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Purpose To integrate imaging performance characteristics, specifically sensitivity and specificity, of magnetic resonance angiography (MRA) and digital subtraction angiography (DSA) into arteriovenous malformation (AVM) radiosurgery planning and evaluation. Methods and Materials Images of 10 patients with AVMs located in critical brain areas were analyzed in this retrospective planning study. The image findings were first used to estimate the sensitivity and specificity of MRA and DSA. Instead of accepting the imaging observation as a binary (yes or no) mapping of AVM location, our alternative is to translate the image into an AVM probability distribution map by incorporating imagers' sensitivity and specificity, and to use this map as a basis for planning and evaluation. Three sets of radiosurgery plans, targeting the MRA and DSA positive overlap, MRA positive, and DSA positive were optimized for best conformality. The AVM obliteration rate (ORAVM) and brain complication rate served as endpoints for plan comparison. Results In our 10-patient study, the specificities and sensitivities of MRA and DSA were estimated to be (0.95, 0.74) and (0.71, 0.95), respectively. The positive overlap of MRA and DSA accounted for 67.8% ± 4.9% of the estimated true AVM volume. Compared with plans targeting MRA and DSA–positive overlap, plans targeting MRA-positive or DSA-positive improved ORAVM by 4.1% ± 1.9% and 15.7% ± 8.3%, while also increasing the complication rate by 1.0% ± 0.8% and 4.4% ± 2.3%, respectively. Conclusions The impact of imagers' quality should be quantified and incorporated in AVM radiosurgery planning and evaluation to facilitate clinical decision making.

Purpose: To investigate how the performance characteristics of ultrasound tissue typing (UTT) affect the design of a population-based prostate dose-painting protocol. Methods and Materials: The performance of UTT is evaluated using the receiver operating characteristic curve. As the imager's sensitivity increases, more tumors are detected, but the specificity worsens, causing more false-positive results. The UTT tumor map, obtained with a specific sensitivity and specificity setup, was used with the patient's CT image to guide intensity-modulated radiotherapy (IMRT) planning. The optimal escalation dose to the UTT positive region, as well as the safe dose to the negative background, was obtained by maximizing the uncomplicated control ( i.e. , a combination of tumor control probability and weighted normal tissue complication probability). For high- and low-risk tumors, IMRT plans guided by conventional ultrasound or UTT with a one-dimensional or two-dimensional spectrum analysis technique were compared with an IMRT plan in which the whole prostate was dose escalated. Results: For all imaging modalities, the specificity of 0.9 was chosen to reduce complications resulting from high false-positive results. If the primary tumors were low risk, the IMRT plans guided by all imaging modalities achieved high tumor control probability and reduced the normal tissue complication probability significantly compared with the plan with whole gland dose escalation. However, if the primary tumors were high risk, the accuracy of the imaging modality was critical to maintain the tumor control probability and normal tissue complication probability at acceptable levels. Conclusion: The performance characteristics of an imager have important implications in dose painting and should be considered in the design of dose-painting protocols.

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 (≥ Grade 2) before 30 months, and nonbleeding (⩽ 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 (VRW) was removed by calculating the average differences in DVHs between all combinations of bleeding and nonbleeding patients with similar VRWs. 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 VRWs 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 VRWs, 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 VRW: 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 VRW 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 VRW 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 (∼ 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.

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.

Purpose: To prospectively assess the effect of supine vs. prone treatment position on the dose to normal tissues in prostate cancer patients treated with the three-dimensional conformal technique. Methods and Materials: Twenty-six patients underwent three-dimensional treatment planning in both the supine and prone treatment positions. The planning target volume and normal tissue structures were outlined on each CAT scan slice, and treatment plans were compared to assess the effect of treatment position on the volume of rectum, bladder, and bowel exposed to the high doses of irradiation. Results: The average dose to the rectal wall and the V95 (volume of rectal wall receiving at least 95% of the prescription dose) for the prone position were 64 and 24% of the prescription dose, respectively, compared to 72 and 29%, respectively, for the supine position (p < 0.05). When the average rectal wall dose was used as an endpoint, 14 of the 26 patients (54%) had an advantage for the prone position compared to 1 (4%) who demonstrated and advantage for the supine position (p < 0.0002). Similarly, when V95 of the rectal wall was used as a measure of comparison, 15 patients (58%) had an advantage for the prone position compared to 1 (4%) who demonstrated an advantage for the supine position (p < 0.0002). In 13 patients (50%), a change from spine to the prone position was associated with reduction of the V95 to levels < 30% of the prescription dose compared to 3 patients (11%) in whom such an advantage resulted from change of the prone to the supine position (p < 0.005). The effect of treatment position on the rectal wall dose was most pronounced in the region of the seminal vesicles. An increased volume of bowel was also noted in the supine position. The treatment position, however, had no significant impact on the dose to the bladder wall. Conclusions: Three-dimensional conformal radiotherapy for prostate cancer in the prone position is associated with significant reduction of the dose to the rectum and bowel resulting in an improvement in the therapeutic ratio.

