Estimation of setup uncertainty using planar and MVCT imaging for gynecologic malignancies.

PURPOSE: This prospective study investigates gynecologic malignancy online treatment setup error corrections using planar kilovoltage/megavoltage (KV/MV) imaging and helical MV computed tomography (MVCT) imaging. METHODS AND MATERIALS: Twenty patients were divided into two groups. The first group (10 patients) was imaged and treated using a conventional linear accelerator (LINAC) with image-guidance capabilities, whereas the second group (10 patients) was treated using tomotherapy with MVCT capabilities. Patients treated on the LINAC underwent planar KV and portal MV imaging and a two-dimensional image registration algorithm was used to match these images to digitally reconstructed radiographs (DRRs). Patients that were treated using tomotherapy underwent MVCT imaging, and a three-dimensional image registration algorithm was used to match planning CT to MVCT images. Subsequent repositioning shifts were applied before each treatment and recorded for further analysis. To assess intrafraction motion, 5 of the 10 patients treated on the LINAC underwent posttreatment planar imaging and DRR matching. Based on these data, patient position uncertainties along with estimated margins based on well-known recipes were determined. RESULTS: The errors associated with patient positioning ranged from 0.13 cm to 0.38 cm, for patients imaged on LINAC and 0.13 cm to 0.48 cm for patients imaged on tomotherapy. Our institutional clinical target volume-PTV margin value of 0.7 cm lies inside the confidence interval of the margins established using both planar and MVCT imaging. CONCLUSION: Use of high-quality daily planar imaging, volumetric MVCT imaging, and setup corrections yields excellent setup accuracy and can help reduce margins for the external beam treatment of gynecologic malignancies.

Novel breathing motion model for radiotherapy.

PURPOSE: An accurate model of breathing motion under quiet respiration is desirable to obtain the most accurate and conformal dose distributions for mobile lung cancer lesions. On the basis of recent lung motion measurements and the physiologic functioning of the lungs, we have determined that the motion of lung and lung tumor tissues can be modeled as a function of five degrees of freedom, the position of the tissues at a user-specified reference breathing phase, tidal volume and its temporal derivative airflow (tidal volume phase space). Time is an implicit variable in this model. METHODS AND MATERIALS: To test this hypothesis, a mathematical model of motion was developed that described the motion of objects p in the lungs as linear functions of tidal volume and airflow. The position of an object was described relative to its position -->P0 at the reference tidal volume and zero airflow, and the motion of the object was referenced to this position. Hysteresis behavior was hypothesized to be caused by pressure imbalances in the lung during breathing and was, in this model, a function of airflow. The motion was modeled as independent tidal volume and airflow displacement vectors, with the position of the object at time t equal to the vector sum -->rP(t) = -->rv(t) + -->rf(t) where -->rv(t) and -->rf(t) were displacement vectors with magnitudes approximated by linear functions of the tidal volume and airflow. To test this model, we analyzed five-dimensional CT scans (CT scans acquired with simultaneous real-time monitoring of the tidal volume) of 4 patients. The scans were acquired throughout the lungs, but the trajectories were analyzed in the couch positions near the diaphragm. A template-matching algorithm was implemented to identify the positions of the points throughout the 15 scans. In total, 76 points throughout the 4 patients were tracked. The lateral motion of these points was minimal; thus, the model was described in two spatial dimensions, with a total of six parameters necessary to describe the 30 degrees of freedom inherent in the 15 positions. RESULTS: For the 76 evaluated points, the average discrepancy (the distance between the measured and prediction positions) of the 15 locations for each tracked point was 0.75 +/- 0.25 mm, with an average maximal discrepancy of 1.55 +/- 0.54 mm. The average discrepancy was also tabulated as a fraction of the breathing motion. Discrepancies of <10% and 15% of the overall motion occurred in 73% and 95% of the tracked points, respectively. CONCLUSION: The motion tracking algorithms are being improved and automated to provide more motion data to test the models. This may allow a measurement of the motion-fitting parameters throughout the lungs. If the parameters vary smoothly, interpolation may be possible, yielding a continuous mathematical model of the breathing motion throughout the lungs. The utility of the model will depend on its stability as a function of time. If the model is only robust during the measurement session, it may be useful for determining lung function. If it is robust for weeks, it may be useful for treatment planning and gating of lung treatments. The use of tidal volume phase space for characterizing breathing motion appears to have provided, for the first time, the potential for a patient-specific mathematical model of breathing motion.

