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The linear-quadratic transformation of dose-volume histograms in fractionated radiotherapy.

BACKGROUND AND PURPOSE: Dose-volume histograms (DVHs) are often used in radiotherapy to provide representations of treatment dose distributions. DVHs are computed from physical dose and do not include radiobiological factors; therefore, the same DVH will be computed for a treatment plan whatever fractionation regimen is used. However, dose heterogeneity resulting from variation of daily treatment dose within the volume will have biological effects due to spatial heterogeneity of fraction size as well as total dose. The purpose of the paper is to present a radiobiological (LQ) transformation of the physical dose distribution which incorporates fraction size effects and may be better suited to the prediction of biological effects. METHODS: An analytic formula is derived for the linear-quadratic transformation of a normal distribution of dose to give the corresponding distribution of biologically equivalent dose given as 2 Gy fractions. This allows LQ-transformed DVHs to be computed from physical DVHs. The resultant LQ-DVH depends on the assumed value of the relevant alpha/beta ratio. It is a modified dose distribution (corrected for spatial heterogeneity of fraction size) but does not incorporate time factors or volume effects. RESULTS: The analysis shows that the LQ-transformed distribution is always broader than the distribution of physical dose. Radiobiological 'hot spots' and 'cold spots' are further from the mean than physical distributions would indicate. The difference between conventional DVHs and LQ-transformed DVHs is dependent on the fractionation regimen used. LQ-DVHs for a single dose distribution (treatment plan) can be computed for different fractionation regimens with some simplifying assumptions (e.g. no time-factor-dependence of late effects). Regimens calculated to be radiobiologically equivalent at a single point nevertheless result in non-equivalent LQ-DVHs when spatial variation of daily treatment dose is included. The difference is especially important for tumour sites (such as breast and head and neck) for which considerable dose heterogeneity may occur and for which different treatment regimens are in use. CONCLUSIONS: LQ-DVHs should be computed in parallel with conventional DVHs and used in the evaluation of treatment plans and fractionation regimens and in the analysis of high-dose side-effects in patients.

Brachytherapy↗

Comparison of miniature multileaf collimation (MMLC) with circular collimation for stereotactic treatment.

PURPOSE: A prototype Miniature Multi-Leaf Collimator (MMLC) designed specifically for radiosurgery and small field radiotherapy has been fabricated and evaluated at the University of Texas M. D. Anderson Cancer Center (UTMDACC). This work demonstrates the advantages of a computer-controlled MMLC vs. conventional circular collimation for the treatment of an irregularly shaped target volume in the brain. METHODS AND MATERIALS: Two patient treatments were selected for this comparison from 38 intracranial tumors treated with radiosurgery at UTMDACC from 8/6/91 to 5/10/94. Target contours and critical structures defined for one of the patients was used to create a simulated target volume and critical structures in a spherical head phantom. Computer simulations were performed using traditional single isocenter treatment with a circular collimator for a set of six arcs. The same arc paths were used to compute the dose distribution for the MMLC and conformed beam geometries were defined using a three-dimensional (3D) treatment planning system with beam's eye view capabilities. Then, the calculated dose distribution for a single isocenter, conformal treatment was delivered to the spherical head phantom under static conditions by shaping the MMLC to conform the target volume shape projected as a function of couch rotation and gantry angle. Planar dose distributions through the target volume were measured using therapy verification film located in the phantom. The measurements were used to verify that the 3D treatment planning system was capable of simulating the MMLC technique. For the second patient with a peanut-shaped tumor, the 3D treatment planning calculations were used to compare dose distributions for the MMLC and for traditional single and multiple isocenter treatments using circular collimators. The resulting integral dose-volume histograms (DVHs) for the target volume, normal brain, and critical structures for the three treatment techniques were compared. RESULTS: (a) Analysis of the film dosimetry data exemplified the degree of conformation of the high-dose region to the target shape that is possible with a computer-controlled MMLC. (b) Comparison of measured and calculated dose distributions indicates that the 3D treatment planning system can simulate the MMLC treatment. (c) Comparison of DVHs from the single isocenter MMLC and circular collimator treatments shows similar coverage of the target volume with increased dose to the brain for circular collimation (4). Comparison of DVHs from the single isocenter MMLC with the multiple isocenter circular collimator treatment approach shows a more inhomogeneous dose distribution through the target volume and increased dose to the brain for the latter. CONCLUSION: Dosimetry data for single isocenter treatments using computer-controlled field shaping with a MMLC demonstrate the ability to conform the dose distribution to an irregularly shaped target volume. DVHs validated that the single isocenter MMLC treatment is preferable to both single and multiple isocenter, circular collimator treatment because it provides a more uniform dose distribution to an irregularly shaped target volume and reduces the dose to surrounding brain tissue for the example cases.

