Biomedical subjects

John W Wong

Publications and source records attributed to John W Wong.

At least 19 recordsLinked to original sources

PubMed2006

MR imaging-guided breast localization system with medial or lateral access.

PURPOSE: To evaluate the degree of error of the authors' magnetic resonance (MR) imaging-guided needle localization system for biopsy of suspicious lesions visualized only with MR imaging, by using both prospectively recorded and retrospectively reviewed data, including MR imaging lesion coordinates as the reference standard, and to determine whether any lesion or breast characteristics affect this error. MATERIALS AND METHODS: Institutional review board approval, along with informed consent, was obtained as directed by the board. In 31 patients (age range, 34-64 years; mean age, 54.5 years), 38 wires were placed for 35 lesions by means of an MR-guided needle localization system with medial or lateral access and computer software assistance for needle placement calculation. Needle and wire placement error measurements were calculated before and after necessary placement correction, accounting for tissue shift in the z plane. The error was statistically correlated with MR imaging lesion variables, breast density, and histopathologic findings by means of univariate and multivariate linear regression analyses or two-tailed paired t test. Procedure times and the frequency of medial or lateral approaches were recorded. RESULTS: Eleven of 35 localizations (31%) were medial, and 24 of 35 (69%) were lateral. The mean total magnet time was 61.6 minutes, and the mean needle deployment time was 9 minutes (range, 4-17 minutes). Sixteen of 35 lesions (46%) were malignant (seven ductal carcinoma in situ, six invasive ductal, two invasive lobular, and one lymphoma). The mean uncorrected needle placement error was 1.3 mm (range, 0-6 mm) for the x plane, 2.4 mm (range, 0-6.5 mm) for the y plane, and 5.6 mm (range, 0-15.6 mm) for the z plane. Fourteen of 38 needles (37%) required repositioning for z-plane error. The corrected z-plane error improved to 3.2 mm (range, 0-10.0 mm). Factors that significantly increased the uncorrected error included tissue shift in the z plane (R = 0.7), small lesion size (R = -0.59), and fatty breast density (P = .029). CONCLUSION: The authors' system is accurate for performing MR-guided needle localizations for both medial and lateral approaches. Factors that increased the uncorrected needle placement error included small lesion size, fatty breast density, and tissue shift in the z plane.

Adult↗

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

The management of respiratory motion in radiation oncology report of AAPM Task Group 76.

This document is the report of a task group of the AAPM and has been prepared primarily to advise medical physicists involved in the external-beam radiation therapy of patients with thoracic, abdominal, and pelvic tumors affected by respiratory motion. This report describes the magnitude of respiratory motion, discusses radiotherapy specific problems caused by respiratory motion, explains techniques that explicitly manage respiratory motion during radiotherapy and gives recommendations in the application of these techniques for patient care, including quality assurance (QA) guidelines for these devices and their use with conformal and intensity modulated radiotherapy. The technologies covered by this report are motion-encompassing methods, respiratory gated techniques, breath-hold techniques, forced shallow-breathing methods, and respiration-synchronized techniques. The main outcome of this report is a clinical process guide for managing respiratory motion. Included in this guide is the recommendation that tumor motion should be measured (when possible) for each patient for whom respiratory motion is a concern. If target motion is greater than 5 mm, a method of respiratory motion management is available, and if the patient can tolerate the procedure, respiratory motion management technology is appropriate. Respiratory motion management is also appropriate when the procedure will increase normal tissue sparing. Respiratory motion management involves further resources, education and the development of and adherence to QA procedures.

Guidelines as Topic↗

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

Cone-beam-CT guided radiation therapy: technical implementation.

