based on mean dose. No threshold dose was observed, and TD(50) was equal to 40 Gy.

The dose to the parotid glands with IMRT for oropharyngeal tumors: the effect of reduction of positioning margins.

PURPOSE The aim of this paper is to quantify the importance of the reduction of positioning margins applied to the clinical target volume (CTV) on the dose distribution of the parotid gland for different intensity-modulated radiotherapy (IMRT) strategies for the treatment of oropharyngeal cancer. METHODS AND MATERIALS CTVs and organs at risk were delineated in the planning computed tomographic (CT) scans of three patients. Margins of 0, 3, 6 and 9mm were applied to the CTVs in order to obtain the planning target volumes (PTVs). Three IMRT strategies were used to optimize the dose distribution. RESULTS The analysis of the three IMRT strategies resulted in: (1) an optimal dose distribution in the PTV; (2) optimal dose distribution in the PTV while sparing the parotid gland and (3) more parotid gland sparing but at expense of the dose homogeneity in the PTV. The mean parotid dose increased linearly with increasing margin by approximately 1.3Gy per mm. As a result, the normal complication probability (NTCP) for xerostomia decreased when smaller margins were applied. Reducing the margin from 6 to 3mm resulted in an NTCP reduction of approximately 20%. CONCLUSION Reducing the CTV-PTV margin by improving the patient position accuracy may lead to a significant reduction of NTCP for the IMRT treatment of the oropharyngeal tumors and lymph nodes level II.

A COMPARISON OF DOSE-RESPONSE MODELS FOR THE PAROTID GLAND IN A LARGE GROUP OF HEAD-AND-NECK CANCER PATIENTS

PURPOSE The dose-response relationship of the parotid gland has been described most frequently using the Lyman-Kutcher-Burman model. However, various other normal tissue complication probability (NTCP) models exist. We evaluated in a large group of patients the value of six NTCP models that describe the parotid gland dose response 1 year after radiotherapy. METHODS AND MATERIALS A total of 347 patients with head-and-neck tumors were included in this prospective parotid gland dose-response study. The patients were treated with either conventional radiotherapy or intensity-modulated radiotherapy. Dose-volume histograms for the parotid glands were derived from three-dimensional dose calculations using computed tomography scans. Stimulated salivary flow rates were measured before and 1 year after radiotherapy. A threshold of 25% of the pretreatment flow rate was used to define a complication. The evaluated models included the Lyman-Kutcher-Burman model, the mean dose model, the relative seriality model, the critical volume model, the parallel functional subunit model, and the dose-threshold model. The goodness of fit (GOF) was determined by the deviance and a Monte Carlo hypothesis test. Ranking of the models was based on Akaikes information criterion (AIC). RESULTS None of the models was rejected based on the evaluation of the GOF. The mean dose model was ranked as the best model based on the AIC. The TD(50) in these models was approximately 39 Gy. CONCLUSIONS The mean dose model was preferred for describing the dose-response relationship of the parotid gland.

Quality of life and salivary output in patients with head-and-neck cancer five years after radiotherapy

BackgroundTo describe long-term changes in time of quality of life (QOL) and the relation with parotid salivary output in patients with head-and-neck cancer treated with radiotherapy.MethodsForty-four patients completed the EORTC-QLQ-C30(+3) and the EORTC-QLQ-H&N35 questionnaires before treatment, 6 weeks, 6 months, 12 months, and at least 3.5 years after treatment. At the same time points, stimulated bilateral parotid flow rates were measured.ResultsThere was a deterioration of most QOL items after radiotherapy compared with baseline, with gradual improvement during 5 years follow-up. The specific xerostomia-related items showed improvement in time, but did not return to baseline. Global QOL did not alter significantly in time, although 41% of patients complained of moderate or severe xerostomia at 5 years follow-up. Five years after radiotherapy the mean cumulated parotid flow ratio returned to baseline but 20% of patients had a flow ratio <25%. The change in time of xerostomia was significantly related with the change in flow ratio (p = 0.01).ConclusionMost of the xerostomia-related QOL scores improved in time after radiotherapy without altering the global QOL, which remained high. The recovery of the dry mouth feeling was significantly correlated with the recovery in parotid flow ratio.

