Rectal morbidity following I-125 prostate brachytherapy in relation to dosimetry

BACKGROUND: To investigate rectal morbidity after I-125 prostate brachytherapy and to analyze predictive factors of rectal morbidity. METHODS: A group of 227 consecutive patients with localized prostate cancer were treated with I-125 prostate brachytherapy with or without external beam radiotherapy (EBRT) between September 2003 and January 2005. Rectal morbidity (diarrhea, bleeding and pain) was evaluated using the Radiation Therapy Oncology Group (RTOG) criteria. Dosimetry was based on computerized tomography (CT) scan 1 month post-implant. The clinical, treatment-related and dosimetric factors were evaluated for the risk of grade 2 rectal morbidity. Rectal dosimetric factors included the rectal volume that received >100% and 150% of the prescribed dose, and the maximal rectal dose which was defined as the sum of the minimal dose received by 1% of the rectum volume and the prescribed dose of EBRT. RESULTS: Grade 2 rectal bleeding occurred in 10 (4.4%): for nine patients within the first year and for one patient between the first and second year. Grade 2 diarrhea occurred in one patient (0.4%) within the first year. No patient reported grade 2 pain. In the univariate analysis with grade 2 rectal bleeding, there were significant correlations with number of seeds, supplemental EBRT, and all of the rectal dosimetric parameters. On subsequent multivariate analysis, the only significant factor was the maximal rectal dose (P < 0.001). Rectal dose > 160 Gy was correlated to grade 2 rectal morbidity. All the patients with rectal dose > 160 Gy received EBRT. CONCLUSIONS: Manifestations of rectal morbidity are acceptable events after I-125 prostate brachytherapy. Rectal dose-volume histogram for the brachytherapy is a predictive method for assessing the risk of developing grade 2 rectal bleeding. Delivery of the rectal dose should not exceed 160 Gy in order to avoid rectal complications.     

Increased risk of biochemical and local failure in patients with distended rectum on the planning CT for prostate cancer radiotherapy

PURPOSE: To retrospectively test the hypothesis that rectal distension on the planning computed tomography (CT) scan is associated with an increased risk of biochemical and local failure among patients irradiated for prostate carcinoma when a daily repositioning technique based on direct prostate-organ localization is not used. METHODS AND MATERIALS: This study included 127 patients who received definitive three-dimensional conformal radiotherapy for prostate cancer to a total dose of 78 Gy at The University of Texas M. D. Anderson Cancer Center. Rectal distension was assessed by calculation of the average cross-sectional rectal area (CSA; defined as the rectal volume divided by length) and measuring three rectal diameters on the planning CT. The impact of rectal distension on biochemical control, 2-year prostate biopsy results, and incidence of Grade 2 or greater late rectal bleeding was assessed. RESULTS: The incidence of biochemical failure was significantly higher among patients with distended rectums (CSA >11.2 cm(2)) on the planning CT scan (p = 0.0009, log-rank test). Multivariate analysis indicates that rectal distension and high-risk disease are independent risk factors for biochemical failure, with hazard ratios of 3.89 (95% C.I. 1.58 to 9.56, p = 0.003) and 2.45 (95% C.I. 1.18 to 5.08, p = 0.016), respectively. The probability of residual tumor without evidence of radiation treatment (as scored by the pathologist) increased significantly with rectal distension (p = 0.010, logistic analysis), and a lower incidence of Grade 2 or greater late rectal bleeding within 2 years was simultaneously observed with higher CSA values (p = 0.031, logistic analysis). CONCLUSIONS: We found strong evidence that rectal distension on the treatment-planning CT scan decreased the probability of biochemical control, local control, and rectal toxicity in patients who were treated without daily image-guided prostate localization, presumably because of geographic misses. Therefore, an empty rectum is warranted at the time of simulation. These results also emphasize the need for image-guided radiotherapy to improve local control in irradiating 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.     

Is the alpha-beta ratio of prostate cancer really low? A prospective, non-randomized trial comparing standard and hyperfractionated conformal radiation therapy.

