Biomedical subjects

T E Schultheiss

Publications and source records attributed to T E Schultheiss.

At least 19 recordsLinked to original sources

PubMed2001

The controversies and pitfalls in modeling normal tissue radiation injury/damage.

Highly conformal fields have become achievable in routine clinical practice. The optimal shape of the resultant dose distributions depends on information that is not currently available. This missing information is the dose-volume response of the normal tissues at risk. These functions are now the subject of aggressive research. The research involves collecting the dose-response data, modeling the dose-response function, and fitting the models to the data. The controversies addressed here influence the selection of the biomathematical model that one might use to describe such a function. The form that the dose-volume response function takes depends on the nature of the volume effect. The nature of the volume effect for a given radiation response is the subject of considerable debate. Related to this debate, this report addresses the existence of the volume effect, the existence of a threshold volume, and the existence of functional subunits. The pitfalls relate to the problems in accurate determination and application of the dose-response functions.

Dose-Response Relationship, Radiation↗

PubMed2000

Ultrasound-based stereotactic guidance in prostate cancer--quantification of organ motion and set-up errors in external beam radiation therapy.

OBJECTIVE: A mobile transabdominal ultrasound-based targeting system (BAT(R)) has been developed which can stereotactically localize the position of the prostate each treatment day and directly integrate this information into the treatment planning system. Daily target verification facilitates a marked reduction in planning treatment margins by correcting potential organ-motion and set-up errors. Previous studies have been performed to establish the precision of ultrasound localization. This report quantifies the magnitude of the patient isocenter shift parameters encountered during clinical implementation of this system. MATERIAL AND METHODS: After five weeks of conformal external beam radiation therapy, 54 patients underwent a second CT simulation. Prostate-only fields based on this scan were created with no PTV margin beyond the CTV. For each of the final conedown treatments (2-4 fractions), patients underwent ultrasound-based stereotactic prostate localization at the treatment machine. The portable system, which electronically imports the CT simulation target-contour and isocenter information, is situated adjacent to the treatment couch. Transverse and sagittal suprapubic ultrasound images are captured, and the system electronically couples this data to the baseline isocenter. The CT contours are maneuvered in three dimensions by a touch-screen menu to visually overlay the ultrasound images. The system then displays the three-dimensional (3D) couch shifts required to produce field alignment. RESULTS: One hundred and eighty-nine daily ultrasound prostate position shifts were recorded for 54 patients. The isocenter field misalignment between the baseline CT and ultrasound ranged from -26.8 to 33.8 mm in the anterior/posterior (A/P) dimension, -10.2 to 30.9 mm in the lateral dimension, and -24.6 to 9.0 mm in the superior/inferior (S/I) dimension. The corresponding directed average disagreements were -3.0 mm (SD 8.3 mm) A/P, 1.86 mm (SD 5.7 mm) lateral, and -2.6 mm (SD 6.5 mm) S/I. The magnitudes of undirected misalignments were frequently larger than 5 mm (51% of A/P, 31% of lateral, and 35% of superior measurements) and oftentimes larger than 10 mm (21% of A/P, 7% of lateral, and 12% of superior measurements). CONCLUSIONS: Organ motion and set-up uncertainties limit optimization of 3D treatment planning by expanding the width of PTV margins required to ensure target coverage. Transabdominal ultrasound-based stereotactic guidance is a safe and direct method for correcting patient positioning. Our experience with the BAT system in a large cohort of prostate cancer patients revealed that substantial daily isocenter corrections were encountered in a large percentage of cases. This data would suggest that daily clinical isocenter misalignments are greater than would be expected from published data on organ motion and set-up variations encountered in the study setting.

Cohort Studies↗

PubMed2000

Ultrasound-based stereotactic guidance of precision conformal external beam radiation therapy in clinically localized prostate cancer.

OBJECTIVES: Use of external beam radiation fields that conform to the shape of the target improves biochemical control in prostate cancer by facilitating dose escalation through increased sparing of normal tissue. By correcting potential organ motion and setup errors, ultrasound-directed stereotactic localization is a method that may improve the accuracy and effectiveness of current conformal technology. The purpose of this study was to quantify the precision of the transabdominal ultrasound-based approach using computed tomography (CT) as a standard. METHODS: Thirty-five consecutive men participated in a prospective comparison of daily CT and ultrasound-guided localization at Fox Chase Cancer Center. Daily CT prostate localization was completed before the delivery of each final boost field. In the CT simulation suite, transabdominal ultrasound-based stereotactic localization was also performed. The main outcome measure was a three-dimensional comparison of prostate position as determined by CT versus ultrasound. RESULTS: Sixty-nine daily CT and ultrasound prostate position shifts were recorded for 35 patients. The magnitude of difference between the CT and ultrasound localization ranged from 0 to 7.0 mm in the anterior/posterior, 0 to 6.4 mm in the lateral, and 0 to 6.7 mm in the superior/inferior dimension. The corresponding directed average disagreements were extremely small: anterior/posterior, -0.09 +/- 2.8 mm SD; lateral, -0.16 +/- 2.4 mm SD; and superior/inferior, -0.03 +/- 2.3 mm SD). Analysis of the paired CT-ultrasound shifts revealed a high correlation between the two modalities in all three dimensions (anterior/ posterior r = 0.88; lateral r = 0.91; and superior/inferior r = 0.87). CONCLUSIONS: Ultrasound-directed stereotactic localization is safe and as accurate as CT scanning in targeting the prostate for conformal external beam radiation therapy. The application of this technology to current conformal techniques will allow the reduction of treatment margins in all dimensions. This should diminish treatment-related morbidity and facilitate further dose escalation, resulting in improved cancer control.