Large cohort dose-volume response analysis of parotid gland function after radiotherapy: intensity-modulated versus conventional radiotherapy.

PURPOSE To compare parotid gland dose-volume response relationships in a large cohort of patients treated with intensity-modulated (IMRT) and conventional radiotherapy (CRT). METHODS AND MATERIALS A total of 221 patients (64 treated with IMRT, 157 with CRT) with various head-and-neck malignancies were prospectively evaluated. The distribution of tumor subsites in both groups was unbalanced. Stimulated parotid flow rates were measured before and 6 weeks, 6 months, and 1 year after radiotherapy. Parotid gland dose-volume histograms were derived from computed tomography-based treatment planning. The normal tissue complication probability (NTCP) model proposed by Lyman was fit to the data. A complication was defined as stimulated parotid flow ratio <25% of the pretreatment flow rate. The relative risk of complications was determined for IMRT vs. CRT and adjusted for the mean parotid gland dose using Poisson regression modeling. RESULTS One year after radiotherapy, NTCP curves for IMRT and CRT were comparable with a TD(50) (uniform dose leading to a 50% complication probability) of 38 and 40 Gy, respectively. Until 6 months after RT, corrected for mean dose, different complication probabilities existed for IMRT vs. CRT. The relative risk of a complication for IMRT vs. CRT after 6 weeks was 1.42 (95% CI 1.21-1.67), after 6 months 1.41 (95% CI; 1.12-1.77), and at 1 year 1.21 (95% CI 0.87-1.68), after correcting for mean dose. CONCLUSIONS One year after radiotherapy, no difference existed in the mean dose-based NTCP curves for IMRT and CRT. Early after radiotherapy (up to 6 months) mean dose based (Lyman) models failed to fully describe the effects of radiotherapy on the parotid glands.

Level II lymph nodes and radiation-induced xerostomia

PURPOSE To investigate the influence of the cranial border of electively irradiated Level II lymph nodes on xerostomia in patients with oropharyngeal cancer using three-dimensional conformal and intensity-modulated radiotherapy (3D-CRT and IMRT). METHODS AND MATERIALS The target volumes and organs at risk were delineated on the planning CT scans of 12 patients. Two elective target volumes were delineated. The first had the transverse process of the C1 atlas and the second had the transverse process of the C2 axis as cranial border of the Level II lymph nodes. 3D-CRT and IMRT planning were performed for both elective volumes, resulting in two plans per patient and technique, called the C1 and C2 plans, respectively. Irradiation of the ipsilateral elective volume up to C1 and the contralateral up to C2 was also performed for IMRT. The normal tissue complication probability (NTCP) for xerostomia 1 year after RT was calculated using the parotid mean dose. RESULTS The average mean dose +/- standard deviation (SD) to the contralateral parotid gland was reduced from 33 +/- 5 Gy for the IMRT C1 plans to 26 +/- 4 Gy for the IMRT C2 plans and from 51 +/- 6 Gy to 49 +/- 7 Gy for the 3D-CRT C1 and C2 plans, respectively. The associated NTCP +/- SD for xerostomia was 38% +/- 10% for IMRT C1 plans and 24% +/- 6% for IMRT up to C2 on the contralateral side, regardless of which cranial border was irradiated on the ipsilateral side. For the 3D-CRT C1 and C2 plans, an NTCP value of 74% +/- 12% and 71% +/- 15% was obtained, respectively. The NTCP for xerostomia of the ipsilateral parotid gland was 53% +/- 17% and 45% +/- 20% for the IMRT C1 and C2 plans and 89% +/- 11% and 87% +/- 12% for the 3D-CRT C1 and C2 plans, respectively. CONCLUSION Lowering the cranial border of the Level II lymph nodes from C1 to C2, in the case of bilateral elective neck irradiation, could be considered on the contralateral side when the risk of metastasis on that side is very low. This is especially true when IMRT is used, because the relative reduction of NTCP for xerostomia 1 year after RT could be up to 68% compared with conventional conformal RT up to C1.

