Inactivation of DNA-PK by knockdown DNA-PKcs or NU7441 impairs non-homologous end-joining of radiation-induced double strand break repair.

The DNA-dependent protein kinase (DNA-PK) complex plays a pivotal role in non-homologous end-joining (NHEJ) repair. We investigated the mechanism of NU7441, a highly selective DNA-PK inhibitor, in NHEJ-competent mouse embryonic fibroblast (MEF) cells and NHEJ-deficient cells and explored the feasibility of its application in radiosensitizing nasopharyngeal carcinoma (NPC) cells. We generated wild-type and DNA-PKcs-/- MEF cells. Clonogenic survival assays, flow cytometry, and immunoblotting were performed to study the effect of NU7441 on survival, cell cycle, and DNA repair. NU7441 profoundly radiosensitized wild-type MEF cells and SUNE-1 cells, but not DNA-PKcs-/- MEF cells. NU7441 significantly suppressed radiation-induced DSB repair post-irradiation through unrepaired and lethal DNA damage, the cell cycle arrest. The effect was associated with the activation of cell cycle checkpoints. The present study revealed a mechanism by which inhibition of DNA-PK sensitizes cells to irradiation suggesting that radiotherapy in combination with DNA-PK inhibitor is a promising paradigm for the management of NPC which merits further investigation.

Empowering Intensity Modulated Proton Therapy Through Physics and Technology: An Overview.

Considering the clinical potential of protons attributable to their physical characteristics, interest in proton therapy has increased greatly in this century, as has the number of proton therapy installations. Until recently, passively scattered proton therapy was used almost entirely. Notably, the overall clinical results to date have not shown a convincing benefit of protons over photons. A rapid transition is now occurring with the implementation of the most advanced form of proton therapy, intensity modulated proton therapy (IMPT). IMPT is superior to passively scattered proton therapy and intensity modulated radiation therapy (IMRT) dosimetrically. However, numerous limitations exist in the present IMPT methods. In particular, compared with IMRT, IMPT is highly vulnerable to various uncertainties. In this overview we identify three major areas of current limitations of IMPT: treatment planning, treatment delivery, and motion management, and discuss current and future efforts for improvement. For treatment planning, we need to reduce uncertainties in proton range and in computed dose distributions, improve robust planning and optimization, enhance adaptive treatment planning and delivery, and consider how to exploit the variability in the relative biological effectiveness of protons for clinical benefit. The quality of proton therapy also depends on the characteristics of the IMPT delivery systems and image guidance. Efforts are needed to optimize the beamlet spot size for both improved dose conformality and faster delivery. For the latter, faster energy switching time and increased dose rate are also needed. Real-time in-room volumetric imaging for guiding IMPT is in its early stages with cone beam computed tomography (CT) and CT-on-rails, and continued improvements are anticipated. In addition, imaging of the proton beams themselves, using, for instance, prompt γ emissions, is being developed to determine the proton range and to reduce range uncertainty. With the realization of the advances described above, we posit that IMPT, thus empowered, will lead to substantially improved clinical results.

Inhibiting DNA-PKcs in a non-homologous end-joining pathway in response to DNA double-strand breaks.

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a distinct factor in the non-homologous end-joining (NHEJ) pathway involved in DNA double-strand break (DSB) repair. We examined the crosstalk between key proteins in the DSB NHEJ repair pathway and cell cycle regulation and found that mouse embryonic fibroblast (MEF) cells deficient in DNA-PKcs or Ku70 were more vulnerable to ionizing radiation (IR) compared with wild-type cells and that DSB repair was delayed. γH2AX was associated with phospho-Ataxia-telangiectasia mutated kinase (Ser1987) and phospho-checkpoint effector kinase 1 (Ser345) foci for the arrest of cell cycle through the G2/M phase. Inhibition of DNA-PKcs prolonged IR-induced G2/M phase arrest because of sequential activation of cell cycle checkpoints. DSBs were introduced, and cell cycle checkpoints were recruited after exposure to IR in nasopharyngeal carcinoma SUNE-1 cells. NU7441 radiosensitized MEF cells and SUNE-1 cells by interfering with DSB repair. Together, these results reveal a mechanism in which coupling of DSB repair with the cell cycle radiosensitizes NHEJ repair-deficient cells, justifying further development of DNA-PK inhibitors in cancer therapy.

