A multi-GPU real-time dose simulation software framework for lung radiotherapy.

PURPOSE: Medical simulation frameworks facilitate both the preoperative and postoperative analysis of the patient's pathophysical condition. Of particular importance is the simulation of radiation dose delivery for real-time radiotherapy monitoring and retrospective analyses of the patient's treatment. METHODS: In this paper, a software framework tailored for the development of simulation-based real-time radiation dose monitoring medical applications is discussed. A multi-GPU-based computational framework coupled with inter-process communication methods is introduced for simulating the radiation dose delivery on a deformable 3D volumetric lung model and its real-time visualization. The model deformation and the corresponding dose calculation are allocated among the GPUs in a task-specific manner and is performed in a pipelined manner. Radiation dose calculations are computed on two different GPU hardware architectures. The integration of this computational framework with a front-end software layer and back-end patient database repository is also discussed. RESULTS: Real-time simulation of the dose delivered is achieved at once every 120 ms using the proposed framework. With a linear increase in the number of GPU cores, the computational time of the simulation was linearly decreased. The inter-process communication time also improved with an increase in the hardware memory. Variations in the delivered dose and computational speedup for variations in the data dimensions are investigated using D70 and D90 as well as gEUD as metrics for a set of 14 patients. Computational speed-up increased with an increase in the beam dimensions when compared with a CPU-based commercial software while the error in the dose calculation was <1%. CONCLUSION: Our analyses show that the framework applied to deformable lung model-based radiotherapy is an effective tool for performing both real-time and retrospective analyses.

Dosimetric evaluation of a novel polymer gel dosimeter for proton therapy.

PURPOSE: The aim of this study is to evaluate the dosimetric performance of a newly developed proton-sensitive polymer gel formulation for proton therapy dosimetry. METHODS: Using passive scattered modulated and nonmodulated proton beams, the dose response of the gel was assessed. A next-generation optical CT scanner is used as the readout mechanism of the radiation-induced absorbance in the gel medium. Comparison of relative dose profiles in the gel to ion chamber profiles in water is performed. A simple and easily reproducible calibration protocol is established for routine gel batch calibrations. Relative stopping power ratio measurement of the gel medium was performed to ensure accurate water-equivalent depth dose scaling. Measured dose distributions in the gel were compared to treatment planning system for benchmark irradiations and quality of agreement is assessed using clinically relevant gamma index criteria. RESULTS: The dosimetric response of the gel was mapped up to 600 cGy using an electron-based calibration technique. Excellent dosimetric agreement is observed between ion chamber data and gel. The most notable result of this work is the fact that this gel has no observed dose quenching in the Bragg peak region. Quantitative dose distribution comparisons to treatment planning system calculations show that most (> 97%) of the gel dose maps pass the 3%/3 mm gamma criterion. CONCLUSIONS: This study shows that the new proton-sensitive gel dosimeter is capable of reproducing ion chamber dose data for modulated and nonmodulated Bragg peak beams with different clinical beam energies. The findings suggest that the gel dosimeter can be used as QA tool for millimeter range verification of proton beam deliveries in the dosimeter medium.

Performance evaluation of an improved optical computed tomography polymer gel dosimeter system for 3D dose verification of static and dynamic phantom deliveries.

The performance of a next-generation optical computed tomography scanner (OCTOPUS-5X) is characterized in the context of three-dimensional gel dosimetry. Large-volume (2.2 L), muscle-equivalent, radiation-sensitive polymer gel dosimeters (BANG-3) were used. Improvements in scanner design leading to shorter acquisition times are discussed. The spatial resolution, detectable absorbance range, and reproducibility are assessed. An efficient method for calibrating gel dosimeters using the depth-dose relationship is applied, with photon- and electron-based deliveries yielding equivalent results. A procedure involving a preirradiation scan was used to reduce the edge artifacts in reconstructed images, thereby increasing the useful cross-sectional area of the dosimeter by nearly a factor of 2. Dose distributions derived from optical density measurements using the calibration coefficient show good agreement with the treatment planning system simulations and radiographic film measurements. The feasibility of use for motion (four-dimensional) dosimetry is demonstrated on an example comparing dose distributions from static and dynamic delivery of a single-field photon plan. The capability to visualize three-dimensional dose distributions is also illustrated.

Evaluation of a diode array for QA measurements on a helical tomotherapy unit.