BACKGROUND AND PURPOSE: The objectives of the current study were to compare genito-urinary (GU) and gastro-intestinal (GI) toxicities as well as biochemical control (bRFS) in prostate cancer, utilizing conventional (2.0 Gy daily) (STD) or hyperfractionated (HFX) conformal irradiation (CRT). HFX (1.2 Gy BID) was chosen as a radiobiological method to try to reduce long term sequelae without compromising local control. PATIENTS AND METHODS: Three-hundred-and-seventy consecutive patients (pts) entered this prospective, non-randomized trial in the period January 1993-January 2003; 209 were treated with STD and 161 with HFX CRT. All were evaluable for acute toxicity analysis, 179 (STD) and 151 pts (HFX) being evaluable for late sequelae and bRFS analyses. Pt characteristics were not statistically different in the two groups. CRT consisted of a 4-field technique for prostate and/or pelvic nodes and a 5-field boost with rectal shielding. Median doses were 74 and 79.2 Gy for STD and HFX patients respectively, the latter dose being isoeffective for tumour control assuming alpha/beta=10 (EQD(2)=73.9 Gy). Median follow-up was 29.4 months (25.2 mos for STD; 37.7 mos for HFX; P<0.01). The two regimens were compared in terms of acute and late GU and GI toxicities and 5-year bRFS by univariate and multivariate analyses. RESULTS: Acute grade> or =2 GU toxicity was higher in the STD group (48.6% versus 37.3% in HFX, P=0.03), while no significant difference was found for acute GI toxicity. Late grade> or =2 GU and GI toxicities were lower in the HFX group (5-year actuarial rate: GU: 10.1% versus 20.3%, P=0.05; GI: 6.0% versus 10.6%, P=0.18). Five-year bRFS were 70% (+/-13.8%, 95% CI) and 82.6% (+/-7.2%) for STD and HFX, respectively (P=0.44); a trend favouring HFX was found in the subgroup of pts who did not receive hormonal therapy (5-year bRFS: 85.9%+/-12.4% versus 63.9%+/-23.8%, P=0.15). Multivariate analysis revealed only risk groups and age statistically related to bRFS but not fractionation regimen. Using the Nahum-Chapman TLCP model and prostate parameter set, which includes hypoxia, the TLCPs are approximately equal for the two regimens, whereas assuming alpha/beta=1.5 and no hypoxia we obtain 73% for the STD group but only 36% for the HFX group. CONCLUSIONS: As expected from radiobiological considerations, HFX reduces GI and GU late toxicities. Concerning early bRFS, our clinical findings suggest that HFX is no less effective than STD when delivering an isoeffective (alpha/beta=10) dose. Despite the relatively short follow-up, this result appears to be inconsistent with a low alpha/beta ratio for prostate cancer.     

Dosimetric comparison of four target alignment methods for prostate cancer radiotherapy

PURPOSE: The aim of this study was to compare the dosimetric consequences of 4 treatment delivery techniques for prostate cancer patients treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: During an 8-week course of radiotherapy, 10 patients underwent computed tomography (CT) scans 3 times per week (243 total) before daily treatment with a CT-linear accelerator. Treatment delivery was simulated by realigning a fixed-margin treatment plan on each CT scan and calculating doses. The alignment methods were those based on the following: skin marks, bony registration, ultrasonography (US), and in-room CT. For the last two methods, prostate was the alignment target. The dosimetric effects of these alignment methods on the prostate, seminal vesicles, rectum, and bladder were compared. The average daily minimum dose to 0.1 cm3 was used as the metric for target coverage. RESULTS: Skin and bone alignments provided acceptable prostate coverage for only 70% of patients, US alignment for 90%, and CT alignment for 100%. CT-based alignment of the prostate provided seminal vesicle (SV) coverage of > or = 69 Gy for all patients; US and bone alignments provided SV coverage of > or = 60 Gy. This SV coverage may be acceptable for early-stage cancer (equivalent SV dose = 55.8 Gy at 1.8 Gy per fraction), but unacceptable for late-stage cancer (SV dose = 75.6 Gy). At 75.6 Gy, the acceptable rate for SV coverage was 40% for skin and bone alignments, 70% for US, and 80% for CT. CONCLUSIONS: Direct target alignment methods (US and CT) provided better target coverage. CT-guided alignment provided the best and most consistent dosimetric coverage. A larger planning target volume margin is needed for SV coverage when the alignment target is the prostate.     

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.     

Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy > or =72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer

PURPOSE: To review the biochemical relapse-free survival (bRFS) rates after treatment with permanent seed implantation (PI), external beam radiotherapy (EBRT) <72 Gy (EBRT <72), EBRT > or =72 Gy (EBRT > or =72), combined seeds and EBRT (COMB), or radical prostatectomy (RP) for clinical Stage T1-T2 localized prostate cancer treated between 1990 and 1998. METHODS AND MATERIALS: The study population comprised 2991 consecutive patients treated at the Cleveland Clinic Foundation or Memorial Sloan Kettering at Mercy Medical Center. All cases had pretreatment prostate-specific antigen (iPSA) levels and biopsy Gleason scores (bGSs). Neoadjuvant androgen deprivation for < or =6 months was given in 622 cases (21%). No adjuvant therapy was given after local therapy. RP was used for 1034 patients (35%), EBRT <72 for 484 (16%), EBRT > or =72 for 301 (10%), PI for 950 (32%), and COMB for 222 patients (7%). The RP, EBRT <72, EBRT > or =72, and 154 PI patients were treated at Cleveland Clinic Foundation. The median radiation doses in EBRT <72 and EBRT > or =72 case was 68.4 and 78.0 Gy, respectively. The median follow-up time for all cases was 56 months (range 12-145). The median follow-up time for RP, EBRT <72, EBRT > or =72, PI, and COMB was 66, 75, 49, 47, and 46 months, respectively. Biochemical relapse was defined as PSA levels >0.2 for RP cases and three consecutive rising PSA levels (American Society for Therapeutic Radiology Oncology consensus definition) for all other cases. A multivariate analysis for factors affecting the bRFS rates was performed using the following variables: clinical T stage, iPSA, bGS, androgen deprivation, year of treatment, and treatment modality. The multivariate analysis was repeated excluding the EBRT <72 cases. RESULTS: The 5-year bRFS rate for RP, EBRT <72, EBRT > or =72, PI, and COMB was 81%, 51%, 81%, 83%, and 77%, respectively (p <0.001). The 7-year bRFS rate for RP, EBRT <72, EBRT > or =72, PI, and COMB was 76%, 48%, 81%, 75%, and 77%, respectively. Multivariate analysis, including all cases, showed iPSA (p <0.001), bGS (p <0.001), year of therapy (p <0.001), and treatment modality (p <0.001) to be independent predictors of relapse. Because EBRT <72 cases had distinctly worse outcomes, the analysis was repeated after excluding these cases to discern any differences among the other modalities. The multivariate analysis excluding the EBRT <72 cases revealed iPSA (p <0.001), bGS (p <0.001), and year of therapy (p = 0.001) to be the only independent predictors of relapse. Treatment modality (p = 0.95), clinical T stage (p = 0.09), and androgen deprivation (p = 0.56) were not independent predictors for failure. CONCLUSION: The biochemical failure rates were similar among PI, high-dose (> or =72 Gy) EBRT, COMB, and RP for localized prostate cancer. The outcomes were significantly worse for low-dose (<72 Gy) EBRT.     

3-D conformal radiotherapy of localized prostate cancer: a subgroup analysis of rectoscopic findings prior to radiotherapy and acute/late rectal side effects.

BACKGROUND AND PURPOSE: To identify endoscopic pathological findings prior to radiotherapy and a possible correlation with acute or chronic rectal side effects after three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. PATIENTS AND METHODS: Between 03/99 and 07/02, a total of 298 patients, who consented in a voluntary rectoscopy prior to radiotherapy were included into the analysis. Patients were treated with a total dose of either 70 or 74 Gy. Pathological rectoscopic findings like hemorrhoids, polyps or diverticula were documented. Acute and late rectal side effects were scored using the EORTC/RTOG score. RESULTS: The most frequent pathological endosopic findings were hemorrhoids (35%), polyps (24%) and diverticula (13%). Rectal toxicity was mostly low to moderate. Grade 0/1 cumulative acute and late rectal side effects were 82 and 84%, grade 2 were 18 and 17%, respectively. We could not identify any correlation between preexisting pathological findings and rectal side effects by statistical analysis. CONCLUSIONS: There is no evidence that prostate cancer patients presenting with endoscopic verified pathological findings in the rectal mucosa at diagnosis are at an increased risk to develop rectal side effects when treated with 3D-CRT of the prostatic region.     