BACKGROUND AND PURPOSE: X-ray volumetric imaging system (XVI) mounted on a linear accelerator is available for image guidance applications. In preparation for clinical implementation, phantom and patient imaging studies were conducted to determine the irradiation parameters that would trade-off image quality, patient dose and scanning time. PATIENTS AND METHODS: The XVI image quality and imaging dose were benchmarked against those obtained with a helical CT scanner for a head and body phantom. The irradiation parameters were varied including the total imaging dose, number of projections, field of view, reconstruction resolution and use of a scatter rejection grid. We characterized the image quality based on relative contrast, noise, contrast to noise ratio (CNR) and point spread function (PSF). XVI scans of pelvis, head and neck and lung patients were acquired and submitted to a range of observers to identify the favorable reconstruction parameters. RESULTS: Phantom studies have demonstrated that a scatter rejection grid reduces photon scattering and improves the image uniformity. For the body phantom, the helical CT and the wide field XVI technique produce similar image quality, with surface doses of 0.025 and 0.044 Gy respectively. We have demonstrated that the local tomography technique improves the image contrast and the CNR while reducing the skin dose by 40-50% compared to the wide field technique. Clinical scans of head and neck, lung and prostate patients present good soft tissue contrast and excellent bone definition. CONCLUSIONS: With adjustment of irradiation parameters and an imaging surface dose of less than 0.05 Gy, high quality XVI images can be obtained for a phantom simulating the body thickness. XVI is currently feasible for image-guided treatments of head and neck, torso and pelvic areas using soft tissue and bony structures.

Humans↗

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↗

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.

Body Weight↗

PubMed2004

A comparative analysis of low-dose metronomic cyclophosphamide reveals absent or low-grade toxicity on tissues highly sensitive to the toxic effects of maximum tolerated dose regimens.

The survival benefits of traditional maximum tolerated dose (MTD) cytotoxic therapy have been modest for the treatment of most types of metastatic malignancy and, moreover, often come with increased acute and chronic toxicity. Recent studies have demonstrated that the frequent administration of comparatively low doses of cytotoxic agents, with no extended breaks [low-dose metronomic (LDM) chemotherapy], may not only be at least as efficient as MTD therapy but also less toxic. This coincides with an apparent selectivity for "activated" endothelial cells of the tumor vasculature. However, the impact of LDM chemotherapy on the most sensitive target cell populations normally affected by MTD therapy (i.e., bone marrow progenitors, gut mucosa, and hair follicle cells) has not been analyzed in experimental detail. Therefore, we compared effects of LDM and MTD cyclophosphamide (CTX) on bone marrow and gut mucosa. Furthermore, we studied the potential impact of LDM CTX on angiogenesis in the context of wound healing and evidence of organ toxicity. We show absent or moderate hematologic and intestinal toxicity of LDM as opposed to MTD CTX. Of note was the finding of sustained lymphopenia, which is not unexpected given the use of CTX as immunosuppressive drug. There was no negative impact on wound healing or evidence of organ toxicity. LDM offers clear safety advantages over conventional MTD chemotherapy and therefore would appear to be ideal for long-term combination therapy with targeted antiangiogenic drugs.

Animals↗

PubMed2004

Impact of breathing motion on whole breast radiotherapy: a dosimetric analysis using active breathing control.

PURPOSE: The active breathing control (ABC) apparatus was used to quantify the effect of breathing motion on whole breast radiotherapy (RT) with standard wedges and intensity-modulated RT (IMRT). METHODS AND MATERIALS: Ten patients with early-stage breast cancer underwent routine free-breathing (FB) CT simulations for whole breast RT. An ABC apparatus was used to obtain two additional CT scans with the breath held at the end of normal inhalation and normal exhalation. The FB scan was used to develop both a standard treatment plan using wedged coplanar tangents and an IMRT plan using multiple static multileaf collimator segments. To simulate breathing, each plan was copied and applied to the normal inhalation and normal exhalation CT scans. RESULTS: The medial field border (defined by a radiopaque catheter) for the normal inhalation and normal exhalation scans moved an average of 0.6 cm anteriorly and 0.3 cm posteriorly compared with the FB position, respectively. The corresponding movement of the lateral field border was an average of 0.4 cm anteriorly and 0.2 cm posteriorly compared with the FB position. For both the wedged and the IMRT techniques, the dose delivered to breast tissue, biopsy cavity, and ipsilateral lung was similar for each of the three CT scan positions. However, the internal mammary node dose varied significantly with breathing. CONCLUSIONS: The dose delivered to breast using standard wedges or step-and-shoot IMRT is relatively insensitive to the effects of breast motion during normal breathing. However, an appreciable portion of the internal mammary nodes are irradiated during normal inhalation, contributing to the uncertainty in the analysis of the efficacy of internal mammary nodal RT in breast treatment.