A helical tomotherapy system is used in our clinic to deliver intensity-modulated radiation therapy (IMRT) treatments. Since this machine is designed to deliver IMRT treatments, the traditional field flatness requirements are no longer applicable. This allows the unit to operate without a field flatness filter and consequently the 400 mm wide fan beam is highly inhomogeneous in intensity. The shape of this beam profile is mapped during machine commissioning and for quality assurance purposes the shape of the beam profile needs to be monitored. The use of a commercial diode array for quality assurance measurements is investigated. Central axis beam profiles were acquired at different depths using solid water built-up material. These profiles were compared with ion chamber scans taken in a water tank to test the accuracy of the diode array measurements. The sensitivity of the diode array to variations in the beam profile was checked. Over a seven week period, beam profiles were repeatedly measured. The observed variations are compared with those observed with an on-board beam profile monitor. The diode measurements were in agreement with the ion chamber scans. In the high dose, low gradient region the average ratio between the diode and ion chamber readings was 1.000 +/- 0.005 (+/- 1 standard deviation). In the penumbra region the agreement was poorer but all diodes passed the distance to agreement (DTA) requirement of 2 mm. The trend in the beam profile variations that was measured with the diode array device was in agreement with the on-board monitor. While the calculated amount of variation differs between the devices, both were sensitive to subtle variations in the beam profile. The diode array is a valuable tool to quickly and accurately monitor the beam profile on a helical tomotherapy unit.

Time and PSA threshold model prognosticates long-term overall and disease-specific survival in prostate cancer patients as early as 3 months after external beam radiation therapy.

The specific aim of this analysis was to evaluate the capability of a time and prostate-specific antigen (PSA) threshold model to prognosticate overall survival (OS) and disease-specific survival (DSS) based on early PSA kinetics after radiotherapy for prostate cancer by retrospective review of outcomes in 918 patients. Crossing below analyzed PSA thresholds at specific defined time points reduced disease-specific death hazard ratios to relative to the cohort above threshold. The time and PSA threshold model demonstrates the ability to prognosticate OS and DSS as early as 3 months post-radiotherapy for prostate cancer.

The use of megavoltage CT (MVCT) images for dose recomputations.

Megavoltage CT (MVCT) images of patients are acquired daily on a helical tomotherapy unit (TomoTherapy, Inc., Madison, WI). While these images are used primarily for patient alignment, they can also be used to recalculate the treatment plan for the patient anatomy of the day. The use of MVCT images for dose computations requires a reliable CT number to electron density calibration curve. In this work, we tested the stability of the MVCT numbers by determining the variation of this calibration with spatial arrangement of the phantom, time and MVCT acquisition parameters. The two calibration curves that represent the largest variations were applied to six clinical MVCT images for recalculations to test for dosimetric uncertainties. Among the six cases tested, the largest difference in any of the dosimetric endpoints was 3.1% but more typically the dosimetric endpoints varied by less than 2%. Using an average CT to electron density calibration and a thorax phantom, a series of end-to-end tests were run. Using a rigid phantom, recalculated dose volume histograms (DVHs) were compared with plan DVHs. Using a deformed phantom, recalculated point dose variations were compared with measurements. The MVCT field of view is limited and the image space outside this field of view can be filled in with information from the planning kVCT. This merging technique was tested for a rigid phantom. Finally, the influence of the MVCT slice thickness on the dose recalculation was investigated. The dosimetric differences observed in all phantom tests were within the range of dosimetric uncertainties observed due to variations in the calibration curve. The use of MVCT images allows the assessment of daily dose distributions with an accuracy that is similar to that of the initial kVCT dose calculation.

Short-course intensity-modulated radiotherapy (70 GY at 2.5 GY per fraction) for localized prostate cancer: preliminary results on late toxicity and quality of life.

PURPOSE: To present our preliminary observations on the late toxicity and quality of life (QOL) of patients treated with short-course intensity-modulated radiotherapy (SCIM-RT). METHODS AND MATERIALS: Fifty-one patients were treated with SCIM-RT at the Cleveland Clinic Foundation between October 1998 and May 1999. The technique consisted of intensity-modulated radiotherapy using 5 static fields (anterior, 2 laterals, and 2 anterior obliques). Inverse plans were generated by the Corvus treatment-planning system. The treatment delivery was performed with a dynamic multileaf collimator. A total of 70.0 Gy was prescribed in all cases at 2.5 Gy per fraction to be delivered in 28 fractions over 5 and a half weeks. The location of the prostate gland was verified and adjusted daily with the BAT transabdominal ultrasound system. The median follow-up was 18 months (range: 11 to 26 months). The Radiation Therapy Oncology Group (RTOG) scales were used to evaluate late toxicity. The Expanded Prostate Cancer Index Composite (EPIC) was used to evaluate QOL. A total of 24 patients completed the EPIC questionnaire at approximately 2 years after therapy (median time from treatment to questionnaire administration: 24 months; range: 21 to 26 months). The results from the EPIC questionnaires were compared to scores from 46 patients treated during the same time period with conformal radiotherapy (CRT) to 78 Gy at 2 Gy per fraction. RESULTS: The dose was prescribed to an isodose line ranging from 82.0% to 90.0% (mean: 87.2%). The range of the individual prostate mean doses was 73.5 to 78.5 Gy (average: 75.3 Gy). To date, only 1 patient had Grade 1 late urinary toxicity. To date, only 4 patients had Grade 1 late rectal toxicity. No Grade 2 or 3 late urinary or rectal complications have occurred. The actuarial rectal bleeding rate observed at 18 months was 7%. There were no differences in scores from the urinary, bowel, hormonal, and overall QOL domains between SCIM-RT patients and patients treated with CRT. The overall physical and mental QOL scores were also nearly identical to scores reported for the general U.S. population. CONCLUSION: Preliminary late toxicity results up to 2 years after SCIM-RT are encouraging, with a median follow-up of 18 months (range 11 to 26 months). Late toxicity assessed by the physicians using RTOG late toxicity scores has been excellent. QOL reported by the patients using the EPIC questionnaire reveals no difference between patients treated with high-dose CRT at standard fractionation and patients treated with SCIM-RT. SCIM-RT is an alternative method of dose escalation in the treatment of localized prostate cancer. The proposed schedule significantly increases convenience to patients due to the decrease in overall treatment time.