The 1989 Patterns of Care Study included treatment planning for early breast cancer. A Consensus Committee of radiation physicists and oncologists determined current guidelines and developed questionnaires to determine treatment planning and delivery processes used by the participating institutions (e.g., use of portal films). This article presents and analyzes the results of that survey.The survey included 449 respondents, distributed as follows: 136 (30%) from Strata I (academic facilities); 169 (38%) from Strata II (hospital based facilities); and 144 (32%) from Strata III (freestanding facilities). The treatment planning procedures surveyed included: whether individualized tissue compensators are used, whether inhomogeneity corrections are used in dose calculations, the use of computerized tomography, whether isodose distributions for external beam tangents and interstitial implants are generated, the use of lymphoscintigraphy, immobilization devices, simulations, portal films, etc.The survey results demonstrated that out of 305 patients from Strata I and II institutions, 237 (78%) had simulated tangential fields. Consistent with this finding is that 76% of patients from Strata I and II institutions were immobilized, while only 51% of Strata III patients were. Moreover, only 18 out of the 449 (4%) of cases did not have any type of external beam dose distribution calculated--presumably, in these cases missing tissue compensation would be unlikely. On the other hand, 41% of the Strata II, 27% of Strata III, but only 19% of Strata I (p0.0002) cases received CT. Surprisingly, 19% of the Strata I, 35% of the Strata II, and 25% of the Strata III (p = 0.0011) patients received lymphoscintigraphy, perhaps reflecting the use of wide tangents to encompass the internal mammary nodes in these patients. In terms of optimizing treatments, 74% of Strata I, 70% of Strata II, and 78% of Strata III patients had wedges used on both tangential fields, although in 5, 12, and 14%, respectively, no beam modification of any sort was used. Furthermore, it should be noted that in 7% of the Strata I, 23% of Strata II, and 37% of Strata III cases there was no attempt to reduce the divergence of the tangential fields into the lung. On the other hand, if one considers the 135 (of 449) patients where matching of the tangential and supraclavicular fields was applicable, 41% of Strata I, 22% of Strata II and 46% of Strata III patients had those fields matched in a vertical plane, which would involve sophisticated alignment procedures. Quality control of treatment delivery was high: 97% of all surveyed received portal films at least once. The use of thermoluminescent dosimetry (TLD) to measure the dose to the contralateral breast was of little interest: only 4 of the 305 Strata I and II patients received in vivo measurements.This national survey has established the patterns of treatment planning for early breast cancer. It shows a generally consistent approach-although a number of statistically significant variations have been identified.

Purpose : We describe a method of incorporating organ motion into three-dimensional (3D) conformal treatment plans, which predict the effect of organ motion on the calculated dose to both the clinical target volume (CTV) and nontarget organs. Methods and Materials : The method is based on measurements of organ motion by means of multiple computed tomography (CT) scans from a group of “reference” patients, in which the data consist of previously drawn contours of the target and nontarget organs. A computer program records the differences in contour position and shape that occurs between scans in the reference data, and according to those differences adjusts the contours and dose calculation points of a study” patient currently being planned, thus simulating organ motion. Dose-volume histograms (DVHs) are accumulated, and the process is repeated over the set of reference patient scans, resulting in a set of treatment plans that are ranked according to a dose-based endpoint. Two plans are selected corresponding to specified lower and upper confidence limits in the endpoint, and the DVHs from these plans are displayed for comparison with the DVHs from the nominal plan in the absence of motion. Results | As an example of the method's use, it is applied to a 6-field conformal treatment plan for prostate cancer. Confidence limit DVHs of the CTV and rectal wall (in which the plans were ranked by probabilities for tumor control and normal tissue complication, respectively) are presented and compared to those from the nominal plan. Conclusion : The method provides a means of estimating the uncertainty in dose delivered by a treatment plan when organ motion is present. It is generally applicable to any treatment site for which data in the form of multiple CT scans are available, and can be extended to include other treatment uncertainties such as variation in patient positioning.

