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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.

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 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.

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.

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., (Copyright 1998 W.B. Saunders Company.)

Purpose: Local failure is a major obstacle to the cure of locally advanced non-small-cell lung cancer. 3-Dimensional conformal radiation therapy (3-DCRT) selects optimal treatment parameters to increase dose to tumor and reduce normal tissue dose, potentially permitting dose escalation. There are several ongoing trials of dose escalation using 3-Dimensional conformal radiation therapy for non-small-cell lung cancer. We performed this analysis to determine if data derived from dose volume histograms could be used as the basis for designing the method of dose escalation in these trials., Methods and Materials: Between 1990 and 1993, 31 patients were treated with 3-DCRT and had complete normal tissue dose volume histograms created as part of the planning process. The stage distribution was stage I/II 13%, stage IIIa in 45%, and stage IIIb in 42%. The median radiation dose to gross disease was 70.2 Gy (52.2-72 Gy). Elective mediastinal irradiation (50.4 Gy) was administered to 52% (16/31) of patients., Results: The major toxicity encountered in this experience was pulmonary. Dose-volume-histogram data were used to analyze the predictors of toxicity and showed a correlation between risk of pulmonary toxicity and indices of dose to lung parenchyma. Grade 3 or higher pulmonary toxicity occurred in 38% (3/8) of pts with >30%of lung volume receiving > or =25 Gy, versus 4% (1/23) of pts. with < or = 30% lung receiving > or = 25 Gy (p=0.04). Grade 3 or higher pulmonary toxicity occurred in 29% (4/14) of patients with a predicted pulmonary normal tissue complication probability of 12% or higher versus 0% (0/17) in patients with a predicted probability of less than 12% (p=0.03). The single fatality occurred in a patient with a calculated pneumonitis probability of 85% and a high percent (49%) lung volume receiving >= 25 GY., Conclusion: This preliminary experience demonstrates a correlation between lung dose-volume-histogram data and the risk of severe pulmonary toxicity. This provides an opportunity to modify the method of radiation dose escalation. Dose-volume-histogram data can allow escalation according to the risk to the lung parenchyma (which is the major organ of concern) rather than escalation according to tumor dose levels. Because of teh major inter-patient variability of intrathoracic tumor bulk and anatomic distribution, this strategy is intuitively appropriate. This approach may facilitate completion of dose escalation studies and identification of maximum tolerable pulmonary dose levels.

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 evaluate the acute morbidity, late toxicity, and response to treatment in patients with prostate cancer treated on a phase I dose-escalation study with three-dimensional conformal radiotherapy., Methods: A group of 432 patients with stages T1c-T3 prostate cancer were treated with three-dimensional conformal radiotherapy targeting the prostate and seminal vesicles, but effectively excluding the surrounding normal tissue structures from the high-dose volume. A minimum tumor dose of 64.8 to 66.6 Gy was given to 89 patients (20%), 70.2 Gy to 199 patients (46%), 75.6 Gy to 98 patients (23%), and 81.0 Gy to 46 patients (11%)., Results: Treatment was well tolerated, and the acute toxicities and long-term complications observed were of minimal severity (grade 1 or 2) regardless of dose. Acute grade 2 rectal symptoms were observed in 15% of patients, whereas 40% developed grade 2 urinary symptoms. Among patients who received from 64.8 to 70.2 Gy, the 2-year actuarial likelihood of grade 2 late toxicity was 2% for rectal and 1% for urinary complications, compared to 11% and 5%, respectively, for those treated with doses ranging from 75.6 to 81 Gy. Only three patients (0.7%) have so far developed severe (grade 3 or 4) late urethral or rectal complications. The rate of prostate-specific antigen normalization from abnormal pretreatment levels to a value of < or = 1.0 ng/mL was used as an endpoint to evaluate the initial response to treatment. When the analysis was restricted to patients with pretreatment prostate-specific antigen levels of < or = 20 ng/mL, patients who received 70.2 Gy had a significantly higher rate of prostate-specific antigen normalization than patients who received 64.8 to 66.6 Gy. Evaluation of the prostate-specific antigen response at 75.6 Gy and 81.0 Gy was not possible because of the short follow-up time in many of these patients., Conclusions: Three-dimensional conformal radiotherapy technique has made it possible safely to escalate radiation doses to unprecedented levels in patients with prostatic cancer. Preliminary evidence for an improved initial prostate-specific antigen response with higher doses indicates a potential for an improved therapeutic ratio with the three-dimensional conformal radiotherapy approach.

Purpose: The detailed knowledge of dose volume distributions available from the three-dimensional (3D) conformal radiation treatment of tumors in the liver (reported elsewhere) offers new opportunities to quantify the effect of volume on the probability of producing radiation hepatitis. We aim to test a new parallel architecture model of normal tissue complication probability (NTCP) with these data., Methods and Materials: Complication data and dose volume histograms from a total of 93 patients with normal liver function, treated on a prospective protocol with 3D conformal radiation therapy and intraarterial hepatic fluorodeoxyuridine, were analyzed with a new parallel architecture model. Patient treatment fell into six categories differing in doses delivered and volumes irradiated. By modeling the radiosensitivity of liver subunits, we are able to use dose volume histograms to calculate the fraction of the liver damaged in each patient. A complication results if this fraction exceeds the patient's functional reserve. To determine the patient distribution of functional reserves and the subunit radiosensitivity, the maximum likelihood method was used to fit the observed complication data., Results: The parallel model fit the complication data well, although uncertainties on the functional reserve distribution and subunit radiosensitivity are highly correlated., Conclusion: The observed radiation hepatitis complications show a threshold effect that can be described well with a parallel architecture model. However, additional independent studies are required to better determine the parameters defining the functional reserve distribution and subunit radiosensitivity.

