Impact of anatomical location on value of CT-PET co-registration for delineation of lung tumors.

PURPOSE: To derive guidelines for the need to use positron emission tomography (PET) for delineation of the primary tumor (PT) according to its anatomical location in the lung. METHODS AND MATERIALS: In 22 patients with non-small-cell lung cancer, thoracic X-ray computed tomography (CT) and PET were performed. Eleven radiation oncologists delineated the PT on the CT and on the CT-PET registered scans. The PTs were classified into two groups. In Group I patients, the PT was surrounded by lung or visceral pleura, without venous invasion, without extension to chest wall or the mediastinum over more than one quarter of its surface. In Group II patients, the PT invaded the hilar region, heart, great vessels, pericardium, mediastinum over more than one quarter of its surface and/or associated with atelectasis. A comparison of interobserver variability for each group was performed and expressed as a local standard deviation. RESULTS: The comparison of delineations showed a good reproducibility for Group I, with an average SD of 0.4 cm on CT and an average SD of 0.3 cm on CT-PET (p = 0.1628). There was also a significant improvement with CT-PET for Group II, with an average SD of 1.3 cm on CT and SD of 0.4 cm on CT-PET (p = 0.0003). The improvement was mainly located at the atelectasis/tumor interface. At the tumor/lung and tumor/hilum interfaces, the observer variation was similar with both modalities. CONCLUSIONS: Using PET for PT delineation is mandatory to decrease interobserver variability in the hilar region, heart, great vessels, pericardium, mediastinum, and/or the region associated with atelectasis; however it is not essential for delineation of PT surrounded by lung or visceral pleura, without venous invasion or extension to the chest wall.

Quality of life after stereotactic body radiation therapy for primary and metastatic liver tumors.

PURPOSE: Stereotactic body radiation therapy (SBRT) provides a high local control rate for primary and metastatic liver tumors. The aim of this study is to assess the impact of this treatment on the patient's quality of life. This is the first report of quality of life associated with liver SBRT. METHODS AND MATERIALS: From October 2002 to March 2007, a total of 28 patients not suitable for other local treatments and with Karnofsky performance status of at least 80% were entered in a Phase I-II study of SBRT for liver tumors. Quality of life was a secondary end point. Two generic quality of life instruments were investigated, EuroQol-5D (EQ-5D) and EuroQoL-Visual Analogue Scale (EQ-5D VAS), in addition to a disease-specific questionnaire, the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ C-30). Points of measurement were directly before and 1, 3, and 6 months after treatment. Mean scores and SDs were calculated. Statistical analysis was performed using paired-samples t-test and Student t-test. RESULTS: The calculated EQ-5D index, EQ-5D VAS and QLQ C-30 global health status showed that mean quality of life of the patient group was not significantly influenced by treatment with SBRT; if anything, a tendency toward improvement was found. CONCLUSIONS: Stereotactic body radiation therapy combines a high local control rate, by delivering a high dose per fraction, with no significant change in quality of life. Multicenter studies including larger numbers of patients are recommended and under development.

Retrospective attenuation correction of PET data for radiotherapy planning using a free breathing CT.

PURPOSE: To evaluate the image quality of retrospectively attenuation corrected Positron Emission Tomography (PET) scans used for gross tumor volume (GTV) delineation in lung cancer patients. MATERIALS AND METHODS: Data of 13 lymph node positive lung cancer patients were acquired on separate CT and PET scanners under free breathing conditions (for radiotherapy planning). First we determined a protocol for CT/PET registration. Second, we compared the image quality of attenuation-corrected PET images using positron transmission images and CT images, in terms of signal-to-noise ratio (SNR) and lesion-to-background ratio (contrast). RESULTS: The largest differences between manual and automatic CT/PET registration were found in the anterior-posterior direction with a mean of 1.8 mm (SD 1.0 mm). Differences in rotations were always smaller than 1.0 degrees . The attenuation-corrected images using CT showed a larger SNR (mean 30%, SD 17%) and larger contrast (mean 14.0%, SD 8.5%) compared to attenuation-corrected images using positron transmission. For lymph nodes, the mean contrast was 16% (SD 6.4%) larger. CONCLUSIONS: This study demonstrated that attenuation correction based on CT provides a better image quality for GTV delineation than when using positron transmission for attenuation correction. Retrospective attenuation correction of PET scans based on registered CT is a good alternative for a dedicated PET/CT scanner if a free-breathing CT is available, e.g., for radiotherapy planning, and allows the use of CT with diagnostic quality for attenuation correction.

Reduction of observer variation using matched CT-PET for lung cancer delineation: a three-dimensional analysis.