The relationship between technical parameters of external beam radiation therapy and complications for localized prostate cancer

BACKGROUND: This study was performed to review retrospectively the clinical course of chronic rectal bleeding as a complication of external beam radiation therapy for localized prostate cancer and to analyze the relationship between technical parameters of radiation therapy and the complications. METHODS: Seventy-one patients with stages A2, B and C were treated with local-field radiotherapy (total dose 52.5-66 Gy, daily dose 2.0-3.28 Gy, field area 30-81 cm2, number of fields 3-15 ports, planning simulations X-ray or CT-based) between 1989 and 1998 at three institutions. The protocols were consistent during this same period at these institutions. RESULTS: Multivariate analysis revealed pretreatment PSA and Gleason sum to be statistically significant predictors of 5 year prostatic specific antigen (PSA) relapse-free rates in a median follow-up period of 42 months (range 12-119 months). The significant risk factors for higher grading of acute morbidity were a biological equivalent dose, alpha/beta = 10(BED10) > or =65 Gy, dose per fraction > or =3.0 Gy, field area > or =42 cm2, fewer ports and X-ray planning simulation. However, no parameter was associated with higher grading of late morbidity. Eleven patients (15.4%) experienced a late GI complication: grade 1 (4.2%), grade 2 (9.8%), grade 3 (1.4%). The median time to occurrence of rectal bleeding was 12 months after radiotherapy and the mean duration of morbidity was 11 months. CONCLUSIONS: Higher total dose and dose per fraction, larger field area, fewer ports and X-ray simulation increased the grades of acute morbidity. A majority of chronic rectal bleedings were transient and responded to conservative treatment.     

Rectal Filling at Planning Does Not Predict Stability of the Prostate Gland during a Course of Radical Radiotherapy if Patients with Large Rectal Filling are Re-imaged

AimsIt has been suggested that large rectal filling is associated with an increased risk of prostate motion in radiotherapy. The aim of the present study was to determine if there is a correlation between rectal distension on planning computed tomography and the intrafraction and interfraction stability of the prostate gland during a course of radical radiotherapy for prostate cancer if a protocol was used to rescan patients with excessive rectal diameter during planning.Materials and methodsThe computed tomography planning scans of 89 patients with adenocarcinoma of the prostate treated with conformal radiotherapy were reviewed. All patients had three gold seed fiducial markers implanted into the prostate before planning computed tomography. About one in five patients had repeat computed tomography because their rectum was judged to be too large at the time of the first planning computed tomography. Rectal distension was assessed on planning computed tomography using outlines following European Organization for Research and Treatment of Cancer guidelines by measuring the rectal volume, the average cross-sectional area and the mean anterior–posterior diameter of the rectum. Daily kV images were obtained before and after treatment delivery to determine positional matching of the fiducial markers in the superior–inferior, anterior–posterior and right–left dimensions.ResultsIn total, 2860 pre- and post-treatment daily kV image pairs were obtained of 89 patients (average 32.1 image pairs per patient). The median rectal cross-sectional area was 7.3 cm² (range 2.8–17.1), the median rectal volume was 54.8 cm³ (range 20.9–128.2), and the median anterior–posterior rectal diameter was 3.03 cm (range 1.58–8.30). Unifactor linear regression models showed no statistically significant relationship between intra- and interfraction prostate stability and rectal volume on planning computed tomography.ConclusionsNo statistically significant relationship between rectal distension on planning computed tomography and the intra- and interfraction stability of the prostate gland was identified if patients with a large rectal volume were rescanned for planning.     

Evidence of limited motion of the prostate by carefully emptying the rectum as assessed by daily MVCT image guidance with helical tomotherapy

PURPOSE: To assess setup and organ motion error by means of analysis of daily megavoltage computed tomography (MVCT) of patients treated with hypofractionated helical tomotherapy (71.4-74.2 Gy in 28 fractions). METHODS AND MATERIALS: Data from 21 patients were analyzed. Patients were instructed to empty the rectum carefully before planning CT and every morning before therapy by means of a self-applied rectal enema. The position of the prostate was assessed by means of automatic bone matching (BM) with the planning kilovoltage CT (BM, setup error) followed by a direct visualization (DV) match on the prostate. Deviations between planning and therapy positions referred to BM and BM + DV were registered for the three main axes. In case of a full rectum at MVCT with evident shift of the prostate, treatment was postponed until after additional rectal emptying procedures; in this case, additional MVCT was performed before delivering the treatment. Data for 522 fractions were available; the impact of post-MVCT procedure was investigated for 17 of 21 patients (410 fractions). RESULTS: Prostate motion relative to bony anatomy was limited. Concerning posterior-anterior shifts, only 4.9% and 2.7% of fractions showed deviation of 3 mm or greater of the prostate relative to BM without and with consideration of post-MVCT procedures, respectively. Interobserver variability for BM + DV match was within 0.8 mm (1 SD). CONCLUSIONS: Daily MVCT-based correction is feasible. The BM + DV matching was found to be consistent between operators. Rectal emptying using a daily enema is an efficient tool to minimize prostate motion, even for centers that have not yet implemented image-guided radiotherapy.     