Fluorine-18-labeled fluoromisonidazole positron emission and computed tomography-guided intensity-modulated radiotherapy for head and neck cancer: a feasibility study.

PURPOSE: Hypoxia renders tumor cells radioresistant, limiting locoregional control from radiotherapy (RT). Intensity-modulated RT (IMRT) allows for targeting of the gross tumor volume (GTV) and can potentially deliver a greater dose to hypoxic subvolumes (GTV(h)) while sparing normal tissues. A Monte Carlo model has shown that boosting the GTV(h) increases the tumor control probability. This study examined the feasibility of fluorine-18-labeled fluoromisonidazole positron emission tomography/computed tomography ((18)F-FMISO PET/CT)-guided IMRT with the goal of maximally escalating the dose to radioresistant hypoxic zones in a cohort of head and neck cancer (HNC) patients. METHODS AND MATERIALS: (18)F-FMISO was administered intravenously for PET imaging. The CT simulation, fluorodeoxyglucose PET/CT, and (18)F-FMISO PET/CT scans were co-registered using the same immobilization methods. The tumor boundaries were defined by clinical examination and available imaging studies, including fluorodeoxyglucose PET/CT. Regions of elevated (18)F-FMISO uptake within the fluorodeoxyglucose PET/CT GTV were targeted for an IMRT boost. Additional targets and/or normal structures were contoured or transferred to treatment planning to generate (18)F-FMISO PET/CT-guided IMRT plans. RESULTS: The heterogeneous distribution of (18)F-FMISO within the GTV demonstrated variable levels of hypoxia within the tumor. Plans directed at performing (18)F-FMISO PET/CT-guided IMRT for 10 HNC patients achieved 84 Gy to the GTV(h) and 70 Gy to the GTV, without exceeding the normal tissue tolerance. We also attempted to deliver 105 Gy to the GTV(h) for 2 patients and were successful in 1, with normal tissue sparing. CONCLUSION: It was feasible to dose escalate the GTV(h) to 84 Gy in all 10 patients and in 1 patient to 105 Gy without exceeding the normal tissue tolerance. This information has provided important data for subsequent hypoxia-guided IMRT trials with the goal of further improving locoregional control in HNC patients.

Reproducibility of intratumor distribution of (18)F-fluoromisonidazole in head and neck cancer.

PURPOSE: Hypoxia is one of the main causes of the failure to achieve local control using radiotherapy. This is due to the increased radioresistance of hypoxic cells. (18)F-fluoromisonidazole ((18)F-FMISO) positron emission tomography (PET) is a noninvasive imaging technique that can assist in the identification of intratumor regions of hypoxia. The aim of this study was to evaluate the reproducibility of (18)F-FMISO intratumor distribution using two pretreatment PET scans. METHODS AND MATERIALS: We enrolled 20 head and neck cancer patients in this study. Of these, 6 were excluded from the analysis for technical reasons. All patients underwent an (18)F-fluorodeoxyglucose study, followed by two (18)F-FMISO studies 3 days apart. The hypoxic volumes were delineated according to a tumor/blood ratio >or=1.2. The (18)F-FMISO tracer distributions from the two (18)F-FMISO studies were co-registered on a voxel-by-voxel basis using the computed tomography images from the PET/computed tomography examinations. A correlation between the (18)F-FMISO intensities of the corresponding spatial voxels was derived. RESULTS: A voxel-by-voxel analysis of the (18)F-FMISO distributions in the entire tumor volume showed a strong correlation in 71% of the patients. Restraining the correlation to putatively hypoxic zones reduced the number of patients exhibiting a strong correlation to 46%. CONCLUSION: Variability in spatial uptake can occur between repeat (18)F-FMISO PET scans in patients with head and neck cancer. Blood data for one patient was not available. Of 13 patients, 6 had well-correlated intratumor distributions of (18)F-FMISO-suggestive of chronic hypoxia. More work is required to identify the underlying causes of changes in intratumor distribution before single-time-point (18)F-FMISO PET images can be used as the basis of hypoxia-targeting intensity-modulated radiotherapy.