Adenocarcinoma↗

Dosimetric analysis of intact breast irradiation in off-axis planes.

PURPOSE/OBJECTIVE: The purpose of this investigation is to quantify dose inhomogeneity of intact breast irradiation in off-axis planes, and determine how dose inhomogeneity varies according to patient breast size and anatomical region of the breast. METHODS AND MATERIALS: Eleven patients treated with intact breast radiation underwent a treatment-planning computer tomography (CT) scan with 1-cm slices through the entire breast. The area of breast tissue was defined on each CT slice. Treatment planning with lung correction factors was performed using a two-dimensional treatment-planning system that calculates off-axis dose distributions on a slice-by-slice basis. Each plan utilized tangential beams with matched nondivergent posterior borders and with collimator rotation to match the chest wall slope. Dose inhomogeneity within the central plane was minimized during treatment planning by the use of a wedge on the lateral tangent field and by the differential weighting of fields. Dose was normalized at the breast and pectoralis major interface at midseparation in the central plane. Off-axis dose inhomogeneity was not considered in the optimization of the treatment plan. Dose distributions were plotted for each 1-cm slice, and the area of each isodose curve within the breast on each CT slice was calculated. The results of each slice were summed to give an approximation of dose-volume relationships. RESULTS: For the entire population, an average of 10% of the breast volume (range 1-40%) received 110% or greater of the prescribed dose. Increasing dose inhomogeneity was positively correlated with increasing breast sizes (r = 0.72, p = 0.01--Spearmen rank test). Analysis of dose as a function of location within the breast, revealed that the greatest dose inhomogeneity occurred in the lower anatomical quadrants of the breast (p = 0.003-Kruskal-Wallis test). For the group, the mean breast volume that received a 110% or greater dose was: 30% at 6 cm below central axis, 14% at 4 cm below central axis, 6% at central axis, 5% at 4 cm above central axis, and 7% at 6 cm above central axis. CONCLUSION: Our study demonstrates that a significant volume of breast tissue receives 110% or greater of the prescribed dose. This inhomogeneity is greatest in women with larger breast sizes, providing a possible explanation for the poorer cosmetic result seen in this subset of patients compared to women with small breast sizes. In addition, our results show the greatest dose inhomogeneity in the lower quadrants of the breast. Off-axis dose inhomogeneity should be considered in the planning of tumor bed boosts in women with lower quadrant tumors.

Adult↗

An analysis of the effect of ovoid shields in a selectron-LDR cervical applicator on dose distributions in rectum and bladder.

PURPOSE: A disadvantage of ovoid shields in a Fletcher-type applicator is that these shields cause artifacts on postimplant CT images. CT images, however, make it possible to calculate the dose distribution in the rectum and the bladder. To be able to estimate the possible advantage of having CT information over the use of ovoid shields without having CT information, we investigated the influence of shielding segments in a Fletcher-type Selectron-LDR applicator on the dose distribution in rectum and bladder. METHODS AND MATERIALS: Contours of rectum and bladder were delineated on transaxial CT slices of 15 unshielded applications. Of the volumes contained within these structures dose-volume histograms (DVHs) were calculated. In a similar way, DVHs of simulated shielded applications were calculated. The reduction, due to shielding, of the dose to the 2 cm3 (D2) and 5 cm3 (D5) volume of the cumulative DVHs of rectum and bladder, were determined. An isodose pattern in the sagittal plane through the center of each applicator was plotted to compare the location of the shielded area with the location of maximum dose in rectum and bladder in the unshielded situation. In two cases local dose reductions to the rectal wall were determined by calculating the dose in points at 10-mm intervals on the rectal contours. RESULTS: For the rectum, the reduction of D2 ranged from 0 to 11.1%, with an average of 5.0%; the reduction of D5 ranged from 2.3 to 12.1%, with an average of 6.4%. The reduction of D2 and D5 for the bladder ranged from 0 to 11.9% and from 0 to 11.6%, with average values of 2.2 and 2.6%, respectively. In 8 out of 15 cases the rectal maximum dose was located inferior to the shielded area. In all cases except one the bladder maximum dose was located superior to the shielded area. Local dose reductions on the rectal wall can be as high as 30% or more in an optimally shielded area. CONCLUSIONS: Reductions of D2 and D5 to rectum and bladder due to shielding are rather small, because the shielded area does usually not coincide with the high dose region and even if it does, the shielded area is too small to result in large reductions of these values. Because local dose reductions vary largely, one should proceed with caution when calculating the dose in just one rectal or bladder reference point. Because large overall dose reductions cannot be achieved with shielding, it is safe to use an unshielded applicator when post implant CT images are used to realize optimized dose distributions.