Purpose : To analyze the effect that immobilization devices used in conjunction with beam modifiers may have on the dose to the skin and build-up region. Methods and Materials : Central axis depth dose measurements were made in a polystyrene phantom in the build-up regions using the 6 and 15 MV photon beams, at two different source-to-phantom distances, and various field sizes. The effects of acrylic blocking trays, lead wedges, and cerrobend blocks were assessed in conjunction with the enhancement of dose in the build-up region due to immobilizing devices using plaster and thermoplastic casting materials of different thicknesses. Results : For the 6 MV photons, solid (3 mm) thermoplastic casting material was found to have the greatest effect on surface dose: for a 12 × 12 cm field we measured 79% of maximum dose when treating through the material versus 22% of maximum dose when no beam modifiers or immobilization devices are used. Measurements were also made to evaluate the effect of the immobilization of patients receiving three-dimensional conformal treatments using a 15 MV photon beam. Conclusions : The relevance of these results to treatments in the pelvis, breast, and head and neck regions is discussed. For 6 MV beams, special consideration should be given if the need arises to treat through the immobilization device, as unacceptable skin reactions may result.

We investigate the use of a multi-leaf collimator for conformal radiation therapy of carcinomas of the prostate and of the nasopharynx. Following verification of dose calculation algorithms for multi-leaf collimated fields using film dosimetry, we compute dose distributions for multi-field conformal treatment using fields shaped with either the multi-leaf collimator or conventional cerrobend blocks. We compare the two sets of treatment plans using graphical isodose displays, tissue specific dose volume histograms, tumor control probabilities, and normal tissue complication probabilities. We also incorporate setup errors into the calculated dose distributions to assess the effect of treatment uncertainties on the various criteria. Based on these comparisons, we conclude that for multi-field conformal radiotherapy for these two disease sites, the use of multi-leaf collimation is equivalent to that of conventional cerrobend blocks.

The recent introduction of new computer technology for treatment planning and computer-driven treatment delivery systems, such as multi-leaf collimators and on-line verification systems, has accelerated the development of 3-dimensional (3-D) radiation therapy as a modality for curative cancer treatment. The goal of 3-D treatment planning is to conform the spatial distribution of the high radiation dose to the shape of the tumor contour while concomitantly decreasing the volume of the surrounding normal tissues receiving high radiation doses. The improved precision of tumor coverage and the exclusion of normal tissues should permit tumor dose escalation and may enhance local tumor control. It has been suggested that any survival gains derived from improvements in local control may be offset by the subsequent appearance of distant metastases arising from micrometastases already present at the time of initial diagnosis. However, clinical and laboratory studies indicate that failure to control the primary tumor at the time of initial treatment significantly increases the incidence of metastatic dissemination. This phenomenon is consistent with the hypothesis that the enhanced mitotic activity associated with the re-growth process of locally recurring primary tumors promotes the multi-step transformation of non-metastatic tumor cells into clonogens with metastatic potential, leading to increased overall rates of metastatic disease. These biologic considerations provide support for the need to focus attention on the identification of more effective therapeutic strategies designed to eradicate the primary local tumor completely at the time of initial therapy and serve as the rationale for clinical studies using 3-D conformal radiation therapy.

This study was designed to demonstrate the feasibility of 3-dimensional (3D) treatment planning in patients with carcinoma of the nasopharynx, and to explore its potential therapeutic advantage over the traditional 2-dimensional (2D) approach in this disease. Qualitative and quantitative comparisons between the two techniques were made for the boost portion of the treatment (19.8 Gy of a total 70.2 Gy treatment schedule) in 10 previously untreated patients and for the entire treatment in 5 patients with locally recurrent disease. The 2D and 3D plans were compared in each patient using dose-volume histograms (DVH's), tumor control probabilities (TCP's), normal tissue complication probabilities (NTCP's), and a new biologic figure of merit that describes the probability of uncomplicated control. Although there was no attempt to optimize the 313 treatment approach by using this method throughout the total treatment course (rather than for the boost only), it was still found that for each of the endpoints examined the 3D approach resulted in improved plans. An average of 22% of the target volume was underdosed at the 95% isodose level with the 2D plans compared to 7% with the 3D plans. The improved treatment planning by 3D increased the mean dose to the tumor volume by an average of 13% over 2D planning. The dose to normal structures such as the mandible and parotid glands was reduced with the 3D plans while the brain stem and spinal cord remained within tolerance limits. The probability of uncomplicated tumor control was increased by an average of 15% with 3D treatment planning compared to the 2D approach. Our findings demonstrate the potential of 3D planning for improving the treatment of carcinoma of the nasopharynx, but prospective studies are required to define the true clinical advantages of this methodology.

