Pre-treatment dosimetric verification by means of a liquid-filled electronic portal imaging device during dynamic delivery of intensity modulated treatment fields.

BACKGROUND AND PURPOSE: Although intensity modulated radiation therapy is characterized by three-dimensional dose distributions which are often superior to those obtained with conventional treatment plans, its routine clinical implementation is partially held back by the complexity of the beam verification. This is even more so when a dynamic multileaf collimator (dMLC) is used instead of a segmented beam delivery. We have therefore investigated the possibility of using a commercially available, liquid-filled electronic portal imaging device (EPID) for the pre-treatment quality assurance of dynamically delivered dose distributions. METHODS AND MATERIALS: A special acquisition mode was developed to optimize the image acquisition speed for dosimetry with the liquid-filled EPID. We investigated the accuracy of this mode for 6 and 18 MV photon beams through comparison with film and ion chamber measurements. The impact of leaf speed and pulse rate fluctuations was quantified by means of dMLC plans especially designed for this purpose. Other factors influencing the accuracy of the dosimetry (e.g. the need for build-up, remanence of the ion concentration in the liquid and bulging of the liquid at non-zero gantry angles) were studied as well. We finally compared dosimetric EPID images with the corresponding image prediction delivered without a patient in the beam. RESULTS: The dosimetric accuracy of the measured dose distribution is approximately 2% with respect to film and ion chamber measurements. The accuracy declines when leaf speed is increased beyond 2 cm/s, but is fairly insensitive to accelerator pulse rate fluctuations. The memory effect is found to be of no clinical relevance. When comparing the acquired and expected distributions, an overall agreement of 3% can be obtained, except at areas of steep dose gradients where slight positional shifts are translated into large errors. CONCLUSIONS: Accurate dosimetric images of intensity modulated beam profiles delivered with a dMLC can be obtained with a commercially available, liquid-filled EPID. The developed acquisition mode is especially suited for fast and accurate pre-treatment verification of the intensity modulated fields.

The utility of SPECT in determining the relationship between radiation dose and salivary gland dysfunction after radiotherapy.

Salivary gland scintigraphy (SGS) is used to depict salivary gland dysfunction after radiotherapy (RT). The aim of this study was to investigate the utility of SGS combined with single photon emission computed tomography (SPECT). Twenty-one patients with a carcinoma of head and neck underwent SGS before and 1 month after RT. After injection of 370 MBq 99Tcm-pertechnetate, a biplanar dynamic acquisition (12 x 1 min) was started, followed by a SPECT acquisition during 4 min. Carbachol was then injected and a second dynamic study (16 x 1 min) was performed, again followed by a SPECT acquisition. The salivary excretion fraction (SEF) was calculated both from the geometric mean planar image for each parotid and from the SPECT data for each transverse plane through the parotids. The RT-induced changes in the SEF (dSEF) were correlated with the mean radiation dose calculated using tomography-based dosimetry. The mean radiation dose to the parotids was 44 Gy (range 4.4-68.1 Gy). The mean range of the variation in radiation dose to the transverse slices within the parotids of a patient was 24 Gy (range 6.2-51.9 Gy). Considering all transverse planes through the parotids in all patients, a linear correlation was found between the dSEF calculated using SGS-SPECT and the radiation dose (r=0.45, P=0.0001). Thirteen patients had a variation in radiation dose within the parotids of more than 20 Gy. In nine of these a significant intra-individual correlation between radiation dose and the dSEF of the transverse parotid slices was found (r range 0.55-0.97; P value range 0.037-0.0001). In conclusion, SGS-SPECT can be used for monitoring radiation-induced parotid gland dysfunction. It offers the unique possibility for the assessment of intra-individual dose-dysfunction curves in patients with large variations in the radiation dose within the parotids.

Late rectal bleeding after conformal radiotherapy of prostate cancer. II. Volume effects and dose-volume histograms.