Short-course, intensity-modulated radiotherapy for localized prostate cancer.

PURPOSE: The purpose of this study was to compare the toxicity, particularly rectal, between short-course, intensity-modulated radiotherapy (SCIM-RT) delivering 70 Gy in 28 fractions and three-dimensional conformal radiotherapy (3D-CRT) delivering 78 Gy in 39 fractions. MATERIALS AND METHODS: A total of 191 patients were treated with SCIM-RT. Seventy Gy was delivered using five intensity-modulated fields via a Varian dynamic multileaf collimator. The BAT transabdominal ultrasound system was used for localization. The comparison group consisted of 101 contemporary cases treated with 3D-CRT to 78.0 Gy (2.0 Gy per fraction). The study sample therefore comprised 292 cases. Seventy Gy in 28 fractions was equivalent to 78 Gy in 39 fractions for late-reacting tissues, according to the linear quadratic model. The median follow-up was 9 months. Radiation Therapy Oncology Group toxicity scores were used. RESULTS: The rates of acute rectal Radiation Therapy Oncology Group toxicity scores 0, 1, 2, and 3 were 30%, 55%, 14%, and 0%, respectively, with SCIM-RT, versus 14%, 67%, 19%, and 0%, respectively, with 3D-CRT. The rates of acute urinary toxicity scores 0, 1, 2, and 3 were 17%, 62%, 20%, and 1%, respectively, with SCIM-RT, versus 22%, 58%, 20%, and 0%, respectively, with 3D-CRT. To date, only two patients who underwent SCIM-RT had grade 2 late urinarytoxicity. No grade 3 late urinary or rectal complications occurred with SCIM-RT. The actuarial late rectal grade 2 toxicity observed at 18 months was 10% after SCIM-RT, versus 12% after 3D-CRT. Only three patients had grade 3 late rectal toxicity; all of them had undergone 3D-CRT. A multivariate analysis of factors affecting grade 2-3 late rectal toxicity was performed by use of the following: age (continuous), race (black vs white), androgen deprivation (yes vs no), technique (SCIM-RT vs 3D-CRT), grade 2-3 acute rectal toxicity (yes vs no), and volume of rectum receiving the prescription dose (VrPr) (< or = 15 mL vs >15 mL). Only the VrPr was a significant independent factor predicting grade 2-3 late rectal toxicity. Only 15 SCIM-RT (7%) and 20 3D-CRT cases (20%) had a VrPr > 15 mL. With SCIM-RT, the grade 2-3 late rectal toxicity rate at 18 months with a VrPr > 15 mL was 29%, versus 5% with a VrPr < or = 15 mL. With 3D-CRT, the grade 2-3 late rectal toxicity rate at 18 months with a VrPr > 15 mL was 25%, versus 8% with a VrPr < or = 15 mL. CONCLUSIONS: SCIM-RT, delivering 70.0 Gy at 2.5 Gy per fraction, had an acute and late toxicity profile up to 18 months after therapy that was similarto that of 3D-CRT delivering 78.0 Gy at 2.0 Gy per fraction. The grade 2 actuarial combined rectal toxicity rate is low (10%) at 18 months, although it increased when rectal volumes > 15 mL received 70 Gy with SCIM-RT. Only 7% of SCIM-RT cases received 70 Gy to > 15 ml of the rectum. If longer follow-up confirms the low late toxicity rates, SCIM-RT will be an alternative and more convenient method of dose-escalation in the treatment of localized prostate cancer.

Radiation dose response in patients with favorable localized prostate cancer (Stage T1-T2, biopsy Gleason < or = 6, and pretreatment prostate-specific antigen < or = 10).

