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Combining external beam radiation therapy (EBRT) and prostate seed implant (PSI) is efficacious in treating intermediate- and high-risk prostate cancer at the cost of increased genitourinary toxicity. Accurate combined dosimetry remains elusive due to lack of registration between treatment plans and different biological effect. The current work proposes a method to convert physical dose to biological effective dose (BED) and spatially register the dose distributions for more accurate combined dosimetry. A PSI phantom was CT scanned with and without seeds under rigid and deformed transformations. The resulting CTs were registered using image-based rigid registration (RI), fiducial-based rigid registration (RF), or b-spline deformable image registration (DIR) to determine which was most accurate. Physical EBRT and PSI dose distributions from a sample of 91 previously-treated combined-modality prostate cancer patients were converted to BED and registered using RI, RF, and DIR. Forty-eight (48) previously-treated patients whose PSI occurred before EBRT were included as a "control" group due to inherent registration. Dose-volume histogram (DVH) parameters were compared for RI, RF, DIR, DICOM, and scalar addition of DVH parameters using ANOVA or independent Student's t tests (α = 0.05). In the phantom study, DIR was the most accurate registration algorithm, especially in the case of deformation. In the patient study, dosimetry from RI was significantly different than the other registration algorithms, including the control group. Dosimetry from RF and DIR were not significantly different from the control group or each other. Combined dosimetry with BED and image registration is feasible. Future work will utilize this method to correlate dosimetry with clinical outcomes. [ABSTRACT FROM AUTHOR]

Purpose: In treatment planning of the lung tumor with 4D-CT, maximum-intensity-projection (MIP) images have been used for delineation of the gross tumor volume plus motion or iGTV, which can then be revised with the multiple phases of the 4D-CT images. Although majority of contouring can be performed with MIP, the MIP images are not recommended for delineation of iGTV if the tumor is near or connected to the diaphragm or other structures of a similar density due to insufficient contrast between the tumor and the surrounding tissues in the MIP images. To remedy this shortcoming, the authors developed a new weighted MIP (wMIP) from cine CT without respiratory gating for contouring the iGTV. Methods: The wMIP images are obtained by keeping one phase of the cine CT images with the largest tumor in the overlap region of the tumor and the diaphragm. Outside the overlap region, the wMIP images are identical to the MIP images. Both MIP and wMIP images are obtained without respiratory gating from cine CT. Results: The authors demonstrated in a study of seven patients that wMIP can achieve 92% of the iGTV from 4D-CT. The maximum surface separation of the two iGTVs between wMIP and 4D-CT was 1.7 mm and six out of the seven studies had less than 1 mm in surface separation between the iGTVs of wMIP and 4D-CT. Conclusions: This development has the potential of enabling many CT scanners capable of cine CT to assess the respiratory motion of a lung tumor without 4D-CT. [ABSTRACT FROM AUTHOR]

Abstract: To compare relative carotid and normal tissue sparing using volumetric-modulated arc therapy (VMAT) or intensity-modulated radiation therapy (IMRT) for early-stage larynx cancer. Seven treatment plans were retrospectively created on 2 commercial treatment planning systems for 11 consecutive patients with T1-2N0 larynx cancer. Conventional plans consisted of opposed-wedged fields. IMRT planning used an anterior 3-field beam arrangement. Two VMAT plans were created, a full 360° arc and an anterior 180° arc. Given planning target volume (PTV) coverage of 95% total volume at 95% of 6300 cGy and maximum spinal cord dose below 2500 cGy, mean carotid artery dose was pushed as low as possible for each plan. Deliverability was assessed by comparing measured and planned planar dose with the gamma (γ) index. Full-arc planning provided the most effective carotid sparing but yielded the highest mean normal tissue dose (where normal tissue was defined as all soft tissue minus PTV). Static IMRT produced next-best carotid sparing with lower normal tissue dose. The anterior half-arc produced the highest carotid artery dose, in some cases comparable with conventional opposed fields. On the whole, carotid sparing was inversely related to normal tissue dose sparing. Mean γ indexes were much less than 1, consistent with accurate delivery of planned treatment. Full-arc VMAT yields greater carotid sparing than half-arc VMAT. Limited-angle IMRT remains a reasonable alternative to full-arc VMAT, given its ability to mediate the competing demands of carotid and normal tissue dose constraints. The respective clinical significance of carotid and normal tissue sparing will require prospective evaluation. [Copyright &y& Elsevier]