Artifacts↗

Efficacy of a belly board device with CT-simulation in reducing small bowel volume within pelvic irradiation fields.

PURPOSE/OBJECTIVE: Acute and chronic small bowel toxicity associated with pelvic irradiation limits dose escalation for both chemotherapy and radiotherapy for rectal cancer. Various surgical and technical maneuvers including compression and belly board devices (BBD) have been used to reduce small bowel volume in treatment fields. However, quantitative dose volume advantages of such methods have not been reported. In this study, the efficacy of BBD with CT-simulation is presented with dose-volume histogram (DVH) analyses for rectal cancer. METHODS AND MATERIALS: Twelve consecutive patients referred to our department with rectal cancer were included in this study. Patients were given oral contrast 1.5 h prior to scanning and instructed not to empty their bladder during the procedure. The initial CT scan without BBD was taken in the prone position with an immobilization cast. A second CT study was performed with a commercially available BBD consisting of an 18-cm thick hard sponge with an adjustable opening (maximum 42 x 42 cm2). All patients were positioned prone over the BBD so that the opening was above the treatment volume and usually extended from the diaphragm to the bottom of the fourth lumbar spine. Image fusion between both sets of CT scans (with and without BBD) was performed using common bony landmarks to maintain the same target volume. The critical structures including small bowel and bladder were delineated on each slice for DVH analysis. On each study, a three-field optimized plan with conformal blocks in beams-eye-view was generated for volumetric analysis. The DVHs with and without BBD were evaluated for each patient. RESULTS: The median age and body weight of 12 patients (4 females and 8 males) were 57.5 years and 82.7 kg, respectively. The changes in posterior-anterior (PA) and lateral separation with and without BBD at central axis slices were analyzed. The changes in lateral separation were minimal (<0.8 cm); however, the PA separation was reduced by 11.3 +/- 3.3% when BBD was used. The reduction in PA separation was directly related to the reduction in small bowel volume. The small bowel volume was significantly reduced with a median reduction of 70% (range 10-100%) compared to the small bowel volume without BBD. The small bowel volume reduction did not correlate either with body weight, age, gender, or sequence of radiation treatment with surgery (pre-op vs. post-op). The DVH analysis of small bowel with BBD showed significant volume reduction at each dose level. For 50% patients, the DVH analysis demonstrated an increase in bladder volume with BBD. All patients treated with the BBD completed their treatment without any break and without significant acute gastrointestinal or genitourinary toxicity. CONCLUSIONS: For rectal cancers, small bowel is the dose-limiting structure for acute and chronic toxicity. The use of the BBD should improve the tolerance of aggressive combined modality treatment by reducing the small bowel volume within the pelvis compared to the prone position alone. The BBD provides an easy, economical, comfortable, and noninvasive technique to displace small bowel from pelvic treatment fields. The small bowel volume is dramatically reduced at each dose level. The volume reduction does not correlate with gender, age, weight, pelvic separation, and sequence of radiation treatment vs. surgery.

Aged↗

Brainstem tolerance to conformal radiotherapy of skull base tumors.