Breast Neoplasms↗

PubMed2004

Evaluation of a 2D diode array for IMRT quality assurance.

BACKGROUND AND PURPOSE: The QA of intensity modulated radiotherapy (IMRT) dosimetry is a laborious task. The goal of this work is to evaluate the dosimetric characteristics of a new 2D diode array (MapCheck from Sun Nuclear Corporation, Melbourne, Florida) and assess the role it can play in routine IMRT QA. MATERIAL AND METHODS: Fundamental properties of the MapCheck such as reproducibility, linearity and temperature dependence are studied for high-energy photon beams. The accuracy of the correction for difference of diode sensitivity is also assessed. The diode array is benchmarked against film and ion chambers for conventional and IMRT treatments. The MapCheck sensitivity to multileaf collimator position errors is determined. RESULTS: The diode array response is linear with dose up to 295 cGy. All diodes are calibrated to within +/-1% of each other, and mostly within +/-0.5%. The MapCheck readings are reproducible to within a maximum SD of +/-0.15%. A temperature dependence of 0.57%/ degrees C was noted and should be taken into account for absolute dosimetric measurement. Clinical performance of the MapCheck for relative and absolute dosimetry is demonstrated with seven beam (6 MV) head and neck IMRT plans, and compares well with film and ion chamber measurements. Comparison to calculated dose maps demonstrates that the planning system model underestimates the dose gradients in the penumbra region. CONCLUSIONS: The MapCheck offers the dosimetric characteristics required for performing both relative and absolute dose measurements. Its use in the clinic can simplify and reduce the IMRT QA workload.

Dose-Response Relationship, Radiation↗

PubMed2004

Percutaneous MR imaging-guided radiofrequency interstitial thermal ablation of tongue base in porcine models: implications for obstructive sleep apnea syndrome.

PURPOSE: To test the feasibility and safety of a percutaneous magnetic resonance (MR) imaging-guided technique for radiofrequency (RF) interstitial thermal ablation of the tongue base and to correlate MR appearance of induced thermal lesions with histopathologic findings in pigs in acute and chronic porcine models. MATERIALS AND METHODS: A 1-cm-tip RF electrode was inserted percutaneously into the tongue in 10 pigs with 0.2-T real-time MR guidance. The RF electrode was advanced up the midline between lingual arteries and stopped short of tongue mucosa. RF interstitial thermal ablation was performed at 90 degrees C +/- 2 and lasted 10 minutes. Postablation images were obtained with a 1.5-T MR imager. Five pigs were sacrificed immediately (acute model), while five were followed up for 1 month (chronic model) before they were sacrificed. MR-compatible fiducial coils were inserted into tongues with MR imaging guidance prior to RF ablation in the chronic group. Tongues were harvested for histopathologic analysis. Mean thermal lesion volume was compared with the Student t test on images obtained immediately, 2 weeks, and 1 month after RF ablation. Interclass correlation coefficients of lesion diameters at gross pathologic analysis and corresponding diameters with each pulse sequence were calculated. RESULTS: Successful MR imaging-guided electrode positioning was achieved in all procedures without intra- or postprocedure complications because there was high vascular conspicuity and tissue contrast. Thermal lesions appeared hypointense with hyperintense surrounding rims with all sequences in both groups. At pathologic analysis, acute lesions appeared as pale necrotic areas surrounded by hyperemic rims, while chronic lesions demonstrated progressive circumferential fibrosis and significant volume shrinkage (P <.01). Thermal lesion diameters measured at gross pathologic analysis best agreed with corresponding diameters measured on short inversion time inversion-recovery images (interclass correlation coefficient = 0.85). CONCLUSION: The results of this investigation demonstrate MR imaging-guided RF interstitial thermal ablation of the tongue base is feasible and safe and illustrate imaging and pathologic phenomena associated with creation and evolution of the induced thermal lesions.