Purpose: Four-dimensional computed tomography (4D-CT) is commonly used to account for respiratory motion of target volumes in radiotherapy to the thorax. From the 4D-CT acquisition, a maximum-intensity projection (MIP) image set can be created and used to help define the tumor motion envelope or the internal gross tumor volume (iGTV). The purpose of this study was to quantify the differences in automatically contoured target volumes for usage in the delivery of stereotactic body radiation therapy using MIP data sets generated from one of the four methods: (1) 4D-CT phase-binned (PB) based on retrospective phase calculations, (2) 4D-CT phase-corrected phase-binned (PC-PB) based on motion extrema, (3) 4D-CT amplitude-binned (AB), and (4) cine CT built from all available images. Methods: MIP image data sets using each of the four methods were generated for a cohort of 28 patients who had prior thoracic 4D-CT scans that exhibited lung tumor motion of at least 1 cm. Each MIP image set was automatically contoured on commercial radiation treatment planning system. Margins were added to the iGTV to observe differences in the final simulated planning target volumes (PTVs). Results: For all patients, the iGTV measured on the MIP generated from the entire cine CT data set (iGTVcine) was the largest. Expressed as a percentage of iGTVcine, 4D-CT iGTV (all sorting methods) ranged from 83.8% to 99.1%, representing differences in the absolute volume ranging from 0.02 to 4.20 cm3; the largest average and range of 4D-CT iGTV measurements was from the PC-PB data set. Expressed as a percentage of PTVcine (expansions applied to iGTVcine), the 4D-CT PTV ranged from 87.6% to 99.6%, representing differences in the absolute volume ranging from 0.08 to 7.42 cm3. Regions of the measured respiratory waveform corresponding to a rapid change of phase or amplitude showed an increased susceptibility to the selection of identical images for adjacent bins. Duplicate image selection was most common in the AB implementation, followed by the PC-PB method. The authors also found that the image associated with the minimum amplitude measurement did not always correlate with the image that showed maximum tumor motion extent. Conclusions: The authors identified cases in which the MIP generated from a 4D-CT sorting process under-represented the iGTV by more than 10% or up to 4.2 cm3 when compared to the iGTVcine. They suggest utilization of a MIP generated from the full cine CT data set to ensure maximum inclusive tumor extent. [ABSTRACT FROM AUTHOR]

Purpose: Hardware integration of fluorodeoxyglucose positron emission tomography (PET) with computed tomography (CT) in combined PET/CT scanners has provided radiation oncologists and physicists with new possibilities for 3-D treatment simulation. The use of PET/CT simulation for target delineation of lung cancer is becoming popular and many studies concerning automatic segmentation of PET images have been performed. Several of these studies consider size and source-to-background (SBR) in their segmentation methods but neglect respiratory motion. The purpose of the current study was to develop a functional relationship between optimal activity concentration threshold, tumor volume, motion extent, and SBR using multiple regression techniques by performing an extensive series of phantom scans simulating tumors of varying sizes, SBR, and motion amplitudes. Segmented volumes on PET were compared with the “motion envelope” of the moving sphere defined on cine CT. Methods: A NEMA IEC thorax phantom containing six spheres (inner diameters ranging from 10 to 37 mm) was placed on a motion platform and moved sinusoidally at 0–30 mm (at 5 mm intervals) and six different SBRs (ranging from 5:1 to 50:1), producing 252 combinations of experimental parameters. PET images were acquired for 18 min and split into three 6 min acquisitions for reproducibility. The spheres (blurred on PET images due to motion) were segmented at 1% of maximum activity concentration intervals. The optimal threshold was determined by comparing deviations between the threshold volume surfaces with a reference volume surface defined on cine CT. Optimal activity concentration thresholds were normalized to background and multiple regression was used to determine the relationship between optimal threshold, volume, motion, and SBR. Standardized regression coefficients were used to assess the relative influence of each variable. The segmentation model was applied to three lung cancer patients and segmented regions of interest were compared with those segmented on cine CT. Results: The resulting model and coefficients provided a functional form that fit the phantom data with an adjusted R2=0.96. The most significant contributor to threshold level was SBR. Surfaces of PET-segmented volumes of three lung cancer patients were within 2 mm of the reference CT volumes on average. Conclusions: The authors successfully developed an expression for optimal activity concentration threshold as a function of object volume, motion, and SBR. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether cine computed tomography (CT) can serve as an alternative to four-dimensional (4D)-CT by providing tumor motion information and producing equivalent target volumes when used to contour in radiotherapy planning without a respiratory surrogate. Methods and Materials: Cine CT images from a commercial CT scanner were used to form maximum intensity projection and respiratory-averaged CT image sets. These image sets then were used together to define the targets for radiotherapy. Phantoms oscillating under irregular motion were used to assess the differences between contouring using cine CT and 4D-CT. We also retrospectively reviewed the image sets for 26 patients (27 lesions) at our institution who had undergone stereotactic radiotherapy for Stage I non–small-cell lung cancer. The patients were included if the tumor motion was >1 cm. The lesions were first contoured using maximum intensity projection and respiratory-averaged CT image sets processed from cine CT and then with 4D-CT maximum intensity projection and 10-phase image sets. The mean ratios of the volume magnitude were compared with intraobserver variation, the mean centroid shifts were calculated, and the volume overlap was assessed with the normalized Dice similarity coefficient index. Results: The phantom studies demonstrated that cine CT captured a greater extent of irregular tumor motion than did 4D-CT, producing a larger tumor volume. The patient studies demonstrated that the gross tumor defined using cine CT imaging was similar to, or slightly larger than, that defined using 4D-CT. Conclusion: The results of our study have shown that cine CT is a promising alternative to 4D-CT for stereotactic radiotherapy planning. [Copyright &y& Elsevier]

Dose calculation for thoracic radiotherapy is commonly performed on a free-breathing helical CT despite artifacts caused by respiratory motion. Four-dimensional computed tomography (4D-CT) is one method to incorporate motion information into the treatment planning process. Some centers now use the respiration-averaged CT (RACT), the pixel-by-pixel average of the ten phases of 4D-CT, for dose calculation. This method, while sparing the tedious task of 4D dose calculation, still requires 4D-CT technology. The authors have recently developed a means to reconstruct RACT directly from unsorted cine CT data from which 4D-CT is formed, bypassing the need for a respiratory surrogate. Using RACT from cine CT for dose calculation may be a means to incorporate motion information into dose calculation without performing 4D-CT. The purpose of this study was to determine if RACT from cine CT can be substituted for RACT from 4D-CT for the purposes of dose calculation, and if increasing the cine duration can decrease differences between the dose distributions. Cine CT data and corresponding 4D-CT simulations for 23 patients with at least two breathing cycles per cine duration were retrieved. RACT was generated four ways: First from ten phases of 4D-CT, second, from 1 breathing cycle of images, third, from 1.5 breathing cycles of images, and fourth, from 2 breathing cycles of images. The clinical treatment plan was transferred to each RACT and dose was recalculated. Dose planes were exported at orthogonal planes through the isocenter (coronal, sagittal, and transverse orientations). The resulting dose distributions were compared using the gamma (γ) index within the planning target volume (PTV). Failure criteria were set to 2%/1 mm. A follow-up study with 50 additional lung cancer patients was performed to increase sample size. The same dose recalculation and analysis was performed. In the primary patient group, 22 of 23 patients had 100% of points within the PTV pass γ criteria. The average maximum and mean γ indices were very low (well below 1), indicating good agreement between dose distributions. Increasing the cine duration generally increased the dose agreement. In the follow-up study, 49 of 50 patients had 100% of points within the PTV pass the γ criteria. The average maximum and mean γ indices were again well below 1, indicating good agreement. Dose calculation on RACT from cine CT is negligibly different from dose calculation on RACT from 4D-CT. Differences can be decreased further by increasing the cine duration of the cine CT scan. [ABSTRACT FROM AUTHOR]