PURPOSE AND OBJECTIVE: Late rectal bleeding is a potentially dose limiting complication of three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. The frequency of late rectal bleeding has been shown to increase as the prescription dose rises above 70 Gy. The purpose of this study is to identify features of the cumulative dose-volume histogram (DVH) for the rectal wall that correlate with late rectal bleeding after 3D-CRT for prostate cancer. METHODS AND MATERIALS: Follow-up information on rectal bleeding is available for 261 and 315 patients treated using 3D-CRT at Memorial Sloan-Kettering Cancer Center for Stage T1c-T3 prostate cancer with minimum target doses of 70.2 and 75.6 Gy, respectively. All patients in this study were treated with a coplanar 6-field technique (2 lateral and 4 oblique fields). Patients were classified as having rectal bleeding if they bled (> or = Grade 2) before 30 months, and nonbleeding (< or = Grade 1) if they were without bleeding at 30 months, using the RTOG morbidity scale. Rectal bleeding was observed in 13 and 38 of the patients treated at 70.2 and 75.6 Gy, respectively. Treatment plans were analyzed for 39 nonbleeding and 13 bleeding patients receiving 70.2 Gy, and 83 nonbleeding and 36 bleeding patients receiving 75.6 Gy. Dose-volume histograms (DVHs) for the anatomic rectal wall were calculated. Average DVHs of the bleeding and nonbleeding patients were generated, and a permutation test was used to assess the significance of differences between them, for each dose group. The confounding effect of total rectal wall volume (V(RW)) was removed by calculating the average differences in DVHs between all combinations of bleeding and nonbleeding patients with similar V(RW)s. Finally, multivariate analysis using logistic regression was performed to test the significance of the DVH variables in the presence of anatomic, geometric, and medical variables previously found to correlate with rectal bleeding in a companion analysis of the same patients. RESULTS: The area under the average percent volume DVH for the rectal wall of patients with bleeding was significantly higher than those of patients without bleeding in both dose groups (p = 0.02, 70.2 Gy; p < 0.0001, 75.6 Gy). However, small V(RW)s were associated with rectal bleeding (p = 0.06, 70.2 Gy; p < 0.01, 75.6 Gy), resulting in an increase in average percent volumes exposed to all doses for patients with rectal bleeding. For patients with similar V(RW)s, rectal bleeding was significantly correlated with the volumes exposed to 46 Gy in both dose groups (p = 0.02, 70.2 Gy; p = 0.005, 75.6 Gy, tolerance in V(RW): 5 ccs). For the 75.6 Gy dose group, the percent volume receiving 77 Gy was significantly correlated with rectal bleeding (p < 0.005). Bivariate analysis using logistic regression, including V(RW) together with a single DVH variable, showed good agreement with the above analysis. Multivariate analysis revealed a borderline significant correlation of the percent volume receiving 71 Gy in the 70.2 Gy dose group. It also showed that the DVH variables were highly correlated with geometric and dosimetric variables previously found to correlate with rectal bleeding in multivariate analysis. CONCLUSION: Significant volume effects were found in the probability of late rectal bleeding for patients undergoing 3D-CRT for prostate cancer with prescription doses of 70.2 and 75.6 Gy. The percent volumes exposed to 71 and 77 Gy in the 70.2 and 75.6 Gy dose groups respectively were significantly correlated with rectal bleeding. The independent correlation of small V(RW) with rectal bleeding may indicate the existence of a functional reserve for the rectum. The independent association with larger percent volumes exposed to intermediate doses ( approximately 46 Gy) seen in both dose groups may indicate that a large surrounding region of intermediate dose may interfere with the ability to repair the effects of a central high dose region.

Palliative radiotherapy practice within Western European countries: impact of the radiotherapy financing system?

PURPOSE: To analyze the reimbursement modalities for radiotherapy in the different Western European countries, as well as to investigate if these differences have an impact on the palliative radiotherapy practice for bone metastases. MATERIALS AND METHODS: A questionnaire was sent to 565 radiotherapy centres included in the 1997 ESTRO directory. In this questionnaire the reimbursement strategy applied in the different centres was assessed, with respect to the use of a budget (departmental or hospital budget), case payment and/or fee-for-service reimbursement. The differences were analyzed according to country and to type and size of the radiotherapy centre. RESULTS: A total of 170 centres (86% of the responders) returned the questionnaire. Most frequent is budget reimbursement: some form of budget reimbursement is found in 69% of the centres, whereas 46% of the centres are partly reimbursed through fee-for-service and 35% through case payment. The larger the department, the more frequent the reimbursement through a budget or a case payment system and the less the importance of fee-for-service reimbursement (chi(2): P=0.0012; logit: P=0.0055). Whereas private centres are almost equally reimbursed by fee-for-service financing as by budget or case payment, radiotherapy departments in university hospitals receive the largest part of their financial resources through a budget or by case payment (83%) (chi(2): P=0.002; logit: P=0.0073). A correlation between the country and the radiotherapy reimbursement system was also demonstrated (P=0.002), radiotherapy centres in Spain, the Netherlands and the United Kingdom being almost entirely reimbursed through a budget and/or case payment and centres in Germany and Switzerland mostly through a fee-for-service system. In budget and case payment financing lower total number of fractions and lower total dose (chi(2): P=0.003; logit: P=0.0120) as well as less shielding blocks (chi(2): P=0.003; logit: P=0.0066) are used. A same tendency is found for the use of isodose calculations and field set-up, but without being statistically significant (P=0.264 and P=0.061 res.). The type of the centre and the reimbursement modality influence the fractionation regimen independently (P=0.0274). This is not the case for the centre size and the reimbursement, which were found to exert correlated effects on the fractionation schedule (P=0.1042). CONCLUSION: Reimbursement systems seem to influence radiotherapy practice. One should therefore aim to develop reimbursement criteria that pursue to deliver, not only the best qualitative, but also the most cost-effective treatments to the patients.