Follow-Up Studies↗

PubMed1999

A comparison of daily CT localization to a daily ultrasound-based system in prostate cancer.

PURPOSE: Daily CT localization has been demonstrated to be a precise method of correcting radiation field placement by reducing setup and organ motion variations to facilitate dose escalation in prostate carcinoma. The purpose of this study was to evaluate the feasibility and accuracy of daily ultrasound-guided localization utilizing daily CT as a standard. The relatively simple computer-assisted ultrasound-based system is designed to be an efficient means of achieving daily accuracy. METHODS AND MATERIALS: After five weeks of conformal external beam radiation therapy, 23 patients underwent a second CT simulation. Prostate-only fields based on this scan were created with no PTV margin. On each of the final conedown treatment days, a repeat CT simulation and isocenter comparison was performed. Ten of the above patients also underwent prostate localization with a newly developed ultrasound-based system (BAT) that is designed to facilitate patient positioning at the treatment machine. The portable system, which electronically imports the CT simulation target contours and isocenter, is situated adjacent to the treatment couch. Transverse and sagittal suprapubic ultrasound images are captured, and the system overlays the corresponding CT contours relative to the machine isocenter. The CT contours are maneuvered in three dimensions by a touch screen menu to match the ultrasound images. The system then displays the 3-D couch shifts required to produce field alignment. RESULTS: The BAT ultrasound system produced good quality images with minimal operator training required. The localization process was completed in less than 5 min. The absolute magnitude difference between CT and ultrasound was small (A/P range 0 to 5.9 mm, mean 3 mm +/- 1.8; Lat. range 0 to 7.9 mm, mean 2.4 mm +/- 1.8; S/I range 0 to 9 mm, mean 4.6 mm +/- 2.8). Analysis confirmed a significant correlation of isocenter shifts (A/P r = 0.66, p < 0.0001; Lat. r = 0.58, p < 0.003; S/I r = 0.78, p < 0.0001) in all dimensions, and linear regression confirmed the equivalence of the two modalities. CONCLUSIONS: Daily CT localization is a precise method to improve daily target localization in prostate carcinoma. However, it requires significant human and technical resources that limit its widespread applicability. Conversely, localization with the BAT ultrasound system is simple and expeditious by virtue of its ability to image the prostate at the treatment machine in the treatment position. Our initial evaluation revealed ultrasound targeting to be functionally equivalent to CT. This ultrasound technology is promising and warrants further investigation in more patients and at other anatomical sites.

Feasibility Studies↗

PubMed1998

Daily CT localization for correcting portal errors in the treatment of prostate cancer.

INTRODUCTION: Improved prostate localization techniques should allow the reduction of margins around the target to facilitate dose escalation in high-risk patients while minimizing the risk of normal tissue morbidity. A daily CT simulation technique is presented to assess setup variations in portal placement and organ motion for the treatment of localized prostate cancer. METHODS AND MATERIALS: Six patients who consented to this study underwent supine position CT simulation with an alpha cradle cast, intravenous contrast, and urethrogram. Patients received 46 Gy to the initial Planning Treatment Volume (PTV1) in a four-field conformal technique that included the prostate, seminal vesicles, and lymph nodes as the Gross Tumor Volume (GTV1). The prostate or prostate and seminal vesicles (GTV2) then received 56 Gy to PTV2. All doses were delivered in 2-Gy fractions. After 5 weeks of treatment (50 Gy), a second CT simulation was performed. The alpha cradle was secured to a specially designed rigid sliding board. The prostate was contoured and a new isocenter was generated with appropriate surface markers. Prostate-only treatment portals for the final conedown (GTV3) were created with a 0.25-cm margin from the GTV to PTV. On each subsequent treatment day, the patient was placed in his cast on the sliding board for a repeat CT simulation. The daily isocenter was recalculated in the anterior/posterior (A/P) and lateral dimension and compared to the 50-Gy CT simulation isocenter. Couch and surface marker shifts were calculated to produce portal alignment. To maintain proper positioning, the patients were transferred to a stretcher while on the sliding board in the cast and transported to the treatment room where they were then transferred to the treatment couch. The patients were then treated to the corrected isocenter. Portal films and electronic portal images were obtained for each field. RESULTS: Utilizing CT-CT image registration (fusion) of the daily and 50-Gy baseline CT scans, the isocenter changes were quantified to reflect the contribution of positional (surface marker shifts) error and absolute prostate motion relative to the bony pelvis. The maximum daily A/P shift was 7.3 mm. Motion was less than 5 mm in the remaining patients and the overall mean magnitude change was 2.9 mm. The overall variability was quantified by a pooled standard deviation of 1.7 mm. The maximum lateral shifts were less than 3 mm for all patients. With careful attention to patient positioning, maximal portal placement error was reduced to 3 mm. CONCLUSION: In our experience, prostate motion after 50 Gy was significantly less than previously reported. This may reflect early physiologic changes due to radiation, which restrict prostate motion. This observation is being tested in a separate study. Intrapatient and overall population variance was minimal. With daily isocenter correction of setup and organ motion errors by CT imaging, PTV margins can be significantly reduced or eliminated. We believe this will facilitate further dose escalation in high-risk patients with minimal risk of increased morbidity. This technique may also be beneficial in low-risk patients by sparing more normal surrounding tissue.