Animals↗

PubMed2003

Three-dimensional evaluation of intra- and interfraction immobilization of lung and chest wall using active breathing control: a reproducibility study with breast cancer patients.

PURPOSE: A CT-based three-dimensional (3D) method was used to analyze the intra- and interfraction reproducibility of lung immobilization during moderate deep inspiration breath hold (mDIBH), defined as 75% of the maximal inspiration using an active breathing control (ABC) apparatus. METHODS AND MATERIALS: The ABC apparatus was used to immobilize the breathing motion with a computer-controlled valve. Immobilization of the lungs in breast cancer patients was used as a model to evaluate the reproducibility of mDIBH using the ABC apparatus. CT scans were acquired twice at mDIBH in the same session for 30 breast cancer patients. Twenty-three of them were immobilized with an alpha-cradle, of which 14 had a repeat scan at mDIBH 1-4 weeks later. Twelve of those patients received intensity-modulated radiotherapy to the left breast at mDIBH to displace the heart from the beam. The remaining patients were treated at free breathing, with either intensity-modulated irradiation to the whole breast or conformal partial breast irradiation. To remove the component of setup error, mDIBH scans were registered with respect to the vertebrae. The lungs and carina were auto-contoured to form 3D surfaces for each data set. The closest distance-to-agreement (DTA) for each point between the 3D surfaces of the corresponding CT scans was displayed on a 3D surface map. For analysis, each lung was divided along its inferior to superior extent into six regions, from the basal 10%, the next four consecutive 20% sections in height, to the last apical 10%. Likewise, the carina was divided into regions of the trachea and bifurcation. The mean and standard deviation (SD) of the DTA for each of these regions was computed. RESULTS: With the patient positioned in an alpha-cradle, the mean +/- SD intrafraction DTA was 1.5 +/- 1.4 mm for the left lung and 1.0 +/- 1.4 mm for the right lung. The corresponding values without the use of an alpha-cradle were significantly greater, with 1.9 +/- 2.1 mm and 2.2 +/- 2.2 mm for the left and right lung, respectively (p <0.005 for the SD of the left lung and p <0.0003 for the SD of the right lung). The interfraction DTA for the left and right lungs was 1.4 +/- 1.7 mm and 1.4 +/- 1.6 mm, respectively. The regional analysis demonstrated better immobilization for the upper two-thirds of the chest wall compared with that for the lung base. The DTA values obtained for the tracheal bifurcation were 0.9 +/- 0.8 mm for intrafraction and 1.4 +/- 1.0 mm for interfraction. CONCLUSION: The ABC device can be used to reduce respiratory motion at mDIBH in breast cancer patients or those patients who can perform the maneuver. This device demonstrated excellent intra- and interfraction reproducibility of chest wall and carina immobilization, especially when combined with alpha-cradle immobilization. Internal margins for suspended breathing can be extrapolated from these data for various anatomic regions within the lung and chest wall.

Breast Neoplasms↗

PubMed2003

Validation of active breathing control in patients with non-small-cell lung cancer to be treated with CHARTWEL.