Differences in palliative radiotherapy for bone metastases within Western European countries.

PURPOSE: To evaluate the differences in palliative radiotherapy for painful bone metastases amongst different Western European countries. MATERIALS AND METHODS: A questionnaire was sent to 565 radiotherapy centres in 19 Western European countries, based on the 1997 ESTRO directory. In this questionnaire the current local palliative radiotherapy practice for bone metastases was assessed in terms of total dose, fractionation, treatment complexity (use of shielding blocks, frequency of isodose calculations, field set-up) and type of machine used. The differences were analyzed according to the country and to the type and size of radiotherapy centre. RESULTS: A total of 205 centres (36%) returned the questionnaire, of which 198 could be further analyzed. The most frequently used antalgic fractionation schedule is 30 Gy in ten daily fractions of 3 Gy (50%), single fractions and conventional 2 Gy fractions being used in a minority of the centres (respectively, 11 and 9%). Most antalgic treatments are performed on a linear accelerator (67% of the centres uses linear accelerators) and 64% of the centres predominantly uses a two-field set-up. The majority of the centres uses shielding blocks and performs isodose calculations in less than 50% of the patients, (respectively, 88 and 81%). There is a correlation between the centre size and the palliative irradiation practice, the largest centres using more hypofractionation (chi(2): P=0.001; logit: P=0. 0003) and a less complex treatment set up as expressed by the use of isodose calculations (chi(2): P=0.027; logit: P=0.0161). There is also a tendency to use less shielding blocks (P=0.177). The same goes for university centres as compared with private centres: university centres use shorter fractionation schedules (chi(2): P=0. 008; logit: P=0.0094), less isodoses (chi(2): P=0.010; logit: P=0. 0115) and somewhat less shielding blocks (P=0.151). Amongst the analyzed countries different tendencies in fractionation (P=0.001) and treatment complexity are observed (use of isodoses: P=0.014, use of shielding blocks: P=0.001). CONCLUSION: These data suggest that beside work-load and clinical evidence, country-related factors such as tradition and habits, past teaching, the national organization of health care and reimbursement criteria may influence the local practice.

The impact of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) lymph node staging on the radiation treatment volumes in patients with non-small cell lung cancer.

PURPOSE: (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) combined with computer tomography (PET-CT) is superior to CT alone in mediastinal lymph node (LN) staging in non-small cell lung cancer (NSCLC). We studied the potential impact of this non-invasive LN staging procedure on the radiation treatment plan of patients with NSCLC. PATIENTS AND METHODS: The imaging and surgical pathology data from 105 patients included in two previously published prospective LN staging protocols form the basis for the present analysis. For 73 of these patients, with positive LN's on CT and/or on PET, a theoretical study was performed in which for each patient the gross tumour volume (GTV) was defined based on CT and on PET-CT data. For each GTV, the completeness of tumour coverage was assessed, using the available surgical pathology data as gold standard. A more detailed analysis was done for the first ten consecutive patients in whom the PET-CT-GTV was smaller than the CT-GTV. Theoretical radiation treatment plans were constructed based on both CT-GTV and PET-CT-GTV. Dose-volume histograms for the planning target volume (PTV), for the total lung volume and the lung volume receiving more than 20 Gy (V(lung(20))), were calculated. RESULTS: Data from 988 assessed LN stations were available. In the subgroup of 73 patients with CT or PET positive LN's, tumour coverage improved from 75% when the CT-GTV was used to 89% with the PET-CT-GTV (P=0.005). In 45 patients (62%) the information obtained from PET would have led to a change of the treatment volumes. For the ten patients in the dosimetry study, the use of PET-CT to define the GTV, resulted in an average reduction of the PTV by 29+/-18% (+/-1 SD) (P=0.002) and of the V(lung(20)) of 27+/-18% (+/-1 SD) (P=0.001). CONCLUSION: In patients with NSCLC considered for curative radiation treatment, assessment of locoregional LN tumour extension by PET will improve tumour coverage, and in selected patients, will reduce the volume of normal tissues irradiated, and thus toxicity. This subgroup of patients could then become candidates for treatment intensification.

Quality assurance in radiotherapy by identifying standards and monitoring treatment preparation.

BACKGROUND AND PURPOSE: Due to the complexity of the treatment preparation in radiotherapy, a number of errors go undetected until after the first treatment session. Some of these errors could easily have been noticed before treatment if an objective filter existed in addition to human supervision. With this in mind, a conceptually novel extension to conventional quality assurance procedures was explored to create a global platform monitoring treatment preparation by comparison with the existing local standards. MATERIALS AND METHODS: The feasibility of developing such a platform was evaluated for a test case on a cohort of 202 patients having received breast irradiation. By statistical analysis of the treatment parameters, mean values and tolerance levels could be defined for most parameters based on the observed standard deviations. Useful correlations were traced providing us with a means to automatically track errors, the detection of which would otherwise solely depend upon the alertness of the supervisor. RESULTS AND CONCLUSIONS: Apart from its possibilities as a mere quality control tool, the platform, developed in the framework of EQUART (European Quality Assurance Program in Radiotherapy by Monitoring Treatment Preparation), can be incorporated in the treatment preparation chain, providing standard setup values for the simulation. A crucial achievement of EQUART lies in the fact that filtering out of errors occurs prior to treatment initiation.