Computer Simulation↗

PubMed1998

Study of lung density corrections in a clinical trial (RTOG 88-08). Radiation Therapy Oncology Group.

PURPOSE: To investigate the effect of lung density corrections on the dose delivered to lung cancer radiotherapy patients in a multi-institutional clinical trial, and to determine whether commonly available density-correction algorithms are sufficient to improve the accuracy and precision of dose calculation in the clinical trials setting. METHODS AND MATERIALS: A benchmark problem was designed (and a corresponding phantom fabricated) to test density-correction algorithms under standard conditions for photon beams ranging from 60Co to 24 MV. Point doses and isodose distributions submitted for a Phase III trial in regionally advanced, unresectable non-small-cell lung cancer (Radiation Therapy Oncology Group 88-08) were calculated with and without density correction. Tumor doses were analyzed for 322 patients and 1236 separate fields. RESULTS: For the benchmark problem studied here, the overall correction factor for a four-field treatment varied significantly with energy, ranging from 1.14 (60Co) to 1.05 (24 MV) for measured doses, or 1.17 (60Co) to 1.05 (24 MV) for doses calculated by conventional density-correction algorithms. For the patient data, overall correction factors (calculated) ranged from 0.95 to 1.28, with a mean of 1.05 and distributional standard deviation of 0.05. The largest corrections were for lateral fields, with a mean correction factor of 1.11 and standard deviation of 0.08. CONCLUSIONS: Lung inhomogeneities can lead to significant variations in delivered dose between patients treated in a clinical trial. Existing density-correction algorithms are accurate enough to significantly reduce these variations.

Algorithms↗

PubMed1998

Dose escalation with 3D conformal treatment: five year outcomes, treatment optimization, and future directions.

PURPOSE: To report the 5-year outcomes of dose escalation with 3D conformal treatment (3DCRT) of prostate cancer. METHODS AND MATERIALS: Two hundred thirty-two consecutive patients were treated with 3DCRT alone between 6/89 and 10/92 with ICRU reporting point dose that increased from 63 to 79 Gy. The median follow-up was 60 months, and any patient free of clinical or biochemical evidence of disease was termed bNED. Biochemical failure was defined as prostate-specific antigen (PSA) rising on two consecutive recordings and exceeding 1.5 ng/ml. Morbidity was reported by the Radiation Therapy Oncology Group (RTOG) scale, the Late Effects Normal Tissue (LENT) scale, and a Fox Chase modification of the latter (FC-LENT). All patients were treated with a four-field technique with a 1 cm clinical target volume (CTV) to planning target volume (PTV) margin to the prostate or prostate boost; the CTV and gross tumor volume (GTV) were the same. Actuarial rates of outcome were calculated by Kaplan-Meier and cumulative incidence methods and compared using the log rank and Gray's test statistic, respectively. Cox regression models were used to establish prognostic factors predictive of the various measures of outcome. Five-year Kaplan-Meier bNED rates were utilized by dose group to estimate logit response models for bNED and late morbidity. RESULTS: PSA <10 ng/ml: No dose response was demonstrated using estimated bNED rates or by analysis of PSA nadir vs. dose. PSA 10-19.9 ng/ml: A bNED dose response was demonstrated (p = 0.02) using the log rank test. The logit response model showed 5-year bNED rates of 35% at 70 Gy and 75% at 76 Gy (p = 0.0049) and illustrated the relative ineffectiveness of conventional dose treatment. PSA 20+ ng/ml: A bNED dose response was demonstrated (p = 0.02) using the log rank test. The logit response model indicated a 5-year bNED rate of 10% at 70 Gy and 32% at 76 Gy (p = 0.10). Morbidity: Dose response was demonstrated for FC-LENT grade 2 and grade 3,4 GI morbidity and for LENT grade 2 GU sequelae. RTOG grade 3,4 GI morbidity at 5 years was <1%. Factors associated with bNED, cause-specific survival, and metastasis were studied using Cox multivariate analysis. Pretreatment PSA (p = 0.0001), Gleason score 7-10 (p = 0.0001), and dose (p = 0.017) were significantly predictive of bNED. For each 1 Gy increase in dose, the hazard of bNED failure decreased by 8%. Palpation stage was associated with cause-specific survival (p = 0.002) and distant metastasis (p = 0.0004). Gleason score was also predictive of distant metastasis (p = 0.02). CONCLUSIONS: A dose response was observed for patients with pretreatment PSA >10 ng/ml based on 5-year bNED results. No dose response was observed for patients with pretreatment PSA < 10 ng/ml. Dose response was observed for FC-LENT grade 2 and grade 3,4 GI sequelae and for LENT grade 2 GU sequelae. Optimization of treatment was made possible by the results in this report. The improvement in 5-year bNED rates for patients with PSA levels > 10 ng/ml strongly suggests that clinical trials employing radiation should investigate the use of 3DCRT and prostate doses of 76-80 Gy.

