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Di Yan

Publications and source records attributed to Di Yan.

At least 19 recordsLinked to original sources
PubMed2026

A Novel Homozygous Mutation in ARL2BP Causes Multiple Morphological Abnormalities of the Flagella and Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) and multiple morphological abnormalities of the sperm flagella (MMAF) frequently co-occur in male infertility. However, the genetic basis of this syndromic presentation remains unclear. Using whole-exome sequencing, we identified a novel homozygous ARL2BP splice-site mutation (c.294-2A>G) in a 23-year-old infertile male from a consanguineous family who presented with syndromic PCD and MMAF. This variant causes aberrant pre-mRNA splicing and triggers nonsense-mediated mRNA decay, resulting in the complete absence of ARL2BP protein expression. Transmission electron microscopy revealed extensive disorganization of flagellar axonemes with consistent central pair (CP) microtubule depletion and disorganization of peripheral doublets. Immunofluorescence confirmed a severe deficiency of the CP protein SPAG6 in the sperm flagella. Notably, the patient presented without retinal symptoms. Given that ARL2BP-related retinitis pigmentosa generally emerges during the third decade, long-term ophthalmological follow-up is essential to detect delayed-onset retinal degeneration. In conclusion, these findings confirm ARL2BP as a causative gene for both PCD and MMAF, expanding the genotypic and phenotypic spectrum of ciliopathies.

Humans↗
PubMed2006

Clinical implications of defining the gross tumor volume with combination of CT and 18FDG-positron emission tomography in non-small-cell lung cancer.

PURPOSE: To compare the planning target volume (PTV) definitions for computed tomography (CT) vs. positron emission tomography (PET) in non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: A total of 21 patients with NSCLC underwent three-dimensional conformal radiotherapy planning. All underwent a staging F-18 fluorodeoxyglucose-position emission tomography (18FDG-PET) scan and underwent treatment simulation using CT plus a separate planning 18FDG-PET scan. Three sets of target volumes were defined: Set 1, CT volumes (CT tumor + staging PET nodal disease); Set 2, PET volumes (planning PET tumor {gross tumor volume (GTV) = [(0.3069 x mean standardized uptake value) + 0.5853])}; Set 3, composite CT-PET volumes (fused CT-PET tumor). Sets 1 and 2 were compared using a matching index. Three-dimensional conformal radiotherapy plans were created using the Set 1 (CT) volumes; and coverage of the Set 3 (composite) volumes was evaluated. Separate three-dimensional conformal radiotherapy plans were designed for the Set 3 volumes. RESULTS: For the primary tumor GTV, the Set 1 (CT) volume was larger than the Set 2 (PET) volume in 48%, smaller in 33%, and equal in 19%. The mean matching index was 0.65 (35% CT-PET mismatch). Although quantitatively similar, the volumes differed qualitatively. The Set 3 (composite) volume was larger than either CT or PET alone in 62%, smaller in 24%, and equal in 14%. The dose-volume histogram parameters did not differ among the plans for Set 1 (CT) vs. Set 3 (composite) volumes. Small portions of the Set 3 PTV were significantly underdosed in 40% of cases using the CT-only plan. CONCLUSION: Computed tomography and PET are complementary and should be obtained in the treatment position and fused to define the GTV for NSCLC. Although the quantitative absolute target volume is sometimes similar, the qualitative target locations can be substantially different, leading to underdosage of the target when planning is done using CT alone without PET fusion.

Carcinoma, Non-Small-Cell Lung↗
PubMed2006

Population and patient-specific target margins for 4D adaptive radiotherapy to account for intra- and inter-fraction variation in lung tumour position.

In this work, five 4D image-guidance strategies (two population, an offline adaptive and two online strategies) were evaluated that compensated for both inter- and intra-fraction variability such as changes to the baseline tumour position and respiratory pattern. None of the strategies required active motion compensation such as gating or tracking; all strategies simulated a free-breathing-based treatment technique. Online kilovoltage fluoroscopy was acquired for eight patients with lung tumours, and used to construct inter- and intra-fraction tumour position variability models. Planning was performed on a mid-ventilation image acquired from a respiration-correlated CT scan. The blurring effect of tumour position variability was included in the dose calculation by convolution. CTV to PTV margins were calculated for variability in the cranio-caudal direction. A population margin of 9.0 +/- 0.7 mm was required to account for setup error and respiration in the study population without the use of image-guidance. The greatest mean margin reduction was introduced by the offline adaptive strategy. A daily online correction strategy produced a small reduction (1.6 mm) in the mean margin from the offline strategy. Adaptively correcting for an inter-fraction change in the respiratory pattern had little effect on margin size due to most patients having only small daily changes in the respiratory pattern. A daily online correction strategy would be useful for patients who exhibit large variations in the daily mean tumour position, while an offline adaptive strategy is more applicable to patients with less variation.

