Biomedical subjects

Patrick A Kupelian

Publications and source records attributed to Patrick A Kupelian.

At least 19 recordsLinked to original sources

PubMed2006

Evaluation of image-guidance protocols in the treatment of head and neck cancers.

PURPOSE: The aim of this study was to assess the residual setup error of different image-guidance (IG) protocols in the alignment of patients with head and neck cancer. The protocols differ in the percentage of treatment fractions that are associated with image guidance. Using data from patients who were treated with daily IG, the residual setup errors for several different protocols are retrospectively calculated. METHODS AND MATERIALS: Alignment data from 24 patients (802 fractions) treated with daily IG on a helical tomotherapy unit were analyzed. The difference between the daily setup correction and the setup correction that would have been made according to a specific protocol was used to calculate the residual setup errors for each protocol. RESULTS: The different protocols are generally effective in reducing systematic setup errors. Random setup errors are generally not reduced for fractions that are not image guided. As a consequence, if every other treatment is image guided, still about 11% of all treatments (IG and not IG) are subject to three-dimensional setup errors of at least 5 mm. This frequency increases to about 29% if setup errors >3 mm are scored. For various protocols that require 15% to 31% of the treatments to be image guided, from 50% to 60% and from 26% to 31% of all fractions are subject to setup errors >3 mm and >5 mm, respectively. CONCLUSION: Residual setup errors reduce with increasing frequency of IG during the course of external-beam radiotherapy for head-and-neck cancer patients. The inability to reduce random setup errors for fractions that are not image guided results in notable residual setup errors.

Algorithms↗

PubMed2006

Nadir prostate-specific antigen within 12 months after radiotherapy predicts biochemical and distant failure.

OBJECTIVES: To determine whether nadir prostate-specific antigen (PSA) levels within 12 months (nadir PSA12) after completion of radiotherapy (RT) can be used as an early marker of recurrence risk. METHODS: A total of 4839 patients were treated with RT and without hormonal therapy from 1986 to 1995 for Stage T1-T2 prostate cancer at nine institutions. Of these 4839 patients, 4833, with a median follow-up of 6.3 years, met the criteria for analysis. The study endpoints included freedom from PSA failure, initiation of androgen deprivation, or documented local or distant failure (PSA-DFS); freedom from clinically apparent distant metastasis (DMFS); and overall survival (OS). RESULTS: Patients with a nadir PSA12 of 2.0 ng/mL or less had an 8-year PSA-DFS, DMFS, and OS rate of 55%, 95%, and 73%, respectively, compared with 40%, 88%, and 69%, respectively, for patients with a nadir PSA12 of more than 2.0 ng/mL. Multivariate analysis confirmed that a nadir PSA12 of greater than 2 ng/mL was an independent predictor of PSA-DFS, DMFS, and OS. Classification and regression tree analysis identified the nadir PSA12 levels after RT associated with PSA-DFS, DMFS, and OS. Nadir PSA12, combined with the pretreatment PSA level, identified patients at particularly high risk of distant metastasis. CONCLUSIONS: The results of this large, multi-institutional study have demonstrated that nadir PSA12 is predictive of clinical outcomes for patients with localized prostate cancer after RT. A high pretreatment PSA level and high nadir PSA12 will identify patients at particularly high risk who might benefit from early adjuvant therapy.

Adenocarcinoma↗

PubMed2006

Daily variations in delivered doses in patients treated with radiotherapy for localized prostate cancer.

PURPOSE: The aim of this work was to study the variations in delivered doses to the prostate, rectum, and bladder during a full course of image-guided external beam radiotherapy. METHODS AND MATERIALS: Ten patients with localized prostate cancer were treated with helical tomotherapy to 78 Gy at 2 Gy per fraction in 39 fractions. Daily target localization was performed using intraprostatic fiducials and daily megavoltage pelvic computed tomography (CT) scans, resulting in a total of 390 CT scans. The prostate, rectum, and bladder were manually contoured on each CT by a single physician. Daily dosimetric analysis was performed with dose recalculation. The study endpoints were D95 (dose to 95% of the prostate), rV2 (absolute rectal volume receiving 2 Gy), and bV2 (absolute bladder volume receiving 2 Gy). RESULTS: For the entire cohort, the average D95 (+/-SD) was 2.02 +/- 0.04 Gy (range, 1.79-2.20 Gy). The average rV2 (+/-SD) was 7.0 +/- 8.1 cc (range, 0.1-67.3 cc). The average bV2 (+/-SD) was 8.7 +/- 6.8 cc (range, 0.3-36.8 cc). Unlike doses for the prostate, there was significant daily variation in rectal and bladder doses, mostly because of variations in volume and shape of these organs. CONCLUSION: Large variations in delivered doses to the rectum and bladder can be documented with daily megavoltage CT scans. Image guidance for the targeting of the prostate, even with intraprostatic fiducials, does not take into account the variation in actual rectal and bladder doses. The clinical impact of techniques that take into account such dosimetric parameters in daily patient set-ups should be investigated.