Dose-Response Relationship, Radiation↗

PubMed1998

Beam characteristics of a retrofitted double-focused multileaf collimator.

Multileaf collimators (MLCs) are generally believed to be convenient and cost-effective tools for intensity modulation and conformal therapy. They are becoming a standard feature on new accelerators; however, the older units can be retrofitted with modern MLCs. Before such a unit can be clinically used, the beam characteristics must be verified. In this study the beam characteristics of a Siemens double-focused MLC retrofitted to an MD2 linear accelerator are presented. The head leakage along with inter- and intra-leaf radiation transmission were measured using film. The collimator (Sc), phantom (Sp), total (Scp) scatter factors, central axis depth dose, beam profiles for off-axis ratios, penumbra, and surface dose were evaluated for square, rectangular, and irregularly shaped fields. The maximum head leakage was estimated to be < 0.05% in any plane at a distance of 1 m and maximum transmission through the MLC leaves was estimated to be < 1.4% and < 1.1% for the 10 MV and 6 MV beams, respectively. The maximum differences between pre- and post-MLC installation data for the Sc and Scp were < or = 0.7% and < or = 1.4%, respectively. Similarly, the percent depth dose data for all fields and both beam energies were within 1.5% of the original data. The beam profiles measured at various depths were also in agreement with those of the pre-MLC installation data. The measured beam penumbra (20%-80%) showed a range of 7.8 mm-11.0 mm for the 6 MV and 8.4 mm-11.1 mm for the 10 MV beams from smallest to largest fields. These ranges differ by less than a millimeter from those of the old data. The surface dose measurements were slightly lower than the conventional jaw values suggesting that MLC does not produce significant electron contamination. It is concluded that the retrofitted MLC maintains the integrity of the original beam and may provide a cost-effective conformal therapy.

Biophysical Phenomena↗

PubMed1997

Rectal bleeding after conformal 3D treatment of prostate cancer: time to occurrence, response to treatment and duration of morbidity.

PURPOSE: Rectal bleeding is the most common late sequelae of high-dose 3D conformal treatment (3DCRT) for prostate cancer and may limit attempts to improve local control by dose escalation. The clinical course of this complication is reported including time to onset, response to treatment, duration of morbidity, and multivariate analysis for predictors. METHODS AND MATERIALS: From March 1989 to June 1995, 670 patients with prostate cancer were treated with 3DCRT at Fox Chase Cancer Center. Eighty-nine patients developed Grade 2 or Grade 3 complications due to rectal bleeding and are analyzed. Multivariate analysis results for predictors of Grade 2 and 3 rectal bleeding are reported as well as time to development, response to initial and retreatment, and duration of morbidity. RESULTS: The median time to occurrence is not significantly different (p = 0.09) for Grade 2 (13 months, range 4-41 months) compared to Grade 3 rectal bleeding (18 months, range 4-40 months), while the corresponding median duration of symptoms was significantly different (p < 0.0001) being 1 month (range 1-12) vs. 10 months (1-34) for Grade 2 and Grade 3 bleeding, respectively. For Grade 2 bleeding, medication or coagulation was highly effective as initial or retreatment resolving 66 of 73 patients. For Grade 3 bleeding, three patients responded without medication following blood transfusion only, while with multiple coagulations and medication 12 of 16 patients improved to < or = Grade 1. Multivariate analysis demonstrates that dose is the only significant factor associated with Grade 2 (p = 0.01) or Grade 3 (p = 0.01) rectal bleeding. Of seven nonresponders to treatment for Grade 2 bleeding, three have died of intercurrent disease at 10, 19, and 26 months, while four are alive with continuing Grade 2 bleeding at 12, 14, 15, and 30 months after onset. The four nonresponders to treatment for Grade 3 bleeding continue to bleed 1, 9, 32, and 35 months after the third coagulation despite continuing care. CONCLUSIONS: Chronic rectal bleeding is a sequelae of high-dose conformal treatment of prostate cancer. Grade 2 morbidity responds to medication or limited coagulation (< or = 2) in 90% of patients. Grade 3 morbidity responds to medication and multiple coagulations (> or = 3) in 75% of patients. The chronicity of Grade 3 morbidity is illustrated by a 10-month median duration for response to treatment, with a range of response extending to 34 months. Nonresponders to treatment have continued to bleed up to 35 months after the third coagulation. Appropriate shielding of the rectal mucosa limiting dose to < 72 Gy is required to avoid a high incidence of these complications, as dose is the only significant variable associated with rectal bleeding.