Adjuvant androgen deprivation impacts late rectal toxicity after conformal radiotherapy of prostate carcinoma

To evaluate whether androgen deprivation impacts late rectal toxicity in patients with localised prostate carcinoma treated with three-dimensional conformal radiotherapy. One hundred and eighty-two consecutive patients treated with 3DCRT between 1995 and 1999 at our Institution and with at least 12 months follow-up were analysed. three-dimensional conformal radiotherapy consisted in 70-76 Gy delivered with a conformal 3-field arrangement to the prostate+/-seminal vesicles. As part of treatment, 117 patients (64%) received neo-adjuvant and concomitant androgen deprivation while 88 (48.4%) patients were continued on androgen deprivation at the end of three-dimensional conformal radiotherapy as well. Late rectal toxicity was graded according to the RTOG morbidity scoring scale. Median follow up is 25.8 (range: 12-70.2 months). The 2-year actuarial likelihood of grade 2-4 rectal toxicity was 21.8+/-3.2%. A multivariate analysis identified the use of adjuvant androgen deprivation (P=0.0196) along with the dose to the posterior wall of the rectum on the central axis (P=0.0055) and the grade of acute rectal toxicity (P=0.0172) as independent predictors of grade 2-4 late rectal toxicity. The 2-year estimates of grade 2-4 late rectal toxicity for patients receiving or not adjuvant hormonal treatment were 30.3+/-5.2% and 14.1+/-3.8%, respectively. Rectal tolerance is reduced in presence of adjuvant androgen deprivation.     

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.     

Direct aperture optimization as a means of reducing the complexity of intensity modulated radiation therapy plans

Background

To evaluate the impact of four different rectum contouring techniques and rectal toxicities in patients with treated with 3D conformal radiotherapy (3DCRT).

Methods

Clinical and dosimetric data were evaluated for 94 patients who received a total dose 3DCRT of 70 Gy, and rectal doses were compared in four different rectal contouring techniques: the prostate-containing CT sections (method 1); 1 cm above and below the planning target volume (PTV) (method 2); 110 mm starting from the anal verge (method 3); and from the anal verge to the sigmoid flexure (method 4). The percentage of rectal volume receiving RT doses (30–70 Gy) and minimum, mean rectal doses were assessed.

Results

Median age was 69 years. Percentage of rectal volume receiving high doses (≥ 70 Gy) were higher with the techniques that contoured smaller rectal volumes. In methods 2 and 3, the percentage of rectal volume receiving ≥ 70 Gy was significantly higher in patients with than without rectal bleeding (method 2: 30.8% vs. 22.5%, respectively (p = 0.03); method 3: 26.9% vs. 18.1%, respectively (p = 0.006)). Mean rectal dose was significant predictor of rectal bleeding only in method 3 (48.8 Gy in patients with bleeding vs. 44.4 Gy in patients without bleeding; p = 0.02).

Conclusion

Different techniques of rectal contouring significantly influence the calculation of radiation doses to the rectum and the prediction of rectal toxicity. Rectal volume receiving higher doses (≥ 70 Gy) and mean rectal doses may significantly predict rectal bleeding for techniques contouring larger rectal volumes, as was in method 3.     

Recurrence-free survival rates after external-beam radiotherapy for patients with clinical T1-T3 prostate carcinoma in the prostate-specific antigen era: what should we expect?