This paper presents a technique for producing uniform dose distributions within the target volume with noncoplanar field arrangements. The method is based upon the principle used for producing homogeneous dose distributions for a pair of fields in two dimensions, namely, that if the isodose distributions for the fields are made parallel to one another, the combined dose distribution will be uniform. For the three-dimensional non-coplanar case, homogeneous target dose distributions are obtained by designing field modifiers which produce a uniform dose distribution on the perpendicular bisector plane for each pair of fields. It is demonstrated that for three noncoplanar fields irradiating a spherical phantom with spherical target volumes, the target dose distribution will be homogeneous for any arbitrary non-coplanar field arrangement. Furthermore, this technique can be extended to any number of fields. Therefore, target dose distributions for non-coplanar plans can be as homogeneous as the coplanar case. An example of the application of the method to the treatment of rectal carcinoma with non-coplanar fields is given. Furthermore, it is demonstrated that the therapeutic ratio is improved over traditional methods for this clinical example.

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 ∼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.

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.

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.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 ofor = 1.0 ng/ml and by sextant prostate biopsies performedor = 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).Induction of an initial clinical response was dose-dependent, with 90% of patients receiving 75.6 or 81.0 Gy achieving a PSA nadiror = 1.0 ng compared with 76% and 56% for those treated with 70.2 Gy and 64.8 Gy, respectively (p0.001). The 5-year actuarial PSA relapse-free survival for patients with favorable prognostic indicators (stage T1-2, pretreatment PSAor = 10.0 ng/ml and Gleason scoreor = 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) (p0.001). PSA relapse-free survival was significantly improved in patients with intermediate and unfavorable prognosis receivingor = 75.6 Gy (p0.05). A positive biopsy ator = 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 (p0.05).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.

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 (≥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 ≤ 75.6 Gy and D10 ≤ 80 Gy for the rectal wall; D15 ≤ 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 ≥ 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.

Purpose/Objective: To determine the spatial distribution of setup errors for patients treated with six-field, three-dimensional (3D) conformal radiation therapy for prostate cancer. Methods and Materials: Port films for 50 patients were analyzed retrospectively. The port films were digitized and compared, using image registration software, to simulator films (representing the ideal treatment position). Patient positioning uncertainty for a given setup was determined using port films from three projections, two obliques, and one lateral. A total of 1239 port films and 300 simulator films were analyzed for the study. Patient position was analyzed for out-of-plane rotations and time trends over the course of treatment. Results: The distribution of systematic setup errors for the 50 patients, defined as the mean patient displacement for the treatment course, had a mean and standard deviation (SD) of (−0.1 ± 1.9) mm, and (−0.3 ± 1.3)mm in the mediolateral (ML), superior-inferior (SI) and anterior-posterior (AP) directions, and (−0.1 ± 0.2) for rotational errors. The distribution of random setup errors about the mean approximated a normal distribution and the standard deviations for the population of patients in the ML, SI, and AP directions, were 2.0 mm, 1.7 mm, and 1.9 mm, respectively. The distribution of out-of-plane rotations had 1 SD of 0.9° and 0.6° about the SI and AP axes. Ten of the 50 patients demonstrated a statistically significant time trend in their setup position resulting in shifts ranging from 2 to 7 mm. Conclusions: The setup verification protocol appears to minimize systematic setup errors to a level that approaches the sensitivity of the image registration techique. The random day to day fluctuations, represented by the average values of the standard deviations, are minor in comparison to the currently used margins, which further emphasizes the effectiveness of this protocol in conjunction with the use of the immobilization device.