Aged↗

PubMed1997

Initial clinical assessment of CT-MRI image fusion software in localization of the prostate for 3D conformal radiation therapy.

PURPOSE: To assess the utility of image fusion software and compare MRI prostate localization with CT localization in patients undergoing 3D conformal radiation therapy of prostate cancer. MATERIALS AND METHODS: After a phantom study was performed to ensure the accuracy of image fusion procedure, 22 prostate cancer patients had CT and MRI studies before the start of radiotherapy. Immobilization casts used during radiation treatment were also used for both imaging studies. After the clinical target volume (CTV) (prostate or prostate + seminal vesicles) was defined on CT, slices from the MRI study were reconstructed to precisely match the CT slices by identifying three common bony landmarks on each study. The CTV was separately defined on the matched MRI slices. Data related to the size and location of the prostate were compared between CT and MRI. The spatial relationship between the tip of urethrogram cone on CT and prostate apex seen on MRI was also estimated. RESULTS: The phantom study showed the registration discrepancies between CT and MRI smaller than 1.0 mm in any pair in comparison. The patient study showed a mean image registration error of 0.9 (+/- 0.6) mm. The average prostate volume was 63.0 (+/- 25.8) cm3 and 50.9 (+/- 22.9) cm3 determined by CT and MRI, respectively. The difference in prostate location with the two studies usually differed at the base and at the apex of the prostate. On the transverse MRI, the prostate apex was situated 7.1 (+/- 4.5) mm dorsal and 15.1 (+/- 4.0) mm cephalad to the tip of urethrogram cone. CONCLUSIONS: CT-MRI image fusion study made it possible to compare the two modalities directly. MRI localization of the prostate is more accurate than CT, and indicates the distance from cone to apex is 15 mm. CT-MRI image fusion technique provides valuable supplements to CT technology for more precise targeting of the prostate cancer.

Aged↗

PubMed1997

Chronic rectal bleeding after high-dose conformal treatment of prostate cancer warrants modification of existing morbidity scales.

PURPOSE: Serious late morbidity (Grade 3/4) from the conformal treatment of prostate cancer has been reported in <1% to 6% of patients based on existing late gastrointestinal (GI) morbidity scales. None of the existing morbidity scales include our most frequently observed late GI complication, which is chronic rectal bleeding requiring multiple fulgerations. This communication documents the frequency of rectal bleeding requiring multiple fulgerations and illustrates the variation in reported late serious GI complication rates by the selection of morbidity scale. METHODS AND MATERIALS: Between May 1989 and December 1993, 352 patients with T1-T3 nonmetastatic prostate cancers were treated with our four-field conformal technique without special rectal blocking. This technique includes a 1-cm margin from the clinical target volume (CTV) to the planning target volume (PTV) in all directions. The median follow-up for these patients was 36 months (range 2-76), and the median center of prostate dose was 74 Gy (range 63-81). Three morbidity scales are assessed: the Radiation Therapy Oncology Group (RTOG), the Late Effects Normal Tissue Task Force (LENT), and our modification of the LENT (FC-LENT). This modification registers chronic rectal bleeding requiring at least one blood transfusion and/or more than two coagulations as a Grade 3 event. Estimates for Grade 3/4 late GI complication rates were determined using Kaplan-Meier methodology. The duration of severe symptoms with chronic rectal bleeding is measured from the first to the last transrectal coagulation. Latency is measured from the end of radiotherapy to surgery, first blood transfusion, or third coagulation procedure. RESULTS: Sixteen patients developed Grade 3/4 complications by one of the three morbidity scales. Two patients required surgery (colostomy or sigmoid resection), three required multiple blood transfusions, two required one or two blood transfusions, and nine required at least three coagulations. The median duration of bleeding for those patients requiring multiple procedures was 7 months (range 3-33) and the median latency was 22 months (range 9-40). The 5-year actuarial rate of Grade 3/4 complications by each scale are: RTOG 0.7%, LENT 2%, and FC-LENT 6%. The rate of chronic rectal bleeding increases with increasing dose and is low in patients treated with conventional techniques owing to lower doses. CONCLUSION: Chronic rectal bleeding requiring any blood transfusion(s) or multiple coagulation procedures is our most frequently observed complication. This complication appears late in follow-up and is present for a long duration. We believe this justifies the inclusion of chronic rectal bleeding requiring multiple coagulation procedures as a Grade 3 event in future morbidity scales. Our data illustrate that published Grade 3/4 morbidity rates are highly dependent on the morbidity scale selected, as our data show 0.7% RTOG, 2% LENT, and 6% FC-LENT. Obviously, a uniform scale is required that includes the newly recognized serious late effects associated with the conformal treatment of prostate cancer.