BACKGROUND: The objective of the current study was to report biochemical recurrence-free survival (bRFS) rates among men with T1-T3 prostate carcinoma who were treated with external-beam radiotherapy (RT) at the Cleveland Clinic Foundation (Cleveland, OH). METHODS: In total, 1352 patients were identified between 1987 and 2000 with a minimum follow-up of 1 year (median follow-up, 55 months; range, 12-189 months). The median radiation dose was 74.0 grays (Gy) (range, 63.0-83.0 Gy). The median radiation doses for patients who received < 68.0 Gy (n = 201), 68.0-72.0 Gy (n = 373), and > or = 72.0 Gy (n = 778) were 66.6 Gy, 70.0 Gy, and 78.0 Gy, respectively. The RT techniques used were standard RT in 41% of patients, 3-dimensional conformal RT in 34% of patients, and intensity-modulated RT in 25% of patients. Androgen-deprivation (AD) therapy lasting < or = 6 months was administered to 34% of patients. RESULTS: The 5-year and 7-year bRFS rates were 63% and 59%, respectively. On multivariate analysis, T classification (P < 0.001), pretreatment prostate-specific antigen level (P < 0.001), biopsy Gleason score (P = 0.001), radiation dose (P < 0.001), and year of therapy (P < 0.001) were independent predictors of biochemical failure. Age, race, AD therapy, and RT technique did not predict for biochemical failure. For patients with low-risk tumors, the 5-year bRFS rates for those who received RT doses of < or = 68.0 Gy, 68.0-72.0 Gy, and > or = 72.0 Gy were 52%, 82%, and 93%, respectively (P < 0.001); for patients with intermediate-risk tumors, the respective 5-year bRFS rates were 27%, 51%, and 83% (P < 0.001); and for patients with high-risk tumors, the respective 5-year bRFS rates were 21%, 29%, and 71%, respectively (P < 0.001). CONCLUSIONS: The most significant therapeutic factor affecting bRFS rates after RT was radiation dose, rather than AD therapy use or radiation technique.     

Intensity-modulated radiation therapy for prostate cancer: late morbidity and results on biochemical control.

PURPOSE: To report on late morbidity and biochemical relapse-free survival (bRFS) after intensity-modulated radiation therapy (IMRT) for prostate cancer. METHODS: Between 1998 and 2005 133 patients were treated with IMRT for T(1-4) N0 M0 prostate cancer. The median follow-up time was 36 months. In a first cohort, patients received a median planning target volume (PTV) dose of 74 Gy with a hard constraint on maximum rectum dose of 72 Gy (74R72, n=51). Later, median PTV and maximum rectum dose were increased to 76 and 74 Gy, respectively (76R74; n=82). We defined low-risk (n=20), intermediate-risk (n=70) and high-risk (n=43) groups. Androgen deprivation was given to patients in the intermediate- and high-risk group. Late gastro-intestinal (GI) and genito-urinary (GU) morbidity and biochemical relapse, in accordance with the ASTRO consensus, were recorded. RESULTS: We observed grade 2 GI (17%) and GU (19%), grade 3 GI (1%) and GU (3%) late toxicities. Except for hematuria, the median duration of side-effects was 6 months. Biochemical relapse-free survival (bRFS) at 3 and 5 years was 88% and 83%, respectively, with a significantly better 3-year bRSF for the 76R74 than for the 74R72 group (p=0.01). Five-year bRFS for patients in the low-risk, intermediate-risk and high-risk group was 100%, 94% and 74%, respectively (p<0.01). CONCLUSION: IMRT for localized or locally advanced prostate cancer combines low morbidity with excellent biochemical control.     

Late rectal symptoms and quality of life after conformal radiation therapy for prostate cancer.

BACKGROUND AND PURPOSE: This study was carried out in order to analyze the prevalence of late rectal and anal symptoms after conformal radiation therapy for prostate cancer and to assess their association with quality of life. PATIENTS AND METHODS: Two-hundred and forty nine patients were interviewed at 24-111 months after definitive conformal radiation therapy of localized prostate cancer with a median dose of 70 Gy. Rectal symptoms and fecal incontinence were evaluated with standardized questionnaires. Quality of life was assessed with the EORTC Quality of Life Questionnaire-C30 and the prostate cancer module PR25. RESULTS: Rectal symptoms were mostly intermittent. Daily symptoms occurred in < or =5% of the patients. Incontinence was mostly mild with only 3% of the patients reporting daily incontinence episodes. Quality of life was comparable to that of the male German general population except that cognitive functioning and diarrhea were worse in the study population and pain was worse in the reference population. Global quality of life was associated with fecal incontinence, fecal urge, tenesmus, therapy for rectal symptoms and hormonal therapy for biochemical/clinical recurrence. CONCLUSIONS: Rectal symptoms and fecal incontinence after conformal radiation therapy for prostate cancer are mostly intermittent. Fecal incontinence, fecal urge and tenesmus are associated with lower global quality of life levels.