The contribution of magnetic resonance imaging to the three-dimensional treatment planning of localized prostate cancer.

PURPOSE: To investigate whether the use of transaxial and coronal MR imaging improves the ability to localize the apex of the prostate and the anterior part of the rectum compared to the use of transaxial CT alone, and whether the incorporation of MR could improve the coverage of the prostate by the radiotherapy field and change the volume of rectum irradiated. METHODS AND MATERIALS: Ten consecutive patients with localized prostate carcinoma underwent a CT and an axial and coronal MR scan in treatment position. The CT and MR images were mathematically aligned, and three observers were asked to contour independently the prostate and the rectum on CT and on MR. The interobserver variability of the prostatic apex location and of the delineation of the anterior rectal wall were assessed for each image modality. A dosimetry study was performed to evaluate the dose to the rectum when MR was used in addition to CT to localize the pelvic organs. RESULTS: The interobserver variation of the prostatic apex location was largest on CT ranging from 0.54 to 1.07 cm, and smallest on coronal MR ranging from 0.17 to 0.25 cm. The interobserver variation of the delineation of the anterior rectum on MR was small and constant along the whole length of the prostate (0.09+/-0.02 cm), while for CT it was comparable to that for the MR delineation at the base of the prostate, but it increased gradually towards the apex, where the variation reached 0.39 cm. The volume of MR rectum receiving more than 80% of the prescribed dose was on average reduced by 23.8+/-11.2% from the CT to the MR treatment plan. CONCLUSION: It can be concluded that the additional use of axial and coronal MR scans, in designing the treatment plan for localized prostate carcinoma, improves substantially the localization accuracy of the prostatic apex and the anterior aspect of the rectum, resulting in a better coverage of the prostate and a potential to reduce the volume of the rectum irradiated to a high dose.

Deep inspiration breath-hold technique for lung tumors: the potential value of target immobilization and reduced lung density in dose escalation.

PURPOSE/OBJECTIVE: This study evaluates the dosimetric benefits and feasibility of a deep inspiration breath-hold (DIBH) technique in the treatment of lung tumors. The technique has two distinct features--deep inspiration, which reduces lung density, and breath-hold, which immobilizes lung tumors, thereby allowing for reduced margins. Both of these properties can potentially reduce the amount of normal lung tissue in the high-dose region, thus reducing morbidity and improving the possibility of dose escalation. METHODS AND MATERIALS: Five patients treated for non-small cell lung carcinoma (Stage IIA-IIIB) received computed tomography (CT) scans under 4 respiration conditions: free-breathing, DIBH, shallow inspiration breath-hold, and shallow expiration breath-hold. The free-breathing and DIBH scans were used to generate 3-dimensional conformal treatment plans for comparison, while the shallow inspiration and expiration scans determined the extent of tumor motion under free-breathing conditions. To acquire the breath-hold scans, the patients are brought to reproducible respiration levels using spirometry, and for DIBH, modified slow vital capacity maneuvers. Planning target volumes (PTVs) for free-breathing plans included a margin for setup error (0.75 cm) plus a margin equal to the extent of tumor motion due to respiration (1-2 cm). Planning target volumes for DIBH plans included the same margin for setup error, with a reduced margin for residual uncertainty in tumor position (0.2-0.5 cm) as determined from repeat fluoroscopic movies. To simulate the effects of respiration-gated treatments and estimate the role of target immobilization alone (i.e., without the benefit of reduced lung density), a third plan is generated from the free-breathing scan using a PTV with the same margins as for DIBH plans. RESULTS: The treatment plan comparison suggests that, on average, the DIBH technique can reduce the volume of lung receiving more than 25 Gy by 30% compared to free-breathing plans, while respiration gating can reduce the volume by 18%. The DIBH maneuver was found to be highly reproducible, with intra breath-hold reproducibility of 1.0 (+/- 0.9) mm and inter breath-hold reproducibility of 2.5 (+/- 1.6) mm, as determined from diaphragm position. Patients were able to perform 10-13 breath-holds in one session, with a comfortable breath-hold duration of 12-16 s. CONCLUSION: Patients tolerate DIBH maneuvers well and can perform them in a highly reproducible fashion. Compared to conventional free-breathing treatment, the DIBH technique benefits from reduced margins, as a result of the suppressed target motion, as well as a decreased lung density; both contribute to moving normal lung tissue out of the high-dose region. Because less normal lung tissue is irradiated to high dose, the possibility for dose escalation is significantly improved.