Aged↗

PubMed1997

Optimization of conformal radiation treatment of prostate cancer: report of a dose escalation study.

PURPOSE: The development of conformal radiation technique including improved patient immobilization has allowed us to test the value of dose escalation in optimizing the radiation treatment of prostate cancer. METHODS AND MATERIALS: Outcome is reported for 233 consecutive patients treated with conformal technique between March 1989 and October 1992. Dose was escalated from 68 Gy to 79 Gy. Patient status is reported at 3 years follow-up, which is available in all alive patients. Pretreatment and serial posttreatment prostate specific antigen (PSA) values are available for all patients. Biochemical freedom of disease (bNED) defines failure as PSA > 1.5 ngm/ml and rising on two consecutive measures. Dose response for bNED control of cancer and late morbidity are represented by logit response models fitted to the data. Kaplan-Meier methods, the log rank test, and Cox Regression models are also used. RESULTS: No dose response is observed for bNED survival for patients with pretreatment PSA <10 ngm/ml comparing patients treated above or below 71.5 Gy or on multivariate analysis. Dose response is observed for bNED survival for pretreatment PSA groups of 10-19.9 ngm/ml and 20+ ngm/ml. The dose associated with 50% bNED survival at 3 years is 64 Gy and 76 Gy, respectively. The slope of the dose responses are 13 and 9%, respectively. Dose response is demonstrated for Grade 2 gastrointestinal (GI), Grade 2 genitourinary (GU), and Grade 3,4 combined GI and GU late morbidity. The slopes of the morbidity responses are steeper than for cancer control (19 to 21%). CONCLUSIONS: Patients with pretreatment PSA < 10 ngm/ml do not benefit from dose escalation, and the serious late morbidity of conformal radiation at 70 Gy is < 3%. Patients with PSA values 10-19.9 ngm/ml and 20+ ngm/ml benefit from dose escalation beyond 70 Gy. Treatment beyond 75 Gy results in > 10% serious morbidity unless special precautions are taken to protect the rectal mucosa. All levels of severity of radiation morbidity show a dose response and combined with the dose response for bNED survival these data allow the optimization of treatment.

Disease-Free Survival↗

PubMed1997

The value of setup portal films as an estimate of a patient's position throughout fractionated tangential breast irradiation: an on-line study.

PURPOSE: To determine if portal setup films are an accurate representation of a patient's position throughout the course of fractionated tangential breast irradiation. METHODS AND MATERIALS: Thirteen patients undergoing external beam irradiation for T1-T2 infiltrating ductal carcinoma of the breast following excisional biopsy and axillary dissection were imaged using an on-line portal imaging device attached to a 6 MV linear accelerator. Medial and lateral tangential fields were imaged and a total of 139 fractions, 225 portal fields, and 4450 images were obtained. Interfractional and intrafractional variations for anatomical parameters including the central lung distance (CLD), central flash distance (CFD), and inferior central margin (ICM) were calculated from these images. A pooled estimate of the random error associated with a given treatment was determined by adding the interfractional and intrafractional standard deviations in quadrature. A 95% confidence level assigned a value of two standard deviations of the random error estimate. Central lung distance, CFD, and ICM distances were then measured for all portal setup films. Significant differences were defined as occurring when the simulation-setup difference was greater than the 95% confidence value. RESULTS: Differences between setup portal and simulation films were less than their 95% confidence values in 70 instances indicating that in 90% of the time these differences are a result of random differences in daily treatment positioning. CONCLUSIONS: In 90% of cases tested, initial portal setup films are an accurate representation of a patients daily treatment setup.

Breast Neoplasms↗

PubMed1997

Late GI and GU complications in the treatment of prostate cancer.