Humans↗

PubMed2006

Biochemical and clinical significance of the posttreatment prostate-specific antigen bounce for prostate cancer patients treated with external beam radiation therapy alone: a multiinstitutional pooled analysis.

BACKGROUND: The posttreatment prostate-specific antigen (PSA) bounce phenomenon has been recognized in at least 20% of all patients treated with radiation. The purpose of the current report was to determine if there was a difference in biochemical and clinical control between the bounce and nonbounce (NB) patients using pooled data on 4839 patients with T1-2 prostate cancer treated with external beam radiation therapy (RT) alone at 9 institutions between 1986 and 1995. METHODS: The median follow-up was 6.3 years. A posttreatment PSA bounce was defined by a minimal rise of 0.4 ng/mL over a 6-month follow-up period, followed by a drop in PSA level of any magnitude. Endpoints included no biochemical evidence of disease (bNED) failure (BF) (ASTRO definition), distant failure (DF), cause-specific failure (CSF), and overall survival (OS). Patients were stratified by pretreatment PSA, Gleason score, T stage, age, dose, and risk group. RESULTS: In all, 978 (20%) patients experienced at least 1 posttreatment PSA bounce. Within 3 subgroups (risk group, pretreatment PSA, and age), statistically significant differences of remaining bounce-free were observed on univariate analysis. Patients < 70 years had a 72% chance of remaining bounce-free at 5 years compared with 75% for older patients (P = .04). The NB patients had 72% bNED control at 10 years compared with 58% for the bounce patients. The effect of a bounce remained statistically significant on multivariate analysis (P < .0001). No statistically significant difference in DF, CSF, or OS was observed. CONCLUSIONS: Patients treated with external beam radiation therapy alone who experience a posttreatment PSA bounce have increased risk of BF. However, this did not translate into a difference in clinical failure with the available follow-up in the current study.

Adult↗

PubMed2006

Daily variations in the position of the prostate bed in patients with prostate cancer receiving postoperative external beam radiation therapy.

PURPOSE: The aim of this study was to evaluate the extent of the variation in the position of the prostate bed with respect to the bony anatomy. METHODS AND MATERIALS: Four patients were treated to 70 Gy in 35 fractions. Before each fraction, a megavoltage computed tomography (CT) of the prostate bed was obtained, resulting in a total of 140 CT studies. Retrospectively, each CT scan was aligned to the simulation kilovoltage scan based on bony anatomy and the prostate bed. The difference between the 2 alignments was calculated for each scan. RESULTS: The average differences (+/-1 SD) between the two alignments were 0.06+/-0.37, 0.10+/-0.86, and 0.39+/-1.27 mm in the lateral, longitudinal (SI), and vertical (AP) directions, respectively. Laterally, there was no difference>or=3 mm. The cumulative frequency of SI differences were as follows; >or=3 mm: 3%, >or=4 mm: 1%, and >or=5 mm: 1% (maximum: 5 mm). The cumulative frequency of AP differences were as follows; >or=3 mm: 7%, and >or=4 mm: 3% (maximum: 4 mm). CONCLUSION: In patients with prostate cancer receiving postoperative radiotherapy, the prostate bed motion relative to the pelvic bony anatomy is of a relatively small magnitude. Significant motion (>or=3 mm) is infrequent. However, small differences between the prostate bed and the bony anatomy still exist. This might have implications on treatment margins when daily alignment on bony anatomy is performed.

Humans↗

PubMed2006

Use of different definitions of biochemical failure after external beam radiotherapy changes conclusions about relative treatment efficacy for localized prostate cancer.