Intensity-modulated tangential beam irradiation of the intact breast.

PURPOSE: To evaluate the potential benefits of intensity modulated tangential beams in the irradiation of the intact breast. METHODS AND MATERIALS: Three-dimensional treatment planning was performed on five left and five right breasts using standard wedged and intensity modulated (IM) tangential beams. Optimal beam parameters were chosen using beams-eye-view display. For the standard plans, the optimal wedge angles were chosen based on dose distributions in the central plane calculated without inhomogeneity corrections, according to our standard protocol. Intensity-modulated plans were generated using an inverse planning algorithm and a standard set of target and critical structure optimization criteria. Plans were compared using multiple dose distributions and dose volume histograms for the planning target volume (PTV), ipsilateral lung, coronary arteries, and contralateral breast. RESULTS: Significant improvements in the doses to critical structures were achieved using intensity modulation. Compared with a standard-wedged plan prescribed to 46 Gy, the dose from the IM plan encompassing 20% of the coronary artery region decreased by 25% (from 36 to 27 Gy) for patients treated to the left breast; the mean dose to the contralateral breast decreased by 42% (from 1.2 to 0.7 Gy); the ipsilateral lung volume receiving more than 46 Gy decreased by 30% (from 10% to 7%); the volume of surrounding soft tissue receiving more than 46 Gy decreased by 31% (from 48% to 33%). Dose homogeneity within the target volume improved greatest in the superior and inferior regions of the breast (approximately 8%), although some decrease in the medial and lateral high-dose regions (approximately 4%) was also observed. CONCLUSION: Intensity modulation with a standard tangential beam arrangement significantly reduces the dose to the coronary arteries, ipsilateral lung, contralateral breast, and surrounding soft tissues. Improvements in dose homogeneity throughout the target volume can also be achieved, particularly in the superior and inferior regions of the breast. It remains to be seen whether the dosimetric improvements achievable with IMRT will lead to significant clinical outcome improvements.

Quantification and predictors of prostate position variability in 50 patients evaluated with multiple CT scans during conformal radiotherapy.

PURPOSE: To determine the extent and predictors for prostatic motion in a large number of patients evaluated with multiple CT scans during radiotherapy, and evaluate the implications of these data on the design of appropriate treatment margins for patients receiving high-dose three-dimensional conformal radiotherapy. MATERIALS AND METHODS: Fifty patients underwent four serial computerized tomography (CT) scans, consisting of an initial planning scan and subsequent scans at the beginning, middle, and end of the treatment course. Each scan was performed with the patient in the prone treatment position within an immobilization device used during therapy. Contours of the prostate and seminal vesicles were drawn on the axial CT slices of each scan, and the scans were matched by alignment of the pelvic bones with a chamfer matching algorithm. Using the contour information, distributions of the displacement of the organ center of mass and organ border from the planning position were determined separately for the prostate and seminal vesicles in each of the three principle directions: anterior-posterior (AP), superior-inferior (SI) and left-right (LR). Each distribution was fitted to a normal (Gaussian) distribution to determine confidence limits in the center of mass and border displacements and thereby evaluate for the optimal margins needed to contain target motion. RESULTS: The most common directions of displacement of the prostate center of mass (COM) were in the AP and SI directions and were significantly larger than any LR movement. The mean prostate COM displacement (+/- 1 standard deviation, SD) for the entire population was -1.2 +/- 2.9 mm, -0.5 +/- 3.3 mm and -0.6 +/- 0.8 mm in the, AP and SI and LR directions respectively (negative values indicate posterior, inferior or left displacement). The mean (+/- 1 SD) seminal vesicle COM displacement for the entire population was - 1.4 +/- 4.9 mm, 1.3 +/- 5.5 mm and -0.8 +/- 3.1 mm in the AP and SI and LR directions, respectively. The data indicate a tendency for the population towards posterior displacements of the prostate from the planning position and both posterior and superior displacements of the seminal vesicles. AP movement of both the prostate and seminal vesicles were correlated with changes in rectal volume (P = 0.0014 and < 0.0001, respectively) more than with changes in bladder volume (P = 0.030 for seminal vesicles and 0.19 for prostate). A logistic regression analysis identified the combination of rectal volume > 60 cm3 and bladder volumes > 40 cm3 as the only predictor of large ( > 3 mm) systematic deviations for the prostate and seminal vesicles (P = 0.05) defined for each patient as the difference between organ position in the planning scan and mean position as calculated from the three subsequent scans. CONCLUSIONS: Prostatic displacement during a course of radiotherapy is more pronounced among patients with initial planning scans with large rectal and bladder volumes. Such patients may require more generous margins around the CTV to assure its enclosure within the prescription dose region. Identification and correction of patients with large systematic errors will minimize the extent of the margin required and decrease the volume of normal tissue exposed to higher radiation doses.