Purpose : To implement radiotherapy with intensity-modulated beams, based on the inverse method of treatment design and using a multileaf collimation system operating in the dynamic mode. Methods and Materials : An algorithm, based on the inverse technique, has been integrated into the radiotherapy treatment-planning computer system in our Center. This method of computer-assisted treatment design was used to derive intensity-modulated beams to optimize the boost portion of the treatment plan for a patient with a T1c cancer of the prostate. A dose of 72 Gy (in 40 fractions) was given with a six-field plan, and an additional 9 Gy (in five fractions) with six intensity-modulated beams. The intensity-modulated fields were delivered using dynamic multileaf collimation 1 , that is, individual leaves were in motion during radiation delivery, with the treatment machine operating in the clinical mode. Exhaustive quality assurance measurement and monitoring were carried out to ensure safe and accurate implementation. Results : Dose distribution and dose-volume histogram of the inverse method boost plan and of the composite (72 Gy primary + 9 Gy boost) plan were judged clinically acceptable. Compared to a manually designed boost plan, the inverse treatment design gave improved conformality and increased dose homogeneity in the planning target volume. Film and ion chamber dosimetry, performed prior to the first treatment, indicated that each of the six intensity-modulated fields was accurately produced. Thermoluminescent dosimeter (TLD) measurements performed on the patient confirmed that the intended dose was delivered in the treatment. In addition, computer-aided treatment-monitoring programs assured that the multileaf collimator (MLC) position file was executed to the specified precision. In terms of the overall radiation treatment process, there will likely be labor savings in the planning and the treatment phases. Conclusions : We have placed into clinical use an integrated system of conformal radiation treatment that incorporated the inverse method of treatment design and the use of dynamic multileaf collimation to deliver intensity-modulated beams. The system can provide better treatment design, which can be implemented reliably and safely. We are hopeful that improved treatment efficacy will result.

PURPOSE Rotations of the patient out of the image plane can significantly degrade the accuracy of two-dimensional (2D) image registration. This study determines the magnitude of the geometric errors introduced by 2D image registration as a result of out-of-plane rotations, and analyzes the dosimetric effects of these errors. METHODS AND MATERIALS The magnitude of the errors introduced by 2D registration were determined by comparing orthogonal view portal images of a rotated phantom to simulator reference images of the same phantom without rotation. Dosimetric effects were calculated for three-dimensional (3D) conformal prostate treatments by applying the registration errors to patient treatment plans. The calculations were performed using a modified version of the dose calculation software used in our Cancer Center for 3D treatment planning based on computed tomography (CT). A method to detect out-of-plane rotations, specific to pelvic treatments, is introduced that uses the relative displacement of the centers of gravity of the acetabula in lateral images. RESULTS The inherent uncertainty in the registration algorithm was 0.6 +/- 0.5 mm in translation and 0.7 +/- 0.8 degree in rotation within the image plane. For a 2 degrees out-of-plane rotation, the errors increase to 2.3 +/- 1.0 mm and 1.2 +/- 1.1 degrees. In some clinically realizable treatment scenarios it was observed that the errors introduced by the registration procedure could result in an overdosing of the rectal wall. The method to detect out-of-plane rotations was found to have an accuracy of better than 1 degree for rotations of less than 10 degrees. CONCLUSIONS The errors introduced to the patient position by 2D image registration have dosimetrically significant consequences for out-of-plane rotations of 2 degrees or more. However, when used in conjunction with the method to detect out-of-plane rotations, 2D registration software was found to cause insignificant dose errors and, thus, become a more reliable and accurate clinical tool.

Purpose : To study the attenuation and scattering effects of ocular implants, made from different materials, on the dose distributions of a 6 MV photon beam, and 6, 9, and 12 MeV electron beams used in orbital radiotherapy. Methods and Materials : Central axis depth-dose measurements were performed in a polystyrene phantom with embedded spherical ocular implants using film dosimetry of a 6 MV photon beam and electron beams of 6, 9, and 12 MeV energy. The isodose distributions were also calculated by a computerized treatment planning system using computerized tomography (CT) scans of a polystyrene phantom that had silicone, acrylic, and hydroxyapatite ocular implants placed into it. Results : Electron beam dose distributions display distortions both on the measured and calculated data. This effect is most accentuated for the hydroxyapatite implants, for which the transmissions through ocular implants are on the order of 93% for the 6 MV photon beam, and range from 60% for 6 MeV electrons to 90% for 12 MeV electrons. Conclusion : We studied the effect of ocular implants of various materials, embedded in a polystyrene phantom, on the dose distributions of a 6 MV photon beam, and 6, 9, and 12 MeV electron beams. Our investigations show that while 6 MV photons experience only a few percent attenuation, lower energy electron beam with 60% transmission is not a suitable choice of treating tumors behind the ocular implants.

Purpose To compare the misalignment error due to the fabrication of custom lead alloy blocks with the displacement error introduced by the finite resolution of a multileaf collimator relative to the prescribed smooth apertures. Methods and materials Treatment field apertures for randomly selected patients for four clinical sites were obtained at various stages of the block fabrication process. These apertures and the corresponding multileaf collimator (MLC) apertures for each field were superimposed with the smooth apertures prescribed by physicians. The deviations from the prescribed apertures were measured at 10 degrees intervals. Comparisons of the magnitude and frequency of errors from block fabrication with those from the geometric displacements introduced by the finite leaf width of the multileaf collimator were made. Results The degree of conformity of the multileaf collimator is treatment-site dependent as, in general, are the shapes of fields. For three of the four sites examined, the multileaf collimator apertures track the prescribed apertures at least as accurately as custom blocking when the block design, construction, mounting, and alignment on the treatment machine are considered. Conclusions The geometric conformality of multileaf collimation is comparable to, and in some cases superior to, that of custom blocks.