OBJECTIVES: To report biochemical relapse-free survival (bRFS) after radiotherapy (RT) for localized prostate cancer with two separate failure definitions and compare the results with those after radical prostatectomy (RP). METHODS: The study sample comprised 2516 patients with a median follow-up of 78 months. Biochemical relapse after RT was defined as either the American Society for Therapeutic Radiology Oncology definition (definition A [DefA]) or a prostate-specific antigen elevation of more than 2 ng/mL greater than the nadir prostate-specific antigen level (definition N [DefN]). Failure after RP was defined as a prostate-specific antigen level greater than 0.2 ng/mL. RESULTS: Compared with DefA, DefN resulted in a 13% greater bRFS rate at 5 years and a 12% lower bRFS rate at 10 years. On multivariate analysis, the treatment modality (RP versus RT) was a significant predictor of bRFS using DefA in favor of RP (P <0.001), but was not with DefN (P = 0.87). Higher radiation doses were independently associated with a better outcome with either definition. CONCLUSIONS: Compared with DefA, DefN resulted in better outcomes for up to 7 years after RT, but worse outcomes thereafter. The use of DefA versus DefN resulted in opposite conclusions about the relative efficacies of RT and RP, with DefN suggesting RT is equivalent to RP and DefA that it is worse than RP. Different definitions of biochemical failure after RT can result in differences in the conclusions about treatment efficacy in men with localized prostate cancer, thereby potentially affecting clinical decisions.

Adenocarcinoma↗

PubMed2006

Deformable registration of the planning image (kVCT) and the daily images (MVCT) for adaptive radiation therapy.

The incorporation of daily images into the radiotherapy process leads to adaptive radiation therapy (ART), in which the treatment is evaluated periodically and the plan is adaptively modified for the remaining course of radiotherapy. Deformable registration between the planning image and the daily images is a key component of ART. In this paper, we report our researches on deformable registration between the planning kVCT and the daily MVCT image sets. The method is based on a fast intensity-based free-form deformable registration technique. Considering the noise and contrast resolution differences between the kVCT and the MVCT, an 'edge-preserving smoothing' is applied to the MVCT image prior to the deformable registration process. We retrospectively studied daily MVCT images from commercial TomoTherapy machines from different clinical centers. The data set includes five head-neck cases, one pelvis case, two lung cases and one prostate case. Each case has one kVCT image and 20-40 MVCT images. We registered the MVCT images with their corresponding kVCT image. The similarity measures and visual inspections of contour matches by physicians validated this technique. The applications of deformable registration in ART, including 'deformable dose accumulation', 'automatic re-contouring' and 'tumour growth/regression evaluation' throughout the course of radiotherapy are also studied.

Algorithms↗

PubMed2006

Evaluation of an infrared camera and X-ray system using implanted fiducials in patients with lung tumors for gated radiation therapy.

PURPOSE: To report on the initial clinical use of a commercially available system to deliver gated treatment using implanted fiducials, in-room kV X-rays, and an infrared camera tracking system. METHODS AND MATERIALS: ExacTrac Adaptive Gating from BrainLab is a localization system using infrared cameras and X-rays. Gating signals are the patient's breathing pattern obtained from infrared reflectors on the patient. kV X-rays of an implanted fiducial are synchronized to the breathing pattern. After localization and shift of the patient to isocenter, the breathing pattern is used to gate the radiation. Feasibility tests included localization accuracy, radiation output constancy, and dose distributions with gating. Clinical experience is reported on treatment of patients with small lung lesions. RESULTS: Localization accuracy of a moving target with gating was 1.7 mm. Dose constancy measurements showed insignificant change in output with gating. Improvements of dose distributions on moving targets improved with gating. Eleven patients with lung lesions were implanted with 20 mmx0.7 mm gold coil (Visicoil). The implanted fiducial was used to localize and treat the patients with gating. Treatment planning and repeat computed tomographic scans showed that the change in center of gross target volume (GTV) to implanted marker averaged 2.47 mm due in part to asymmetric tumor shrinkage. CONCLUSION: ExacTrac Adaptive Gating has been used to treat lung lesions. Initial system evaluation verified its accuracy and usability. Implanted fiducials are visible in X-rays and did not migrate.

Calibration↗

PubMed2006

Aggressiveness of familial prostate cancer.