Psychotic symptoms in combat-related posttraumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is known often to be comorbid with other anxiety, mood, and substance use disorders. Psychotic symptoms have also been noted in PTSD and have been reported to be more common in Hispanic veterans. However, the occurrence of psychotic symptoms, including the degree to which they are accounted for by comorbid disorders, have received limited systematic investigation. Our study objectives were to assess psychotic symptoms according to DSM-III-R criteria in patients with a primary diagnosis of combat-related PTSD and determine the associations of those symptoms with psychiatric comorbidity and ethnicity. METHOD: Fifty-three male combat veterans consecutively admitted to a PTSD rehabilitation unit were assessed for psychotic symptoms and Axis I disorders. Ninety-one percent were Vietnam veterans; 72% were white, 17% were Hispanic, and 11% were black. Associations between psychotic symptoms and comorbid depression, substance use disorders, and minority status were compared by chi-square analyses; associations between psychotic symptoms and both PTSD and dissociative symptom severity were compared by t test analysis. RESULTS: Forty percent of patients reported a psychotic symptom or symptoms in the preceding 6 months. These symptoms featured auditory hallucinations in all but 1 case. The psychotic symptoms typically reflected combat-themes and guilt, were nonbizarre, and were not usually associated with formal thought disorder or flat or inappropriate affect. Psychotic symptoms were significantly associated with current major depression (p < .02), but not with alcohol or drug abuse or with self-rated PTSD and dissociation severity. Psychotic symptoms and current major depression were more common in minority (black and Hispanic) than white veterans (p < .002). CONCLUSION: Psychotic symptoms can be a feature of combat-related PTSD and appear to be associated with major depression. The association with minority status may be a function of comorbidity.

Computerized design of target margins for treatment uncertainties in conformal radiotherapy.

PURPOSE: We describe a computerized method of determining target margins for beam aperture design in conformal radiotherapy plans. MATERIALS AND METHODS: The method uses previously measured data from a population of patients to simulate setup error and organ motion in the patient currently being planned. Starting with a clinical target volume (CTV) and nontarget organs from the patient's planning CT scan, the simulation is repeated many times to produce a spatial probability distribution for each organ in the treatment machine coordinate system. This is used to determine a prescribed dose volume (PDV), defined as the volume to receive the prescribed dose, which encompasses the CTV while restricting the volume of nontarget organs within it, according to planner-specified values. The PDV is used to design beam apertures using a conventional margin for beam penumbra. RESULTS: The method is applied to 6-field prostate conformal treatment plans, in which the PDV encloses the prostate and seminal vesicles while limiting the enclosed rectal wall volume. The effect of organ motion is assessed by applying the plans on subsequent CT scans of the same patients, calculating probabilities for tumor control (TCP) and normal tissue complication (NTCP), and comparing with plans designed from a physician-drawn planning target volume (PTV). Although prostate TCP and rectal wall NTCP are found to be similar in the two sets of plans, TCP for the seminal vesicles is significantly higher in the PDV-based plans. CONCLUSIONS: The method can improve the dose conformality of treatment plans by incorporating population-based measurements of treatment uncertainties and consideration of nontarget tissues in the design of nonuniform target margins.

American Association of Physicists in Medicine Radiation Therapy Committee Task Group 53: quality assurance for clinical radiotherapy treatment planning.

In recent years, the sophistication and complexity of clinical treatment planning and treatment planning systems has increased significantly, particularly including three-dimensional (3D) treatment planning systems, and the use of conformal treatment planning and delivery techniques. This has led to the need for a comprehensive set of quality assurance (QA) guidelines that can be applied to clinical treatment planning. This document is the report of Task Group 53 of the Radiation Therapy Committee of the American Association of Physicists in Medicine. The purpose of this report is to guide and assist the clinical medical physicist in developing and implementing a comprehensive but viable program of quality assurance for modern radiotherapy treatment planning. The scope of the QA needs for treatment planning is quite broad, encompassing image-based definition of patient anatomy, 3D beam descriptions for complex beams including multileaf collimator apertures, 3D dose calculation algorithms, and complex plan evaluation tools including dose volume histograms. The Task Group recommends an organizational framework for the task of creating a QA program which is individualized to the needs of each institution and addresses the issues of acceptance testing, commissioning the planning system and planning process, routine quality assurance, and ongoing QA of the planning process. This report, while not prescribing specific QA tests, provides the framework and guidance to allow radiation oncology physicists to design comprehensive and practical treatment planning QA programs for their clinics.

Locally advanced prostatic cancer: long-term toxicity outcome after three-dimensional conformal radiation therapy--a dose-escalation study.