Purpose : To conduct a study of the structure and process of treatment planning in the United States. Methods and Materials : A Patterns of Care treatment planning consensus committee developed a survey form that was used to gather data for 106 items relating to the structure and process of treatment planning. These questions were general in nature and not specific to any particular disease site. Seventy-three facilities were randomly selected for site visits from the 1321 radiation therapy facilities in the United States: 21 academic, 26 hospital, and 26 free-standing. During the site visit the facility physicist, assisted by the site-visit physicist, completed the form. Results : Twenty-nine percent of facilities have cobalt-60 machines; 25% have 4 MV linacs; 75% have photon energies in the range of 5–8 mV; and less than 10% have energies greater than 20 MV. Academic facilities led hospital and free-standing facilities by about 30 percentage points in the availability of all electron energies (88 vs. 58%, approximately, in the rage 4–13 MeV and scaling downward to about 60 vs. 30% at the highest energies). The national averages for the availability of Cs-137, Ir-192, and I-125 were 87, 73, and 44%, respectively. Computerized tomography (CT) scanning is not available or not used in 15% of hospital and free-standing facilities. Ninety-six percent of facilities have treatment planning computers; at 10% of facilities physicians do not participate in treatment planning. The estimated national averages of facilities having formal quality assurance (QA) programs for treatment planning systems, simulators, film processors, and blocking systems are 44, 79, 62, and 55%, respectively. Sixty-three percent of facilities obtain independent machine calibrations. Conclusion : This is the first patterns of treatment planning study carried out in the United States and the results reported here will establish a baseline for future studies. The present study has identified some elements that were unexpected, such as the percentage of facilities lacking formal QA programs for treatment planning systems; however, it has not established any impact of such findings. It is recommended that future studies include the availability of new technologies such as multileaf collimation, dynamic wedges, digital portal imaging, and CT simulation. With the increasing nationwide concern with the cost of health care, we must continue to monitor the implementation, use, and impact on treatment outcome of new and expensive technologies.

Purpose : The acute morbidity of doses of 64.8-75.6 Gy and preliminary observations of late complications and tumor response using 3-dimensional conformal radiation therapy in carcinoma of the prostate are assessed. Methods and Materials : 123 patients (Stage A2–12, B1–17, B2–43, C–51) were irradiated to the prostate and seminal vesicles using a 3-dimensional conformal radiation therapy technique. The median follow-up time was 15.2 months. The minimum tumor dose was 64.8–66.6 Gy in 49 patients, 70.2 Gy in 46, and 75.6 Gy in 28. Toxicity was scored according to the Radiation Therapy Oncology Group morbidity grading system. Results : This technique of 3-dimensional conformal radiation therapy was well-tolerated with minimal acute morbidity. Only 32% of patients had grade 2 or 3 acute morbidity requiring short-term medication for relief of urinary symptoms or diarrhea. Only one patient (0.8%) has so far developed a severe (grade 4) late complication. Serum prostate specific antigen concentrations normalized in 67% of patients (64/96) within 1–14 months (median 4.5 months) after treatment and were progressively decreasing at last measurement in an additional 22% (21/96). Abnormal rising prostate specific antigen levels were observed in 15 patients, 11 of whom have already developed other evidence of relapsing disease. Conclusion : Acute toxicity for the doses tested with this 3-dimensional conformal radiation therapy technique is reduced compared to traditional treatment techniques, and the initial tumor response as assessed by prostate specific antigen measurement is highly encouraging with prostate specific antigen levels returning to normal in the majority of patients. Based on these results, a further increase of the dose to 81 Gy has been implemented in accordance with the schema of an ongoing Phase I dose-escalation study.