Adenovirus-mediated expression of a dominant negative Ku70 fragment radiosensitizes human tumor cells under aerobic and hypoxic conditions.

Ku70 is one component of a protein complex, the Ku70/Ku80 heterodimer, which binds to DNA double-strand breaks and activates DNA-dependent protein kinase (DNA-PK), leading to DNA damage repair. Our previous work has confirmed that Ku70 is important for DNA damage repair in that Ku70 deficiency compromises the ability of cells to repair DNA double-strand breaks, increases the radiosensitivity of cells, and enhances radiation-induced apoptosis. Because of the radioresistance of some human cancers, particularly glioblastoma, we examined the use of a radio-gene therapy paradigm to sensitize cells to ionizing radiation. Based on the analysis of the structure-function of Ku70 and the crystal structure of Ku70/Ku80 heterodimer, we designed and identified a candidate dominant negative fragment involving an NH(2)-terminal deletion, and designated it as DNKu70. We generated this mutant construct, stably overexpressed it in Rat-1 cells, and showed that it has a dominant negative effect (i.e., DNKu70 overexpression results in decreased Ku-DNA end-binding activity, and increases radiosensitivity). We then constructed and generated recombinant replication-defective adenovirus, with DNKu70 controlled by the cytomegalovirus promoter, and infected human glioma U-87 MG cells and human colorectal tumor HCT-8 cells. We show that the infected cells significantly express DNKu70 and are greatly radiosensitized under both aerobic and hypoxic conditions. The functional ramification of DNKu70 was further shown in vivo: expression of DNKu70 inhibits radiation-induced DNA-PK catalytic subunit autophosphorylation and prolongs the persistence of gamma-H2AX foci. If radiation-resistant tumor cells could be sensitized by down-regulating the cellular level/activity of Ku/DNA-PK, this approach could be evaluated as an adjuvant to radiation therapy.

Integrating respiratory gating into a megavoltage cone-beam CT system.

We have previously described a low-dose megavoltage cone beam computed tomography (MV CBCT) system capable of producing projection image using one beam pulse. In this study, we report on its integration with respiratory gating for gated radiotherapy. The respiratory gating system tracks a reflective marker on the patient's abdomen midway between the xiphoid and umbilicus, and disables radiation delivery when the marker position is outside predefined thresholds. We investigate two strategies for acquiring gated scans. In the continuous rotation-gated acquisition, the linear accelerator (LINAC) is set to the fixed x-ray mode and the gantry makes a 5 min, 360 degree continuous rotation, during which the gating system turns the radiation beam on and off, resulting in projection images with an uneven distribution of projection angles (e.g., in 70 arcs each covering 2 degrees). In the gated rotation-continuous acquisition, the LINAC is set to the dynamic arc mode, which suspends the gantry rotation when the gating system inhibits the beam, leading to a slightly longer (6-7 min) scan time, but yielding projection images with more evenly distributed projection angles (e.g., approximately 0.8 degrees between two consecutive projection angles). We have tested both data acquisition schemes on stationary (a contrast detail and a thoracic) phantoms and protocol lung patients. For stationary phantoms, a separate motion phantom not visible in the images is used to trigger the RPM system. Frame rate is adjusted so that approximately 450 images (13 MU) are acquired for each scan and three-dimensional tomographic images reconstructed using a Feldkamp filtered backprojection algorithm. The gated rotation-continuous acquisition yield reconstructions free of breathing artifacts. The tumor in parenchymal lung and normal tissues are easily discernible and the boundary between the diaphragm and the lung sharply defined. Contrast-to-noise ratio (CNR) is not degraded relative to nongated scans of stationary phantoms. The continuous rotation-gated acquisition scan also yields tomographic images with discernible anatomic features; however, streak artifacts are observed and CNR is reduced by approximately a factor of 4. In conclusion, we have successfully developed a gated MV CBCT system to verify the patient positioning for gated radiotherapy.

Reduction of organ motion in lung tumors with respiratory gating.