Fluoroscopy↗
PubMed2006

Clinicopathologic analysis of extracapsular extension in prostate cancer: should the clinical target volume be expanded posterolaterally to account for microscopic extension?

PURPOSE: We performed a complete pathologic analysis examining extracapsular extension (ECE) and microscopic spread of malignant cells beyond the prostate capsule to determine whether and when clinical target volume (CTV) expansion should be performed. METHODS AND MATERIALS: A detailed pathologic analysis was performed for 371 prostatectomy specimens. All slides from each case were reviewed by a single pathologist (N.S.G.). The ECE status and ECE distance, defined as the maximal linear radial distance of malignant cells beyond the capsule, were recorded. RESULTS: A total of 121 patients (33%) were found to have ECE (68 unilateral, 53 bilateral). Median ECE distance=2.4 mm [range: 0.05-7.0 mm]. The 90th-percentile distance = 5.0 mm. Of the 121 cases with ECE, 55% had ECE distance>or=2 mm, 19%>or=4 mm, and 6%>or=6 mm. ECE occurred primarily posterolaterally along the neurovascular bundle in all cases. Pretreatment prostrate-specific antigen (PSA), biopsy Gleason, pathologic Gleason, clinical stage, bilateral involvement, positive margins, percentage of gland involved, and maximal tumor dimension were associated with presence of ECE. Both PSA and Gleason score were associated with ECE distance. In all 371 patients, for those with either pretreatment PSA>or=10 or biopsy Gleason score>or=7, 21% had ECE>or=2 mm and 5%>or=4 mm beyond the capsule. For patients with both of these risk factors, 49% had ECE>or=2 mm and 21%>or=4 mm. CONCLUSIONS: For prostate cancer with ECE, the median linear distance of ECE was 2.4 mm and occurred primarily posterolaterally. Although only 5% of patients demonstrate ECE>4 to 5 mm beyond the capsule, this risk may exceed 20% in patients with PSA>or=10 ng/ml and biopsy Gleason score>or=7. As imaging techniques improve for prostate capsule delineation and as radiotherapy delivery techniques increase in accuracy, a posterolateral CTV expansion should be considered for patients at high risk.

Aged↗
PubMed2006

Geometric and dosimetric evaluations of an online image-guidance strategy for 3D-CRT of prostate cancer.

PURPOSE: To evaluate an online image-guidance strategy for conformal treatment of prostate cancer and to estimate margin-reduction benefits. METHODS AND MATERIALS: Twenty-eight patients with at least 16 helical computed tomography scans were each used in this study. Two prostate soft-tissue registration methods, including sagittal rotation, were evaluated. Setup errors and rigid organ motion were corrected online; non-rigid and intrafraction motion were included in offline analysis. Various clinical target volume-planning target volume (CTV-PTV) margins were applied. Geometrical evaluations included analyses of isocenter shifts and rotations and overlap index. Dosimetric evaluations included minimum dose and equivalent uniform dose (EUD) for prostate and gEUD for rectum. RESULTS: Average isocenter shift and rotation were (dX,dY,dZ,theta) = (0.0 +/- 0.7,-1.1 +/- 4.0,-0.1 +/- 2.5,0.7 degrees +/- 2.0 degrees ) mm. Prostate motion in anterior-posterior (AP) direction was significantly higher than superior-inferior and left-right (LR) directions. This observation was confirmed by isocenter shift in perspectives AP (1.8 +/- 1.8 mm) and RL (3.7 +/- 3.0 mm). Organ motion degrades target coverage and reduces doses to rectum. If 2% dose reduction on prostate D(99) is allowed for 90% patients, then minimum 3 mm margins are necessary with ideal image registration. CONCLUSIONS: Significant margin reduction can be achieved through online image guidance. Certain margins are still required for nonrigid and intrafraction motion. To further reduce margin, a strategy that combines online geometric intervention and offline dose replanning is necessary.

Algorithms↗
PubMed2006

Changes in the respiratory pattern during radiotherapy for cancer in the lung.

