Biomedical subjects

Cornelis P J Raaijmakers

Publications and source records attributed to Cornelis P J Raaijmakers.

14 recordsLinked to original sources

PubMed2007

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

BACKGROUND: To 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. METHODS: Forty-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. RESULTS: There 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). CONCLUSION: Most 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.

Adult↗

PubMed2006

Intensity-modulated radiotherapy significantly reduces xerostomia compared with conventional radiotherapy.

PURPOSE: Xerostomia is a severe complication after radiotherapy for oropharyngeal cancer, as the salivary glands are in close proximity with the primary tumor. Intensity-modulated radiotherapy (IMRT) offers theoretical advantages for normal tissue sparing. A Phase II study was conducted to determine the value of IMRT for salivary output preservation compared with conventional radiotherapy (CRT). METHODS AND MATERIALS: A total of 56 patients with oropharyngeal cancer were prospectively evaluated. Of these, 30 patients were treated with IMRT and 26 with CRT. Stimulated parotid salivary flow was measured before, 6 weeks, and 6 months after treatment. A complication was defined as a stimulated parotid flow rate <25% of the preradiotherapy flow rate. RESULTS: The mean dose to the parotid glands was 48.1 Gy (SD 14 Gy) for CRT and 33.7 Gy (SD 10 Gy) for IMRT (p < 0.005). The mean parotid flow ratio 6 weeks and 6 months after treatment was respectively 41% and 64% for IMRT and respectively 11% and 18% for CRT. As a result, 6 weeks after treatment, the number of parotid flow complications was significantly lower after IMRT (55%) than after CRT (87%) (p = 0.002). The number of complications 6 months after treatment was 56% for IMRT and 81% for CRT (p = 0.04). CONCLUSIONS: IMRT significantly reduces the number of parotid flow complications for patients with oropharyngeal cancer.

Adult↗

PubMed2005

Comparing step-and-shoot IMRT with dynamic helical tomotherapy IMRT plans for head-and-neck cancer.

PURPOSE: The goal of this planning study was to compare step-and-shoot intensity-modulated radiotherapy (IMRT) plans with helical dynamic IMRT plans for oropharynx patients on the basis of dose distribution. METHODS AND MATERIALS: Five patients with oropharynx cancer had been previously treated by step-and-shoot IMRT at the University Medical Centre Utrecht, The Netherlands, applying five fields and approximately 60-90 segments. Inverse planning was carried out using Plato, version 2.6.2. For each patient, an inverse IMRT plan was also made using Tomotherapy Hi-Art System, version 2.0, and using the same targets and optimization goals. Statistical analysis was performed by a paired t test. RESULTS: All tomotherapy plans compared favorably with the step-and-shoot plans regarding sparing of the organs at risk and keeping an equivalent target dose homogeneity. Tomotherapy plans in particular realized sharper dose gradients compared with the step-and-shoot plans. The mean dose to all parotid glands (n = 10) decreased on average 6.5 Gy (range, -4 to 14; p = 0.002). The theoretical reduction in normal tissue complication probabilities in favor of the tomotherapy plans depended on the parotid normal tissue complication probability model used (range, -3% to 32%). CONCLUSION: Helical tomotherapy IMRT plans realized sharper dose gradients compared with the clinically applied step-and shoot plans. They are expected to be able to reduce the parotid normal tissue complication probability further, keeping a similar target dose homogeneity.

Head and Neck Neoplasms↗

PubMed2005

Long-term parotid gland function after radiotherapy.