PURPOSE: Target delineation using only CT information introduces large geometric uncertainties in radiotherapy for lung cancer. Therefore, a reduction of the delineation variability is needed. The impact of including a matched CT scan with 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and adaptation of the delineation protocol and software on target delineation in lung cancer was evaluated in an extensive multi-institutional setting and compared with the delineations using CT only. METHODS AND MATERIALS: The study was separated into two phases. For the first phase, 11 radiation oncologists (observers) delineated the gross tumor volume (GTV), including the pathologic lymph nodes of 22 lung cancer patients (Stages I-IIIB) on CT only. For the second phase (1 year later), the same radiation oncologists delineated the GTV of the same 22 patients on a matched CT-FDG-PET scan using an adapted delineation protocol and software (according to the results of the first phase). All delineated volumes were analyzed in detail. The observer variation was computed in three dimensions by measuring the distance between the median GTV surface and each individual GTV. The variation in distance of all radiation oncologists was expressed as a standard deviation. The observer variation was evaluated for anatomic regions (lung, mediastinum, chest wall, atelectasis, and lymph nodes) and interpretation regions (agreement and disagreement; i.e., >80% vs. <80% of the radiation oncologists delineated the same structure, respectively). All radiation oncologist-computer interactions were recorded and analyzed with a tool called "Big Brother." RESULTS: The overall three-dimensional observer variation was reduced from 1.0 cm (SD) for the first phase (CT only) to 0.4 cm (SD) for the second phase (matched CT-FDG-PET). The largest reduction in the observer variation was seen in the atelectasis region (SD 1.9 cm reduced to 0.5 cm). The mean ratio between the common and encompassing volume was 0.17 and 0.29 for the first and second phases, respectively. For the first phase, the common volume was 0 in 4 patients (i.e., no common point for all GTVs). In the second phase, the common volume was always >0. For all anatomic regions, the interpretation differences among the radiation oncologists were reduced. The amount of disagreement was 45% and 18% for the first and second phase, respectively. Furthermore, the mean delineation time (12 vs. 16 min, p<0.001) and mean number of corrections (25 vs. 39, p<0.001) were reduced in the second phase compared with the first phase. CONCLUSION: For high-precision radiotherapy, the delineation of lung target volumes using only CT introduces too great a variability among radiation oncologists. Implementing matched CT-FDG-PET and adapted delineation protocol and software reduced observer variation in lung cancer delineation significantly with respect to CT only. However, the remaining observer variation was still large compared with other geometric uncertainties (setup variation and organ motion).

Impact of coronal and sagittal views on lung gross tumor volume delineation.

BACKGROUND AND PURPOSE: To study the impact of coronal and sagittal views (CSV) on the gross tumor volume (GTV) delineation on CT and matched PET/CT scans in non-small cell lung cancer. MATERIAL AND METHODS: GTV delineations were performed by 11 experienced radiation oncologists on CT and PET/CT in 22 patients. Two tumor groups were defined: Group I: Primary tumors surrounded by lung or visceral pleura, without venous invasion, and without large extensions to the chest wall or the mediastinum. Group II: Tumors invading the hilar region, heart, large vessels, pericardium, and the mediastinum and/or associated with atelectasis. Tumor volumes and inter-observers variations (SD) were calculated and compared according to the use of axial view only (AW), axial/coronal/sagittal views (ACSW) and ACSW/PET (ACSWP). RESULTS: CSV were not frequently used (57.4% out of 242 delineations on CT). For group I, ACSW didn't improve significantly mean GTVs. SDs were small on CT and on PET (SD=0.3cm). For group II, ACSW had 27-46% smaller observer variation (mean SD=0.7cm) than AW (mean SD=1.1cm). The smaller observer variation of ACSW users was associated with, on average, a 40% smaller delineated volume (p=0.038). Mean GTV of ACSWP was 21% larger than mean GTV of ACSW on CT. CONCLUSIONS: For smaller lung tumors surrounded by healthy lung tissue the effect of multiple axis delineation is limited. However, application of coronal and sagittal windows is highly beneficial for delineation of more complex tumors, with atelectasis and/or pathological lymph nodes even if PET is used.

Effectiveness of fractionated stereotactic radiotherapy for uveal melanoma.