Purpose: To assess the need for gross tumor volume (GTV) delineation protocols in head-and-neck cancer (HNC) treatment planning by use of positron emission tomography (PET)/computed tomography (CT) fusion imaging. Assessment will consist of interobserver and intermodality variation analysis. Methods and Materials: Sixteen HNC patients were accrued for the study. Four physicians (2 neuroradiologists and 2 radiation oncologists) contoured GTV on 16 patients. Physicians were asked to contour GTV on the basis of the CT alone, and then on PET/CT fusion. Statistical analysis included analysis of variance for interobserver variability and Student's paired sample t test for intermodality and interdisciplinary variability. A Boolean pairwise analysis was included to measure degree of overlap. Results: Near-significant variation occurred across physicians' CT volumes (p = 0.09) and significant variation occurred across physicians' PET/CT volumes (p = 0.0002). The Boolean comparison correlates with statistical findings. One radiation oncologist's PET/CT fusion volumes were significantly larger than his CT volumes (p < 0.01). Conversely, the other radiation oncologist's CT volumes tended to be larger than his fusion volumes (p = 0.06). No significant interdisciplinary variation was seen. Significant disagreement occurred between radiation oncologists. Conclusion: Significant differences in GTV delineation were found between multiple observers contouring on PET/CT fusion. The need for delineation protocol has been confirmed. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions Optically stimulated luminescent dosimeters (OSLDs) can be bleached and reused, but questions remain about the effects of repeated bleaching and fractionation schedules on OSLD performance.The aim of this study was to investigate how light sources with different wavelengths and different fractionation schemes affect the performance of reused OSLDs.OSLDs (N = 240) were irradiated on a cobalt‐60 beam in different step sizes until they reached an accumulated dose of 50 Gy. Between irradiations they were bleached using light sources of different wavelengths: the Imaging and Radiation Oncology Core (IROC) bleaching system (our control); monochromatic red, green, yellow, and blue lights; and a polychromatic white light. Sensitivity and linearity‐based correction factors were determined as a function of dose step‐size. The rate of signal removal from different light sources was characterized by sampling these OSLDs at various time points during their bleaching process. Relative doses were calculated according to the American Association of Physicists in Medicine Task Group‐191. Signal repopulation was investigated by irradiating OSLDs (N = 300) to various delivered doses of 2, 10, 20, 30, 40, and 50 Gy in a single fraction, bleached with one of the colors, and read over time. Fractionation effects were evaluated by irradiating OSLDs up to 30 Gy in different size steps. After reading, the OSLDs were bleached following IROC protocol. OSLDs (N = 40) received irradiations in 5, 10, 15, 30 Gy fractions until they had an accumulated dose of 30 Gy; The sensitivity response of these OSLDs was compared with reference OSLDs that had no accumulated dose.Light sources with polychromatic spectrums (IROC and white) bleached OSLDs faster than did sources with monochromatic spectra. Polychromatic light sources (white light and IROC system) provided the greatest dose stability for OSLDs that had larger amounts of accumulated dose. Signal repopulation was related to the choice of bleaching light source, timing of bleaching, and amount of accumulated dose. Changes to relative dosimetry were more pronounced in OSLDs that received larger fractions. At 5‐Gy fractions and above, all OSLDs had heightened sensitivity, with OSLDs exposed to 30‐Gy fractions being 6.4% more sensitive than reference dosimeters.The choice of bleaching light plays a role in how fast an OSLD is bleached and how much accumulated dose an OSLD can be exposed to while maintaining stable signal sensitivity. We have expanded upon investigations into signal repopulation to show that bleaching light plays a role in the migration of deep traps to dosimetric traps after bleaching. Our research concludes that the bleaching light source and fractionation need to be considered when reusing OSLD. [ABSTRACT FROM AUTHOR]