Purpose: As radiation treatment techniques become more complicated, the need to understand the effect of uncertainties on dose distributions increases. This study investigates the effect of positional uncertainities for patients with nasopharynx carcinoma treated with a multiple field conformal boost technique. Three dimensional setup errors were measured for six patients and the effect on patient dose was evaluated using dose volume histograms. Methods and Materials: A method is presented for determining 3-dimensional translational and rotational setup errors by identifying anatomical landmarks on two treatment field images and their corresponding simulation images. Measurements were made on a daily basis for six patients undergoing conformal treatment. Results: The average magnitude of the tmnsiational errors was between 1.5 and 3 mm while the average distance between simulation and treatment isocenters was 5 mm. Both systematic and random setup errors were observed. Dose volume histograms incorporating these uncertainties for standard parallel opposed and conformal techniques were generated for patients experiencing random and systematic setup errors. Conclusion: The data imply that positional uncertainties effect the daily dose distributions for target and critical structures differently and that the effect may be treatment technique dependent. These results demonstrate the need to measure setup uncertainties for all sites and to develop techniques for incorporating dose uncertainties in treatment plans.

In this issue Lee ef al. (5 ) report that rectal toxicity can be moderated in high-dose therapy of the prostate by reducing the volume of the rectal wall irradiated to a high dose. In their study, 257 patients were treated to isocenter doses in the range of 75 Gy, 88 of whom had rectal shielding blocks added to the lateral fields for the last 10 fractions of a four-field plan. The estimated dose reduction to the anterior rectal wall was 4-5 Gy. This approach reduces the observed rectal Grade 2-3 morbidity from 30 out of 137 (22%) to 6 out of 88 (7%). An unstated implication of this approach is that the dose to the posterior of the prostate is also reduced. This article and other recent work addresses the need to clarify the nature of dose escalation in the application of conformal therapy. Similar to Lee et al. (5)) we have long been aware of the need for dose-volume constraints in escalating the dose to the prostatic target. The “classical” approach uniformly increases the dose to the entire planning target volume (PTV ) until the adjacent organs reach their tolerance level. An alternative approach escalates the dose to almost all of the PTV, while a minor volume of tissue adjacent to a critical normal organ may receive a somewhat lower dose to accommodate the dose-volume constraints of a critical organ. One consequence of this latter strategy is the possibility of delivering a higher mean target dose than would have otherwise been possible. Furthermore, it has been theoretically argued in a model of tumor response by Brahme (3) that-with confined target dose heterogeneity-the mean, rather than the minimum, target dose is the sine qua non of local control. Although this strategy, within limits, may meet the goals of dose escalation in prostate cancer, its validity needs to be tested in prospective studies. In our dose escalation studies for prostate cancer we have adapted the latter approach incorporating two essential features. The first is the use of nonuniform margins around the clinical target volume (CTV) to account for treatment uncertainties: 6 mm adjacent to the rectum and 10 mm elsewhere. An additional margin is added to the beam aperture to account for penumbra. The second is the use of rectal dose-volume data as a constraint on dose escalation. Based upon an analysis of rectal toxicity and rectal wall DVH in our patients, and using other published data (2), we estimated that 75 Gy to 30% of the rectal wall would keep the rate of KTOG Grade 2 rectal complications below 10%. In order to escalate to a prescribed dose of 8 1 Gy we treat the prostate uniformly to as high a dose as possible (72 Gy) and then use a conformal plan with tight margins for an additional 9 Gy such that the composite dose distribution carries less than 30% of the rectal wall to 75 Gy. Detailed DVH calculations in a random sample of 10 (of 44) patients demonstrates that the PTV isocenter dose was increased to 86.7 Gy and the mean dose to 84.8 Gy. The dose inhomogeneity might best be expressed by noting that for the PTV the percent volume receiving 78 Gy (VT8cy) is 96% and the VW+ is 89.5%; while for the CTV the VT8cy is 99.5% and the V8,cy is 95.7%-that is, 4% of the CTV ranges in dose between 78 and 8 1 Gy (unpublished data). Thus, this technique produces high mean and isocenter doses with the exception of a transition zone between the posterior of the prostate and the anterior rectal wall. A full description of the technique and the dosimetry will be forthcoming. This strategy of constrained dose escalation, using the technique discussed above, was implemented by us in 44 patients with Stages T2c and T3 prostate cancer treated to a prescribed dose of 81 Gy. Three patients (7% ) developed late Grade 2 rectal toxicity within a median followup time of 21 months. No higher grade toxicities have been observed (unpublished data). Encouraged by the apparent lack of toxicity, we are beginning a phase II