PURPOSE: The aim of this study was to analyze the long-term incidence of brainstem toxicity in patients treated for skull base tumors with high dose conformal radiotherapy. METHODS AND MATERIALS: Between 1974 and 1995, 367 patients with chordomas (n = 195) and chondrosarcomas (n = 172) of the base of skull have been treated with combined megavoltage photon and 160 MeV proton radiotherapy. Following 3D treatment planning with delineation of target volumes and critical nontarget structures dose distributions and dose-volume histograms were calculated. Radiotherapy was given an 1.8 Gy or CGE (=Cobalt Gray Equivalent) dose per fraction, with prescribed target doses ranging from 63 CGE to 79.2 CGE (mean = 67.8 CGE). Doses to the brainstem surface were limited to < or = 64 CGE and to the brainstem center to < or = 53 CGE. RESULTS: Follow-up time ranged from 6 months to 21.4 years (mean = 42.5 months). Brainstem toxicity was observed in 17 of 367 patients attributable to treatment, resulting in death of three patients. Actuarial rates of 5 and 10-year high-grade toxicity-free survival were 94 and 88%, respectively. Increased risk of brainstem toxicity was significantly associated with maximum dose to brainstem, volume of brainstem receiving > or = 50 CGE, > or = 55 CGE, and > or = 60 CGE, number of surgical procedures, and prevalence of diabetes or high blood pressure. Multivariate analysis identified three independent factors as important prognosticators: number of surgical procedures (p < 0.001), volume of the brainstem receiving 60 CGE (p < 0.001), and prevalence of diabetes (p < 0.01). CONCLUSIONS: Tolerance of brainstem to fractionated radiotherapy appears to be a steep function of tissue volume included in high dose regions rather than the maximum dose of brainstem alone. In addition, presence of predisposing factors as well as extent of surgical manipulation can significantly lower brainstem tolerance in the individual patient.

Adolescent↗

Cost benefit of emerging technology in localized carcinoma of the prostate.

PURPOSE: In a health care environment strongly concerned with cost containment, cost-benefit studies of new technology must include analyses of loco-regional tumor control, morbidity, impact on quality of life, and financial considerations. METHODS AND MATERIALS: This nonrandomized study analyzes 124 patients treated with three-dimensional conformal radiation therapy (3D CRT) and 153 with standard irradiation (SRT) between January 1992 and December 1995, for histologically proven adenocarcinoma of prostate, clinical Stage T1 or T2. Mean follow-up is 1.4 years. Three-dimensional CRT consisted of six or seven coplanar oblique and lateral and, in some patients, AP fields designed to treat the prostate with a 1 to 1.7 cm margin. SRT consisted of 120 degrees bilateral arc rotation. Total doses to prostate were 67 to 70 Gy when pelvic lymph nodes were irradiated or 68.4 to 73.8 Gy when prostatic volume only was treated; dose per fraction was 1.8 Gy. Patients were interviewed weekly for severity of 12 acute intestinal and urinary pelvic irradiation side effects (0 to 4+ grading). Time and effort for 3D RTP and daily treatment with 3D CRT and SRT were recorded. Dose-volume histograms (DVHs) were calculated for gross tumor volume, planning target volume, bladder, and rectum. Actual reimbursement to the hospital and university was determined for 41 3D CRT, 43 SRT, and 40 radical prostatectomy patients treated during the same period. RESULTS: Average treatment planning times (in minutes) were: 101 for 3D conformal therapy simulation, 66 for contouring of target volume and sensitive structures, 55 for virtual simulation, 39 for plan preparation and documentation, 65 for physical simulation, and 20 for approval of treatment plan. Daily mean treatment times were 19 min for 3D CRT with Cerrobend blocking, 16 with multileaf collimation, and 10 with bilateral arc rotation. Dosimetric analysis (DVHs) showed a reduction of 50% in volume of bladder or rectum receiving doses higher than 65 Gy. Acute side effects included dysuria, moderate difficulty in urinating, and nocturia in 25-39% of both SRT and CRT patients; loose stools or diarrhea in 5-12% of 3D CRT and 16-22% of SRT patients; moderate proctitis in 3% of 3D CRT and 12% of SRT patients (p = 0.01). Chemical disease-free survival (prostate-specific antigen < or =2 ng/ml) at 3 years was 90% with 3D CRT and 80% with SRT (p = 0.01). Average initial treatment reimbursements were $13,823 (3D CRT), $10,864 (SRT), and $12,250 (radical prostatectomy). Average total treatment reimbursement and projected cost of management of initial therapy failures per patients were $15,173, $16,264, and $16,405, respectively. CONCLUSIONS: Three-dimensional CRT irradiated less bladder and rectum volume than SRT; CRT initial reimbursement was 28% higher than SRT and 12% higher than radical prostatectomy. Because of projected better local tumor control, average total cost of treating a patient with 3D CRT or radical prostatectomy is equivalent to cost of SRT. Treatment morbidity was lower with 3D CRT. Our findings reflect an overall benefit with 3D CRT as a new promising technology in treatment of localized prostate cancer. Dose-escalation studies may enhance its efficacy and cost benefit.