Postoperative radiation therapy for grade II and III intracranial ependymoma.

PURPOSE: To retrospectively determine the long-term outcome of intracranial ependymoma patients treated with surgery and postoperative radiation therapy. METHODS AND MATERIALS: Sixty patients were treated at our institution between 1964 and 2000. Forty patients had World Health Organization Grade II ependymoma, and 20 patients had Grade III ependymoma. The median patient age was 10.7 years. The majority of patients were male (55%), had infratentorial tumors (80%), and had subtotal resections (72%). Postoperative radiation therapy was delivered to all patients to a median total dose of 50.4 Gy. Craniospinal radiation therapy was used in the earlier era in only 12 patients (20%). RESULTS: The median follow-up of surviving patients was 12.5 years. The 5-year and 10-year disease-free survival rates for all patients were 58.4% and 49.5%, respectively. The 5-year and 10-year overall survival rates for all patients were 71.2% and 55.0%, respectively. Supratentorial tumor location was independently associated with a worse disease-free survival. Subtotal resection and supratentorial location predicted a worse overall survival, but this failed to reach statistical significance. No statistically significant effect on prognosis was observed with tumor grade, patient age, or radiation dose or volume. CONCLUSION: Our long-term follow-up indicates that half of ependymoma patients will have disease recurrences, indicating the need for more effective treatments.

Comparison of spirometry and abdominal height as four-dimensional computed tomography metrics in lung.

An important consideration in four-dimensional CT scanning is the selection of a breathing metric for sorting the CT data and modeling internal motion. This study compared two noninvasive breathing metrics, spirometry and abdominal height, against internal air content, used as a surrogate for internal motion. Both metrics were shown to be accurate, but the spirometry showed a stronger and more reproducible relationship than the abdominal height in the lung. The abdominal height was known to be affected by sensor placement and patient positioning while the spirometer exhibited signal drift. By combining these two, a normalization of the drift-free metric to tidal volume may be generated and the overall metric precision may be improved.

Quantitation of the reconstruction quality of a four-dimensional computed tomography process for lung cancer patients.

We have developed a four-dimensional computed tomography (4D CT) technique for mapping breathing motion in radiotherapy treatment planning. A multislice CT scanner (1.5 mm slices) operated in ciné mode was used to acquire 12 contiguous slices in each couch position for 15 consecutive scans (0.5 s rotation, 0.25 s between scans) while the patient underwent simultaneous quantitative spirometry measurements to provide a sorting metric. The spirometry-sorted scans were used to reconstruct a 4D data set. A critical factor for 4D CT is quantifying the reconstructed data set quality which we measure by correlating the metric used relative to internal-object motion. For this study, the internal air content within the lung was used as a surrogate for internal motion measurements. Thresholding and image morphological operations were applied to delineate the air-containing tissues (lungs, trachea) from each CT slice. The Hounsfield values were converted to the internal air content (V). The relationship between the air content and spirometer-measured tidal volume (v) was found to be quite linear throughout the lungs and was used to estimate the overall accuracy and precision of tidal volume-sorted 4D CT. Inspection of the CT-scan air content as a function of tidal volume showed excellent correlations (typically r>0.99) throughout the lung volume. Because of the discovered linear relationship, the ratio of internal air content to tidal volume was indicative of the fraction of air change in each couch position. Theoretically, due to air density differences within the lung and in room, the sum of these ratios would equal 1.11. For 12 patients, the mean value was 1.08 +/- 0.06, indicating the high quality of spirometry-based image sorting. The residual of a first-order fit between v and V was used to estimate the process precision. For all patients, the precision was better than 8%, with a mean value of 5.1% +/- 1.9%. This quantitative analysis highlights the value of using spirometry as the metric in sorting CT scans. The 4D reconstruction provides the CT data required to measure the three-dimensional trajectory of tumor and lung tissue during free breathing.