PURPOSE: To determine the long-term effects of 75.6- and 81.0-Gy doses of three-dimensional conformal radiation therapy in a dose-escalation study in patients with stage T2c-T3 prostatic cancer. MATERIALS AND METHODS: Fifty patients received an initial 75.6-Gy dose, and the dose in 46 patients was subsequently escalated to 81.0-Gy. Median follow-up was 60 and 40 months, respectively. RESULTS: The rates of effects of acute toxicity during the course of treatment were similar for both dose levels. Among the 96 patients, the rate of grade 2 morbidities necessitating medication to relieve acute symptoms was 17% (16 patients) for rectal and 36% (35 patients) for urinary morbidities. All other patients had either no or grade 1 morbidities. Fourteen patients (15%) developed late grade 2 rectal morbidities. There were no differences in 5-year actuarial rates of late grade 2 rectal or urinary morbidities among patients who received 75.6 Gy versus those who received 81.0 Gy. One patient treated with 81.0 Gy developed a grade 3 urethral stricture, which was resolved with dilatation. CONCLUSION: Tumor dose escalation beyond conventional radiation doses for localized prostatic cancer is feasible when delivered with three-dimensional conformal radiation therapy, with no increase in morbidity in normal tissue.

Dose escalation with three-dimensional conformal radiation therapy affects the outcome in prostate cancer.

PURPOSE: Three-dimensional conformal radiation therapy (3D-CRT) is a technique designed to deliver prescribed radiation doses to localized tumors with high precision, while effectively excluding the surrounding normal tissues. It facilitates tumor dose escalation which should overcome the relative resistance of tumor clonogens to conventional radiation dose levels. The present study was undertaken to test this hypothesis in patients with clinically localized prostate cancer. METHODS AND MATERIALS: A total of 743 patients with clinically localized prostate cancer were treated with 3D-CRT. As part of a phase I study, the tumor target dose was increased from 64.8 to 81 Gy in increments of 5.4 Gy. Tumor response was evaluated by post-treatment decrease of serum prostate-specific antigen (PSA) to levels of < or = 1.0 ng/ml and by sextant prostate biopsies performed > or = 2.5 years after completion of 3D-CRT. PSA relapse-free survival was used to evaluate long-term outcome. The median follow-up was 3 years (range: 1-7.6 years). RESULTS: Induction of an initial clinical response was dose-dependent, with 90% of patients receiving 75.6 or 81.0 Gy achieving a PSA nadir < or = 1.0 ng compared with 76% and 56% for those treated with 70.2 Gy and 64.8 Gy, respectively (p < 0.001). The 5-year actuarial PSA relapse-free survival for patients with favorable prognostic indicators (stage T1-2, pretreatment PSA < or = 10.0 ng/ml and Gleason score < or = 6) was 85%, compared to 65% for those with intermediate prognosis (one of the prognostic indicators with a higher value) and 35% for the group with unfavorable prognosis (two or more indicators with higher values) (p < 0.001). PSA relapse-free survival was significantly improved in patients with intermediate and unfavorable prognosis receiving > or = 75.6 Gy (p < 0.05). A positive biopsy at > or = 2.5 years after 3D-CRT was observed in only 1/15 (7%) of patients receiving 81.0 Gy, compared with 12/25 (48%) after 75.6 Gy, 19/42 (45%) after 70.2 Gy, and 13/23 (57%) after 64.8 Gy (p < 0.05). CONCLUSIONS: The data provide evidence for a significant effect of dose escalation on the response of human prostate cancer to irradiation and defines new standards for curative radiotherapy in this disease.

Three-dimensional conformal radiotherapy and dose escalation: where do we stand?

Three-dimensional conformal radiotherapy is an effective means of delivering high doses of radiation with enhanced precision. Several institutions have gained substantial experience using this modality for patients with clinically localized prostate cancer. Reports from these centers have demonstrated not only excellent tolerance despite the administration of higher radiation doses, but improved biochemical and local control outcomes as well. Meticulous attention to treatment technique and dose volume histogram analysis are critical for the safe implementation of these higher doses. The emergence of intensity-modulated treatment planning has provided the opportunity at our institution to further escalate the radiation dose to 86.4 Gy while still respecting the surrounding normal tissue tolerance. Phase I studies will need to continue to define more clearly the maximal dose of radiation that can be delivered safely with this modality. Current studies indicate a direct correlation between dose and prostate-specific antigen (PSA) relapse-free survival response for patients with intermediate and high-risk prognostic features. These patients likely represent the ideal cohort for future studies designed to investigate the impact of dose on biochemical and disease-free survival outcome.

A feasibility study of automated inverse treatment planning for cancer of the prostate.