Materials/Methods: Ultrasonic tissue-typing imaging using spectrum analysis technique reveals the physical properties (e.g., size, shape and stiffness) of biological tissues noninvasively. Two studies were carried out, after IRB approval, to determine how well this ultrasound technique can differentiate cancerous tissues inside the prostate. Ten patients with localized prostate cancer were enrolled in the in vivo study. Each patient was scanned with a conventional transrectal ultrasound (B & K Medical System, Hawk, 7.5 MHz probe) before the brachytherapy procedure. 3-D ultrasound radio-frequency (rf) data were acquired in a sequence of parallel axial scans which were 1 mm apart. Prior prostate needle biopsies were used as the gold standard. For the ex vivo study, prostate specimens were immersed in saline and scanned with the same ultrasound system immediately after radical prostatectomy. Entire surgical specimens were then embedded for histologic examination. The ultrasound rf data were analyzed using a 2-D Fourier transform algorithm. The resulting spectral parameters of both cancerous regions and noncancerous regions were computed to quantitatively assess the prostatic tissue.

Materials and Methods: One hundred and twenty-one patients treated on a phase I/II dose escalation study underwent irradiation directed to the prostate and seminal vesicles. The clinical stage of these patients were as follows: TlC=2 (2%); T2A=5 (4%); T2B=20 (17%); T2C=41 (34%); T3A=17 (14%); T3B=2 (2%); T3C=33 (28%). All patients were treated with a 6 field conformal technique. Seventy-six patients received a prescription dose of 75.6 Gy to the target volume and 45 patients received 81 Gy. The median pretreatment PSA value was 15.4 ng/ml. Toxicity was scored according to the RTOG scheme. The median follow-up was 15 months.

A combined photon-electron beam treatment for diffuse pleural mesothelioma is discussed in this paper. The technique consists of parallel opposed 10 MV X rays prescribed to 4250 cGy using customized blocks to shield the lung. The pleura is then boosted with electrons to a dose of 3600 cGy. The combination yields a TDF of 74 ret to the pleura. As discussed in an earlier paper, this treatment method when combined with subtotal pleurectomy and I-125 implantation leads to improved survivals with minimal complications. The details of this 3-dimensional radiation treatment method were not described in detail. To improve target coverage and local control, the technique has been modified. CT is now used along with simulation plane films to define the entire pleural surface. The target volume has also been extended from the dome to the base of this diaphragm. These changes have led to improved pleural dose distributions; by blocking the liver or stomach, and boosting the crus of the diaphragm with electrons, there is little added morbidity. As is demonstrated by dose volume histograms, we have been able to deliver 4250 cGy 10% to most of the pleura with ; of the lung parenchyma receiving less than 2100 cGy.

Computerized tomography (CT) was used in the pretreatment evaluation of 23 patients who had bronchogenic carcinoma and applied to planning radiation therapy treatments. It was used to supplement conventional radiologic and clinical methods. Major changes in radiation therapy treatment were based on CT scans in nine patients, either through demonstration of larger or smaller treatment volumes or additional sites of disease, including distant metastasis. In two patients, CT scans falsely indicated absence of metastasis or benign rather than malignant disease. Changes in treatment techniques, e.g. electron beams for superficial lesions, were made based on CT scans in an additional eight patients. Follow-up studies were obtained at three-month intervals; however, CT scans did not distinguish conclusively between tumor recurrence and radiation fibrosis of the lung, although the possible value of contrast material was noted.

It is difficult to make an accurate calculation of dose distribution incorporating blocks using a ray model. One approach is to simulate the blocking in a treatment planning distribution by using negatively weighted beams. A second is to employ an external contour. The parameters of the negative beam or contour can be adjusted using empirical dosimetric data. This paper discusses the calculation of the dose distributions using negatively weighted beams and external contours, compares them with measurements in and around blocked areas for a range of field sizes, block sizes, and depths of interest in treatment planning applications, for 60Co, 6 MV, and 10 MV beams, and assesses their applicability.

An estimation of normal tissue complication probability factors is important, particularly for evaluating 3-dimensional treatment plans. A method has been developed to calculate complication probability factors for non-uniformly irradiated normal organs using dose volume histograms and complication probabilities for uniform partial organ irradiation. In the effective volume method each volume element of the histogram is considered independently and subject to a power law dose volume relationship. Thus, a non-uniform dose volume histogram is reduced to a uniform one with an effective volume, and a dose equal to the maximum dose to the organ. The complication probability is then obtained from known complication probabilities for uniform partial organ irradiation. The effective volume histogram transformation method is shown to obey various boundary conditions, and is illustrated by comparing probability calculations for alternative 3-dimensional treatment plans for the pelvis. In addition, the limitations of this histogram reduction method are discussed and compared to other calculational techniques. The use of probability factor calculations in treatment plan evaluation, and their role in numerical scoring is explored.