Elective nodal failures are uncommon in medically inoperable patients with Stage I non-small-cell lung carcinoma treated with limited radiotherapy fields.

PURPOSE: To review the outcome for 56 Stage I non-small-cell lung cancer treated definitively with three-dimensional conformal radiotherapy (3D-CRT) and to investigate the value of elective nodal irradiation in this patient population. METHODS AND MATERIALS: Between 1992 and 2001, 56 patients were treated with 3D-CRT for inoperable Stage I histologically confirmed non-small-cell lung cancer; 31 with T1N0 and 25 with T2N0 disease. All patients were treated with 3D-CRT to a median isocenter dose of 70 Gy (range 59.94-83.85) given in daily doses of 1.8 or 2 Gy. Prognostic factors were analyzed with respect to their impact on overall survival. Twenty-two patients received radiotherapy (RT) directed to elective regional lymphatics to doses of 45-50 Gy. The remaining 33 patients were treated to limited fields confined to the primary lung cancer with a margin. The patterns of failure were reviewed. RESULTS: The median follow-up was 20 months (range 6 months to 6 years). The actuarial local control rate was 88%, 69%, and 63%, at 1, 2, and 3 years, respectively. The actuarial cause-specific survival rate was 82%, 67%, and 51% at 1, 2, and 3 years, respectively. The actuarial overall survival rate was 73%, 51%, and 34% at 1, 2, and 3 years, respectively. The actuarial metastasis-free survival rate was 90%, 85%, and 81% at 1, 2, and 3 years, respectively. The RT dose was the only factor predictive of overall survival in our analysis. No statistically significant difference was noted in cause-specific or overall survival according to whether patients received elective nodal irradiation. Two of 33 patients treated with limited fields had regional nodal failure. CONCLUSION: Many patients with medically inoperable Stage I lung cancer die of intercurrent causes. The omission of the elective nodal regions from the RT portals did not compromise either the cause-specific or overall survival rate. Elective nodal failures were uncommon in the group treated with limited RT fields. A radiation dose 70 Gy was predictive of better survival in our population. We await the results of prospective trials evaluating high-dose RT in patients treated with RT alone for Stage I lung cancer.

Ionization chamber volume averaging effects in dynamic intensity modulated radiation therapy beams.

The commercial cylindrical ionization chamber ionization integration accuracy of dynamically moving fields was evaluated. The ionization chambers were exposed to long (14 cm), narrow (0.6, 1.0, 2.0, and 4.0 cm) 6 MV and 18 MV fields. Rather than rely on the linear accelerator to reproducibly scan across the chamber, the chambers were scanned beneath fixed portals. A water-equivalent phantom was constructed with cavities that matched the chambers and placed on a computer-controlled one-dimensional table. Computer-controlled electrometers were utilized in continuous charge integrate mode, with 10 samples of the charge, along with time stamps, acquired for each chamber location. A reference chamber was placed just beneath the linear accelerator jaws to adjust for variations in linear accelerator dose rate. The scan spatial resolution was selected to adequately sample regions of steep dose gradient and second spatial derivative (curvature). A fixed measurement in a 10 x 10 cm2 field was used to normalize the profiles to absolute chamber response. Three ionization chambers were tested, a microchamber (0.009 cm3), a Farmer chamber (0.6 cm3) and a waterproof scanning chamber (0.125 cm3). The larger chambers exhibited severe under-response at the small field's centers, but all of the chambers, independent of orientation, accurately integrated the ionization across the scanned portal. This indicates that the tested ionization chambers provide accurate integrated charges in regions of homogeneous dose regions. Partial integration (less than the field width plus the chamber length plus 2 cm), yielded integration errors of greater than 1% and 2% for 6 MV and 18 MV, respectively, with errors for the Farmer chamber of greater than 10% even for the 4 cm wide field.