PURPOSE: Active breathing control (ABC) was validated using patients with non-small-cell lung cancer (NSCLC) to be treated with continuous hyperfractionated accelerated radiotherapy weekend-less (CHARTWEL). Effects of breath hold (BH) on accuracy and normal tissue doses were evaluated. METHODS AND MATERIALS: Eleven patients were studied. Immediately after a free breathing (FB) planning scan, two ABC scans (ABC 1 and 2) were performed to assess intrafraction variation. A third ABC scan (ABC 3) was performed some weeks later to assess interfraction variation. Assisted BH was set at 75% of vital capacity and reproducibility assessed using computed tomography (CT) lung volumes. Planning target volumes (PTVs), doses to lung and spinal cord for FB and ABC 1 scans were compared. RESULTS: Results were available for 10 patients. Disease and elective nodal regions were easier to define on ABC scans making PTVs smaller. ABC lung volumes showed no significant variation over several weeks, percentage volume of whole lung receiving > or =20 Gy (V(20)) was reduced in all (median 6.4%, p = 0.005), and spinal cord dose in 80% (median 1.03 Gy, p = 0.02), of the plans. CONCLUSION: ABC allowed reproducible BH, and enabled better delineation of tumor and normal structures, as well as reduction in PTV, V(20), and spinal cord dose.

Aged↗

PubMed2003

Potential for reduced toxicity and dose escalation in the treatment of inoperable non-small-cell lung cancer: a comparison of intensity-modulated radiation therapy (IMRT), 3D conformal radiation, and elective nodal irradiation.

PURPOSE: To systematically evaluate four different techniques of radiation therapy (RT) used to treat non-small-cell lung cancer and to determine their efficacy in meeting multiple normal-tissue constraints while maximizing tumor coverage and achieving dose escalation. METHODS AND MATERIALS: Treatment planning was performed for 18 patients with Stage I to IIIB inoperable non-small-cell lung cancer using four different RT techniques to treat the primary lung tumor +/- the hilar/mediastinal lymph nodes: (1) Intensity-modulated radiation therapy (IMRT), (2) Optimized three-dimensional conformal RT (3D-CRT) using multiple beam angles, (3) Limited 3D-CRT using only 2 to 3 beams, and (4) Traditional RT using elective nodal irradiation (ENI) to treat the mediastinum. All patients underwent virtual simulation, including a CT scan and (18)fluorodeoxyglucose positron emission tomography scan, fused to the CT to create a composite tumor volume. For IMRT and 3D-CRT, the target included the primary tumor and regional nodes either > or =1.0 cm in short-axis dimension on CT or with increased uptake on PET. For ENI, the target included the primary tumor plus the ipsilateral hilum and mediastinum from the inferior head of the clavicle to at least 5.0 cm below the carina. The goal was to deliver 70 Gy to > or =99% of the planning target volume (PTV) in 35 daily fractions (46 Gy to electively treated mediastinum) while meeting multiple normal-tissue dose constraints. Heterogeneity correction was applied to all dose calculations (maximum allowable heterogeneity within PTV 30%). Pulmonary and esophageal constraints were as follows: lung V(20) < or =25%, mean lung dose < or =15 Gy, esophagus V(50) < or =25%, mean esophageal dose < or =25 Gy. At the completion of all planning, the four techniques were contrasted for their ability to achieve the set dose constraints and deliver tumoricidal RT doses. RESULTS: Requiring a minimum dose of 70 Gy within the PTV, we found that IMRT was associated with a greater degree of heterogeneity within the target and, correspondingly, higher mean doses and tumor control probabilities (TCPs), 7%-8% greater than 3D-CRT and 14%-16% greater than ENI. Comparing the treatment techniques in this manner, we found only minor differences between 3D-CRT and IMRT, but clearly greater risks of pulmonary and esophageal toxicity with ENI. The mean lung V(20) was 36% with ENI vs. 23%-25% with the three other techniques, whereas the average mean lung dose was approximately 21.5 Gy (ENI) vs. 15.5 Gy (others). Similarly, the mean esophagus V(50) was doubled with ENI, to 34% rather than 15%-18%. To account for differences in heterogeneity, we also compared the techniques giving each plan a tumor control probability equivalent to that of the optimized 3D-CRT plan delivering 70 Gy. Using this method, IMRT and 3D-CRT offered similar results in node-negative cases (mean lung and esophageal normal-tissue complication probability [NTCP] of approximately 10% and 2%-7%, respectively), but ENI was distinctly worse (mean NTCPs of 29% and 20%). In node-positive cases, however, IMRT reduced the lung V(20) and mean dose by approximately 15% and lung NTCP by 30%, compared to 3D-CRT. Compared to ENI, the reductions were 50% and >100%. Again, for node-positive cases, especially where the gross tumor volume was close to the esophagus, IMRT reduced the mean esophagus V(50) by 40% (vs. 3D-CRT) to 145% (vs. ENI). The esophageal NTCP was at least doubled converting from IMRT to 3D-CRT and tripled converting from IMRT to ENI. Finally, the total number of fractions for each plan was increased or decreased until all outlined normal-tissue constraints were reached/satisfied. While meeting all constraints, IMRT or 3D-CRT increased the deliverable dose in node-negative patients by >200% over ENI. In node-positive patients, IMRT increased the deliverable dose 25%-30% over 3D-CRT and 130%-140% over ENI. The use of 3D-CRT without IMRT increased the deliverable RT dose >80% over ENI. Using a limited number of 3D-CRT beams decreased the lung V(20), mean dose, and NTCP in node-positive patients. CONCLUSION: The use of 3D-CRT, particul mean dose, and NTCP in node-positive patients. The use of 3D-CRT, particularly with only 3 to 4 beam angles, has the ability to reduce normal-tissue toxicity, but has limited potential for dose escalation beyond the current standard in node-positive patients. IMRT is of limited additional value (compared to 3D-CRT) in node-negative cases, but is beneficial in node-positive cases and in cases with target volumes close to the esophagus. When meeting all normal-tissue constraints in node-positive patients, IMRT can deliver RT doses 25%-30% greater than 3D-CRT and 130%-140% greater than ENI. Whereas the possibility of dose escalation is severely limited with ENI, the potential for pulmonary and esophageal toxicity is clearly increased.