Intrafraction motions of the larynx during radiotherapy

PURPOSE To quantify the intrafraction motions of the larynx during radiotherapy of laryngeal cancer. Depending on the magnitude, duration, and incidence, these motions may have clinical consequences for the choice of margins around the clinical target volume. METHODS AND MATERIALS The intrafraction motions were analyzed for 10 patients, treated in 33 or 35 fractions. The intrafraction motions of the larynx were visualized using an a-Si flat panel imager. Images were obtained every 200 ms, resulting in a movie of images for each beam. In addition to visual analysis of all movies, the tip of the epiglottis was delineated and used as a landmark, the coordinates of which were followed in time. RESULTS Movies were obtained during 79% of the total number of radiotherapy fractions. The total duration of swallowing was on average 0.45% (range 0.0-1.5) of the total irradiation time. Deviations of motions other than swallowing ranged between 0.3 and 11.5 mm. Some of these motions were more sudden, and others were probably related to breathing, because the frequency of these motions was 8-20/min. CONCLUSION The incidence and total duration of swallowing is low. Therefore, it is not necessary to apply an internal margin to take into account these displacements. Other motions, however, occur more often. In 95% of the irradiation time, the tip of the epiglottis moves within a range of 7.1 mm. A margin should be applied to the clinical target volume to take into account these motions.

Magnetic Resonance Imaging Protocol Optimization for Delineation of Gross Tumor Volume in Hypopharyngeal and Laryngeal Tumors

PURPOSE To optimize the use of MRI for delineation of gross tumor volume for radiotherapy treatment planning purposes in hypopharyngeal and laryngeal tumors. METHODS AND MATERIALS Magnetic resonance images (T1 weighted and T2 weighted) of a healthy volunteer were acquired using a 1.5 T and 3.0 T MR scanner. Various receiver coils were investigated that were compatible with the immobilization mask needed for reliable coregistration with computed tomography data. For the optimal receiver coil, the influence of resolution, slice thickness, and strength of magnetic field on the signal-to-noise ratio (SNR) was studied. Feasibility of the definitive protocol was tested on patients with hypopharyngeal (n = 19) and laryngeal (n = 42) carcinoma. RESULTS Large differences in SNR were obtained for the various coils. The SNR values obtained using surface coils that were compatible with the immobilization mask were three times higher than those obtained using a standard head-and-neck coil and five times higher than those obtained using a body coil. High-resolution images (0.4 x 0.4 x 4 mm(3)) showed superior anatomic detail and resulted in a 4-min scan time. Image quality at 3.0 T was not significantly better compared with 1.5 T. In 3 patients the MR study could not be performed; for 5 patients images were severely deteriorated by motion artefacts. High-quality MR images were obtained in 53 patients. CONCLUSIONS High-resolution MR images of the hypopharynx and larynx can be obtained in the majority of patients using surface receiver coils in combination with the radiotherapy mask. These MR images can be successfully used for tumor delineation in radiotherapy.

Sparing the contralateral submandibular gland in oropharyngeal cancer patients: a planning study.

BACKGROUND AND PURPOSE The submandibular glands are proposed to be important in preventing xerostomia in head-and-neck cancer patients. We investigated the feasibility of sparing the contralateral submandibular gland (cSMG) by reducing the dose to the contralateral planning target volume (PTV) and by reducing the clinical target volume (CTV)-to-PTV margin. MATERIALS AND METHODS Ten oropharyngeal cancer patients with a contralateral elective PTV were included in this planning study, using intensity modulated radiotherapy (IMRT). The effect on the mean dose to the cSMG of reducing the dose coverage to the contralateral elective PTV from 95 to 90% of the prescribed dose (54Gy in 1.8Gy daily fractions) was determined. The influence of reducing the margin for position uncertainty from 5 to 2mm was investigated. RESULTS The mean dose to the cSMG was reduced from 54Gy to approximately 40Gy if the dose coverage to the contralateral PTV was reduced to 90% of the prescribed dose. The estimated normal tissue complication probability (NTCP) was reduced below 50%. Reducing the margin from 5 to 2mm resulted in a decrease in the mean dose to the cSMG of approximately 6Gy. CONCLUSIONS Reducing the mean dose to the cSMG below 40Gy is possible with a reasonable dose coverage of the contralateral elective PTV.