PURPOSE: To study the radiation dose response as determined by biochemical relapse-free survival in patients with favorable localized prostate cancers, i.e., Stage T1-T2, biopsy Gleason score (bGS) < or = 6, and pretreatment prostate-specific antigen (iPSA) < or = 10 ng/mL. METHODS AND MATERIALS: A total of 292 patients with favorable localized prostate cancer were treated with radiotherapy alone between 1986 and 1999. The median age was 69 years. Sixteen percent of cases (n = 46) were African-American. The distribution by clinical T stage was as follows: T1/T2A, 243 (83%); and T2B/T2C, 49 (17%). The distribution by iPSA was as follows: < or = 4 ng/mL, 49 (17%); and > 4 ng/mL, 243 (83%). The mean iPSA level was 6.2 (median, 6.4). The distribution by bGS was as follows: or = 5 in 89 cases (30%) and 6 in 203 cases (70%). The median radiation dose was 70.0 Gy (range, 63.0-78.0 Gy). Doses of < or = 70.0 Gy were delivered in 175 cases, 70.2-72.0 Gy in 24 cases, 74 Gy in 30 cases, and 78 Gy in 63 cases. For patients receiving < 72 Gy, the median dose was 68 Gy, vs. 78 Gy for patients receiving > or = 72 Gy. A conformal technique was used in 129 (44%) of cases. The median follow-up was 43 months (range, 3-153). RESULTS: For the entire cohort, the projected 5- and 8-year biochemical relapse-free survival (bRFS) rates were both 81%. For patients receiving > or = 72 Gy, the 5- and 8-year bRFS rates were both 95% vs. only 77% for patients receiving < 72 Gy, p = 0.010. For patients receiving 74 Gy, the 4-year bRFS rate was 94% vs. 96% for patients receiving 78 Gy, p = 0.90. A multivariate analysis for factors affecting bRFS rates using Cox proportional hazards was performed for all cases using the following variables: age (continuous variable), race (black vs. white), iPSA (continuous variable), bGS (< or = 5 vs. 6), Stage (T1-2A vs. T2B-C), radiation dose (continuous variable), and radiation technique (conformal vs. standard). From the multivariate analysis, only iPSA (p = 0.017, chi(2) = 5.7), and radiation dose (p = 0.021, chi(2) = 5.3) were independent predictors of outcome. Age (p = 0.94), race (p = 0.89), stage (p = 0.45), biopsy GS (p = 0.40), and radiation technique (p = 0.45) were not. CONCLUSION: There is a clear radiation dose response in patients with favorable localized prostate cancers (i.e., Stage T1-T2, biopsy Gleason score < or = 6, and iPSA < or = 10 ng/mL). At least 74 Gy should be delivered to the prostate and periprostatic tissues. With our cohort of patients, longer follow-up will be needed to assess the importance of doses exceeding 74 Gy.

Locally advanced prostate cancer.

Standard therapy for clinically localized prostate cancer includes radical prostatectomy, external beam radiotherapy, or transperineal interstitial brachytherapy. Patients eligible for standard therapy are those with low risk features as defined by various risk group classifications, which generally include clinical stage T1 or T2a, serum prostate-specific antigen (PSA) less than 10 ng/mL, and biopsy Gleason sum of 6 or less. Although there has been important evolution in the performance of these techniques, particularly with respect to functional outcomes, these approaches for low-risk disease are relatively mature, and the cure rates with each of these therapies are similar in this patient population; locally advanced disease is more difficult to cure, however. Biochemical disease-free survival rates in men undergoing radical prostatectomy are clearly related to the pathologic stage. Prognostic groups can be defined based on pathologic stage with increasingly worse outcomes based on extracapsular extension (ECE), margin status, and the status of the lymph nodes and seminal vesicles. In patients with low risk features, the positive margin rate is generally low, making the presence or absence of ECE the dominant variable in predicting the likelihood of treatment failure. These observations suggest that more aggressive therapy is needed to cure those who are likely to have ECE or other adverse histologic features. Several nomograms predicting the likelihood of ECE or 5-year biochemical failure rates are now in routine clinical use, and can be used to select men at high risk of failure with single modality therapy for more aggressive treatment strategies. However, the optimal form of aggressive therapy for these patients is unknown.

Pretreatment nomogram for predicting the outcome of three-dimensional conformal radiotherapy in prostate cancer.

PURPOSE: Several studies have defined risk groups for predicting the outcome after external-beam radiotherapy of localized prostate cancer. However, most models formed patient risk groups, and none of these models considers radiation dose as a predictor variable. The purpose of this study was to develop a nomogram to improve the accuracy of predicting outcome after three-dimensional conformal radiotherapy. MATERIALS AND METHODS: This study was a retrospective, nonrandomized analysis of patients treated at the Memorial Sloan-Kettering Cancer Center between 1988 and 1998. Clinical parameters of the 1,042 patients included stage, biopsy Gleason score, pretreatment serum prostate-specific antigen (PSA) level, whether neoadjuvant androgen deprivation therapy was administered, and the radiation dose delivered. Biochemical (PSA) treatment failure was scored when three consecutive rises of serum PSA occurred. A nomogram, which predicts the probability of remaining free from biochemical recurrence for 5 years, was validated internally on this data set using a bootstrapping method and externally using a cohort of patients treated at the Cleveland Clinic, Cleveland, OH. RESULTS: When predicting outcomes for patients in the validation data set from the Cleveland Clinic, the nomogram had a Somers' D rank correlation between predicted and observed failure times of 0.52. Predictions from this nomogram were more accurate (P<.0001) than the best of seven published risk stratification systems, which achieved a Somers' D coefficient of 0.47. CONCLUSION: The development process illustrated here produced a nomogram that seems to predict more accurately than other available systems and may be useful for treatment selection by both physicians and patients.