We evaluated the ability of a commercial respiratory gating system to assure the reproducibility of internal anatomy in respiration synchronized CT (RS-CT) scans. This passive system uses an infrared sensitive camera to track the motion of reflective markers mounted on the abdomen. Eighteen patients, nine with lung tumors and nine with liver tumors, were selected for evaluation of the Varian Real-Time Position Monitor respiratory gating system. Liver tumors were chosen as surrogate for lower lobe tumors. Each patient underwent at least two identical RS-CT scans, at end-inspiration (EI) or end-expiration (EE), to assess intra-fraction reproducibility. Twelve patients also underwent a free breathing scan and an opposed-respiration phase synchronized scan (EI if the two first were an EE and vice versa). On each CT, a physician contoured the liver, the kidneys, the spleen, and the diaphragms for the liver patients; and similarly, the lungs, the gross tumor volume (GTV), the trachea, the heart and the diaphragms for the lung patients. After registering the different CT images using bony anatomy, the changes of each structure between the respective data sets were quantified in terms of its volume, the displacement of its center of mass (COM), and an "index" coefficient of reproducibility. An analysis of the CT scans obtained at EI and EE phases yielded an average superior-inferior (SI) difference of the diaphragm position of 14.4 mm (range: 45.9-0.9). A similar analysis of CT scans acquired at the same breathing phase yielded 0.7 mm (range: 3.1-0, p=0.0001). Similar conclusions were derived in analysis of COM positions of the following structures: lungs, heart, lung's GTV, liver, spleen and kidneys. Evaluation of volume changes for lungs, liver, and spleen confirmed reproducibility of RS-CT while the "index" coefficient confirmed reproducibility of RS-CT of all organs. A commercial gating system using external markers for RS-CT significantly improves the positional reproducibility of thoracic and upper abdominal structures. This reproducible decrease in organ motion will allow a reduction of the margin of expansion facilitating increase in target dose beyond that allowed by conventional radiation treatments.

Intensity-modulated radiotherapy as the boost or salvage treatment of nasopharyngeal carcinoma: the appropriate parameters in the inverse planning and the effect of patient's anatomic factors on the planning results.

The current study demonstrates that the large increase in normal tissue penalty often degrades target dose uniformity without a concomitant large improvement in normal tissue dose, especially in anatomically unfavorable patients. The excessively large normal tissue penalties do not improve treatment plans for patients having unfavorable geometry.

Evaluation of rapid dose map acquisition of a scanning liquid-filled ionization chamber electronic portal imaging device.

PURPOSE: We evaluated the performance of a new dosimetry module in the LC250 scanning liquid-filled ionization chamber (SLIC) electronic portal imaging device (EPID) for intensity-modulated radiotherapy (IMRT) verification. This module permits one to convert EPID readings to two-dimensional (2D) maps of IMRT dose rate in real time, and to integrate them over time to produce a profile of accumulated dose for treatment verification. METHODS AND MATERIALS: The EPID was calibrated using an iterative procedure, from which a lookup table for dose integration was generated and transferred to the image-acquisition hardware. To evaluate the EPID's integration capability, we investigated the linearity of imaging time (vs. monitor unit [MU]) and integrated dose (vs. planned dose) for static and IMRT fields, in both standard ( approximately 2.7 s/image) and fast ( approximately 1 s/image) synchronous acquisition modes (S- and F-modes). We also compared the EPID-measured profiles with that measured using film and ionization chamber, or calculated from the treatment planning system. For the EPID's patient dose verification capability, we compared the integrated central-axis (CAX) dose with the planned dose for 25 prostate IMRT fields. We also compared the measured relative profiles with the planned ones using a linear regression model, which returns an index sigma (root mean squared error) for the goodness of fit. We identified errors that are either associated with the timing of the EPID-start delay and end truncation, or with the integration process-detector memory effects (decrease in detector's sensitivity with time during the fast continuous acquisition) and beam hold-off effects (the withholding of linac beam pulses when multileaf collimator leaves are not in the correct positions). The CAX doses of static fields were corrected using the ratio of the irradiation time to the imaging time. A linear decay model was proposed to correct the detector memory effect. To investigate the beam hold-off effect, we verified the relative profiles of a five-field prostate IMRT plan for five different MU settings, and correlated the goodness of fit with the percent of beam hold-off. RESULTS: The imaging time is linearly proportional to the given MU with a slope of 0.250 MU/s (ideal slope is 0.250 MU/s) and a R(2) = 1.0. Although the R(2) of the linearity for the measured vs. planned dose is 1.0 for both modes, only the slopes for the S-mode are within 3% of unity. The slopes for the F-mode deviate from unity due to detector memory effects, and are accurately corrected using the linear decay model. The EPID measured profiles agree well (within 2.0%) with the planned dose and profiles for both modes. For the CAX dose of the 25 IMRT fields, the S-mode is within 2% of the planned dose, whereas the F-mode is off significantly (>3%) if not corrected for detector memory effects. For the relative profile verification, lower MU always produces higher sigma for the same mode. The F-mode is more accurate than the S-mode for the same MU; however, the improvement is not proportional to the difference in imaging speed. Analysis of the correlation of the goodness of fit with the percent of beam hold-off indicates that the accuracy of profile verification for the F-mode is predominantly determined by the beam hold-off effect for lower MU. CONCLUSION: The S-mode of LC250 combined with a large MU can be used for the pretreatment verification of IMRT beam delivery with a significant reduction of processing time and computer resources in comparison to off-line processing. Real-time verification during treatment requires the F-mode. Although the detector memory effects encountered in the F-mode can be compensated using the proposed linear decay model, sufficient accuracy for real-time verification requires a resolution of the beam hold-off problem.