BACKGROUND AND PURPOSE: To quantify changes in patients' diaphragm motion pattern over the course of radiotherapy and to evaluate the implications of these changes for 4D radiotherapy. PATIENTS AND METHODS: From January 2004 to October 2004, 10 patients with lung malignancies treated at our department underwent weekly respiratory motion verification during the course of external beam radiation. An onboard kilovoltage imaging system was used to acquire fluoroscopy weekly for patients with lung neoplasms. The diaphragm position as a function of time was extracted automatically from the fluoroscopy and used to calculate the daily mean and daily SD of motion. The diaphragm position was related to both a bony reference point and machine isocenter. Changes in the daily mean and daily SD in relation to the reference (first day) daily mean and reference daily SD were measured. RESULTS: The mean change in the daily mean was 0.32 mm+/-6.11 mm in relation to the bony reference point and 0.38 mm+/-6.28 mm in relation to isocenter. The mean change in the daily SD was 0.91 mm+/-1.81 mm. The mean systematic change in the daily mean was 4.97 mm, and the mean random change in the daily mean was 3.61 mm. CONCLUSIONS: Daily verification of 4D radiotherapy techniques to assess the necessity of online set-up correction may be required due to the large change in the mean diaphragm position observed for these patients. However, the variation of the daily SD was small for most patients. Adaptive adjustment of the margin may be necessary for those patients with larger variation of the daily SD.

Adaptation, Physiological↗
PubMed2006

Application of dose compensation in image-guided radiotherapy of prostate cancer.

In image-guided radiation therapy (IGRT), volumetric information on patient anatomy at treatment conditions is made available with in-room imaging devices capable of cone-beam CT. Setup error and inter-fraction rigid motion can be corrected online. The planning margin can therefore be reduced significantly. However, to compensate for uncertainties including organ deformation and intra-fraction motion, offline evaluation and replanning are necessary. The purpose of this study is to investigate the use of an offline dose compensation technique to further reduce the margin safely. In IGRT, online CT scan, rigid image registration and setup correction are performed at each fraction. Later the regions of interest are registered offline between treatment and planning CTs using a finite element method to account for non-rigid organ motion. Cumulative dose distribution is calculated and compared with the prescription dose. The discrepancy, if found significant, is repaired using the dose compensation technique, in which the cumulative dose distribution is incorporated in adaptive IMRT planning for future fractions. Two compensation schedules were tested in this study: single compensation at the end of the treatment course and compensation performed weekly. One patient with one planning CT and 16 treatment CTs were used in this simulation study. Due to the aggressive smaller planning margin used, severe underdose was observed in the clinical target volume. The size and magnitude of the underdose were reduced substantially with online guidance but were still significant. Both dose compensation strategies were able to reduce the dose deficit to an acceptable level without additional planning margin. Weekly compensation is more biologically beneficial and can spread the execution error into multiple fractions. The offline dose compensation technique allows further margin reduction and can complement the online guidance by compensating for uncertainties that cannot be reduced online, thereby increasing the confidence in IGRT delivery.

Dose-Response Relationship, Radiation↗
PubMed2006

Addressing glucose sensitivity measured by F-18 FDG PET in lung cancers for radiation treatment planning and monitoring.

PURPOSE: To address glucose sensitivity in lung cancers before and after radiation treatment (Tx). METHODS AND MATERIALS: Twelve patients were each studied with two pre-Tx positron emission tomography (PET) scans and 3 patients each with one post-Tx PET scan, with glucose concentration [Glc] and maximum standard uptake value (SUV) recorded. The pre-Tx glucose sensitivity, g from SUV1/SUV2= {[Glc]1/[Glc]2}g and Tx index, tau from SUVpost-Tx/SUVpre-Tx = {[Glc]post-Tx/[Glc]pre-Tx}tau was calculated by linear regression. Pre-Tx SUVs were corrected to post-Tx Glc with g (SUV'pre-Tx) for a pure Tx effect, R = ln(SUVpost-Tx/SUV'pre-Tx). RESULTS: There were no significant differences in SUV but [Glc] were different (96.4 +/- 10.9 vs. 88.3 +/- 10.5, p = 0.015) between two pre-Tx PET scans. Linear regression yielded g = -0.79 and tau = -1.78 to -2.41 (p < 0.0005 in all). The %DeltaSUV after Tx for 3 patients without vs. with g correction were different by -12%, 0%, and + 7%, suggesting varying effects from glucose. R values were also different and mean R (-0.81 +/- 0.38) was significantly different from zero (p = 0.03), consistent with successful Tx as confirmed by clinico-radiologic follow-up. CONCLUSIONS: The extra dimension of glucose sensitivity, g besides SUV incorporated in the combined Tx-derived tau may be a useful global Tx evaluation index even with differing [Glc].

Aged↗
PubMed2005

Phase II dose escalation study of image-guided adaptive radiotherapy for prostate cancer: use of dose-volume constraints to achieve rectal isotoxicity.