PURPOSE: Irradiation of the parotid glands causes salivary dysfunction, resulting in reduced salivary flow. Recovery can be seen with time; however, long-term prospective data are lacking. The objective of this study was to analyze the long-term parotid gland function after irradiation for head-and-neck cancer. METHODS AND MATERIALS: A total of 52 patients with head-and-neck cancer and treated with radiotherapy (RT) were prospectively evaluated. Stimulated bilateral parotid salivary flow rates were measured before RT and 6 weeks, 6 months, 12 months, and at least 3.5 years after RT completion. A complication was defined as a stimulated parotid flow rate of <25% of the pre-RT flow rate. The normal tissue complication probability model proposed by Lyman was fit to the data. Multilevel techniques were used to model the patterns of flow rates with time. RESULTS: The mean stimulated flow rate of the parotid glands before RT was 0.31 mL/min (standard deviation [SD], 0.21). This was reduced to 0.14 mL/min (SD, 0.15) at 6 weeks after RT and recovered to 0.20 mL/min (SD, 0.22) at 6 months and 0.19 mL/min (SD, 0.21) at 12 months after RT. The mean stimulated flow rate was 0.25 mL/min (SD, 0.28) 5 years after RT. The mean dose to the parotid gland resulting in a 50% complication probability increased from 34 Gy at 6 weeks to 40 Gy at 6 months, 42 Gy at 12 months, and 46 Gy at 5 years after RT. Multilevel modeling indicated that both dose and time were significantly associated with the flow ratio. CONCLUSION: Salivary output can still recover many years after RT. At 5 years after RT, we found an increase in the salivary flow rate of approximately 32% compared with at 12 months after RT.

Adult↗

PubMed2005

A comparison of mean parotid gland dose with measures of parotid gland function after radiotherapy for head-and-neck cancer: implications for future trials.

PURPOSE: To determine the most adequate parameter to measure the consequences of reducing the parotid gland dose. METHODS AND MATERIALS: One hundred eight patients treated with radiotherapy for various malignancies of the head and neck were prospectively evaluated using three methods. Parotid gland function was objectively determined by measuring stimulated parotid flow using Lashley cups and scintigraphy. To assess xerostomia-related quality of life, the head-and-neck cancer module European Organization for Research and Treatment of Cancer QLQ (Quality of Life Questionnaire) H&N35 was used. Measurements took place before radiotherapy and 6 weeks and 12 months after the completion of radiotherapy. Complication was defined for each method using cutoff values. The correlation between these complications and the mean parotid gland dose was investigated to find the best measure for parotid gland function. RESULTS: For both flow and scintigraphy data, the best definition for objective parotid gland toxicity seemed to be reduction of stimulated parotid flow to < or =25% of the preradiotherapy flow. Of all the subjective variables, only the single item dry mouth 6 weeks after radiotherapy was found to be significant. The best correlation with the mean parotid gland dose was found for the stimulated flow measurements. The predictive ability was the highest for the time point 1 year after radiotherapy. Subjective findings did not correlate with the mean parotid dose. CONCLUSIONS: Stimulated flow measurements using Lashley cups, with a complication defined as flow < or =25% of the preradiotherapy output, correlated best with the mean parotid gland dose. When reduction of the mean dose to the parotid gland is intended, the stimulated flow measurement is the best method for evaluating parotid gland function.

Head and Neck Neoplasms↗

PubMed2005

Adequate margins for random setup uncertainties in head-and-neck IMRT.

PURPOSE: To investigate the effect of random setup uncertainties on the highly conformal dose distributions produced by intensity-modulated radiotherapy (IMRT) for clinical head-and-neck cancer patients and to determine adequate margins to account for those uncertainties. METHODS AND MATERIALS: We have implemented in our clinical treatment planning system the possibility of simulating normally distributed patient setup displacements, translations, and rotations. The planning CT data of 8 patients with Stage T1-T3N0M0 oropharyngeal cancer were used. The clinical target volumes of the primary tumor (CTV(primary)) and of the lymph nodes (CTV(elective)) were expanded by 0.0, 1.5, 3.0, and 5.0 mm in all directions, creating the planning target volumes (PTVs). We performed IMRT dose calculation using our class solution for each PTV margin, resulting in the conventional static plans. Then, the system recalculated the plan for each positioning displacement derived from a normal distribution with sigma = 2 mm and sigma = 4 mm (standard deviation) for translational deviations and sigma = 1 degrees for rotational deviations. The dose distributions of the 30 fractions were summed, resulting in the actual plan. The CTV dose coverage of the actual plans was compared with that of the static plans. RESULTS: Random translational deviations of sigma = 2 mm and rotational deviations of sigma = 1 degrees did not affect the CTV(primary) volume receiving 95% of the prescribed dose (V(95)) regardless of the PTV margin used. A V(95) reduction of 3% and 1% for a 0.0-mm and 1.5-mm PTV margin, respectively, was observed for sigma = 4 mm. The V(95) of the CTV(elective) contralateral was approximately 1% and 5% lower than that of the static plan for sigma = 2 mm and sigma = 4 mm, respectively, and for PTV margins <5.0 mm. An additional reduction of 1% was observed when rotational deviations were included. The same effect was observed for the CTV(elective) ipsilateral but with smaller dose differences than those for the contralateral side. The effect of the random uncertainties on the mean dose to the parotid glands was not significant. The maximal dose to the spinal cord increased by a maximum of 3 Gy. CONCLUSIONS: The margins to account for random setup uncertainties, in our clinical IMRT solution, should be 1.5 mm and 3.0 mm in the case of sigma = 2 mm and sigma = 4 mm, respectively, for the CTV(primary). Larger margins (5.0 mm), however, should be applied to the CTV(elective), if the goal of treatment is a V(95) value of at least 99%.