Identification and fine mapping of a region showing a high frequency of allelic imbalance on chromosome 16q23.2 that corresponds to a prostate cancer susceptibility locus.

Linkage to a prostate cancer susceptibility locus was recently reported on chromosome 16q23. We now report a region exhibiting a high frequency of allelic imbalance (AI) corresponding to this locus in tumors from 51 men diagnosed with prostate cancer using the same linked markers. The highest frequency of AI was found at markers D16S3096 (45%) and D16S516 (53%) that map to chromosome 16q23.2. In addition, 19 of the 51 (37%) prostate tumors showed interstitial AI involving one or both of these markers. This result strongly suggests that a candidate prostate cancer tumor suppressor gene maps between markers D16S3096 and D16S516. We estimate that the distance between these markers is approximately 118 kb using a Stanford radiation hybrid panel. We observed a positive association with family history (P = 0.048) when comparing those men showing interstitial AI at markers D16S3096 and/or D16S516 with those without any imbalance at these two markers. Taken together, these data suggest that we have precisely localized a region of chromosome 16q23.2 that may harbor a prostate cancer tumor suppressor gene implicated in the development of non-familial and possibly familial forms of prostate cancer.

Results of linear accelerator-based stereotactic radiosurgery for recurrent and newly diagnosed acoustic neuromas.

Stereotactic radiosurgery (SRS) is used to treat acoustic neuromas, but additional information is needed to firmly establish its safety and efficacy. We review our experience over 7 years treating 29 consecutive patients with a modified linear accelerator (linac) SRS system. Between August 1989 and October 1995, 29 patients with a median age of 67 years (range 26 to 83) underwent linac SRS treatment. Twenty-five patients had unilateral acoustic neuromas, and four patients with neurofibromatosis type II had bilateral vestibular schwannoma. Eligibility criteria for SRS were recurrent tumors (n = 9), age >65 (n = 16), or patient preference (n = 6). Follow-up magnetic resonance imaging scans were performed on all patients. The most common presenting symptoms were hearing impairment (18 patients) and gait difficulties (17 patients). Ten patients were deaf in the affected ear prior to treatment. Doses to the periphery of the tumor ranged from 800 to 2,400 cGy (median 1, 600 cGy) prescribed to the 50% to 80% isodose line (median 80%). After a median radiographic follow-up of 49 months (range 4 to 110 months), 11 tumors were smaller, 17 were stable, and one had evidence of progression (at 41 months). The 5-year local disease control rate (Kaplan-Meier estimate) was 94%. Acute complications were minimal, with only two patients experiencing nausea and vomiting after the procedure. Long-term complications included new or progressive trigeminal and facial nerve deficits with estimated 5-year incidences of 15% and 32%, respectively. Subjective hearing reduction or loss occurred in 14 (74%) of the 19 patients who had useful hearing prior to treatment. Five patients died from unrelated causes. These results suggest that linac SRS provides excellent short-term tumor control rates. Since there was a high risk of cranial nerve neuropathy, we do not recommend using only computed tomography-based planning and high prescription doses. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 145-151 (2000).

No difference in biochemical failure rates with or without pelvic lymph node dissection during radical prostatectomy in low-risk patients.

OBJECTIVES: To detect the short-term differences in biochemical relapse-free rates between patients with and without pelvic lymph node dissection (PLND). Recently, a trend has begun to omit PLND in patients undergoing radical prostatectomy considered at low risk of pelvic lymph node metastases. METHODS: The records of 1152 consecutive radical prostatectomy cases were reviewed. A total of 575 patients with favorable tumor characteristics (prostate-specific antigen [PSA] 10 ng/mL or less, Gleason score 6 or less, and clinical Stage T1 or T2) who were not receiving adjuvant or neoadjuvant therapy were divided into two groups according to whether PLND was performed (PLND group, n = 372) or omitted (no PLND group, n = 203). Proportional hazards were used to analyze the effect of age, race, family history, stage, biopsy Gleason score, initial PSA, PLND, and pathologic findings on the likelihood of biochemical failure. Biochemical failure-free survival for each group was estimated by Kaplan-Meier analysis. The mean follow-up was 38 months (range 1 to 141). RESULTS: The actuarial 4-year biochemical relapse-free rate for the PLND versus no PLND groups was 91% and 97%, respectively (P = 0.16). On multivariate analysis, PLND was not an independent predictor of outcome (P = 0.24). CONCLUSIONS: The results of our study indicate that the omission of PLND in patients with favorable tumor characteristics does not adversely affect biochemical relapse rates.