A treatment planning study comparing HDR and AGIMRT for cervical cancer.

The customization of brachytherapy dose distributions for gynecologic malignancies is limited by the spatial positioning of the applicators. We tested the hypothesis that applicator-guided intensity modulated radiation therapy (AGIMRT) has the potential to deliver highly conformal dose distributions to cervical tumors, representing improvement over distributions obtained with intracavitary brachytherapy. A commercial three-dimensional (3-D) treatment planning system was used to create plans for ten cervical cancer patients treated at our institution. Dose distributions of conventionally designed high dose rate (HDR) plans were compared against those of AGIMRT. Tumor delineation was based on a previously published binary threshold technique, using image intensity on positron emission tomography (PET) scans. AGIMRT treatment schedules were designed using two fraction sizes: 6.5 Gy, to directly reproduce the HDR fractionation, and 1.8 Gy, to simulate traditional external beam fractionation. The average minimum tumor dose was significantly greater for the AGIMRT dose distributions than for the HDR distributions (64.2 Gy vs 33.6 Gy; p = 0.005). The mean percent tumor volume at the prescription dose was higher for the AGIMRT plans (90.0% vs 58.2%; p = 0.005). Using AGIMRT, the mean percent volume at the tolerance limit was decreased for the bladder (6.1% vs 16.6%; p = 0.047) but increased for the rectum (4.1% vs 2.2%; p = 0.646). Our study suggests that there may be conceptual and dosimetric advantages to replacing HDR with AGIMRT for patients with large-volume cervical tumors. This investigation is being expanded using sequential PET images to model tumor regression and compare brachytherapy and AGIMRT throughout the course of therapy.

A method for the reconstruction of four-dimensional synchronized CT scans acquired during free breathing.

Breathing motion is a significant source of error in radiotherapy treatment planning for the thorax and upper abdomen. Accounting for breathing motion has a profound effect on the size of conformal radiation portals employed in these sites. Breathing motion also causes artifacts and distortions in treatment planning computed tomography (CT) scans acquired during free breathing and also causes a breakdown of the assumption of the superposition of radiation portals in intensity-modulated radiation therapy, possibly leading to significant dose delivery errors. Proposed voluntary and involuntary breath-hold techniques have the potential for reducing or eliminating the effects of breathing motion, however, they are limited in practice, by the fact that many lung cancer patients cannot tolerate holding their breath. We present an alternative solution to accounting for breathing motion in radiotherapy treatment planning, where multislice CT scans are collected simultaneously with digital spirometry over many free breathing cycles to create a four-dimensional (4-D) image set, where tidal lung volume is the additional dimension. An analysis of this 4-D data leads to methods for digital-spirometry, based elimination or accounting of breathing motion artifacts in radiotherapy treatment planning for free breathing patients. The 4-D image set is generated by sorting free-breathing multislice CT scans according to user-defined tidal-volume bins. A multislice CT scanner is operated in the ciné mode, acquiring 15 scans per couch position, while the patient undergoes simultaneous digital-spirometry measurements. The spirometry is used to retrospectively sort the CT scans by their correlated tidal lung volume within the patient's normal breathing cycle. This method has been prototyped using data from three lung cancer patients. The actual tidal lung volumes agreed with the specified bin volumes within standard deviations ranging between 22 and 33 cm3. An analysis of sagittal and coronal images demonstrated relatively small (<1 cm) motion artifacts along the diaphragm, even for tidal volumes where the rate of breathing motion is greatest. While still under development, this technology has the potential for revolutionizing the radiotherapy treatment planning for the thorax and upper abdomen.