PURPOSE: To report on the aggressiveness of sporadic versus familial prostate cancer. PATIENTS AND METHODS: The study sample consisted of 4,112 stage T1-3 prostate cancer patients. The outcome of interest was biochemical relapse-free survival (bRFS). The analysis was performed for two distinct time periods, 1986 to 1992 (year < or = 1992) and 1993 to 2002 (year > or = 1993), to encompass both the early and late prostate-specific antigen (PSA) eras. RESULTS: A positive family history (FH positive) was reported in 16%. The 10-year bRFS rates for patients with negative family history (FH negative) versus FH positive were 59% and 63%, respectively (P = .90). However, in the year < or = 1992 period, the 10-year bRFS rates for FH negative versus FH positive were 45% and 34%, respectively (P = .015). In the year > or = 1993 period, the 10-year bRFS rates for FH negative versus FH positive were 61% and 67%, respectively (P = .54). Multivariate analysis failed to reveal family history as an independent predictor of relapse (P = .42). However, in the subset of patients in each era, family history was an independent predictor of relapse only for those treated in the year < or = 1992 period (P = .038). CONCLUSION: Family history was an independent predictor of biochemical failure only early in the PSA era, and men with an FH positive presented with more favorable disease later in the PSA era. This suggests that with stage migration and improved therapy, the impact of family history on prognosis has become minimal. However, underlying genetic factors affecting prostate cancer behavior in individuals with familial prostate cancer may still be important in determining individual prognosis.

Aged↗

PubMed2006

Increasing external beam dose for T1-T2 prostate cancer: effect on risk groups.

PURPOSE: The aim of this study was to investigate effect of increasing dose on risk groups for clinical failure (CF: local failure or distant failure or hormone ablation or PSA>or=25 ng/ml) in patients with T1-T2 prostate cancer treated with external beam radiotherapy. METHODS AND MATERIALS: Patients (n=4,537) were partitioned into nonoverlapping dose ranges, each narrow enough that dose was not a predictor of CF, and risk groups for CF were determined using recursive partitioning analysis (RPA). The same technique was applied to the highest of these dose ranges (70-76 Gy, 1,136 patients) to compare risk groups for CF in this dose range with the conventional risk-group classification. RESULTS: Cutpoints defining low-risk groups in each dose range shifted to higher initial PSA levels and Gleason scores with increasing dose. Risk groups for CF in the dose range 70-76 Gy were not consistent with conventional risk groups. CONCLUSIONS: The conventional classification of risk groups was derived in the early PSA era, when total doses<70 Gy were common, and it is inconsistent with risk groups for patients treated to doses>70 Gy. Risk-group classifications must be continuously re-examined whenever the trend is toward increasing total dose.

Humans↗

PubMed2006

Target localization and real-time tracking using the Calypso 4D localization system in patients with localized prostate cancer.

PURPOSE: The Calypso 4D Localization System is being developed to provide accurate, precise, objective, and continuous target localization during radiotherapy. This study involves the first human use of the system, to evaluate the localization accuracy of this technique compared with radiographic localization and to assess its ability to obtain real-time prostate-motion information. METHODS AND MATERIALS: Three transponders were implanted in each of 20 patients. Eleven eligible patients of the 20 patients participated in a study arm that compared radiographic triangulated transponder locations to electromagnetically recorded transponder locations. Transponders were tracked for 8-min periods. RESULTS: The implantations were all successful, with no major complications. Intertransponder distances were largely stable. Comparison of the patient localization on the basis of transponder locations as per the Calypso system with the radiographic transponder localization showed an average (+/-SD) 3D difference of 1.5 +/- 0.9 mm. Upon tracking during 8 min, 2 of the 11 patients showed significant organ motion (>1 cm), with some motion lasting longer that 1 min. CONCLUSION: Calypso transponders can be used as magnetic intraprostatic fiducials. Clinical evaluation of this novel 4D nonionizing electromagnetic localization system with transponders indicates a comparable localization accuracy to isocenter, (within 2 mm) compared with X-ray localization.

Electromagnetic Phenomena↗

PubMed2006

Evaluation of two tomotherapy-based techniques for the delivery of whole-breast intensity-modulated radiation therapy.