PURPOSE: To study the effectiveness and acute side effects of fractionated stereotactic radiation therapy (fSRT) for uveal melanoma. METHODS AND MATERIALS: Between 1999 and 2003, 38 patients (21 male, 17 female) were included in a prospective, nonrandomized clinical trial (mean follow-up of 25 months). A total dose of 50 Gy was given in 5 consecutive days. A blinking light and a camera (to monitor the position of the diseased eye) were fixed to a noninvasive relocatable stereotactic frame. Primary end points were local control, best corrected visual acuity, and toxicity at 3, 6, 12, and 24 months, respectively. RESULTS: After 3 months (38 patients), the local control was 100%; after 12 months (32 patients) and 24 months (15 patients), no recurrences were seen. The best corrected visual acuity declined from a mean of 0.21 at diagnosis to 0.06 2 years after therapy. The acute side effects after 3 months were as follows: conjunctival symptoms (10), loss of lashes or hair (6), visual symptoms (5), fatigue (5), dry eye (1), cataract (1), and pain (4). One eye was enucleated at 2 months after fSRT. CONCLUSIONS: Preliminary results demonstrate that fSRT is an effective and safe treatment modality for uveal melanoma with an excellent local control and mild acute side effects. The follow-up should be prolonged to study both long-term local control and late toxicity.

Quantification of shape variation of prostate and seminal vesicles during external beam radiotherapy.

PURPOSE: The prostate is known to translate and rotate under influence of rectal filling changes and many studies have addressed the magnitude of these motions. However, prostate shape variations also have been reported. For image-guided radiotherapy, it is essential to know the relative magnitude of translations, rotations, and shape variation so that the most appropriate correction strategy can be chosen. However, no quantitative analysis of shape variation has been performed. It is, therefore, the purpose of this article to develop a method to determine shape variation of complex organs and apply it to determine shape variation during external beam radiotherapy of a GTV (gross tumor volume) consisting of prostate and seminal vesicles. METHODS AND MATERIALS: For this study, the data of 19 patients with prostate cancer were used. Each patient received a planning computed tomography (CT) scan and 8-12 (11 on average) repeat CT scans that were made during the course of conformal radiotherapy. One observer delineated the GTV in all scans, and volume variations were measured. After matching the GTVs for each patient for translation and rotation, a coverage probability matrix was constructed and the 50% isosurface was taken to determine the average GTV surface. Perpendicular distances between the average GTV and the individual GTVs were calculated for each point of the average GTV, and their variation was expressed in terms of local standard deviation (SD). The local SDs of the shape variation of all 19 patients were mapped onto a reference case by matching and morphing of the individual average GTVs. Repeated delineation of the GTV was done for 6 patients to determine intraobserver variation. Finally, the measured shape variation was corrected for intraobserver variation to estimate the "real" shape variation. RESULTS: No significant variations in GTV volume were observed. The measured shape variation (including delineation variation) was largest at the tip of the vesicles (SD = 2.0 mm), smallest at the left and right side of the prostate (SD = 1.0 mm), and average elsewhere (SD = 1.5 mm). At the left, right, and cranial sides of the prostate, the intraobserver variation was of the same order of magnitude as the measured shape variation; elsewhere it was smaller. However, the accuracy of the estimated SD for intraobserver variation was about half of the accuracy of the estimated SD for the measured shape variation, giving an overall uncertainty of maximum 0.6 mm SD in the estimate of the "real" shape variation. The "real" shape variation was small at the left, right, and cranial side of the prostate (SD <0.5 mm) and between 0.5 mm and 1.6 mm elsewhere. CONCLUSIONS: We developed a method to quantify shape variation of organs with a complex shape and applied it to a GTV consisting of prostate and seminal vesicles. Deformation of prostate and seminal vesicles during the course of radiotherapy is small (relative to organ motion). Therefore, it is a valid approximation in image-guided radiotherapy of prostate cancer, in first order, to correct only for setup errors and organ motion. Prostate and seminal vesicles deformation can be considered as a second-order effect.

Observer variation in target volume delineation of lung cancer related to radiation oncologist-computer interaction: a 'Big Brother' evaluation.