Video surface image guidance for external beam partial breast irradiation.

OBJECTIVE: Accelerated partial breast irradiation is an emerging treatment option for early stage breast cancer. With accelerated partial breast irradiation, patient setup, and target registration accuracy is vital. The current study compared various methods for isocenter placement accuracy. METHODS AND MATERIALS: Twenty-three patients treated on an institutional-approved partial breast irradiation protocol were monitored at each treatment fraction. All patients included in this study underwent clip placement at the time of surgery. Patients underwent computed tomographic simulation and surface contours were used to reconstruct a reference surface map. At the treatment machine, patients were initially positioned by laser alignment to tattoos. Orthogonal kilovoltage imaging of the chest wall, followed by video surface mapping of the breast, was performed. This video surface map was matched to the reference surface map to adjust the couch position. Verification orthogonal chest wall imaging and video surface mapping was again performed. The accuracy of setup by laser, orthogonal imaging of the chest wall, and surface alignment was retrospectively compared using the centroid clip position as the reference standard. The impact of setup error by surface alignment and by orthogonal kilovoltage imaging on planning target volume coverage was then calculated. RESULTS: Laser-based positioning resulted in a residual setup error of 3.9 ± 3.7 mm, 4.6 ± 3.9 mm, and 4.3 ± 4.5 mm in the posterior-anterior (P-A), inferior-superior (I-S), and left-right (L-R) directions, respectively, using clips as the reference standard. Setup based on bony anatomy with orthogonal imaging resulted in residual setup error of 3.2 ± 2.9 (P-A), 4.2 ± 3.5 (I-S), and 4.7 ± 5.3 mm (L-R). Setup with video surface mapping resulted in a residual setup error of 1.9 ± 2.2, 1.8 ± 1.9, and 1.8 ± 2.1 mm in the P-A, I-S, and L-R directions, respectively. Vector spatial deviation was 8.8 ± 4.2, 8.3 ± 3.8, and 4.0 ± 2.3 mm with laser, chest wall on board imaging, and video surface mapping based setup, respectively. Setup by video surface mapping resulted in improved dosimetric coverage of the planning target volume when compared with orthogonal imaging of the chest wall (V100 96.0% ± 0.1% vs 89.3% ± 0.2%; V95 99.7% ± 0.01% vs 98.6% ± 0.01%, P < .05). CONCLUSIONS: Video surface mapping of the breast is a more accurate method for isocenter placement in comparison to conventional laser-based alignment or orthogonal kilovoltage imaging of the chest wall.

Dosimetric consequences of uncorrected setup errors in helical Tomotherapy treatments of breast-cancer patients.

BACKGROUND AND PURPOSE: The Tomotherapy Hi-Art II system allows acquisition of pre-treatment MVCT images to correct patient position. This work evaluates the dosimetric impact of uncorrected setup errors in breast-cancer radiation therapy. MATERIALS AND METHODS: Breast-cancer patient-positioning errors were simulated by shifting the patient computed-tomography (CT) dataset relative to the planned photon fluence and re-computing the dose distributions. To properly evaluate the superficial region, film measurements were compared against the Tomotherapy treatment planning system (TPS) calculations. A simulation of the integrated dose distribution was performed to evaluate the setup error impact over the course of treatment. RESULTS: Significant dose differences were observed for 11-mm shifts in the anterolateral and 3-mm shifts in the posteromedial directions. The results of film measurements in the superficial region showed that the TPS overestimated the dose by 14% at a 1-mm depth, improving to 3% at depths >or=5mm. Significant dose reductions in PTV were observed in the dose distributions simulated over the course of treatment. CONCLUSIONS: Tomotherapy's rotational delivery provides sufficient photon fluence extending beyond the skin surface to allow an up to 7-mm uncorrected setup error in the anterolateral direction. However, the steep dose falloff that conforms to the lung surface leads to compromised dose distributions with uncorrected posteromedial shifts. Therefore, daily image guidance and consequent patient repositioning is warranted for breast-cancer patients.