PURPOSE: To assess the factors that predict late GI and GU morbidity in radiation treatment of the prostate. METHODS AND MATERIALS: Seven hundred twelve consecutive prostate cancer patients treated at this institution between 1986 and 1994 (inclusive) with conformal or conventional techniques were included in the analysis. Patients had at least 3 months follow-up and received at least 65 Gy. Late GI Grade 3 morbidity was rectal bleeding (requiring three or more procedures) or proctitis. Late Grade 3 GU morbidity was cystitis or stricture. Multivariate analysis (MVA) was used to assess factors related to the complication-free survival. The factors assessed were age, occurrence of side effects > or = Grade 2 during treatment, irradiated volume parameters (use of pelvic fields, treatment of seminal vesicles to full dose or 57 Gy, and use of additional rectal shielding), dose, comorbidities, and other treatments (hormonal manipulation, TURP). RESULTS: Acute GI and GU side effects (Grade 2 or higher) were noted in 246 and 201 patients, respectively; 67 of these patients exhibited both. GI side effects were not correlated with GU side effects acutely. Late and acute morbidities were correlated (both GI and GU). Fifteen of the 712 patients expressed Grade 3 or 4 GI injuries 3 to 32 months after the end of treatment, with a mean of 14.3 months. One hundred fifteen patients expressed Grade 2 or higher GI morbidity (mean: 13.7 months). The 43 Grade 2 or higher GU morbidities occurred significantly later (mean: 22.7 months). Central axis dose was the only independent variable significantly related to the incidence of late GI morbidity on MVA. No treatment volume parameters were significant for Grade 3. The following parameters were significantly related (by MVA) to Grade 2 GI morbidity: central axis dose, use of the increased rectal shielding, androgen deprivation therapy starting before RT. Acute and late GI morbidities were highly correlated. History of diabetes, treatment of pelvic nodes, and age less than 60 years were significantly related to acute GI side effects. The parameters significantly related to late Grade 2 or higher GU morbidity were central axis dose, androgen deprivation therapy (Zoladex or Lupron) prior to radiation therapy (RT), history of obstructive symptoms, and acute GU side effects. There were too few late Grade 3 GU morbidities to perform multivariate analysis. Acute GU side effects were highly correlated with late GU injury. The following were correlated with acute GU side effects: history of diabetes (+), treatment with conformal fields (-), TURP before RT (-), presentation with urinary obstructive symptoms. CONCLUSION: Both late GI and GU morbidity demonstrate a dose dependence, but only the volume dependence observed is a reduction in late Grade 2-4 GI morbidity by increasing the rectal shielding in the lateral fields for the final 10 Gy. Moreover, both late GI and GU morbidity was increased in patients treated with hormone manipulation prior to RT. GI and GU injuries were correlated with their corresponding acute side effects. GI and GU complications must not be combined for analysis to determine the factors related to their occurrence.

Antineoplastic Agents, Hormonal↗

PubMed1997

Radiation therapy as treatment for stage T1c prostate cancers.

Preliminary outcomes are reported for 202 patients with T1c prostate cancer treated with three-dimensional conformal radiation treatment (3DCRT). At 5 years, actuarial freedom from failure is demonstrated in 97% of patients with pretreatment PSA levels of < 10 ng/ml, in 88% of those with PSA levels of 10-19.9 ng/ml, and in 91% of young patients (< or = 65 years) with PSA levels of < 20 ng/ml. The late morbidity following this technology is extremely favorable, with < 1% of patients developing serious GI sequelae, < 1% using a daily pad for incontinence, and 61% maintaining sexual potency. Continued development and use of 3DCRT technology is indicated for patients who elect external beam radiation treatment.

Androgen Antagonists↗

PubMed1997

Conformal external beam treatment of prostate cancer.

OBJECTIVES: This study reports the 5-year outcomes of treatment for patients with prostate cancer treated largely with conformal three-dimensional radiation therapy. METHODS: Results are presented for 456 consecutive patients treated prior to December 31, 1993 whose pretreatment prostate-specific antigen (PSA) levels are known. Biochemical failure was defined as two consecutive rises in the PSA that equals or exceeds 1.5 ng/mL. Kaplan-Meier product limit methods, the log-rank test, and Cox regression models were used in evaluating the data. No patient was lost to follow-up. RESULTS: The 5-year biochemically free of failure (bNED) rate for all patients was 61% and 57% at 7 years. In the group with pretreatment PSA less than 10 ng/mL, the 5-year bNED rate for patients with localized disease (T1,2AB disease, Gleason sum of 6 or less) was 85% and for those with locally advanced disease (T2C,3), 70%. In the group with pretreatment PSA of 10 to 19.9 ng/mL, the 5-year bNED rate for patients with localized disease was 66% and for those with locally advanced disease, 44%. In the group with pretreatment PSA of 20 ng/mL or above, the patients with localized or locally advanced disease had 5-year bNED rates of 31% and 21%, respectively. CONCLUSIONS: The results of largely conformal three-dimensional external beam treatment of localized prostate cancer produced 5-year bNED results that are comparable to recent reports of nerve-sparing prostatectomy. Preliminary 7-year bNED results in all patients and in patients with localized tumors indicated a modest decrease in the cancer-free rate from that observed at 5 years, suggesting the results are durable.

Humans↗

PubMed1996

Conformal technique dose escalation for prostate cancer: biochemical evidence of improved cancer control with higher doses in patients with pretreatment prostate-specific antigen > or = 10 NG/ML.