Adenocarcinoma↗

The integral biologically effective dose to predict brain stem toxicity of hypofractionated stereotactic radiotherapy.

OBJECTIVE: The aim of this work was to develop a parameter for use during fractionated stereotactic radiotherapy treatment planning to aid in the determination of the appropriate treatment volume and fractionation regimen that will minimize risk of late damage to normal tissue. MATERIALS & METHODS: We have used the linear quadratic model to assess the biologically effective dose at the periphery of stereotactic radiotherapy treatment volumes that impinge on the brain stem. This paper reports a retrospective study of 77 patients with malignant and benign intracranial lesions, treated between 1987 and 1995, with the dynamic rotation technique in 6 fractions over a period of 2 weeks, to a total dose of 42 Gy prescribed at the 90% isodose surface. From differential dose-volume histograms, we evaluated biologically effective dose-volume histograms and obtained an integral biologically-effective dose (IBED) in each case. RESULTS: Of the 77 patients in the study, 36 had target volumes positioned so that the brain stem received more than 1% of the prescribed dose, and 4 of these, all treated for meningioma, developed serious late damage involving the brain stem. Other than type of lesion, the only significant variable was the volume of brain stem exposed. An analysis of the IBEDs received by these 36 patients shows evidence of a threshold value for late damage to the brain stem consistent with similar thresholds that have been determined for external beam radiotherapy. CONCLUSION: We have introduced a new parameter, the IBED, that may be used to represent the fractional effective dose to structures such as the brain stem that are partially irradiated with stereotactic dose distributions. The IBED is easily calculated prior to treatment and may be used to determine appropriate treatment volumes and fractionation regimens minimizing possible toxicity to normal tissue.

Adolescent↗

Timing of computed tomography-based postimplant assessment following permanent transperineal prostate brachytherapy.

PURPOSE: To establish the rate of resolution of prostatic edema following transperineal interstitial permanent prostate brachytherapy, and to determine the results and impact of timing of the postimplant assessment on the dose-volume relationship. METHODS AND MATERIALS: A series of 19 consecutive patients with early-stage adenocarcinoma of the prostate receiving transperineal interstitial permanent prostate brachytherapy, were enrolled in this study. Twelve received 125I and seven received 103Pd. Postoperative assessment included a computed tomographic (CT) scan on postoperative days 1, 8, 30, 90, and 180. On each occasion, CT scans were performed on a GE helical unit at 3-mm abutting slices, 15-cm field of view. Prostate volumes were outlined on CT scans by a single clinician. Following digitization of the volumes and radioactive sources, volumes and dose-volume histograms were calculated. The prostate volume encompassed by the 80% and 100% reference isodose volumes was calculated. RESULTS: Preimplant transrectal ultrasound determined volumes varied from 17.5 to 38.6 cc (median 27.9 cc). Prostate volumes previously defined on 40 randomly selected postimplant CT scans were compared in a blinded fashion to a second CT-derived volume and ranged from -32% to +24%. The Pearson correlation coefficient for prostate CT volume reproducibility was 0.77 (p < 0.03). CT scan-determined volume performed on postoperative day 1 was an average of 41.4% greater than the volume determined by preimplant ultrasound. Significant decreases in average volume were seen during the first month postoperatively. Average volume decreased 14% from day 1 to day 8, 10% from day 8 to day 30, 3% from day 30 to day 90, and 2% thereafter. Coverage of the prostate volume by the 80% isodose volume increased from 85.6% on postoperative day 1 to 92.2% on postoperative day 180. The corresponding increase in the 100% reference dose coverage of the prostate volume ranged from 73.1% to 83.3% between postoperative days 1, and 180, respectively. CONCLUSIONS: Most of the prostatic edema induced by brachytherapy appears to resolve by postoperative day 30. Scans performed on postimplant day 30 appear to adequately describe the time-averaged dose coverage of the prostate. This suggests that waiting approximately 1 month to perform postimplant analysis gives the most accurate prostatic volume and, consequently, dosimetric description of the implant.