Head and Neck Neoplasms↗

PubMed2005

Interobserver variability of clinical target volume delineation of glandular breast tissue and of boost volume in tangential breast irradiation.

BACKGROUND AND PURPOSE: To determine the interobserver variability of clinical target volume delineation of glandular breast tissue and of boost volume in tangential breast irradiation. PATIENTS AND METHODS: Eighteen consecutive patients with left sided breast cancer treated by breast conserving surgery agreed to participate in our study. Volumes of the glandular breast tissue (CTV breast) and of the boost (CTV boost) were delineated by five observers. We determined 'conformity indices' (CI) and the ratio between the volume of each CTV and the mean volume of all CTVs (CTV ratio). Subsequently we determined the most medial, lateral, anterior, posterior, cranial and caudal extensions both of CTV breast and CTV boost for all observers separately. RESULTS: The mean CI breast was 0.87. For one observer we noted the highest CTV ratio in 17 out of 18 cases. No association was noted between CI breast and menopausal status. The mean CI boost was 0.56. We did not find a relation between the presence or absence of clips and the CI boost. For another observer we noted the lowest CTV boost ratio in 10 out of 17 cases. CONCLUSIONS: We recommend that each institute should determine its interobserver variability with respect to CTV breast and CTV boost before implementing the delineation of target volumes by planning CT in daily practice.

Breast Neoplasms↗

PubMed2004

Implanted gold markers for position verification during irradiation of head-and-neck cancers: a feasibility study.

PURPOSE: To assess the toxicity and reliability of the use of implanted gold markers for position verification during irradiation of head-and-neck cancer. METHODS AND MATERIALS: Ten patients with localized head-and-neck tumors received two gold markers in the parapharyngeal region. The acute and late radiation-related toxicity were scored prospectively using the Common Toxicity Criteria. The patients were immobilized during irradiation using a five-point mask. The marker location was detected in portal images taken with an a-Si flat panel imager. The intermarker distance, as well as the interfraction motion of the markers, was determined for all patients. RESULTS: No acute major complications were observed. The acute toxicity grade was not greater than normally detected. The markers were visible in all images. On average, the projected intermarker distance varied 0.8 mm (1 standard deviation). A small time trend was observed in the intermarker distance for 3 patients. For these patients, at least one marker was located in the mucosa or pharyngeal constrictor muscle. Deeper-seated gold markers did not show a time trend in the intermarker distance. The random positioning uncertainty determined using the markers was on average 1.1 and 1.4 mm (1 SD) in the craniocaudal and AP direction, respectively. CONCLUSION: The use of implanted gold markers for position verification during radiotherapy for head-and-neck cancer patients seems safe and feasible. To avoid any chance of migration, markers should be placed in deep muscular compartments.

Feasibility Studies↗

PubMed2004

Location of cervical lymph node metastases in oropharyngeal and hypopharyngeal carcinoma: implications for cranial border of elective nodal target volumes.