Long term outcome with post-operative radiation therapy for spinal canal ependymoma.

PURPOSE: A retrospective study was performed to evaluate the long term efficacy and safety of post-operative radiation therapy in the management of spinal canal ependymoma at our institution. METHODS AND MATERIALS: Between 1954 and 1997, 22 patients with spinal canal ependymoma were treated with post-operative radiotherapy at our institution. The median age at diagnosis was 34.7 years (range 9.8-56.1 years). All patients underwent open biopsy with histologic diagnosis: 13 patients (59%) had ependymoma (WHO Grade II) and 9 patients (41%) had myxopapillary ependymoma (WHO Grade I). The median tumor size was 4.0 cm (range 1.5-15.0 cm). Twenty patients received subtotal resection and 2 patients received gross-total resection. Median radiation dose was 45.0 Gy. RESULTS: The median follow up for surviving patients was 11.4 years (range 0.6-37.0 years). An 80% progression-free-survival (PFS) was observed for all patients at 5-, 10- and 15-year endpoints. All recurrences were within 3 years of treatment. The 5-, 10- and 15-year overall-survivals (OS) for all patients were 85%, 78% and 64%, respectively. Patients with tumors larger than 6.0 cm at time of presentation demonstrated 5- and 10-year PFS of 58.3% compared to 92.3% for patients with tumors 6.0 cm or smaller (P = 0.047). There was no significant correlation between tumor size and OS. CONCLUSIONS: Post-operative radiation after subtotal resection is safe and offers durable tumor control and long term patient survival.

A prospective study of differences in duodenum compared to remaining small bowel motion between radiation treatments: implications for radiation dose escalation in carcinoma of the pancreas.

PURPOSE: As a foundation for a dose escalation trial, we sought to characterize duodenal and non-duodenal small bowel organ motion between fractions of pancreatic radiation therapy. PATIENTS AND METHODS: Nine patients (4 women, 5 men) undergoing radiation therapy were enrolled in this prospective study. The patients had up to four weekly CT scans performed during their course of radiation therapy. Pancreas, duodenum and non-duodenal small bowel were then contoured for each CT scan. On the initial scan, a four-field plan was generated to fully cover the pancreas. This plan was registered to each subsequent CT scan. Dose-volume histogram (DVH) analyses were performed for the duodenum, non-duodenal small bowel, large bowel, and pancreas. RESULTS: With significant individual variation, the volume of duodenum receiving at least 80% of the prescribed dose was consistently greater than the remaining small bowel. In the patient with the largest inter-fraction variation, the fractional volume of non-duodenal small bowel irradiated to at least the 80% isodose line ranged from 1% to 20%. In the patient with the largest inter-fraction variation, the fractional volume of duodenum irradiated to at least the 80% isodose line ranged from 30% to 100%. CONCLUSION: The volume of small bowel irradiated during four-field pancreatic radiation therapy changes substantially between fractions. This suggests dose escalation may be possible. However, dose limits to the duodenum should be stricter than for other segments of small bowel.

Comparison of spirometry and abdominal height as four-dimensional computed tomography metrics in lung.

An important consideration in four-dimensional CT scanning is the selection of a breathing metric for sorting the CT data and modeling internal motion. This study compared two noninvasive breathing metrics, spirometry and abdominal height, against internal air content, used as a surrogate for internal motion. Both metrics were shown to be accurate, but the spirometry showed a stronger and more reproducible relationship than the abdominal height in the lung. The abdominal height was known to be affected by sensor placement and patient positioning while the spirometer exhibited signal drift. By combining these two, a normalization of the drift-free metric to tidal volume may be generated and the overall metric precision may be improved.