Adenocarcinoma↗

[Hyperfractionated reirradiation after salvage surgery in cervico-facial carcinoma. Result of a pilot study in 14 patients].

PURPOSE: Between November 1988 and May 1992, 14 patients were enrolled in a pilot study to evaluate the feasibility and results of hyperfractionated reirradiation for the treatment of head and neck recurrences or of second primary tumors developed in a previously irradiated volume. MATERIALS AND METHODS: All patients underwent a surgical resection for the treatment of their recurrence or second cancer. Reirradiation was proposed because of positive margins and/or lymph node metastasis with extra-capsular spread. The planned reirradiation dose was 60 Gy over 5 weeks, with two daily fractions of 1.2 Gy delivered 6-8 hours apart. RESULTS: Of the 14 patients, 10 received the reirradiation scheduled dose (ie, 60 Gy). All patients experienced an acute mucositis that never led to disruption of the treatment. Ten patients died 3 to 41 months after reirradiation (mean: 14 months), three were disease-free 48 to 71 months after reirradiation and one was alive with local progressive disease 74 months after reirradiation. The overall local control rate within the reirradiated volume was 43%. The 24- and 36-month overall survival rates were 50 and 35%, respectively. Overall, 13 late complications were noted: four were grade 1, seven were grade 2, and two were grade 3. Three patients still alive in September 1993 and whose initial files were available were enrolled in an additional study to assess from dose-volume histograms the cumulative doses delivered by the two irradiations. CONCLUSION: Despite poor local control, reirradiation using a hyperfractionation schedule with high dose level is feasible in terms of acute and late toxicity.

Adult↗

Proton beams in radiation therapy.

The rationale for study of proton radiation therapy is that, for some anatomic sites and tumors, the treatment volume is smaller; i.e., there is less irradiation of nontarget tissue while the target is included in three dimensions at each treatment session. As a result, the dose to the target can be raised. The consequence is that the tumor control probability improves and the frequency and severity of treatment-related morbidity decrease. These results come about from the physical fact that the proton range in tissue is finite; in comparison, absorption of photons is an exponential function and, hence, some dose is received for the full-beam path through the body. Accordingly, the dose deep to the target for proton treatments can be zero for each beam path. This situation provides a virtually certain means of improving the treatment outcome for selected categories of patients. Experience to date with proton radiation therapy has been quite limited. As of June 1991, the total number of proton radiation-treated patients was 11,763 from the various centers. Of that number, approximately 46% and 32% have been treated for small benign intracranial lesions (principally pituitary adenomas and arteriovenous malformations) and for tumors of the eye, respectively. Thus, only some 2500 patients have been treated for all other tumor types. The results from three centers and approximately 2800 patients with uveal melanoma are that the local control rate was 96% (for failures in-field, marginal, and in other parts of the eye). The local control results for chondrosarcomas and chordomas of the skull base are 91% and 65%, respectively. These percentages compare with some 35% achieved with conventional treatment. Experience with arteriovenous malformations indicates that control of bleeding and disappearance of the lesion are comparable to those achieved by other procedures. The developments from the proton therapy programs have contributed greatly to radiation treatment planning, e.g., the first three-dimensional treatment planning system put into regular clinical use (uveal melanoma), beam's eye view, digital-reconstructed radiograph, dose-volume histograms, and definitions of the uncertainty in dose around any defined point. The potential for clinical gains is high. In May 1991, the Proton Radiation Oncology Group was formed to design, supervise, and coordinate clinical trials and to assist in data analysis. The efficacy of proton radiation therapy will be compared with that of photon therapy of the very highest technology.