Optimization of conformal thoracic radiotherapy using cone-beam CT imaging for treatment verification.

PURPOSE: Megavoltage cone-beam computed tomography (MVCBCT) has been proposed for treatment verification in conformal radiotherapy. However, the doses required for such imaging may compromise the quality of the delivered dose distribution. The present paper explores the effect of cone-beam imaging on dose homogeneity and critical organ dose and the use of our new tool, adapted intensity-modulated radiation therapy (AIMRT). METHODS AND MATERIALS: Three types of treatment plans were devised (3D-CRT [three-dimensional conformal radiotherapy], IMRT [intensity-modulated radiotherapy], and AIMRT) based on 4 patients with thoracic malignancies. MVCBCT fields were then integrated into the plans. The MVCBCT technique used 21 imaging portals at 10 degrees intervals. The MVCBCT apertures were shaped to conform to the planning target volume with a 6-mm margin. In a second set of plans, the field size was expanded by a further 2 cm. The unoptimized MVCBCT dose distribution was incorporated into the IMRT plan using AIMRT. RESULTS: Normal-tissue complication probability with MVCBCT is acceptable for all plans at the 66.6 Gy level, but exceeds tolerance for both 3D-CRT alone and 3D-CRT with MVCBCT at higher doses. In contrast, the use of AIMRT planning with MVCBCT allowed safe dose escalation to 85 Gy. Expanding the MVCBCT aperture provided better anatomic visibility with an acceptable lung dose. The results using IMRT with MVCBCT fell between the values measured for 3D-CRT and AIMRT with MVCBCT. CONCLUSION: The present study is the first to demonstrate that MVCBCT can be incorporated into 3D-CRT and IMRT planning with minimal effect on planning target volume homogeneity and dose to critical structures. This paves the way for highly conformal radiotherapy at greater doses delivered with increased confidence and safety.

Development of a semi-automatic alignment tool for accelerated localization of the prostate.