BACKGROUND AND PURPOSE: To evaluate the process of target volume delineation in lung cancer for optimization of imaging, delineation protocol and delineation software. PATIENTS AND METHODS: Eleven radiation oncologists (observers) from five different institutions delineated the Gross Tumor Volume (GTV) including positive lymph nodes of 22 lung cancer patients (stages I-IIIB) on CT only. All radiation oncologist-computer interactions were recorded with a tool called 'Big Brother'. For each radiation oncologist and patient the following issues were analyzed: delineation time, number of delineated points and corrections, zoom levels, level and window (L/W) settings, CT slice changes, use of side windows (coronal and sagittal) and software button use. RESULTS: The mean delineation time per GTV was 16 min (SD 10 min). The mean delineation time for lymph node positive patients was on average 3 min larger (P = 0.02) than for lymph node negative patients. Many corrections (55%) were due to L/W change (e.g. delineating in mediastinum L/W and then correcting in lung L/W). For the lymph node region, a relatively large number of corrections was found (3.7 corr/cm2), indicating that it was difficult to delineate lymph nodes. For the tumor-atelectasis region, a relative small number of corrections was found (1.0 corr/cm2), indicating that including or excluding atelectasis into the GTV was a clinical decision. Inappropriate use of L/W settings was frequently found (e.g. 46% of all delineated points in the tumor-lung region were delineated in mediastinum L/W settings). Despite a large observer variation in cranial and caudal direction of 0.72 cm (1 SD), the coronal and sagittal side windows were not used in 45 and 60% of the cases, respectively. For the more difficult cases, observer variation was smaller when the coronal and sagittal side windows were used. CONCLUSIONS: With the 'Big Brother' tool a method was developed to trace the delineation process. The differences between observers concerning the delineation style were large. This study led to recommendations on how to improve delineation accuracy by adapting the delineation protocol (guidelines for L/W use) and delineation software (double window with lung and mediastinum L/W settings at the same time, enforced use of coronal and sagittal views) and including FDG-PET information (lymph nodes and atelectasis).

Dosimetric comparison between high-precision external beam radiotherapy and endovascular brachytherapy for coronary artery in-stent restenosis.

PURPOSE: Several drawbacks of endovascular brachytherapy for the treatment of coronary artery in-stent restenosis may be addressed by high-precision external beam radiotherapy (EBRT). The dosimetric characteristics of both treatment techniques were compared. METHODS AND MATERIALS: The traversed volume of 10 coronary artery stents during the cardiac cycle was determined by electrocardiographically gated multislice spiral CT in 10 patients. By use of this traversed volume, high-precision EBRT treatment plans were generated for stents in the left circumflex (LCx), left anterior descending (LAD), and right coronary artery (RCA). The maximum dose to the nontargeted major coronary arteries was determined and compared to similar data calculated for endovascular brachytherapy. RESULTS: High-precision EBRT targeted at LCx stents contributed a mean maximum dose (D(max)) of 83.5% (range: 71.6-95.3%) and 16.3% to the LAD and RCA, respectively. Targeted LAD stents contributed a mean D(max) of 39.3% (range: 14.5-94.8%) and 5.2% (range: 0-13.4%) to the LCx and RCA, respectively. Targeted RCA stents contributed a mean D(max) of 6.2% (range: 0-12.4%) and 5.8% (range: 0-11.5%) to the LCx and LAD, respectively. Endovascular brachytherapy targeted at LCx stents contributed a mean D(max) of 1.7% (range: 0.7-2.7%) and 1.0% (range: 0.6-1.4%) to the LAD and RCA, respectively. Targeted LAD stents contributed a mean D(max) of 5.2% (range: 0.5-11.4%) and 0.7% (range: 0.4-1.1%) to the LCx and RCA, respectively; targeted RCA stents contributed a mean D(max) of 0.3% (range: 0.2-0.5%) and 0.2% (range: 0.1-0.3%) to the LCx and LAD, respectively. CONCLUSIONS: Although the doses distributed throughout the heart were higher for high-precision EBRT compared to endovascular brachytherapy, they are expected to be clinically irrelevant when nontargeted major coronary arteries are not closely situated to the targeted vessel segment. These encouraging results warrant further investigation of high-precision EBRT as a potential alternative to endovascular brachytherapy for the treatment of coronary artery in-stent restenosis.

Definition of a moving gross target volume for stereotactic radiation therapy of stented coronary arteries.

PURPOSE: To measure the effect of cardiac motion on coronary artery stent position during the cardiac cycle as a first step toward exploring the feasibility of stereotactic external beam radiation therapy targeted at restenotic stented coronary arteries. METHODS AND MATERIALS: The three-dimensional (3D) position of eight coronary artery stents in 8 patients immobilized in a stereotactic body frame was studied noninvasively by single-breathhold ECG-gated multislice spiral computed tomography (MSCT) during 10 retrospectively selected phases, equally distributed throughout the R-R interval of consecutive cardiac cycles. The volume encompassing all measured 3D positions of the stent was measured. RESULTS: Stent volumes measured by MSCT closely agreed with measurements by quantitative coronary angiography (r > 0.99). The mean of the maximum 3D stent center of mass displacement between any two phases during the cardiac cycle for all eight coronary arteries was 7.5 mm (range 3.3-20.5 mm) in the lateral direction, 8.6 mm (range 2.7-21.6 mm) in the ventrodorsal direction, and 8.2 mm (range 2.5-19.7 mm) in the craniocaudal direction. As was anticipated, the volume encompassing all measured 3D positions of the stent represented only a fraction of the whole heart volume in all patients, i.e., less than 0.6%. CONCLUSIONS: ECG-gated MSCT allowed the measurement of the volume encompassing multiphase 3D positions of coronary artery stents during the cardiac cycle. This volume, a measure of the cardiac motion effect on coronary artery stent position during the cardiac cycle, represents a moving gross target for stereotactic external beam radiation therapy.