Acute morbidity, late complications and tumor response were evaluated in 324 prostate cancer patients treated with 3-dimensional conformal radiation therapy in a phase I dose-escalation study. This radiotherapy technique targeted the prostate and seminal vesicles but effectively excluded the surrounding normal tissues. The minimum tumor dose was 64.8 to 66.6 Gy. in 87 patients, 70.2 Gy. in 138, 75.6 Gy. in 69 and 81.0 Gy. in 30. The treatment was well tolerated with minimal acute morbidity, observed in 15% of the patients who required medication for relief of rectal symptoms and in 34% for urinary symptoms. Two patients (0.6%) to date have had grades 3 and 4 late complications (Radiation Therapy Oncology Group morbidity grading system). The 3-year actuarial probability of survival with a normal serum prostate specific antigen level was 97% for patients with stages T1c and T2a, 86% with stage T2b, 60% with stage T2c and 43% with stage T3 disease. A multivariate analysis demonstrated that initial prostate specific antigen (20 ng./ml. or less versus more than 20 ng./ml.), stage (T2c or less versus T3) and Gleason score (6 or less versus 7 or more) were each significant independent variables that affected subsequent chemical relapse. The acute and long-term toxicities have been less compared with traditional treatment techniques. After the maximal tolerable dose with 3-dimensional conformal radiotherapy is established, future studies will test whether high dose conformal therapy has the potential to improve local tumor control and survival of patients with localized prostatic carcinoma.

The objective of the work presented in this paper is to explore the scope of the applicability of the inverse radiotherapy technique for designing optimized intensity distributions to achieve a desired dose distribution. A specified desired uniform dose to the target volume is inverted, subject to constraints on the surrounding normal tissue dose, to produce optimum intensity distributions in a set of beams arranged around the target volume. We employed the inverse technique and software developed by Bortfeld and evaluated results both qualitatively and quantitatively using dose distribution displays, dose-volume histograms and biological indices including tumor control probability and normal tissue complication probabilities. So far we have applied this methodology to prostate and lung treatment plans. For prostate the inverse technique produces satisfactory approximations of the desired dose distributions. However, for lung its performance is considerably inferior. Our investigations point to a number of factors for this difference, the primary ones being differences in the tolerance doses of neighboring normal tissues, magnitudes of volume effect, tissue architectures, and the achievability of the specified desired dose distributions. We conclude that, for certain clinical situations, it is not sufficient to specify the objectives of optimization purely in terms of the desired pattern of the dose. The objectives must also include dose-volume effects and biological indices. Furthermore, the mathematics of optimization must be able to incorporate these factors into the process. We find that the inverse technique is not suitable for situations where dose-volume considerations and biological indices are important and that other methods of optimization of intensity distributions should be explored.

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 x 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.

Purpose: To determine the extent of reduction of volume of normal tissue structures exposed to high doses of radiation therapy (RT) after administration of neoadjuvant hormonal therapy (NHT) in patients with bulky, geometrically unfavorable prostatic cancers., Methods and Materials: Twenty-two patients with bulky prostatic cancers were treated with a 3 month course of neoadjuvant leuprolide acetate and eulexin prior to three-dimensional (3-D) conformal radiotherapy. Patients were included if 3-D treatment planning revealed that either > 30% of the rectal wall would receive 95% of the prescription dose (D95) (n = 13); > or = 50% of the bladder wall would receive D95 (n = 10); or that any volume of small bowel would receive > or = 65% of the prescription dose (n = 16). All patients underwent simulation and conformal treatment planning before and after NHT. Pre and posthormone cumulative dose volume histogram (DVH) calculations for all normal tissue structures were analyzed and compared for each patient., Results: The median percentage of target volume reduction after NHT was 25% (range: 3-52%). Ten of 13 patients (78%) whose prehormone rectal DVH demonstrated > 30% of the rectal wall receiving D95 responded to NHT with a median 25% (range: 16-48%) reduction of rectal volume receiving the D95. A median reduction of 50% (range: 6-64%) of the bladder volume receiving D95 was observed in nine of ten patients (90%), while 13 of 16 (81%) showed a reduction of small bowel volume to a median percentage of 88% (range: 67-100%) of the prehormonal values., Conclusion: Neoadjuvant hormonal therapy is an effective method for decreasing the size of bulky prostatic tumors as well as for optimizing the geometry of the target volume in relation to the adjacent normal tissue structures prior to radiation therapy. Such an approach allows for reduction of the volume of normal tissues exposed to high doses in the majority of treated patients. Currently, studies are underway to determine whether NHT will lead to a decreased likelihood of long-term complications associated with radiotherapy of bulky, geometrically unfavorable prostatic tumors, and permit the safe delivery of escalated dose levels using conformal treatment techniques.