PURPOSE: To evaluate two different techniques for whole-breast treatments delivered using the Hi-ART II tomotherapy device. METHODS AND MATERIALS: Tomotherapy uses the standard rotational helical delivery. Topotherapy uses a stationary gantry while delivering intensity-modulated treatments. CT scans from 5 breast cancer patients were used. The prescription dose was 50.4 Gy. RESULTS: On average, 99% of the target volume received 95% of prescribed dose with either technique. If treatment times are restricted to less than 9 min, the average percentage ipsilateral lung receiving > or =20 Gy was 22% for tomotherapy vs. 10% for topotherapy. The ipsilateral lung receiving > or =50.4 Gy was 4 cc for tomotherapy vs. 27 cc for topotherapy. The percentage of left ventricle receiving > or =30 Gy was 14% with tomotherapy vs. 4% for topotherapy. The average doses to the contralateral breast and lung were 0.6 and 0.8 Gy, respectively, for tomotherapy vs. 0.4 and 0.3 Gy for topotherapy. CONCLUSIONS: Tomotherapy provides improved target dose homogeneity and conformality over topotherapy. If delivery times are restricted, topotherapy reduces the amount of heart and ipsilateral lung volumes receiving low doses. For whole-breast treatments, topotherapy is an efficient technique that achieves adequate target uniformity while maintaining low doses to sensitive structures.

Breast↗

PubMed2006

Comparison of ultrasound and implanted seed marker prostate localization methods: Implications for image-guided radiotherapy.

PURPOSE: To analyze two methods of image-guided radiotherapy (IGRT) for external beam radiotherapy of prostate cancer. METHODS AND MATERIALS: The prostate was localized by ultrasound (US) in lateral (left/right), vertical (anteroposterior), and longitudinal (superior/inferior) dimensions and then by fiducial seed marker (SM) kV X-ray. Assuming initial setup to skin marks as the origin, the mean suggested shifts (for all dimensions) were hypothesized to be similar and within 1 mm of the origin. The three-dimensional distance discrepancy between suggested SM and US shift points was calculated. We hypothesized a mean discrepancy >5 mm as clinically significant. RESULTS: From 40 patients, 1019 US/SM measurements were obtained. Lateral, vertical, and longitudinal dimensional comparisons reveal statistically significant differences in mean shifts (p < 0.0001 for all). US dimensional shifts reveal significantly greater variability. The US three-dimensional vector is greater and more variable than the SM vector (p < 0.0001). The mean US/SM three-dimensional distance discrepancy is 8.8 mm (significantly >5 mm, p < 0.0001). CONCLUSIONS: Ultrasound and SM methods suggest different shifts. US data reveal greater systematic/random error vs. SM data. The US data suggest larger PTV expansion margins (approximately 9 mm) are necessary for US IGRT vs. SM IGRT (approximately 3 mm). The hypotheses that US and SM methods suggest similar shifts and that the mean US/SM three-dimensional distance discrepancy is < or =5 mm are rejected.

Algorithms↗

PubMed2006

Influence of intrafraction motion on margins for prostate radiotherapy.

PURPOSE: To assess the impact of intrafraction intervention on margins for prostate radiotherapy. METHODS AND MATERIALS: Eleven supine prostate patients with three implanted transponders were studied. The relative transponder positions were monitored for 8 min and combined with previously measured data on prostate position relative to skin marks. Margins were determined for situations of (1) skin-based positioning, and (2) pretreatment transponder positioning. Intratreatment intervention was simulated assuming conditions of (1) continuous tracking, and (2) a 3-mm threshold for position correction. RESULTS: For skin-based setup without and with inclusion of intrafraction motion, prostate treatments would have required average margins of 8.0, 7.3, and 10.0 mm and 8.2, 10.2, and 12.5 mm, about the left-right, anterior-posterior, and cranial-caudal directions, respectively. Positioning by prostate markers at the start of the treatment fraction reduced these values to 1.8, 5.8, and 7.1 mm, respectively. Interbeam adjustment further reduced margins to an average of 1.4, 2.3, and 1.8 mm. Intrabeam adjustment yielded margins of 1.3, 1.5, and 1.5 mm, respectively. CONCLUSION: Significant reductions in margins might be achieved by repositioning the patient before each beam, either radiographically or electromagnetically. However, 2 of the 11 patients would have benefited from continuous target tracking and threshold-based intervention.

Algorithms↗

PubMed2006

A technique for adaptive image-guided helical tomotherapy for lung cancer.