Higher than standard radiation doses (> or =72 Gy) with or without androgen deprivation in the treatment of localized prostate cancer.

PURPOSE: To study the effect on biochemical relapse-free survival (bRFS) and clinical disease-free survival of radiation doses delivered to the prostate and periprostatic tissues for localized prostate cancer. METHODS AND MATERIALS: A total of 1041 consecutive localized prostate cancer cases treated with external beam radiotherapy (RT) at our institution between 7/86 and 2/99 were reviewed. All cases had available pretreatment parameters including pretreatment prostate-specific antigen (iPSA), biopsy Gleason score (bGS), and clinical T stage. The median age was 69 years. Twenty-three percent of cases (n = 238) were African-American. The distribution by clinical T stage was as follows: T1 in 365 cases (35%), T2 in 562 cases (54%), and T3 in 114 cases (11%). The median iPSA level was 10.1 ng/ml (range: 0.4-692.9). The distribution by biopsy Gleason score (bGS) was as follows: < or =6 in 580 cases (56%) and > or =7 in 461 cases (44%). Androgen deprivation (AD) in the adjuvant or neoadjuvant setting was given in 303 cases (29%). The mean RT dose was 71.9 Gy (range: 57.6-78.0 Gy). The median RT dose was 70.2 Gy, with 458 cases (44%) receiving at least 72.0 Gy. The average dose in patients receiving <72 Gy was 68.3 Gy (median 68.4) versus 76.5 Gy (median 78.0) for patients receiving > or =72 Gy. The mean follow-up was 38 months (median 33 months). The number of follow-up prostate-specific antigen (PSA) levels available was 5998. RESULTS: The 5- and 8-year bRFS rates were 61% (95% CI 55-65%) and 58% (95% CI 51-65%), respectively. The 5-year bRFS rates for patients receiving radiation doses > or =72 Gy versus <72 Gy were 87% (95% CI 82-92%) and 55% (95% CI 49-60%), respectively. The 8-year bRFS rates for patients receiving radiation doses > or =72 Gy versus <72 Gy were 87% (95% CI 82-92%) and 51% (95% CI 44-58%), respectively (p < 0.001). A multivariate analysis of factors affecting bRFS was performed using the following parameters: age (continuous variable), race, T-stage (T1-T2 vs. T3), iPSA (continuous variable), bGS (< or =6 vs. > or =7), use of AD (yes vs. no), radiation technique (conformal versus standard), and radiation dose (continuous variable). T-stage (p < 0.001), iPSA (p < 0.001), bGS (p < 0.001), and RT dose (p < 0.001) were independent predictors of outcome. Age (p = 0.74), race (p = 0.96), radiation technique (p = 0.15), and use of AD (p = 0.31) were not. We observed 11% clinical failures (local, distant, or both) at 5 years and 15% at 8 years for the entire cohort. There was a statistically significant improvement with higher radiation doses (p = 0.032). The 5-year clinical relapse rates for patients receiving > or =72 Gy versus <72 Gy were 5% and 12%, respectively. The 8-year clinical relapse rates for patients receiving radiation doses > or =72 Gy versus <72 Gy were 5% and 17%, respectively (p = 0.026). CONCLUSION: Patients receiving radiation doses exceeding 72 Gy had significantly better bRFS and clinical disease-free survival rates. Although results need to be confirmed with longer follow-up, these preliminary results are extremely encouraging. If these results are confirmed by other institutions and by longer follow-up, RT doses exceeding 72 Gy should be considered as standard of care.

Short-course intensity-modulated radiotherapy for localized prostate cancer with daily transabdominal ultrasound localization of the prostate gland.