PURPOSE: In our Phase II prostate cancer Adaptive Radiation Therapy (ART) study, the highest possible dose was selected on the basis of normal tissue tolerance constraints. We analyzed rectal toxicity rates in different dose levels and treatment groups to determine whether equivalent toxicity rates were achieved as hypothesized when the protocol was started. METHODS AND MATERIALS: From 1999 to 2002, 331 patients with clinical stage T1 to T3, node-negative prostate cancer were prospectively treated with three-dimensional conformal adaptive RT. A patient-specific confidence-limited planning target volume was constructed on the basis of 5 CT scans and 4 sets of electronic portal images after the first 4 days of treatment. For each case, the rectum (rectal solid) was contoured in its entirety. The rectal wall was defined by use of a 3-mm wall thickness (median volume: 29.8 cc). The prescribed dose level was chosen using the following rectal wall dose constraints: (1) Less than 30% of the rectal wall volume can receive more than 75.6 Gy. (2) Less than 5% of the rectal wall can receive more than 82 Gy. Low-risk patients (PSA < 10, Stage < or = T2a, Gleason score < 7) were treated to the prostate alone (Group 1). All other patients, intermediate and high risk, where treated to the prostate and seminal vesicles (Group 2). The risk of chronic toxicity (NCI Common Toxicity Criteria 2.0) was assessed for the different dose levels prescribed. HIC approval was acquired for all patients. Median follow-up was 1.6 years. RESULTS: Grade 2 chronic rectal toxicity was experienced by 34 patients (10%) (9% experienced rectal bleeding, 6% experienced proctitis, 3% experienced diarrhea, and 1% experienced rectal pain) at a median interval of 1.1 year. Nine patients (3%) experienced grade 3 or higher chronic rectal toxicity (1 Grade 4) at a median interval of 1.2 years. The 2-year rates of Grade 2 or higher and Grade 3 or higher chronic rectal toxicity were 17% and 3%, respectively. No significant difference by dose level was seen in the 2-year rate of Grade 2 or higher chronic rectal toxicity. These rates were 27%, 15%, 14%, 17%, and 24% for dose levels equal to or less than 72, 73.8, 75.6, 77.4, and 79.2 Gy, respectively (p = 0.3). Grade 2 or higher chronic rectal bleeding was significantly greater for Group 2 than for Group 1, 17% vs. 8% (p = 0.035). CONCLUSIONS: High doses (79.2 Gy) were safely delivered in selected patients by our adaptive radiotherapy process. Under the rectal dose-volume histogram constraints for the dose level selection, the risk of chronic rectal toxicity is similar among patients treated to different dose levels. Therefore, rectal chronic toxicity rates reflect the dose-volume cutoff used and are independent of the actual dose levels. On the other hand, a larger PTV will increase the rectal wall dose and chronic rectal toxicity rates. PTV volume and dose constraints should be defined, considering their potential benefit.

Aged↗
PubMed2005

Dose-volume analysis of predictors for chronic rectal toxicity after treatment of prostate cancer with adaptive image-guided radiotherapy.