PURPOSE: Delivering high dose to prostate with external beam radiation has been shown to improve local tumor control. However, it has to be carefully performed to avoid partial target miss and delivering excessive dose to surrounding normal tissues. One way to achieve safe dose escalation is to precisely localize prostate immediately before daily treatment. Therefore, the radiation can be accurately delivered to the target. Once the prostate position is determined with high confidence, planning target volume (PTV) safety margin might be reduced for further reduction of rectal toxicity. A rapid computed tomography (CT)-based online prostate localization method is presented for this purpose. METHODS AND MATERIALS: Immediately before each treatment session, the patient is immobilized and undergoes a CT scan in the treatment position using a CT scanner situated in the treatment room. At the CT console, posterior, anterior, left, and right extents of the prostate are manually identified on each axial slice. The translational prostate displacements relative to the planned position are estimated by simultaneously fitting these identified extents from this CT scan to a template created from the finely sliced planning CT scan. A total of 106 serial CT scans from 8 prostate cancer patients were performed immediately before treatments and used to retrospectively evaluate the precision of this daily prostate targeting method. The three-dimensional displacement of the prostate with respect to its planned position was estimated. RESULTS: Five axial slices from each treatment CT scan were sufficient to produce a reliable correction when compared with prostate center of gravity (CoG) displacements calculated from physician-drawn contours. The differences (mean +/- SD) between these two correction schemes in the right-left (R/L), posterior-anterior (P/A), and superior-inferior (S/I) directions are 0.0 +/- 0.4 mm, 0.0 +/- 0.7 mm, and -0.4 +/- 1.9 mm, respectively. With daily CT extent-fitting correction, 97% of the scans showed that the entire posterior prostate gland was covered by PTV given a margin of 6 mm at the rectum-prostate interface and 10 mm elsewhere. In comparison, only 74% and 65% could be achieved by the corrections based on daily and weekly bony matching on portal images, respectively. CONCLUSIONS: Results show that daily CT extent fitting provides a precise correction of prostate position in terms of CoG. Identifying prostate extents on five axial CT slices at the CT console is less time-consuming compared with daily contouring of the prostate on many slices. Taking advantage of the prostate curvature in the longitudinal direction, this method also eliminates the necessity of identifying prostate base and apex. Therefore, it is clinically feasible and should provide an accelerated localization of the prostate immediately before daily treatment.

Evaluation of concave dose distributions created using an inverse planning system.

PURPOSE: To evaluate and develop optimum inverse treatment planning strategies for the treatment of concave targets adjacent to normal tissue structures. METHODS AND MATERIALS: Optimized dose distributions were designed using an idealized geometry consisting of a cylindrical phantom with a concave kidney-shaped target (PTV) and cylindrical normal tissues (NT) placed 5-13 mm from the target. Targets with radii of curvature from 1 to 2.75 cm were paired with normal tissues with radii between 0.5 and 2.25 cm. The target was constrained to a prescription dose of 100% and minimum and maximum doses of 95% and 105% with relative penalties of 25. Maximum dose constraint parameters for the NT varied from 10% to 70% with penalties from 10 to 1000. Plans were evaluated using the PTV uniformity index (PTV D(max)/PTV D(95)) and maximum normal tissue doses (NT D(max)/PTV D(95)). RESULTS: In nearly all situations, the achievable PTV uniformity index and the maximum NT dose exceeded the corresponding constraints. This was particularly true for small PTV-NT separations (5-8 mm) or strict NT dose constraints (10%-30%), where the achievable doses differed from the requested by 30% or more. The same constraint parameters applied to different PTV-NT separations yielded different dose distributions. For most geometries, a range of constraints could be identified that would lead to acceptable plans. The optimization results were fairly independent of beam energy and radius of curvature, but improved as the number of beams increased, particularly for small PTV-NT separations or strict dose constraints. CONCLUSION: Optimized dose distributions are strongly affected by both the constraint parameters and target-normal tissue geometry. Standard site-specific constraint templates can serve as a starting point for optimization, but the final constraints must be determined iteratively for individual patients. A strategy whereby NT constraints and penalties are modified until the highest acceptable PTV uniformity index is achieved is discussed. This strategy can be used, in simple patient geometries, to ensure the lowest possible normal tissue dose. Strategies for setting the optimum dose constraints and penalties may vary for different optimization algorithms and objective functions. Increasing the number of beams can significantly improve normal tissue dose and target uniformity in situations where the PTV-NT separation is small or the normal tissue dose limits are severe. Setting unrealistically severe constraints in such situations often results in dose distributions that are inferior to plans achieved with more lenient constraints.

Effect of respiratory gating on quantifying PET images of lung cancer.