PURPOSE: The gross tumor volume (GTV) for many lung cancer patients can decrease during the course of radiation therapy. As the tumor reduces in size during treatment, the margin added around the GTV effectively becomes larger, which can result in the excessive irradiation of normal lung tissue. The specific goal of this study is to evaluate the feasibility of using image-guided adaptive radiation therapy to adjust the planning target volume weekly based on the previous week's CT image sets that were used for image-guided patient setup. METHODS AND MATERIALS: Megavoltage computed tomography (MVCT) images of the GTV were acquired daily on a helical tomotherapy system. These images were used to position the patient and to measure reduction in GTV volume. A planning study was conducted to determine the amount of lung-sparing that could have been achieved if adaptive therapy had been used. Treatment plans were created in which the target volumes were reduced after tumor reduction was measured. RESULTS: A total of 158 MVCT imaging sessions were performed on 7 lung patients. The GTV was reduced by 60-80% during the course of treatment. The tumor reduction in the first 60 days of treatment can be modeled using the second-order polynomial R = 0.0002t(2) - 0.0219t + 1.0, where R is the percent reduction in GTV, and t is the number of elapsed days. Based on these treatment planning studies, the absolute volume of ipsilateral lung receiving 20 Gy can be reduced between 17% and 23% (21% mean) by adapting the treatment delivery. The benefits of adaptive therapy are the greatest for tumor volumes > or =25 cm3 and are directly dependent on GTV reduction during treatment. CONCLUSIONS: Megavoltage CT-based image guidance can be used to position lung cancer patients daily. This has the potential to decrease margins associated with daily setup error. Furthermore, the adaptive therapy technique described in this article can decrease the volume of healthy lung tissue receiving above 20 Gy. However, further study is needed to determine whether adaptive therapy could result in the underdosing of microscopic extension.

Carcinoma, Non-Small-Cell Lung↗

PubMed2006

Characterization and use of EBT radiochromic film for IMRT dose verification.

We present an evaluation of a new and improved radiochromic film, type EBT, for its implementation to IMRT dose verification. Using a characterized flat bed color CCD scanner, the film's dose sensitivity, uniformity, and speed of development post exposure were shown to be superior to previous types of radiochromic films. The film's dose response was found to be very similar to ion chamber scans in water through comparisons of depth dose and lateral dose profiles. The effect of EBT film polarization with delivered dose and film scan orientation was shown to have a significant effect on the scanner's OD readout. In addition, the film's large size, flexibility, and the ability to submerge it in water for relatively short periods of time allowed for its use in both water and solid water phantoms to verify TomoTherapy IMRT dose distributions in flat and curved dose planes. Dose verification in 2D was performed on ten IMRT plans (five head and neck and five prostate) by comparing measured EBT dose distributions to TomoTherapy treatment planning system calculated dose. The quality of agreement was quantified by the gamma index for four sets of dose difference and distance to agreement criteria. Based on this study, we show that EBT film has several favorable features that allow for its use in routine IMRT patient-specific QA.

Dose-Response Relationship, Radiation↗

PubMed2005

PSA nadir predicts biochemical and distant failures after external beam radiotherapy for prostate cancer: a multi-institutional analysis.