PURPOSE: To analyze the exact location of the most cranial metastatic cervical lymph node in patients with oropharyngeal or hypopharyngeal carcinoma. This was done to specify the cranial border of the elective nodal target volume for improvement of parotid-sparing irradiation. METHODS AND MATERIALS: The most cranial metastatic lymph node, ipsilateral and, when present, contralateral, was delineated on 58 diagnostic CT scans of patients with node-positive oropharyngeal or hypopharyngeal carcinoma. The distances from the delineated lymph node to the base of the skull were measured in all planes. RESULTS: The mean ipsilateral and contralateral distance to the base of the skull in the coronal plane was 25.6 mm (range 2.6-73.8; SD 14.7) and 34.7 mm (range 10.4-78.9; SD 14.0), respectively (p = 0.002). Ipsilateral and contralateral metastatic lymph nodes were located within 20 mm below the base of the skull in 24 patients (41%) and 3 patients (5%), respectively. CONCLUSION: Contralateral metastatic lymph nodes are more caudally located than are ipsilateral metastatic lymph nodes. In elective irradiation, lowering the cranial border of the contralateral nodal target volume with 20 mm below the base of the skull should be considered.

Carcinoma, Squamous Cell↗

PubMed2004

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.

Cervical Vertebrae↗

PubMed2004

Loco-regional conformal radiotherapy of the breast: delineation of the regional lymph node clinical target volumes in treatment position.

BACKGROUND AND PURPOSE: As the location of the regional lymph nodes (LNs) of the breast varies largely between patients and may be dependant on the position of the arm, adequate localization of these nodes is mandatory in order to fully take advantage of optimized conformal radiotherapy. For this purpose, the anatomical boundaries of the regional lymph node (LN) clinical target volumes (CTVs) for delineation on transverse CT-slices, made in treatment position, were established. PATIENTS AND METHODS: Anatomical and surgical descriptions of the regional LNs of the breast, as well as a shoulder dissection, were studied. Axial slices of a human cadaver with one arm in abduction and the other in adduction were investigated, to assess the displacement of LNs by abduction of the arm into treatment position. Based on these findings, we defined the anatomical boundaries of the regional LN CTVs visible on transverse CT-slices. RESULTS: Standard anatomical and surgical descriptions appeared to be inadequate for determination of the boundaries of the regional LN CTVs in treatment position. With abduction of the arm, a change in position of all regional LNs, except for the medial supraclavicular LNs and internal mammary LNs, was observed in the anatomical cross-sections. This was also taken into account in our delineation protocol proposal. CONCLUSIONS: Anatomically based guidelines for delineation of the regional LN CTVs for loco-regional irradiation of the breast on transverse CT-slices, made in treatment position, have been developed in this study. These could be used as a basis for conformal radiotherapy.

Arm↗

PubMed2003

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.

Deglutition↗

PubMed2003

Segmental IMRT for oropharyngeal cancer in a clinical setting.

BACKGROUND AND PURPOSE: To develop a segmental intensity-modulated radiotherapy (IMRT) technique for the treatment of oropharyngeal cancer. PATIENTS AND METHODS: Eight patients previously treated for oropharyngeal cancer were replanned with segmental IMRT. The dose distribution was optimized using beam geometries consisting of 3, 5, 7 and 9 equiangular beams. The optimization procedure resulted in a theoretical fluence for each beam. In order to vary the number of segments, the optimized fluence was divided into four different equidistant levels. The final dose distribution was calculated using clinically deliverable segments obtained from optimized fluence. RESULTS: For our segmental IMRT technique the dose homogeneity within the target volumes improved when the total number of segments increased and reached a saturation level at approximately 150 segments. Seven beams were sufficient to achieve the saturation level for dose homogeneity. The mean dose to the parotid glands depended on the beam geometry and tumor location and did not depend on the number of segments. On average the mean dose to the contralateral parotid gland was 35.7 Gy (27.1-39.9 Gy) for all seven beam plans. CONCLUSIONS: Seven beams are sufficient to achieve an acceptable dose homogeneity within the target volumes and significant parotid sparing. These results will be used to introduce IMRT in routine clinical practice.

Humans↗

PubMed2002

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.

Humans↗