Optically stimulated luminescent dosimeters (OSLDs) are used in clinical radiation dosimetry, but their sensitivity changes with the accumulated dose, limiting their reusability. Different studies have reported inconsistent results regarding the changes in sensitivity at different accumulated doses, and the reasons for this inconsistency remain unclear. In addition, the extent to which the OSLD linearity and element sensitivity correction factor (k s , i ) change with the accumulated dose has not been well established. We sought to characterize how the individual k s , i and dose non-linearity correction factor (k L) change with accumulated dose and how such changes affect the measurement of the dose to water (D w). Determining the extent to which these parameters change with the accumulated dose can help clinics, institutions, and the Imaging and Radiation Oncology Core (IROC) at MD Anderson extend the OSLD accumulated dose limit above 10 Gy and thus increase the efficiency of use of these detectors, including for the remote audit output audits run by IROC for the National Clinical Trials Network. 95 nanoDot OSLDs were individually irradiated in 4-Gy cycles with 90 cGy used to determine sensitivity, irradiated between 0.25- to 3-Gy to determine linearity, and then irradiated to return all dosimeters to the same total dose history. Repeated measurements between 10 and 23 Gy were performed with the same batch (N = 129) and with a different batch (batch 2, N = 130). Dosimeters were read with a microSTARii system 5–8 h following each irradiation, and each OSLD was bleached for 24 h in the IROC bleaching box prior to every irradiation. A combination of single-factor ANOVA, Levene tests, and linear regressions was used to quantify changes in OSLD characteristics as a function of accumulated dose. The D w was calculated using Equation (1)in the American Association of Physicists in Medicine Task Group 191 report. The signal response of the OSLDs showed stability within 1% up to an accumulated dose of 23 Gy before decreasing with dose. The k s , i remained the same, while linearity changed with accumulated dose but did so in a linear and predictable manner. Our findings improve our understanding of accumulated dose and could help improve overall process efficiency by extending the reusability of OSLDs. • Systematically evaluated how TG-191 factors change with accumulated dose. • Dose-nonlinearity correction factor changes linearly with accumulated dose. • No change in element sensitivity correction factor with accumulated dose. • OSLDs can be used up to 23 Gy with the irradiation and bleaching scheme at IROC. • OSLDs can be reused to higher dose limits with well characterized factors. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to assess the efficacy of a gross tumor volume (GTV) contouring protocol on interobserver variability between 4 physicians in positron emission therapy/computed tomography (PET/CT) treatment planning of head-and-neck cancer. A GTV contouring protocol for PET/CT treatment planning was developed utilizing 4 stages: Preliminary contouring on CT alone, determination of appropriate PET windowing, accurate image registration, and modification of CT contouring with correctly formatted PET/CT display and rules for modality disagreement. Two neuroradiologists and 2 radiation oncologists (designated as A, B, C, and D, respectively) were given a tutorial of PET/CT coregistered imaging individualized to their skill level, which included a step-by-step explanation of the protocol with clinical examples. Opportunities for questions and hands-on practice were given. The physicians were asked to re-contour 16 head-and-neck patients from Part I on PET/CT fusion imaging. Differences in volume magnitude were analyzed for statistical significance by analysis of variance (ANOVA) and paired t-tests (α < 0.05). Volume overlap was analyzed for statistical significance using Wilcoxon signed-rank tests (α < 0.05). Volume overlap increased significantly from Part I to Part II (p < 0.05). One previously significant difference between physicians disappeared with the protocol in place. The mean fusion volume of Physician C, however, remained significantly larger than that of Physician D (p < 0.01). This result is unchanged from Part I. The multidisciplinary contouring protocol significantly improved the coincidence of GTVs contoured by multiple physicians. The magnitudes of the volumes showed marginal improvement in consistency. Developing an institutional contouring protocol for PET/CT treatment planning is highly recommended to reduce interobserver variability. [Copyright &y& Elsevier]

Background: Long‐term breast cancer survivors are at risk for cardiotoxicity after treatment, but there is insufficient evidence to provide long‐term (~10 years) cardiovascular disease (CVD) screening recommendations. We sought to evaluate a tri‐modality CVD screening approach. Methods: This single‐arm, feasibility study enrolled 201 breast cancer patients treated ≥6 years prior without CVD at diagnosis. Patients were sub‐grouped: cardiotoxic (left‐sided) radiation (RT), cardiotoxic (anthracycline‐based) chemotherapy, both cardiotoxic chemotherapy and RT, and neither cardiotoxic treatment. Patients underwent electrocardiogram (EKG), transthoracic echocardiogram with strain (TTE with GLS), and coronary artery calcium computed tomography (CAC CT). The primary endpoint