PURPOSE: We analyzed our experience treating localized prostate cancer with image-guided off-line correction with adaptive high-dose radiotherapy (ART) in our Phase II dose escalation study to identify factors predictive of chronic rectal toxicity. MATERIALS AND METHODS: From 1999-2002, 331 patients with clinical stage T1-T3N0M0 prostate cancer were prospectively treated in our Phase II 3D conformal dose escalation ART study to a median dose of 75.6 Gy (range, 63.0-79.2 Gy), minimum dose to confidence limited-planning target volume (cl-PTV) in 1.8 Gy fractions (median isocenter dose = 79.7 Gy). Seventy-four patients (22%) also received neoadjuvant/adjuvant androgen deprivation therapy. A patient-specific cl-PTV was constructed using 5 computed tomography scans and 4 sets of electronic portal images by applying an adaptive process to assure target accuracy and minimize PTV margin. For each case, the rectum (rectal solid) was contoured from the sacroiliac joints or rectosigmoid junction (whichever was higher) to the anal verge or ischial tuberosities (whichever was lower), with a median volume of 81.2 cc. The rectal wall was defined using the rectal solid with an individualized 3-mm wall thickness (median volume = 29.8 cc). Rectal wall dose-volume histogram was used to determine the prescribed dose. Toxicity was quantified using the National Cancer Institute Common Toxicity Criteria 2.0. Multiple dose-volume endpoints were evaluated for their association with chronic rectal toxicity. RESULTS: Median follow-up was 1.6 years. Thirty-four patients (crude rate = 10.3%) experienced Grade 2 chronic rectal toxicity at a median interval of 1.1 years. Nine patients (crude rate = 2.7%) experienced Grade > or =3 chronic rectal toxicity (1 was Grade 4) at a median interval of 1.2 years. The 3-year rates of Grade > or =2 and Grade > or =3 chronic rectal toxicity were 20% and 4%, respectively. Acute toxicity predicted for chronic: Acute Grade 2-3 rectal toxicity (p < 0.001) including any acute rectal Grade 2-3 tenesmus (p = 0.02) and pain (p = 0.008) were significant predictors of chronic Grade > or =2 rectal toxicity. Any acute rectal toxicity (p = 0.001), any acute tenesmus (p = 0.03), and any acute diarrhea (p < 0.001) were also found to be predictive for chronic toxicity, as continuous variables. Dose-volume histogram predicted for chronic toxicity: Rectal wall absolute and relative V50, V60, V66.6, V70, and V72 and rectal solid relative V60-V72 were significantly associated with chronic Grade > or =2 rectal toxicity both as categorical and continuous variables (t test, linear regression) and when divided into subgroups (chi-square table). The chronic rectal toxicity Grade > or =2 risk was 9%, 18%, and 25% for the rectal wall relative V70 <15%, 25%-40%, and >40% respectively. The volume of rectum or rectal wall radiated to > or =50 Gy was a strong predictor for chronic rectal toxicity. Nonpredictive factors: Rectal solid/wall absolute or relative volumes irradiated to < or =40 Gy, dose level, and use of androgen deprivation were not found predictive. CONCLUSIONS: In our ART dose escalation study, rectal wall or rectum relative > or =V50 are closely predictive for chronic rectal toxicity. If rectal dose-volume histogram constraints are used to select the dose level, the risk of chronic rectal toxicity will reflect the risk of toxicity of the selected constraint rather than the dose selected as found in our study using an adaptive process. To select the prescribed dose, different dose-volume histogram constraints may be used including the rectal wall V70. Patients experiencing acute rectal toxicity are more likely to experience chronic toxicity.

Acute Disease↗
PubMed2005

Assessment of residual error for online cone-beam CT-guided treatment of prostate cancer patients.

PURPOSE: Kilovoltage cone-beam CT (CBCT) implemented on board a medical accelerator is available for image-guidance applications in our clinic. The objective of this work was to assess the magnitude and stability of the residual setup error associated with CBCT online-guided prostate cancer patient setup. Residual error pertains to the uncertainty in image registration, the limited mechanical accuracy, and the intrafraction motion during imaging and treatment. METHODS AND MATERIALS: The residual error for CBCT online-guided correction was first determined in a phantom study. After online correction, the phantom residual error was determined by comparing megavoltage portal images acquired every 90 degrees to the corresponding digitally reconstructed radiographs. In the clinical study, 8 prostate cancer patients were implanted with three radiopaque markers made of high-winding coils. After positioning the patient using the skin marks, a CBCT scan was acquired and the setup error determined by fusing the coils on the CBCT and planning CT scans. The patient setup was then corrected by moving the couch accordingly. A second CBCT scan was acquired immediately after the correction to evaluate the residual target setup error. Intrafraction motion was evaluated by tracking the coils and the bony landmarks on kilovoltage radiographs acquired every 30 s between the two CBCT scans. Corrections based on soft-tissue registration were evaluated offline by aligning the prostate contours defined on both planning CT and CBCT images. RESULTS: For ideal rigid phantoms, CBCT image-guided treatment can usually achieve setup accuracy of 1 mm or better. For the patients, after CBCT correction, the target setup error was reduced in almost all cases and was generally within +/-1.5 mm. The image guidance process took 23-35 min, dictated by the computer speed and network configuration. The contribution of the intrafraction motion to the residual setup error was small, with a standard deviation of +/-0.9 mm. The average difference between the setup corrections obtained with coil and soft-tissue registration was greatest in the superoinferior direction and was equal to -1.1 +/- 2.9 mm. CONCLUSION: On the basis of the residual setup error measurements, the margin required after online CBCT correction for the patients enrolled in this study would be approximatively 3 mm and is considered to be a lower limit owing to the small intrafraction motion observed. The discrepancy between setup corrections derived from registration using coils or soft tissue can be due in part to the lack of complete three-dimensional information with the coils or to the difficulty in prostate delineation and requires further study.

Algorithms↗
PubMed2005

MRI-based volumetric assessment of cardiac anatomy and dose reduction via active breathing control during irradiation for left-sided breast cancer.