Carcinoma, Non-Small-Cell Lung↗

PubMed2003

Initial clinical experience with moderate deep-inspiration breath hold using an active breathing control device in the treatment of patients with left-sided breast cancer using external beam radiation therapy.

INTRODUCTION: We present our initial clinical experience using moderate deep-inspiration breath hold (mDIBH) with an active breathing control (ABC) device to reduce heart dose in the treatment of patients with early-stage, left-sided breast cancer using external beam radiation therapy (EBRT) limited to the whole breast. METHODS AND MATERIALS: Between February and August 2002, 5 patients with Stages I/II left-sided breast cancer received EBRT limited to the whole breast using an ABC device. After standard virtual simulation, patients with >2% of the heart receiving >30 Gy in free breathing were selected. All patients underwent a training session with the ABC apparatus to determine their ability to comfortably maintain mDIBH at 75% of the maximum inspiration capacity. Three patients received 45 Gy to the whole breast in 25 fractions, and 2 patients received 50.4 Gy in 28 fractions. For each of the medial and lateral tangential beams, radiation was delivered during 2 or 3 breath hold durations that ranged from 18 to 26 s. "Step-and-shoot" intensity modulation was employed to achieve uniform dose distribution. Open beam segments were purposely delivered over 2 breath hold sessions and captured on electronic portal images to allow intra- and interfraction setup error analysis. All electronic portal images of the tangential beams were analyzed off-line using an in-house treatment verification tool to assess the anteroposterior, craniocaudal, and rotational uncertainties. Corrections were applied if necessary. RESULTS: A comparison of treatment plans performed on breath-hold and free-breathing CTs showed that ABC treatments achieved a mean absolute reduction of 3.6% in heart volume receiving 30 Gy (heart V(30)) and 1.5% in the heart normal tissue complication probability. A total of 134 ABC treatment sessions were performed in the 5 patients. The average number of breath holds required per beam direction was 2.5 (4-6 per treatment) with a median duration of 22 s per breath hold (range: 10-26 s). Patients tolerated mDIBH well. The median treatment time was 18.2 min (range: 13-32 min), which was progressively shortened with increasing experience. A total of 509 portal images were analyzed. Combining measurements for all patients, the interfraction setup errors (1 SD) in the lateral and craniocaudal directions and in rotation were 2.4 mm, 3.2 mm, and 1 degrees, respectively, for the medial beam and 2.3 mm, 3.1 mm, and 1 degrees, respectively, for the lateral beam. For all patients, the intrafraction setup errors were about 1 mm and always less than 2 mm (1 SD). CONCLUSION: Reduction in heart V(30) can be achieved in patients with left-sided breast cancer using mDIBH assisted with an ABC device. With increasing experience, ABC treatments were streamlined and could be performed within a 15-min treatment slot. Our results suggest that mDIBH using an ABC device may provide one of the most promising methods of improving the efficacy of EBRT in patients with left-sided breast cancer, particularly when wide tangential beams are employed. Breast cancer; Breath hold; Radiation therapy; Intensity modulated radiation therapy