PURPOSE: To present our initial observations on the clinical feasibility of the technique of short-course intensity-modulated radiotherapy (SCIM-RT) in the treatment of localized prostate cancer coupled with daily transabdominal ultrasound localization of the prostate. The proposed regimen consists of a hypofractionated course delivering 70.0 Gy in 28 fractions. METHODS AND MATERIALS: The treatment data of the first 51 patients treated with SCIM-RT at the Cleveland Clinic Foundation are presented in this report. The technique consisted of intensity-modulated radiotherapy using 5 static fields (anterior, 2 laterals, and 2 anterior obliques). Inverse plans were generated by the Corvus treatment-planning system. The treatment delivery was performed with a Varian Dynamic Multileaf Collimator. The target was the prostate only in patients with low-risk disease (stage T1-T2, pretreatment PSA < or =10, and biopsy Gleason < or =6). The target was the prostate and seminal vesicles in patients with high-risk disease (stage T3 or pretreatment PSA > 10 or biopsy Gleason > or =7). In the Corvus planning system, the margins for the planning target volume (PTV) were 4 mm posteriorly, 8 mm laterally, and 5 mm in all other directions. A total of 70.0 Gy (mean prostate dose approximately 75 Gy) was prescribed in all cases at 2.5 Gy per fraction to be delivered in 28 fractions over 5 1/2 weeks. Prior to treatment delivery, the patients were minimally immobilized on the treatment table, only using lasers and skin marks. The location of the prostate gland was verified daily with the BAT transabdominal ultrasound system and patient position adjustments were performed accordingly. Fifty-one patients completed therapy between October 1998 and May 1999. RESULTS: The dose was prescribed to an isodose line ranging from 82.0% to 90.0% (mean: 87.2%). The range of the individual prostate mean doses was 73.5 to 78.5 Gy (average: 75.3 Gy). The range of the maximum doses was 77.4 to 84.5 Gy (average: 80.2 Gy). The range of the minimum doses was 64.3 to 69.2 Gy (average: 67.5 Gy). The average time for the prostate position verification and alignment of the prostate using the BAT system was 5 minutes. The entire localization/alignment process was performed by the radiation therapists. The daily alignment images were automatically saved and reviewed by the radiation oncologist, a process similar to port film checks. The total treatment (beam-on) time was around 6 minutes using the 5 static intensity-modulated fields. The mean and standard deviation (SD) of bladder volumes irradiated to 50, 60, and 70 Gy were as follows: 24 +/- 11 cc, 16 +/- 8 cc, and 8 +/- 6 cc. The mean and SD of rectal volumes irradiated to 50, 60, and 70 Gy were as follows: 22 +/- 11 cc, 15 +/- 8 cc, and 7 +/- 5 cc. The RTOG acute bladder toxicity scores were as follows: 0 in 3 (6%), 1 in 38 (74%), and 2 in 10 (20%). The RTOG acute rectal toxicity scores for SCIM-RT cases were as follows: 0 in 10 (20%), 1 in 33 (65%), and 2 in 8 (16%). No Grade 3 or 4 acute toxicities were observed. CONCLUSION: The delivery of our proposed hypofractionated-schedule SCIM-RT in combination with daily target localization/alignment with the BAT transabdominal ultrasound system is clinically feasible. It is an alternative method of dose escalation in the treatment of localized prostate cancer. The proposed schedule would significantly increase convenience to patients due to the decrease in overall treatment time. Preliminary acute toxicity results are extremely encouraging. Long-term follow-up is needed to assess late complications and treatment efficacy.

Extent of extracapsular extension in localized prostate cancer.

OBJECTIVES: To measure the radial extent of extracapsular penetration by tumor cells, thereby providing estimates of the margins needed around target volumes. New radiotherapeutic techniques, like brachytherapy and conformal radiotherapy, irradiate small volumes and reduce the dose to periprostatic tissues. Even in the early stages of localized prostate cancer, extracapsular extension (ECE) is commonly seen. METHODS: Two hundred sixty-five consecutive radical prostatectomy specimens were analyzed for the presence of ECE. ECE was found in 92 of all cases (35%); measurements were performed in 79 of the 92 cases. A total of 98 ECE sites were evaluated in the 79 cases. The distance of tumor outside the capsule was measured in millimeters. Extension less than 0.1 mm was considered as "focal". RESULTS: The site of ECE was posterolateral in 53% of cases, lateral in 24%, posterior in 13%, and at the base in 10%. The median amount of ECE at all sites was 1. 1 mm (mean 1.7). However, the range was wide; the minimum measurable extent was 0.1 mm and the maximum 10.0 mm. The extent was within 3.8 mm for 90% of all cases. By stratifying cases with favorable and unfavorable tumors, the 90th percentiles of ECE were as follows: 3.3 mm for favorable tumors (clinical Stage T1-2, initial prostate-specific antigen 10 ng/mL or less, and biopsy Gleason score 6 or less) and 3.9 mm for unfavorable tumors (clinical Stage T3, initial prostate-specific antigen greater than 10 ng/mL, or biopsy Gleason score 7 or greater). CONCLUSIONS: Most of the ECE was at posterolateral sites. The extent of disease outside the prostate was within 4 mm in 90% of cases. Since ECE was observed in 30% to 60% of all patients with clinical Stage T1-2 prostate cancer, only 3% to 7% of all such cases would have disease extent exceeding 4 mm. The present study provides useful estimates of the amount of ECE. These estimates could be potentially used in planning the target volumes for treatment of prostate cancer with either conformal radiotherapy or brachytherapy.

Importance of high radiation doses (72 Gy or greater) in the treatment of stage T1-T3 adenocarcinoma of the prostate.