PURPOSE: Conformal radiation technology results in fewer late complications and allows testing of the value of higher doses in prostate cancer. METHODS AND MATERIALS: We report the biochemical freedom from disease (bNED) rates (bNED failure is Prostate Specific Antigen (PSA) > or = 1.5 ng/ml and rising) at 2 and 3 years for 375 consecutive patients treated with conformal technique from 66 to 79 Gy. Median follow-up was 21 months. Biochemical freedom from disease was analyzed for patients treated above and below 71 Gy as well as above and below 73 Gy. Each dose group was subdivided by pretreatment PSA level (< 10, 10-19.9, and > or = 20 ng/ml). Dose was stated to be at the center of the prostate gland. RESULTS: There was significant improvement in bNED survival for all patients divided by a dose above or below 71 Gy (p = 0.007) and a marginal improvement above or below 73 Gy (p = 0.07). Subdividing by pretreatment PSA level showed no benefit to the PSA < 10 ng/ml group at the higher dose but there was a significant improvement at 71 and 73 Gy for pretreatment PSA 10-19.9 ng/ml (p = 0.03 and 0.05, respectively) and for pretreatment PSA > or = 20 ng/ml (p = 0.003 and 0.02, respectively). CONCLUSIONS: Increasing dose above 71 or 73 Gy did not result in improved bNED survival for patients with pretreatment PSA < 10 ng/ml at 2 or 3 years. Further dose escalation studies may not be useful in these patients. A significant improvement in bNED survival was noted for patients with pretreatment PSA > or = 10 ng/ml treated above 71 or 73 Gy; further dose escalation studies are warranted.

Aged↗

PubMed1996

Lateral rectal shielding reduces late rectal morbidity following high dose three-dimensional conformal radiation therapy for clinically localized prostate cancer: further evidence for a significant dose effect.

PURPOSE: Using conventional treatment methods for the treatment of clinically localized prostate cancer central axis doses must be limited to 65-70 Gray (Gy) to prevent significant damage to nearby normal tissues. A fundamental hypothesis of three-dimensional conformal radiation therapy (3DCRT) is that, by defining the target organ(s) accurately in three dimensions, it is possible to deliver higher doses to the target without a significant increase in normal tissue complications. This study examines whether this hypothesis holds true and whether a simple modification of treatment technique can reduce the incidence of late rectal morbidity in patients with prostate cancer treated with 3DCRT to minimum planning target volume (PTV) doses of 71-75 Gy. METHODS AND MATERIALS: The 257 patients with clinically localized prostate cancer who completed 3DCRT by December 31, 1993 and received a minimum PTV dose of 71-75 Gy are included in this report. The median follow-up time was 22 months (range: 4-67 months); 98% of patients had follow-up of longer than 12 months. The calculated dose at the center of the prostate was < 74 Gy in 19 patients, 74-76 Gy in 206 patients, and > 76 Gy in 32 patients. Late rectal morbidity was graded according to the Late Effects Normal Tissue (LENT) scoring system. Eighty-eight consecutive patients were treated with a rectal block added to the lateral fields. In these patients the posterior margin from the prostate to the block edge was reduced from the standard 15 to 5 mm for the final 10 Gy, which reduced the dose to portions of the anterior rectal wall by approximately 4-5 Gy. Estimates of rates for rectal morbidity were determined by Kaplan-Meier actuarial analysis. Differences in morbidity percentages were evaluated by the Pearson chi-square test. RESULTS: Grade 2-3 rectal morbidity developed in 46 out of 257 patients (18%) and in the majority of cases consisted of rectal bleeding. No patient has developed Grade 4 or 5 rectal morbidity. The actuarial rate of Grade 2-3 morbidity is 23% at 24 months and the median time to the development of Grade 2-3 complications is 15 months. A statistically significant dose effect is evident. The incidence of Grade 2-3 rectal morbidity increased as the dose at the center of the prostate increased (p = 0.05). In patients receiving minimum PTV doses of < or = 76 Gy the use of a rectal block significantly reduced the incidence of Grade 2-3 toxicity; 6 out of 88 (7%) with a block vs. 30 out of 137 (22%) without a block, (p = 0.003). CONCLUSION: The incidence of late rectal morbidity with 3DCRT to minimum PTV doses of 71-75 Gy is acceptable and to date no Grade 4-5 rectal morbidities have been observed. In our experience, higher doses to the center of the prostate are associated with an increased likelihood of developing Grade 2-3 rectal morbidity but treatment techniques that reduce the total dose to the anterior rectal wall have reduced the incidence of late rectal morbidity. If clinical studies indicate improved tumor control with minimum PTV doses above 71 Gy, then dose escalation above 76 Gy to the center of the prostate should be pursued cautiously with treatment techniques that limit the total dose to the anterior rectal wall.

Adult↗