Adult↗

PubMed2003

Significant reductions in heart and lung doses using deep inspiration breath hold with active breathing control and intensity-modulated radiation therapy for patients treated with locoregional breast irradiation.

PURPOSE: To evaluate the heart and lung sparing effects of moderate deep inspiration breath hold (mDIBH) achieved using an active breathing control (ABC) device, compared with free breathing (FB) during treatment with deep tangents fields (DT) for locoregional (LR) irradiation of breast cancer patients, including the internal mammary (IM) nodes (IMNs). To compare the DT-mDIBH technique to other standard techniques and to evaluate the dosimetric effect of intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: Fifteen patients (9 left-sided and 6 right-sided lesions) with Stages 0-III breast cancer underwent standard FB and ABC computed tomographic (CT) scans in the treatment position. A dosimetric planning study was performed. In FB, the 9 left-sided patients were planned with a 5-field technique where electron fields covering the IM region were matched to shallow tangents using wedges (South West Oncology Group [SWOG] protocol S9927 technique A). This method was compared with a 3-field DT technique covering the breast and the IMNs (SWOG S9927 technique B). Compensation with IMRT was then compared with wedges for each technique. For the 15 total patients, dosimetric planning using DT with IMRT was then reoptimized on the mDIBH CT data set for comparison. Dose-volume histograms for the clinical target volume (CTV) (including the IMNs), planning target volume (PTV), ipsilateral and contralateral breast, and organs at risk (OAR) were analyzed. In addition, normal tissue complication probabilities (NTCP) for lung and heart, mean lung doses, and the number of monitor units (MUs) for a 1.8 Gy fraction were compared. RESULTS: For the 9 left-sided patients, the mean percentage of heart receiving more than 30 Gy (heart V30) was lower with the 5-field wedged technique than with the DT wedged technique (6.8% and 19.1%, respectively, p < 0.004). For the DT technique, the replacement of wedges with IMRT slightly diminished the mean heart V30 to 16.3% (p < 0.51). The introduction of mDIBH to the DT-IMRT technique reduced the heart V30 by 81% to a mean of 3.1% (p < 0.0004). Compared with 5-field IMRT, DT-IMRT with mDIBH reduced the heart V30 for 6 of the 9 patients, entirely avoiding heart irradiation in 2 of these 6 patients. For DT-IMRT, mDIBH reduced the mean lung dose and NTCP to levels obtained with the 5-field IMRT technique. For the 15 patients planned with DT-IMRT in FB, the use of mDIBH reduced the mean percentage of both lungs receiving more than 20 Gy from 20.4% to 15.2% (p < 0.00007). With DT-IMRT, more than 5% of the contralateral breast received more than 10 Gy for 6 of the 9 left-sided patients in FB, 3 of those 9 patients in mDIBH, and only 1 of those 9 patients planned with 5 fields. The mean % of the PTV receiving more than 55 Gy (110% of the prescribed dose) was 36.4% for 5-field wedges, 33.4% for 5-field IMRT, 28.7% for DT-wedges, 12.5% for DT-IMRT, and 18.4% for DT-IMRT mDIBH. The CTV remained covered by the 95% isodose in all the DT plans but one (99.1% of the volume covered). DT-wedges required more MUs than DT-IMRT (mean of 645 and 416, respectively, p < 0.00004). CONCLUSION: mDIBH significantly reduces heart and lung doses when DT are used for LR breast irradiation including the IMNs. Compared with shallow tangents matched with electrons, DT with mDIBH reduces the heart dose (in most patients) and results in comparable lung toxicity parameters, but may increase the dose to the contralateral breast. IMRT improves dose homogeneity, slightly reduces the dose to the heart, and diminishes the number of MUs required.