OBJECTIVES: To analyze the effect of total radiation dose on the outcome of patients treated with external beam radiotherapy for early-stage prostate cancer. METHODS: The records of a total of 738 patients with localized prostate cancer treated with external beam radiotherapy (RT) and no androgen deprivation at our institution between July 1986 and February 1999 were reviewed. Two risk groups were defined: favorable (Stage T1-T2, pretreatment prostate-specific antigen [PSA] level 10.0 ng/mL or less, and biopsy Gleason score 6 or less) and unfavorable (Stage T3 lesion or pretreatment PSA level greater than 10.0 ng/mL or biopsy Gleason score 7 or greater). The median RT dose was 70.0 Gy (range 57.6 to 78.0), with 192 patients (26%) receiving at least 72.0 Gy. The mean follow-up was 45 months. RESULTS: The 5-year biochemical relapse-free survival (bRFS) rate was 58%. The 5-year bRFS rate for patients who received radiation doses of 72 Gy or greater versus less than 72 Gy was 85% and 54%, respectively (P <0.001). On multivariate analysis of factors affecting bRFS rates, the number of follow-up PSA levels (P <0.001), tumor stage (P <0.001), pretreatment PSA (P <0.001), biopsy Gleason score (P <0.00 1), and RT dose (P = 0.001) were the only independent predictors of outcome. For favorable tumors, the 5-year bRFS rate for patients who received radiation doses of 72 Gy or greater versus less than 72 Gy was 98% and 81 %, respectively (P = 0.023). For unfavorable tumors, the 5-year bRFS rate for patients who received radiation doses of 72 Gy or greater versus less than 72 Gy was 75% and 41 %, respectively (P = 0.001). CONCLUSIONS: Patients receiving radiation doses of 72 Gy or higher had a significantly better outcome. The improvement was seen in all subgroups of patients. If these results are confirmed, radiation doses exceeding 72 Gy should be considered the standard of care. Inc.

Localized prostate cancer.

Much controversy still surrounds the diagnosis and treatment of localized prostate cancer. Urologists generally believe that early detection and aggressive surgical therapy saves lives despite the absence of confirmatory randomized trials. Furthermore, a recent survey of radiation oncologists and urologists revealed marked polarization toward their own specialties when asked how they would counsel patients on therapy for newly diagnosed localized disease. Some issues are not controversial, however. There is general agreement that pretreatment tumor characteristics, including serum prostate-specific antigen level at diagnosis, tumor grade, and clinical stage as judged by digital rectal examination, are important prognosticators for treatment outcomes independent of the type of treatment. Also, there is sufficient experience with standard therapies (radical prostatectomy and external beam radiotherapy) to counsel patients on the chance for cure and the expected incidence of acute and chronic toxicities. A comparative evaluation of various therapies for prostate cancer should include consideration of cancer control, acute toxicity, treatment-related quality of life issues, salvage of treatment failures, and cost. Within this context, we believe that newly diagnosed patients should be counseled on all available treatment options before embarking on a course of therapy.

Treatment outcome for patients with primary nonsmall-cell lung cancer and synchronous brain metastasis.

The purpose of this study was to evaluate the outcome of treatment for patients with newly diagnosed nonsmall-cell lung cancer (NSCLC) with an isolated, single, synchronous brain metastasis. A retrospective review was performed evaluating any patient diagnosed between 1982 and 1996 at the Cleveland Clinic Foundation with NSCLC metastatic only to the brain. Patients with multiple brain metastases or with systemic metastases to any other organ were excluded. Survival was measured from the date of the first treatment for malignancy. All hospital records were thoroughly reviewed in a retrospective manner. Thirty-three patients were identified who met the study criteria. Twelve patients had primary disease limited to the lung and hilar nodes, and 21 had more advanced primary disease with involvement of the mediastinum. Treatment of the chest was considered aggressive in 13 patients and palliative in 15. The primary tumor was observed in 5 patients. The management of the brain metastasis was as follows: 21 patients underwent surgical resection and postoperative whole brain radiotherapy (WBRT), 5 underwent stereotactic radiosurgery (SRS) and WBRT, 3 had resection alone, 2 had SRS alone, and 2 underwent WBRT alone. The median overall and disease-free survival for all patients was 6.9 months and 3.3 months, respectively. Overall survival was markedly improved with the addition of WBRT (P = 0.002) and with the aggressive management of the primary tumor (P = 0.005). A total of 9 patients experienced CNS failure, including both patients receiving WBRT alone. CNS failures were divided as follows: 3 local, 5 distant, and 1 local and distant. Two of the 4 patients with a local failure were salvaged, and ultimate local control of the original brain metastasis was achieved in 93.6% of cases. Survival remains poor for patients with Stage IV NSCLC even when metastatic disease is limited to a single site within the brain; however, aggressive therapy of both the lung primary and the brain metastasis may provide a survival advantage. Excellent local control of single brain metastases was achieved with a combination of WBRT with either surgical resection or SRS.