PURPOSE: To determine the significance of prostate-specific antigen (PSA) nadir (nPSA) and the time to nPSA (T(nPSA)) in predicting biochemical or clinical disease-free survival (PSA-DFS) and distant metastasis-free survival (DMFS) in patients treated with definitive external beam radiotherapy (RT) for clinical Stage T1b-T2 prostate cancer. METHODS AND MATERIALS: Nine participating institutions submitted data on 4839 patients treated between 1986 and 1995 for Stage T1b-T2cN0-NxM0 prostate cancer. All patients were treated definitively with RT alone to doses > or =60 Gy, without neoadjuvant or planned adjuvant androgen suppression. A total of 4833 patients with a median follow-up of 6.3 years met the criteria for analysis. Two endpoints were considered: (1) PSA-DFS, defined as freedom from PSA failure (American Society for Therapeutic Radiology and Oncology definition), initiation of androgen suppression after completion of RT, or documented local or distant failure; and (2) DMFS, defined as freedom from clinically apparent distant failure. In patients with failure, nPSA was defined as the lowest PSA measurement before any failure. In patients without failure, nPSA was the lowest PSA measurement during the entire follow-up period. T(nPSA) was calculated from the completion of RT to the nPSA date. RESULTS: A greater nPSA level and shorter T(nPSA) were associated with decreased PSA-DFS and DMFS in all patients and in all risk categories (low [Stage T1b, T1c, or T2a, Gleason score < or =6, and PSA level < or =10 ng/mL], intermediate [Stage T1b, T1c, or T2a, Gleason score < or =6, and PSA level >10 but < or =20 ng/mL, or Stage T2b or T2c, Gleason score < or =6, and PSA level < or =20 ng/mL, or Gleason score 7 and PSA level < or =20 ng/mL], and high [Gleason score 8-10 or PSA level >20 ng/mL]), regardless of RT dose. The 8-year PSA-DFS and DMFS rate for patients with nPSA <0.5 ng/mL was 75% and 97%; nPSA > or =0.5 but <1.0 ng/mL, 52% and 96%; nPSA > or =1.0 but <2.0 ng/mL, 40% and 91%; and nPSA > or =2.0 ng/mL, 17% and 73%, respectively. The 8-year PSA-DFS and DMFS rate for patients with T(nPSA) <6 months was 27% and 66%; T(nPSA) > or =6 but <12 months, 31% and 85%; T(nPSA) > or =12 but <24 months, 42% and 94%; and T(nPSA) > or =24 months, 75% and 99%, respectively. A shorter T(nPSA) was associated with decreased PSA-DFS and DMFS, regardless of the nPSA. Both nPSA and T(nPSA) were significant predictors of PSA-DFS and DMFS in multivariate models incorporating clinical stage, Gleason score, initial PSA level, and RT dose. The significance of nPSA and T(nPSA) was supported by landmark analysis, as well as by analysis of nPSA and T(nPSA) as time-dependent covariates. A dose > or =70 Gy was associated with a lower nPSA level and longer T(nPSA) in all risk categories, and a greater dose was significantly associated with greater PSA-DFS and DMFS in multivariate analysis. Regression analysis confirmed that higher clinical stage, Gleason score, and initial PSA were associated with a greater nPSA level. CONCLUSION: The results of this large, multi-institutional analysis of 4833 patients have provided important evidence that nPSA and T(nPSA) after definitive external beam RT are not only predictive of a predominantly PSA endpoint (PSA-DFS), but are also predictive of distant metastasis in all clinical risk categories. Greater RT doses were associated with lower nPSA, longer T(nPSA), and improved PSA-DFS and DMFS.

Disease-Free Survival↗

PubMed2005

Hypofractionated intensity-modulated radiotherapy (70 gy at 2.5 Gy per fraction) for localized prostate cancer: long-term outcomes.

PURPOSE: To analyze the long-term relapse-free survival and toxicity rates in patients treated with hypofractionated intensity-modulated radiotherapy. METHODS AND MATERIALS: The study sample includes the first 100 consecutive localized prostate cancer patients treated to 70.0 Gy at 2.5 Gy per fraction. The median follow-up was 66 months (range, 3 to 75 months). Biochemical failure was the study endpoint, using both the ASTRO definition (A-bRFS) and the alternate "nadir + 2 ng/mL" definition (N-bRFS). RTOG scores were used to assess toxicity. RESULTS: The 5-year A-bRFS and N-bRFS rates were 85% (95%CI, 78-93%) and 88% (95%CI, 82-95%) for all cases, respectively. For low, intermediate and high-risk disease, the 5-year A-bRFS rates were 97%, 88%, and 70%. The corresponding 5-year N-bRFS rates were 97%, 93%, and 75%, respectively. The acute rectal toxicity scores were 0 in 20, 1 in 61, and 2 in 19 patients. The acute urinary toxicity scores were 0 in 9, 1 in 76, and 2 in 15 patients. The late rectal toxicity scores were 0 in 71, 1 in 19, 2 in 7, and 3 in 3 patients. The actuarial late Grade 3 rectal toxicity rate at 5 years was 3%. A number of the toxicities observed either resolved spontaneously or were corrected. At last follow-up, the rate of combined Grades 2 and 3 late rectal toxicity at 5 years was only 5%. The late urinary toxicity scores were 0 in 75, 1 in 13, 2 in 11, and 3 in 1 patients. The actuarial late Grade 3 urinary toxicity rate at 5 years was 1%. CONCLUSION: With a median follow-up of 66 months, the long-term results after high-dose hypofractionation are excellent. Late toxicity, urinary and rectal, has been limited. High-dose hypofractionation is an alternative dose escalation method in the treatment of localized prostate cancer.

Aged↗