UNLABELLED: We have developed a new technique to gate lung 18F-FDG PET images in synchronization with the respiratory motion to reduce smearing due to breathing and improve quantitation of 18F-FDG uptake in lung lesions. METHODS: A camera-based respiratory gating system, the real-time position management (RPM), is used to monitor the respiratory cycle. The RPM provides a trigger to the PET scanner to initiate the gating cycle. Each respiratory cycle is divided into discrete bins triggered at a defined amplitude or phase within the patient's breathing motion, into which PET data are acquired. The acquired data within the time bins correspond to different lesion positions within the breathing cycle. The study includes 5 patients with lung cancer. RESULTS: Measurements of the lesions' volumes in the gated mode showed a reduction of up to 34% compared with that of the nongated measurement. This reduction in the lesion volume has been accompanied by an increase in the intensity in the 18F-FDG signal per voxel. This finding has resulted in an improvement in measurement of the maximum standardized uptake value (SUV(max)), which increased in 1 patient by as much as 159%. The total lesion glycolysis, defined as the product of the SUV(max) and the lesion volume, was also measured in gated and nongated modes and showed a consistency between the 2 measurements. CONCLUSION: We have shown that image smearing can be reduced by gating 18F-FDG PET images in synchronization with the respiratory motion. This technique allows a more accurate definition of the lesion volume and improves the quantitation specific activity of the tracer (in this case, 18F-FDG), which are distorted because of the breathing motion.

Intensity-modulated radiotherapy versus conventional three-dimensional conformal radiotherapy for boost or salvage treatment of nasopharyngeal carcinoma.

PURPOSE: To compare intensity-modulated radiotherapy (IMRT) and conventional three-dimensional conformal radiotherapy (3D-CRT) for the boost treatment of new-onset nasopharyngeal carcinoma (NPC) or the salvage treatment of locally recurrent NPC. METHODS AND MATERIALS: Between January 14 and February 23, 2000, 5-field 3D-CRT treatment plans were generated for 14 consecutive NPC patients using the ADAC Pinnacle planning system in Chang Gung Memorial Hospital, Kaohsiung, Taiwan. The planning data of these patients were later transferred to Memorial Sloan-Kettering Cancer Center, where new IMRT plans, also using 5-7 radiation fields were created for each patient using an inverse treatment planning system. The IMRT and 3D-CRT plans were compared for all 14 patients. The relationship between the anatomic shapes and locations of targets and the results of different plans were studied. RESULTS: Target doses were more homogeneous in IMRT plans. The average maximal brainstem dose (D(05), the dose received by 5% of the brainstem volume) decreased from 30.9% of the prescription dose with 3D-CRT to 15.3% and 14.7% with 5- and 7-field IMRT, respectively (p = 0.004 and 0.003, respectively, compared with 3D-CRT, paired Student's t test). Five anatomic factors were found that predicted greater benefits with IMRT. These factors were (1) vertical length of target >7 cm, (2) minimal distance between target and brainstem <0.1 cm, (3) maximal AP overlap of target and brainstem >0.6 cm, (4) maximal AP overlap of target and spinal cord >1 cm, and (5) vertical overlap of target and eyes >0 cm. For the 7 patients with at least 1 of these 5 anatomic factors, the benefits achieved by IMRT planning would have been greater than the benefits for the other 7 patients (p = 0.005, Fisher's exact test). CONCLUSION: For boost or salvage treatment of NPC, lower normal tissue doses and more homogeneous target doses were achieved with IMRT plans. For NPC patients with at least 1 of the 5 anatomic factors, IMRT is highly recommended.

Changes in FDG Tumor Uptake during and after Fractionated Radiation Therapy in a Rodent Tumor Xenograft.

OBJECTIVE: The uptake of FDG was measured before, during, and after fractionated radiation in order to evaluate the potential of FDG-PET imaging as an indicator of tumor response.METHODS: The study was performed with nude rats bearing the human neuroblastoma BE(2)C tumor xenografts. Tumors were irradiated with 10 fractions of 2 Gy using a 320 kV(p) X-ray unit. Following a baseline FDG-PET scan, repeat scans were performed weekly until animal sacrifice. The rodents were given up to 10 FDG-PET scans, over a period of up to 75 days posttreatment.RESULTS AND CONCLUSIONS: Neither, the average and maximum activity/cc of FDG tumor uptake, nor the respective standardized uptake values (SUV), correlated with tumor response. Instead, the total FDG uptake (defined as the product of the average FDG activity/cc with the tumor volume) correlated better with tumor response.