A modified relocatable stereotactic frame for irradiation of eye melanoma: design and evaluation of treatment accuracy.

PURPOSE: To describe a reliable, patient-friendly relocatable stereotactic frame for irradiation of eye melanoma and to evaluate the repositioning accuracy of the stereotactic treatment. METHODS AND MATERIALS: An extra construction with a blinking light and a camera is attached to a noninvasive relocatable Gill-Thomas-Cosman stereotactic frame. The position of the blinking light is in front of the unaffected eye and can be adjusted to achieve an optimal position for irradiation. The position of the diseased eye is monitored with a small camera. A planning CT scan is performed with the affected eye in treatment position and is matched with an MR scan to improve the accuracy of the delineation of the tumor. Both the translation and rotation of the affected eye are calculated by comparing the planning CT scan with a control CT scan, performed after the radiation therapy is completed. RESULTS: Nineteen irradiated eye melanoma patients were analyzed. All patients received 5 fractions of 10 Gy within 5 days. The depth-confirmation helmet measurements of the day-to-day treatment position of the skull within the Gill-Thomas-Cosman frame were analyzed in the anteroposterior, lateral, and vertical directions and were 0.1 +/- 0.3, 0.0 +/- 0.2, and 0.2 +/- 0.2 mm (mean +/- SD), respectively. The average translations of the eye on the planning and control CT scan were 0.1 +/- 0.3 mm, 0.1 +/- 0.4, and 0.1 +/- 0.5 mm, respectively. The median rotation of the diseased eye was 8.3 degrees. CONCLUSIONS: The described Rotterdam eye fixation system turned out to be a feasible, reliable, and patient-friendly system.

Reduction of dose delivered to the rectum and bulb of the penis using MRI delineation for radiotherapy of the prostate.

PURPOSE: The prostate volume delineated on MRI is smaller than on CT. The purpose of this study was to determine the influence of MRI- vs. CT-based prostate delineation using multiple observers on the dose to the target and organs at risk during external beam radiotherapy. MATERIALS AND METHODS: CT and MRI scans of the pelvic region were made of 18 patients and matched three-dimensionally on the bony anatomy. Three observers delineated the prostate using both modalities. A fourth observer delineated the rectal wall and the bulb of the penis. The planning treatment volume (PTV) was generated from the delineated prostates with a margin of 10 mm in three-dimensions. A three-field treatment plan with a prescribed dose of 78 Gy to the International Commission on Radiation Units and Measurements point was automatically generated from each PTV. Dose-volume histograms were calculated of all PTVs, rectal walls, and penile bulbs. The equivalent uniform dose was calculated for the rectal wall using a volume exponent (n = 0.12). RESULTS: The equivalent uniform dose of the CT rectal wall in plans based on the CT-delineated prostate was, on average, 5.1 Gy (SEM 0.5) greater than in the plans based on the MRI-delineated prostate. For the MRI rectal wall, this difference was 3.6 Gy (SEM 0.4). Allowing for the same equivalent uniform dose to the CT rectal wall, the prescribed dose to the PTV could be raised from 78 to 85 Gy when using the MRI-delineated prostate for treatment planning. The mean dose to the bulb of the penis was 11.6 Gy (SEM 1.8) lower for plans based on the MRI-delineated prostate. The mean coverage (volume of the PTV receiving > or =95% of the prescribed dose) was 99.9% for both modalities. The interobserver coverage (coverage of the PTV by a treatment plan designed for the PTV delineated by another observer in the same modality) was 97% for both modalities. The MRI rectum was significantly more ventrally localized than the CT rectum, probably because of the rounded tabletop and no knee support on the MRI scanner. CONCLUSIONS: The dose delivered to the rectal wall and bulb of the penis is significantly reduced with treatment plans based on the MRI-delineated prostate compared with the CT-delineated prostate, allowing a dose escalation of 2.0-7.0 Gy for the same rectal wall dose. The interobserver coverage was the same for CT and MRI delineation of the prostate. A statistically significant difference in position between the CT- and MRI-delineated rectum was observed, probably owing to a different tabletop and use of knee support.

A biplane angiographic study on cardiac motion of coronary artery stents: options to minimize the target volume for high-precision external beam radiotherapy of coronary artery in-stent restenosis.