Arteriovenous Malformations↗

Alternating conformal neutron and photon irradiation for locally advanced adenocarcinoma of the prostate.

The substantial local failure rate for patients with locally advanced carcinoma of the prostate (LACaP) following photon irradiation, the association of local failure with a poor prognosis, and the promising results of mixed neutron/photon (40%/60%) radiotherapy supplied the rationale for this study. The purpose of this study was to evaluate the combined advantages of mixed neutron/photon (75%/25%) irradiation, 3D treatment planning, as well as fully conformal beam shaping capabilities in reducing the morbidity associated with neutron irradiation. The first 35 patients treated with this technique are the basis for this analysis. After CT stimulation and treatment planning, the normal tissue and target structures were entered into the 3D planning system. The neutron dose was delivered in 15 fractions at 1.0 Gy/fraction (NGy) to the prostate and seminal vesicles (PSV) and 0.6 NGy/fraction to the pelvic lymph nodes (LN). The photon dose was given in 10 fractions of 1.8 Gy each to both the PSV and LN volumes. Neutron and photon dose-volume histograms (DVHs) were generated in each patient for the prostate, seminal vesicles, lymph nodes, bladder, and rectum. The adequacy of the neutron and photon components of the treatment were compared with respect to target volume and normal tissue irradiation. Based on the DVH analysis, the prostate and seminal vesicles received the prescribed dose with both neutrons (99% +/- 2%) and photons (99% +/- 2%). There was no significant difference in the dose to the bladder and rectum for both the neutrons and photons. The acute treatment related reactions have been mild, with only one grade III bladder reaction. The 3D conformal technology utilized in this study has been shown to allow for the delivery of neutron irradiation with no increase in dose to the adjacent normal tissues compared with that achieved with conformal photon treatment. Further follow-up will reveal whether the dosimetric advantage demonstrated by this technique translates into an improved therapeutic ratio.

Adenocarcinoma↗

Results of re-irradiation of primary intracranial neoplasms with three-dimensional conformal therapy.

We evaluated the potential of three-dimensional conformal therapy for re-irradiation of selected intracranial neoplasms and reviewed the retreatment of 20 patients at the University of Michigan between May 1988 and August 1991. All patients had previously undergone a full course of external beam radiotherapy (RT) to a median dose of 5,940 cGy (range 5,100-6,500 cGy), including five whole brain treatments. All recurrences were unsuitable for brachytherapy or radiosurgery. Various histologies were retreated, including 14 high-grade gliomas. Median time to re-irradiation was 38 months (range 9 months to 19 years, 6 months). RT was delivered with complex plans designed using fully integrated computed tomography/magnetic resonance imaging (CT/ MRI) tumor volume information, and regions of previous parenchymal treatment were avoided if possible. Composite (initial+retreatment) dose-volume histograms (DVH) of dose to nontarget brain allowed comparison of alternative plans to select beam orientations which minimized normal brain irradiation. Mean target dose of re-irradiation was 3,600 cGy (range 3,060-5,940 cGy). Total cumulative dose ranged from 8,060 to 11,940 cGy. Median survival was 9 months, and 1-year actuarial survival was 26%. After retreatment, 8 of 12 patients (67%) had steroid dose decrement and neurologic improvement at 4-48 months (median duration 14 months). Radiographic regression or stabilization of disease was noted in 11 of 16 patients (68%). Re-irradiation with highly conformal three-dimensional planning provides frequent clinical improvement with acceptable morbidity and should be considered in selected patients with recurrent intracranial neoplasms.

Actuarial Analysis↗

3-D dose-volume compensation using nonlinear least-squares regression technique.

A method for external beam dose-volume optimization is presented. The Gauss-Marquardt nonlinear least-squares regression technique is applied to compensator design and determination. The dose distribution (uniform or otherwise) desired throughout a volume is specified. Compensators optimized to produce the necessary variation of beam intensity across the surface of each beam are simultaneously determined for all the beams. Solutions for homogeneous dose, homogeneous target dose, and restricted dose to exterior target volume structures, and inhomogeneous target dose cases are presented. Dependence of the results on the number of parameters as well as the role of degree of desirability weighting is explained and illustrated via examples. Discussion of the significance and limitations of this optimization method is also presented.