PURPOSE: Heart dose-volume analysis using computed tomography (CT) is limited because of motion artifact and poor delineation between myocardium and ventricular space. We used dedicated cardiac magnetic resonance imaging (MRI) to quantify exclusion of left ventricular (LV) myocardium via active breathing control (ABC) during left breast irradiation and to determine the correlation between irradiated whole heart and LV volumes. METHODS AND MATERIALS: Fifteen patients who completed adjuvant irradiation for early-stage left breast cancer participated. Treatment consisted of 45 Gy to the entire breast using ABC followed by a 16-Gy electron boost to the lumpectomy cavity. Patients underwent planning CT scans in free breathing (FB) and moderate deep inspiration breath hold (mDIBH). Electrocardiogram-gated cardiac MRI was performed in the treatment position using alpha-cradle immobilization. MRI scans were acquired in late diastole (LD), mid-diastole (MD), and systole (S) for both FB and mDIBH. After image fusion with the patients' radiation therapy planning CT scan, MRI LV volumes were defined for the three examined phases of the cardiac cycle, and comparative dose-volume analysis was performed. RESULTS: Cardiac volume definition was found to differ significantly because of combinations of respiratory and intrinsic heart motion. The fraction of LV myocardium receiving 50% (22.5 Gy) of the prescribed whole breast dose (V(22.5)) was reduced by 85.3%, 91.8%, and 94.6% via ABC for LD, MD, and S, respectively. Linear regression revealed strong correlation between MRI-defined whole heart and LV V(22.5) reduction via ABC, suggesting that LV myocardium accounts for up to approximately 50% of the excluded heart volume through this technique. Significant but weaker correlations were noted between CT-defined whole heart and LV V(22.5) reductions with marked variability in the measurements of patients with larger amounts of heart in the treatment field. CONCLUSIONS: Cardiac MRI demonstrated a significant reduction in LV myocardium irradiated with the use of ABC. The correlation between reduction in V(22.5) values for LV wall and CT-defined whole heart suggests that CT is adequate for determining which patients are likely to benefit from ABC treatment, but inaccuracies inherent to standard CT dictate that more detailed imaging studies such as MRI are required for accurate cardiotoxicity assessment.

Breast Neoplasms↗
PubMed2005

A dose-escalation trial with the adaptive radiotherapy process as a delivery system in localized prostate cancer: analysis of chronic toxicity.

PURPOSE: To evaluate the validity of the chosen adaptive radiotherapy (ART) dose-volume constraints while testing the hypothesis that toxicity would not be greater at higher tumor dose levels. MATERIALS AND METHODS: In the ART dose escalation/selection trial, treatment was initiated with a generic planning target volume (PTV) formed as a 1-cm expansion of the clinical target volume (CTV). After the first week of therapy, the patient was replanned with a patient-specific PTV, constructed with CT and electronic portal images obtained in the first 4 days of treatment. A new multileaf collimator beam aperture was used. A minimum dose prescribed to the patient-specific PTV, ranging 70.2-79.2 Gy, was determined on the basis of the following rectal and bladder constraints: <5% of the rectal wall has a dose >82 Gy, <30% of the rectal wall has a dose >75.6 Gy, <50% of the bladder volume has a dose >75.6 Gy, and the maximum bladder dose is 85 Gy. A conformal four-field and/or intensity-modulated radiotherapy (IMRT) technique was used. Independent reviewers scored toxicities. The worst toxicity score seen was used as per the Common Toxicity Criteria grade scale (version 2). We divided the patients into three separate groups: 70.2-72 Gy, >72-75.6 Gy, and >75.6-79.2 Gy. Toxicities in each group were quantified and compared by the Pearson chi-squared test to validate our dose escalation/selection model. Grades 0, 1, 2, and 3 were censored as none vs. each category and none vs. any. RESULTS: We analyzed patients with follow-up greater than 1 year. The mean duration of follow-up was 29 months (range, 12-46 months). We report on 280 patients, mean age 72 years (range, 51-87 years). Only 60 patients received adjuvant hormones. Mean pretreatment prostate-specific antigen level was 9.3 ng/mL (range, 0.6-120 ng/mL). Mean Gleason score was 6 (range, 3-9). The lowest dose level was given to 49 patients, the intermediate dose to 131 patients, and 100 patients received the highest dose escalation. One hundred eighty-one patients (65%) were treated to a prostate field only and 99 patients (35%) to prostate and seminal vesicles. Chronic genitourinary and/or gastrointestinal categories were incontinence, persistent urinary retention, increased urinary frequency/urgency, urethral stricture, hematuria, diarrhea, rectal pain, bleeding, ulcer, fistula, incontinence, and proctitis. Toxicity at the high dose level was not different from toxicity at the intermediate or lower dose levels. No significant difference was observed in any of the individual toxicity categories. CONCLUSIONS: By applying the ART process--namely, developing a patient-specific PTV--to prostate cancer patients, significant dose escalation can be achieved without increases in genitourinary or gastrointestinal toxicity. Our data validate the rectal and bladder dose-volume constraints chosen for our three-dimensional conformal and IMRT prostrate radiotherapy planning.