PURPOSE: High-precision external beam radiotherapy (EBRT) has been suggested as a potential alternative to endovascular brachytherapy for the treatment of coronary artery in-stent restenosis. The purpose of our study was to investigate and compare different options to define a smallest feasible target volume. METHODS AND MATERIALS: The cardiac motion of 17 coronary artery stents in 17 patients was studied by use of biplane conventional angiography, recorded during breath-hold. Each stent was reconstructed in three dimensions by use of biplane sets of frames covering an entire cardiac cycle. The volume traversed by the stent during the entire or part of the cardiac cycle was determined. Four options to define the stent-traversed volume (STV) as a target for high-precision EBRT were investigated. RESULTS: The mean STV during the entire cardiac cycle was 3.5 cm3; the STV represented less than 1% of the heart volume in all patients. The STV during the diastolic and systolic phase resulted in a mean reduction of 26.6% and 29.1%, respectively, compared with the STV during the entire cardiac cycle. The smallest STV, measured during a 160-ms interval within the cardiac cycle, resulted in a mean maximal reduction of 75.9% compared with the STV during the entire cardiac cycle. CONCLUSIONS: The STV during the entire cardiac cycle represents a small potential target volume for high-precision EBRT. A significant reduction of this target volume is possible in case of definition during a selected interval within the cardiac cycle.

Role of endocavitary brachytherapy with or without chemotherapy in cancer of the nasopharynx.

PURPOSE: We previously reported our preliminary experience with nasopharyngeal cancer boosted after 60-70 Gy external beam radiotherapy (EBRT) by fractionated endocavitary brachytherapy (ECBT) to cumulative doses of 78-82 Gy. As for Stage III-IVB disease, cisplatin (CDDP)-based neoadjuvant chemotherapy (CHT) was given. The aim of the present study was to define the role of ECBT more accurately. METHODS AND MATERIALS: Ninety-one patients with primary nasopharyngeal cancer, staged according to the 1997 UICC/AJCC classification system, were treated between 1991 and 2000 with 60-70 Gy external beam radiotherapy and 11-18 Gy ECBT. Of the 91 patients, 21 were treated in conjunction with CHT and 70 without CHT. Tumors were subdivided into undifferentiated (UD) and well, moderately, and poorly differentiated (WMP-D) subtypes. Treatment results were analyzed for local control (LC), disease-free survival (DFS), freedom from distant metastasis, and overall survival (OS). RESULTS: A univariate and multivariate Cox regression analysis found stage, treatment period, age, and grade significant for LC, DFS, and OS. At 2 years, for Stage I-IIB (1st period, 1991-1996), the LC, DFS, and OS were 96%, 88%, and 80%, respectively, vs. 65%, 46%, and 52% for Stage III-IVB. For the 2nd treatment period (1996-2000; CHT for Stage III-IVB), the LC, DFS, and OS at 2 years was 100%, 90%, and 61% (Stage I-IIB), respectively, vs. 86%, 74%, and 66% (Stage III-IVB). Three prognostic groups (PGs) were constructed. For the 1991-1996 period, at 2 years, patients in the good PG (UD Stage I-IIB disease) had 100% LC and 92% OS; those in the intermediate PG (UD Stage III-IVB or WMP-D Stage I-IIB), had 94% LC and 71% OS; and those in the poor PG (WMP-D Stage III-IVB) had 47% LC and 40% OS. For the 1996-2000 period, at 2 years, the good PG had 100% LC and 88% OS; the intermediate PG had 100% LC and 64% OS; and the poor PG had 71% LC and 60% OS. CONCLUSION: For Stage I-IIB disease treated between 1991 and 2000, at 3 years, the LC and OS was 97% and 67%, respectively. The results with 77-81 Gy without CHT warrant EBRT combined with ECBT to remain our standard of care for Stage I-IIB disease. For N2-3 and/or T3-4 tumors, in addition to high doses of RT, neoadjuvant CHT was administered as of 1996. For the 1991-2000 period, at 3 years, the LC was 86% and the OS was 72% with CHT, with little extra morbidity; they were 68% and 35% without CHT. Because of better target coverage and sparing, T3-4 tumors are currently boosted by stereotactic RT to 81.2 Gy.

Impact of knee support and shape of tabletop on rectum and prostate position.