Humans↗

Dose-volume histogram computations for small intracranial volumes.

A sampling formalism is presented to accurately compute the absolute volumes and integral dose-volume histograms of small volumes treated in stereotactic radiosurgery. The presence of small volumes and sharp dose gradients places special constraints on the computational formalism and the accuracy required to compute the dose-volume relationships. We use a spatially nonuniform random sampling method to allow an efficient and accurate computation of the dose-volume histograms for an arbitrary number of volumes. The computation of absolute volume vs dose allows intercomparison of dose delivered to target and dose-critical volumes and allows a quantitative trade-off analysis often critical to an optimal treatment of the lesion.

Algorithms↗

Dose-volume distributions: a new approach to dose-volume histograms in three-dimensional treatment planning.

A new approach to calculating and displaying dose-volume relationships in 3D radiation therapy is presented. We have developed a concept of a dose-volume distribution (DVD) and its corresponding differential dose-volume distribution (DDVD), based on organization of the data in the volume rather than in the dose domain. The new concepts make full use of the information that can be obtained from the dose calculation points and the sampling pattern and are designed to overcome shortcomings of the classical concepts of dose-volume histograms (DVH) and differential dose-volume histograms (DDVH). The new concepts can be applied to any number of dose calculation points, but they are especially advantageous when a small number of points is used. DVDs are particularly well suited to pseudo- and quasi-random sampling of dose distributions. We have developed an error analysis for DVDs and DDVDs in the case of pseudorandom sampling. We also describe an adaptive technique for minimizing the amount of data needed for purposes of display.

Biophysical Phenomena↗

Dose-surface histograms as treatment planning tool for prostate conformal therapy.

Dose-surface histograms are studied and compared with dose-volume histograms, as an evaluation tool for prostate treatment planning. For thin walled hollow organs, such as the rectum and bladder, the surface area irradiated is a more appropriate measure of the biological effect than the full volume. It is also more accurate and efficient to define the surface for a hollow structure and compute the surface area histograms. Application of the dose-surface histograms provide new insights into prostate treatment planning. A simple idealized geometry model demonstrates that the percentage surface area intersected by the geometric beam edge differs from the percentage volume intersected. For a group of prostate patients, it is shown that the dose-surface histograms yield substantially different results from the dose-volume histograms in ranking four-, six-, and, eight-field treatment plans and in calculating the fraction of the rectum irradiated to high dose. The difference in terms of surface area between these plans in the high-dose region is usually less than that in terms of the volume, and a reverse of plan ranking order can consequently occur. The percentage of organ surface irradiated to high dose is typically greater than the percentage volume by 5% to 10%. The use of the dose-surface histograms in analysis of organ motion and/or patient setup uncertainty, and analysis of rectal complications, is also discussed.

Biophysical Phenomena↗

Reporting and analyzing dose distributions: a concept of equivalent uniform dose.

Modern treatment planning systems for three-dimensional treatment planning provide three-dimensionally accurate dose distributions for each individual patient. These data open up new possibilities for more precise reporting and analysis of doses actually delivered to irradiated organs and volumes of interest. A new method of summarizing and reporting inhomogeneous dose distributions is reported here. The concept of equivalent uniform dose (EUD) assumes that any two dose distributions are equivalent if they cause the same radiobiological effect. In this paper the EUD concept for tumors is presented, for which the probability of local control is assumed to be determined by the expected number of surviving clonogens, according to Poisson statistics. The EUD can be calculated directly from the dose calculation points or, from the corresponding dose-volume distributions (histograms). The fraction of clonogens surviving a dose of 2 Gy (SF2) is chosen to be the primary operational parameter characterizing radiosensitivity of clonogens. The application of the EUD concept is demonstrated on a clinical dataset. The causes of flattening of the observed dose-response curves become apparent since the EUD concept reveals the finer structure of the analyzed group of patients in respect to the irradiated volumes and doses actually received. Extensions of the basic EUD concept to include nonuniform density of clonogens, dose per fraction effects, repopulation of clonogens, and inhomogeneity of patient population are discussed and compared with the basic formula.

Cell Division↗