PURPOSE: The development of automated "inverse planning," utilizing intensity-modulated radiation therapy (IMRT) raises the question of whether this new technique can provide a practical and efficient means of dose escalation in conformal treatment of cancer of the prostate. The purpose of this feasibility study was to determine a single set of inverse-planning parameters that can be used for a variety of different prostate patient geometries to automatically generate escalated dose (> or = 81 Gy) IMRT plans that satisfy normal tissue constraints for rectal and bladder walls. METHODS: We studied a subset of the 46 patients who were previously treated at Memorial Sloan Kettering Cancer Center (MSKCC) to a total dose of 81 Gy using a 3D conformal approach. Six patients were selected for our study and replanned using an analytical inverse-planning algorithm (referred to as OPT3D) applied to 8 intensity modulated, co-axial radiation beams. A set of more than a dozen inverse planning parameters were adjusted by trial and error until the resulting dose distributions satisfied the critical organ dose-volume constraints imposed by our study rules (D30 < or = 75.6 Gy and D10 < or = 80 Gy for the rectal wall; D15 < or = 80 Gy for the bladder wall) for the sample of patients selected. The OPT3D-generated plans were compared to hand-generated BEV plans using cumulative DVH analysis. RESULTS: A single set of inverse-planning parameters was found that was able to automatically generate IMRT plans meeting all critical organ dose-volume constraints for all but one of the patients in our study. [The exception failed to meet bladder dose constraints for both IMRT and BEV methods, due to extensive overlap between the planning target volume (PTV) and bladder contours]. Based upon analysis of the cumulative dose-volume histogram (DVH) for the prostate PTV, the D95 (DX is defined such that x% of the volume receives a dose > or = DX), averaged over all patients, was approximately 81 Gy. The average D90 and mean dose values were 85 Gy and 93 Gy, respectively. Although a similar D95 was achieved using the BEV-generated plans, the D90 and mean dose values were substantially higher for the inverse planning (OPT3D) method. CONCLUSION: This limited "paper study" shows IMRT with inverse planning to be a promising technique for the treatment of prostate cancer to high doses. We determined a small set of inverse-planning parameter values that was able to automatically design intensity-modulated radiotherapy (IMRT) plans for a subset of 6 patients previously treated at MSKCC to 81 Gy using BEV planning techniques. With one minor exception, the resulting plans succeeded in meeting predetermined dose-volume constraints while at the same time allowing an increase in the mean dose and D90 to the prostate PTV. These 8 field plans also resulted in reduced dosage to the femoral heads. This automated technique is efficient in terms of planning effort and, with proper software for computer-controlled MLC, may be appropriate for clinical use. The clinical feasibility of this approach for a larger group of patients is currently under study.

Planning, delivery, and quality assurance of intensity-modulated radiotherapy using dynamic multileaf collimator: a strategy for large-scale implementation for the treatment of carcinoma of the prostate.

PURPOSE: To improve the local control of patients with adenocarcinoma of the prostate we have implemented intensity modulated radiation therapy (IMRT) to deliver a prescribed dose of 81 Gy. This method is based on inverse planning and the use of dynamic multileaf collimators (DMLC). Because IMRT is a new modality, a major emphasis was on the quality assurance of each component of the process and on patient safety. In this article we describe in detail our procedures and quality assurance program. METHODS AND MATERIALS: Using an inverse algorithm, we have developed a treatment plan consisting five intensity-modulated (IM) photon fields that are delivered with DMLC. In the planning stage, the planner specifies the number of beams and their directions, and the desired doses for the target, the normal organs and the "overlap" regions. Then, the inverse algorithm designs intensity profiles that best meet the specified criteria. A second algorithm determines the leaf motion that would produce the designed intensity pattern and produces a DMLC file as input to the MLC control computer. Our quality assurance program for the planning and treatment delivery process includes the following components: 1) verification of the DMLC field boundary on localization port film, 2) verification that the leaf motion of the DMLC file produces the planned dose distribution (with an independent calculation), 3) comparison of dose distribution produced by DMLC in a flat phantom with that calculated by the treatment planning computer for the same experimental condition, 4) comparison of the planned leaf motions with that implemented for the treatment (as recorded on the MLC log files), 5) confirmation of the initial and final positions of the MLC for each field by a record-and-verify system, and 6) in vivo dose measurements. RESULTS: Using a five-field IMRT plan we have customized dose distribution to conform to and deliver 81 Gy to the PTV. In addition, in the overlap regions between the PTV and the rectum, and between the PTV and the bladder, the dose is kept within the tolerance of the respective organs. Our QA checks show acceptable agreement between the planned and the implemented leaf motions. Correspondingly, film and TLD dosimetry indicates that doses delivered agrees with the planned dose to within 2%. As of September 15, 1996, we have treated eight patients to 81 Gy with IMRT. CONCLUSION: For complex planning problems where the surrounding normal tissues place severe constraints on the prescription dose, IMRT provides a powerful and efficient solution. Given a comprehensive and rigorous quality-assurance program, the intensity-modulated fields can be efficaciously and accurately delivered using DMLC. IMRT treatment is now ready for routine implementation on a large scale in our clinic.