Aged↗
PubMed2005

Cone-beam-CT guided radiation therapy: A model for on-line application.

BACKGROUND AND PURPOSE: This paper presents efficient and generalized processes for the clinical application of on-line X-ray volumetric cone-beam CT imaging (XVI) to improve the accuracy of patient set-up in radiation therapy. XVI image-guided therapy is illustrated by application to two contrasting sites, intra-cranial radiosurgery and prostate radiation therapy, with very different characteristics regarding organ motion, treatment precision, and imaging conditions. PATIENTS AND METHODS: On-line set-up errors are determined in a two-step process. First the XVI data is registered to the planning data by matching the machine-isocenter with the planning-isocenter, respectively. The machine isocenter is defined in the XVI data during the reconstruction. The planning-isocenter is defined during the planning process in the planning CT data. Set-up errors are then determined from a second registration to remove residual displacements. The accuracy of the entire procedure for on-line set-up error correction was investigated in precision radiosurgery phantom studies. RESULTS: The phantom studies showed that sub-pixel size set-up errors (down to 0.5mm) can be correctly determined and implemented in the radiosurgery environment. XVI is demonstrated to provide quality skull detail enabling precise skull based on-line alignment in radiosurgery. A 'local XVI' technique was found to give encouraging soft-tissue detail in the high-scatter pelvic environment, enabling on-line soft-tissue based set-up for prostate treatment. The two-step process for determination of set-up errors was found to be efficient and effective when implemented with a dedicated six panel interface enabling simultaneous visualization on the XVI and planning CT data sets. CONCLUSIONS: XVI has potential to significantly improve the accuracy of radiation treatments. Present image quality is highly encouraging and can enable bony and soft-tissue patient set-up error determination and correction. As with all image guided treatment techniques the development of efficient procedures to utilize on-line data are of paramount importance.

Brain Neoplasms↗
PubMed2005

Computed tomography guided management of interfractional patient variation.

Interfractional patient variation occurs regularly and considerably during the radiotherapy course. Consequently, a generic but large planning target margin has to be applied when patient treatment plan design based on a single pre-treatment computed tomography scan is used to guide multifraction radiation treatment, which creates a major limiting factor for radiotherapy improvement. Planning target margins can be significantly reduced using multiple (or 4-dimensional) image feedback management in the routine treatment process. The most effective method in multiple-image feedback management of radiotherapy is the adaptive control methodology. The adaptive radiotherapy technique aims to customize each patient's treatment plan to patient-specific variation by evaluating and characterizing the systematic and random variations through image feedback and including them in adaptive planning. Adaptive radiotherapy will become a new treatment standard, in which a predesigned adaptive treatment strategy, including the schedules of imaging and replanning, will eventually replace the predesigned treatment plan in the routine clinical practice.

Dose Fractionation, Radiation↗
PubMed2004

Online image-guided intensity-modulated radiotherapy for prostate cancer: How much improvement can we expect? A theoretical assessment of clinical benefits and potential dose escalation by improving precision and accuracy of radiation delivery.