PURPOSE: To evaluate the impact of different tabletops with or without a knee support on the position of the rectum, prostate, and bulb of the penis; and to evaluate the effect of these patient-positioning devices on treatment planning. METHODS AND MATERIALS: For 10 male volunteers, five MRI scans were made in four different positions: on a flat tabletop with knee support, on a flat tabletop without knee support, on a rounded tabletop with knee support, and on a rounded tabletop without knee support. The fifth scan was in the same position as the first. With image registration, the position differences of the rectum, prostate, and bulb of the penis were measured at several points in a sagittal plane through the central axis of the prostate. A planning target volume was generated from the delineated prostates with a margin of 10 mm in three dimensions. A three-field treatment plan with a prescribed dose of 78 Gy to the International Commission on Radiation Units and Measurements point was automatically generated from each planning target volume. Dose-volume histograms were calculated for all rectal walls. RESULTS: The shape of the tabletop did not affect the rectum and prostate position. Addition of a knee support shifted the anterior and posterior rectal walls dorsally. For the anterior rectal wall, the maximum dorsal shift was 9.9 mm (standard error of the mean [SEM] 1.7 mm) at the top of the prostate. For the posterior rectal wall, the maximum dorsal shift was 10.2 mm (SEM 1.5 mm) at the middle of the prostate. Therefore, the rectal filling was pushed caudally when a knee support was added. The knee support caused a rotation of the prostate around the left-right axis at the apex (i.e., a dorsal rotation) by 5.6 degrees (SEM 0.8 degrees ) and shifts in the caudal and dorsal directions of 2.6 mm (SEM 0.4 cm) and 1.4 mm (SEM 0.6 mm), respectively. The position of the bulb of the penis was not influenced by the use of a knee support or rounded tabletop. The volume of the rectal wall receiving the same dose range (e.g., 40-75 Gy) was reduced by 3.5% (SEM 0.9%) when a knee support was added. No significant differences were observed between the first and fifth scan (flat tabletop with knee support) for all measured points, thereby excluding time trends. CONCLUSIONS: The rectum and prostate were significantly shifted dorsally by the use of a knee support. The rectum shifted more than the prostate, resulting in a dose benefit compared with irradiation without knee support. The shape of the tabletop did not influence the rectum or prostate position.

High-dose, high-precision treatment options for boosting cancer of the nasopharynx.

PURPOSE: The aim of the study is to define the role and type of high-dose, high-precision radiation therapy for boosting early staged T1,2a, but in particular locally advanced, T2b-4, nasopharyngeal cancer (NPC). MATERIALS AND METHODS: Ninety-one patients with primary stage I-IVB NPC, were treated between 1991 and 2000 with 60-70Gy external beam radiation therapy (ERT) followed by 11-18Gy endocavitary brachytherapy (ECBT) boost. In 1996, for stage III-IVB disease, cisplatinum (CDDP)-based neoadjuvant chemotherapy (CHT) was introduced per protocol. Patients were analyzed for local control and overall survival. For a subset of 18 patients, a magnetic resonance imaging (MRI) scan at 46Gy was obtained. After matching with pre-treatment computed tomogram, patients (response) were graded into four categories; i.e. LD (T1,2a, with limited disease, i.e. disease confined to nasopharynx), LRD (T2b, with limited residual disease), ERD (T2b, with extensive residual disease), or patients initially diagnosed with T3,4 tumors. Dose distributions for ECBT (Plato-BPS v. 13.3, Nucletron) were compared to parallel-opposed three-dimensional conformal radiation therapy (Cadplan, Varian Dosetek v. 3.1), intensity modulated radiation therapy (IMRT) (Helios, Varian) and stereotactic radiotherapy (SRT) (X-plan, Radionics v. 2.02). RESULTS: For stage T1,2N0,1 tumors, at 2 years local control of 96% and overall survival of 80% were observed. For the poorest subset of patients, well/moderate/poorly differentiated T3,4 tumors, local control and overall survival at 2 years with CHT were 67 and 67%, respectively, vs. local control of 20% and overall survival of 12% without CHT. For LD and LRD, conformal target coverage and optimal sparing can be obtained with brachytherapy. For T2b-ERD and T3,4 tumors, these planning goals are better achieved with SRT and/or IMRT. CONCLUSIONS: The dosimetric findings, ease of application of the brachytherapy procedure, and the clinical results in early staged NPC, necessitates ERT combined with brachytherapy boost to be the therapy of preference for LD and LRD. For locally advanced T3,4 tumors, our current protocol indicates neoadjuvant chemotherapy in conjunction with high cumulative doses of radiotherapy (81Gy); IMRT and/or SRT to be the preferred technique for boosting the primary tumor.

Coronary stent traversed volume during the cardiac cycle defined as a target for high-precision radiotherapy by using biplane angiograms.

Three-dimensional reconstructions of 19 coronary artery stents from biplane angiograms were used for measurement of the volume through which the stents traversed during the cardiac cycle. This volume, less than 0.8% of the whole heart volume in all patients, represents a target volume for high-precision radiotherapy to treat coronary artery in-stent restenosis.