Breast Neoplasms↗

PubMed2002

Flat-panel cone-beam computed tomography for image-guided radiation therapy.

PURPOSE: Geometric uncertainties in the process of radiation planning and delivery constrain dose escalation and induce normal tissue complications. An imaging system has been developed to generate high-resolution, soft-tissue images of the patient at the time of treatment for the purpose of guiding therapy and reducing such uncertainties. The performance of the imaging system is evaluated and the application to image-guided radiation therapy is discussed. METHODS AND MATERIALS: A kilovoltage imaging system capable of radiography, fluoroscopy, and cone-beam computed tomography (CT) has been integrated with a medical linear accelerator. Kilovoltage X-rays are generated by a conventional X-ray tube mounted on a retractable arm at 90 degrees to the treatment source. A 41 x 41 cm(2) flat-panel X-ray detector is mounted opposite the kV tube. The entire imaging system operates under computer control, with a single application providing calibration, image acquisition, processing, and cone-beam CT reconstruction. Cone-beam CT imaging involves acquiring multiple kV radiographs as the gantry rotates through 360 degrees of rotation. A filtered back-projection algorithm is employed to reconstruct the volumetric images. Geometric nonidealities in the rotation of the gantry system are measured and corrected during reconstruction. Qualitative evaluation of imaging performance is performed using an anthropomorphic head phantom and a coronal contrast phantom. The influence of geometric nonidealities is examined. RESULTS: Images of the head phantom were acquired and illustrate the submillimeter spatial resolution that is achieved with the cone-beam approach. High-resolution sagittal and coronal views demonstrate nearly isotropic spatial resolution. Flex corrections on the order of 0.2 cm were required to compensate gravity-induced flex in the support arms of the source and detector, as well as slight axial movements of the entire gantry structure. Images reconstructed without flex correction suffered from loss of detail, misregistration, and streak artifacts. Reconstructions of the contrast phantom demonstrate the soft-tissue imaging capability of the system. A contrast of 47 Hounsfield units was easily detected in a 0.1-cm-thick reconstruction for an imaging exposure of 1.2 R (in-air, in absence of phantom). The comparison with a conventional CT scan of the phantom further demonstrates the spatial resolution advantages of the cone-beam CT approach. CONCLUSIONS: A kV cone-beam CT imaging system based on a large-area, flat-panel detector has been successfully adapted to a medical linear accelerator. The system is capable of producing images of soft tissue with excellent spatial resolution at acceptable imaging doses. Integration of this technology with the medical accelerator will result in an ideal platform for high-precision, image-guided radiation therapy.

Algorithms↗

PubMed2002

CJ-15,696 and its analogs, new furopyridine antibiotics from the fungus Cladobotryum varium: fermentation, isolation, structural elucidation, biotransformation and antibacterial activities.

CJ-15,696 and 7 novel furopyridine antibiotics were isolated from the fungus Cladobotryum varium CL12284. Their structures were determined by X-ray crystallography and spectral analysis. Three biotransformed analogs were also prepared from CJ-15,696. CJ-15,696 showed moderate activity against various Gram-positive bacteria including some drug resistant strains such as methicillin resistant Staphylococcus aureus (MRSA).

Anti-Bacterial Agents↗