PURPOSE: To quantify the theoretical benefit, in terms of improvement in precision and accuracy of treatment delivery and in dose increase, of using online image-guided intensity-modulated radiotherapy (IG-IMRT) performed with onboard cone-beam computed tomography (CT), in an ideal setting of no intrafraction motion/deformation, in the treatment of prostate cancer. METHODS AND MATERIALS: Twenty-two prostate cancer patients treated with conventional radiotherapy underwent multiple serial CT scans (median 18 scans per patient) during their treatment. We assumed that these data sets were equivalent to image sets obtainable by an onboard cone-beam CT. Each patient treatment was simulated with conventional IMRT and online IG-IMRT separately. The conventional IMRT plan was generated on the basis of pretreatment CT, with a clinical target volume to planning target volume (CTV-to-PTV) margin of 1 cm, and the online IG-IMRT plan was created before each treatment fraction on the basis of the CT scan of the day, without CTV-to-PTV margin. The inverse planning process was similar for both conventional IMRT and online IG-IMRT. Treatment dose for each organ of interest was quantified, including patient daily setup error and internal organ motion/deformation. We used generalized equivalent uniform dose (EUD) to compare the two approaches. The generalized EUD (percentage) of each organ of interest was scaled relative to the prescription dose at treatment isocenter for evaluation and comparison. On the basis of bladder wall and rectal wall EUD, a dose-escalation coefficient was calculated, representing the potential increment of the treatment dose achievable with online IG-IMRT as compared with conventional IMRT. RESULTS: With respect to radiosensitive tumor, the average EUD for the target (prostate plus seminal vesicles) was 96.8% for conventional IMRT and 98.9% for online IG-IMRT, with standard deviations (SDs) of 5.6% and 0.7%, respectively (p < 0.0001). The average EUDs of bladder wall and rectal wall for conventional IMRT vs. online IG-IMRT were 70.1% vs. 47.3%, and 79.4% vs. 72.2%, respectively. On average, a target dose increase of 13% (SD = 9.7%) can be achieved with online IG-IMRT based on rectal wall EUDs and 53.3% (SD = 15.3%) based on bladder wall EUDs. However, the variation (SD = 9.7%) is fairly large among patients; 27% of patients had only minimal benefit (<5% of dose increment) from online IG-IMRT, and 32% had significant benefit (>15%-41% of dose increment). CONCLUSIONS: The ideal maximum dose increment achievable with online IG-IMRT is, on average, 13% with respect to the dose-limiting organ of rectum. However, there is a large interpatient variation, ranging <5%-41%. The results can be applied to calibrate other practical online image-guided techniques for prostate cancer radiotherapy, when intratreatment organ motion/deformation and machine delivery accuracy are considered.

Humans↗
PubMed2004

Defining a radiotherapy target with positron emission tomography.

PURPOSE: F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging is now considered the most accurate clinical staging study for non-small-cell lung cancer (NSCLC) and is also important in the staging of multiple other malignancies. Gross tumor volume (GTV) definition for radiotherapy, however, is typically based entirely on computed tomographic data. We performed a series of phantom studies to determine an accurate and uniformly applicable method for defining a GTV with FDG-PET. METHODS AND MATERIALS: A model-based method was tested by a phantom study to determine a threshold, or unique cutoff of standardized uptake value based on body weight (standardized uptake value [SUV]) for FDG-PET based GTV definition. The degree to which mean target SUV, background FDG concentration, and target volume influenced that GTV definition were evaluated. A phantom was constructed consisting of a 9.0-L cylindrical tank. Glass spheres with volumes ranging from 12.2 to 291.0 cc were suspended within the tank, with a minimum separation of 4 cm between the edges of the spheres. The sphere volumes were selected based on the range of NSCLC patient tumor volumes seen in our clinic. The tank and spheres were filled with a variety of known concentrations of FDG in several experiments and then scanned using a General Electric Advance PET scanner. In the initial experiment, six spheres with identical volumes were filled with varying concentrations of FDG (mean SUV = 1.85 approximately 9.68) and suspended within a background bath of FDG at a similar concentration to that used in clinical practice (0.144 muCi/mL). The second experiment was identical to the first, but was performed at 0.144 and 0.036 muCi/mL background concentrations to determine the effect of background FDG concentration on sphere definition. In the third experiment, six spheres with volumes of 12.2 to 291.0 cc were filled with equal concentrations of FDG and suspended in a standard background FDG concentration of 0.144 muCi/mL. Sphere images in each experiment were auto-contoured (simulating a GTV) using the threshold SUV that yielded a volume matching that of the known sphere volume. A regressive function was constructed to represent the relationship between the threshold SUV and the mean target SUV. This function was then applied to define the GTV of 15 NSCLC patients. The GTV volumes were compared to those determined by a fixed image intensity threshold proposed by other investigators. RESULTS: There was a strong linear relationship between the threshold SUV and the mean target SUV. The linear regressive function derived was: threshold SUV = 0.307 x (mean target SUV) + 0.588. The background concentration and target volume indirectly affect the threshold SUV by way of their influence on the mean target SUV. We applied the linear regressive function, as well as a fixed image intensity threshold (42% of maximum intensity) to the sphere phantoms and 15 patients with NSCLC. The results indicated that a much smaller deviation occurred when the threshold SUV regressive function was utilized to estimate the phantom volume as compared to the fixed image intensity threshold. The average absolute difference between the two methods was 21% with respect to the true phantom volume. The deviation became even more pronounced when applied to true patient GTV volumes, with a mean difference between the two methods of 67%. This was largely due to a greater degree of heterogeneity in the SUV of tumors over phantoms. CONCLUSIONS: An FDG-PET-based GTV can be systematically defined using a threshold SUV according to the regressive function described above. The threshold SUV for defining the target is strongly dependent on the mean target SUV of the target, and can be uniquely determined through the proposed iteration process.

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