Optimisation of conformal radiation therapy by intensity modulation: cancer of the larynx and salivary gland function.

PURPOSE: Prevention of damage to critical normal tissues is of paramount importance for the quality of life of patients irradiated for cancers in the head and neck. The purpose of this paper was to evaluate the parotid gland sparing 3D conformal radiation therapy technique (3DCRT) in a prospective study in node negative cancer of the larynx. MATERIALS AND METHODS: Twenty-six patients with node negative squamous cell cancer of the larynx were irradiated by a 3DCRT technique (class solution) to both sides of the neck (elective dose 46 Gy to levels II, III and IV) and primary tumour (70 Gy). Dose distributions of the major salivary glands were correlated with objective (stimulated whole saliva flow, WS) and subjective (questionnaire; visual analogue scale, VAS) salivary gland function. Apart from the clinically used 3DCRT technique, in order to optimise 3DCRT dose distributions, intensity modulated (IMRT) treatment plans were generated for the same patient population. Dose-volume histograms of 3DCRT and IMRT treatment plans were analysed and compared. RESULTS: For the 26 patients irradiated with the 3DCRT class solution technique: VAS scores and questionnaires reached their nadir 3 months post-radiotherapy; WS reached its nadir 6 months post-radiotherapy. WS flow rates improved significantly, but never normalised; 2 years post-treatment WS measurements were 48% of the pre-treatment values. VAS scores deteriorated during ERT from 0 pre-treatment to 6.1 immediately post-treatment. Compared to pre-treatment, questionnaires were answered affirmative by increasing numbers of patients. For all patients, IMRT treatment plans resulted in a significant reduction of the dose delivered to the parotid glands compared to the 3DCRT-treatment technique. CONCLUSIONS: The class solution for the 3DCRT salivary gland sparing technique is inadequate for fully preserving salivary gland function, given the dose distributions (DVHs) as well as the subjective- and objective salivary gland function assessments. The results can be optimised in the future, that is a further reduction of xerostomia can be achieved, by using IMRT techniques focused at sparing major and minor salivary glands.

Unexpected response of a pulmonary blastoma on radiotherapy: a case report and review of the literature.

Pulmonary blastoma (PB) is a rare malignant tumor of the lung. Treatment is primarily surgical, although, combination chemotherapy has been reported to result in objective responses in inoperable tumors or after incomplete resections. To our knowledge, this is the first report of a very radiosensitive PB, which showed major tumor reduction after several fractions of radiotherapy without further tumor regression after additional chemotherapy with cisplatin and etoposide. The literature on the treatment of PB is reviewed.

Comparison of macroscopic pathology measurements with magnetic resonance imaging and assessment of microscopic pathology extension for colorectal liver metastases.

PURPOSE: To compare pathology macroscopic tumor dimensions with magnetic resonance imaging (MRI) measurements and to establish the microscopic tumor extension of colorectal liver metastases. METHODS AND MATERIALS: In a prospective pilot study we included patients with colorectal liver metastases planned for surgery and eligible for MRI. A liver MRI was performed within 48 hours before surgery. Directly after surgery, an MRI of the specimen was acquired to measure the degree of tumor shrinkage. The specimen was fixed in formalin for 48 hours, and another MRI was performed to assess the specimen/tumor shrinkage. All MRI sequences were imported into our radiotherapy treatment planning system, where the tumor and the specimen were delineated. For the macroscopic pathology analyses, photographs of the sliced specimens were used to delineate and reconstruct the tumor and the specimen volumes. Microscopic pathology analyses were conducted to assess the infiltration depth of tumor cell nests. RESULTS: Between February 2009 and January 2010 we included 13 patients for analysis with 21 colorectal liver metastases. Specimen and tumor shrinkage after resection and fixation was negligible. The best tumor volume correlations between MRI and pathology were found for T1-weighted (w) echo gradient sequence (r(s) = 0.99, slope = 1.06), and the T2-w fast spin echo (FSE) single-shot sequence (r(s) = 0.99, slope = 1.08), followed by the T2-w FSE fat saturation sequence (r(s) = 0.99, slope = 1.23), and the T1-w gadolinium-enhanced sequence (r(s) = 0.98, slope = 1.24). We observed 39 tumor cell nests beyond the tumor border in 12 metastases. Microscopic extension was found between 0.2 and 10 mm from the main tumor, with 90% of the cases within 6 mm. CONCLUSIONS: MRI tumor dimensions showed a good agreement with the macroscopic pathology suggesting that MRI can be used for accurate tumor delineation. However, microscopic extensions found beyond the tumor border indicate that caution is needed in selecting appropriate tumor margins.