was preclinical or clinical CVD. Results: Median age was 50 (29–65) at diagnosis and 63 (37–77) at imaging; median interval was 11.5 years (6.7–14.5). Among sub‐groups, 44% had no cardiotoxic treatment, 31.5% had cardiotoxic RT, 16% had cardiotoxic chemotherapy, and 8.5% had both. Overall, 77.6% showed preclinical and/or clinical CVD and 51.5% showed clinical CVD. Per modality, rates of any CVD and clinical CVD were, respectively: 27.1%/10.0% on EKG, 50.0%/25.3% on TTE with GLS, and 50.8%/45.8% on CAC CT. No statistical difference was seen among the treatment subgroups (NS, χ2 test, p = 0.58/p = 0.15). Conclusion: This study identified a high incidence of CVD in heterogenous long‐term breast cancer survivors, most >10 years post‐treatment. Over half had clinical CVD findings warranting follow‐up and/or intervention. Each imaging test independently contributed to the detection rate. This provides early evidence that long‐term cardiac screening may be of value to a wider group of breast cancer survivors than previously recognized. [ABSTRACT FROM AUTHOR]

This study examined the relationship of achievable mean dose and percent volumetric overlap of salivary gland with the planning target volume (PTV) in volumetric-modulated arc therapy (VMAT) plan in radiotherapy for a patient with head-and-neck cancer. The aim was to develop a model to predict the viability of planning objectives for both PTV coverage and organs-at-risk (OAR) sparing based on overlap volumes between PTVs and OARs, before the planning process. Forty patients with head-and-neck cancer were selected for this retrospective plan analysis. The patients were treated using 6 MV photons with 2-arc VMAT plan in prescriptions with simultaneous integrated boost in dose of 70 Gy, 63 Gy, and 58.1 Gy to primary tumor sites, high-risk nodal regions, and low-risk nodal regions, respectively, over 35 fractions. A VMAT plan was generated using Varian Eclipse (V13.6), in optimization with biological-based generalized equivalent uniform dose (gEUD) objective for OARs and targets. Target dose coverage (D95, Dmax, conformity index) and salivary gland dose (Dmean and Dmax) were evaluated in those plans. With a range of volume overlaps between salivary glands and PTVs and dose constraints applied, results showed that dose D95 for each PTV was adequate to satisfy D95 >95% of the prescription. Mean dose to parotid <26 Gy could be achieved with <20% volumetric overlap with PTV58 (parotid-PTV58). On an average, the Dmean was seen at 15.6 Gy, 21.1 Gy, and 24.2 Gy for the parotid-PTV58 volume at <5%, <10%, and <20%, respectively. For submandibular glands (SMGs), an average Dmean of 27.6 Gy was achieved in patients having <10% overlap with PTV58, and 36.1 Gy when <20% overlap. Mean doses on parotid and SMG were linearly correlated with overlap volume (regression R2 = 0.95 and 0.98, respectively), which were statistically significant (P < 0.0001). This linear relationship suggests that the assessment of the structural overlap might provide prospective for achievable planning objectives in the head-and-neck plan. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether cine computed tomography (CT) can serve as an alternative to four-dimensional (4D)-CT by providing tumor motion information and producing equivalent target volumes when used to contour in radiotherapy planning without a respiratory surrogate.Methods and Materials: Cine CT images from a commercial CT scanner were used to form maximum intensity projection and respiratory-averaged CT image sets. These image sets then were used together to define the targets for radiotherapy. Phantoms oscillating under irregular motion were used to assess the differences between contouring using cine CT and 4D-CT. We also retrospectively reviewed the image sets for 26 patients (27 lesions) at our institution who had undergone stereotactic radiotherapy for Stage I non-small-cell lung cancer. The patients were included if the tumor motion was >1 cm. The lesions were first contoured using maximum intensity projection and respiratory-averaged CT image sets processed from cine CT and then with 4D-CT maximum intensity projection and 10-phase image sets. The mean ratios of the volume magnitude were compared with intraobserver variation, the mean centroid shifts were calculated, and the volume overlap was assessed with the normalized Dice similarity coefficient index.Results: The phantom studies demonstrated that cine CT captured a greater extent of irregular tumor motion than did 4D-CT, producing a larger tumor volume. The patient studies demonstrated that the gross tumor defined using cine CT imaging was similar to, or slightly larger than, that defined using 4D-CT.Conclusion: The results of our study have shown that cine CT is a promising alternative to 4D-CT for stereotactic radiotherapy planning. [ABSTRACT FROM AUTHOR]